Objective To observe the clinical efficacy and safety of tirofiban in stent-assisted coil(SAC)embolization for patients with acutely ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured wide-necked intracranial aneurysms who underwent SAC embolization were divided into the control group and the treatment group according to cohort method.The control group was treated with aspirin enteric-coated tablets(300 mg,qd)and clopidogrel bisulfate tablets(300 mg,qd,oral administration)at 2 h before surgery.The treatment group was treated with tirofiban hydrochloride and sodium chloride injection at 10 μg·kg-1 during surgery,which was administrated via intravenous injection at a constant speed within 10 min.Then,the injection rate was adjusted to 0.1 μg·kg-1·min-1 for 12-24 h.The two groups were compared on clinical efficacy,platelet activation function[platelet alpha granule membrane glucoprotein(CD62p)positive rate,platelet adhesion rate and platelet aggregation rate],and perioperative complications.The patients were followed up for 6 months after surgery.The Glasgow Outcome Scale(GOS)scores,recurrence rate and safety were recorded.Results Fifty-three cases and forty-seven cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates of embolization in the treatment group and the control group were 91.49％(43 cases/47 cases)and 81.13％(43 cases/53 cases),without statistically significant difference(P＞0.05).On day 7 after surgery,CD62p positive rates were(56.31±7.41)％and(60.71±7.38)％;platelet adhesion rates were(37.56±3.64)％and(38.04±3.89)％;platelet aggregation rates were(27.03±3.39)％and(30.19±3.63)％.The differences in above indicators between the treatment group and the control group were statistically significant(all P＜0.05).During 6 months of follow-up,the good prognosis rates in the treatment group and the control group were 89.36％and 81.13％;recurrence rates were 4.26％and 9.43％.There were not statistically significant differences in above indicators between the treatment group and the control group(all P＞0.05).The perioperative complications in the two groups mainly included rerupture and bleeding of arterial aneurysms,subdermal ecchymosis,gingival bleeding,thrombotic events,etc.The total incidences of complications in the treatment group and the control group were 10.64％and 28.30％,with statistically significant difference(P＜0.05).Conclusion Tirofiban hydrochloride and sodium chloride injection can effectively reduce the incidence of thrombotic events in patients with acutely ruptured wide-necked intracranial aneurysms during perioperative period of SC A embolization,and improve platelet activation function.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective To assess the clinical short-term outcomes of implanting D-shant atrial shunt device(aSD)in a single center for patients with heart failure with reduced ejection fraction(HFrEF).Methods From January 2022 to January 2023,a retrospective analysis was conducted on 12 patients with HFrEF who underwent percutaneous implantation of a D-shant aSD.We assessed cardiac chamber size and ventricular function using echocardiography,right heart catheterization measurements and patient clinical indicators were collected,follow up data of 12 months postoperative and pre-implantation D-shant were compared.The primary endpoint of the study was the cumulative occurrence of adverse cardiac,neurologic,or renal events during the follow-up period.Secondary endpoints were improvements in functional status included cardiac function,quality of life,and exercise capacity.Results All 12 patients underwent successful percutaneous inter-atrial shunting procedures using the D-shant.Postoperative immediately fluoroscopy and echocardiography confirmed accurate localization and patency of the atrial shunt devices in all cases.Postoperative hemodynamic assessment revealed a significant decrease in pulmonary capillary wedge pressure[(29.8±3.4)mmHg vs.(17.8±0.8)mmHg,P＜0.001].During 12 months follow-up,the cumulative adverse event rate was 8.3％(one patient received a heart transplant),a significant reduction in left atrial diameter from(65.8±6.5)mm to(48.0±4.5)mm(P＜0.001)was observed.Furthermore,there was notable improvement in clinical cardiac function indices quality of life,and exercise capacity of the patients.Conclusions This single-center retrospective study found that the use of a D-shant aSD to perform percutaneous interatrial shunting in patients with HFrEF is safe and effective.Short-term follow-up demonstrated sustained patency of the shunt and that the intervention was associated with improved functional status.

Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

Objective:To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city.Methods:A total of 210 RhD-samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population.Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene.Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene,and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype.Results:Among 210 RhD-specimens,128 cases(60.38％)had RHD gene deletion.27 cases had partial exons of RHD,including 2 cases with RHD*DVI.3/RHD*01N.01,24 cases with RHD*01N.04/RHD*01N.01,and 1 case with RHD-CE(2-10)/RHD*01N.01.55 cases had retained all of 10 exons,including 4 cases with RHD*01/RHD*01N.01,6 cases with RHD*15/RHD*01N.01,1 case with RHD*01W.72/RHD*01N.01,1 case with RHD*15/RHD*01EL.01,39 cases with RHD*01EL.01/RHD*01N.01,and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G＞A mutation loci.Conclusion:There is polymorphism in the molecular mechanism of RhD-D gene in Wuhu blood donor population,among which RHD*01EL.01 and RHD*15 are the main variants in this region.The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.

