BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

Objective:To discuss the role of angiopoietin-like protein 6(ANGPTL6)in liver fibrosis,and to analyze the improving effect of engineered exosome(Exo)-delivered ANGPTL6 mRNA on liver fibrosis.Methods:A total of 12 C57BL/6 mice were randomly divided into olive oil group(OIL group)(intraperitoneally injected with olive oil)and carbon tetrachloride(CCl4)group(intraperitoneally injected with a mixture of olive oil and CCl?),with 6 mice in each group;another 12 C57BL/6 mice were randomly divided into control group(fed a with methionine-choline sufficient diet)and methionine-choline deficient(MCD)group(fed a with MCD diet),and two kinds of mouse liver fibrosis models were established.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in various groups.A total of 30 mice were randomly divided into olive oil+phosphate buffered saline(PBS)group(OIL+PBS group)(intraperitoneally injected with olive oil twice a week for 8 weeks,then injected with PBS buffer by tail vein twice a week for 6 weeks),CCl4+Exo-green fluorescent protein(GFP)mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with GFP mRNA for 6 weeks),and CCl?+Exo-ANGPTL6 mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with ANGPTL6 mRNA for 6 weeks),with 10 mice in each group.The mice in CCl4+Exo-GFP mRNA group and CCl4+Exo-ANGPTL6 mRNA group were injected with engineered Exo twice a week,20 μg per mouse each time(volume 100 μL).ELISA method was used to detect the serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities in the mice in various groups;Masson staining and Sirius red staining were used to observe the collagen deposition in liver tissue of the mice in various groups;immunohistochemistry method was used to detect the α-smooth muscle actin(α-SMA)expression levels in liver tissue of the mice in various groups;RT-qPCR method was used to detect the expression levels of α-SMA,collagen type Ⅰ alpha 1 chain(Col1a1),transforming growth factor β1(TGF-β1),and tissue inhibitor of metalloproteinase 1(TIMP-1)mRNA in liver tissue of the mice in various groups.Results:The bioinformatics analysis results showed that ANGPTL6 expression was significantly down-regulated in activated hepatic stellate cell(aHSC).The ultrasound examination results showed that the liver surface of the mice in OIL group was fine and smooth;compared with OIL group,the liver section of the mice in CCl? group was rough and uneven.The RT-qPCR and Western blotting results showed that compared with OIL group,the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in CCl? group were significantly decreased(P<0.05).The engineered Exo extracted from the supernatant of HEK293T cells had intact structure and could be largely enriched in the fibrotic liver after tail vein injection,with GFP protein being largely expressed in the liver.The ELISA assay results showed that compared with OIL+PBS group,the ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-ANGPTL6 mRNA group,the serum ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly decreased(P<0.05).The Masson staining and Sirius red staining results showed that compared with OIL+PBS group,the collagen deposition in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased,and the relative collagen area was increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the collagen deposition in tissue liver of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased,and the relative collagen area was decreased(P<0.05).The immunohistochemistry results showed that compared with OIL+PBS group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased(P<0.05).The RT-qPCR results showed that compared with OIL+PBS group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group were significantly decreased(P<0.05).Conclusion:Engineered Exo-delivered ANGPTL6 mRNA injected via the tail vein in the mice is mainly enriched in the liver,and engineered Exo delivery of ANGPTL6 mRNA has an improving effect on liver fibrosis in the mice.

