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.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

The tumor microenvironment,particularly the hypoxic property and glutathione(GSH)overexpression,substantially inhibits the efficacy of cancer therapy.In this article,we present the design of a magnetic nanoplatform(MNPT)comprised of a photosensitizer(Ce6)and an iron oxide(Fe3O4)/manganese oxide(MnO2)composite nanozyme.Reactive oxygen species(ROS),such as singlet oxygen(1O2)radicals produced by light irradiation and hydroxyl radicals(·OH)produced by catalysis,are therapeutic species.These therapeutic substances stimulate cell apoptosis by increasing oxidative stress.This apoptosis then triggers the immunological response,which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer.Furthermore,MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

Objective To investigate the difference of CT features of gastrointestinal stromal tumors(GIST),neurogenic tumors,and leiomyomas in stomach.Methods A retrospective analysis was performed on clinical and CT features from 312 cases of GIST,21 cases of neurogenic tumors,and 35 cases of leiomyomas in stomach.Results GIST were most commonly found in the body of stomach and exhibited large tumor sizes and late onset.CT showed GIST predominantly showed intraluminal and mixed growth pattern with irregular or round shapes and uneven density,and cystic degeneration and calcification were frequently observed.The CT values of GIST in the arterial phase and the degree of arterial enhancement were higher,with light to moderate arterial phase enhancement and moderate to marked venous phase enhancement.Gastric leiomyomas had smaller tumor sizes and presented mainly in the cardia,gastric fundus,and lesser curvature of gastric body.CT showed the intraluminal growth pattern,primarily in round shapes with uniform density,lower incidence of cystic degeneration and calcification,both the arterial and venous phase CT values and the extent of enhancement in these phases were lower,showed no or slight enhancement during the arterial phase and light to moderate enhancement during the venous phase.Gastric neurogenic tumors were predominantly located in the gastric body and antrum.CT showed the tumors demonstrated extraluminal and mixed growth patterns,most with oval-shaped appearace,uniform density and the venous phase CT values and the degree of enhancement were higher,with light to moderate arterial enhancement and moderate to marked venous enhancement.Conclusion GIST,neurogenic tumors,and leiomyomas in stomach can be differentiated based on their distinct CT features.Accurate recognition of these features aids in the differential diagnosis of these kinds of tumors.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To evaluate the diagnostic value of endoscopic ultrasonography(EUS)in the preoperative staging and ductal dilatation of duodenal papillary carcinoma and analyze the factors influencing its diagnostic accuracy.Methods A cross-sectional trial was conducted on the patients with pathologically-diagnosed duodenal papillary carcinoma and undergoing EUS in the First Affiliated Hospital of Army Medical University from January 2018 to August 2023.The diagnostic value of EUS for the preoperative staging of duodenal papillary carcinoma was evaluated using sensitivity,specificity,positive predictive value,negative predictive value,and accuracy.Univariate and multivariate analyses were performed to determine the factors affecting the diagnostic accuracy of EUS.Results A total of 102 patients with duodenal papillary carcinoma were included,including 59 males and 43 females,at a mean age of 62 years,and all of them underwent EUS before diagnosis.The accuracy of EUS for tumor T-staging was 86.27％,the sensitivity and specificity for T1,T2,T3,and T4 lesions were 84.21％,92.31％,85.00％,60.00％,and 95.31％,88.89％,96.34％,and 98.97％,respectively.The positive predictive value for T-staging of T1,T2,T3,and T4 lesions was 91.43％,83.72％,85.00％,and 75.00％,and the negative predictive values were 91.04％,94.92％,96.34％,and 97.96％,respectively.There were 14 patients whose T-staging was incorrectly staged by EUS.The accuracy of EUS in assessing intraductal dilatation was 75.49％,and the sensitivity,specificity,positive predictive value,and negative predictive value for ductal dilatation were 96.97％,66.67％,98.97％,and 40.00％,respectively.In addition,the independent predictors of diagnostic accuracy of EUS for pancreatic duct dilatation were nerve infiltration,tumor size,and T stage;whereas the independent risk factors for diagnostic accuracy of bile duct dilatation were nerve infiltration and alkaline phosphatase.Conclusion EUS has quite higher diagnostic value for preoperative staging of duodenal papillary carcinoma,and nerve infiltration,tumor size,T stage,T stage and alkaline phosphatase may be the influencing factors for its diagnostic accuracy.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective To evaluate the safety and efficacy of CT-guided percutaneous transhepatic gallbladder drainage(PTGBD)in treatment of high-risk acute cholecystitis(AC)patients.Methods CT-guided PTGBD was performed in 29 patients with high-risk AC.The therapeutic results were evaluated by comparing the preoperation and postoperation clinical manifestations and laboratory results.Results The implantation of PTGBD catheter was successfully accomplished with single procedure in all patients.Complica-tions occurred in 2 cases,including abdominal pain in 1 case and a small amount of gallbladder bleeding in 1 case,and the incidence of complications was 6.9%.Compared with preoperation,the pain number rating scale(NRS)score,temperature(T),white blood cell count(WBC),C-reactive protein(CRP),total bilirubin(TBIL),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were significantly decreased 3 days after PTGBD(P<0.001).Except for 1 case of choledocholithiasis with continuous abdominal pain after PTGBD,the postoperation symptoms of the other patients were significantly relieved.Followed up for 3 months,2 cases of calculous AC recurred after PTGBD,and the recurrence rate of cholecystitis was 25.0%.Conclusion For high-risk AC,the CT-guided PTGBD is a safe and effective treatment method,and it can remarkably relieve the clinical symptoms.Patients with calculous AC have higher risk of recurrence and might benefit from definitive cholecystectomy.

ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.