Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wa...To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity （PWV） was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.展开更多
The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier ...The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier partitioning behavior(log BB) of various drugs and organic compounds. Different molecular descriptors were calculated using a dragon package to represent the molecular structures of the compounds studied. The enhanced replacement method(ERM) was used to select the variables and construct the SVM model. The correlation coefficient, R^2, between experimental results and predicted log BB was 0.878 and 0.986, respectively. The results obtained demonstrated that, for all compounds, the log BB values estimated by SVM agreed with the experimental data, demonstrating that SVM is an effective method for model development, and can be used as a powerful chemometric tool in QSPR studies.展开更多
Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platform...Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy： ＂QT interval＂ or ＂QT＂ and ＂age＂ or ＂aging＂. The entry criteria were： over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate （QTc） and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation 〉 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.展开更多
Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocati...Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.展开更多
Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, ...Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.展开更多
OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of ...OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of Older Persons’Prescriptions(STOPP)criteria version 2 and to identify the risk factors related to PIP.METHODS The 2016 National Aged Patient Sample data,comprising National Health Insurance claim records for a random sample of 20%of patients aged≥65 years,were used to calculate PIP prevalence of outpatient prescriptions.For criteria including drugdisease interactions,PIP prevalence per indication was estimated.RESULTS Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims,100,085 patients(7.85%)and 341,664 claims(1.27%)had one or more PIP.The most frequent PIP was“nonsteroidal antiinflammatory drug with concurrent antiplatelet agent(s)without protonpump inhibitor prophylaxis”in the claimlevel(0.97%)and patientlevel(6.33%)analyses.“Betablocker with bradycardia”(16.47%of claims)and“angiotensin receptor blockers in patients with hyperkalaemia”(23.89%of claims)showed the highest PIP prevalence per indication.Logistic regression analysis revealed that,among the patient and health care provider characteristics,female,older age,more severe comorbidities,polypharmacy,higher level of healthcare organization,and specialty of prescriber were significantly associated with a higher risk of PIP.CONCLUSIONS Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs.展开更多
Objective To evaluate the trend of change in the efficacy and safety of catheter ablation compared with antiarrhythmic drug therapy （ADT） for rhythm control in patients with atrial fibrillation （AF） over time. Met...Objective To evaluate the trend of change in the efficacy and safety of catheter ablation compared with antiarrhythmic drug therapy （ADT） for rhythm control in patients with atrial fibrillation （AF） over time. Methods The online databases PubMed and EMBASE were searched for relevant studies. STATA software （version 12.0） was used to perform the meta-analysis and meta-regression. Results Fifteen randomized controlled trials including 2249 patients with AF were identified. The pooled results showed that catheter ablation was associated with a 52% reduction in the risk of AF recurrence compared with ADT [risk ratio （RR） = 0.48, 95% confidence interval （CI）： 0.40-0.57, I2 = 70.7%）. Subgroup analyses showed that catheter ablation exhibited less efficacy in studies after 2011 compared to studies before 2011 （RR = 0.61, 95% CI： 0.54-0.68, I2 = 9.3% and RR = 0.34, 95% CI： 0.24-0.47, I2 = 69.9%, respectively）, and the safety outcome showed a 1.08-fold higher incidence of adverse events （14.2% vs. 7.3%; RR = 1.08, 95% CI： 1.04-1.13） in studies after 2011. Conclusions Catheter ablation appears to be superior to ADT for rhythm control. However, less efficacy and a higher rate of adverse events were observed in studies after 2011 compared to studies before 2011.展开更多
Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and resten...Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.展开更多
About 100 crude Chinese mineral drug samples were investigated with M&’ssbauer spectroscopy, X-ray diffraction analysis and atomic absorption spectroscopy. The classifications, species and components of Chinese m...About 100 crude Chinese mineral drug samples were investigated with M&’ssbauer spectroscopy, X-ray diffraction analysis and atomic absorption spectroscopy. The classifications, species and components of Chinese mineral drugs are elucidated. The pharmaceutic and curative mechanisms of these mineral drugs are discussed.展开更多