Objective To investigate the effects of CD151 down-regulation combined with bevacizumab on colorectal cancer growth and microvessel density.Methods Human colorectal cancer cell line HT-29 and CD151--HT-29 cells strain(CD151 down-regulated HT-29 cells)were treated with bevacizumab.The cells were divided into four groups:control(HT-29)group,bevacizumab-treatment group,CD151--HT-29 group,and CD151--HT-29+bevacizumab-treatment group.Cell proliferation was observed in each group using the MTS assay.A subcutaneous xenograft model in nude mice was established,and the HT-29 control group and CD151--HT-29 group were treated with either 0.9％NaCl solution or bevacizumab.The growth of subcutaneous tumors in the four groups was ob-served,and the volume and weight of the tumors were recorded.Tumor tissues were collected for immunohistochem-ical staining of endothelial cells to assess microvessel density(MVD).Results Compared with the control group,cell proliferation was significantly reduced in the bevacizumab-treated group and CD151--HT-29 group(P<0.001).Cell proliferation in the CD151--HT-29+bevacizumab-treated group was slower than that in the single treatment groups(P<0.001).In the subcutaneous tumor model,the volume,weight,and MVD of tumors in the bevacizumab-treated and CD151--HT-29 groups were significantly reduced compared to the control group(P<0.01).In the CD151--HT-29+bevacizumab group,the tumor volume,weight,and CD34 expression were significantly lower than in the single treatment groups(P<0.01).Conclusions CD151 protein may play a role in the regulation of angiogenesis in colorectal cancer tissues and may have a synergistic effect with bevacizumab in in-hibiting microvessel formation in tumor tissues.

Objective To summarize the clinical experience of using 3D planar guide plate combined with bundle diameter technology for extracorporeal pre-fenestration in treating complex thoracoabdominal aortic diseases.Methods The clinical data of 31 patients with complex thoracoabdominal aortic diseases,who were treated with 3D planar guide plate combined with bundle diameter technology of extracorporeal pre-fenestration at the First Affiliated Hospital of Soochow University of China from January 2017 to February 2024,were retrospectively analyzed.The patients' preoperative thin-layer chest and abdominal vascular CTA data were imported into specialized software and to create a 3D planar guide plate.Under the guidance of 3D planar guide plate technology,precise extracorporeal pre-fenestration of aortic covered stent was performed,and combined with bundle diameter technology the endovascular repair of complex thoracoabdominal aortic disease was accomplished.Results Successful operation was accomplished in all patients,and two patients had failed visceral artery reconstruction surgery.The median follow-up time was 55 months,with a technical success rate of 97.6％.The postoperative follow-up blood flow patency rate was 100％,and the phase Ⅰ patency rate of branch arteries was 98％.Three patients experienced internal leakage after surgery,and none of them developed paraplegia or died during the perioperative period.Conclusion In treating complex thoracoabdominal aortic diseases,the use of 3D planar guide plate combined with bundle diameter technology of extracorporeal pre-fenestration is simple,safe and effective,with good short-term therapeutic effect,although its long-term efficacy need to be further investigated.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

Objective:To evaluate the efficacy of remimazolam for induction of anesthesia in patients with colorectal cancer.Methods:This was a prospective study. Eighty-two patients scheduled for elective colon and rectal tumor surgery under general anesthesia from June to November 2023 at our hospital, aged 18-80 yr, with body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, were divided into 2 groups ( n=41 each) using a random number table method: propofol group (group P) and remimazolam group (group R). Propofol 1.5 mg/kg was intravenously injected in group R and remimazolam 0.3 mg/kg was intravenously injected in group P. When the bispectral index (BIS) value≤60, sufentanil 0.5 μg/kg and cisatracurium 0.2 mg/kg were intravenously injected in both groups. Heart rate and mean arterial pressure were recorded before induction of anesthesia (T 0), 3 min after induction (T 1), immediately after intubation (T 2), and 5 min after tracheal intubation (T 3). The occurrence of hypotension, hypertension, tachycardia and bradycardia during induction, use of vasoactive drugs, and injection pain were recorded. The time to loss of consciousness, time from the beginning of administration to BIS value ≤60, time from the beginning of administration to tracheal intubation, occurrence of BIS value > 60 immediately after intubation and rescue sedation were recorded. Results:Eighty patients were finally included, with 40 in group P and 40 in group R. Compared with group P, the heart rate and mean arterial pressure were significantly increased at T 1 and T 2, the incidence of hypotension and bradycardia was decreased, and the time from the beginning of administration to BIS value ≤60 was prolonged ( P<0.05), and no statistically significant changes were found in the other parameters in group R ( P>0.05). Conclusions:Remimazolam 0.3 mg/kg can be safely and effectively used for anesthesia induction and provides better efficacy in maintaining hemodynamic stability when compared with propofol 1.5 mg/kg in patients with colorectal cancer.

