Objective To investigate the mechanism of modified Huanglian Wendan Decoction in improving insulin resistance(IR)HepG2 cells by regulating JAK2/STAT3 signaling pathway.Methods HepG2 cells were incubated with 0.25 mmol/L palmitic acid for 24 h to induce IR model.The cells were divided into model group,drug containing serum group and metformin hydrochloride group.Blank serum,modified Huanglian Wendan Decoction drug containing serum and 2 mmol/L metformin hydrochloride intervention were administered,respectively.Normal cultured HepG2 cells were used as control group.The glucose assay kit was used to detect the glucose content in the cell supernatant,the liver glycogen assay kit was used to detect the glycogen content in the cells,the triglycerides(TG)assay kit was used to detect the TG content in the cells,PAS staining was used to observe the glycogen status of the cells,oil red O staining was used to observe the lipid droplet status of the cells,ELISA assay kit was used to detect the contents of interleukin-6(IL-6)and tumor necrosis factor(TNF)-α in cell supernatant,Western blot was used to detect the protein expressions of Janus kinase 2(JAK2),signal transduction and transcription activator 3(STAT3),LC3 and Beclin-1 in the cells.Results Compared with the control group,the glucose content in the supernatant of HepG2 cells in the model group increased(P<0.01),the intracellular glycogen content decreased(P<0.01),the TG content increased(P<0.01),the glycogen staining area decreased(P<0.01),the lipid droplet staining area increased(P<0.01),the contents of IL-6 and TNF-α in the supernatant increased(P<0.01),the expressions of JAK2 and STAT3 proteins increased(P<0.01),and the protein expression of LC3Ⅱ/LC3Ⅰ and Beclin-1 decreased(P<0.01).Compared with the model group,the glucose content decreased in the drug containing serum group and metformin hydrochloride group(P<0.01),the intracellular glycogen content increased(P<0.01),the TG content decreased(P<0.01),the glycogen staining area increased(P<0.01),the lipid droplet staining area decreased(P<0.01),the contents of IL-6 and TNF-α in cell supernatant decreased(P<0.01),the expressions of JAK2 and STAT3 proteins decreased(P<0.01),and the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins increased(P<0.05,P<0.01).The effect of modified Huanglian Wendan Decoction was better than that of metformin hydrochloride(P<0.05,P<0.01).Conclusion Modified Huanglian Wendan Decoction can possibly improve glucose and lipid metabolism and reduce inflammation in IR-HepG2 cells through intervening JAK2/STAT3 signaling pathway and mediating autophagy.

Objective To investigate the mechanism of modified Huanglian Wendan Decoction in improving insulin resistance(IR)HepG2 cells by regulating JAK2/STAT3 signaling pathway.Methods HepG2 cells were incubated with 0.25 mmol/L palmitic acid for 24 h to induce IR model.The cells were divided into model group,drug containing serum group and metformin hydrochloride group.Blank serum,modified Huanglian Wendan Decoction drug containing serum and 2 mmol/L metformin hydrochloride intervention were administered,respectively.Normal cultured HepG2 cells were used as control group.The glucose assay kit was used to detect the glucose content in the cell supernatant,the liver glycogen assay kit was used to detect the glycogen content in the cells,the triglycerides(TG)assay kit was used to detect the TG content in the cells,PAS staining was used to observe the glycogen status of the cells,oil red O staining was used to observe the lipid droplet status of the cells,ELISA assay kit was used to detect the contents of interleukin-6(IL-6)and tumor necrosis factor(TNF)-α in cell supernatant,Western blot was used to detect the protein expressions of Janus kinase 2(JAK2),signal transduction and transcription activator 3(STAT3),LC3 and Beclin-1 in the cells.Results Compared with the control group,the glucose content in the supernatant of HepG2 cells in the model group increased(P<0.01),the intracellular glycogen content decreased(P<0.01),the TG content increased(P<0.01),the glycogen staining area decreased(P<0.01),the lipid droplet staining area increased(P<0.01),the contents of IL-6 and TNF-α in the supernatant increased(P<0.01),the expressions of JAK2 and STAT3 proteins increased(P<0.01),and the protein expression of LC3Ⅱ/LC3Ⅰ and Beclin-1 decreased(P<0.01).Compared with the model group,the glucose content decreased in the drug containing serum group and metformin hydrochloride group(P<0.01),the intracellular glycogen content increased(P<0.01),the TG content decreased(P<0.01),the glycogen staining area increased(P<0.01),the lipid droplet staining area decreased(P<0.01),the contents of IL-6 and TNF-α in cell supernatant decreased(P<0.01),the expressions of JAK2 and STAT3 proteins decreased(P<0.01),and the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins increased(P<0.05,P<0.01).The effect of modified Huanglian Wendan Decoction was better than that of metformin hydrochloride(P<0.05,P<0.01).Conclusion Modified Huanglian Wendan Decoction can possibly improve glucose and lipid metabolism and reduce inflammation in IR-HepG2 cells through intervening JAK2/STAT3 signaling pathway and mediating autophagy.

