OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） as first-line therapy for advanced gastric cancer. METHODS PubMed， Web of Science， Embase， The Cochrane Library， Wanfang Data， CNKI， and VIP databases were searched to collect phase Ⅲ clinical randomized controlled trials （RCTs） on ICIs as first-line therapy for advanced gastric cancer， as well as abstracts from relevant oncology academic conferences. The search period spanned from database inception to June 1， 2025. After screening literature， extracting data， and assessing quality， a network meta-analysis was performed using R software version 4.3.2. RESULTS A total of 8 studies involving 7 801 patients were included. Network meta-analysis results showed that， in terms of efficacy， compared with chemotherapy （Chemo）， SHR-1701_Chemo， Cadonilimab_Chemo， Sintilimab_Chemo， Pembrolizumab_Chemo， and Tislelizumab_Chemo significantly prolonged median overall survival （OS） and median progression free survival （PFS） in patients （P＜0.05）； whereas Nivolumab_Chemo only significantly improved median PFS （P＜0.05）. Surface under the cumulative ranking curve （SUCRA） results indicated that the top 2 interventions for median OS were SHR-1701_Chemo and Cadonilimab_Chemo； for PFS， the top 2 were Cadonilimab_Chemo and SHR-1701_Chemo. For patients with combined positive score （CPS） ≥5 points for programmed death-ligand 1 （PD-L1）， Cadonilimab_Chemo and SHR- 1701_Chemo also demonstrated the optimal OS and PFS benefits （P＜0.05）. Regarding safety， there were no statistically significant differences among the interventions in the incidence of any adverse events （AEs） or grade ≥3 AEs （P＞0.05）. The SUCRA ranking for the incidence of any AEs showed the top 2 were SHR-1701_Chemo and Chemo； for grade ≥3 AEs， the top 2 were Chemo and Sugemalimab_Chemo. CONCLUSIONS For patients with advanced gastric cancer， Cadonilimab_Chemo and SHR-1701_Chemo demonstrate the best benefits in terms of OS and PFS， with their advantages remaining clear in patients with PD-L1 CPS≥5 points. In terms of safety， the risk of developing any AEs and grade ≥3 AEs is relatively lowest with Chemo.

Objective: To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis. Methods: Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting. Results: There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05). Conclusion The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.

This paper summarizes Professor ZHAI Shuangqing's clinical experience in using metal and mineral medicines to treat mental disorders. Based on xiang thinking， the symptoms of mental disorders are classified into five categories， depression-xiang， wind-xiang， fire-xiang， phlegm-xiang， and deficiency-xiang， and the mechanisms of disease development are discussed accordingly. Metal and mineral medicines are key treatments for mental disorders， not only having the function of calming the mind but also promoting qi， stabilizing wind， expelling evil， and tonifying. In clinical practice， the emphasis is placed on harmonizing the disease and its symptoms. Based on self-developed prescription formulas， the appropriate metal and mineral medicines are selected according to the properties， flavors， meridian tropism， and actions of the medicines， as well as the xiang patterns of the mental disorder. For example， Attention Deficit Hyperactivity Disorder （ADHD） is treated by Modified Xiehuang Powder （泻黄散） with Sijunzi Decoction （四君子汤） and adding Fulonggan （Testudinis Carapax） and Longgu （Os Draconis）. Persistent insomnia is treated by combining a self-developed insomnia formula with Longgu （Os Draconis）， Hupo （Succinum）， and Cishi （Magnetitum）. Obsessive-compulsive disorder （OCD） is treated by combining a self-developed OCD formula with Longchi （Dens Draconis）， Qingmengshi （Fluoritum）， and Zheshi （Haematitum）. Epilepsy is treated by combining an anti-epilepsy decoction with Qingmengshi （Fluoritum）， Longchi （Dens Draconis）， and Shengtieluo （Ferrum Rudis）.

