OBJECTIVE: To explore the changes of CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) and programmed death-ligand 1 (PD-L1) expression in gastric mucosal epithelial cells after Helicobacter pylori infection and the regulation of CMTM6 on PD-L1, and to analyze the mRNA expression differences before and after CMTM6 gene knock-out in helicobacter pylori infected gastric epithelial cells by microarray analysis. METHODS: The standard Helicobacter pylori strain ATCC 26695 was co-cultured with human gastric epithelial cell GES-1 for 6, 24 and 48 hours, and the mRNA and protein levels of CMTM6 and PD-L1 were detected by real-time quantitative PCR and Western blot. Using CRISPR/Cas9 to construct CMTM6 gene knockout plasmid and knockout CMTM6 gene of GES-1 cells. Helicobacter pylori was co-cultured with CMTM6 gene knockout and wild type GES-1 cells for 48 hours to detect PD-L1 transcription and protein level changes, and CMTM6 gene knockout GES-1 cells were treated with the proteasome inhibitor MG-132 to detect the changes in PD-L1 protein levels. Agilent Human ceRNA Microarray 2019 was used to detect the differentially expressed genes in CMTM6 gene knockout and wild-type GES-1 cells co-cultured with Hp for 48 hours, and the signal pathway of differentially expressed genes enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: The mRNA and protein levels of CMTM6 and PD-L1 in GES-1 cells were significantly up-regulated after Helicobacter pylori infection, and CMTM6 mRNA was most significantly up-regulated 48 hours after infection. After CMTM6 gene knockout, the CD274 gene transcription level of Helicobacter pylori infected GES-1 cells did not change significantly, but PD-L1 protein level was significantly down-regulated, and the PD-L1 level increased after the application of proteasome inhibitor MG-132. After CMTM6 gene knockout, 67 genes had more than two times of differential expression. The transcription levels of TMEM68, FERMT3, GPR142, ATP6V1FNB, NOV, UBE2S and other genes were significantly down-regulated. The transcription levels of PCDHGA6, CAMKMT, PDIA2, NTRK3, SPOCK1 and other genes were significantly up-regulated. After CMTM6 gene knockout, ubiquitin-conjugating enzyme E2S (UBE2S) gene expression was significantly down-regulated, which might affect protein ubiquitination degradation. After CMTM6 gene knockout, adrenoceptor alpha 1B (ADRA1B), cholinergic receptor muscarinic 1 (M1), CHRM1, platelet activating factor receptor (PTAFR) gene expression was significantly up-regulated. CONCLUSION Helicobacter pylori infection up-regulates the expression level of CMTM6 in gastric mucosa cells, and CMTM6 can stabilize PD-L1 and maintain the protein level of PD-L1. CMTM6 gene knockout may affect biological behaviors such as protein ubiquitination and cell surface receptor expression.
Humans ; MARVEL Domain-Containing Proteins/metabolism* ; Helicobacter pylori/physiology* ; B7-H1 Antigen/genetics* ; Helicobacter Infections/metabolism* ; Epithelial Cells/metabolism* ; Gastric Mucosa/metabolism* ; Chemokines/metabolism* ; Cell Line ; Gene Knockout Techniques ; Myelin Proteins