Semicarbazide-sensitive the metabolism of glucose and fat, amine oxidase （SSAO） has been considered to be associated with and elevated SSAO activity was observed in obese patients. In the present study, an in vitro ...Semicarbazide-sensitive the metabolism of glucose and fat, amine oxidase （SSAO） has been considered to be associated with and elevated SSAO activity was observed in obese patients. In the present study, an in vitro SSAO activity-based method was developed to screen inhibitors from 15 an- ti-obesity drugs. Among the fifteen anti-obesity drugs, four drugs including caffeine, fenfluramine, bumetanide and amfebutamone inhibited SSAO activity, and caffeine was the most effective one. When the concentration of caffeine was 1.4 mmol/L, the inhibition ratio was 31.9% and 18.8% in rabbit serum and rat adipose tissue, respectively. Inhibition of SSAO activity by caffeine was also confirmed in the in vivo study, showing the inhibition ratio of 15.6% on serum SSAO. Caffeine pro- vides a natural source of inhibition of SSAO activity and may be a promising inhibitor for the study of SSAO.展开更多
The terahertz time-domain spectroscopy(THz-TDS) was used for sensing and identifying illicit drugs.The absorption spectra of seven illicit drug samples(morphine and its hydrochloride,cocaine hydrochloride,codeine phos...The terahertz time-domain spectroscopy(THz-TDS) was used for sensing and identifying illicit drugs.The absorption spectra of seven illicit drug samples(morphine and its hydrochloride,cocaine hydrochloride,codeine phosphate,papaverine hydrochloride,pethidine hydrochloride,and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature.The geometric structure and vibration frequencies of morphine were calculated by density functional theory.The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes.Each illicit drug has a distinct signature in its THz spectra.The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints.展开更多
Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-infl...Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.展开更多
Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively ...Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.展开更多
Natural polysaccharides named PEP-0.1-1,PEP-0-1 and PEP-0-2 from edible mushroom species Pleurotus eryngii were obtained in the present study.Results showed that molecular weights of these polysaccharides were 3235,20...Natural polysaccharides named PEP-0.1-1,PEP-0-1 and PEP-0-2 from edible mushroom species Pleurotus eryngii were obtained in the present study.Results showed that molecular weights of these polysaccharides were 3235,2041 and 23933 Da,respectively.Further,structural characterization revealed that PEP-0.1-1 had a→4-α-D-Glcp-1→backbone and contained→4)-α-D-Glcp and→4)-β-D-Glcp reducing end groups.PEP-0-1 backbone contained→4-α-D-Glcp-1→and→6-α-3-O-Me-D-Galp-1→,and the side chains containedα-D-Glcp,β-D-Manp-1→andα-D-Glcp-3→.However,PEP-0-2 backbone consisted of→4-α-DGlcp-1→and→6-α-3-O-Me-D-Galp-(1→6)-α-D-Galp-1→while the side chains containedα-D-Glcp andβ-D-Manp-1→.Biological activity analysis was then carried out and found that all these polysaccharides could significantly suppress the relative mRNA expression of toll-like receptor 4,nitric oxide(NO),tumor necrosis factor-α,interleukin(IL)-1βand IL-6 in lipopolysaccharide(LPS)-induced inflammation of RAW264.7 cells,as well as the over secretion of the above cell cytokines.Moreover,Western blotting analysis revealed that all these purified fractions displayed significant inhibition effects on the expression of c-Jun N-terminal kinases protein induced by LPS in mitogen activated protein kinase pathway,along with the relieving on the inhibition effect of LPS on IκB-αprotein expression.In summary,the information generated by the present study could provide a theoretical basis for the exploration of novel healthy food materials from edible mushroom with antiinflammation activities.展开更多
Dry-fermented sausages are a good source of bioactive peptides,whose stability against gastrointestinal(GI)digestion determines their bioaccessibility.This study focused on evaluating the effect of peptide extracts fr...Dry-fermented sausages are a good source of bioactive peptides,whose stability against gastrointestinal(GI)digestion determines their bioaccessibility.This study focused on evaluating the effect of peptide extracts from sausages fermented with Staphylococcus simulans QB7 during in vitro simulated GI digestion,including peptide profiles and antioxidant and anti-inflammatory activities.Peptides present in sausages were degraded during digestion,with molecular weight reduced from>12 kDa to<1.5 kDa.Besides,the content of amino acids increased from 381.15 to 527.07 mg/g,especially tyrosine being found only after GI digestion.The anti-inflammatory activities were increased after GI digestion,however,the changes in antioxidant activities were the opposite.A total number of 255,252 and 386 peptide sequences were identified in undigested,peptic-digested and GI-digested samples,respectively.PeptideRanker,BIOPEP-UWM and admetSAR were used to further predict the functional properties and intestinal absorption of the identified peptide sequences from GI digestion.Finally,18 peptides were discovered to possess either antioxidant or anti-inflammatory capacities.展开更多
