OBJECTIVE To offer references and implementation paths for updating and enhancing the China’s current essential medicines list system， formulating a specific list of essential medicines for children in China， promoting the research and development of pediatric medications， and improving the accessibility and safety of pediatric medications for children. METHODS Comparative and descriptive analysis was utilized to statistically analyze the classification， dosage forms， specifications， disease spectrum， and symbolic annotations of the 9th edition of the WHO Model List of Essential Medicines for Children （WHO EMLc）. Differences were compared among WHO EMLc， the 2018 National Essential Medicines List （NEML）， and five batches of the List of Encouraged R&D and Declaration of Pediatric Drugs issued by the National Health Commission from 2016 to 2024. The availability of drugs in the 9th edition of WHO EMLc in China was discussed. RESULTS & CONCLUSIONS The differences between the two lists were relatively substantial. A total of 101 drugs overlapped， accounting for 27.98% of the total number of drugs in the 9th edition of the WHO EMLc. Compared with the 2018 NEML， the 9th edition of the WHO EMLc showed notable advantages in the diversity of pediatric-appropriate drug types， dosage form adaptability， and specification precision. The List of Encouraged R&D and Declaration of Pediatric Drugs， to some extent， had filled the gap in China’s pediatric medications， enriching the variety of drug types and dosage forms for children. However， nearly 80% of the drugs on the list were not yet marketed， still facing problems such as a low R&D conversion rate and insufficient policy incentive effects. It is recommended to establish a tiered and classified pediatric essential medicines list based on China’s national conditions， drawing on the selection experience of the WHO and developed countries/regions； strengthen support for the R&D of appropriate pediatric dosage forms and specifications； implement policy preferences throughout the entire cycle of application， review and procurement； encourage evidence-based pediatric practices， accelerate the R&D， market launch， and selection processes of pediatric essential medicines， and ensure the accessibility of pediatric medicines.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

Following the release of the Technical Requirements on Quality Control and Standard Establishment of Traditional Chinese Medicine Formula Granules by the National Medical Products Administration in 2021, Chinese Pharmacopoeia Commission has promulgated 296 national drug standards so far, and most provinces have started the work of establishing provincial standards as supplements. The promulgation of standards fostered high-quality development of the industry. Since the implementation of national and provincial standards for more than three years, enterprises have gained deep understanding and hands-on experiences on the characteristics, technical requirements, production process, and quality control of traditional Chinese medicine(TCM) formula granules. Meanwhile, challenges have emerged restricting the high-quality development of this industry, including how to formulate quality control strategies for medicinal materials and decoction pieces, how to reduce manufacturing costs, and how to improve the pass rate and product stability under high standards. Based on the work experiences from standard management and process research, this article analyzed the distribution of sources, processing methods, dry extract rate ranges, process requirements for volatile oil-containing decoction pieces, control measures of safety indices, characteristics and trends of setting characteristic chromatograms or fingerprints, characteristics and trends of setting content ranges, and main differences between national standards and provincial standards. On the one hand, this article aims to present main characteristics for deeply understanding different indicators in standards and provide basic ideas for establishing quality and process control systems. On the other hand, from the perspective of industrial practice, suggestions are put forward on the important aspects that need to be focused on in the quality and process control of TCM formula granules.
Drugs, Chinese Herbal/chemistry* ; Quality Control ; Medicine, Chinese Traditional/standards* ; China ; Drug Industry/standards*

Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/10⁵ [95% UI: (6.27/10⁵, 9.51/10⁵)], 0.02/10⁵ [95% UI: (0.01/10⁵, 0.02/10⁵)], and 1.32/10⁵ [95% UI: (0.99/10⁵, 1.69/10⁵)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.

Protein acylation is a group of recently identified chemical modification closely linked to me-tabolism with the metabolic intermediate acyl-coenzyme A(acyl-coA)as the substrate.Acylation posses-ses similar chemical structures to acetylation,with differences in carbon chain length,hydrophobicity,and charge.Most acyl-CoAs are intermediate metabolites,the level of which are influenced by the intra-cellular metabolic state.Therefore,protein acylation is greatly affected by cellular metabolism.Metabolic reprogramming is an important feature of tumor cells.In addition to the classic"Warburg effect",cancer cells exhibit abnormal regulation in lipid metabolism,amino acid metabolism and biological oxidation.Acylation on histones can impact chromatin structure,regulating gene expression and DNA repair critical-ly involved in cancer progression.On the other hand,acylation on non-histones can regulate signal trans-duction,enzymatic activity,or protein-protein interactions to affect cancer cell behaviors such as prolifer-ation,invasion,immune evasion,and vascular remodeling.Focusing on three types of acylation closely related to metabolism:lactylation,succinylation,and crotonylation,this article introduces the produc-tion,raw materials,regulatory mechanism and factors of protein acylation.We then review representative studies to show how cancer cell metabolic reprogramming can regulate these processes and histone/non-histone acylation levels,which subsequently affect the expression and function metabolism-related genes/proteins to form a bidirectional dialogue and accelerate cancer progression.In addition,we present sever-al prospects for potential research directions and translational applications in the field.

