Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

Liver cancer imposes a substantial global disease burden.Hepatocellular carcinoma(HCC),as the primary pathological type of primary liver cancer,accounts for approximately 90％of all cases.As a minimally invasive treatment,thermal ablation causes minimal impact on liver function and trauma,serving as the first-line treatment option for early-stage HCC patients unsuit-able for surgical resection.However,clinical data indicate that 5-year recurrence rate of HCC pa-tients after thermal ablation treatment is as high as 50％～70％,and incomplete ablation remains a core factor leading to recurrence.Therefore,exploring and optimizing complete ablation strategies has become a critical direction for improving the efficacy of thermal ablation in HCC and enhanc-ing long-term survival rates of patients.This paper systematically reviews the current applications of thermal ablation in HCC treatment and focuses on discussing key technologies and strategies for achieving complete ablation,with the aim of providing theoretical foundations and technical refer-ences for improving the complete ablation rate of thermal ablation in clinical practice and formu-lating personalized diagnosis and treatment plans.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

Liver cancer imposes a substantial global disease burden.Hepatocellular carcinoma(HCC),as the primary pathological type of primary liver cancer,accounts for approximately 90％of all cases.As a minimally invasive treatment,thermal ablation causes minimal impact on liver function and trauma,serving as the first-line treatment option for early-stage HCC patients unsuit-able for surgical resection.However,clinical data indicate that 5-year recurrence rate of HCC pa-tients after thermal ablation treatment is as high as 50％～70％,and incomplete ablation remains a core factor leading to recurrence.Therefore,exploring and optimizing complete ablation strategies has become a critical direction for improving the efficacy of thermal ablation in HCC and enhanc-ing long-term survival rates of patients.This paper systematically reviews the current applications of thermal ablation in HCC treatment and focuses on discussing key technologies and strategies for achieving complete ablation,with the aim of providing theoretical foundations and technical refer-ences for improving the complete ablation rate of thermal ablation in clinical practice and formu-lating personalized diagnosis and treatment plans.

Objective    To study the safety of right vertical infra-axillary thoracotomy (RVIAT) in the repair of ventricular septal defect (VSD) and the optimal age for RVIAT. Methods    Between June 2014 and June 2018, 441 children underwent VSD repair via RVIAT in our hospital. According to the age, they were divided into four groups: a 4 months to 1 year old group (R1 group, n=123), a 1-2 years old group (R2 group, n=106), a 2-5 years old group (R3 group, n=166), a >5 years old group (R4 group, n=46). The clinical effects of the patients were compared. Results    All the operations were successfully performed and no serious complication was found in all groups. No statistical difference was observed in the operation time, blood loss during operation, thoracic drainage 24 h after operation among groups (P>0.05). The cardiopulmonary bypass time, aortic cross-blocking time and ICU stay time in the R1 and R2 groups were longer than those in the R3 and R4 groups (P<0.05). In the R1 group, the postoperative ventilating time and postoperative hospital stay time were longer, and the blood transfusion volume was more than those in the R3 and R4 groups (P<0.05). The incidence of postoperative complications was higher in the R4 group than that in the R1 and R3 groups (P<0.05). Conclusion    VSD repair via RVIAT may be more effective in children >2 years old, and 2-5 years old may be the optimal age.

Objective To investigate the global research status and trends ofrehabilitation after arthroplasty.Methods The Wed of Science database was used to search the publications on rehabilitation after arthroplasty from 1994 to 2018.The included publish items were statistically analyzed by bibliometrics.VOSviewer software was used to analyze the visual transformation of literature coupling (including author coupling,mechanism coupling and country coupling) and co-occurrence analysis.The research status and trends of rehabilitation after arthrop]asty in recent years were analyzed and predicted.Results A total of 1 702 studies were included in the present study.The number of literatures increased year by year globally,including 612 in the United States as the top number of studies in the world.The total citation frequency (15 433 times) and H index (61) of the research publications were also the highest in the world.China (79 literatures) ranked 6th in the number of global research publications,with total citation frequency (451 times) and H index (12) ranked 14th.The number of publications published by JOURNAL OF ARTHROPLASTY and ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION on rehabilitation after arthroplasty was the highest.The University of Pittsburgh and the University of Toronto were the biggest contributors to publications on rehabilitation after arthroplasty.The theme of rehabilitation after arthroplasty can be divided into five categories:pain management,functional exercise,hospital management,complications and clinical trials.Hospital management wasthe main research field recently and the orthopedic specialty hospital would become a hot research topic in the fulure.Conclusion According to the current global trends,rehabilitation study is deepening and the number of publications will increase continuously.The United States is the largest contributor in this area.The current researches focus on the "hospital management" after arthroplasty.The new type of orthopedic specialty hospital may be the next research hotspot for arthroplasty.