In recent years,with the policy reform of new drug review and approval,China has ushered in a surge of innovative drug development.Based on the Pharnexcloud database and the Pharmcube database,we analyzed the innovati...In recent years,with the policy reform of new drug review and approval,China has ushered in a surge of innovative drug development.Based on the Pharnexcloud database and the Pharmcube database,we analyzed the innovative drugs approved for marketing and entered clinical trials in China,sorted out the major research and development(R&D)institutions and enterprises,the distribution of innovative drug target types,and the primary therapeutic areas of the approved innovative drugs,and compared with the global innovative drug R&D landscape.Since 2020,China's innovative drug development has shown a rapid growth trend,with intense competition among biopharmaceutical companies,and the emergence of a number of leading biopharmaceutical enterprises.Popular targets for clinical-stage and approved drugs include protein tyrosine kinase,epidermal growth factor receptor,vascular endothelial growth factor receptor,and others.Oncological diseases are the most active domain for new drug R&D in China,followed by infectious diseases and neurological diseases.Suggestions for future development are proposed to increase policy support,enhance R&D innovation investment,optimize pipeline layout,strengthen international cooperation,and focus on innovative targets.This review provides a reference for pharmaceutical R&D enterprises,scientific researchers,and government administrators.展开更多
This study demonstrates the feasibility of producing three polysaccharides(neutral LJP-1,acidic LJP-2 and acidic LJP-3)with significant in vitro and in vivo anti-inflammatory activities from the flowers of Lonicera ja...This study demonstrates the feasibility of producing three polysaccharides(neutral LJP-1,acidic LJP-2 and acidic LJP-3)with significant in vitro and in vivo anti-inflammatory activities from the flowers of Lonicera japonica.The three polysaccharides differed in chemical composition,molecular weight(Mw)distribution,glycosidic linkage pattern,functional groups and morphology.They exhibited excellent protective effects(in a dose-dependent manner)in lipopolysaccharide-injured RAW264.7 macrophages and Cu SO4-damaged zebrafish via reducing NO production and inhibiting the overexpressions of inflammation-related transcription factors,inflammatory proteins and cytokines in the NF-κB/MAPK signaling pathways.Their antiinflammatory effects varied owing to their different molecular characteristics and chemical compositions.Overall,LJP-2 at 400μg/m L was the most effective.LJP-2 consisted mainly of→5)-α-L-Araf(1→,→4)-α-LGalp A(1→and→2)-α-L-Rhap(1→residues with terminal T-β-D-Glcp.Thus,honeysuckle flowers are good sources of anti-inflammatory polysaccharides,and precise fractionation enables the production of potent antiinflammatory agents for the development of functional foods and healthcare products.展开更多
Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory ca...Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.展开更多
Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, f...Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.展开更多
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
文摘To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity （PWV） was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.
文摘The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier partitioning behavior(log BB) of various drugs and organic compounds. Different molecular descriptors were calculated using a dragon package to represent the molecular structures of the compounds studied. The enhanced replacement method(ERM) was used to select the variables and construct the SVM model. The correlation coefficient, R^2, between experimental results and predicted log BB was 0.878 and 0.986, respectively. The results obtained demonstrated that, for all compounds, the log BB values estimated by SVM agreed with the experimental data, demonstrating that SVM is an effective method for model development, and can be used as a powerful chemometric tool in QSPR studies.
文摘Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy： ＂QT interval＂ or ＂QT＂ and ＂age＂ or ＂aging＂. The entry criteria were： over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate （QTc） and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation 〉 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.
文摘Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.
文摘Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.
文摘OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of Older Persons’Prescriptions(STOPP)criteria version 2 and to identify the risk factors related to PIP.METHODS The 2016 National Aged Patient Sample data,comprising National Health Insurance claim records for a random sample of 20%of patients aged≥65 years,were used to calculate PIP prevalence of outpatient prescriptions.For criteria including drugdisease interactions,PIP prevalence per indication was estimated.RESULTS Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims,100,085 patients(7.85%)and 341,664 claims(1.27%)had one or more PIP.The most frequent PIP was“nonsteroidal antiinflammatory drug with concurrent antiplatelet agent(s)without protonpump inhibitor prophylaxis”in the claimlevel(0.97%)and patientlevel(6.33%)analyses.“Betablocker with bradycardia”(16.47%of claims)and“angiotensin receptor blockers in patients with hyperkalaemia”(23.89%of claims)showed the highest PIP prevalence per indication.Logistic regression analysis revealed that,among the patient and health care provider characteristics,female,older age,more severe comorbidities,polypharmacy,higher level of healthcare organization,and specialty of prescriber were significantly associated with a higher risk of PIP.CONCLUSIONS Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs.