Objective To observe the value of non-parallel transmission(non-PTX)reduced field-of-view(rFOV)echo planar imaging(EPI)sequence applied in diffusion weighted imaging(DWI)for displaying prostate lesions.Methods Conventional EPI-DWI and non-PTX rFOV-EPI-DWI were prospectively acquired in 30 patients with prostate lesions,including 22 cases of prostatic hyperplasia and 8 cases of prostate cancer.Subjective scoring of imaging quality,as well as objective evaluation on indexes including signal-to-noise ratio(SNR),contrast ratio(CR),contrast-to-noise ratio(CNR)and lesions'apparent diffusion coefficient(ADC)values were performed and compared between two kinds of DWI.Results The subjective score of non-PTX rFOV-EPI-DWI was higher than that of conventional EPI-DWI(P＜0.001).SNR,CR,CNR of non-PTX rFOV-EPI-DWI and lesions'ADC values measured on non-PTX rFOV-EPI-DWI were all higher than those of conventional EPI-DWI(all P＜0.05).Conclusion non-PTX rFOV-EPI DWI could display prostate lesions better than conventional EPI-DWI.

Objective To explore the diagnostic and prognostic value of insulin growth factor 1 receptor(IGF1R)as a biomarker for the progression of heart failure with preserved ejection fraction(HFpEF)in patients with type 2diabetes mellitus(T2DM).Methods A total of 383 patients with type 2diabetes who received treatment in the hospital from June 2019 to March 2023 were selected as the study objects,and they were divided into non-HFPEF group(n=190)and HFpEF group(n=193)according to diagnostic criteria of HF-pEF.The clinical data of the patients were collected,and the IGF1R level was determined by enzyme-linked immunosorbent assay(ELISA).Paired sample t-test,nonparametric test or x2 test were used to compare clinical data and echocardiographic results.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of IGF1R in HFpEF.Nonparametric test was used to com-pared baseline and post-follow-up echocardiography;Kaplan-Meier curves were used to assess the effects of IGF1R levels on readmis-sion.Results Analysis by whether to merge HFpEF groups showed that,in HFpEF group,the patients were older,the proportion of atri-al fibrillation patients was higher,the duration of diabetes was longer(P＜0.05),the levels of blood glucose,creatinine,N-terminal pro-brain natriuretic peptide(NT-proBNP)and IGF1R were significantly increased(P＜0.05),and echocardiography also showed that the systolic and diastolic function of the heart was significantly decreased(P＜0.05).Similar results were obtained by IGF1R hori-zontal grouping.The ROC curve showed that the area under the curve(AUC)of IGF1R for predicting HFpEF in T2DM patients was 0.79.Subgroup analysis of non-HFPEF and HFpEF groups based on IGF1R levels showed that patients with high IGF1R in both the non-HFPEF and HFpEF groups had worse systolic and diastolic function(P＜0.05).Follow-up revealed that the systolic and diastolic function in the high IGF1R group decreased significantly from baseline(P＜0.05).Kaplan-Meier curve analysis showed a significantly increased risk of re-hospitalization due to cardiovascular events in the high IGF1R group(P=0.007).Conclusion IGF1R can be used as a biomarker to monitor structural and functional damage of heart,diagnosing the risk of HFpEF,and predicting the long-term de-terioration of cardiac structure and function in T2DM patients.

Objective:The aim of this study is to evaluate the clinical efficacy of Oxalicao Formula combined with transacu-puncture in the treatment of chronic nonbacterial prostatitis(CNP)characterized by dampness-heat stasis.Methods:A total of 70 patients diagnosed with CNP and characterized by dampness-heat stasis were randomly divided into control group and treatment group,with 35 cases in each group.The patients in control group received Qianlie Beixi capsules.While the patients in treatment group were administered with oxalis decoction in conjunction with acupuncture therapy which lasted for 8 weeks.Pre-and post-treatment evalua-tions for NIH-Chronic Prostatitis Symptom Index(NIH-CPSI),Traditional Chinese Medicine(TCM)symptom scores,urodynamic pa-rameters,immune cell subsets and inflammatory factors were performed.Results:Ultimately,65 patients completed the study with 33 in the treatment group and 32 in the control group.After 8 weeks of intervention,the patients in both of groups demonstrated signifi-cant improvements(P＜0.05).Specifically,remarkable reductions in the NIH-CPSI total score including pain score,urination score,quality of life impact score,TCM symptom score and inflammatory cytokine levels were observed.Additionally,there were upward trends in maximum and average urinary flow rates as well as the CD4+/CD8+ratio of immune cells(P＜0.05).Compared to the con-trol group,the treatment group exhibited superior outcomes in reducing the NIH-CPSI total score,pain score,urination score,quality of life impact score,TCM symptom score,and inflammatory cytokine levels,and increasing in CD4+/CD8+ratios,maximum and av-erage urine flow rates(P＜0.05).Conclusion:The combination of Oxalicao Formula and transacupuncture for treating CNP charac-terized by dampness-heat stasis demonstrates significant therapeutic benefits,which has considerable clinical application value.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.