Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis.Methods Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer.Literature screening and data extraction were performed according to random-ized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane man-ual.Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software.Results Seven RCT studies(424 patients)were included,296 patients in bone replacement group and 128 patients in autograft group.Operative time[MD=-16.79,95％CI(-25.72,-7.85),P=0.000 2]and blood loss[MD=-70.49,95％CI(-79.34,-61.65),P＜0.000 01]between two groups had statistically differ-ences,while joint depression[MD=-0.17,95％CI(-0.91,0.58),P=0.66],secondary collapse rate of joint surface[RR=-0.74,95％CI(0.35,1.57),P=0.43],infection rate[RR=1.21,95％CI(0.31,4.70),P=0.78]between two groups had no differences.Conclusion The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate.However,compared with autologous bone trans-plantation,bone replacement could reduce blood loss and shorten operation time.

Objective To analyze the clinical characteristics of patients with acute esophageal injuries in order to improve clinicians'diagnosis and treatment of such diseases.Methods The general data and treatment methods of 61 patients with acute esophageal injury from January 2013 to March 2023 were retrospectively analyzed.Results Majority of the patients with esophageal and cardia mucosal tear syndrome were male(72.2%),age(52.04±17.96)years,triggering factor was gastroscopy in 29 patients(53.7%),and vomiting of blood and black stools was the main clinical manifestation(63.0%),the average length of hospital stay was(6.39±3.53)d and 13(24.1%)patients had anaemic complications,blood transfusion was given to 8 patients(14.8%),39 patients(72.2%)were discharged after conservative treatment with transfusion,and only 15 patients(27.8%)required endoscopic hemostasis.1 case of esophageal hematoma combined with esophageal cardia mucosal tear syndrome was an elderly male patient with a history of hypertension,cerebral infarction,and long term use of oral aspirin,complicated by severe anemia,who was given desiprofloxacin to stop the hemostasis endoscopically,the total length of hospital stay was 22 d.4 patients with esophageal hematoma were young and middle-aged males,2 patients had a predisposing factor of poor diet prior to the onset of the disease,2 patients presented with vomiting of blood,1 with chest pain and 1 with a foreign body sensation in the throat,2 patients were discharged with endoscopic intervention,and the remaining 2 patients were discharged after conservative treatment.2 patients with spontaneous esophageal rupture were young and middle-aged males,clinical manifestations were chest tightness or retrosternal discomfort,and one patient had esophageal rupture with left-sided liquid pneumothorax,esophageal rupture repair+pleural adhesion branding+open thoracic hemostasis+intrathoracic foreign body removal was performed,and an esophageal stent was placed endoscopically after the operation,and the patient was discharged from the hospital after 52 d,in another case,the patient's esophageal fistula was small,and a three-lumen nutrient tube was placed under gastroscopic guidance,the patient's esophagus recovered well after 7 d,and the patient was discharged from the hospital.Conclusion Acute esophageal injury is a clinical emergency,among them,esophageal hematoma and spontaneous esophageal rupture are relatively rare.Prompt endoscopic clot removal is a viable option for patients with ruptured esophageal hematomas who have failed conservative treatment,and patients with spontaneous esophageal rupture who have surgically placed esophageal stents have good mucosal recovery.Clinicians need to be vigilant for patients with esophageal injuries that are associated with anemia,or even require blood transfusion,should make a clear diagnosis at an early stage,with timely endoscopic or surgical intervention to avoid progression of the disease.

