1.Clinical significance of determining the level of biliary calprotectin in patients with cholangiocarcinoma or choledocholithiasis
Tingting JI ; Bingqing BAI ; Yufang CUI ; Shaofei WANG ; Jianglong HONG ; Yang LI ; Junjun BAO ; Qiao MEI
Journal of Clinical Hepatology 2024;40(3):568-572
ObjectiveTo investigate the difference in the level of biliary calprotectin between patients with cholangiocarcinoma and those with choledocholithiasis. MethodsClinical data and bile samples were collected from 34 patients with cholangiocarcinoma and 78 patients with choledocholithiasis who were diagnosed and treated with endoscopic retrograde cholangiopancreatography in The First Affiliated Hospital of Anhui Medical University from May 2021 to September 2022. Fluorescence lateral flow immunoassay was used to measure the levels of calprotectin, hemoglobin, and lactoferrin in bile. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Spearman correlation test was used for correlation analysis; the DeLong test was used for comparison of the area under the ROC curve (AUC). ResultsCompared with the choledocholithiasis group, the cholangiocarcinoma group had significant increases in the levels of calprotectin [4 795.50 (2 286.79 — 20 179.73) ng/mL vs 411.16 (67.03 — 1 991.88) ng/mL, Z=5.572, P<0.001] and fluoride [115.70 (109.10 — 125.50) mmol/L vs 106.60 (98.60 — 114.40) mmol/L, Z=2.702, P=0.007]. The patients with cholangiocarcinoma were further divided into high cholangiocarcinoma group and low cholangiocarcinoma group, and there was no significant difference between the two groups in the level of calprotectin [3 867.71 (2 235.66 — 26 407.40) ng/mL vs 4 795.50 (2 361.15 — 13 070.53) ng/mL, Z=0.129, P>0.05]. Biliary calprotectin level was correlated with white blood cell count, hemoglobin concentration, and lactoferrin concentration in bile (r=0.316, 0.353, and 0.464, all P<0.05). The ROC curve analysis showed that biliary calprotectin (with a sensitivity of 79.4% and a specificity of 75.6%), blood CA19-9 (with a sensitivity of 82.4% and a specificity of 78.2%), and their combination (with a sensitivity of 88.2% and a specificity of 73.1%) had good sensitivity and specificity in the diagnosis of cholangiocarcinoma. ConclusionThere is an increase in the level of biliary calprotectin in patients with cholangiocarcinoma, and therefore, it might become a biomarker for the diagnosis of cholangiocarcinoma.
2.Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study
Li LI ; Yunhe GAO ; Liang SHANG ; Zhaoqing TANG ; Kan XUE ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Bin KE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Hongqing XI ; Yun TANG ; Zhi QIAO ; Han LIANG ; Jiafu JI ; Lin CHEN
Chinese Journal of Digestive Surgery 2024;23(1):114-124
Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.
3.Expression and significance of N-WASP in placentas with preeclampsia
Shuo ZHANG ; Yunpeng GE ; Tingting WANG ; Hongfei SHEN ; Jiapo LI ; Guiyu SONG ; Chong QIAO
Journal of China Medical University 2024;53(2):97-101,120
Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P<0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P<0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P<0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P<0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.
4.Eukaryotic translation initiation factor 4A3-regulated circular RanGTPase activating protein 1 participates in pathogenesis of preeclampsia by regulating proliferation, migration, and invasion of trophoblast cells
Tingting WANG ; Yunpeng GE ; Hongfei SHEN ; Jiapo LI ; Yilin LIU ; Chong QIAO
Chinese Journal of Perinatal Medicine 2024;27(9):742-749
Objective:To investigate the impact of circular RanGTPase activating protein 1 (circRANGAP1) on the biological behavior of trophoblast cells in preeclampsia and its potential mechanisms.Methods:Placental tissues were collected from preeclampsia patients and age- and gestational age- matched control pregnant women admitted to Shengjing Hospital of China Medical University from August 2020 to December 2022 (eight cases each in the early-onset preeclampsia group and early-onset control group, and 24 cases each in the late-onset preeclampsia group and late-onset control group). The expression levels of circRANGAP1 and eukaryotic translation initiation factor 4A3 (EIF4A3) mRNA in placental tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and EIF4A3 protein expression was assessed by Western blotting. In HTR-8/Svneo cells, the proliferation, migration, and invasion abilities were evaluated by cell counting assay, scratch assay, Transwell invasion assay, and the regulatory effect of EIF4A3 on circRANGAP1 was examined by RNA binding protein immunoprecipitation (RIP). Changes of circRANGAP1 expression in HTR-8/Svneo cells were detected by RT-qPCR after EIF4A3 knockdown. Statistical analysis was performed using independent