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Objective To explore the risk factors for hospital acquired pneumonia (HAP) in patients with neural-intensive care unit (NICU).Methods The clinical data were analyzed retrospectively for 207 patients in NICU ≥ 5 d,to determine possible risk factors with HAP.Results The incidence of HAP was 14.01％(29/207).Correlation analysis showed that old age,disturbance of consciousness,dysphagia,vomiting,low pre albumin,NICU residence time ≥ 30 d,indwelling nasogastric tube,the use of the acid-blocking drugs,tracheal intubation,tracheal incision,mechanical ventilation and deep bronchoscopic suctioning were the related factors of HAP (P ＜ 0.05 or ＜ 0.01),but blood glucose,sedative drugs were unrelated with HAP (P ＞ 0.05).Conclusion There is a high incidence of NICU in patients with HAP,taking comprehensive measures actively,reduce risk factors,can effectively control the occurrence of HAP in NICU.

β2-Microglobulin is a small molecule protein, consisting of a polypeptide chain.Previous studies have confirmed that serum β2-microglobulin is a biomarker that reflects early renal function injury, and renal function injury is closely correlated with ischemic stroke.Studies in recent years have shown that the level of serum β2-microglobulin increases significantly in patients with ischemic stroke.Thus, it can be used as a biomarker for the risk of ischemic stroke.

Objective:This study aimed to establish an eXtreme Gradient Boosting(XGBoost) model that can predict the recurrence of hepatocellular carcinoma(HCC)patients after laparoscopic hepatectomy (LH) surgery.Methods:A total of 440 patients with primary HCC who received LH treatment for the first time from January 2013 to September 2016 in Affiliated Hospital of Chengde Medical University were selected as the research objects. The diagnosis method was pathological diagnosis. Research objects were divided into training group ( n=88) and verification group ( n=352) at a ratio of 2∶8 by random number table method. The Kaplan-Meier method was used to draw the recurrence-free survival curve, and the Log-rank test was used to compare the survival of the two groups; the training group was used to establish the COX regression model and the XGBoost model to screen independent predictors of recurrence after LH; receiver operating characteristic(ROC) curve was used to analyze the predictive abilities of the two models, and conducted internal verification in the verification group; Hosmer and Lemeshow Test was used to evaluate the calibration of the two models, and P>0.05 was used as a good fit between the model and the actual situation. Results:Both the COX regression model and the XGBoost model screened out tumor thrombus, low degree of differentiation, tumor microvascular infiltration (MVI), number of tumors, large tumors, and positive hepatitis B surface antigen were independent predictors of tumor recurrence( HR=2.477, 0.769, 1.786, 1.905, 1.544, 1.805; 95% CI: 1.465-4.251, 0.619-0.819, 1.263-2.546, 1.354-2.704, 1.272-1.816, 1.055-2.555). The XGboost model scores were 32 points, 29 points, 24 points, 18 points, 16 points, 11 points, respectively. In the training group, the area under the curve (AUC) of the COX regression model and XGBoost model for predicting recurrence were 0.746 (0.730-0.762) and 0.802 (0.785-0.818), respectively. The XGBoost model had strong predictive ability and was confirmed in the validation cohort. Conclusions:This study had established and verified the XGBoost model that can predict the recurrence of HCC patients after receiving LH for the first time. It can be used in clinics to assist doctors in formulating personalized postoperative monitoring programs for patients. Early detection, early diagnosis and early treatment of tumors and strengthening of postoperative follow-up are important measures to improve the prognosis of patients.

