OBJECTIVE To evaluate the efficacy and safety of guideline-directed medical therapy （GDMT） combined with vericiguat in treating heart failure with reduced ejection fraction （HFrEF）. METHODS A retrospective study was conducted on 346 patients with HFrEF who received standardized diagnosis and treatment at the First People’s Hospital of Changzhou from January 2023 to May 2024. They were divided into standard treatment group （n＝215） and vericiguat group （n＝131）. Patients in the standard treatment group received GDMT， while patients in the vericiguat group received GDMT combined with vericiguat. Propensity score matching （PSM） was used to balance confounding factors between two groups， and the effectiveness （including outcome and prognostic indicators） and safety （occurrence of adverse events） of both groups were evaluated. Kaplan-Meier survival curves for primary and secondary outcome events were drawn， and the influential factors of primary outcome events were screened through univariate and multivariate Cox regression analysis. RESULTS After PSM， there were 100 patients in the standard treatment group and 100 patients in the vericiguat group， and there was no statistically significant differences in baseline data between two groups （P＞0.05）. During a 1-year follow-up， there were statistically significant differences in the cumulative incidence of major outcome events between the standard treatment group and the vericiguat group， cumulative incidence of hospitalization events due to heart failure， changes in N-terminal pro-B-type natriuretic peptide levels before and after treatment between the standard treatment group and the vericiguat group （P＜0.05）. There was no statistically significant difference in the incidence of adverse events between the two groups （P＞0.05）. Multivariate Cox regression analysis results showed that left ventricular ejection fraction ≤35% was a risk factor for the occurrence of major outcome events within 1 year [hazard ratio （HR）＝ 2.090， 95% confidence interval （CI）： 1.175-3.718， P＝0.012]， while the use of vericiguat was a protective factor for the occurrence of major outcome events within 1 year （HR＝0.505， 95%CI： 0.284-0.899， P＝0.020）. CONCLUSIONS Compared with GDMT， GDMT combined with vericiguat can improve the clinical symptoms and prognosis of HFrEF patients， and has good safety.

ObjectiveTo investigate the expression and role of response gene to complement 32 （RGC32） in liver regeneration after partial hepatectomy （PH）. MethodsA total of 42 male C57BL/6 mice， aged 10 weeks， were randomly divided into control group， postoperative day 1 group （1－d group）， postoperative day 2 group （2－d group）， postoperative day 4 group （4－d group）， postoperative day 6 group （6－d group）， postoperative day 8 group （8－d group）， and postoperative day 10 group （10－d group）， with 6 mice in each group. In the control group， the complete liver of the mice was resected for weighing and photography as the normal control group （sham group）； further， the left and middle lobes of the liver were resected for weighing and photography as the surgical control group （0－day group）； the sham group and the 0－day group shared the same group of mice. After successful modeling by PH， the mice were sacrificed on days 1， 2， 4， 6， 8， and 10 after surgery， and the liver was collected to measure the change in size. HE staining and oil red O staining were used to evaluate liver histomorphological changes； serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured to evaluate the changes in liver function； immunohistochemical staining was used to measure the expression of proliferating cell nuclear antigen （PCNA） and Ki67 and analyze the change in cell proliferation during liver regeneration； quantitatie real－time PCR and immunohistochemical staining were uused to measure the expression and subcellular distribution of RGC32 during liver regeneration； EdU cell proliferation assay was used to analyze the effect of RGC32 overexpression or knocknout on hepatocyte proliferation in L02 cells. For continuous data， comparison between multiple groups was made by analysis of variance， and further pairwise comparisons were conducted using the LSD－t test. The independent samples t－test was used for comparison of continuous data between two groups. A Pearson correlation analysis was performed. ResultsThe liver gradually enlarged after PH， and the liver/body weight ratio rose to the peak from days 0 to 6， with significant differences between different time points （all P<0.05）， while there was no significant change in liver size from days 6 to 10. The number of liver lipid droplets significantly increased after PH surgery and gradually decreased with liver regeneration， with a significant difference between the portal vein region and the central vein region （all P<0.05）. Compared with the sham group， the 1d group had significant increases in the serum levels of ALT and AST （all P<0.05）， which gradually returned to the levels of the sham group on day 6 and day 2 after surgery， respectively （P>0.05）. Immunohistochemical staining showed that there were rapid increases in the numbers of PCNA－ and Ki67－positive liver parenchymal cells after PH surgery， with the highest numbers of 86±5 and 89±5， respectively， on day 2， which then gradually decreased； however， there were gradual increases in the numbers of PCNA－ and Ki67－positive nonparenchymal cells， with the peak numbers of 34±5 and 25±3， respectively， on day 6， which then gradually decreased. The total expression of RGC32 increased to the highest level on day 2 after PH surgery and then gradually decreased， and the changing trend of RGC32 expression in cytoplasm was consistent with that of total RGC32 expression； however， the expression of RGC32 in nucleus decreased to the lowest level on day 2 after PH surgery and then increased gradually. The correlation analysis showed that the expression of RGC32 in nucleus was negatively correlated with the proliferation of liver parenchymal cells （R²=0.308 3， P=0.016 7）， and the expression of RGC32 in cytoplasm was positively correlated with the proliferation of liver parenchymal cells （R²=0.808 6， P<0.000 1）. Cell experiments showed that compared with the control group， the EdU－positive rate was reduced by 15.6% after RGC32 overexpression （P<0.01） and was increased by 19.2% after RGC32 knockdown （P<0.01）. ConclusionLiver parenchymal cells and nonparenchymal cells show asynchronous proliferation and participate in liver regeneration together. During liver regeneration after hepatectomy， there are differences in the expression of RGC32 between nucleus and cytoplasm， and RGC32 in nucleus may inhibit hepatocyte proliferation.