The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus.The paper focuses on reviewing the clinical applications of several novel ultrasound technologies,including the use of advanced hemodynamic parameters such as blood flow dispersion(Tur index)and wall shear stress(WSS).Carotid artery stenosis is closely associated with cardiovascular disease.Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent,with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity,the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.

Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.

Abstract OBJECTIVE To explore the effect of the polymorphisms of ATM(rs11212617), KCNJ11(rs5219), CYP2C9(rs1799853, rs1057910), TCF7L2(rs12255372, rs290487) and IRS1(rs1801278) on efficacy of metformin and gliclazide combined treatment for diabetes mellitus type 2. METHODS Eighty-one patients with newly diagnosed diabetes mellitus type 2 in Standardized Metabolic Disease Management Center of the Endocrinology Department of of Zhejiang Chinese Medical University Affiliated Jiaxing TCM Hospital were enrolled in this study, and they were treated with metformin hydrochloride tablets and gliclazide modified release tablets. MassARRAY was used to type the above single nucleotide polymorphism(SNP), and followed up for 3 months. Fasting plasma glucose(FPG), glycosylated hemoglobin type Alc(HbA1c) and fasting insulin(FINS) were compared before and after treatment. RESULTS The gene frequencies of all SNPs were compliant to Hardy-Weinberg equilibrium, the samples were well represented. The rs1799853, rs1057910, rs12255372 and rs1801278 had low mutation frequencies with poor clinical significance. The benefits of FPG compliance rate, increase of FINS, decrease of HbAlc after treatment were stronger in patients with homozygous rs5219 C allele than those with T-allele carriers (P<0.05). However, there were no significant differences in treatment effects among the genotypes of rs11212617 and rs290487. CONCLUSION The rs5219 polymorphism of KCNJ11 gene is associated with the efficacy of metformin hydrochloride tablets and gliclazide modified release tablets in treating diabetes mellitus type 2, with a more significant effect observed in individuals homozygous for the C allele. This finding can serve as a reference for personalized medication in clinical treatment of diabetes mellitus type 2.

