Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

AIM To investigate the clinical effects of Feining Paidu Decoction combined with conventional treatment on patients with Mycoplasma pneumoniae lobar pneumonia.METHODS Ninety patients were randomly assigned into control group(45 cases)for 2-week intervention of conventional treatment,and observation group(45 cases)for 2-week intervention of both Feining Paidu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,inflammatory indices(WBC,N,CRP,ESR,PCT),inflammatory cytokines(TNF-α,IL-6,IL-8),coagulation indices(PLT,TT,PT,APTT,Fib,D-D),pulmonary imaging intergal and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,inflammatory indices,inflammatory cytokines,PLT,pulmonary imaging intergal(P<0.05),especially for the observation group(P<0.05);the observation group exhibited prolonged TT,PT,APTT(P<0.05),and decreased Fib,D-D(P<0.05),which were more obvious than those in the control group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with Mycoplasma pneumoniae lobar pneumonia,Feining Paidu Decoction combined with conventional treatment can safely and effectively alleviate clinical symptoms,and improve inflammatory responses,coagulation functions.

Objective:To investigate the effect of progression of disease within 24 months(POD24)on overall survival(OS)in patients with mantle cell lymphoma(MCL),and compare the clinical characteristics between POD24 and non-POD24 patients.Methods:A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020.According to the occurrence of POD24,the patients were grouped for prognostic evaluation and clinical characteristics comparison.Results:Univariate Cox regression analysis showed that POD24,PLT,albumin,MIPI score,ECOG PS score,LDH were the factors influencing OS in newly diagnosed MCL patients(all P＜0.05).The results of multivariate Cox regression analysis showed that POD24[HR=16.797(95％CI:3.671-76.861),P＜0.001],albumin＜40 g/L[HR=3.238(95％CI:1.095-9.572),P=0.034]and ECOG PS score≥2[HR=4.005(95％CI:1.033-15.521),P=0.045]were independent risk factors influencing OS in MCL patients.The incidence of PLT＜100 × 109/L(33.3％vs 5.9％,P=0.033)and ECOG PS score≥2(45.5％vs 5.9％,P=0.040)were significantly higher in POD24 patients than those in non-POD24 patients.Conclusion:POD24 is an independent poor prognostic factor affecting the OS of MCL patients,and the patients with PLT＜100 × 109/L and ECOG PS score ≥2 at diagnosis have a higher probability of POD24.

Objective:To investigate the effect of endothelial activation and stress index(EASIX)on the prognosis of patients with angioimmunoblastic T-cell lymphoma(AITL)and peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS),and to compare the clinical characteristics of patients in the low EASIX and high EASIX groups.Methods:The clinical data of 59 newly diagnosed AITL and PTCL-NOS patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to September 2021 were retrospectively analyzed.The optimal cut-off value of EASIX was determined by receiver operating characteristic(ROC)curve;The chi-square test was used to analyze the correlation between EASIX and clinical features of patients with AITL and PTCL-NOS;The Kaplan-Meier survival curve was used to analyze the overall survival(OS)and progression-free survival(PFS)of the patients;Univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:The optimal cut-off value of EASIX was 0.95,based on which the patients were divided into a low EASIX(＜0.95)group and a high EASIX(≥ 0.95)group.Compared with the low EASIX group,the high EASIX group had a higher proportion of patients with advanced Ann Arbor stage,higher risk according to IPI,elevated LDH,hypoproteinemia,anemia,B symptoms,extranodal involvement,and bone marrow involvement.Survival analysis showed that the OS and PFS of patients in the high EASIX group were significantly shorter than those in the lower EASIX group(P＜0.001).The multivariate analysis showed that EASIX was an independent risk factor for OS[HR=7.217(95％CI:1.959-26.587),P=0.003]and PFS[HR=2.718(95％CI:1.032-7.161),P=0.043]of PTCL patients.Conclusion:High EASIX in newly diagnosed patients with AITL and PTCL-NOS suggests a poor prognosis,and high EASIX is a risk factor affecting prognosis of the patients.

Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

OBJECTIVE To mine the adverse drug events （ADE） signals for gilteritinib， and provide a reference for safe drug use in clinic. METHODS ADE reports with gilteritinib as the primary suspected drug were extracted from the FDA Adverse Event Reporting System （FAERS） database from February 1st， 2018 to December 31st， 2023. Reporting odds ratio （ROR） and proportional reporting ratio （PRR） were applied to detect the risk signals from the data in the FAERS database. The classification and statistics of collected signal data were conducted by using the preferred term （PT） and systemic organ class （SOC） in ADE terminology set of the Medical Dictionary for Regulatory Activities （24.1 edition）. RESULTS Totally， 2 755 gilteritinib-related ADE reports were collected from the database， involving 676 ADE signals （95 positive signals）， 313 PTs and 25 SOCs. Among them， nine signals were not recorded in the package insert. The top 5 PTs consisted of abnormal liver function， decreased platelet count， febrile neutropenia， pneumonia and myelosuppression. The top 6 SOCs for positive signal counts were examinations， general disorders and administration site conditions， respiratory， thoracic and mediastinal disorders， infections and infestations， heart organ disorders， and nervous system disorders. ADEs not recorded in the drug package insert included pneumonia， myelosuppression， decreased blood cell count， sepsis， hemorrhage， infection （not specifically referred to）， septic shock， respiratory failure， and aspergillosis. CONCLUSIONS In addition to paying attention to common ADEs such as liver dysfunction and thrombocytopenia， it is necessary to monitor ADEs with strong signals that are not mentioned in the drug instructions when using gefitinib， such as pneumonia， bone marrow suppression， cytopenia， sepsis， bleeding， infection （not specifically referred to）， septic shock， respiratory failure， Aspergillus infection， elevated serum creatinine and interstitial lung disease.