ObjectiveTo examine the impact of Toll-like receptor 4 （TLR4）-mediated neutrophil extracellular traps （NETs） formation on isoproterenol （ISO）-induced heart failure （HF） in aged mice. MethodsThe mice were randomly divided into Control group， Model group， TAK-242 （TLR4 inhibitor） group， LPS （TLR4 agonist） group and LPS+DNaseⅠ （NETs inhibitor） group， with 8 mice in each group. The HF model was established by continuous infusion of ISO through an osmotic pump， and TAK-242， LPS， and LPS+DNaseⅠ interventions were administered during the last week of infusion for 7 consecutive days. ELISA was used to detect the N-terminal pro-B-type natriuretic peptide （NT-pro BNP）， cardiac troponin I （cTnI）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and serum and myocardial tissue myeloperoxidase-DNA （MPO-DNA） and neutrophil elastase-DNA （NE-DNA） levels. HE staining was used to observe the pathological changes of myocardial tissue. Masson staining was used to observe the deposition of collagen fibers in myocardial tissue. Immunofluorescence was used to observe the colocalization of Ly6G and MPO in myocardial tissue. The protein expressions of TLR4， MPO， NE and cit-H3 in myocardial tissue were detected by Western blot. ResultsCompared with the Control group， the end-diastolic interventricular septal thickness （IVSD）， left ventricular end-diastolic diameter （LVEDD） and left ventricular end-systolic diameter （LVESD） in the Mode group significantly increased （P<0.01）， fractional shortening （FS） and ejection fraction （EF） significantly decreased （P<0.01）， and the myocardial structure was significantly damaged. The myocardial collagen fiber precipitation， serum NT-pro BNP， cTnI， IL-1β， IL-6 and TNF-α contents， MPO-DNA and NE-DNA contents in serum and myocardial tissue significantly increased （P<0.01）. The co-localization of Ly6G and MPO and the expression of TLR4， MPO， NE and cit-H3 proteins in myocardial tissue significantly increased （P<0.01）. After TAK-242 intervention， the above indicators were significantly reversed， while the injury was further aggravated in LPS group. DNaseⅠ treatment could partially alleviate the deterioration of myocardial structure and function induced by LPS. ConclusionTLR4 and NETs are abnormally elevated in the myocardial tissue of aged HF mice. Treatment with the TLR4 inhibitor TAK-242 effectively suppresses NET formation， attenuates inflammatory responses， and enhances cardiac function in aged HF mice.

Objective The athletic performance and physiological indicators of two top seated cross-country skiers during simulated competitions were analyzed,and the characteristics of exercise intensity and pacing strategies in different terrains were explored,so as to provide a scientific basis for physical fitness allocation and speed rhythm optimization of the athletes.Methods Differential global positioning system and Momentum Technology MT-Sports T2 were used to test athlete A and athlete B with class of locomotor winter 10(LW 10),who were the first and second runners-up of Beijing Winter Paralympic mid-distance cross-country ski race.The athletes' real-time gliding speed and heart rate during five consecutive 15 km cross-country skiing time trials were collected,and the time spent on each section,speed and heart rate changes in each course were analyzed.Results The coefficient of variation(CV)of mean heart rate on uphill and flat terrain sections were significantly correlated with total scores.The average gliding speed and average heart rate as a percentage of maximum heart rate(HRmax)of the athletes in three terrains were significantly correlated with total scores.The correlation between the mean time spent on uphill and flat terrain and total performance was stronger than that between the mean time spent on downhill terrain and total scores.Both athletes used a cumulative acceleration speed rhythm.Conclusions Uphill and flat terrain time are critical to race performance.Athletes adopt a progressive pacing strategy,gradually increasing speed in the first half,maintaining stable output in the mid-race,and finishing the last lap at a high-speed.Heart rates are mainly distributed between 70％-90％HRmax,and balancing high-intensity efforts on uphills with recovery on downhills helps optimize energy expenditure.

