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 systematically evaluated clinical efficacy of Kirschner's needle and elastic intramedullary nail fixation in treating proximal humeral fractures in children by Meta-analysis. METHODS: Literature on the treatment of proximal humeral fractures in children with Kirschler needles and elastic intramedullary nails published on Wanfang, VIP, CNKI and China biology medicine (CBM), PubMed, Embase, and Web of Science databases were searched from the establishment of databases to October, 2023. Literature extraction, management and data entry were performed by Endnote X9 and Excel 2019, and Meta-analysis was conducted by RevMan 5.3 software. The operation time, hospital stay, fracture healing time, shoulder joint extension range of motion, disabilities of arm, shoulder and hand(DASH) questionnaire score, Neer score or Constant-Murley score and complications were compared between two groups. RESULTS: A total of 7 literatures were included, 1 was prospective study, 6 were retrospective cohort study. There were 521 children, 264 children in Kirschner wire group and 257 children in elastic intramedullary nail fixation group. The results of Meta analysis showed operation time[WMD=-12.61, 95%CI(-24.89, -0.33), P=0.04], fracture healing time[WMD=-0.26, 95%CI(-0.49, -0.02), P=0.03], total complication rate [OR=6.83, 95%CI(3.33, 14.01), P<0.001], nail tract infection rate[OR=6.77, 95%CI(1.72, 26.69), P=0.006] and displacement fracture rate[OR=3.57, 95%CI(1.35, 9.44), P=0.01] between two groups had statistically differences(P>0.05), while there were no statistically significant difference in comparison of hospital stay, shoulder joint extension range of motion, DASH, Neer score, Constant-Murley score, and incidence of skin irritation between two groups (P>0.05). CONCLUSION Kirschner's needle internal fixation has a short operation time and simple operation, but it has a higher incidence of complications compared with elastic nail internal fixation technique. In terms of efficacy and safety, elastic intramedullary nail fixation is one of the options for the treatment of proximal humeral fractures in children.
Humans ; Fracture Fixation, Intramedullary/instrumentation* ; Child ; Shoulder Fractures/physiopathology* ; Bone Nails ; Bone Wires ; Male ; Needles ; Female

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

Objective:To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration.Methods:A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson′s correlation to assess the relationship between MAA and degree of hearing loss.Results:MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss ( r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration ( F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions:The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Objective:To investigate the safety,efficacy,and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM). Methods:The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety,efficacy,and prognosis of this treatment approach were evaluated. Results:Of the 17 patients,10 were male and 7 were female,with a median age of 56 (45-64) years. The stem cell engraftment rate was 100％,with a median neutrophil engraftment time of+10 (9-12) days and a median platelet engraftment time of+12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100％,with 2 cases of pulmonary infection,1 case of urinary tract infection,1 case of skin infection,and 11 cases of transient elevation of serum amylase. After transplantation,13 patients achieved a complete response (CR) or better,and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17;P=0.078). The median follow-up time was 18 (6-36) months,and 15 patients survived without progression,1 patient experienced disease progression,and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0％ and 83.9％,respectively. Conclusion:High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response,further improve therapeutic efficacy,and the transplant-related complications are controllable,making it a viable option worth promoting in clinical practice.