OBJECTIVE To establish a interview outline design process and quality control evaluation method based on grounded theory， providing ideas for qualitative research interview outline design in medical fields. METHODS A literature review was conducted to understand the current research status； a preliminary interview outline was developed around the research content. The triangulation method， group evaluation， expert review and pre-interview were adopted to execute the interview outline and conduct quality control. The evaluation indicators and target values were formulated （an average score for the overall quality evaluation of all indicators ≥4.5， and an average score for individual indicators ≥4.00） to evaluate the effect of the interview outline. Taking the research on the mechanism of physicians’ prescribing behavior under the background of Diagnosis Related Groups （DRGs） payment as an example， the methodological contents of above interview outline were applied in practical research. RESULTS The interview outline included basic information and interview questions. The interview questions were divided into three parts：influencing factors survey， promoting and hindering factors of standardizing physician prescription behavior， and communication， with a total of 12 questions. After being reviewed by members of the research group， experts review and pre- interview， a total of 9 people participated in the quality control evaluation of the interview outline. The overall evaluation score was 4.94 （＞4.50）， and the average score of each indicator was greater than 4.00， indicating that the quality of the outline met the requirements for the interview and could be used for the formal interview. CONCLUSIONS The established interview outline design and quality control method based on grounded theory provides ideas for the qualitative research interview outline design in the medical field， and lays the foundation for further using grounded theory to study the influencing factors and mechanisms of physician prescription behavior under the DRG background.

A wealth of prior studies has confirmed that intratumoral microbiota can survive within tumor tissue, thereby promoting or inhibiting tumor growth. With the development of high-throughput sequencing and metabolomics, increasing attention has been paid to the correlation between intratumoral microbiota and host metabolism, and their effect on tumorigenesis and progression. This review focuses on the interaction between intratumoral microbiota and tumor metabolism. It emphasizes the effects of intratumoral microbiota on tumor sugar, lipid, and amino acid metabolism and explores emerging therapeutic strategies for guiding tumor prevention and treatment by modulating tumor metabolism. Although the specific role of intratumoral microbiota in tumor metabolism remains to be further studied, a deepened understanding of the interaction between tumor-specific microbiota and tumor metabolism may provide new directions and application prospects for tumor prevention and treatment.

Objective To explore the potential causality between visceral adipose tissue (VAT) and inflammatory bowel disease, peptic ulcer disease, irritable bowel syndrome and gastroesophageal reflux disease. Methods Two-sample Mendelian randomization (MR) investigations were carried out, employing genetic variants closely linked with VAT as instrumental variables. The summary data for aforementioned gastrointestinal disorders were obtained from the genome-wide association study (GWAS) in UK biobank and Finn Gen databases, respectively. The inverse variance-weighted method (IVW) was employed as the primary analytical method, bolstered by a sequence of sensitivity analyses to verify the robustness of MR. Subsequently, a meta-analysis was conducted to amalgamate the findings derived from both databases. Results This study included a total of 42 single nucleotide polymorphisms that were strongly associated with visceral adipose tissue as instrumental variables. Statistically significant correlations were found between VAT and peptic ulcer (OR=1.17, 95% CI: 1.08-1.27, P < 0.01), gastroesophageal reflux disease (OR=1.10, 95% CI: 1.03-1.18, P = 0.02), and irritable bowel syndrome (OR=1.12, 95% CI: 1.04-1.12, P = 0.03). There was no statistical significance between VAT and inflammatory bowel disease (OR=0.94, 95% CI: 0.79-1.12, P = 0.65). Conclusion VAT exhibits a causal linkage with peptic ulcer, gastroesophageal reflux disease, and irritable bowel syndrome. Accurately assessing VAT levels via imaging methods, screening individuals at high-risk, and actively controlling abdominal obesity bear important clinical significance.