Objective:To evaluate the efficacy of peroral super minimally invasive incision for esophageal diverticulum.Methods:The clinical data of patients with esophageal diverticulum who underwent super minimally invasive surgery (SMIS) at the First Medical Center of the PLA General Hospital from April 2022 to September 2024 were retrospectively analyzed. These data include clinical baseline data, endoscopic surgical parameters, preoperative and postoperative Eckardt scores, surgical costs, and the duration of hospitalization.Results:Thirteen patients successfully completed submucosal tunneling endoscopic septum division (STESD) surgery without any postoperative adverse events. The duration of operation was (37.00 ± 5.82) min, the application time of proton pump inhibitors (PPI) was 4 (4, 4) d, the application time of antibiotics was 3 (2, 4) d, the surgical cost was 22 580 (27 044, 34 255) yuan, and the hospital stay was 12 (10, 22) d. The Eckardt scores before and after the operation were 3 (2, 4) scores and 1 (0, 1) score respectively, the Eckardt score after the operation decreased significantly compared with that before the operation.Conclusions:STESD is a safety and efficient operation for the treatment of esophageal diverticulitis. It has the advantages of short term curative effect and obvious improvement of the patient′s symptoms.

Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.

Objective:To investigate the indications for prenatal diagnosis using copy number variation-sequencing (CNV-seq) and the abnormalities detected by the method.Methods:This retrospective analysis involved 17 994 singleton pregnant women who underwent prenatal CNV-seq at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022. These cases were divided into five groups based on the following indications for CNV-seq: abnormal fetal ultrasound findings, high-risk results indicated by non-invasive prenatal testing (NIPT) or Down's syndrome serological screening (Down's screening), adverse pregnancy history, and advanced maternal age. The proportions of cases with the indications for prenatal CNV-seq, the detection rates of abnormalities (numerical abnormalities of chromosomes, pathogenic/likely pathogenic CNV in structural abnormalities) in the five groups, and the distribution of these abnormalities were analyzed. Statistical analysis was performed using Chi-square test. Results:Among the 17 994 pregnant women, the women with abnormal fetal ultrasound findings, high-risk NIPT results, high-risk Down's screening results, adverse pregnancy history, and advanced maternal age accounted for 32.65% (5 875/17 994), 11.90% (2 142/17 994), 31.62% (5 690/17 994), 11.70% (2 105/17 994), and 12.13% (2 182/17 994), respectively. The detection rates of abnormalities in the five groups were 10.60% (623/5 875), 34.64% (742/2 142), 4.69% (267/5 690), 2.99% (63/2 105), and 3.67% (80/2 182), respectively. The overall detection rate of abnormalities was 9.86% (1 775/17 994). The cases with numerical abnormalities of chromosomes accounted for 68.79% (1 221/1 775), trisomy 21 was predominant (49.30%, 602/1 221). Chromosomal structural abnormalities were detected in 31.21% (554/1 775) of the cases with abnormalities, with 57.76% (320/554) harboring pathogenic CNVs and 42.24% (234/554) harboring likely pathogenic CNVs. The detection rate of chromosomal numerical abnormalities was higher than that of structural abnormalities in the abnormal fetal ultrasound group, NIPT high-risk group, and advanced maternal age group [6.81% (400/5 875) vs. 3.80% (223/5 875), χ2=53.10; 27.96% (599/2 142) vs. 6.68% (143/2 142), χ2=338.40; 2.43% (53/2 182) vs. 1.24% (27/2 182), χ2=8.61; all P<0.01]. A total of 416 microdeletions and 255 microduplications were detected in the 554 cases. The top three regions with the highest frequencies in microdeletions were Xp22.31 (12.74%, 53/416), 22q11.21 (7.93%, 33/416), and 17q12 (5.77%, 24/416); in microduplications, they were 22q11.21 (14.90%, 38/255), 17q12 (3.53%, 9/255), and 7q11.23 (3.53%, 9/255). Conclusions:Abnormal fetal ultrasound findings accounted for the highest proportion of prenatal diagnostic indications. The overall detection rate of abnormalities by CNV-seq is relatively high, especially in those with high-risk NIPT results as an indication for prenatal diagnosis. Among the chromosomal structural abnormalities detected in this study, the frequencies of Xp22.31 microdeletion and 22q11.21 microduplication are higher.

