The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Background and Amis:Gallbladder cancer(GBC)is the most common malignant tumor of the biliary tract,accounting for approximately 80%-95%of biliary tract cancers.This type of tumor has a poor prognosis,and currently,there are no effective tools for evaluating the prognosis of GBC.Therefore,this study was performed to investigate the factors influencing the prognosis of GBC patients to provide a reference for clinical practice.Methods:The clinical data and follow-up information from 160 GBC patients treated in the Hunan Provincial People's Hospital from January 2018 to January 2024 was retrospectively conducted.The clinicopathologic characteristics of GBC patients were analyzed.Kaplan-Meier and Log-rank tests were used to calculate and compare the differences in overall survival(OS)among GBC patients with different clinicopathologic characteristics and treatment methods.Multivariate analysis using Cox regression was performed to identify independent prognostic factors for GBC.Results:Among the 160 patients,113 were females and 47 were males.The median age of the patients was 62 years,with the main clinical manifestations being abdominal pain/distention(55.63%),jaundice(40.63%),appetite loss(30.62%),and weight loss(19.38%).Serum tumor markers,including CA19-9,CA125,CEA,and CA724,were elevated in 58.75%,30.63%,30.00%,and 20.63%of GBC patients,respectively.Clinical stage classification revealed that 139 patients(86.87%)had stage Ⅲ/Ⅳ disease,132 patients(82.5%)had T3/T4 stage,91 patients(56.87%)had N1/N2 stage,and 54 patients(33.75%)had M1 stage.The pathological type of GBC was predominantly adenocarcinoma(92.50%),with the majority classified as moderately differentiated(19.38%),moderately to poorly differentiated(34.37%),and poorly differentiated(24.37%).Neural or vascular invasion was present in 29.37%and 21.25%of patients,respectively.Univariate analysis showed that diabetes,jaundice,liver function(Child-Pugh classification),tumor marker levels(CA19-9,CA125,CEA,CA724,CYFRA 21-1),clinical TNM stage,degree of differentiation,vascular or neural invasion,surgical treatment,and other treatments(chemotherapy,immunotherapy,targeted therapy,traditional Chinese medicine,etc.)were significantly associated with the prognosis of GBC patients(all P<0.05).Multivariate Cox regression analysis revealed that diabetes,elevated CA125,and TNM stage were independent risk factors for poor prognosis in GBC,while chemotherapy-based drug treatment was an independent protective factor(all P<0.05).Conclusion:Diabetes,elevated CA125,TNM staging,and treatment methods are closely related to the prognosis of GBC patients.Targeted treatment strategies should be developed for patients with risk factors,and surgery or chemotherapy-based drug therapy should be prioritized to improve patient prognosis.

Background and Amis:Gallbladder cancer(GBC)is the most common malignant tumor of the biliary tract,accounting for approximately 80%-95%of biliary tract cancers.This type of tumor has a poor prognosis,and currently,there are no effective tools for evaluating the prognosis of GBC.Therefore,this study was performed to investigate the factors influencing the prognosis of GBC patients to provide a reference for clinical practice.Methods:The clinical data and follow-up information from 160 GBC patients treated in the Hunan Provincial People's Hospital from January 2018 to January 2024 was retrospectively conducted.The clinicopathologic characteristics of GBC patients were analyzed.Kaplan-Meier and Log-rank tests were used to calculate and compare the differences in overall survival(OS)among GBC patients with different clinicopathologic characteristics and treatment methods.Multivariate analysis using Cox regression was performed to identify independent prognostic factors for GBC.Results:Among the 160 patients,113 were females and 47 were males.The median age of the patients was 62 years,with the main clinical manifestations being abdominal pain/distention(55.63%),jaundice(40.63%),appetite loss(30.62%),and weight loss(19.38%).Serum tumor markers,including CA19-9,CA125,CEA,and CA724,were elevated in 58.75%,30.63%,30.00%,and 20.63%of GBC patients,respectively.Clinical stage classification revealed that 139 patients(86.87%)had stage Ⅲ/Ⅳ disease,132 patients(82.5%)had T3/T4 stage,91 patients(56.87%)had N1/N2 stage,and 54 patients(33.75%)had M1 stage.The pathological type of GBC was predominantly adenocarcinoma(92.50%),with the majority classified as moderately differentiated(19.38%),moderately to poorly differentiated(34.37%),and poorly differentiated(24.37%).Neural or vascular invasion was present in 29.37%and 21.25%of patients,respectively.Univariate analysis showed that diabetes,jaundice,liver function(Child-Pugh classification),tumor marker levels(CA19-9,CA125,CEA,CA724,CYFRA 21-1),clinical TNM stage,degree of differentiation,vascular or neural invasion,surgical treatment,and other treatments(chemotherapy,immunotherapy,targeted therapy,traditional Chinese medicine,etc.)were significantly associated with the prognosis of GBC patients(all P<0.05).Multivariate Cox regression analysis revealed that diabetes,elevated CA125,and TNM stage were independent risk factors for poor prognosis in GBC,while chemotherapy-based drug treatment was an independent protective factor(all P<0.05).Conclusion:Diabetes,elevated CA125,TNM staging,and treatment methods are closely related to the prognosis of GBC patients.Targeted treatment strategies should be developed for patients with risk factors,and surgery or chemotherapy-based drug therapy should be prioritized to improve patient prognosis.

