Objective: To investigate changes in lactate and histone lactylation during senescence of mouse bone marrow mesenchymal stem cells (BMSCs), to clarify the effects of regulating lactate metabolism on the osteogenic differentiation of senescent BMSCs, and to provide theoretical evidence and an experimental basis for metabolic regulatory interventions in aging-related osteoporosis and impaired bone repair. Methods: Approval was obtained from the Institutional Laboratory Animal Ethics Committee. BMSCs were isolated using the whole bone marrow adherence method and surface markers (CD29, CD90, CD11b and CD45) and identified by flow cytometry. A cellular model of BMSCs senescence was established using different concentrations of etoposide (0, 5, 10, 15, and 20 μmol/L). The gene and protein expression levels of senescence-related markers, namely, p53, p21, and p16, were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, and the optimal induction concentration was determined using CCK-8 and SA-β-gal assays. BMSCs were divided into a control group and an etoposide-induced senescence group to examine lactate production and the expression of histone lactylation-related enzymes, including Ldha, Ep300, and Sirt2. Western blot analysis was used to analyze pan-lysine lactylation（Pan-Kla） and histone H3 lysine 18 lactylation （H3K18la). During the lactate production inhibition experiments, BMSCs were divided into three groups: control, senescence group (treated with 10 μmol/L etoposide), and senescence+ GNE-140 group (treated with 10 μmol/L etoposide and 1 μmol/L GNE-140). qRT-PCR, Western blot, and SA-β-gal staining were performed to assess the effects of lactate production inhibition on cellular senescence phenotypes. During osteogenic differentiation, BMSCs were assigned to a control group, senescence group (treated with 10 μmol/L etoposide), senescence+ 5 mmol/L sodium lactate group, and senescence+ 10 mmol/L sodium lactate group. The levels of Pan-Kla and H3K18la were detected by Western blot. The mRNA expressions of runt-related transcription factor 2 (Runx2), transcription factor Sp7 (Sp7) and alkaline phosphatase (Alpl) were detected by qRT-PCR. The protein expressions of collagen type I (COL1), RUNX2, osterix (OSX) and osteocalcin (OCN) were detected by Western blot, and mineralized nodule formation was observed by Alizarin Red S staining. Results: Flow cytometry analysis indicated that the isolated BMSCs highly expressed CD29 (97.3%) and CD90 (95.7%). Etoposide induced BMSC senescence by activating the p53-p21 signaling pathway, with an optimal concentration of 10 μmol/L. Compared with the control group, BMSCs exhibited decreased lactate production, reduced mRNA expression of Ldha and Ep300 (P<0.001), upregulated Sirt2 expression (P<0.01), and diminished levels of Pan-Kla and H3K18la modification (P<0.001). Further inhibition of lactate production with GNE 140 further increased the expression levels of p53 and p21 and the percentage of SA β gal positive cells (P<0.01). In osteogenic differentiation experiments, the expression levels of Runx2, Sp7, Alpl mRNA and COL1, RUNX2, OSX, OCN proteins, as well as the mineralized nodule formation ability of senescent BMSCs, were decreased (P<0.05); exogenous supplementation with 5 mmol/L and 10 mmol/L sodium lactate can increase the levels of panolactic lactation and histone lactation, and improved the osteogenic differentiation capacity and mineralized nodule formation of senescent BMSCs. Conclusion BMSC senescence is associated with reduced lactate production and decreased histone lactylation levels. Exogenous supplementation with sodium lactate partially rescues osteogenic differentiation impairment in senescent BMSCs.

Public health decision-making is often accompanied by intense ethical controversies， demanding decision-makers not only to possess the moral courage and sense of responsibility to address challenges， but also to master the refined skills of ethical reasoning and value trade-offs. This underscores the increasingly vital role of public health ethics in medical education. Taking the film Contagion as a case， this paper delved into the practical pathways and teaching effectiveness of integrating pandemic films as instructional materials into public health ethics education. It elucidated the unique value of films in teaching public health ethics， namely， they not only stimulate learning interest through emotional resonance but also construct realistic ethical dilemmas via highly immersive cinematic narratives， thereby promoting deeper learning. On this basis， a set of teaching implementation pathways was constructed， including critical steps such as clarification of instructional intent， formulation of learning objectives， development of teaching materials， implementation of classroom instruction， and evaluation and reflection on teaching effectiveness. A qualitative research method was used to assess the teaching effectiveness. The results showed that integrating pandemic films into public health ethics teaching can significantly enhance learners’ enthusiasm for exploration and research， strengthen their ethical decision-making and reasoning abilities in complex situations， and promote the development of their moral literacy. This teaching model provides feasible ideas and practical strategies for methodological innovation in public health ethics education， possessing strong potential for broader application.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

