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.

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 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.

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 explore the relationship between rs2010963, rs3025039 and rs699947 gene polymorphism of vascular endothelial growth factor(VEGF) gene and bronchopulmonary dysplasia(BPD) in Mongolian premature infants.Methods:A case-control design was used to collect 50 cases of Mongolian premature infants who were hospitalized at the Affiliated Hospital of Inner Mongolia Medical University and diagnosed with BPD from January 2016 to December 2020 as the observation group, while 56 cases of non-BPD premature infants of the same nationality and time period were selected as the control group.Using PCR method to detect the genotype and allele distribution of the VEGF gene rs2010963, rs3025039 and rs699947 locus.Combining clinical data to analyze whether the above gene loci were related to the onset of premature infants with Mongolian BPD in our area.Results:Through genetic testing, it was found that CC, CA and AA genotypes can be detected at the rs699947 site of VEGF gene in premature infants in both the observation group and the control group.The frequencies of the three genotypes in the observation group were 16.0%, 24.0%, and 60.0%, respectively; the frequency of the C allele was 28.0%, the frequency of the A allele was 72.0%, and the frequency of the three genotypes in the control group was 32.1.%, 32.1% and 35.7%, respectively.The frequency of C allele was 48.2%, the frequency of G allele was 51.8%, and the allele and genotype frequencies of this locus between the observation group and the control group were significant differences from those of the control group( P<0.05). Conclusion:The polymorphism of VEGF gene rs699947 locus is associated with the occurrence and development of BPD in Mongolian premature infants, and allele A may be a susceptible factor.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.