Objective By analyzing the problems existed in the Investigator Initiated Trial (IIT),this article put forward the corresponding countermeasures and therefore provides reference for the standardization of clinical research project management.Methods Four types of problems identified in the supervision of hospital IIT projects are analyzed according to literature review,data analysis of clinical research project,comparative study and summary.Identified problems are existed in the following aspects:scientific research supervision function,research method guidelines,technical specification of the diagnosis and treatment,scientific research design and project approval review,research funds,medical ethics committee,construction of Biobank and Regulation Conflicts.Results This article put forward 6 countermeasures for improvement:establishing and perfect IIT project scientific research supervision entity,bring in the IIT project steering group to strengthen the scientific review;Strengthen risk management to ensure medical safety,carry out IIT training,establish IIT management database information system,build a comprehensive integrated development multi-point application model of hospital BioBank.Conclusions The establishment of the hospital's IIT scientific research supervision system,management mode and technical standard system is of great importance to standardize clinical research,ensure research quality and guide the clinical research work of the hospital effectively.

Objective Epithelial mesenchymal transition (EMT) has a role in the proliferation and metastasis of various types of cells.This study investigates the hepatic oval cell's mechanism of EMT induced by histone deacetylase inhibition and the resulting cell motility increase from EMT.Methods Hepatic oval cell stem cell markers and marker changes were detected by flow cytometry,and after histone deacetylase inhibition induced EMT,the morphological changes were recorded.Western blot and quantitative real-time polymerase chain reaction detected the expression of E-cadherin,vimentin and Snail.Furthermore,confocal microscopy analysis recognized the nuclear translocation of Snail.Results Flow cytometry revealed no changes in the stem cell properties of hepatic oval cells in the cell culture process.Oval cell EMT,induced by HDACi,was observed through morphological changes,a reduction of the epithelial cell marker E cadherin,and an increase of the mesenchymal cell marker Vimentin.HDACi can promote the expression and nuclear translocation of Snail,which is the key hepatic oval cell transcription factor for both EMT and enhanced motility.Therefore,Snail RNA interference can suppress HDACi induced EMT in hepatic oval cells.Conclusions In conclusion,histone deacetylase inhibition induces hepatic oval cell epithelial-mesenchymal transition by Snail.

End stage liver disease is a serious threat to human health.Existing conventional therapies are far from ideal,and orthotopic liver transplantation is limited by the lack of donor liver.A new therapy,transplantation of hepatic stem cell,is a promising approach.Hepatic oval cells are hepatic stem/progenitor cells(HSC/HPC)during hepatic regeneration,and they are being referred to as hepatic precursor cells.It got its name because of its oval nucleus,high nuclear/cytoplasmic ratio and other morphological features.Research has shown increasingly importance in the knowledge of hepatic oval cells.There are many signaling pathways in hepatic oval cells activation and proliferation.As a branch of the Wnt signaling pathway,Wnt/β-catenin signaling pathway has a significant effect on hepatic oval cells activation and proliferation.However,the exact mechanisms of this process have not been completely elucidated.This review describes the role of Wnt/β-catenin signaling pathway in hepatic oval cell activation and proliferation.

Objective To investigate the galectin-3 (Gal-3) and osteopontin (OPN) expression in esophageal carcinoma and analyze its clinical significance.Methods Thirty-seven patients who suffered from esophageal carcinoma were selected from 2006 to 2008.There were 28 males and 9 females,aged from 41 to 82 vears old.The levels of Gal-3 mRNA and OPN mRNA in tissues were detected by Fluorescent PCR,and the levels of Gal-3 and OPN in blood plasma were measured by ELISA.Result The expression of Gal-3 mRNA and OPN mRNA were significantly different between the esophageal carcinoma,side of carcinoma and normal esophagus tissues (F=11.934,F=4.269,P<0.05);The expression of galectin-3 and osteopontin were correlated with pathological grading (F=3.216,P