ObjectiveTo investigate the role and potential mechanism of microRNA-544 （miRNA-544） in lipopolysaccharide （LPS）-induced liver injury in mice with sepsis， and to provide a new target for the treatment of liver injury in sepsis. MethodsA total of 40 C57BL/6J mice were randomly divided into control group （intraperitoneal injection of normal saline）， model group （intraperitoneal injection of LPS at a dose of 5 mg/kg）， agonist group （intraperitoneal injection of LPS and miR-544 agonist at a dose of 5 mg/kg）， and miR-544 inhibitor group （intraperitoneal injection of LPS and miR-544 inhibitor at a dose of 5 mg/kg）， with 10 mice in each group. An automatic biochemical analyzer was used to measure the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBil） in serum and the liver； Western blot was used to measure the expression levels of monocyte chemotactic protein-1 （MCP-1）， CD16/32， and proteins associated with the NF-κB signaling pathway in the liver； q-PCR and ELISA were used to measure the expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in serum. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group of LPS-induced sepsis had a significant reduction in the expression level of miR-544 in serum and liver tissue （P0.01）， significant pathological changes of the liver （such as inflammatory cell infiltration and central vein congestion）， and significant increases in the levels of liver injury markers （ALT， AST， and TBil） in serum and the liver （all P0.001）， the expression levels of inflammatory factors （MCP-1， CD16/32， TNF-α， IL-6， and IL-1β） （all P0.01）， and the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-NF-κ， and p-p65） （all P0.01）. Compared with the model group， the miR-544 inhibitor group had a significant reduction in the expression level of miR-544 in serum and liver tissue （P0.01）， aggravated pathological changes of the liver， and significant increases in the levels of liver injury markers and inflammatory factors （ALT， AST， TBil， MCP-1， CD16/32， TNF-α， IL-6， and IL-1） （all P0.05）， as well as significant increases in the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-κB-α， and p-p65） （all P0.01）. On the contrary， the miR-544 agonist group had a significant increase in the expression level of miR-544 in serum and liver tissue （P0.01）， significant alleviation of liver pathological changes， and significant reductions in the levels of liver injury markers and inflammatory factors （ALT， AST， TBil， MCP-1， CD16/32， TNF-α， IL-6， and IL-1β） （all P0.05）， as well as significant reductions in the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-κB-α， and p-p65） （all P0.05）. ConclusionThis study shows that miR-544 can alleviate LPS-induced liver injury in mice with sepsis by inhibiting the expression of inflammatory-related proteins and the activation of the NF-κB signaling pathway.

Gastric cancer (GC) is a globally prevalent malignancy with a particularly heavy burden in China. Helicobacter pylori ( H. pylori ) is a Group I carcinogen for GC, with a higher seroprevalence rate indicating a higher GC incidence. However, only approximately 3% of the individuals with H. pylori infection eventually develop GC, and about 2.6% still progress to GC even 10-20 years after the eradication of H. pylori . Thus, the pathogenic mechanism of H. pylori for GC must be elucidated, and high-risk individuals precisely identified. Furthermore, GC can occur even in individuals who have never been infected with H. pylori . As H. pylori infection rates decline, the proportion of H. pylori -negative GC cases is increasing annually, gaining significant research attention. In this review, potential pathogenic mechanisms of H. pylori infection are explored from the aspects of H. pylori virulence factors and host factors (genetic susceptibility and immune microenvironment). Possible risk factors for H. pylori -negative GC include infections by other microorganisms (e.g., bacteria, fungi, and viruses), autoimmune gastritis, bile reflux, genetic mutations, and environmental factors. We aim to review the potential mechanisms for GC with varying H. pylori infection statuses, identify the high-risk individuals, and pose questions that need to be addressed. In the future, as the prevalence of H. pylori infection gradually decreases, GC prevention and management must evolve to address host-specific factors and the growing challenge of H. pylori -negative GC by integrating multidisciplinary perspectives.
Stomach Neoplasms/genetics* ; Humans ; Helicobacter Infections/complications* ; Helicobacter pylori/pathogenicity* ; Risk Factors

