Alcohol drinking triggered decrease of oxidative balance score is associated with high all-cause and cardiovascular mortality in hypertensive individuals:findings from NHANES 1999–2014

BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to investigate the association between OBS and mortality in hypertensive patients.METHODS This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)1999-2014.Several models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of mortality.RESULTS Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity analyses.RCS after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never drinkers.CONCLUSIONS In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular mortality.Encouraging hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.

Mitochondrial dysfunction in glaucomatous degeneration

Glaucoma is a kind of optic neuropathy mainly manifested in the permanent death of retinal ganglion cells(RGCs),atrophy of the optic nerve,and loss of visual ability.The main risk factors for glaucoma consist of the pathological elevation of intraocular pressure(IOP)and aging.Although the mechanism of glaucoma remains an open question,a theory related to mitochondrial dysfunction has been emerging in the last decade.Reactive oxygen species(ROS)from the mitochondrial respiratory chain are abnormally produced as a result of mitochondrial dysfunction.Oxidative stress takes place when the cellular antioxidant system fails to remove excessive ROS promptly.Meanwhile,more and more studies show that there are other common features of mitochondrial dysfunction in glaucoma,including damage of mitochondrial DNA(mt DNA),defective mitochondrial quality control,ATP reduction,and other cellular changes,which are worth summarizing and further exploring.The purpose of this review is to explore mitochondrial dysfunction in the mechanism of glaucomatous optic neuropathy.Based on the mechanism,the existing therapeutic options are summarized,including medications,gene therapy,and red-light therapy,which are promising to provide feasible neuroprotective ideas for the treatment of glaucoma.

Establishment of an adult zebrafish model of retinal neurodegeneration induced by NMDA

AIM: To establish a model of retinal neurodegeneration induced by N-Methyl-D-aspartic acid(NMDA) in adult zebrafish.METHODS: We compared the effects of three different NMDA delivery methods on retinal neurodegeneration in adult zebrafish: immersion(I.M.), intravitreal injection(I.V.), and intraperitoneal injection(I.P.), and examined retinal pathology and degeneration by hematoxylin and eosin and TUNEL staining in the treated zebrafish. Effects of the NMDA receptor antagonist MK-801 and the natural product resveratrol on NMDA-induced retinal neurodegeneration were also assessed.RESULTS: The thickened inner retina was seen in histology with 100 μmol/L NMDA by I.M. administration. Significant apoptosis in the retinal ganglion cell layer and retinal thickness reduction occurred in 0.5 mol/L NMDA I.P. administration group.Seizure-like behavioral changes, but no retinal histological alteration occurred in 16 mg/kg NMDA I.P. administration group. Resveratrol and MK-801 prevented NMDA-induced retinal neurodegeneration in the zebrafish. CONCLUSION: Among the three drug administration methods, I.V. injection of NMDA is the most suitable for establishment of an acute retinal damage model inzebrafish. I.M. with NMDA is likely the best for use as a chronic retinal damage model. I.P. treatment with NMDA causes brain damage. Resveratrol and MK801 may be a clinically valuable treatment for retinal neurodegeneration.

Induced pluripotent stem cells as a potential therapeutic source for corneal epithelial stem cells

Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered by the shortage of donors. Pluripotent stem cell technology including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs) have opened new avenues for treating this disease. iPSCs-derived corneal epithelial cells provide an autologous and unlimited source of cells for the treatment of LSCD. On the other hand, iPSCs of LSCD patients can be used for iPSCs-corneal disease model and new drug discovery. However, prior to clinical trial, the efficacy and safety of these cells in patients with LSCD should be proved. Here we focused on the current status of iPSCs-derived corneal epithelial cells used for cell therapy as well as for corneal disease modeling. The challenges and potential of iPSCs-derived corneal epithelial cells as a choice for clinical treatment in corneal disease were also discussed.