sample t-test, non-parametric Chi-square test, or Pearson correlation analysis. Results:(1) There was no significant difference in circRANGAP1 expression between the early-onset preeclampsia group and the early-onset control group. However, circRANGAP1 expression was higher in the late-onset preeclampsia group compared to the late-onset control group [(3.764±3.297) vs. (0.960±0.720), t=4.07, P<0.001]. In late-onset preeclampsia patients, circRANGAP1 expression was positively correlated with both systolic and diastolic blood pressure (systolic: r=0.639, P<0.01; diastolic: r=0.800, P<0.001). There was no significant difference in EIF4A3 mRNA and protein expression between the early-onset preeclampsia group and the early-onset control group, but EIF4A3 mRNA and protein expression were higher in the late-onset preeclampsia group compared to the late-onset control group [mRNA: (2.963±3.081) vs. (1.149±0.667), t=2.30, P=0.028; protein: (2.504±1.008) vs. (0.258±0.180), t=4.39, P=0.005]. (2) After small interfering (si) RNA knockdown, there was no significant difference in mRANGAP1 expression, but circRANGAP1 expression decreased [(1.000±0.004), (0.465±0.031), and (0.621±0.030)], with si-1 showing the highest knockdown efficiency ( t=23.59, P=0.002). Specific knockdown of circRANGAP1 resulted in increased proliferation [(1.297±0.058) vs. (1.456±0.030), t=-5.97, P<0.001], invasion [(94.400± 6.504) vs. (219.000±19.870), t=-13.32, P<0.001], and migration [(25.493±3.498)% vs. (58.456±3.277)%, t=-15.38, P<0.001] abilities of trophoblast cells. (3) There are six binding sites for EIF4A3 in the upstream region of circRANGAP1 pre-mRNA. EIF4A3 can bind through regions a and b, but not region c. After siRNA knockdown, EIF4A3 expression decreased [(1.003±0.101), (0.276±0.060), (0.398±0.074), and (0.184±0.017)], with si-3 showing the highest knockdown efficiency. After EIF4A3 knockdown, circRANGAP1 expression in trophoblast cells decreased [(1.004±0.118) vs. (0.480±0.039), t=5.96, P=0.027]. Conclusion:circRANGAP1, regulated by EIF4A3, inhibits the proliferation, migration, and invasion abilities of trophoblast cells, thereby participating in the pathogenesis of preeclampsia.
5.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
6.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
7.Research progress on the training of ultrasound specialist nurses in the field of acute and critical care
Tingting QIAO ; Shu LIU ; Yuan ZHONG ; Yangyang QIN ; Xian SUN ; Danshi HAO
Chinese Journal of Modern Nursing 2024;30(30):4078-4081
The evaluation, diagnosis, real-time monitoring, and guided operation conducted by ultrasound specialist nurses in acute and critical care can provide an objective basis for nursing decision-making, which is of great significance for optimizing nursing procedures and improving the survival rate and rehabilitation rate of patients. This paper summarizes the concept, origin, training status, and practice scope of ultrasound specialist nurses in the field of acute and critical care and puts forward the prospect of development in order to provide a reference for the training of ultrasound specialist nurses in the field of acute and critical care in China.
8.Meta-integration of health promoting behaviors in stroke survivors:a qualitative study
Xiaohan HU ; Tingting ZHAN ; Wangsheng HE ; Hailin JIANG ; Xue LI ; Shutong QIAO
Modern Clinical Nursing 2023;22(11):49-58
Objective To systematically integrate qualitative studies on health promoting behaviors of stroke patients and provide references for the development of relevant behavioral interventions.Methods Qualitative studies on health promotion behaviors of stroke patients were retrieved from CNKI,Wanfang,China Biomedical Database,VIP,PubMed,Web of Science,the Cochrane Library,and Embase from the inscription to February 2023.The JBI Model of Evidence-Based Healthcare was employed to assess the quality of the acquired literature,with the results treated with meta-integration.Results A total of 9 articles were included in the study.From the literature acquired 49 complete themes were abstracted and 3 novel types of literature were yielded.By meta-integration,11 factors affecting the health promoting behaviors of the stroke patients were concluded,including ability of patients such as physical dysfunction,disease cognition,disease risk management,motivation such as negative emotional distress,positive emotional experience,psychological self-regulation,and opportunity such as family caring degree,iatrogenic support,peer mutual support,access to information,and environmental restrictions.Conclusions The factors influencing health promoting behaviors of stroke patients consist of ability,motivation,and opportunity.Medical staff should care about their mental and physical experience,establishing a multi-social support system and working hard to promote the transformation of their health behaviors.