To construct a recombinant expression system for a single-domain antibody targeting the urease of Helicobacter pylori (Hp), this study employed several strategies. First, using artificial intelligence (AI) auxiliary tools such as Pymol, I-TASSER, and ClussPro2, the molecular interactions between different antibodies and Hp urease subunit B (UreB) were analyzed. The fully humanized single-domain antibody UreBAb was identified as the primary research target. Next, the UreBAb gene sequence was optimized based on Escherichia coli codon preferences, and was inserted into expression vectors such as pET28a and pE-SUMO. The resulting recombinant expression strains were obtained by transforming Escherichia coli Rosetta(DE3). Recombinant antibody proteins were prepared through IPTG induction, and its activity was detected using extracted Hp urease as the antigen. SDS-PAGE analysis confirmed the correct expression of both UreBAb and SUMO-UreBAb, with protein yields of 0.34 mg/mL and 0.41 mg/mL, respectively. Unidirectional immunodiffusion experiments further confirmed that both recombinant antibodies exhibited strong affinity for Hp UreB antigen, with inhibition rates of 51.27% and 74.07%, respectively. Additionally, leveraging artificial intelligence tools such as AlphaFold2, cluspro2, mCSM-AB, OSPREY, and FoldX, the study evaluated and analyzed key binding sites and mutational strategies affecting the stability of the antigen-antibody complex. Subsequently, nine UreBAb evolution mutants were constructed, and their binding activities with the antigen were enhanced. Among these, the I107W mutant showed the most significant improvement, achieving a 24.95% increase compared to the wild-type UreBAb. This research lays a solid foundation for the development of fully humanized single-domain antibodies against Hp.

Objective:To investigate the inhibitory effect of specific inhibitor of necroptosis necrostatin-1 (Nec-1) on necroptosis of retinal ganglion cells (RGCs) in rats with acute ocular hypertension.Methods:Twenty-four adult male Sprague Dawley rats were randomly divided into normal control group, model control group, Nec-1 treatment group and negative control group by random number table method, with 6 rats in each group.High intraocular pressure (IOP)-induced ischemia and reperfusion model was established through anterior chamber irrigation of 0.9% sodium chloride solution in left eyes of the rats, raising the IOP to 110 mmHg (1 mmHg=0.133 kPa) for 60 minutes.Nec-1 (4 mmol/L, 2 μl) or dimethyl sulfoxide (2 μl) was intravitreally injected immediately in Nec-1 treatment group and negative control group following modeling, respectively, according to grouping.No intervention was administered to the normal control group.Paraffin sections of rat retinas of the left eyes in different groups were prepared seven days after modeling.The retinal structure was observed by hematoxylin-eosin staining, and the expression levels of thymocyte antigen-1 (Thy-1) and glial fibrillary acidic protein (GFAP) were detected via immunohistochemical staining.All animal experiments were approved by an Ethics Committee of Tianjin Union Medical Center (No.2017 Quick audit C01).Results:Seven days after modeling, compared with normal control group, the retinal nerve fiber layer was thinner in model control group and negative control group, and the RGCs were arranged loosely, and cells in the inner nuclear layer were reduced and arranged disorderly, and cells in the outer nuclear layer were normal or enlarged.Compared with model control group and negative control group, the nerve fiber layer was thickened and the number of RGCs was significantly increased in Nec-1 treatment group.The number of Thy-1-positive RGCs was decreased in model control group, negative control group and Nec-1 treatment group than normal control group, and there were more Thy-1-positive RGCs in Nec-1 treatment group than model control group and negative control group.The integrated absorbance ( A) value of GFAP protein in normal control group, model control group, negative control group and Nec-1 treatment group was 47.209±15.311, 116.220±18.194, 116.382±19.020, 92.818±10.236, respectively, showing statistically significant differences among them ( F=24.675, P<0.001). The integrated A value of GFAP protein was significantly increased in model control group, negative control group and Nec-1 treatment group than normal control group, and the integrated A value of GFAP protein in Nec-1 treatment group was lower than that in model control group and negative control group, with statistically significant differences (all at P<0.05). Conclusions:Nec-1 can promote RGCs survival by inhibiting the necroptosis of RGCs in rats with acute intraocular hypertension.