文摘Objective To evaluate the trend of change in the efficacy and safety of catheter ablation compared with antiarrhythmic drug therapy （ADT） for rhythm control in patients with atrial fibrillation （AF） over time. Methods The online databases PubMed and EMBASE were searched for relevant studies. STATA software （version 12.0） was used to perform the meta-analysis and meta-regression. Results Fifteen randomized controlled trials including 2249 patients with AF were identified. The pooled results showed that catheter ablation was associated with a 52% reduction in the risk of AF recurrence compared with ADT [risk ratio （RR） = 0.48, 95% confidence interval （CI）： 0.40-0.57, I2 = 70.7%）. Subgroup analyses showed that catheter ablation exhibited less efficacy in studies after 2011 compared to studies before 2011 （RR = 0.61, 95% CI： 0.54-0.68, I2 = 9.3% and RR = 0.34, 95% CI： 0.24-0.47, I2 = 69.9%, respectively）, and the safety outcome showed a 1.08-fold higher incidence of adverse events （14.2% vs. 7.3%; RR = 1.08, 95% CI： 1.04-1.13） in studies after 2011. Conclusions Catheter ablation appears to be superior to ADT for rhythm control. However, less efficacy and a higher rate of adverse events were observed in studies after 2011 compared to studies before 2011.
文摘Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.
基金The Project Supported by National Natural Science Foundation of China
文摘About 100 crude Chinese mineral drug samples were investigated with M&’ssbauer spectroscopy, X-ray diffraction analysis and atomic absorption spectroscopy. The classifications, species and components of Chinese mineral drugs are elucidated. The pharmaceutic and curative mechanisms of these mineral drugs are discussed.
基金Supported by the Ministry of Science and Technology of China(2008AA12A218 2009BAK59B01)
文摘Semicarbazide-sensitive the metabolism of glucose and fat, amine oxidase （SSAO） has been considered to be associated with and elevated SSAO activity was observed in obese patients. In the present study, an in vitro SSAO activity-based method was developed to screen inhibitors from 15 an- ti-obesity drugs. Among the fifteen anti-obesity drugs, four drugs including caffeine, fenfluramine, bumetanide and amfebutamone inhibited SSAO activity, and caffeine was the most effective one. When the concentration of caffeine was 1.4 mmol/L, the inhibition ratio was 31.9% and 18.8% in rabbit serum and rat adipose tissue, respectively. Inhibition of SSAO activity by caffeine was also confirmed in the in vivo study, showing the inhibition ratio of 15.6% on serum SSAO. Caffeine pro- vides a natural source of inhibition of SSAO activity and may be a promising inhibitor for the study of SSAO.
基金Supported by the National Natural Science Foundation of China(Grant No.10675158)the Shanghai Municipal Commission of Science and Technology(Grant No.06dj14008)
文摘The terahertz time-domain spectroscopy(THz-TDS) was used for sensing and identifying illicit drugs.The absorption spectra of seven illicit drug samples(morphine and its hydrochloride,cocaine hydrochloride,codeine phosphate,papaverine hydrochloride,pethidine hydrochloride,and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature.The geometric structure and vibration frequencies of morphine were calculated by density functional theory.The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes.Each illicit drug has a distinct signature in its THz spectra.The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints.
文摘Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.
文摘Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.
基金supported by the National Natural Science Foundation of China(31901623)Major Public Welfare Projects in Henan Province(201300110200)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Natural polysaccharides named PEP-0.1-1,PEP-0-1 and PEP-0-2 from edible mushroom species Pleurotus eryngii were obtained in the present study.Results showed that molecular weights of these polysaccharides were 3235,2041 and 23933 Da,respectively.Further,structural characterization revealed that PEP-0.1-1 had a→4-α-D-Glcp-1→backbone and contained→4)-α-D-Glcp and→4)-β-D-Glcp reducing end groups.PEP-0-1 backbone contained→4-α-D-Glcp-1→and→6-α-3-O-Me-D-Galp-1→,and the side chains containedα-D-Glcp,β-D-Manp-1→andα-D-Glcp-3→.However,PEP-0-2 backbone consisted of→4-α-DGlcp-1→and→6-α-3-O-Me-D-Galp-(1→6)-α-D-Galp-1→while the side chains containedα-D-Glcp andβ-D-Manp-1→.Biological activity analysis was then carried out and found that all these polysaccharides could significantly suppress the relative mRNA expression of toll-like receptor 4,nitric oxide(NO),tumor necrosis factor-α,interleukin(IL)-1βand IL-6 in lipopolysaccharide(LPS)-induced inflammation of RAW264.7 cells,as well as the over secretion of the above cell cytokines.Moreover,Western blotting analysis revealed that all these purified fractions displayed significant inhibition effects on the expression of c-Jun N-terminal kinases protein induced by LPS in mitogen activated protein kinase pathway,along with the relieving on the inhibition effect of LPS on IκB-αprotein expression.In summary,the information generated by the present study could provide a theoretical basis for the exploration of novel healthy food materials from edible mushroom with antiinflammation activities.