9.Clinical study on the level of neutrophil extracellular trap in the bile of patients with choledocholithiasis
Xin FU ; Yufang CUI ; Shaofei WANG ; Tingting JI ; Bingqing BAI ; Jianglong HONG ; Yang LI ; Junjun BAO ; Qiao MEI
Chinese Journal of Digestion 2023;43(6):371-375
Objective:To investigate the activation level of neutrophil extracellular trap (NET) in the bile of patients with choledocholithiasis and its clinical significance.Methods:From May 2021 to October 2022, 130 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University were enrolled. The patients were divided into choledocholithiasis group (90 cases) and non-choledocholithiasis group (40 cases), and the choledocholithiasis group was further divided into large stone group (maximum diameter >1 cm, 36 cases) and small stone group (maximum diameter≤1 cm, 54 cases). The bile samples were collected from 130 patients during operation and 16 choledocholithiasis patients with nasobiliary drainage at 24 h after operation.The levels of myeloperoxidase(MPO), neutrophilelastase(NE), and citrullinated histone H3(CitH3) in bile were detected by enzyme-linked immunosorbent assay.The levels of MPO, NE, and CitH3 were compared between choledocholithiasis group and non-choledocholithiasis group, between large stone group and small stone group, as well as between choledocholithiasis patients before ERCP and after ERCP. Mann-Whitney U test and Wilcoxon signed rank test were used for statistical analysis. Results:The levels of MPO, NE and CitH3 in the bile of choledocholithiasis group were 32.6 U/L(28.5 U/L), 30.6 ng/L(35.2 ng/L) and 0.37 μg/L(0.73 μg/L), respectively, which were all higher than those of non-choledocholithiasis group (19.9 U/L(36.4 U/L), 18.2 ng/L(27.4 ng/L), and 0.10 μg/L(0.25 μg/L)), and the differences were statistically significant ( Z=2.91, 3.20 and 3.34; P=0.004, 0.001 and 0.001). The levels of MPO, NE and CitH3 of large stone group were 47.0 U/L(49.4 U/L), 48.4 ng/L(39.5 ng/L) and 0.83 μg/L(1.08 μg/L), respectively, which were all higher than those of small stone group (29.3 U/L(17.5 U/L), 24.0 ng/L(25.8 ng/L), and 0.27 μg/L(0.45 μg/L)), and the differences were statistically significant ( Z=2.01, 3.58 and 3.63; P=0.044, <0.001 and <0.001). The levels of MPO, NE and CitH3 in the bile of choledocholithiasis patients after ERCP significantly decreased compare with those before ERCP (19.4 U/L(19.8 U/L) vs. 33.6 U/L(36.7 U/L), 12.7 ng/L(15.1 ng/L) vs. 22.7 ng/L(25.9 ng/L), 0.05 μg/L(0.12 μg/L) vs. 0.14 μg/L(0.27 μg/L)), and the differences were statistically significant ( Z=3.52, 3.30 and 3.18; all P<0.001). Conclusion:The activation level of NET in the bile of patients with choledocholithiasis increase, while the activation level of NET decrease after ERCP, which indicate that NET may be involved in the formation of choledocholithiasis.
10.Alleviation of isoproterenol-induced myocardial fibrosis in mice by autophagy regulated by Astragaloside Ⅳ through activating ROCK/JNK pathway
Feifei WU ; Xiaoqi ZHANG ; Jing LIAN ; Jing YANG ; Mengen ZHAI ; Rui QIAO ; Chennian XU ; Tingting YANG
Journal of Pharmaceutical Practice 2023;41(8):478-484
Objective To investigate the effect and mechanism of astragaloside Ⅳ(AS-Ⅳ) activating ROCK/JNK to regulate autophagy in improving isoproterenol (ISO) induced myocardial fibrosis (MF) in mice. Methods The mice were randomly divided into control operation group (Control group), ISO induced myocardial fibrosis group (MF group), AS-Ⅳ treatment group (AS-Ⅳ group) and combination group of astragaloside IV and Y-33075 (ROCK inhibitor) (astragaloside IV+Y-33075 group). After repeated administration for 30 days. The serum levels of LDH, BNP, CTGF in each group were detected. The cardiac function was detected by ultrasound. Myocardial structure and tissue fibrosis degree in each group were detected by Sirius Red and Masson staining. Oxidative stress (ROS) levels in myocardial tissue of each group were detected by DHE staining and the expression of ROCK, JNK, Atg5, Beclin 1, and LC3 Ⅰ/Ⅱ in myocardial tissue were detected by Western blotting. Results Compared with AS-Ⅳ group, the EF value of AS-Ⅳ+Y-33075 group decreased and the degree of myocardial fibrosis increased (P<0.05). The serum level of LDH, BNP, CTGF increased and the level of ROS in myocardial tissue increased while the expression of ROCK, JNK, Atg5, Beclin 1, LC3 Ⅰ/Ⅱ decreased (P<0.05). Y-33075 could block the protective effect of AS-Ⅳ on myocardial injury induced by MF and inhibit the regulation of AS-Ⅳ on ROCK and JNK. Conclusion AS-Ⅳ could attenuate myocardial fibrosis in mice by activating ROCK/JNK signal and promoting autophagy.

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