Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

Over 40%of critically ill patients will develop coagulopathy.Once critically ill patients are complicated with coagulopathy,the incidence of bleeding and mortality can increase by more than 4 times.Early identification of coagulopathy and accurate evaluation of coagulation function are essential for correcting coagulopathy as soon as possible.Therefore,Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association,together with Chinese People's Liberation Army Professional Committee of Critical Care Medicine updated the"Chinese expert consensus on standardized assessment of severe coagulopathy(2025 Edition)"on the basis of the"Consensus of Chinese experts on standardized evaluation of coagulation dysfunction in severe patients"formulated in 2022.This consensus includes four parts:classification and typing,etiology and mechanism,assessment methods,and diagnostic criteria of severe coagulopathy,with a total of 14 recommendations,aiming to provide corresponding guidance for clinical practice.

Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To conduct comprehensive clinical evaluation of injectable anti-inflammatory and hepatoprotective drugs with different mechanisms of action,and to provide a basis for drug selection and rational drug use in medical institutions.Methods Twenty-two experts in clinical and pharmacological fields were organized to construct a quantitative rating scale for the comprehensive clinical evaluation of drugs by applying the literature research method,expert interview method,and Delphi method,through seminars and interviews,and by referring to the real-world clinical data and evidence-based medical evidence such as the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs,so as to conduct a comprehensive evaluation of eight injectable anti-inflammatory and hepatoprotective drugs in terms of six dimensions:effectiveness,safety,economy,appropriateness,accessibility and maturity.Results A comprehensive clinical evaluation index system of injectable anti-inflammatory and hepatoprotective drugs for the treatment of drug-induced liver injury was constructed,including 6 first-level indexes,14 second-level indexes,and 27 third-level indexes,with a total of 100 points.The scoring results showed that among the evaluated varieties,the scores were,in descending order,magnesium isoglycyrrhizinate injection,compound glycyrrhizin injection,polyene phosphatidylcholine injection,reduced glutathione for injection,thiopronin injection,compound ammonium glycyrrhizinate injection,acetylcysteine injection and diammonium glycyrrhizinate injection.Conclusion The constructed quantitative rating scale for comprehensive clinical evaluation of drugs is operable,and the evaluation process can provide academic guidance for exploring the standardized path of comprehensive clinical evaluation of drugs,which needs to be applied in combination with the actual drug varieties of the medical institutions as well as the specific conditions of the patients to make individualized therapeutic choices.