Comparison of three administration modes for establishing a zebrafish seizure model induced by N-Methyl-D-aspartic acid

BACKGROUND Epilepsy is a complex neurological disorder characterized by recurrent,unprovoked seizures resulting from the sudden abnormal discharge of brain neurons.It leads to transient brain dysfunction,manifested by abnormal physical movements and consciousness.It can occur at any age,affecting approximately 65 million worldwide,one third of which are still estimated to suffer from refractory seizures.There is an urgent need for further establishment of seizure models in animals,which provides an approach to model epilepsy and could be used to identify novel anti-epileptic therapeutics in the future.AIM To compare three administration modes for establishing a seizure model caused by N-Methyl-D-aspartic acid(NMDA)in zebrafish.METHODS Three administration routes of NMDA,including immersion,intravitreal injection and intraperitoneal injection,were compared with regard to their effects on inducing seizure-like behaviors in adult zebrafish.We evaluated neurotoxicity by observing behavioral changes in zebrafish and graded those behaviors with a seizure score.In addition,the protective effects of MK-801(Dizocilpine)and natural active constituent resveratrol against NMDA-induced alterations were studied.RESULTS The three NMDA-administration methods triggered different patterns of the epileptic process in adult zebrafish.Seizure scores were increased after increasing NMDA concentration regardless of the mode of administration.However,the curve of immersion continuously rose to a high plateau(after 50 min),while the curves of intravitreal injection and intraperitoneal injection showed a spike in the early stage(10-20 min)followed by a steady decrease in seizure scores.Furthermore,pretreatment with resveratrol and MK-801 significantly delayed seizure onset time and lowered seizure scores.CONCLUSION By comparing the three methods of administration,intravitreal injection of NMDA was the most suitable for establishing an acute epileptic model in zebrafish.Thus,intraperitoneal injection in zebrafish can be applied to simulate diseases such as epilepsy.In addition,NMDA immersion may be an appropriate method to induce persistent seizures.Moreover,MK-801 and resveratrol showed strong anti-epileptic effects;thus,both of them may be clinically valuable treatments for epilepsy.

The Function of miR-31 Expression in Differentiation of Neural Stem Cells

Spinal cord injury (SCI) is a severe complication of acute spinal injury, it can lead to axonal degeneration and necrosis of neurons, causing damage cross section below the movement, then loss of sensory, reflex and autonomous control function below the damage section. Nowadays, there is increasing evidence that transplantation of neural stem cells can help to repair spinal cord injury after spinal cord injury. The aim of this study was to research the function of miR-31 expression in differentiation of neural stem cells. Mir-31 was transfected the mimics and inhibitor into neural stem cells. By the morphological observation, the cell over expression of miR-31 was closer to NSCs. With the RT-PCR, Hb9 and STMN1 were up-regulate when miR-31 was inhibited, and Nestin was down-regulate. When miR-31 was over expression, the expression of Nestin and Hb9 was up-regulate. These findings suggest that miR-31 may play a significant role in proliferation and differentiation of neural stem cell and are potential targets for therapeutic interventions following spinal cord injury.

Recombinant E.coli LLO/OVA Induces Murine BMDCs Maturation via TLR4 and NOD1 Receptor and Promotes Specific Cytotoxic T Cell Immunity

Objective To explore the immune stimulation effect of recombinant E.coli LLO/OVA on mice bone marrow-derived dendritic cells （BMDCs） and T lymphocytes in vitro.Methods After BMDCs stimulated by E.coli LLO/OVA,their Toll-like receptor （TLR） and nucleotide-binding oligomerization domain （NOD） receptor signalling pathway were examined by superarray hybridization;and the priming effect of the vaccine activated BMDCs on CD4＋T and CD8＋T was determined by [3H]thymidine uptake and ELISA,the tumor cytotoxic effect of activated CD8＋T cells was determined by cytotoxic assay.Results After BMDCs were activated by E.coli LLO/OVA via TLR4,NOD1 receptor and NF-κB signalling pathway,the expression of their surface molecules including MHC class Ⅰ,MHC class Ⅱ,CD40,CD80 and CD86 significantly up-regulated;the secretion of IL-12 and IFN-？ increased also.The mature BMDCs stimulated the allergic CD4＋T and CD8＋T cells proliferation and their IL-2 and IFN-γ secretion,and the activated CD8＋T cells effectively killed B16-OVA melanoma cells and RMA-S/OVA lymphoma cells in vitro.Conclusion E.coli LLO/OVA is effective in inducing BMDCs maturation via activating TLR4 and NOD1 receptor signalling pathway and promoting specific anti-tumor T cell immunity in vitro.