OBJECTIVE: To observe the efficacy and safety of Tiaowei Jiannao acupuncture (acupuncture for regulating defensive qi and nourishing brain) for post-ischemic stroke insomnia (PISI). METHODS: A total of 96 patients with PISI were randomized into an acupuncture group (32 cases, 1 case was excluded), a medication group (32 cases, 1 case dropped out, 1 case was excluded) and a sham-acupuncture group (32 cases, 1 case dropped out, 1 case was excluded). In the acupuncture group, Tiaowei Jiannao acupuncture was applied at bilateral Shenmai (BL62), Zhaohai (KI6), Hegu (LI4), Taichong (LR3), and Baihui (GV20), Sishencong (EX-HN1), Yintang (GV24⁺), Shenting (GV24), once a day, 1-day interval was taken after 6-day treatment, for 3 weeks totally. In the medication group, eszopiclone tablet was given orally, 1-3 mg a time, once a day for 3 weeks. In the sham-acupuncture group, non-invasive sham acupuncture was applied, the acupoint selection, frequency and course of treatment were the same as the acupuncture group. Before treatment, after 2,3 weeks of treatment, the scores of Pittsburgh sleep quality index (PSQI), self-rating sleep scale (SRSS), National Institutes of Health Stroke scale (NIHSS), Hamilton depression scale-17 (HAMD-17) were observed; before and after treatment, the sleep parameters were recorded using polysomnography (PSG); and the efficacy and safety were evaluated after treatment in the 3 groups. RESULTS: After 2,3 weeks of treatment, the scores of PSQI, HAMD-17 and SRSS in the acupuncture group and the medication group, as well as the SRSS scores in the sham-acupuncture group were decreased compared with those before treatment (P<0.05); after 2 weeks of treatment, the NIHSS score in the acupuncture group was decreased compared with that before treatment (P<0.05); after 3 weeks of treatment, the NIHSS scores in the acupuncture group, the medication group and the sham-acupuncture group were decreased compared with those before treatment (P<0.05). After 3 weeks of treatment, the scores of PSQI, SRSS, HAMD-17 and NIHSS in the acupuncture group and the medication group, as well as the NIHSS score in the sham-acupuncture group were decreased compared with those after 2 weeks of treatment (P<0.05). After 2,3 weeks of treatment, the scores of PSQI, SRSS and HAMD-17 in the acupuncture group and the medication group were lower than those in the sham-acupuncture group (P<0.05), the NIHSS scores in the acupuncture group were lower than those in the medication group and the sham-acupuncture group (P<0.05); after 3 weeks of treatment, HAMD-17 score in the acupuncture group was lower than that in the medication group (P<0.05), the NIHSS score in the medication group was lower than that in the sham-acupuncture group (P<0.05). Compared before treatment, after treatment, the total sleep time was prolonged (P<0.05), the wake after sleep onset, sleep latency, and non-rapid eye movement (NREM) sleep latency were shortened (P<0.05), the sleep efficiency was improved (P<0.05), the number of awakenings was reduced (P<0.05), the percentage of rapid eye movement (REM%) and the percentage of NREM stage 1 (N1%) were decreased (P<0.05), the percentage of NREM stage 2 (N2%) and the percentage of NREM stage 3 (N3%) were increased (P<0.05) in the acupuncture group and the medication group; the sleep latency was shortened in the sham-acupuncture group (P<0.05). After treatment, the PSG indexes in the acupuncture group and the medication group were superior to those in the sham-acupuncture group (P<0.05); in the acupuncture group, the number of awakenings was less than that in the medication group (P<0.05), the REM% and N1% were lower than those in the medication group (P<0.05), the N2% and N3% were higher than those in the medication group (P<0.05). The total effective rate were 93.5% (29/31) and 90.0% (27/30) in the acupuncture group and the medication group respectively, which were higher than 10.0% (3/30) in the sham-acupuncture group (P<0.05). There was no serious adverse events in any of the 3 groups. CONCLUSION Tiaowei Jiannao acupuncture improves the insomnia symptoms in patients with ischemic stroke, improves the quality of sleep, increases the deep sleep, promotes the recovery of neurological function, and relieves the depression. It is effective and safe for the treatment of PISI.
Humans ; Acupuncture Therapy ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Ischemic Stroke/complications* ; Stroke/complications* ; Sleep

