Background and Aims:Adhesive intestinal obstruction(AIO)is a type of mechanical bowel obstruction caused by abdominal or intestinal adhesions,and its onset and progression are closely associated with impaired intestinal mucosal barrier function.Danshen injection,a commonly used traditional Chinese medicine preparation with properties of promoting blood circulation and removing blood stasis,has shown therapeutic potential in various gastrointestinal diseases by improving microcirculation and promoting vasodilation.However,its specific mechanism of action in AIO remains unclear.This study was conducted to investigate the effects and potential mechanisms of Danshen injection on intestinal mucosal barrier function in a rat model of AIO.Methods:Forty rats with experimentally induced AIO were equally randomized into four groups:the model group(receiving intraperitoneal saline)and three Danshen-treated groups administered low,medium,and high doses of Danshen injection(1,2,and 4 mL/kg,respectively),once daily for 7 consecutive d.An additional 10 healthy rats received saline injections in the same manner and served as the normal control group.After the final intervention,all rats were euthanized under anesthesia.Hematoxylin and eosin(HE)staining was performed to evaluate the histopathological morphology of small intestinal tissues.Levels of D-lactic acid and endotoxin in peripheral blood were measured using enzyme-linked immunosorbent assay(ELISA).The expression levels of mucin 2(MUC2),mucin 3(MUC3),and human defensin 5(HD5)—key components of the intestinal mucus layer and innate immune response—were analyzed using quantitative real-time PCR(qRT-PCR).Colorimetric assays were conducted to assess oxidative stress markers in intestinal tissue,including nitric oxide synthase(NOS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px).Western blot was used to determine the protein expression levels of endogenous antioxidant pathway components:nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1).Results:HE staining showed no significant histological changes in the intestinal tissues of the normal control group,with a mucosal injury score of 0.The model and treatment groups exhibited varying degrees of villous disorganization and tissue edema,with injury scores of 4.69±0.62,3.36±0.41,2.29±0.22,and 1.53±0.14 in the model,low-,medium-,and high-dose groups,respectively(all P＜0.05 vs.model group).Compared with the normal control group,the other groups showed significantly increased levels of D-lactic acid and endotoxin in the blood(all P＜0.05);elevated expression of MUC2 and MUC3,reduced HD5 expression(all P＜0.05);increased NOS and MDA levels,decreased SOD and GSH-Px levels(all P＜0.05);downregulated expression of Nrf2,HO-1,and NQO1 proteins in intestinal tissues(all P＜0.05).These changes were significantly attenuated in the Danshen-treated groups in a dose-dependent manner(all P＜0.05).Conclusion:Danshen injection can alleviate intestinal mucosal injury in AIO rats,possibly by activating the Nrf2/HO-1/NQO1 signaling pathway and reducing oxidative stress,thereby enhancing the intestinal mucosal barrier function.

Background and Aims:Adhesive intestinal obstruction(AIO)is a type of mechanical bowel obstruction caused by abdominal or intestinal adhesions,and its onset and progression are closely associated with impaired intestinal mucosal barrier function.Danshen injection,a commonly used traditional Chinese medicine preparation with properties of promoting blood circulation and removing blood stasis,has shown therapeutic potential in various gastrointestinal diseases by improving microcirculation and promoting vasodilation.However,its specific mechanism of action in AIO remains unclear.This study was conducted to investigate the effects and potential mechanisms of Danshen injection on intestinal mucosal barrier function in a rat model of AIO.Methods:Forty rats with experimentally induced AIO were equally randomized into four groups:the model group(receiving intraperitoneal saline)and three Danshen-treated groups administered low,medium,and high doses of Danshen injection(1,2,and 4 mL/kg,respectively),once daily for 7 consecutive d.An additional 10 healthy rats received saline injections in the same manner and served as the normal control group.After the final intervention,all rats were euthanized under anesthesia.Hematoxylin and eosin(HE)staining was performed to evaluate the histopathological morphology of small intestinal tissues.Levels of D-lactic acid and endotoxin in peripheral blood were measured using enzyme-linked immunosorbent assay(ELISA).The expression levels of mucin 2(MUC2),mucin 3(MUC3),and human defensin 5(HD5)—key components of the intestinal mucus layer and innate immune response—were analyzed using quantitative real-time PCR(qRT-PCR).Colorimetric assays were conducted to assess oxidative stress markers in intestinal tissue,including nitric oxide synthase(NOS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px).Western blot was used to determine the protein expression levels of endogenous antioxidant pathway components:nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1).Results:HE staining showed no significant histological changes in the intestinal tissues of the normal control group,with a mucosal injury score of 0.The model and treatment groups exhibited varying degrees of villous disorganization and tissue edema,with injury scores of 4.69±0.62,3.36±0.41,2.29±0.22,and 1.53±0.14 in the model,low-,medium-,and high-dose groups,respectively(all P＜0.05 vs.model group).Compared with the normal control group,the other groups showed significantly increased levels of D-lactic acid and endotoxin in the blood(all P＜0.05);elevated expression of MUC2 and MUC3,reduced HD5 expression(all P＜0.05);increased NOS and MDA levels,decreased SOD and GSH-Px levels(all P＜0.05);downregulated expression of Nrf2,HO-1,and NQO1 proteins in intestinal tissues(all P＜0.05).These changes were significantly attenuated in the Danshen-treated groups in a dose-dependent manner(all P＜0.05).Conclusion:Danshen injection can alleviate intestinal mucosal injury in AIO rats,possibly by activating the Nrf2/HO-1/NQO1 signaling pathway and reducing oxidative stress,thereby enhancing the intestinal mucosal barrier function.