Objective:To explore and evaluate the optimization and application of case-based learning (CBL) in the reform practice for integrated curriculum of the digestive system.Methods:The 174 undergraduate students majoring in eight-year clinical medicine enrolled in 2019 at the Peking University Health Science Center were selected as research objects. CBL was used in the integration and optimization of the digestive system curriculum. These included increasing class hours, selecting disease modules, lesson preparation involving multi-disciplinary teachers, and joint teaching. Upon completion of teaching, a comprehensive evaluation of teaching effectiveness was conducted through questionnaires administrated to teachers and students, feedback from supervision experts, and scores of students. SPSS 21.0 was used for the t-test and a reliability analysis was conducted on the questionnaire results. Results:Teachers, students, and supervision experts were highly satisfied with CBL. More than 95% of teachers believed that joint teaching facilitated the sharing of diverse professional knowledge among teachers, enhanced the in-depth instruction of imaging knowledge, promoted the transformation of teaching ideas, and improved teaching ability. More than 70% of students agreed that joint teaching deepened their understanding of diseases, stimulated learning interest, and established a theoretical foundation for clinical practice. The average score of class performance was (47.60±2.41) points (a total score of 50 points). The answers of students to case-based questions in final exams were satisfactory. The average score of final evaluation was (82.24±8.82) points.Conclusions:The optimization and application of CBL in the integrated curriculum of the digestive system is highly accepted by teachers and students. This method improves the interest of learning and facilitates the establishment of overall medical thinking and clinical thinking in students.

Rheumatoid arthritis is an autoim-mune disease characterized by progressive bone destruction,with joint swelling caused by synovial inflammation in the early stage,and joint deformi-ty caused by cartilage and bone destruction occur-ring in the middle and late stages as inflammation develops,resulting in a 75％disability and deformi-ty rate within three years,and the prevention and treatment of RA bone and joint destruction is of ur-gency,and it is therefore of great significance to search for effective drugs to treat RA bone destruc-tion.Studies have shown that wrinkled skin papaya can treat RA bone destruction,but the composition and mechanism of action are unknown,so this re-view aims to provide an overview of the mecha-nism of action of the effective active ingredients in wrinkled skin papaya for the treatment of rheuma-toid arthritis bone destruction,and to provide a ba-sis and direction for the development of novel for-mulations of traditional Chinese medicines for anti-RA bone destruction.

Objective:To evaluate the efficacy of dexmedetomidine-scalp nerve block (SNB) combined with general anesthesia in the patients with acute traumatic brain injury (TBI) undergoing craniotomy.Methods:In this randomized controlled trial, 74 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex with acute TBI, aged 30-78 yr, with body mass index of 18-30 kg/m 2, underwent craniotomy for hematoma evacuation combined with decompressive craniectomy at the Traditional Chinese Medicine Hospital of Kunshan from January to December 2024, of the Glasgow Coma Scale score 8-12, were selected and divided into 2 groups ( n=37 each) using a random number table method: dexmedetomidine combined with ultrasound-guided SNB group (DS group) and ultrasound-guided SNB group (S group). Before anesthesia, dexmedetomidine was infused as a loading dose of 1 μg/kg over 10 min followed by an infusion of 0.3 μg·kg -1·h -1 until the end of operation. Ultrasound-guided SNB was performed after completion of intubation in both groups. The consumption of intraoperative fentanyl, propofol and remifentanil and the usage of vasoactive drugs were recorded. Before surgery (T 0), at 1 h after the start of surgery (T 1) and at the end of surgery (T 2), blood samples from the jugular bulbar and radial artery were collected, the jugular venous oxygen saturation was recorded, the arteriovenous oxygen content and cerebral oxygen uptake rate were calculated, and the occurrence of postoperative complications was also recorded. Results:Compared with group S, the consumption of fentanyl, propofol and remifentanil was significantly reduced, the usage rate of vasoactive drugs was decreased, the arteriovenous oxygen content and cerebral oxygen uptake rate were decreased at T 1 and T 2, the jugular venous oxygen saturation was increased, and the incidence of postoperative agitation was decreased in group DS ( P<0.05). Conclusions:Dexmedetomidine-SNB combined with general anesthesia can optimize the analgesic effect, improve cerebral oxygen supply and demand, reduce the occurrence of postoperative agitation when used in patients with acute TBI undergoing craniotomy.

