Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

The integration of medical treatment and disease prevention(hereinafter referred to as"med-prevent integra-tion")constitutes a vital strategy for achieving universal health objectives.Party-building initiatives in university-affiliated hospi-tals present a novel approach to enhance this integration at the primary care level.This study identifies three major challenges in current practice,including insufficient conceptual integration between medical and preventive services,inadequate cross-depart-mental coordination and resource allocation,and imperfect accountability mechanisms within Party-building frameworks.From the perspective of integrated governance,we propose a comprehensive pathway where party-building facilitates the systematic conver-gence of ideological orientation,organizational structure,cultural values,and institutional mechanisms.These findings provide both theoretical framework and practical guidance for university-affiliated hospitals to deepen primary-level med-prevent integration through Party-building initiatives.

The integration of medical treatment and disease prevention(hereinafter referred to as"med-prevent integra-tion")constitutes a vital strategy for achieving universal health objectives.Party-building initiatives in university-affiliated hospi-tals present a novel approach to enhance this integration at the primary care level.This study identifies three major challenges in current practice,including insufficient conceptual integration between medical and preventive services,inadequate cross-depart-mental coordination and resource allocation,and imperfect accountability mechanisms within Party-building frameworks.From the perspective of integrated governance,we propose a comprehensive pathway where party-building facilitates the systematic conver-gence of ideological orientation,organizational structure,cultural values,and institutional mechanisms.These findings provide both theoretical framework and practical guidance for university-affiliated hospitals to deepen primary-level med-prevent integration through Party-building initiatives.

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

Objective:To investigate the feasibility and safety of endoscopic ultrasound (EUS)-guided intrahepatic portal vein puncture through jugular vein implantation in transjugular intrahepatic portosystemic shunt (TIPS).Methods:As research subjects, 5 beagle dogs were anesthetized, and EUS was placed through the jugular vein to observe the intrahepatic portal vein. Under real-time guidance, the portal vein was punctured and a stent was placed to complete the TIPS.Results:Among the 5 beagles, EUS was unable to be placed in 1 due to the small diameter of the external jugular vein, and it was implanted successfully in 4 others through the external jugular vein who underwent real-time guidance of portal vein puncture. Subsequent stent placement and balloon dilation were completed. All animals survived after the experiment.Conclusion:EUS-guided intrahepatic portal vein puncture through jugular vein implantation is safe and feasible in TIPS.

Objective:To explore the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt.Methods:The basic information, laboratory test results, preoperative portal venous pressure, postoperative anticoagulation time, postoperative stent stenosis or occlusion, followed-up and other data of all patients who underwent TIPS surgery in Shandong Provincial Hospital from 2010 to 2019 were retrospectively analyzed. Data were analyzed using t-test, χ2 test, and multivariate analysis (logistic regression and Cox-regression-analysis). Results:A total of 280 cases were finally included in the study, of which 110 (39.3%) had stent stenosis or occlusion, and 170 (60.7%) had stent patency. New or worsening ascites were identified in 194 cases during the follow-up period, including 14 (31.1%) cases in the stent stenosis or occlusion group and 19 (12.8%) cases in the stent patency group. Univariate analysis showed that presence or absence of platelet ( P=0.037) and total bilirubin ( P=0.038) were correlated with stent stenosis or occlusion. Postoperative continuous anticoagulation was correlated with stent blockage ( P=0.029) in patients with partial portal vein thrombosis. Postoperative continuous anticoagulation and stent occlusions were not significantly correlated in patients with preoperative portal cavernoma and preoperative portal vein patency ( P=0.848; P=0.744). Multivariate analysis results showed that whether long-term anticoagulation ( P=0.017), all-cause rebleeding ( P<0.001), postoperative significant hepatic encephalopathy ( P<0.012), and postoperative new or worsening ascites ( P<0.001) was significantly associated with stent occlusion ( P<0.05), while platelets ( P=0.134), total bilirubin ( P=0.229), international normalized ratio ( P=0.436), and portal vein pressure ( P=0.230) were not significantly associated with stent occlusion after surgery. Conclusion:In patients with partial portal vein thrombosis before surgery, continuous anticoagulation for 30 days post-TIPS therapy can effectively prevent stent stenosis or occlusion; while in patients with portal vein patency, portal cavernoma and complete portal vein blockage before surgery, postoperative anticoagulation has no significant effect on stent stenosis or occlusion.

