A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.

Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

AIM To establish an HPLC method for the simultaneous content determination of 3′-hydroxy-puerarin,hydroxysafflor yellow A,puerarin,puerarin apigenin,3′-methoxypuerarin,daidzein,stilbene glycoside,luteolin side,genistein side,luteolin B and rosmarinic acid in Naomaitai Capsules.METHODS The analysis was performed on a 30℃ thermostatic Kromasil C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-water(containing 1.0 g/L phosphoric acid)flowing at 0.8 mL/min in a gradient elution manner,and the detection wavelength was set at 280 nm.Subsequently,principal component analysis and cluster analysis were made.RESULTS Twelve components showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 97.00%-99.00% with the RSDs of 0.86%-1.82% .Ten batches of samples were clustered into four categories,the accumulative variance contribution rate of four principal components reached 86.262% .CONCLUSION This simple,stable,reliable and accurate method can be used for the quality control of Naomaitai Capsules.

Objective:To investigate serum levels of retinol-binding protein 4(RBP4)and cystatin C(CysC)in pa-tients with coronary heart disease(CHD)and their association with intestinal flora.Methods:A total of 97 CHD patients admitted in our Department of Critical Care Medicine from December 2019 to December 2020 were treated as CHD group,another 99 healthy subjects undergoing physical examination simultaneously were regarded as control group.Serum levels of RBP4 and CysC,positive rates and number of intestinal flora were compared between two groups.With serum mean levels of RBP4 and CysC in CHD patients as critical value,they were divided into serum RBP4 high level group(RBP4≥35.97 ng/ml,n=53)and low level group(RBP4＜35.97 ng/ml,n=44),serum CysC high level group(CysC≥ 1.49 ng/ml,n=49)and low level group(CysC＜1.49 ng/ml,n=48).Number of intestinal flora were compared between different level subgroups,and Pearson method was used to analyze the asso-ciation of RBP4,CysC levels with flora number.Results:Compared with control group,there were significant rise in RBP4 and CysC levels,and significant reductions in culture positive rates and flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus(P＜0.001 all),and significant rise in culture positive rates and flora numbers of Staphylococcus and Escherichia coli in CHD group(P＜0.001 all).Compared with RBP4 low level group,there were significant reductions in flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus,and signifi-cant rise in flora numbers of Staphylococcus and Escherichia coli in RBP4 high level group(P＜0.001 all);com-pared with CysC low level group,there were significant reductions in flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus,and significant rise in flora numbers of Staphylococcus and Escherichia coli in CysC high level group(P＜0.001 all).Pearson correlation analysis indicated that RBP4 level was significant inversely correla-ted with flora numbers of Bifidobacterium,Firmicutes,Lactobacillus and Proteus(r=-0.626～-0.482,P＜0.001 all),and significant positively correlated with flora numbers of Staphylococcus and Escherichia coli(r=0.302,0.337,P＜0.01 both);CysC level was significant inversely correlated with flora numbers of Bifidobacteri-um,Firmicutes,Lactobacillus and Proteus(r=-0.621～-0.502,P＜0.001 all),and significant positively corre-lated with flora numbers of Staphylococcus and Escherichia coli(r=0.308,0.340,P＜0.01 both).Conclusion:Se-rum levels of RBP4 and CysC increase in CHD patients,and they are closely related to the composition of intestinal flora.