Objective To analyze the CT staging and evaluate its role in assessing the resectability of the gallbladder carcinoma.Methods The CT scans of 47 patients who had pathologically confirmed gallbladder carcinoma were retrospectively reviewed and the CT stages of gallbladder carcinoma were used to evaluate the resectability.Results Before operation,three patients were in stage Ⅰ(6.4%,3/47),14stageⅡ(29.8%,14/47),10 stageⅢ(21.7%,3/47),20 stage Ⅳ(42.6%,20/47),however,after operation,three patients were in stage Ⅰ(6.4%,3/47),14 stageⅡ(29.8%,14/47),8 stage Ⅲ(17.0%%,8/47),22 stage Ⅳ(42.6%,20/47).The accurate rate of CT staging confirmed by operation was 91.5%(43/47).The treatment procedures of gallbladder carcinomas included radical operation,palliative excision and exploratory laparotomy.For 47 patients with gallbladder carcinomas,radical operation was performed in 30 cases(3 stage Ⅰ,14 stageⅡ,7 stage Ⅲ,6 stage Ⅳ),palliative excision 15 cases(1 stage Ⅲ,14 stage Ⅳ),exploratory laporatory 2 eases(2 stage Ⅳ).Conclusion The staging of gallbladder carcinoma with CT may provide definite value in evaluating respectability of gallbladder carcinoma.

Objective To study the expression of chemokine stromal cell-derived factor-1 and its receptor CXCR4 in gallbladder carcinoma and evaluate the relationship between the expression of SDF-1 and CXCR4 protein and the clinicopathology,and lymph node metastasis of gallbladder carcinoma.Methods The expression of SDF-1 and CXCR4 protein in 41 cases of gallbladder adenoma carcinoma was examined by immunohistochemical technique(SP),and the relation of SDF-1/CXCR4 biology axis to clinicopathological parameter was also analyzed.Results The positive expression rate of SDF-1 and CXCR4 in gallbladder carcinoma was 68.3%(28/41)and 51.2%(21/41)respectively,in normal gallbladder mucous was 5%(1/20)and 5%(1/20)respectively,in cholecystitis and gallstone was 6.7%(6/90)and 5.6%(5/90)respectively,and there is significantly different among the three groups in SDF-1 and CXCR4 expression values(P＜0.001,P＜0.001,respectively).There is significant difference among histological grade group,Nevin stage group,histological differentiation,lymph node or distal organ metastasis group in SDF-1 and CXCR4 expression value(P＜0.05,respectively).However,there is no significant difference among sex group,age group,tumor size group,and gallstone presence group in SDF-1 and CXCR4 expression value(P＞0.05,respectively).The expression of SDF-1 was positively correlated to CXCR4(r=0.68,P＜0.01).Conclusion Up-regulated SDF-1 and CXCR4 is associated with the carcinogenesis and metastasis of gallbladder carcinoma.

Objective Shh and Ptch have been known to play critical roles in the hedgehog pathway and the hedgehog pathway activation occurs in the gastrointestinal cancers. This study was to detect the expression of Shh and Ptch in gallbladder carcinoma, and explore their correlation to gallbladder carcinoma. Methods The expression of Shh and Patch protein in 41 specimens of primary gallbladder carcinoma, 20 specimens of normal gallbladder and 21 specimens of adenoma tissue were assessed by immunohistochemistry.Results The positive expression rate of Shh and Ptch in gallbladder carcinoma was 75.6% (31/41) and 78.0% (32/40) respectively, in normal gallbladder mucous was 5% ( 1/20 ) and 5% ( 1/20 ) respectively,in gallbladder adenoma was 4.7% ( 1/21 ) and 9.6% (2/21) respectively, and there was significant differenee between the three groups in Shh and Patch expression values(P ＜0.001 ). However, there was no significant difference between age group, histological grade group, histologic type group, Nevin stage group,lymph node or distal organ metastasis group, and gallstone presence group in Shh and Ptch expression value (P ＞ 0.05, respectively). The expression of Shh was positively correlated to Ptch (r = 0.72, P ＜ 0.01 ).Conclusion These data support our hypothesis that Hh signaling is dysregulated in human gallbladder carcinognesis.

Background and objective Apolipoprotein E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. We investigated the relationship between apo E gene polymorphism and the occurrence of coronary artery disease(CAD) in the older population of northern China. Methods The distribution of the HhaI polymorphisms of the apolipoprotein E gene was determined among 55 patients with CAD (CAD group), which was compared with that of 36 elderly subjects without CAD(control group). Results Genotype distributions at both sites (apo E gene 112-bp and 158-bp sites ) were different between the CAD and control groups. The CAD group had lower apolipoprotein Eε2frequencies than the control group (P＜0.05). Conclusion Individuals with apolipoprotein Eε2are likely to have a reduced risk of developing coronary artery disease as demonstrated by elderly subjects in Northern China.