Rheumatoid arthritis is an autoim-mune disease characterized by progressive bone destruction,with joint swelling caused by synovial inflammation in the early stage,and joint deformi-ty caused by cartilage and bone destruction occur-ring in the middle and late stages as inflammation develops,resulting in a 75％disability and deformi-ty rate within three years,and the prevention and treatment of RA bone and joint destruction is of ur-gency,and it is therefore of great significance to search for effective drugs to treat RA bone destruc-tion.Studies have shown that wrinkled skin papaya can treat RA bone destruction,but the composition and mechanism of action are unknown,so this re-view aims to provide an overview of the mecha-nism of action of the effective active ingredients in wrinkled skin papaya for the treatment of rheuma-toid arthritis bone destruction,and to provide a ba-sis and direction for the development of novel for-mulations of traditional Chinese medicines for anti-RA bone destruction.

Objective:To investigate the effect of ultrasound-guided scalp nerve block (SNB) combined with dexmedetomidine on cerebral blood flow after craniotomy in patients with acute traumatic brain injury (TBI).Methods:A randomized controlled design was conducted. Patients aged 25-65 years, with ASA physical status I–III and Glasgow Coma Scale scores of 9-12, who underwent craniotomy for acute TBI at Kunshan Traditional Chinese Medicine Hospital between January 2024 and February 2025 were selected. Patients with unstable vital signs, cranial tumors, cardiovascular diseases, local anesthetic allergies, or infections at the puncture site were excluded. Using a random number table, patients were divided into two groups: the ultrasound-guided SNB combined with dexmedetomidine group (SD group) and the dexmedetomidine-alone group (D group). General clinical data, peak systolic velocity (PSV), mean blood flow velocity (MBFV), intracranial pressure (ICP), S100 calcium-binding protein beta (S-100β protein), neuron-specific enolase (NSE) levels, and postoperative complications were compared. Dynamic changes in PSV and MBFV were analyzed using repeated measures analysis of variance, while inter-group comparisons used independent sample t-tests. Results:A total of 79 patients were included, with 40 in the SD group and 39 in the D group. There were no significant differences in general clinical data between the two groups (all P>0.05). In the D group, PSV and MBFV at T 1 and T 2 were significantly higher than at T0 [(125.04±20.43) cm/s vs. (126.83±21.76) cm/s vs. (110.63±18.49) cm/s, P=0.001; (61.75±8.34) cm/s vs. (62.81±8.54) cm/s vs. (57.82±6.93) cm/s, P=0.017], whereas no significant differences were observed in the SD group (all P>0.05). PSV, MBFV, ICP, S-100β protein, and NSE levels at T1 and T2 in the SD group were lower than those in the D group (all P<0.05). The incidence of postoperative hypertension, agitation, and the use rate of vasoactive drugs were also lower in the SD group compared to the D group (all P<0.05). Conclusion:The application of ultrasound-guided SNB combined with dexmedetomidine in TBI patients after craniotomy can help stabilize cerebral blood flow and ICP, mitigate neuronal injury, and reduce the incidence of postoperative complications.