Exocrine pancreatic insufficiency(EPI)is a condition caused by a reduction in the secretion or activity of pancreatic juice and its digestive enzymes,particularly pancreatic lipase.EPI can lead to symptoms such as abdominal pain,bloating,steatorrhea,malnutrition,and weight loss,and may even increase the risk of osteoporosis and cardiovascular diseases.Diagnosis mainly relies on direct and indirect functional tests,while treatment is centered on pancreatic enzyme replacement therapy combined with comprehensive management strategies.This article summarizes the research progress on the definition,common causes,diagnostic methods,treatment,and prevention strategies of EPI,aiming to provide insights for optimizing its diagnosis and management.

Exocrine pancreatic insufficiency(EPI)is a condition caused by a reduction in the secretion or activity of pancreatic juice and its digestive enzymes,particularly pancreatic lipase.EPI can lead to symptoms such as abdominal pain,bloating,steatorrhea,malnutrition,and weight loss,and may even increase the risk of osteoporosis and cardiovascular diseases.Diagnosis mainly relies on direct and indirect functional tests,while treatment is centered on pancreatic enzyme replacement therapy combined with comprehensive management strategies.This article summarizes the research progress on the definition,common causes,diagnostic methods,treatment,and prevention strategies of EPI,aiming to provide insights for optimizing its diagnosis and management.

In recent years, the prevalence rate of nonalcoholic fatty liver disease (NAFLD) has increased significantly and NAFLD has gradually become one of the common chronic liver diseases in China. Patients with NAFLD-related end-stage or deteriorative liver diseases have become one of the main populations for liver transplantation. The increasing prevalence rate of NAFLD and the severe outcomes of nonalcoholic steatohepatitis (NASH) make it necessary to use effective methods to identify NAFLD. Therefore, this article summarizes the current serological methods for the diagnosis of NAFLD, including steatosis, NASH, and liver fibrosis, and discusses their advantages and disadvantages. Although most of the serum markers have limited clinical value, serum marker models have a good application prospect in the diagnosis of hepatic steatosis, the evaluation of fibrosis degree, and preliminary screening. Since a combination of different serological models can improve the accuracy of diagnosis, multi-angle and multicenter joint diagnosis will be a research hotspot in the future.

Objective To investigate the feasibility,safety and surgical technique of treating type Ⅲ and Ⅳ hilar cholangiocarcinoma by laparoscopy.Methods Clinical data and surgical process of 6 patients who underwent laparoscopic radical resection of hilar cholangiocarcinoma in the Hunan Provincial People's Hospital between April 2015 and October 2018 were retrospectively analyzed.The operations were performed by total laparoscopy in all the patients.Surgical procedure included the basic operation type (gallbladder,hilar and common bile duct resection,lymph node dissection of hepatoduodenal ligament),combined with the resectionof liver,caudate lobe,and portal vein resection and reconstruction.The follow-up time ranged from 1 to 42 months.Results The operation time was 540 ～ 660 min,the blood loss was 300 ～ 500 ml.One case of biliary leakage occurred after operation and healed within 2 weeks after drainage.The patients were all discharged succesfully and still alive.Conclusions Laparoscopic radical resection of type Ⅲ and Ⅳ hilar cholangiocarcinoma is safe and feasible under adequate preoperative evaluation,reasonable case selection and rigorous surgical planning.The short-term efficacy of the patients was good.