Objective The athletic performance and physiological indicators of two top seated cross-country skiers during simulated competitions were analyzed,and the characteristics of exercise intensity and pacing strategies in different terrains were explored,so as to provide a scientific basis for physical fitness allocation and speed rhythm optimization of the athletes.Methods Differential global positioning system and Momentum Technology MT-Sports T2 were used to test athlete A and athlete B with class of locomotor winter 10(LW 10),who were the first and second runners-up of Beijing Winter Paralympic mid-distance cross-country ski race.The athletes' real-time gliding speed and heart rate during five consecutive 15 km cross-country skiing time trials were collected,and the time spent on each section,speed and heart rate changes in each course were analyzed.Results The coefficient of variation(CV)of mean heart rate on uphill and flat terrain sections were significantly correlated with total scores.The average gliding speed and average heart rate as a percentage of maximum heart rate(HRmax)of the athletes in three terrains were significantly correlated with total scores.The correlation between the mean time spent on uphill and flat terrain and total performance was stronger than that between the mean time spent on downhill terrain and total scores.Both athletes used a cumulative acceleration speed rhythm.Conclusions Uphill and flat terrain time are critical to race performance.Athletes adopt a progressive pacing strategy,gradually increasing speed in the first half,maintaining stable output in the mid-race,and finishing the last lap at a high-speed.Heart rates are mainly distributed between 70％-90％HRmax,and balancing high-intensity efforts on uphills with recovery on downhills helps optimize energy expenditure.

Objective To investigate the effect of two treatment regimens combining Tacrolimus(TAC)with different Rituximab(RTX)dosages,and to provide clinical reference for treatment strategies.Methods A retrospective analysis was conducted on patients diagnosed with idiopathic membranous nephropathy(IMN)and treated with RTX combined with TAC regimen(RTX+TAC group and low-dose RTX+TAC group)in The First Affiliated Hospital of Xinxiang Medical University.Propensity score matching(PSM)was performed at a 1:1 ratio,and a total of 60 patients were enrolled,with 30 in each group.In low-dose RTX(375 mg/m2 at the first and fifteenth day respectively)+TAC group,if circulating B cells(CD19?)exceeded 5 cells/μL after 3 months,a 200 mg RTX infusion was administered.In RTX(1g at the first and fifteenth day respectively)+TAC group,if complete remission(CR)was not achieved by 6 months,an additional 1000 mg RTX infusion was administered.The incidence of CR,partial remission,and adverse events were followed up for 12 months after medication in both groups.Results(1)Both groups showed significant reductions in 24-hour proteinuria,with the RTX+TAC group demonstrating a notably higher decrease compared to the low-dose RTX+TAC group.Statistical differences were observed between the two groups at the 1st and 3rd months of treatment(P<0.05).Albumin levels gradually increased,and there were differ-ences between the two groups at both the 1st and 3rd months(P<0.05).The anti-phospholipase A2 antibody levels decreased significantly after one month of treatment[3.45(1.90,22.10)vs.3.28(8.30,23.08)RU/mL],P>0.05.At 3 months of treatment,the overall clinical remission rate was 63.3％for the RTX+TAC group compared to 36.7％for the low-dose RTX+TAC group(P<0.05).At 12 months,the RTX+TAC group achieved an overall remission rate of 86.7％,while the low-dose RTX+TAC group reached 83.3％,showing no statistical significance(P>0.05).After one month of treatment,the RTX+TAC group achieved a complete serological immunological remission rate of 33.3％,significantly higher than the 3.3％in the low-dose RTX+TAC group(P<0.05).(2)The cumulative remission rate of the RTX+TAC group was higher than that of the low-dose RTX+TAC group during the first 6 months of follow-up.The remission rate in the low-dose RTX+TAC group increased significantly after 6 months.Log-rank test showed no statistical difference between the survival curves of the two groups(P=0.37).(3)Based on a multifactorial COX regression analysis of factors related to remission in patients with IMN,for every unit increase in serum immunological remission time,the risk of patients achieving remission decreased by 13.5％(HR=0.87,P=0.016).The risk of remission for patients with high titers of anti-PLA2R antibodies decreased by 60.2％(HR=0.39,P=0.018).Conclusions Different RTX dosages yielded comparable overall clinical remission rates without significantly increasing adverse events.RTX+TAC regimen achieves higher early CR rate.Serological remission time and high titer anti-PLA2R antibodies are associated with clinical outcomes.