Background and Aims:Unplanned reoperation is a critical indicator for evaluating the quality of surgical treatment and prognosis in patients with gastrointestinal perforation.Identifying its underlying causes,recognizing relevant risk factors,and developing effective preventive strategies are essential for optimizing treatment outcomes and improving patient prognosis.This study aimed to investigate the causes and risk factors of unplanned reoperation following surgery for gastrointestinal perforation,in order to provide clinical guidance for targeted interventions.Methods:The clinical data of 303 patients who underwent surgery for gastrointestinal perforation at the Department of General Surgery,Shijiazhuang People's Hospital,from January 2020 to July 2023,were retrospectively analyzed.Among them,218 were males and 85 were females,with a mean age of(61.05±17.95)years.Seventeen patients experienced unplanned reoperations after operation,while 286 did not.Univariate analysis and multivariate Logistic regression were performed to identify the risk factors associated with unplanned reoperation.A predictive model was developed and its performance was assessed using the receiver operating characteristic(ROC)curve.Results:Among the 17 patients who underwent unplanned reoperation,14 were males and 3 were females,with a mean age of(65.76±15.11)years.The primary causes of reoperation included postoperative fistula(7 cases),postoperative bleeding(4 cases),surgical site infection(2 cases),wound dehiscence(2 cases),and stoma-related complications(2 cases).Univariate analysis indicated that gender,comorbidities,hypoproteinemia,history of abdominal surgery,ASA score,surgical grade,and disease duration were significantly associated with unplanned reoperation(all P<0.05).Multivariate Logistic regression revealed that male gender(OR=99.62,95%CI=4.90-2 025.29,P<0.05),hypoproteinemia(OR=8.59,95%CI=1.81-40.91,P<0.05),history of abdominal surgery(OR=17.28,95%CI=3.42-87.32,P<0.05),higher ASA score(OR=11.89,95%CI=2.73-51.72,P<0.05),higher surgical grade(OR=17.15,95%CI=2.47-118.93,P<0.05),and longer disease duration(OR=1.04,95%CI=1.02-1.07,P<0.05)were independent risk factors.The ROC curve analysis showed that the predictive model constructed based on the above factors had a sensitivity of 0.90,a specificity of 0.88,and an area under the curve of 0.94(95%CI=0.88-0.99,P<0.001).Conclusion:The leading causes of unplanned reoperation after gastrointestinal perforation surgery are postoperative fistula and bleeding.Male gender,hypoproteinemia,and other high-risk factors significantly increase the likelihood of reoperation.Although most such surgeries are performed emergently,comprehensive preoperative assessment of relevant risk factors is crucial to reduce the incidence of unplanned reoperation,and improve patient outcomes.

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

Background and Aims:Unplanned reoperation is a critical indicator for evaluating the quality of surgical treatment and prognosis in patients with gastrointestinal perforation.Identifying its underlying causes,recognizing relevant risk factors,and developing effective preventive strategies are essential for optimizing treatment outcomes and improving patient prognosis.This study aimed to investigate the causes and risk factors of unplanned reoperation following surgery for gastrointestinal perforation,in order to provide clinical guidance for targeted interventions.Methods:The clinical data of 303 patients who underwent surgery for gastrointestinal perforation at the Department of General Surgery,Shijiazhuang People's Hospital,from January 2020 to July 2023,were retrospectively analyzed.Among them,218 were males and 85 were females,with a mean age of(61.05±17.95)years.Seventeen patients experienced unplanned reoperations after operation,while 286 did not.Univariate analysis and multivariate Logistic regression were performed to identify the risk factors associated with unplanned reoperation.A predictive model was developed and its performance was assessed using the receiver operating characteristic(ROC)curve.Results:Among the 17 patients who underwent unplanned reoperation,14 were males and 3 were females,with a mean age of(65.76±15.11)years.The primary causes of reoperation included postoperative fistula(7 cases),postoperative bleeding(4 cases),surgical site infection(2 cases),wound dehiscence(2 cases),and stoma-related complications(2 cases).Univariate analysis indicated that gender,comorbidities,hypoproteinemia,history of abdominal surgery,ASA score,surgical grade,and disease duration were significantly associated with unplanned reoperation(all P<0.05).Multivariate Logistic regression revealed that male gender(OR=99.62,95%CI=4.90-2 025.29,P<0.05),hypoproteinemia(OR=8.59,95%CI=1.81-40.91,P<0.05),history of abdominal surgery(OR=17.28,95%CI=3.42-87.32,P<0.05),higher ASA score(OR=11.89,95%CI=2.73-51.72,P<0.05),higher surgical grade(OR=17.15,95%CI=2.47-118.93,P<0.05),and longer disease duration(OR=1.04,95%CI=1.02-1.07,P<0.05)were independent risk factors.The ROC curve analysis showed that the predictive model constructed based on the above factors had a sensitivity of 0.90,a specificity of 0.88,and an area under the curve of 0.94(95%CI=0.88-0.99,P<0.001).Conclusion:The leading causes of unplanned reoperation after gastrointestinal perforation surgery are postoperative fistula and bleeding.Male gender,hypoproteinemia,and other high-risk factors significantly increase the likelihood of reoperation.Although most such surgeries are performed emergently,comprehensive preoperative assessment of relevant risk factors is crucial to reduce the incidence of unplanned reoperation,and improve patient outcomes.

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.