Objective:To explore the efficacy and safety of Ganhai Weikang capsule (GWC) in the treatment of functional dyspepsia (FD).Methods:A randomized, double-blind, placebo-controlled parallel, multi-center, superiority clinical trial was conducted. From March 2018 to April 2020, totally 324 patients with dyspepsia symptoms, who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the Rome Ⅳ diagnostic criteria for FD from 7 top hospitals were enrolled, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Heilongjiang Hospital of Traditional Chinese Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Qilu Hospital of Shandong University, the First Affiliated Hospital of Zhejiang University, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University. The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1. The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant. The patients of both groups orally took capsules before meals, 2.4 g each time and 3 times per day, and the course of treatment was 4 weeks. The main efficacy index was the total clinical effective rate after 4 weeks, and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety. The safety index included laboratory tests and adverse events. Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 320 FD patients were enrolled in the full analysis set (FAS), which included 161 cases in GWC group and 159 cases in placebo group. A total of 298 cases were in the per-protocol set (PPS), 149 cases each in GWC group and placebo group. The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group (84.5%, 136/161 vs. 44.0%, 70/159 and 83.9%, 125/149 vs. 46.3%, 69/149), and the differences were statistically significant ( χ2=57.07 and 46.32, both P<0.001). In addition, the differences of the total score of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (FAS: 10 (7, 14) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 3); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs. 1 (0, 3). PPS: 10 (7, 13) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 2); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs.1 (0, 3)), and the differences were statistically significant (FAS: Z=5.80, 5.91, 3.19, 3.72 and 3.30; PPS: Z=5.14, 5.11, 2.86, 3.21 and 2.84; all P<0.01). The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) of GWC group were all higher than those of the placebo group (FAS: 77.8% (54.6%, 91.3%) vs. 42.9% (28.6%, 61.5%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 60.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 41.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%). PPS: 77.8% (54.2%, 89.5%) vs. 44.0% (28.6%, 65.0%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 46.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%)), and the differences were statistically significant (FAS: Z=8.60, 7.72, 4.98, 4.24 and 5.61; PPS: Z=7.90, 7.03, 4.49, 3.88 and 4.83; all P<0.001). After 2 weeks of treatment, the differences of the total score of main symptoms and score of each symptom (upper abdominal pain, upper abdominal burning and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0); 2.0 (1.0, 2.0) vs. 2.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0)), and the differences were statistically significant ( Z=2.95, 3.44, 2.43 and 2.79, all P<0.05). There was no significant difference in the incidence of adverse events between the GWC group and the placebo group (0.6%, 1/163 vs. 0, 0/159). Conclusion:The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.

Objective:To evaluate the differences in pregnancy outcomes of patients and cost variance with hormone replacement therapy for frozen-thawed embryo transfer (HRT-FET) under different luteal support scheme.Methods:A retrospective cohort study was performed. A total of 1009 cycles of HRT-FET from October 2017 to April 2019 were collected and the patients were recruited from Reproductive Hospital Affiliated to Shandong University. According to different luteal support protocol, patients in group A ( n=504) were treated with oral progesterone capsule while patients in group B ( n=505) were treated with progesterone vaginal sustained release gel and dydrogesterone. The pregnancy outcomes, pregnancy complications and cost-effectiveness ratio were compared between the two groups. Results:There were no significant differences in embryo implantation rate, clinical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late abortion rate, premature birth rate, live birth rate, incidence of pregnancy complications and birth defect rate between the two groups (all P>0.05). But the incidence of vaginal bleeding in group B was significantly higher than that in group A [6.0% (30/504) vs. 10.3% (52/505), P=0.015], cost-effectiveness ratio (C/E) in group A was better than that in group B (17.76 vs. 77.30). Conclusion:For patients undergoing HRT-FET cycles, oral progesterone capsule can reduce vaginal bleeding and medical cost, while achieving a pregnancy outcome similar to that of progesterone vaginal sustained release gel and dydrogesterone, so it can be used as a luteal support scheme in clinic.

Objective:To evaluate the differences in pregnancy outcomes of patients and cost variance with hormone replacement therapy for frozen-thawed embryo transfer (HRT-FET) under different luteal support scheme.Methods:A retrospective cohort study was performed. A total of 1009 cycles of HRT-FET from October 2017 to April 2019 were collected and the patients were recruited from Reproductive Hospital Affiliated to Shandong University. According to different luteal support protocol, patients in group A ( n=504) were treated with oral progesterone capsule while patients in group B ( n=505) were treated with progesterone vaginal sustained release gel and dydrogesterone. The pregnancy outcomes, pregnancy complications and cost-effectiveness ratio were compared between the two groups. Results:There were no significant differences in embryo implantation rate, clinical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late abortion rate, premature birth rate, live birth rate, incidence of pregnancy complications and birth defect rate between the two groups (all P>0.05). But the incidence of vaginal bleeding in group B was significantly higher than that in group A [6.0% (30/504) vs. 10.3% (52/505), P=0.015], cost-effectiveness ratio (C/E) in group A was better than that in group B (17.76 vs. 77.30). Conclusion:For patients undergoing HRT-FET cycles, oral progesterone capsule can reduce vaginal bleeding and medical cost, while achieving a pregnancy outcome similar to that of progesterone vaginal sustained release gel and dydrogesterone, so it can be used as a luteal support scheme in clinic.