Objective To investigate the effect of two treatment regimens combining Tacrolimus(TAC)with different Rituximab(RTX)dosages,and to provide clinical reference for treatment strategies.Methods A retrospective analysis was conducted on patients diagnosed with idiopathic membranous nephropathy(IMN)and treated with RTX combined with TAC regimen(RTX+TAC group and low-dose RTX+TAC group)in The First Affiliated Hospital of Xinxiang Medical University.Propensity score matching(PSM)was performed at a 1:1 ratio,and a total of 60 patients were enrolled,with 30 in each group.In low-dose RTX(375 mg/m2 at the first and fifteenth day respectively)+TAC group,if circulating B cells(CD19?)exceeded 5 cells/μL after 3 months,a 200 mg RTX infusion was administered.In RTX(1g at the first and fifteenth day respectively)+TAC group,if complete remission(CR)was not achieved by 6 months,an additional 1000 mg RTX infusion was administered.The incidence of CR,partial remission,and adverse events were followed up for 12 months after medication in both groups.Results(1)Both groups showed significant reductions in 24-hour proteinuria,with the RTX+TAC group demonstrating a notably higher decrease compared to the low-dose RTX+TAC group.Statistical differences were observed between the two groups at the 1st and 3rd months of treatment(P<0.05).Albumin levels gradually increased,and there were differ-ences between the two groups at both the 1st and 3rd months(P<0.05).The anti-phospholipase A2 antibody levels decreased significantly after one month of treatment[3.45(1.90,22.10)vs.3.28(8.30,23.08)RU/mL],P>0.05.At 3 months of treatment,the overall clinical remission rate was 63.3％for the RTX+TAC group compared to 36.7％for the low-dose RTX+TAC group(P<0.05).At 12 months,the RTX+TAC group achieved an overall remission rate of 86.7％,while the low-dose RTX+TAC group reached 83.3％,showing no statistical significance(P>0.05).After one month of treatment,the RTX+TAC group achieved a complete serological immunological remission rate of 33.3％,significantly higher than the 3.3％in the low-dose RTX+TAC group(P<0.05).(2)The cumulative remission rate of the RTX+TAC group was higher than that of the low-dose RTX+TAC group during the first 6 months of follow-up.The remission rate in the low-dose RTX+TAC group increased significantly after 6 months.Log-rank test showed no statistical difference between the survival curves of the two groups(P=0.37).(3)Based on a multifactorial COX regression analysis of factors related to remission in patients with IMN,for every unit increase in serum immunological remission time,the risk of patients achieving remission decreased by 13.5％(HR=0.87,P=0.016).The risk of remission for patients with high titers of anti-PLA2R antibodies decreased by 60.2％(HR=0.39,P=0.018).Conclusions Different RTX dosages yielded comparable overall clinical remission rates without significantly increasing adverse events.RTX+TAC regimen achieves higher early CR rate.Serological remission time and high titer anti-PLA2R antibodies are associated with clinical outcomes.

This study reviews recent publications on the biomechanical causes and treatment of flat foot,through searching PubMed,Web of Science,CNKI,Wanfang and other databases.The reasons for the formation of flat foot include congenital factors and acquired factors,while the treatment methods mainly include orthopedic insoles,physical therapy,surgical therapy and exercise therapy.These methods,to a certain extent,can correct foot structural abnormalities,optimize biomechanical properties and improve foot stability and range of motion.For future research,the advanced imaging and simulation technology will be used for accurate assessment,the application of novel materials and non-surgical therapies will relieve long-term symptoms,genetic researches will promote the development of early diagnosis and personalized treatment,and the use of intelligent orthosis will realize real-time monitoring and dynamic adjustment,to provide more and more effective methods and means for the evaluation,intervention and treatment of flat foot.

Objective:To evaluate the efficacy of peroral super minimally invasive incision for esophageal diverticulum.Methods:The clinical data of patients with esophageal diverticulum who underwent super minimally invasive surgery (SMIS) at the First Medical Center of the PLA General Hospital from April 2022 to September 2024 were retrospectively analyzed. These data include clinical baseline data, endoscopic surgical parameters, preoperative and postoperative Eckardt scores, surgical costs, and the duration of hospitalization.Results:Thirteen patients successfully completed submucosal tunneling endoscopic septum division (STESD) surgery without any postoperative adverse events. The duration of operation was (37.00 ± 5.82) min, the application time of proton pump inhibitors (PPI) was 4 (4, 4) d, the application time of antibiotics was 3 (2, 4) d, the surgical cost was 22 580 (27 044, 34 255) yuan, and the hospital stay was 12 (10, 22) d. The Eckardt scores before and after the operation were 3 (2, 4) scores and 1 (0, 1) score respectively, the Eckardt score after the operation decreased significantly compared with that before the operation.Conclusions:STESD is a safety and efficient operation for the treatment of esophageal diverticulitis. It has the advantages of short term curative effect and obvious improvement of the patient′s symptoms.