Objective:To investigate clinical characteristics for in-stent reocclusion lesions after coronary stent implantations in aged patients.Methods:229 patients diagnosed with chronic total reocclusions were recruited from Jan 2005 to Dec 2019 in this retrospective study.According to age, patients were divided into a 40-49 year-old group(n=60), a 50-59 year-old group(n=58), a 60-69 year-old group(n=55), and a 70-80 year-old group(n=56)to examine different lesion characteristics after coronary stent implantations.Results:In the 40-49 year-old group, the 50-59 year-old group, the 60-69 year-old group and the 70-80 year-old group, the rates of multi-vessel reocclusions were 11.6%, 15.5%, 21.8% and 25.0%, respectively( χ2=10.03, P=0.01). For each group, lesions with concurrent proximal and middle coronary reocclusions accounted for 8.3%, 12.0%, 30.9% and 35.7%, respectively( χ2=11.83, P=0.005); Reocclusions with severe coronary calcification accounted for 6.6%, 15.5%, 36.3% and 37.5%, respectively( χ2=11.56, P=0.006); Long coronary reocclusion lesions(36-47 mm)accounted for 15.0%, 17.2%, 21.8% and 25.0%, respectively( χ2=11.56, P=0.007); Coronary reocclusions with diffuse long calcified lesions accounted for 8.3%, 13.7%, 32.7% and 35.7%, respectively( χ2=10.80, P=0.01). Conclusions:The clinical characteristics of in-stent reocclusion lesions after coronary stent implantations include multiple chronic total coronary reocclusions, concurrent proximal and middle coronary reocclusions, heavily calcified coronary reocclusions, long coronary reocclusions and diffuse long calcified coronary reocclusions in aged patients.

OBJECTIVES: Hypertension is a serious complication of pregnancy-related acute kidney injury (PR-AKI). This study aimed to determine the effect of hypertension on the prognosis of PR-AKI, maternal outcomes, and fetal outcome. METHODS: Patients with PR-AKI in a hospital from January 2008 to June 2018 were enrolled for this study. Patients with or without hypertension were grouped by 1꞉1 propensity matching score. The effect of hypertension on the prognosis of PR-AKI was evaluated by multivariate Cox regression before and after matching. RESULTS: Of the 30 680 women who attended the Department of Obstetrics, 126 patients were diagnosed as PR-AKI, the incidence was 0.41%. The age was (29.04±2.32) years. There were 50 cases in the hypertension group, accounting for 39.68%. Using the propensity score method, 48 pairs of patients were successfully matched, and the covariates between the two groups were balanced. After matching and adjusting for relevant clinical factors, Cox regression analysis showed that risk of end-stage renal disease (ESRD) was increased in the hypertension group compared with the normal blood pressure group (HR=2.951, 95％ CI 1.067 to 8.275, =0.034). The risk of risk of adverse maternal outcome was increased (HR=2.815, 95% CI 1.271 to 6.233, =0.009), and the risk of fetal adverse outcome was increased (HR=1.437, 95% CI 1.028 to 4.623, =0.021). CONCLUSIONS Hypertension is an independent risk factor for ESRD, adverse maternal outcomes, and adverse fetal outcomes in the PR-AKI patients.
Acute Kidney Injury ; Cohort Studies ; Female ; Humans ; Hypertension ; complications ; Incidence ; Pregnancy ; Prognosis ; Propensity Score ; Retrospective Studies ; Risk Factors