Objective To compare the efficacy and safety of vedolizumab(VDZ)and infliximab(IFX)for moderate to severe ulcerative colitis(UC)patients through a multicenter retrospective cohort study.Methods All patients with moderate to severe UC who were naive to biologic agents and treated with IFX or VDZ for at least 14 weeks at 3 hospitals in Southwest China between January 2021 and January 2023 were retrospectively enrolled.The efficacy evaluation indicators,including steroid-free clinical remission rates,clinical remission rates and endoscopic remission rates at weeks 14 and 52 were compared between the 2 groups.The occurrence of adverse events during treatment were recorded.Taking whether mucosal healing could be achieved after 14 and 52 weeks of treatment as the dependent variable,firstly,univariate analysis was performed to analyze the risk factors affecting mucosal healing at weeks 14 and 52,and then multivariate logistic regression analysis was applied to identify the independent risk factors of mucosal healing at the 2 time points.Results A total of 151 patients with moderate to severe UC were included,after propensity score matching(PSM),each group included 57 patients.There were no significant differences in the steroid-free clinical remission rate and clinical remission rate between the 2 groups at weeks 14 and 52(P＞0.05).The endoscopic remission rate at week 14 was significantly higher in the VDZ group than the IFX group[40.4％(23/57)vs 22.8％(13/57),P=0.044],but no such difference was observed at week 52[64.5％(20/31)vs 59.5％(22/37),P=0.669].Multivariate logistic regression analysis showed that left-sided disease(E2)[vs pancolitis(E3)](OR=0.46,95％CI:0.21～0.98,P=0.045)was independent risk factor for mucosal healing at week 14 and a disease duration ≥36 months(OR=0.25,95％CI:0.09～0.66,P=0.005)was independent risk factor for mucosal healing at week 52.No statistical difference was observed in the incidence of adverse events between the 2 groups(1.8％vs 7.0％,P=0.360).Conclusion VDZ and IFX have similar efficacy and safety,and both can be used as first-line options for patients with moderate to severe UC.

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
Humans ; Cleft Palate/genetics* ; Cleft Lip/genetics* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide

ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy （uIRIx） model. MethodsIn vivo： C57BL/6J mice were randomly divided into Sham group， uIRIx group and uIRIx+ lithcholic acid （LCA） group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model， kidney function was evaluated by blood and urine biochemical indexes， and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis， and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5^+/+ mice and TGR5^-/- mice respectively， with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro： TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line （HK2 cells）， LCA was used for drug intervention， cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo： Compared with the Sham group， plasma creatinine level （P=0.007） and urinary albumin/creatinine ratio （P=0.041） in uIRIx group were significantly increased， renal cortical protein TGR5 expression （P=0.002） was decreased， Fibronectin expression （P=0.020） and COL1A1 expression （P<0.001） were increased. At the same time， the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression （P<0.001） and COL1A1 expression （P=0.001） compared with TGR5^+/+ mice. In vitro： TGF-β1 induced morphological changes of HK2 cells， cytoskeletal depolymerization and recombination， and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1， and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model， and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis； In HK2 cells， LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.

Acute transient or permanent retinal arterial ischemia is ocular and systemic emergency requiring immediate diagnosis and treatment. Transient monocular vision loss is transient retinal arterial ischemia which leaves no permanent deficits. Central retinal arterial occlusion and branch retinal arterial occlusion lead to permanent visual function deficits in the majority of patients. Current treatment include lowering intraocular pressure, dilating blood vessels, hyperbaric oxygen therapy, intravenous or intra-arterial thrombolysis and so on, but there is still no standard treatment procedure. High risk groups should receive primary prevention measures in order to reduce the incidence of the disease. Patients with acute retinal arterial ischemia are at high risk of subsequent stroke and adverse cardiovascular events. Relevant risk factors should be identified in time, the primary disease should be treated actively, and appropriate secondary prevention measures should be taken to improve the prognosis. This review summarizes the recent treatment and prevention procedures of acute retinal arterial ischemia, to provide references for the management of these diseases.

Aim To study the apoptosis of human hep-atoma cell line ( HepG2 ) induced by different polar parts of Arnebia euchroma ( Royle ) Johnst ( AE ) and to verify its anti-hepatoma effect by a mouse orthotopic liver cancer model so as to explore the anti-cancer effect of AE extract. Methods Firstly, MTT method and Annexin V-FITC/PI double staining method were used to detect the anti-proliferative and pro-apoptotic effects of each polar part of AE on HepG2 cells, and Western blot was used to detect the expression of Bcl-2 apoptosis family proteins incells. Based on the above experimental results, the effective parts with significant pro-apoptotic effect were screened out for anti-in situ liver cancer experiments in mice, and the organ indexes, liver function indexes and tissue sections of mice with orthotopic liver cancer before and after administration were evaluated. Results With the decrease of the polarity of AE extract,the anti-proliferation and pro-apoptotic effects on HepG2 cells were enhanced, and the anti-proliferation and apoptosis-inducing effects of AE petroleum ether fraction ( AEP) were the most significant. When AEP dose was 1.56 (μg • L