The Evaluation of Visual Cadavers in Medical Laboratory: from Teaching to Practical Applications

Visual Cadavers is anemerging study method which promotes medical education and practical applications.It is benefited from other techniques and evaluated as having huge advantages,which is not only accelerating teaching and learning,but also improving scientific study,nevertheless,with limited cons.

口服伊曲康唑治疗脂溢性皮炎的一项开放性非对照试验

Background: Seborrhoeic dermatitis is an inflammatory cutaneous disorder in which the colonization of the affected area by Malassezia has been proved to play a key role. Objective: To perform a noncomparative open clinical study with oral itraconazole capsule (200 mg/day× 7 days) and consecutive usage 200 mg/day for the first 2 days of the following 2 months in patients with seborrhoeic dermatitis. Methods: Twenty- nine patients were enrolled to determine the efficacy and safety of oral itraconazole. The patients were evaluated according to itching, burning, erythema, desquamation and seborrhoea, each scored on a 0- 4 scaleon days 15 (T15), 30 (T30), 60 (T 60) and 90 (T90). Itraconazole capsule 100 mg was given twice a day for 1 week and then, after a 3- week interval, patients used itraconazole capsule 200 mg/day for the first 2 days of the following 2 months. The clinical response was graded as markedly effective, effective, moderate or ineffective. Results: A clinical improvement (evaluated as markedly effective or effective) was observed in 23 patients (83% ) at T15, 21 (76% ) at T30, 20 (72% ) at T60 and 17 (61% ) at T90. At baseline, the mean ± .SD total clinical scores were 10.44 ± 2.45, 1.98 ± 0.5, 2.97 ± .1.12, 3.15 ± 1.74 and 3.30 ± 1.90 at T0, T15, T30, T60 and T90, respectively. Compared with baseline values, itraconazole capsule significantly reduced the mean ± SD total score as well as individual erythema and desquamation (Wilcoxon’ s signed test- twotailed)(P < 0.0001). No drug- related systemic adverse event was observed during the study. Conclusions: Seborrhoeic dermatitis shows marked reduction in inflammation when treated with itraconazole. The anti- inflammatory activity of oral itraconazole and efficacy on Malessezia suggests that itraconazole capsule will be first oral treatment option in future in severe seborrhoeic dermatitis.

An Interpretable Prediction Model for Stroke Based on XGBoost and SHAP

Objective:To establish a stroke prediction and feature analysis model integrating XGBoost and SHAP to aid the clinical diagnosis and prevention of stroke.Methods:Based on the open data set on Kaggle,with the help of data preprocessing and grid parameter optimization,an interpretable stroke risk prediction model was established by integrating XGBoost and SHAP and an explanatory analysis of risk factors was performed.Results:The XGBoost model’s accuracy,sensitivity,specificity,and area under the receiver operating characteristic(ROC)curve(AUC)were 96.71%,93.83%,99.59%,and 99.19%,respectively.Our explanatory analysis showed that age,type of residence,and history of hypertension were key factors affecting the incidence of stroke.Conclusion:Based on the data set,our analysis showed that the established model can be used to identify stroke,and our explanatory analysis based on SHAP increases the transparency of the model and facilitates medical practitioners to analyze the reliability of the model.

Combination therapy using low‐dose anlotinib and immune checkpoint inhibitors for extensive‐stage small cell lung cancer

