ObjectiveTo compare the therapeutic effects of carvedilol alone and carvedilol combined with endoscopic variceal ligation （EVL） in the prevention of re-bleeding from gastroesophageal varices， and to provide strategies for clinical treatment. MethodsWe retrospectively included 178 patients who had received carvedilol alone or carvedilol plus EVL to prevent gastroesophageal variceal re-hemorrhage from October 2010 to June 2023. They were divided into carvedilol alone group （47 cases） and carvedilol+EVL group （131 cases）. Between-group comparisons were conducted using the paired t test for normally distributed continuous data， the Mann-Whitney U test for non-normally distributed continuous data， and the chi-square test for categorical data. A Cox proportional hazards model was employed for univariable and multi-variable analyses. The cumulative incidence rates of re-bleeding and mortality were estimated using the Kaplan-Meier method. The baseline characteristics of the two groups were matched through propensity score matching （PSM） to reduce selection bias and enhance the credibility of causal inference. ResultsThe re-bleeding rate of the carvedilol+EVL group was significantly lower than that of the carvedilol alone group （10-year cumulative incidence： 29.8% vs 36.2%， hazard ratio ［HR］=0.505， 95% confidence interval ［CI］： 0.292‍ ‍—‍ ‍0.847， P=0.015）. There was no significant difference in liver-related mortality （10-year cumulative incidence： 21.3% vs 21.4%， HR=0.799， 95%CI： 0.406‍ ‍—‍ ‍1.578， P=0.518）. The results were stable with PSM analysis. The Cox regression analysis revealed that creatinine was an independent risk factor affecting re-bleeding （HR=1.004， 95%CI： 1.001‍ ‍—‍ ‍1.008， P=0.011） and liver-related mortality （HR=1.004， 95%CI： 1.001‍ ‍—‍ ‍1.007， P=0.019）. ConclusionCarvedilol combined with EVL is better than carvedilol alone in the prevention of gastroesophageal variceal re-bleeding.

[摘 要] 目的：观察白细胞介素-37（IL-37）在乳腺癌患者的表达变化对CD8+ T细胞活性的影响。方法：纳入2020年7月至2022年9月在新乡医学院第一附属医院就诊的46例乳腺癌患者、24例乳腺良性肿瘤患者、20例对照者。采集外周血，分离血浆和外周血单个核细胞（PBMC），收集接受手术治疗的乳腺癌患者肿瘤组织和癌旁组织，分离组织中肿瘤浸润淋巴细胞（TIL），纯化CD8+ T细胞。ELISA法检测IL-37、可溶型单免疫球蛋白IL-1受体相关蛋白（SIGIRR）表达，实时定量PCR法检测组织中IL-37 mRNA，流式细胞术检测CD8+ T细胞中IL-18受体α链（IL-18Rα）和SIGIRR表达。外源性IL-37刺激纯化的CD8+ T细胞，与乳腺癌细胞系MCF-7共培养，通过测定乳酸脱氢酶水平计算靶细胞死亡比例，ELISA法检测上清中穿孔素、颗粒酶B、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）水平。结果：乳腺癌患者血浆IL-37水平高于乳腺良性肿瘤患者[（554.17 ± 96.63）pg/mL vs （499.52 ± 78.66）pg/mL，P = 0.020]和对照者[（483.97 ± 47.23）pg/mL，P = 0.003]。乳腺癌患者肿瘤组织中IL-37 mRNA相对表达量高于癌旁组织[（1.88 ± 0.21） vs （1.00 ± 0.53）pg/mL，P < 0.001]。外周血IL-18Rα+ CD8+细胞比例、SIGIRR+ CD8+细胞比例、血浆可溶型SIGIRR水平在乳腺癌患者、乳腺良性肿瘤患者、对照者之间的差异无统计学意义（均P > 0.05）。CD8+ TIL表达IL-18Rα和SIGIRR的比例在肿瘤组织和癌旁组织之间的差异无统计学意义（P > 0.05）。重组人IL-37刺激后，CD8+ T细胞诱导靶细胞死亡比例、上清中IFN-γ和TNF-α水平在直接接触和间接接触共培养系统中均低于无刺激（均P < 0.05）。在直接接触共培养系统中，IL-37刺激后上清中穿孔素和颗粒酶B水平均低于无刺激（均P < 0.001），但在间接接触共培养系统中，上清中穿孔素和颗粒酶B水平在无刺激和IL-37刺激之间的差异无统计学意义（均P > 0.05）。结论：乳腺癌患者中IL-37水平升高可能参与诱导外周血和肿瘤微环境中CD8+ T细胞功能衰竭。