Objective: To assess the collateral grade based on 4-dimensional magnetic resonance angiography (4D-MRA) in predicting short-term outcome in patients with acute ischemic stroke (AIS) . Methods: Forty-seven patients with unilateral MCA stroke were enrolled in this study. All patients underwent multi-modality MRI within 4.5 to 24.0 hours onset of stroke. The collateral grade was assessed through the dynamic MRI angiograms derived from perfusion raw data. The AIS patients were divided into favorable and unfavorable outcome group according to the improvement of national institutes of health stroke scale (NIHSS) score. The differences in baseline data, infarct volume, the ratio of volume of ischemic tissue on perfusion to infarct core on diffusion (rVPD) and collateral grade between the two groups were analyzed. Logistic regression analysis was used to identify variable influencing the short-term clinical outcomes. The Kappa coefficient was used to analyze the consistency of the collateral grade assessed between the two observers. Spearman rank-order correlation test was used to analyze the relationship between the collateral grade, infarct volume, hypoperfusion volume and rVPD. Results: The collateral grade used ASITN/SIR based on 4D-MRA was performed in 47 patients. Grade 1 in 4 patients, grade 2 in 21paitients, grade 3 in 16 patients and grade 4 in 6 patients, respectively. The collateral grade had a high consistency among the observers (Kappa=0.806, P<0.01). Of the patients who enrolled the study, the median of infarct volume was 29.63 (4.92, 69.17) ml, the hypoperfusion volume was 73.76 (29.75, 178.42) ml, and the rVPD was 3.1 (1.5, 5.8). It was negatively correlated with initial infarct volume (r=-0.627, P<0.01) and hypoperfusion volume (r=-0.354, P<0.01) . There was a significant positive correlation between the collateral grade and rVPD (r=0.575, P<0.001). There was also significant differences in infarct volume, rVPD, and collateral grade between favorable and unfavorable outcome group (P<0.05). The collateral grade based on 4D-MRA was an independent predictor of favorable clinical outcome (OR=4.419, P<0.05) . Conclusions The collateral circulation classification based on 4D-MRA proved to be a significant predictor of clinical outcome, it can be considered as a reliable method for analyzing the cerebral hemodynamic changes and collateral grade in AIS patients.

Objective To summarize the treatment experience and strategies of patients with acute type A aortic dissection involving coronary arteries in order to improve the efficacy of such patients.Methods Between March 2013 and April 2016,we recruited 37 patients with coronary involvement caused by acute type A aortic dissection,26 men,11 women;mean age (49.7 ± 10.4) years.All procedures were done on an emergency basis within 24 hours after the patient's arrival.Results Acute type A aortic dissection with coronary involvement is a more complex operation associated with high in-hospital mortality(18.9％,7/37) and low short-term survival(64.9％,13/37).There were 9 patients underwent coronary artery bypass graft after completion of the root procedure because of ventricular wall motion abnormality(7 patients) and new ST-segment elevation (2 patients) during weaning from cardiopulmonary bypass.Four of them were survival during follow-up due to the success from rescue coronary artery bypass graft.Conclusion Acute type A aortic dissection with coronary involvement is associated with high in-hospital mortality and low short-term survival.If patients suffered abnormal ventricular wall motion or new ST-segment elevation during weaning from cardiopulmonary bypass,rescue coronary artery bypass graft is essential to salvage these critically ill patients.

OBJECTIVETo evaluate the efficacy and safety of fecal microbiota transplantation (FMT) combined with soluble dietary fiber and probiotics for slow transit constipation(STC).

METHODSTwenty-three patients with STC from Jinling Hospital, Medical School of Nanjing University were prospectively enrolled between April 2015 and January 2016. STC patients received FMT combined with soluble dietary fiber and probiotics. Fresh stool(100 g) was immediately mixed in a blender with 500 ml of 0.9% sterile saline for several seconds, which was then filtered through a gauze pad and a decreasing number of gauze screen (2.0 to 0.5 mm). The fecal bacteria suspension was stored frozen at -20centi-degree. The preparation time of FMT material was less than 1 hour. Total time of treatment was 9 days. An initial oral antibiotics(vancomycin 500 mg orally twice per day) was given for 3 consecutive days. Then the fecal microbiota(100 ml) was infused slowly(5 min) through nasojejunal tube for 6 consecutive days. After FMT, patients were recommended to receive soluble dietary fiber (pectin, 8 g/d) and probiotics (bifid triple viable capsules, twice per day) for 4 weeks. Rates of clinical improvement and remission, adverse events, constipation-related symptoms (PAC-SYM scores), bowel movements per week and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. This study was registered in the Clinical Trials.gov (NCT02016469).

RESULTSAmong 23 patients, 7 were male, 16 were female, the mean age was (49.6±14.7) years, the body mass index was (21.2±2.2) kg/m, the duration of constipation was (8.3±5.9) years, and the defecation frequency was 1.8±0.7 per week. Compared with pre-treatment, PAC-SYM scores decreased significantly from 2.3±0.5 to 1.3±0.4 at week 12 (P<0.01), defecation frequency increased from 1.8±0.7 per week to 4.8±2.0 per week at week 12 (P<0.01), and patients felt satisfied with improved GIQLI score (from 78.5±15.5 to 120.8±21.3, P<0.01). During the follow-up, the clinical improvement and remission of STC patients reached 69.6%(16/23) and 52.2%(12/23), respectively. No serious adverse events were observed.

CONCLUSIONFMT combined with soluble dietary fiber and probiotics is safe and effective in treating slow transit constipation, which can improve the symptom and quality of life significantly.