Objective:To clarify the role of Heat shock proteins (HSPs) on the cardiac function during acute myocardial infarction (AMI) after bone marrow cell implantation (BMT), we examined the expression of HSP32 and HSP70 in a rat model of myocardial infarction. Methods: Myocardial infarction model was induced in the inbred Lewis rats by left anterior descending artery ligation,and 5?10 6 of bone marrow mononuclear cells (BM MNCs) were injected into an ischemic zone. On days 1, 3, 7 and 14 post infarct, the differentiations of transplanted cells and the expressions of HSP32 and HSP70 were determined by immunofluorescence or RT-PCR. The cardiac function was evaluated by echocardiography. Results: Immunofluorescence microscopy of hearts from BMT group revealed that expressions of HSP32 and HSP70 were promoted within cardiomyocytes in the infarction zone and the peri infarct zone,and expressed within some transplanted bone marrow cells as well. RT-PCR also showed the mRNA expression levels of HSP32 and HSP70 in BMT group were significantly higher than those of the control group, peaked on day 3 post infarct (5.0 fold and 2.9 fold, respectively, P

Objective To investigate the role and underlying mechanism of dexmedetomidine in protecting mouse neuroblastoma N2a cells against oxidative stress injury,and to discuss the effect of ERK signaling pathway.Methods Na2 cell oxidative stress injury model was established by H2O2 treatment.Cells were divided into 5 groups:control group (group C),H2O2group (group H), dexmedetomidine group (group D),H2O2+dexmedetomidine group (group HD),H2O2+dexme-detomidine+ERK inhibitor group (group HDP).Group H,group HD and group HDP were given 200 μmol/L H2O2with or without 100 ng/ml dexmedetomidine and 20 μmol/L ERK inhibitor PD98059,group D was treated with dexmedetomidine at the corresponding point,group C was treated with equal normal saline,After 1,4 hours of H2O2stimulation,cell survival,morphology changes,SOD production and ERK intracellular signaling pathway were compared between groups. Results Compared to group C,N2a cells in the group H demonstrated significantly ruduced cell sur-vival,much worse cell morphology and less SOD production (P<0.05).Compared to group H,N2a cells in group HD demonstrated significantly increased cell survival,much better preserved cell mor-phology,higher levels of SOD and enhanced ERK activation (P<0.05);Compared to group HD, cells in the group HDP had markedly decreased cell survival,worse cell morphology and lower SOD level (P<0.05).No significant changes were found in cell survival,morphology changes,SOD pro-duction and ERK intracellular signaling pathway between the groups C and D.Conclusion Dexme-detomidine protected mouse neuroblastoma N2a cells against oxidative stress injury by regulating ERK activation and SOD production.

Objective:To explore the association and gene-environment interaction between single nu-cleotide polymorphisms (SNPs)involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P)among Chinese population.Methods:A total of 806 NSCL/P trios were drawn by an international consortium,which conducted a genome-wide association study (GWAS)using a case-parent trio design to investigate genes affecting risks to NSCL/P.The transmission disequilibrium test (TDT)was used to explore the association between cell-cell adhesion genes,including CDH1,CT-NNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P.Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children.Four common maternal exposures including maternal smoking,environmental tobacco smoke,alcohol consumption and multivita-min supplementation during pregnancy were included in this study.Results:A total of 226 SNP markers were tested after quality control in this study.Although 23 SNPs in three genes (CTNNB1,CDH1, ACTN1)showed nominal significant association with NSCL/P in the TDT (P <0.05).There were no sig-nificant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P >0.000 2).Tests for gene-environment interaction yielded significant results be-tween rs7431 27 in ACTN1 and environmental tobacco smoke (P =0.000 1 )with an estimated OR (case |G and E)=2.00(95%CI:1 .23 -3.26)and OR (case |G no E)=0.59 (95%CI:0.38 -0.90).Among the lower P value results in gene-environment tests,there were no significant results be-tween rs1 475034,rs370535,rs227341 9 in ACTN1,rs1 06871 in CTNNB1 and environmental tobacco smoke interaction.There were also no significant results between rs7634000,rs2971 366,rs2634553, rs1 489032,rs762481 2 in PVRL3 and multivitamin supplementation during pregnancy in gene-environ-ment tests(P >0.000 2).Conclusion:There is no association between cell-cell adhesion genes,inclu-ding CDH1,CTNNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P when the genes are considered alone.But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.

In recent years, the concept of " microbiome-gut-brain axis" has been proposed to reveal the wide connection between gut microbiome and nervous system diseases. As a common and frequently occurring disease of nervous system, the occurrence and outcome of ischemic stroke are closely related to gut microbiome. This article reviews the relationship between gut microbiome and risk factors of ischemic stroke and immune inflammation after stroke.