BACKGROUND: Inflammatory and proliferating effect after mechanical injury of vascular wall is the major cause of restenosis. Nuclear factor-kappa B (NF-κB) in the NF-κB/Rel family is expressed in a variety of cell types and activates a series of target genes, which are related to the pathophysioiogy of vascular wall.OBJECTIVE: To investigate the effect of antisense and decoy NF-κB oligonucleotides on vascular smooth muscle cell (VSMS) proliferation in vitro and neointimal proliferation and monocyte chemotactic protein-1 (MCP-1) in the balloon-injured carotid artery of rats.DESTGN: Randomized controlled animal trial.SETTTNG: Department of Cardiology, Ruijin Hospital, Medical College, Shanghai Jiaotong University.MATERTALS: Totally 126 male Sprague-Dawley (SD) rats, aged 3 months, weighing 350 to 380 g, were involved in this study. Synthesis of primer and oligonucleotide: they were synthesized and designed by Shanghai Bioengineering Co. Ltd according to literatures and international internet cDNA library.METHODS: This study was carried out in the Laboratory of Cell Biology, Medical College, Shanghai Jiao Tong University and Cardiovascular Laboratory, Ruijin Hospital Affiliated to Shanghai Jiaotong University from May 2001 to March 2003.Rat aortic smooth muscle cells were isolated from May 2001 to March 2003. Rat thoracic aorta vascular smooth muscle cells were cultured by primary-explant method. And the third to fifth generations of VSMCs were involved in the experiment. Proliferating cell nuclear antigen (PCNA) NF-κB p65 protein synthesis in proliferating smooth muscle cells were detected. SD rat carotid artery underwent balloon injury. The involved 126 rats were randomly divided into 7 groups with 18in each group: normal group: normal group (the procedure was the same as other group except for balloon injury), sense group, antisense group, decoy group, scramble group, antisense plus decoy group, model group. Each group includes 6time points (6 hours, and 1,3,5,7,14 days, n =3). Then, the effect of antisense and decoy NF-κB oligonucleotides on intimai proliferation and MCP-1 and NF-κB p65 and extracellular signal regulated kinase(ERK2) expression in the balloon-injured carotid artery of rats were detected.MAIN OUTCOME MEASURES: ①Effect of oligonucleotide of NF-κB p65 on VSMCs proliferation; ② NF-κB p65 gene expression and protein synthesis; ③ Patho-morphological change after carotid balloon-injury. ④ Vascular MCP-1 mRNA Expression in balloon-injured rat carotid artery; ⑤ MCP-1 immunoreactivity in the injured arterial wall detected by immunohistochemistry; ⑥ NF-κBp65 and ERK2 protein synthesis after balloon-injury detected by Western blot in injured rat carotid arteries.RESULTS: ①PCNA protein synthesis increased in proliferating smooth muscle cells. ②NF-κB p65 gene expression was found in the cytoplasm and nucleus of proliferating smooth musclecells by in situ hybridization and NF-κB p 65 protein level increased in proliferating smooth muscle cells by flow cytometry. NF-κB p65 gene expression in antisense group decreased 53.66% compared with in sense group; it decreased 57.35% in decoy group compared with in scramble group. There were all statistical differences(P＜0.05).③ PCNA expression were inhibited in proliferating smooth musclecells by antisense and decoy oligonucleotides. Compared with positive control group, PCNA protein expression in antisense group and decoy group decreased 45.12% and 45.05%,respectively. ④ In model group, sense group and scramble group, vessel intimal area, medial area and intimal area/medial area increased at the 5th day after balloon-injury and reached the maximum at the 7th day after injury. The intimal area/medial area was significantly decreased in the antisense group and decoy group. The effect of antisense plus decoy oligonucleotides was more obvious than that of antisense group and decoy group alone but there were not significant differences among three groups. ⑤ Reverse transcription-polymerase chain reaction showed that MCP-1 mRNA expression was significantly increased 6 hours after balloon-injury, but not evident after 1 day. It was increased at the 3th, 5th and 7th days continuously, but decreased at the 14th day. MCP-1 mRNA expression was decreased at each time point in antisense group, decoy group, antisense plus decoy group (P＜0.05). ⑥Western blot analysis showed that NF-κB p65 was weakly expressed at 6 hours after vascular balloon-injury, increased significantly at 1 day, reached the peak at 7 days and weakened at 14 days, while ERK2 protein was weakly expressed, a little increased at 1 day, reached the peak at 7 days and weakened at 14 days. Treatment of antisense group, decoy group and antisense plus decoy group inhibited protein synthesis more significantly than those of model group, sense group and scramble group (P＜0.05).CONCLUSTON: NF-κB expression increases in proliferating smooth muscle cells. NF-κB modulates genes expression and protein synthesis of MCP-1 and ERK2. Cellular proliferation in vessel wall dynamically changes after balloon angioplasty injury. Antisense and decoy oligonucleotide of NF-κB by local lipofectamine transfer inhibit the expression of regulated target gene.

Aim To examine the in vivo effect of the antisense or/and decoy oligonucleotide of NF-?B on vessel proliferation and balloon-injured monocytes chemotactic protein-1(MCP-1) and extracellular signal regulated kinase in the carotid artery of rats.Methods Sprague-Dawley rats underwent balloon-dilation injury of the left carotid artery.The rats were divided into 7 groups(n=18) and each group were further divided into 6 sub-groups for study at 6 time points(1,3,5,7,14 days,n=3).Uninjured artery of the same rat was used as the control.Results In model group,sense group and scramble group,intima/media ratio increased after 5 days and reached the maximum after 14 days;intima/media ratio in antisense group,decoy group,antisense plus decoy group decreased significantly(P