This study investigated the prevalence of Borrelia burgdorferi,Anaplasma phagocy tophilum,Rickettsia typhi,Orientia tsutsugamushi,Leptospira interrogans,Francisella tularensis,and Babesia spp.in small mammals in the Qinghai plateau region,to provide a scientific basis for the prevention and control of local zoonotic diseases.Small mammals were cap-tured with snap traps at six sampling sites in the Qinghai plateau region.Liver,spleen,and kidney tissues were collected for detection of six bacterial pathogens with real-time PCR.Conventional PCR(cPCR)was used for Babesia detection,and the positive PCR products were sequenced and analyzed.The differences in pathogen detection rates among species and habitats were analyzed with x2 test or Fisher's exact test.In to-tal,235 small mammals from 15 species were captured.B.burgdorferi,L.interrogans,and Babesia were detected in 11 spe-cies of small mammals,whereas A.phagocytophilum,R.typhi,O.tsutsugamushi,and F.tularensis were not detected.B.burgdorferi was detected in 41 small mammals from nine species(Cricetulus longicaudatus,Apodemus peninsulae,Ochotona curzoniae,Mus m usc ulus,Meriones meridians,Microtus arvalis,Cricetidae,Ochotona cansus,and Allactaga sibirica),with an infection rate of 17.45％(41/235).L.interrogans was detected in eight small mammals from four species(C.longicaudatus,M.musculus,M.arvalis,and Microtus oeconomus),with an infection rate of 3.40％(8/235).Babesia was detected in only one Mustela altaica,with an infection rate of 0.85％(1/235).Statistically significant differences were ob-served in the detection rates of pathogens among small mammal species(x2=200.54,P＜0.05).Among habitats,the detection rate of B.burgdorferi was highest in the forest(Fisher's exact test,P＜0.05).B.burgdorferi and L.interrogans co-infection was observed in three M.arvalis and two C.longicaudatus.In addition,one Babesia sequence was obtained,which clustered with Babesia vulpes in the phylogenetic tree.B.burgdorferi,L.interrogans,and Babesia were the main pathogens prevalent in small mammals in the Qinghai plateau region and have potential to cause human diseases.Local authori-ties should strengthen the surveillance of corresponding zoonotic diseases,and formulate corresponding prevention and control measures.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.

Objective:To observe the efficacy of different needling depths for knee osteoarthritis(KOA)and the effects on effusion,cartilage thickness,and synovium under ultrasound imaging. Methods:A total of 90 patients with KOA were randomly divided into a conventional acupuncture group,a Western medication group,and a shallow acupuncture group,with 30 cases in each group.In the conventional acupuncture group,the needling depth was 15-30 mm,and the needle was twisted for a few moments after insertion so that a sore,numb,distending,and electrified sensation was obtained;in the shallow acupuncture group,the points were punctured perpendicularly by 2 mm,and no manipulation was performed after insertion.The same points were used in the two acupuncture groups,and the needles were retained for 20 min.The treatment was performed 3 times a week.The Western medication group was given glucosamine sulfate capsules for oral administration,2 capsules once,3 times a day.All three groups were treated for 8 weeks.The Western Ontario and McMaster Universities osteoarthritis index(WOMAC)and the visual analog scale(VAS)were scored before treatment,after 4 weeks and 8-week treatment,respectively;while the changes in knee cartilage,synovial membrane,and joint fluid were observed by knee ultrasound before and after 8-week treatment.The clinical efficacy was evaluated after 8-week treatment. Results:After 8-week treatment,the effusion and the synovial thickness improved significantly in both the conventional and shallow acupuncture groups compared with that before treatment(P<0.01);the effusion improved in the Western medication group compared with that before treatment(P<0.05);the synovial thickness improved better in the conventional acupuncture group than in the Western medication group(P<0.05).There was no statistically significant difference in the cartilage thickness among the three groups compared with that before treatment(P>0.05).The WOMAC(pain,stiffness,and function)and VAS scores decreased in all three groups after 4-and 8-week treatment compared with those before treatment(P<0.05).After 4-and 8-week treatment,the pain scores in WOMAC of the conventional acupuncture group were lower than those of the Western medication group and the shallow acupuncture group(P<0.05),and the VAS scores of the conventional acupuncture group were lower than those of the shallow acupuncture group(P<0.05).After 8-week treatment,the stiffness and functional scores in WOMAC of the conventional acupuncture group were lower than those of the Western medication group(P<0.05). Conclusion:Conventional acupuncture,oral Western medication,and shallow acupuncture all relieved knee pain and improved knee stiffness and functional movement.Among them,conventional acupuncture had the best efficacy in relieving knee pain and the best efficacy in improving joint function after 8-week treatment.Both conventional acupuncture and shallow acupuncture significantly reduced synovial thickness lesions in the knee;all three groups improved joint effusion and were more effective with conventional and shallow acupuncture.