Background Coal workers' pneumoconiosis (CWP) is a serious occupational lung disease and one of the prescript occupational diseases in China. Epithelial-mesenchymal transition (EMT) is involved in the diffuse fibrosis of lung tissue of pneumoconiosis patients, and its mechanism may be related to the polarization of macrophages regulated by let-7c. Objective To investigate the effect of let-7c on the regulation of macrophage polarization in EMT in rats induced by coal dust exposure with different content of free SiO₂. Methods SD rats were randomly divided into a control group, a 5% SiO₂ group, a 30% SiO₂ group, and a 99.9% SiO₂ group, with 16 rats in each group. The rats in each group were tracheally titrated with 100 μL of 20 mg·mL⁻¹ suspension (5% SiO₂, 30% SiO₂, and 99.9% SiO₂) or normal saline, respectively. Alveolar lavage fluid was collected at the ends of the 1st month and the 3rd month. The relative expression levels of M1 or M2 markers, CD86 or CD206, in alveolar macrophages (AMs) were detected by immunofluorescence. The inflammation and fibrosis of lung tissue were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), E-cadherin, and vimentin were detected by Western blotting. The expression levels of let-7c and c/EBP-δ genes were detected by real-time fluorescence quantitative PCR. Results The HE and Masson staining results showed that compared with the control group, the degree of pulmonary fibrosis in the 5% SiO₂ group, the 30% SiO₂ group, and the 99.9% SiO₂ group gradually increased with the increase of dust exposure time. Compared with the control group, the expressions of CD86 and CD206 in the 5% SiO₂ group, the 30% SiO₂ group, and the 99.9% SiO₂ group gradually increased at the end of the 1st month (F=330.904, 146.801, P<0.05), and the expression of CD86 in each group decreased gradually at the end of the 3rd month (F=331.781, P<0.05), but the expression of CD206 increased (F=1164.190, P<0.05). At the end of the 1st month, the expressions of TGF-β1 (F=8.847, P<0.05) and vimentin (F=13.275, P<0.05) gradually increased, and the expression of E-cadherin (F=6.253, P<0.05) gradually reduced in the 5% SiO₂ group, the 30% SiO₂ group, and the 99.9% SiO₂ group. At the end of the 3rd month, the expressions of TGF-β1 (F=16.833, P<0.05) and vimentin (F=55.021, P<0.05) increased, and the expression of E-cadherin (F=12.790, P<0.05) gradually decreased in all groups. The PCR results showed that compared with the control group, the expression of let-7c mRNA in the 5% SiO₂ group, the 30% SiO₂ group, and the 99.9% SiO₂ group increased at the ends of the 1st month and the 3rd month (F=11.251, 28.136, P<0.05). The expression of c/EBP-δ mRNA decreased in all groups at the ends of the 1st month and the 3rd month (F=49.204, 177.090, P<0.05). Conclusion In response to dust stimulation, let-7c promotes EMT by modulating macrophage polarization, which is involved in the formation of pulmonary fibrosis and thus influences the progression of CWP .

Objective:To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs.Methods:An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-? t test was used for pairwise comparison. Results:ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2 +/+), heterozygous mutant (ALDH2 +/-), and homozygous mutant (ALDH2 -/-), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P ?

Objective To compare the efficacy and safety of endoscopic ligation treatment and endoscopic tissue glue injection for secondary prevention of gastric variceal bleeding.Methods Patients with cirrhosis and esophagogastric variceal bleeding treated with gastric variceal ligation in Zhongshan Hospital,Fudan University,from January 2017 to December 2019 were screened(ligation group).And during the same period,patients underwent endoscopic cyanoacrylate treatment were also screened(tissue glue group).59 patients were included in the two groups after propensity score matching.Univariate and multivariate Cox proportional hazard regression models were used to anslyze risk factors for re-bleeding.Kaplan-Meier curves were plotted to analyze re-bleeding rate and mortality of the two treatment groups.Results There was no statistically significant difference in the eradication rate of esophagogastric varices between the ligation group and the tissue glue group(83.05％vs 79.66％,P=0.778);the ligation group required fewer median endoscopic treatments for variceal eradication(2 vs 3,P=0.017)and a lower average dosage of cyanoacrylate(0.70 mL vs 2.67 mL,P＜0.001).Multivariate Cox regression analysis showed that portal shunt was a risk factor for esophagogastric varices re-bleeding(HR=3.14,95％CI 1.02-9.68,P=0.046),endoscopic variceal ligation was a protective factor against re-bleeding(HR=0.25,95％CI 0.08-0.71,P=0.010).Compared with endoscopic cyanoacrylate injection,endoscopic ligation treatment did not significantly increase the 2-year risk of esophagogastric variceal re-bleeding(18.69％vs 36.29％,P=0.067)or risk of death(1.69％vs 3.39％,P=1.000);patients with GOV1 type had a significantly lower risk of re-bleeding after endoscopic ligation treatment(0 vs 40.27％,P=0.012)and there was a trend towards a lower re-bleeding risk in patients with GOV2 type after endoscopic ligation treatment(13.27％vs 34.16％,P=0.056).Conclusions Endoscopic ligation treatment has higher eradication rate for esophagogastric varices,and does not increase the risk of re-bleeding,death,or other adverse events.Therefore,it can be considered an effective secondary prevention way for patients with gastric varices.