基金financially supported by the National Natural Science Foundation of China (32272359)Natural Science and Engineering Research Council of Canada (NSERC,RGPIN-2018-04680)the scholarship from the China Scholarship Council (202106670005)。
文摘Dry-fermented sausages are a good source of bioactive peptides,whose stability against gastrointestinal(GI)digestion determines their bioaccessibility.This study focused on evaluating the effect of peptide extracts from sausages fermented with Staphylococcus simulans QB7 during in vitro simulated GI digestion,including peptide profiles and antioxidant and anti-inflammatory activities.Peptides present in sausages were degraded during digestion,with molecular weight reduced from>12 kDa to<1.5 kDa.Besides,the content of amino acids increased from 381.15 to 527.07 mg/g,especially tyrosine being found only after GI digestion.The anti-inflammatory activities were increased after GI digestion,however,the changes in antioxidant activities were the opposite.A total number of 255,252 and 386 peptide sequences were identified in undigested,peptic-digested and GI-digested samples,respectively.PeptideRanker,BIOPEP-UWM and admetSAR were used to further predict the functional properties and intestinal absorption of the identified peptide sequences from GI digestion.Finally,18 peptides were discovered to possess either antioxidant or anti-inflammatory capacities.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M 1-033).
文摘In recent years,with the policy reform of new drug review and approval,China has ushered in a surge of innovative drug development.Based on the Pharnexcloud database and the Pharmcube database,we analyzed the innovative drugs approved for marketing and entered clinical trials in China,sorted out the major research and development(R&D)institutions and enterprises,the distribution of innovative drug target types,and the primary therapeutic areas of the approved innovative drugs,and compared with the global innovative drug R&D landscape.Since 2020,China's innovative drug development has shown a rapid growth trend,with intense competition among biopharmaceutical companies,and the emergence of a number of leading biopharmaceutical enterprises.Popular targets for clinical-stage and approved drugs include protein tyrosine kinase,epidermal growth factor receptor,vascular endothelial growth factor receptor,and others.Oncological diseases are the most active domain for new drug R&D in China,followed by infectious diseases and neurological diseases.Suggestions for future development are proposed to increase policy support,enhance R&D innovation investment,optimize pipeline layout,strengthen international cooperation,and focus on innovative targets.This review provides a reference for pharmaceutical R&D enterprises,scientific researchers,and government administrators.
基金supported by Key R&D Program of Shandong Province,China(2021CXGC010508)。
文摘This study demonstrates the feasibility of producing three polysaccharides(neutral LJP-1,acidic LJP-2 and acidic LJP-3)with significant in vitro and in vivo anti-inflammatory activities from the flowers of Lonicera japonica.The three polysaccharides differed in chemical composition,molecular weight(Mw)distribution,glycosidic linkage pattern,functional groups and morphology.They exhibited excellent protective effects(in a dose-dependent manner)in lipopolysaccharide-injured RAW264.7 macrophages and Cu SO4-damaged zebrafish via reducing NO production and inhibiting the overexpressions of inflammation-related transcription factors,inflammatory proteins and cytokines in the NF-κB/MAPK signaling pathways.Their antiinflammatory effects varied owing to their different molecular characteristics and chemical compositions.Overall,LJP-2 at 400μg/m L was the most effective.LJP-2 consisted mainly of→5)-α-L-Araf(1→,→4)-α-LGalp A(1→and→2)-α-L-Rhap(1→residues with terminal T-β-D-Glcp.Thus,honeysuckle flowers are good sources of anti-inflammatory polysaccharides,and precise fractionation enables the production of potent antiinflammatory agents for the development of functional foods and healthcare products.
基金supported by the National Natural Science Foundation of China(11871238,11931019,12371486)。
文摘Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.
基金supported by National Natural Science Foundation of China(Nos.52277150,51977096,12005076 and 52130701)the National Key Research and Development Program of China(No.2021YFE0114700)。
文摘Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.
