Serotonin-selective reuptake inhibitors （SSRIs）， as widely used antidepressants in clinical practice， exhibit significant individual differences in antidepressant efficacy. Gut microbiota plays an important role in the development and progression of depression， and the use of SSRIs exerts a significant impact on the gut microbiota of patients with depression. Based on this， this article reviews the research progress on the interactions between the antidepressant effects of SSRIs and gut microbiota. It has been found that SSRIs can influence the diversity， abundance， and function of the gut microbiota directly or indirectly. Conversely， the composition of the gut microbiota and differences in its functional metabolic pathways， and other factors， can in turn affect the antidepressant effects of SSRIs. Therefore， in clinical practice， gut microbiota diversity can be utilized as a predictive indicator for the antidepressant effects of SSRIs. Probiotics can be employed as an adjunct therapy alongside SSRIs， and dietary adjustments， as well as fecal microbiota transplantation， can be used to enhance the therapeutic efficacy of SSRIs. In the future， large-scale， multicenter clinical studies should be conducted， enrolling a broadly representative cohort of patients with depression， to uncover the true association between the antidepressant effects of SSRIs and gut microbiota， thereby opening up more effective avenues for the comprehensive treatment of depression.

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

OBJECTIVE To design the implementation path around the key links of the management in the clinical comprehensive evaluation of drug in China， and to provide suggestions for optimizing and perfecting the management in the clinical comprehensive evaluation of drug. METHODS Based on the relevant experience of drug evaluation management in typical countries regions at home and abroad， the discussion was performed and the management mechanism was designed from seven aspects， such as funding source， selection of topics， staff management， information management， data management， evaluation process and quality assessment. RESULTS & CONCLUSIONS In terms of funding sources， the financial department can provide funding guarantees or other alternative forms such as performance evaluations to encourage all parties to undertake the clinical comprehensive evaluation of drug projects. In terms of the selection of topics， a “top-down” or “bottom-up” selection mode can be determined according to the project’s nature and actual situation， and a selection process of “forming alternatives-setting up theme selection list-demonstrating and publishing theme selection list” can be formed. In terms of staff management， the specialty of team members should be specified， and the expert team should be established to provide clinical comprehensive evaluation of drug. In terms of information management， the national/provincial basic informational platform should be established， and the registration system should be established. In terms of data management， a regional health data-sharing platform should be formed and the “application-checking-utilization” mechanism should be conducted. In terms of the evaluation process， the evaluation procedures that concern on project implementation plan demonstration system and project closing review system should be constructed. In terms of quality assessment， quality assessment and reward and punishment mechanism for project completion，that consider the quality of management first while focusing on the technical quality， can be established. The management mechanism based on the standardized implementation of the seven key links will standardize the development of clinical comprehensive evaluation of drugs in China to some extent， and help improve the quality of clinical comprehensive evaluation projects for drugs.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

OBJECTIVE To establish the quality control method of Flueggea suffruticosa. METHODS The microscopical identification and thin layer chromatography （TLC） of F. suffruticosa were carried out， and the mass fractions of moisture， total ash， acid-insoluble ash and alcohol-soluble extracts in F. suffruticosa were measured based on the 2020 version of Chinese Pharmacopoeia （part Ⅳ）. The content of securinine in medicinal materials was determined by high performance liquid chromatography. RESULTS The powder of F. suffruticosa was gray-green， with obvious microscopic characteristics such as pores， pollen grains， calcium oxalate cluster crystals， ducts. The results of TLC identification showed that in the chromatograms of 16 batches of medicinal samples， the same color spots were found on the corresponding positions of the chromatograms of securinine， rutin， quercetin and F. suffruticosa control. The average mass fractions of moisture， total ash， acid-insoluble ash and alcohol- soluble extracts in 16 batches of medicinal materials were 9.26%， 6.96%， 1.17% and 28.89%， respectively. The injection volume of securinine in the range of 0.052 4-0.524 0 µg had a good linear relationship with the peak area （R2＝0.999 8）. RSDs of precision， repeatability and stability （24 h） test were all less than 3% （n＝6 or 7）. The average recovery of sample was 97.47%， RSD was 1.63% （n＝6）. The content of securinine in 16 batches of medicinal materials was 1.003-6.872 mg/g. CONCLUSIONS The quality control method of F. suffruticosa is established， and the mass fractions of moisture， total ash and acid-insoluble ash should not exceed 12.0%， 9.0% and 2.0%， respectively； the alcohol-soluble extract should not be less than 20%， and the content of securinine should not be less than 1.00 mg/g.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

OBJECTIVE To establish a method for qualitative and quantitative analysis of Shangkeling spray ，which can be a certain foundation for the overall quality evaluation of Shangkeling spray . METHODS Eleven batches of Shangkeling spray were determined by high performance liquid chromatography （HPLC）.The separation was performed on Ultimate ® XB-C18 column with mobile phase consisted of acetonitrile -0.1% phosphoric acid （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 35 ℃.Similarity Evaluation Software of Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）was used for the establishment of HPLC characteristic chromatogram and similarity analysis；the chromatographic peaks were identified by comparing with the chromatogram of the reference substance . The contents of matrine ，oxymatrine，scopoletin and isoazinopyridine were determined by HPLC .RESULTS Totally 18 common characteristic peaks were demarcated for 11 batches of samples ，4 of them were identified ，i.e. peak 2（matrine），peak 3（oxymatrine），peak 6 （scopoletin），peak 7（isoazinopyridine）. The similarity between the characteristic chromatogram of 11 batches of samples and the control characteristic chromatogram R was ≥0.990. The results of content determination methodology conformed to the relevant requirements. The contents of matrine ，oxymatrine，scopoletin and isoazinopyridine in 11 batches of Shangkeling spray were 14.48-44.86，32.53-69.76，11.28-20.96 and 10.36-22.49 μg/mL，respectively. CONCLUSIONS HPLC characteristic chroma -togram and quantitative analysis method of 4 indicator components are successfully established in this study ，which can be used to evaluate the quality of this preparation .

OBJECTIV E To optimize the s alt-processing technology of Rosa laevigata ，and to study high performance liquid chromatography（HPLC）fingerprints and chromaticity values of R. laevigata before and after salt-processing. METHODS The comprehensive scoring method was adopted to optimize the salt-processing technology of R. laevigata using appearance character ， moisture and polysaccharide content as index. Fingerprints were established by HPLC method before and after salt-processing ，and chromaticity values （L*，a*，b*）of the powder before and after salt-processing were determined. The multivariate statistical analysis was carried out for raw product and salt-processing product of R. laevigata by using common peak areas and chromaticity values as index. RESULTS The optimal salt-processing technology of R. laevigata was to mix it with appropriate amount of salt water ，place them in the preheated frying wok at 140 ℃，fry them for 25 min，and rotate frying wok 20 times/min. Ten common peaks were calibrated by HPLC fingerprints before and after salt-processing ，and 3 components were identified ，such as gallic acid ，catechin and ellagic acid. The chromaticity values L*，b* and E* changed significantly after salt-processing. The multivariate statistical analysis method could distinguish raw products and salt-processing products into two categories ，in which peaks 1，5，6 and 10 and chromaticity values b* and E* were important characteristic factors. CONCLUSIONS The optimized salt-processing technology is stable and reliable ，and the established fingerprint has good repeatability and stability. Fingerprint and chromaticity values combined with multivariate statistical analysis can provide reference for the identification and quality analysis of R. laevigata before and after salt-processing.