ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Objective To explore the mechanism of somatostatin in improving acute lung injury associated with acute pancreatitis.Methods Wistar rats were randomly divided into sham operation group(injection of normal saline),model group(puncture of common bile duct and injection of 5％sodium taurocholate with wire ligation),somatostatin group(injection of somatostatin into tail vein of model group),somatostatin+miR-146a-5p inhibitor group(on the basis of somatostatin group,tail vein injection of miR-146a-5p inhibitor and somatostatin+oe-angiogenin-like protein 4(ANGPTL4)group(on the basis of somatostatin group,tail vein injection of oe-ANGPTL4 plasmid).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic and lung tissues;pathological score and tissue wet-dry weight ratio were determined,real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect miR-146a-5p and ANGPTL4 mRNA expression and Western blot was used to detect the expression of related proteins in lung tissues of rats.Tumor necrosis factor-α(TNF-α)was detected by enzyme-linked immunosorbent assay(ELISA).Results In sham operation group,model group and somatostatin group,the damage degree of pancreas tissue(based on modified computed tomography severity index)were 1.25±0.28,3.20±0.34,2.15±0.31,respectively;the damage degree of lung tissue(based on the Smith lung injury score system)were 1.40±0.13,5.10±0.58,3.10±0.38,respectively.The relative expression levels of ANGPTL4 mRNA in sham operation group,model group,somatostatin group and somatostatin+miR-146a-5p inhibitor group were 1.00±0.17,1.63±0.20,1.21±0.18 and 1.73±0.28.The levels of TNF-α in sham operation group,model group,somatostatin group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group were(76.33±7.25),(125.05±13.56),(80.11±10.68),(118.62±14.32)and(105.32±13.52)pg·mL-1,respectively;the relative expression levels of nuclear factor E2-related factor 2(Nrf2)protein were 1.00±0.27,0.51±0.07,0.88±0.14,0.68±0.12,0.51±0.09,respectively;the relative expression levels of heme oxygenase-1(HO-1)protein were 1.00±0.25,0.58±0.11,0.79±0.18,0.48±0.07 and 0.50±0.08,respectively.The above indexes of the model group were compared with those of the sham operation group,and the above indexes of the somatostatin group were compared with those of the model group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group,and the differences were statistically significant(all P＜0.05).Conclusion Somatostatin has antioxidant and anti-inflammatory effects and can ameliorate acute lung injury associated with acute pancreatitis.The mechanism may be related to Nrf2/HO-1 pathway mediated by miR-146a-5p/ANGPTL4.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective To investigate the alleviation of Nippostrongylus brasiliensis infection on dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice, and to explore the underlying mechanism. Methods Thirty male C57BL/6J mice of the SPF grade, each weighing approximately 25 g, were randomly divided into three groups, including the blank control group (NC group), DSS modeling group (DSS group), and N. brasiliensis treatment group (Nb + DSS group), of 10 mice in each group. Mice in the DSS group were orally administered with 3.5% DSS daily since day 1 (D0) for 6 successive days, and given normal drinking water since D6, and animals in the Nb + DSS group were subcutaneously injected with the third-stage larvae of N. brasiliensis at a dose of 500 larvae per mice 5 days prior to D0, followed by oral administration with 3.5% DSS daily since D0 for 6 successive days and normal drinking water since D6, while mice in the NC group were given normal drinking water. Mouse body weight and stool were observed and the disease activity index (DAI) was scored in each group during the study period. All mice were sacrificed on D9. The mouse colon length was measured, and mouse colon specimens were subjected to hematoxylin-eosin (HE) staining and histopathological scoring. In addition, the mRNA and protein expression of interleukin (IL)-1β and IL-10 was quantified in mouse colon specimens using quantitative fluorescent real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expression of mucosal repair-associated molecules zonula occludens-1 (ZO-1), mucin 2 (MUC2) and claudin-1 was detected in mouse colon specimens using qPCR assay and immunofluorescence assay. Results The mice body weights, DAI scores and colon lengths were (26.26 ± 1.93), (22.39 ± 1.65), (25.00 ± 1.58) g (F = 8.06, P < 0.01); (1.89 ± 0.34), (0.47 ± 0.39), 0 points (F = 57.61, P < 0.000 1); and (42.50 ± 5.75), (56.20 ± 5.96) mm and (61.17 ± 7.88) mm (F = 13.72, P < 0.001) in the NC, DSS and Nb + DSS groups on D9, respectively, and elevated mouse body weight (P < 0.05), reduced DAI score (P < 0.000 1) and increased colon length (P < 0.01) were observed in the Nb + DSS group relative to the DSS group on D9. Pathological examinations showed that the colonic crypts were relatively intact and the inflammatory cell infiltration was lower in the mouse colon specimens in the Nb + DSS group than in DSS the group. There was a significant difference in the histopathological scores of mouse colon specimens among the NC group (0 point), the DSS group [(2.00 ± 1.22) points] and the Nb + DSS group [(0.20 ± 0.45) points] (F = 10.71, P < 0.01), respectively, and the histopathological score of mouse colon specimens was significantly higher in the DSS group than in the NC and Nb + DSS groups (both P values < 0.01). qPCR assay quantified that the relative IL-10 and IL-1β mRNA expression was 1.25 ± 0.08, 0.44 ± 0.14 and 1.30 ± 0.45 (F = 10.66, P < 0.01), and 0.22 ± 0.13, 1.14 ± 0.31 and 0.41 ± 0.19 (F = 16.89, P < 0.001) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and higher IL-10 mRNA expression and lower IL-1β mRNA expression were found in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.01). The relative MUC2, claudin-1 and ZO-1 mRNA expression was 0.87 ± 0.25, 0.34 ± 0.26 and 4.21 ± 0.55 (F = 121.60, P < 0.000 1), 1.05 ± 0.41, 0.16 ± 0.09 and 0.22 ± 0.11 (F = 14.00, P < 0.01), and 1.03 ± 0.10, 0.60 ± 0.11 and 1.64 ± 0.28 (F = 32.16, P < 0.000 1) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and significantly higher MUC2 and ZO-1 mRNA expression was quantified in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). The mean fluorescence intensities of ZO-1 and claudin-1 were 17.18 ± 2.08, 12.38 ± 1.21 and 18.06 ± 2.59 (F = 8.95, P < 0.01) and 13.50 ± 1.63, 9.66 ± 2.03 and 13.61 ± 0.97 (F = 6.96, P < 0.05) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and the mean fluorescence intensities of ZO-1 and claudin-1 were significantly greater in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). Conclusion N. brasiliensis infection may remarkably alleviate DSS-induced ulcerative colitis in mice through promoting expression of anti-inflammatory cytokines, inhibiting expression of pro-inflammatory cytokines and facilitating mucosal repair in colon tissues.