Patients with local advanced rectal cancer (LARC) can benefit from neoadju-vant chemoradiotherapy (nCRT) of reducing local recurrence rate and improving survival rate. However, tissue edema after nCRT may lead to unclear tissue spaces, making it challenging for lymph node dissection and nervous system protection. The difficulty in locating inferior margin of tumor after clinical complete remission or closing to clinical complete remission, as well as the increasing risk of anastomotic leakage after nCRT, pose difficulties and new challenges of total mesorectal excision for middle and low rectal cancer. Based on literatures and clinical experiences, the authors summarize the difficulties and strategies of total mesorectal excision after nCRT, in order to provide reference for colleagues.

Background and Objectives: Circulating endothelial progenitor cells (EPCs) participate in vascular repair and predict cardiovascular outcomes. The aim of this study was to investigate the correlation between EPCs and abdominal aortic aneurysms (AAAs). Methods: and Results: Patients (age 67±9.41 years) suffering from AAAs (aortic diameters 58.09±11.24 mm) were prospectively enrolled in this study. All patients received endovascular aneurysm repair (EVAR). Blood samples were taken preoperatively and 14 days after surgery from patients with aortic aneurysms. Samples were also obtained from age-matched control subjects. Circulating EPCs were defined as those cells that were double positive for CD34 and CD309. Rat models of AAA formation were generated by the peri-adventitial elastase application of either saline solution (control; n=10), or porcine pancreatic elastase (PPE; n=14). The aortas were analyzed using an ultrasonic video system and immunohistochemistry. The levels of CD34＋/CD309＋ cells in the peripheral blood mononuclear cell populations were measured by flow cytometry. The baseline numbers of circulating EPCs (CD34＋/CD309＋) in the peripheral blood were significantly smaller in AAA patients compared with control subjects. The number of EPCs doubled by the 14th day after EVAR. A total of 78.57% of rats in the PPE group (11/14) formed AAAs (dilation ratio ＞150%). The numbers of EPCs from defined AAA rats were significantly decreased compared with the control group. Conclusions EPC levels may be useful for monitoring abdominal aorta aneurysms and rise after EVAR in patients with aortic aneurysms, and might contribute to the rapid endothelialization of vessels.

Objective     To investigate the influence of prior percutaneous coronary intervention (PCI) on the outcome of coronary artery bypass grafting (CABG). Methods     Clinical data of 5 216 patients from Jiangsu Province CABG registry who underwent primary isolated CABG from 2016 to 2019 were retrospectively analyzed. Patients were divided into a PCI group (n=673) and a non-PCI group (n=4 543) according to whether they had received PCI treatment. The PCI group included 491 males and 182 females, aged 62.6±8.2 years, and the non-PCI group included 3 335 males and 1 208 females, aged 63.7±8.7 years. Multivariable logistic regression and propensity score matching (PSM) were used to compare 30-day mortality, incidence of major complications and 1-year follow-up outcomes between the two groups. Results     Both in original cohort and matched cohort, there was no statistical difference in the 30-day mortality [14 (2.1%) vs. 77 (1.7%), P=0.579; 14 (2.1%) vs. 11 (1.6%), P=0.686], or the incidence of major complications (myocardial infarction, stroke, mechanical ventilation≥24 h, dialysis for new-onset renal failure, deep sternal wound infection and atrial fibrillation) (all P>0.05). The rate of reoperation for bleeding in the PCI group was higher than that in the non-PCI group [19 (2.8%) vs. 67 (1.5%), P=0.016; 19 (2.8%) vs. 7 (1.0%), P=0.029]. Both in original cohort and matched cohort, there was no statistical difference in 1-year survival rate between the two groups [613 (93.1%) vs. 4 225 (94.6%), P=0.119; 613 (93.1%) vs. 630 (95.2%), P=0.124], while the re-admission rate in the PCI group was significantly higher than that in the non-PCI group [32 (4.9%) vs. 113 (2.5%), P=0.001; 32 (4.9%) vs. 17 (2.6%), P=0.040]. Conclusion     This study shows that a history of PCI treatment does not significantly increase the perioperative mortality and major complications of CABG, but increases the rate of cardiogenic re-admission 1 year postoperatively.