Objective:To compare the advantages of high or low inferior mesenteric artery (IMA) ligation in laparoscopic anterior resection of rectum based on CT precise guidance.Methods:One hundred and twenty patients with rectal cancer who underwent laparoscopic anterior resection of rectum in Shanghai Sixth People′s Hospital South Campus from January 2016 to June 2020 were selected. Surgical protocol was selected according to the principle of voluntariness. Sixty-eight cases underwent high IMA ligation (high IMA ligation group), and 52 cases underwent low IMA ligation (low IMA ligation group). The perioperative conditions (operative time, intraoperative blood loss, postoperative anal exhaust time, abdominal drainage, hospitalization time and ileostomy), postoperative pathological data (proximal margin distance, distal margin distance, total number of dissected lymph nodes and number of positive lymph nodes) and postoperative recovery (anastomotic stoma fistula, urinary retention, sexual dysfunction and daily number of defecation) were recorded. The quality of life 6 months after surgery was evaluated by the quality of life instruments for colorectal cancer scale (QLQ-CR38). Patients were followed up for 6 to 36 months, and the local recurrence and distant metastasis were recorded.Results:The postoperative anal exhaust time in low IMA ligation group was significantly shorter than that in high IMA ligation group: (2.87 ± 1.04) d vs. (3.26 ± 1.00) d, and there was statistical difference ( P<0.05); there were no statistical differences in operative time, intraoperative blood loss, abdominal drainage, hospitalization time and rate of ileostomy between 2 groups ( P>0.05). There were no statistical difference in proximal margin distance, distal margin distance, total number of dissected lymph nodes and number of positive lymph nodes between 2 groups ( P>0.05). The incidences of anastomotic stoma fistula, urinary retention and sexual dysfunction in low IMA ligation group were significantly lower than those in high ligation group: 3.85% (2/52) vs. 13.24% (9/68), 3.85% (2/52) vs. 11.76% (8/68) and 5.77% (3/52) vs. 14.71% (10/68), the daily number of defecation was significantly less than that in high ligation group: (2.87 ± 0.98) times vs. (4.05 ± 1.56) times, and there were statistical differences ( P<0.05 or <0.01). The functional dimension, symptom dimension and aggregate score of QLQ-CR38 in low IMA ligation group were significantly higher than those in high ligation group: (15.46 ± 4.22) scores vs. (13.68 ± 3.56) scores, (51.82 ± 13.54) scores vs. (45.65 ± 12.42) scores and (67.28 ± 14.28) scores vs. (59.33 ± 12.85) scores, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the rates of local recurrence and distant metastasis between 2 groups ( P>0.05). Conclusions:The application of low IMA ligation based on CT precise guidance in laparoscopic anterior resection of rectum can obtain the same surgical effect as the high IMA ligation. It can promote the recovery of gastrointestinal function after surgery, reduce the risk of complications, have less effect on the defecation function, which can improve the life quality after the surgery.

Objective To investigate the expression of FNDC5 in hepatocellular carcinoma (HCC) and its relationship with clinicopathological characteristics and prognosis of HCC patients.Methods Immunohistochemistry and qRT-PCR were used to detect the expression of FNDC5 in HCC tissues,and the relationship between its expression and clinicopathological parameters and prognosis.Results FNDC5 was mainly expressed in the cytoplasm of HCC cells,weakly expressed in the nucleus.Among the 30 liver cancer tissues,FNDC5 was weakly positive in 5,positive in 19,and strongly positive in 6 cases.QRT-PCR assay showed that FNDC5 was highly expressed in HCC tissues with vascular invasion.The incidence of vascular invasion in the high-expression of FNDC5 was 30％ (9/30),which was significantly higher than that of the FNDC5 low-expression group [6.7％ (2/30),] and the difference was significant (x2 =15.026,P ＜0.05).There was no significant correlation between FNDC5 level and age,sex,HBsAg,and alpha-fetoprotein (AFP) level in HCC (P ＞ 0.05).Conclusion FNDC5 level in the liver cancer tissues is closely related to the occurrence of vascular invasion.