Objective:Analyze the medical reimbursement rate and influencing factors under the DIP payment method to refine the DIP payment policy,promote the optimization of internal operations in medical institutions,and ensure reasonable compensation.Methods:Based on the 2022 DIP fund settlement data from 196 medical institutions in City A,the study used multiple linear regression to analyze the factors affecting medical reimbursement rate and conducted a heterogeneity analysis for medical institutions of different levels.Results:The medical reimbursement rate for medical institutions in City A in 2022 was 103.32%.Medical institutions with lower CMI standardized inpatient costs,lower rates of deviation cases,tertiary care institutions,lower proportion of level-four surgeries,and lower ratios of resident to employee medical insurance cases have higher medical reimbursement rate(P<0.05).Heterogeneity analysis reveals that therates of deviation cases,the proportion of primary care diseases,the ratio of resident to employee medical insurance cases,and the low-standard admission rate have different impacts on medical institutions of different levels.Conclusion:Medical insurance departments should improve policies for primary care diseases,dynamically adjust disease catalogs and payment standards,optimize funding levels and institutional coefficients,and increase penalties for violations to ensure effective use of funds.Medical institutions need to strengthen their understanding of policies,focus on refined internal management,promote standardized and rational diagnosis and treatment through performance assessment transformation,and leverage their own advantages in medical services to reasonably increase the medical reimbursement rate.

Objective:To analyze the effects of preoperative renin-angiotensin system inhibitor (RASi) use on postoperative renal function and short-term and long-term prognosis in patients undergoing coronary artery bypass grafting (CABG).Methods:A retrospective cohort analysis was conducted. Based on the registration study data of CABG patients at Fuwai Hospital, Chinese Academy of Medical Sciences, the clinical data of adult patients who underwent CABG from January 2013 to December 2022 were analyzed. Preoperative use of RASi (PreRASi) was defined as receiving RASi treatment within 48 hours before surgery. Postoperative acute kidney injury (AKI) was defined using the diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO). Demographic characteristics, past medical history, comorbidities, preoperative medication, preoperative laboratory test results, specific information on surgical procedures, and postoperative treatment related data were extracted. The primary endpoint was the incidence of postoperative AKI. Secondary endpoints included in-hospital all-cause mortality and all-cause mortality within the longest follow-up period. According to whether RASi was used before surgery, the patients were divided into PreRASi group and No-PreRASi group. The baseline data of the two groups were balanced by propensity score matching (PSM). Logistic regression model and Cox proportional hazards model were used to assess the correlation between PreRASi and postoperative AKI and clinical outcomes, and analyze the subgroups of hypertension and heart failure with preserved ejection fraction (HFpEF) in the cohort.Results:A total of 33?884 patients who underwent CABG were included, with a mean follow-up duration of (3.0±2.4) years and the longest follow-up duration up to 8.5 years. There were 9?128 cases (26.94%) in the PreRASi group and 24?756 cases (73.06%) in the No-PreRASi group. The incidence of postoperative AKI in the PreRASi group was 47.61% (4?346 cases), compared to 52.37% (12?964 cases) in the No-PreRASi group. Two groups were matched with 5?094 patients each. Compared to the No-PreRASi group, both before and after PSM, PreRASi was associated with a reduction of risk of postoperative AKI [before PSM: odds ratio ( OR) = 0.834, 95% confidence interval (95% CI) was 0.793-0.877, P < 0.001; after PSM: OR = 0.875, 95% CI was 0.808-0.948, P = 0.001]. Subgroup analysis of hypertensive and HFpEF patients showed that PreRASi was associated with a decreased risk of postoperative AKI before and after PSM. The in-hospital mortality for the PreRASi and No-PreRASi groups were 0.61% (56 cases) and 0.49% (121 cases), respectively. Analysis of the overall cohort and subgroups with hypertension and HFpEF showed no correlation between PreRASi and in-hospital mortality or longest follow-up mortality. Conclusion:The perioperative use of RASi can reduce the risk of postoperative AKI in patients undergoing CABG, has a certain renal protective effect, but is not associated with short-term or long-term death risk after surgery.