ObjectiveTo investigate the efficacy of percutaneous transhepatic variceal embolization （PTVE） alone or in combination with partial splenic embolization （PSE） in the treatment of portal hypertensive hemorrhage in liver cirrhosis through a meta-analysis. MethodsThis study was conducted according to PRISMA guideline， with a PROSPERO registration number of CRD42023396690. Wanfang Med Online， CNKI， CBM， VIP Databases， PubMed， Embase， the Cochrane Library， and Web of Science databases were searched for articles on PTVE alone or in combination with PSE in the treatment of portal hypertensive hemorrhage in liver cirrhosis published up to December 23， 2022. The articles were selected based on inclusion and exclusion criteria， and related data were extracted. The RevMan 5.4.1 statistical analysis software was used to perform the meta-analysis. ResultsEight articles were finally included， with a total sample size of 592 cases， among which there were 316 cases in the PTVE+PSE group and 276 cases in the PTVE group. The meta-analysis showed that compared with the PTVE group， the PTVE+PSE group had significantly lower postoperative portal vein pressure （standardized mean difference ［SMD］=-1.75， 95% confidence interval ［CI］： -2.33 to -1.16， P<0.05）， postoperative diameter of the portal vein （SMD=-0.87， 95%CI： -1.64 to -0.10， P<0.05）， postoperative rebleeding rate （odds ratio ［OR］=0.17， 95%CI： 0.11 — 0.28， P<0.05）， mortality rate （OR=0.13， 95%CI： 0.04 — 0.37， P<0.05）， and incidence rate of postoperative portal hypertensive gastrointestinal disease （OR=0.17， 95%CI： 0.07 — 0.45， P<0.05］， as well as a significantly higher postoperative platelet level （SMD=0.79， 95%CI： 0.52 — 1.06， P<0.05）， while there were no significant differences between the two groups in the incidence rates of postoperative ascites. ConclusionCompared with PTVE alone， PTVE combined with PSE can effectively reduce the rebleeding rate and mortality rate of portal hypertensive hemorrhage in liver cirrhosis， the incidence rate of portal hypertensive gastrointestinal disease， and portal vein pressure， and it can also shorten the diameter of the portal vein and increase platelet level. Therefore， it is an effective interventional method for the treatment of portal hypertension hemorrhage in liver cirrhosis.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective The objective of this study was to investigate the expression of interleukin-38(IL-38)in patients with breast cancer and its regulatory function to CD8+T cell activity.Methods 44 patients with breast cancer,25 patients with benign breast tumor,and 20 controls,who were treated in the First Affiliated Hospital of Xinxiang Medical University from July 2020 and Sep-tember 2022.Mononuclear cells from plasma and peripheral blood of all subjects were isolated,tumor-infiltrating lymphocytes from tumor tissues of breast cancer patients were isolated,and CD8+T cells were purified.IL-38 protein level in the plasma was measured by enzyme-linked immunosorbent assay(ELISA).The relative level of IL-38 mRNA in the tissue was semi-quantified by real-time quantitative PCR.Recombinant human IL-38 was used to stimulate CD8+T cells from peripheral blood and tumor tissue from patients with breast cancer.A co-culture system was established between CD8+T cells and breast cancer MCF-7 cell line.The percentage of target cell death was calculated by measuring lactate dehydrogenase level in the supernatants.The levels of perforin,granzyme B,inter-feron-γ and tumor necrosis factor-α(TNF-α)in the supernatants were measured by ELISA.The immune checkpoint molecules ex-pression in CD8+T cells were detected by flow cytometry.Results The levels of plasma IL-38 were significantly higher in patients with breast cancer(74.23±19.88 pg/mL)compared with in patients with benign breast tumor(62.87±16.27 pg/mL,P=0.018)and controls(61.77±12.75 pg/mL,P=0.013).The relative expression of IL-38 mRNA in tumor tissues was significantly higher than in para-tumor tissues(1.57±0.22 vs.1.00±0.18,P<0.001).The proportion of target cell death induced by peripheral and tumor-in-filtrating CD8+T cells,and the levels of perforin and granzyme B secretion in direct contact co-culture group were higher than those in indirect contact co-culture group(P<0.05).There were no significant differences of either interferon-γ or TNF-α levels between di-rect contact and indirect contact co-culture group(P>0.05).In the direct contact co-culture group,the levels of target cell death pro-portion,perforin,granzyme B,interferon-γ and TNF-α l in the IL-38 stimulation group were lower than those in the non-stimulation group(P<0.05).In the indirect contact co-culture group,the target of cell death proportion,interferon-γ and TNF-α the IL-38 stimulation group were also lower than those in the non-stimulation group(P<0.05).However,there were no statistical differences of either perforin or granzyme B levels between the IL-38 stimulation group and non-stimulation group within the indirect contact co-culture group(P>0.05).There were also no differences in the levels of immune checkpoint molecules in CD8+T cells between the non-stimulation group and the IL-38 stimulation group(P>0.05).Conclusion Highly expressed IL-38 in patients with breast cancer may be involved in inducing CD8+T cell functional failure.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To investigate the feasibility and safety of endoscopic ultrasound (EUS)-guided intrahepatic portal vein puncture through jugular vein implantation in transjugular intrahepatic portosystemic shunt (TIPS).Methods:As research subjects, 5 beagle dogs were anesthetized, and EUS was placed through the jugular vein to observe the intrahepatic portal vein. Under real-time guidance, the portal vein was punctured and a stent was placed to complete the TIPS.Results:Among the 5 beagles, EUS was unable to be placed in 1 due to the small diameter of the external jugular vein, and it was implanted successfully in 4 others through the external jugular vein who underwent real-time guidance of portal vein puncture. Subsequent stent placement and balloon dilation were completed. All animals survived after the experiment.Conclusion:EUS-guided intrahepatic portal vein puncture through jugular vein implantation is safe and feasible in TIPS.

Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.

Objective:To retrospectively analyze prognostic factors and patterns of recurrence in locally advanced gastric cancer patients receiving chemoradiotherapy (CRT) after radical gastrectomy, aiming to provide reference for postoperative CRT of locally advanced gastric cancer.Methods:Clinical data of 171 patients with curatively resected gastric carcinoma who received postoperative CRT in our hospital between 2008 and 2020 were retrospectively analyzed. The disease-free survival and overall survival (OS) rates were calculated by Kaplan- Meier method. Univariate prognostic analysis was performed by log- rank test. Multivariate prognostic analysis was conducted by Cox model. Results:The median follow-up duration was 63 months. The follow-up rate was 93.6%. 31.0% and 66.7% of the enrolled patients were classified in pathological stage Ⅱ and Ⅲ. The acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 8.8% and 9.9%, respectively. In total, 166 patients completed the entire CRT regimen. No toxicity-related death occurred. Regarding patterns of recurrence, 17 patients had locoregional recurrence, 29 had distant metastasis and 12 had peritoneal metastasis. The 1-, 3-and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, while the 1-, 3-and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. In the multivariate analysis, pathological T stage, perineural invasion and lymph node ratio (LNR) were found to be the independent predictors of OS.Conclusions:Postoperative intensity-modulated radiation therapy and chemotherapy are well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. LNR can be used as an independent prognostic indicator for OS. Adjuvant CRT should be considered for all patients with a high risk of locoregional recurrence.

Objective:To explore the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt.Methods:The basic information, laboratory test results, preoperative portal venous pressure, postoperative anticoagulation time, postoperative stent stenosis or occlusion, followed-up and other data of all patients who underwent TIPS surgery in Shandong Provincial Hospital from 2010 to 2019 were retrospectively analyzed. Data were analyzed using t-test, χ2 test, and multivariate analysis (logistic regression and Cox-regression-analysis). Results:A total of 280 cases were finally included in the study, of which 110 (39.3%) had stent stenosis or occlusion, and 170 (60.7%) had stent patency. New or worsening ascites were identified in 194 cases during the follow-up period, including 14 (31.1%) cases in the stent stenosis or occlusion group and 19 (12.8%) cases in the stent patency group. Univariate analysis showed that presence or absence of platelet ( P=0.037) and total bilirubin ( P=0.038) were correlated with stent stenosis or occlusion. Postoperative continuous anticoagulation was correlated with stent blockage ( P=0.029) in patients with partial portal vein thrombosis. Postoperative continuous anticoagulation and stent occlusions were not significantly correlated in patients with preoperative portal cavernoma and preoperative portal vein patency ( P=0.848; P=0.744). Multivariate analysis results showed that whether long-term anticoagulation ( P=0.017), all-cause rebleeding ( P<0.001), postoperative significant hepatic encephalopathy ( P<0.012), and postoperative new or worsening ascites ( P<0.001) was significantly associated with stent occlusion ( P<0.05), while platelets ( P=0.134), total bilirubin ( P=0.229), international normalized ratio ( P=0.436), and portal vein pressure ( P=0.230) were not significantly associated with stent occlusion after surgery. Conclusion:In patients with partial portal vein thrombosis before surgery, continuous anticoagulation for 30 days post-TIPS therapy can effectively prevent stent stenosis or occlusion; while in patients with portal vein patency, portal cavernoma and complete portal vein blockage before surgery, postoperative anticoagulation has no significant effect on stent stenosis or occlusion.