Objective:To investigate the predictive value of acute gastrointestinal injury (AGI) score for the severity of acute pancreatitis (AP), infectious pancreatic necrosis and patients′ death.Methods:Clinical data of 719 patients with AP were collected from the AP database of the National Clinical Research Center for Digestive System Diseases from January 2016 to June 2018. According to the severity of the disease, they were divided into MAP group (506 cases), MSAP group (112 cases) and SAP group (101 cases). AGI, APACHEⅡ, MCTSI and BISAP scores were calcululated in the three groups. Receiver operating characteristic curve (ROC) was drawn and the area under the curve (AUC) was calculated. The predictive value of the above four scoring systems for the hospitalization days, disease severity, infectious pancreatic necrosis and death was analyzed, respectively.Results:There were no cases of infectious pancreatic necrosis or death in the MAP group, but there were 9 cases of infectious pancreatic necrosis and 2 deaths in the MSAP group and 19 cases of infectious pancreatic necrosis and 8 deaths in the SAP group. There was a strong correlation between AGI score and AP patients′ hospitalization days ( r=0.619). AUC of AGI, APACHEⅡ, MCTSI and BISAP score in predicting the AP patients′ severity (MSAP+ SAP) was 0.967 (95% CI 0.951-0.982), 0.769(95% CI 0.720-0.899), 0.842(95% CI 0.809-0.875), 0.862 (95% CI0.832-0.893). AUC for forecasting infectious pancreatic necrosis was 0.803, 0.677, 0.692, 0.724, and the 95% CI was 0.724-0.882, 0.573-0.781, 0.582-0.636, 0.801-0.812. AUC for predicting death in patients with AP were 0.915, 0.597, 0.659, 0.812, and the 95% CI were 0.843-0.986, 0.444-0.751, 0.498-0.698 and 0.882-0.926. AGI score had the highest predictive value, followed by BISAP score, and the correlation between these two scores was the closest. The predictive value of AGI combined with BISAP score for infectious pancreatic necrosis and patient death (AUC were 0.837, 0.942, 95% CI were 0.770-0.903, 0.897-0.987) was better than that of AGI and BISAP score alone. Conclusions:AGI score combined with BISAP score is more effective in predicting the severity of AP, the occurrence of infectious pancreatic necrosis or patient death.

Objective:To retrospectively analyze the data of patients undergoing extracorporeal membrane oxygenation (ECMO) during perioperative period of cardiac transplantation and provide objective and reliable evidence for further clinical promotion.Methods:Collect the clinical data of patients undergoing heart transplantation and ECMO support in Fuwai Hospital, analyze the duration of ECMO support, combined use of aortic balloon counterpulsation (IABP), and complications during the supporting period. All statistical analyses were processed by SPSS 23.0 software. Independent sample Student's test was employed for normal distribution and Mann-Whitney U test for abormal distribution. χ2 or Fisher exact test was utilized for comparinge the classification data between groups. Results:All ECMO support models were intravenous-arterial ECMO (V-A ECMO). Eight patients successfully bridging heart transplantation through VA-ECMO. Sixty-one patients (89.7%) who had undergone cardiac transplantation were successfully weaned from ECMO while 48 patients (70.5%) survived and discharged. The most common complications during circulation support are bleeding, acute renal insufficiency, and pulmonary infection. Patients with ECMO support in the operating room had a better rate of survival and weaning off(95.6%, 84.4%) than those with ECMO at the bedside of ICU(72.2%, 27.8%).Conclusions:ECMO can provide adequate circulation and respiratory function support for heart transplant patients, and it is an indispensable treatment for patients to go through the perioperative period of heart transplant surgery smoothly. It is advocated to use IABP combined with ECMO in the early stage and at the same time to increase the perfusion of vital organs, improve the prognosis of patients and obtain good outcomes.