OBJECTIVE To explore the clinical characteristics of the nontuberculous Mycobacteria pulmonary dis-ease(NTMPD)patients with previous pulmonary tuberculosis(PPTB)and analyze the clinical difference from the recurrence of pulmonary tuberculosis.METHODS By means of retrospective survey,the patients who were diag-nosed with NTMPD and recurrent pulmonary tuberculosis in Wuhan Pulmonary Hospital from Mar.2021 to Oct.2023 were recruited as the research subjects,a total of 395 patients with NTMPD were enrolled in the study and were divided into the PPTB-NTMPD group with 92 cases and the NPPTB-NTMPD group with 303 cases according to the history of PPTB.The baseline data,clinical symptoms,imaging findings,underlying diseases,pulmonary diseases,and species of nontuberculous Mycobacteria(NTM)were observed and compared.Totally 92 patients with recurrent pulmonary tuberculosis were randomly screened and assigned as the recurrent pulmonary tuberculo-sis group in a 1:1 ratio by matching the PPTB-NTMPD group with the gender and age.The major clinical charac-teristics were compared between the two groups.The 92 patients with PPTB-NTMPD were divided into the 1-10 years group with 40 cases,the 10-30 years group with 37 cases,and the more than 30 years group with 15 cases according to the interval between the initial diagnosis of pulmonary tuberculosis and the diagnosis of NTMPD.The major clinical characteristics were compared among the groups.RESULTS The age was(64.21±10.71)years old in the PPTB-NTMPD group,(60.26±11.83)years old in the NPPTB-NTMPD group(t=3.020,P=0.003).The proportion of patients with body mass index less than 18.5 kg/m2 was 59.78％in the PPTB-NTMPD group,41.25％in the NPPTB-NTMPD group(x2=6.155,P=0.013);the proportion of patients with cough was 77.17％in the PPTB-NTMPD group,65.68％in the NPPTB-NTMPD group(x2=4.313,P=0.038);the inci-dence of cavitary shadow was 50.00％in the PPTB-NTMPD group,35.31％in the NPPTB-NTMPD group(x2=6.414,P=0.011);the incidence of emphysema and pulmonary bullae was 29.35％in the PPTB-NTMPD group,12.87％in the NPPTB-NTMPD group(x2=13.766,P＜0.001);the incidence of chronic obstructive pulmonary disease(COPD)was 22.83％in the PPTB-NTMPD group,14.19％in the NPPTB-NTMPD group(x2=3.875,P=0.049);the incidence of damaged lung was 9.78％in the PPTB-NTMPD group,2.97％in the NPPTB-NT-MPD group(x2=7.530,P=0.014);there were significant differences.Mycobacterium intracellulare and Myco-bacterium abscessus were the predominant species of NTM in both the PPTB-NTMPD group and the NPPTB-NT-MPD group,there was no significant difference in the distribution of NTM species between the two groups of pa-tients.The incidence of patch shadow of the PPTB-NTMPD group was lower than that of the recurrent pulmonary tuberculosis group(P＜0.05),the incidence of bronchiectatic shadow of the PPTB-NTMPD group was higher than that of the recurrent pulmonary tuberculosis group(P＜0.05).There were significant differences in the age,incidence of pleural thickening and incidence of COPD among the patients with different time intervals between ini-tial diagnosis of pulmonary tuberculosis and the diagnosis of NTMPD in the PPTB-NTMPD group(P＜0.05).CONCLUSIONS The previous pulmonary tuberculosis mainly affect the body mass index less than 18.5 kg/m2 and the post-tuberculosis pulmonary diseases such as cough,pulmonary cavity,emphysema,pulmonary bullae,COPD and damaged lung of the NTMPD patients.The NTMPD patients with previous pulmonary tuberculosis are more likely to have bronchiectasia than the patients with recurrent tuberculosis.It is necessary for the clinicians to attach great importance.

Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective To investigate the effect of erioside E on myocardial injury after myocardial infarction(MI)by regulating hypoxia-inducible factor-2α(HIF-2α)-mediated pyroptosis of cardiomyocytes and its possible mechanism.Methods Thirty rats were randomly divided into sham-operation group,MI group,and erioside E group,with 10 rats in each group.Cardiomyocytes H9C2 were cultured and divided into control group,hypoxia group,erioside E group and HIF-2α overexpression group.Masson staining was used to observe myocardial fibrosis and infarct size.The protein expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD were detected by Western blotting.RT-qPCR was used to detect the mRNA expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD.EdU kit was used to detect the proliferation of cardiomyocytes.The expressions of NLRP3,Caspase-1 and GSDMD proteins in cardiomyocytes were detected by immunofluorescence staining.Results Compared with the sham-operation group,the myocardial fibrosis level and infarct size were significantly increased in the MI group(P＜0.05),and the protein expressions of HIF-2α,pyroptosis-related proteins of NLRP3,Caspase-1 and GSDMD in myocardial tissue were increased(P＜0.05).Compared with the MI group,the level of myocardial fibrosis and infarct size were significantly decreased(P＜0.05),the protein expression of HIF-2α in myocardial tissue was increased,and the protein expressions of NLRP3,Caspase-1 and GSDMD were decreased in the erioside E group(P＜0.05).Compared with the control group,the hypoxia group had a significant reduction in the proliferation of cardiomyocytes and significant increase in the mRNA and protein expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD(P＜0.05).Compared with the hypoxia group,the proliferation ability of cardiomyocytes was significantly increased,and the expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD mRNA in cardiomyocytes were decreased in the erioside E group(P＜0.05),while the protein expression of HIF-2α in cardiomyocytes was increased in the HIF-2αoverexpression group.The protein expressions of NLRP3,Caspase-1 and GSDMD were significantly decreased(P＜0.05).Conclusion Erioside E can improve myocardial injury by upregulating HIF-2α to inhibit myocardial pyroptosis.