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 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:Utilizing a seven-year panel data set of a targeted admission medical student cohort,this study aims to examine their career development and provide insights for retaining healthcare talent in township health centers and village clinics in the central and western rural areas of China.Method:Starting from 2015,cohorts of targeted and general clinical graduates from four medical colleges in central and western China were selected and tracked for their career progression.Results:The targeted graduates'standardized residency training and medical licensing examination pass rates were similar to those of general clinical graduates.They advanced more quickly in professional titles and positions,with 82.5%becoming attending physicians and 16.2%obtaining positions in the seventh year after graduation.However,their monthly income was significantly lower than that of general clinical graduates,and this income discrepancy expanded annually.As of December 2022,among the 493 targeted graduates who completed their contracts,38.5%stayed in grassroots positions.Of those who left,60%moved to county-level or higher public hospitals,7.9%pursued further studies,and 27.7%were unemployed.Conclusion:Targeted graduates are well-trained and advance rapidly in their careers,but their lower income significantly impacts their willingness to remain at the grassroots level.After completing their service period,about one-third of the targeted graduates choose to stay in grassroots positions.

Based on the species-specific peptides of Pheretima and its common counterfeit (Metaphire magna), an identification method was established using ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) for quality evaluation of Pheretima and its preparations. Separation was performed on a CORTECS T3 C18 column with 0.1% formic acid and acetonitrile as the mobile phases. Mass spectrometry with multiple reaction monitoring (MRM) using ESI⁺ mode was used to simultaneously monitor three ion pairs. The results indicated that the method was specific and could distinguish Guang Dilong, Hu Dilong, and M. magna, which were consistent with those of DNA barcode identification. The adulteration test showed that the LOD of peptide M was 1 μg·g^-1. Peptide M could be detected when 1% M. magna was added to Guang Dilong, indicating the high sensitivity of the method. Fifty-four batches of commercially available samples contained 35% Guang Dilong, 35% Hu Dilong, and 15% M. magna. No ions were detected in 15% of the samples, and DNA barcode identification revealed that they were mainly from Amynthas, with similar appearance to Hu Dilong. The analysis results of the formulation showed that no peptide ions were detected in 3 batches of Xiaohuoluo pills (3/6) and M. magna were detected in 2 batches of Shenjindan capsules (2/4). The developed method in the study has good specificity, sensitivity, and feasibility, and could be used for quality control of Pheretima and its related preparations. It is of great significance for improving quality standards and regulating the medicinal market of Pheretima.

Objective To explore the application value of Xuanbai Chengqi Decoction combined with enteral nutrition support in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)guided by the theory of simultaneous treatment of lung and intestine.Methods A total of 92 patients with AECOPD were randomly divided into an observation group and a control group,46 cases in each group.Both groups were given routine symptomatic treatment.In addition,the control group was given enteral nutrition support intervention,and the observation group was given Xuanbai Chengqi Decoction combined with enteral nutrition support intervention.The course of treatment lasted for two weeks.The changes in the nutritional parameters such as serum albumin(ALB),prealbumin(PA),and transferrin(TF),and in the distribution of intestinal flora of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)After two weeks of treatment,the total effective rate of the observation group was 97.83％(45/46),and that of the control group was 82.61％(38/46).The comparison between the two groups(tested by chi-square test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the serum levels of nutritional parameters of ALB,PA and TF in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of serum ALB,PA and TF levels in the observation group was significantly superior to that in the control group,the differences being statistically significant(P＜0.05 or P＜0.01).(3)After treatment,the number of Lactobacillus and Bifidobacterium strains of intestinal flora in the two groups was significantly higher than that before treatment(P＜0.05),and the number of Enterococcus strain was significantly lower than that before treatment(P＜0.05).The increase in the number of Lactobacillus and Bifidobacterium strains and the decrease in the number of Enterococcus strains in the observation group were significantly superior to those in the control group,and the differences were statistically significant(P＜0.05 or P＜0.01).(4)The incidence of adverse reactions in the observation group was 4.35％(2/46),which was significantly lower than that in the control group(19.57％,9/46).The difference between the two groups was statistically significant(P＜0.05).Conclusion Significant clinical efficacy has been achieved after the application of Xuanbai Chengqi Decoction combined with enteral nutrition support in treating AECOPD patients with lung heat and bowel excess syndrome guided by the theory of simultaneous treatment of lung and intestine.The combined therapy is effective on improving the nutritional status and intestinal flora imbalance of patients,and reducing the incidence of adverse reactions.

A target screening methodology was developed for detection of 63 kinds of chemical hazards substances,including 17 kinds of flame retardants,14 kinds of perfluorinated compounds,15 kinds of phthalate esters,5 kinds of fluorescent whitening agents and 12 kinds of ultraviolet absorbers,in various types of face masks using ultra high performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry based on an in-house database and mass spectral library.And the quantification was achieved using the external standard method.The results showed that the linear correlation coefficient(r)of all compounds was greater than 0.99,the limits of detection(LODs)ranged from 3.3 to 26.7 μg/kg(S/N=3),the limits of quantification(LOQs)ranged from 10.0 to 80.0 μg/kg(S/N=10),the average recoveries(n=6)were 72.3%-102.6%,and the relative standard deviations(RSDs)were 0.8%-9.9%.The validation of the screening results from both the database and mass spectral library was conducted,and benzophenone and dibutyl phthalate were detected from three positive samples.The human health exposure assessment of the inhalation exposure doses based on the relevant exposure models showed that the contents of benzophenone and dibutyl phthalate were within the recommended reference doses.The method represented a valuable technical reference for ensuring the quality and safety of face mask products and protecting consumer health.

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 evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

italic>Ardisia crispa (Thunb.) A. DC. is a traditional Miao medicinal herb with significant therapeutic effects in the treatment of sore throat, tonsillitis, edema of nephritis and bruising and rheumatism, etc. Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii are varieties of A. crispa. A. crispa var. amplifolia and A. crispa var. dielsii are controversial in terms of species evolutionary relationships and taxonomic identification. In this study, we sequenced the whole genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii chloroplasts using Illumina platform, assembled, annotated and characterized them, compared the structural features and degree of variation among chloroplast genomes using bioinformatics methods, and also downloaded constructing phylogenetic trees to analyze the phylogenetic relationships of chloroplasts in Primulaceae and Myrsinaceae using whole genome sequence information. The results showed that the complete chloroplast genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii were 156 749 bp and 156 748 bp in length, with 132 genes annotated, including 87 protein-coding genes; the codon preference of A/U was greater than that of G/C; The differences in the coding regions of rps15 and rpoB genes in the comparative genome analysis can be used as loci for molecular identification of the two species; the differences in the coding regions of ycf1, ycf2, rpoC1, ycf3, petD and rpl16 genes in the chloroplast genome compared with those of the same genus can be used as loci for identification of the genus. In the phylogenetic results, A. crispa var. amplifolia and A. crispa var. dielsii were clustered together with 100% support, indicating that they are closely related. In this research, we analyzed the chloroplast genome structure and phylogenetic relationships of A. crispa var. amplifolia and A. crispa var. dielsii, providing an important theoretical basis for their molecular identification, genetic variation, breeding and phylogenetic analysis.