Objective:To investigate the endoscopic and pathological characteristics of metachronous early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) for EGC.Methods:Data of 451 consecutive EGC patients treated with ESD at the Department of Gastroenterology, Peking University Third Hospital between 1 January, 2005 and 31 December, 2022 were retrospectively collected, of which 252 patients who met the criteria and had endoscopic follow-up ≥ 1 year were enrolled in the retrospective dynamic cohort. Multivariate Cox regression analysis was used to identify independent risk factors for metachronous EGC after ESD. Pearson's contingency coefficient was applied to analyze endoscopic correlation between the index and metachronous lesions. T-test, χ2 test, and Fisher exact test were used to compare endoscopic pathological features between index and metachronous lesions, the proportion of lesions meeting absolute ESD indication and their maximum diameters between patients undergoing annual vs bi-annual follow-up. Kaplan-Meier analysis assessed the cumulative incidence of metachronous EGC. Results:During a median follow-up of 40 months, 26 patients [10.3% (26/252)] developed metachronous EGC, with a mean interval of 43.9 months. Multivariate Cox regression identified the independent risk factors of index lesions including location in the middle third of the stomach ( HR=3.783, 95% CI: 1.300-11.011, P=0.015), in the anterior wall ( HR=3.934, 95% CI: 1.113-13.904, P=0.033), and the maximum diameter <15 mm ( HR=3.034, 95% CI: 1.074-8.571, P=0.036). Pearson's contingency coefficient showed no significant concordance between index and metachronous lesions for vertical location (C=0.375, P=0.372), horizontal location (C=0.508, P=0.434), gross morphology (C=0.287, P=0.675), or ulcer presence (C=0.194, P=0.313). Compared to index lesions, metachronous lesions were more frequently located on the posterior wall (lesser curvature/greater curvature/anterior wall/posterior wall: 11/2/1/12 VS 96/49/46/61, P=0.031), more often differentiated (differentiated/undifferentiated: 26/0 VS 214/38, P=0.032), and smaller in maximum diameter (8.08±5.99 mm VS 13.95±10.26 mm, t=4.383, P<0.001). No significant differences were observed between patients undergoing annual vs bi-annual follow-up in the proportion of metachronous lesions meeting absolute ESD indication (14/16 VS 9/9, P=0.520) or in maximum diameter (8.11±6.94 mm VS 6.67±4.35 mm, t=-0.275, P=0.535). The cumulative incidence curve of metachronous EGC plateaued after 10 years. Conclusion:Patients with EGC located in the middle third of the stomach, in the anterior wall, or of smaller diameter need intensive endoscopic surveillance after ESD. Posterior wall deserves particular attention during follow-up, with annual endoscopy recommended for at least 10 years post-ESD.

Objective:To evaluate the efficacy of dexmedetomidine-scalp nerve block (SNB) combined with general anesthesia in the patients with acute traumatic brain injury (TBI) undergoing craniotomy.Methods:In this randomized controlled trial, 74 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex with acute TBI, aged 30-78 yr, with body mass index of 18-30 kg/m 2, underwent craniotomy for hematoma evacuation combined with decompressive craniectomy at the Traditional Chinese Medicine Hospital of Kunshan from January to December 2024, of the Glasgow Coma Scale score 8-12, were selected and divided into 2 groups ( n=37 each) using a random number table method: dexmedetomidine combined with ultrasound-guided SNB group (DS group) and ultrasound-guided SNB group (S group). Before anesthesia, dexmedetomidine was infused as a loading dose of 1 μg/kg over 10 min followed by an infusion of 0.3 μg·kg -1·h -1 until the end of operation. Ultrasound-guided SNB was performed after completion of intubation in both groups. The consumption of intraoperative fentanyl, propofol and remifentanil and the usage of vasoactive drugs were recorded. Before surgery (T 0), at 1 h after the start of surgery (T 1) and at the end of surgery (T 2), blood samples from the jugular bulbar and radial artery were collected, the jugular venous oxygen saturation was recorded, the arteriovenous oxygen content and cerebral oxygen uptake rate were calculated, and the occurrence of postoperative complications was also recorded. Results:Compared with group S, the consumption of fentanyl, propofol and remifentanil was significantly reduced, the usage rate of vasoactive drugs was decreased, the arteriovenous oxygen content and cerebral oxygen uptake rate were decreased at T 1 and T 2, the jugular venous oxygen saturation was increased, and the incidence of postoperative agitation was decreased in group DS ( P<0.05). Conclusions:Dexmedetomidine-SNB combined with general anesthesia can optimize the analgesic effect, improve cerebral oxygen supply and demand, reduce the occurrence of postoperative agitation when used in patients with acute TBI undergoing craniotomy.