Objective To explore the effect of mixed antibiotics on the intestinal flora of mice to affect the immune regulation of the body,explore the role of intestinal flora in the development of obesity,and provide new ideas and ways for the prevention and treatment of obesity.Methods Seventy-two 10-week-old male C57BL/6 mice were randomly divided into blank control(Ctrl)group,high-fat diet(HF)group,antibiotic(ABX)group,and combined(COMB)group(n=18).At the first 2 weeks(lavage intervention weeks),Ctrl and HF group were given normal saline gavage;ABX and COMB group were given mixed antibiotics gavage,and the gavage volume was 0.2 mL/animal/day.For the following 8 weeks(feeding weeks),Ctrl and ABX group were fed with ordinary diet,HF and COMB group were fed with high-fat diet.Body weight was measured weekly,and fasting blood glucose was measured before and after gavage,and at the 4th and 8th week of feeding.Oral glucose tolerance test was performed at the end of the experiment.The organ coefficient was measured and the cell morphology of white and brown adipose tissue was observed.Serum was collected for the determination of free fatty acid,high-density lipoprotein,low-density lipoprotein,triglyceride,and total cholesterol.Serum TNF-α,IL-10,IL-4,IL-13,IL-33 and MCP-1 was detected by ELISA.The stool of mice was collected for second generation sequencing.Results High-fat diet increased body weight,serum total cholesterol,low-density lipoprotein,IL-13,IL-33,TNF-α,MCP-1 content,and decreased glucose tolerance and organ coefficient in mice(P＜0.05).From the first feeding week to the end of the experiment,body weight in COMB group was significantly lower than that in HF group(P＜0.05).The level of glucose tolerance,serum total cholesterol,low density lipoprotein,IL-13,IL-33,TNF-α and MCP-1 in COMB group was lower than those in HF group(P＜0.05).The α diversity of intestinal flora in ABX group was lower than that in Ctrl group(P＜0.05).Congestion and bleeding in WAT were obvious in HF group,but not in COMB group.The microbial community composition of ABX and HF group was similar to that of Ctrl and COMB group,respectively.Conclusion High-fat diet induces obesity,disorder of glucose and lipid metabolism and inflammation in mice.Short-term mixed antibiotic use can regulate the intestinal flora of mice,mediate increased expression of related anti-inflammatory factors,up-regulate host immunity,and improve glucose and lipid metabolism in mice.

Purpose/Significance To apply deep learning technology to achieve the purpose of tongue image analysis automation,so as to provide references for the standardization of tongue image of traditional Chinese medicine(TCM),and further promote the moderni-zation of TCM diagnosis and treatment technology.Method/Process It develops a new semantic segmentation loss function with region-based correlation and label relaxation to enhance the capability of tongue image segmentation model to learn pixel relationships and handle mislabeled data.Additionally,leveraging inherent color-related priors in tongue image features,the model is simplified by decomposing it into two multi-label classification tasks,thereby accelerating model training and reducing its complexity.Result/Conclusion The pro-posed algorithm is proven effective on a self-constructed dataset,attaining a high 96.57％MIoU in tongue segmentation,and demon-strating strong performance with a macro F1-score of 88.58％and average accuracy of 82.59％.

Objective To analyze the distribution and antimicrobial resistance of pathogens from wounds of burned patients,providing reference for the rational use of antimicrobial agents and healthcare-associated infection(HAI)prevention and control.Methods Clinical data of burned patients admitted to a tertiary first-class hospital from Ja-nuary 2020 to December 2022 were analyzed retrospectively,pathogens in the wound was cultured,identified,and performed antimicrobial susceptibility analysis.Results From 2020 to 2022,a total of 588 burned patients were ad-mitted,734 strains of pathogens were detected,including 415 strains(56.54％)of Gram-negative bacteria,306 strains(41.69％)of Gram-positive bacteria,and 13(1.77％)strains of fungi.The top 5 pathogens were Staphy-lococcus aureus,Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumoniae,and Enterobacter cloacae.Staphylococcus aureus had higher resistance rates(93.02％-97.37％)to penicillin G,resistance rate to oxacillin increased from 11.63％to 21.92％.Pseudomonas aeruginosa mainly exhibited resistance to ticarcillin/clavulanic acid,aztreonam,and levofloxacin,resistance rates to imipenem and meropenem were 15.00％-38.10％and 10.00％-33.33％,respectively.Susceptibility of Enterobacterales bacteria to cephalosporins enhanced with the increased of cephalosporin generations,and exhibited higher resistance to commonly used antimicrobial agents.Conclusion Over the past three years,there has been no significant change in the detection of major pathogens and antimicrobial resistance in wounds of burned patients in this hospital.Antimicrobial resistance of Staphylococcus aureus and En-terobacterales is relatively severe,and it is necessary to carry out surveillance on pathogens from burn wounds in corresponding areas.