Abstract: Objective　To explore clinical characteristics and the related factors of multidrug-resistant tuberculosis and rifampicin-resistant tuberculosis (MDR/RR-TB) patients with decreased peripheral blood CD4+T lymphocytes, providing a basis for the prevention and treatment of multidrug-resistant tuberculosis. Methods　A retrospective analysis was conducted on 311 MDR/RR-TB patients hospitalized at Chengdu Public Health Clinical Center from January 2018 to December 2020. according to whether accompanied by peripheral blood CD4+T lymphocyte reduction, patients were divided into two groups, the decreased group (n=115) with CD4+T lymphocytes count <414 cell/μL and the normal group (n=196) with CD4+T lymphocytes count ≥ 414 cell/μL. Clinic data, including demographics, types of tuberculosis, complications, clinical symptoms, chest imaging, and treatment outcomes were collected. The binary logistic regression equation was used to analyze the risk factors of MDR/RR-TB with peripheral blood CD4+T lymphocyte reduction. Results　In total, 311 cases with MDR/RR-TB were enrolled, with a male-to-female ratio of 1.68∶1. The median age [M(P25, P75)] was 32 (24, 45) years. The median CD4+T lymphocyte count was 492.0 (328.0, 661.0) cells/μL, and 115 patients had CD4+T lymphocyte counts <414 cells/μL. Compared with the normal group, the proportion of older patients, male, baseline anemia, baseline leukopenia, baseline hypoalbuminemia, combined with other chronic respiratory diseases, hematogenous disseminated pulmonary tuberculosis, tuberculous pleurisy, and tuberculous meningitis were higher (P<0.05), while the success rate of treatment was lower in the decreased group (P=0.024). Being male (OR=2.045, 95%CI : 1.147-3.648), older age (OR=1.032, 95%CI : 1.012-1.052), baseline anemia (OR=2.246, 5%CI : 1.457-3.426), and baseline leukopenia (OR=2.398, 95%CI : 1.387-4.148) were risk factors for decreased CD4+T lymphocyte count in MDR/RR-TB patients. Conclusions　MDR/RR-TB patients with decreased CD4+T lymphocytes are more likely to suffer from severe tuberculosis (hematogenic disseminated tuberculosis, tuberculous meningitis) and tuberculous pleurisy, meanwhile the success rate of treatment was lower. Male, elder age, baseline anemia, and baseline leukopenia are associated with decreased CD4+T lymphocyte count in MDR/RR-TB patients, and the immune status of these patients needs to be paid attention to in clinical work.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Objective To retrieve and extract the best evidence for preventing intracranial infections related to ex-ternal cerebrospinal fluid(CSF)drainage,and provide evidence-based support for reducing the incidence of intracra-nial infection caused by external CSF drainage.Methods Evidence-based care issues were determined according to PIPOST,and the best evidence on intracranial infection related to external CSF drainage tube was retrieved from top to bottom.The literature retrieval period was 2013-2023.Quality control of the literatures,as well as extraction and summary of the evidence were carried out by 2 trained graduate students.Results A total of 17 literatures were included in the analysis,including 3 guidelines,5 expert consensus,8 systematic reviews,and 1 randomized con-trolled trial.Management strategies from 3 dimensions(pre-catheterization,in-catheterization and post-catheteriza-tion)were obtained,including 20 pieces of evidence for preventing intracranial infection,such as preparation for ex-ternal CSF drainage tube,precautions during catheterization,and post-catheterization disposal.Conclusion There are differences in the management of external CSF drainage tube in clinical practice.It is necessary to develop uni-fied,standardized,and rational bundle strategies to prevent intracranial infection,so as to reduce the incidence of catheter-related intracranial infection.

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Objective To investigate the clinical efficacy of Xuanfei Tongluo Pingchuan Decoction in treating patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and to explore its regulatory mechanism on immune function and inflammatory response.Methods A retrospective study was conducted in 122 patients with AECOPD of phlegm-stasis obstructing lung type,and the patients were divided into an observation group and a control group according to the therapy,with 61 patients in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xuanfei Tongluo Pingchuan Decoction on the basis of treatment for the control group.The treatment lasted for 14 days.Before and after treatment,the patients of the two groups were observed in the changes of pulmonary function indicators,6-minute walking distance(6MWD),COPD Assessment Test(CAT)scores,immune function indicators,and serum inflammatory factors.After treatment,the clinical efficacy and the overall occurrence rate of the adverse reactions were compared between the two groups.Results(1)After 14 days of treatment,the total effective rate of the observation group was 95.08%(58/61),and that of the control group was 77.05%(47/61).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,pulmonary function indexes such as the forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and peak expiratory flow(PEF)of the two groups were significantly improved compared with those before treatment(P＜0.05),and the effect on improving all pulmonary function indexes in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the 6MWD of the two groups were significantly higher(P＜0.05)and the CAT scores were significantly lower than those before treatment(P＜0.05),and the observation group was significantly superior to the control group in terms of improving the 6MWD and decreasing CAT scores(P＜0.01).(4)After treatment,the levels of immune function indicators of T lymphocyte subsets CD4+ and CD4+/CD8+ in the two groups were significantly higher than those before treatment(P＜0.05),and CD8+ level was significantly lower than that before treatment(P＜0.05),and the observation group had stronger effect on increasing T lymphocyte subsets CD4+ and CD4+/CD8+ levels and on decreasing CD8+ level than the control group(P＜0.01).(5)After treatment,the serum levels of inflammatory factors C-reactive protein(CRP)and tumor necrosis factor alpha(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the levels of serum CRP and TNF-α in the observation group was significantly superior to that in the control group(P＜0.01).(6)During the trial,the total incidence of adverse reactions in the observation group was 3.28%(2/61)and that in the control group was 6.56%(4/61),and the intergroup comparison showed that the difference was not statistically significant between the two groups(P＞0.05).Conclusion Xuanfei Tongluo Pingchuan Decoction can effectively alleviate the symptoms of cough and expectoration in AECOPD patients,improve the lung function and immune function,and reduce the inflammatory response.During the treatment,no obvious adverse reactions occur and the therapy is safe and effective.