Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Objective:To explore the application value of problem-based learning (PBL) combined with mini-clinical evaluation exercise (Mini-CEX) in the development of post competency for interns in the Department of Neurology.Methods:A total of 56 interns rotating at the Department of Neurology of The First Affiliated Hospital of Chongqing Medical University from June 2023 to January 2024 were enrolled as the study subjects. They were randomly divided into a control group and an experiment group using the random number table method, with 28 interns in each group. The control group received traditional methods including small lectures and teaching rounds, while the experimental group received the PBL teaching method combined with Mini-CEX. The teaching effectiveness was evaluated through theoretical assessments, practical skill evaluations, teacher and student satisfaction surveys, and Mini-CEX scale assessments conducted at the beginning, middle, and end of the rotation for the experimental group. The data were analyzed using SPSS 23.0 software. For continuous data, the independent-samples t test or Mann-Whitney U test was used for comparison between groups. The chi-square test was used for categorical data and the Kruskal-Wallis H test for repeated-measurement data. Results:The theoretical scores [(45.36±2.67) vs. (42.00±4.29), P<0.01] and practical skill scores [(45.11±2.53) vs. (42.39±4.53), P<0.01] were significantly higher in the experimental group compared to the control group. The Mini-CEX score of the experimental group at the end of the rotation was notably higher than that at the beginning of rotation ( P<0.05), and their abilities improved continuously. The satisfaction rates of teachers and students in the experimental group were 71.43% (20/28) and 67.86% (19/28), respectively, which were significantly higher than those in the control group [39.29% (11/28) and 35.71% (10/28), P<0.05]. Conclusions:The teaching model integrating PBL and Mini-CEX can effectively enhance the post competency of interns in the Department of Neurology, thus offering a new perspective for clinical undergraduate teaching.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.