Objective To explore the treatment experience and efficacy of precise surgery for hepatic caudate lobe involved lesions.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 127 patients with hepatic caudate lobe involved lesions who were admitted to Hunan Provincial People's Hospital between January 2012 and December 2016 were collected,including 71 of malignant tumors,52 of benign lesions and 4 of other diseases.Anatomical hepatectomy was performed in patients via left approach,right approach,anterior approach,left combined with right approach,left and right combined with anterior approach,left and right combined with para-liver hanging tape approach,anterior combined with left approach,retrograde approach according to their conditions.Observation indicators:(1) intraoperative and postoperative recovery situations;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was done to detect postoperative survival of patients up to February 2018.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).Kaplain-Meier method was used to calculate survival rate.Results (1) Intraoperative and postoperative recovery situations:all the 127 patients underwent successful operation without perioperative death,including 111 of open surgery and 16 of laparoscopic surgery.Of 127 patients,single total caudate lobectomy and partial caudate lobectomy were performed in 2 and 13 patients,single hepatic segmentectomy combined with total caudate lobectomy,double hepatic segmentectomy combined with total caudate lobectomy,hepatic trisegmentectomy combined with total caudate lobectomy,left hemitectomy combined with total caudate lobectomy,left hepatic trilobectomy combined with total caudate lobectomy,right hemitectomy combined with total caudate lobectomy,right hepatic trilobectomy combined with total caudate lobectomy were performed in 6,4,5,1,1,30,3 patients respectively,single hepatic segmentectomy combined with partial caudate lobectomy,double hepatic segmentectomy combined with partial caudate lobectomy,left hemitectomy combined with partial caudate lobectomy,left hepatic trilobectomy combined with partial caudate lobectomy,right hemitectomy combined with partial caudate lobectomy,right hepatic trilobectomy combined with partial caudate lobectomy were performed in 3,3,41,2,5,8 patients respectively,including 78 via left approach,29 via right approach,2 via anterior approach,7 via left combined with right approach,2 via left and right combined with anterior approach,6 via left and right combined with para-liver hanging tape approach,1 via anterior combined with left approach,2 via retrograde approach.The operation time,time of first hepatic hilum occlusion,volume of intraoperative blood loss and duration of postoperative hospital stay were 285 minutes (range,188-670 minutes),47 minutes(range,30-150 minutes),294 mL(range,20-2 500 mL) and 10 days (range,6-27 days) respectively.Thirty-four patients had postoperative complications,including 21 with abdominal ascites,20 with pleural effusion,6 with incisional infection,5 with hemorrhage,4 with bile leakage,2 with pulmonary infection (1 patient combined with multiple complications).One patient underwent reoperation after ineffective conservative treatment for hemorrhage within postoperative 24 hours and other 33 were cured by conservative treatment.(2) Follow-up and survival situations:of 127 patients,124 including 68 of malignant tumors and 56 of non-malignant tumors were followed up for 2-71 months with a median time of 33 months.During the follow-up,1-,3-,5-year overall survival rates were 83.1％,63.4％,22.5％ in 68 patients with malignant tumors,89.3％,71.4％,57.1％ in 28 patients with hilar cholangiocarcinoma and 76.9％,46.2％,23.1％ in 26 with hepatocellular carcinoma.All the 56 patients with non-malignant tumors survived well.Conclusions Anatomical hepatectomy using precise surgery is safe and feasible.Preoperative precise evaluation and surgical procedure design,intraoperative vascular control and surgical plane mastering are keys to success.

Objective To investigate the expression of survivin/Human leukocyte antigen class I ( HLA-Ⅰ) proteins and its physiological significance in clear cell renal cell carcinoma ( CCRCC ) . Methods Immunohistochemistry was used to analyze survivin/HLA-Ⅰ protein expression in 90 cases of CCRCC and 10 normal tissues to study relationships with clinical symptoms and disease prognosis . Resutl s The level of survivin protein expression was found to be significantly higher in CCRCC tissues 82.2%( 74/90) than in normal tissues( 0/10).However, the relative amount of HLA-Ⅰprotein in colorectal cancer tis-sue was also found to be significantly lower 67.8%(61/90) than in normal tissues 90%(9/10).Survivin expression was associated with tumor grade , stage,and lymph node metastasis ( P=0.000, P=0.016, and P=0.001, respectively ) .Conversely , lost HLA-Ⅰexpression did not have any associations with clinicopath-ological data (P>0.05).Survivin negative patients (25.0%, 4/16) had a higher tumor-free survival rate than patients (52.7%, 39/74)with survivin expression (P=0.037).Patients (27.6%, 8/29) with normal HLA-Ⅰlevels had a higher tumor-free survival rate than those ( 60.7%, 37/61) with reduced HLA-Ⅰlev-els (P=0.020).The univariate and multivariate analyses indicated that expression of survivin and HLA indi -vidually and in combination were independent predictors for CCRCC patient survival . Conclusions Over-expression of survivin but reduced HLA-Ⅰ expression is associated with CCRCC development and progres-sion.