Background:This study evaluated the efficacy and safety of low‐dose anlotinib combined with immune checkpoint inhibitors as second‐line or later treatment for extensive‐stage small cell lung cancer(ES‐SCLC).Methods:The study included 42 patients with ES‐SCLC who were treated with low‐dose anlotinib combined with programmed cell death protein 1/programmed cell death‐ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022.We retrospectively analyzed the efficacy and safety data for these patients.Indicators assessed included progression‐free survival(PFS),overall survival(OS),the overall response rate(ORR),the disease control rate(DCR),and adverse events(AEs).Prognostic factors were identified in univariate and multivariate analyses.Results:Median PFS was 11.0 months(95%CI:7.868–14.132)and median OS was 17.3 months(95%CI:11.517–23.083).The ORR was 28.5%and the DCR was 95.2%.Treatment‐related AEs were noted in 27 patients(64.3%),the most common of which was thyroid dysfunction(26.2%).Grade 3/4 treatmentrelated AEs were observed in two patients(4.8%).Conclusions:A combination of low‐dose anlotinib and immune checkpoint inhibitors as second‐line or later treatment for ES‐SCLC may achieve longer PFS and OS and have manageable AEs.

Evaluation of Helicobacter pylori Infection in Patients with Chronic Hepatic Disease

Background： The ^13C urea breath test （^13C-UBT） is the gold standard for detecting Helicobacterpylori infection. H. pylori pathogenesis in patients with hepatitis B virus （HBV） and related diseases remains obscure. We used ^13C-UBT to detect H. p.vlori infection in patients with chronic HBV infection, HBV-related cirrhosis, HBV-related hepatic carcinoma, and other chronic hepatic diseases. Methods： A total of 131 patients with chronic hepatitis B （HB）, 179 with HBV-related cirrhosis, 103 with HBV-related hepatic carcinoma, 45 with HBV-negative hepatic carcinoma, and 150 controls were tested for H. pylori infection using ^13C-UBT. We compared H. pylori infection rate, liver function, complications of chronic hepatic disease, serum HBV-DNA, serum alpha-fetoprotein （AFP）, and portal hypertensive gastropathy （PHG） incidence among groups. Results： HBV-related cirrhosis was associated with the highest H. pylori infection rate （79.3%）. H. pylori infection rate in chronic HB was significantly higher than in the HBV-negative hepatic carcinoma and control groups （P 〈 0.001 ）. 11. pylori infection rate in patients with HBV-DNA ≥10^3 copies/ml was significantly higher than in those with HBV-DNA 〈103 copies/ml （76.8% vs. 52.4%, P 〈 0.001）. Prothrombin time （21.3 ± 3.5 s vs. 18.8 ±4.3 s）, total bilirubin （47.3±12.3 μmol/L vs. 26.6±7.9 μmol/L）, aspartate aminotransferase （ 184.5 ±37.6 U/L vs. 98.4 ± 23.5 U/L）, blood ammonia （93.4 ± 43.6 μmol/L vs. 35.5 ± 11.7 μmol/L）, and AFP （203.4±62.6 μg/L vs. 113.2± 45.8 μg/L） in the ^13C-UBT-positive group were significantly higher than in the ^13C-UBT-negative group （P 〈 0.01）. The incidence rates of esophageal fundus variceal bleeding （25.4% vs. 16.0%）, ascites （28.9% vs. 17.8%）, and hepatic encephalopathy （24.8% vs. 13.4%） in the ^13C-UBT-positive group were significantly higher than in the 13C-UBT-negative group （P 〈 0.01 ）. The percentages of patients with liver function in Child-Pugh Grade C （29.6% vs. 8.1%） and PHG （43.0% vs. 24.3%） in the ^13C-UBT-positive group were significantly higher than in the ^13C-UBT-negative group （P 〈 0.05）. Conclusions： It is possible that H. pylori infection could increase liver damage caused by HBV. 1t. pylori eradication should be performed in patients with complicating H. pylori infection to delay hepatic disease progression.

Analysis of the Relationship between Helicobacter pylori Infection and Diabetic Gastroparesis

Background： Whether Helicobacter pylori infection is associated with diabetic gastroparesis （DGP） is unclear. This study aimed to investigate the potential correlation between H. pylori infection and DGP. Methods： In this study, 163 patients with type 2 diabetes mellitus and 175 nondiabetic patients who were treated in our department were divided into DGP, simple diabetes, non-DGP （NDG）, and normal groups based on their conditions. The H. pyh）ri infection rate in each group was calculated. H. pylori eradication therapy was performed for patients with H. pylori infection in each group. The eradication rates were compared between the groups, and the improvements in gastroparesis-associated symptoms were compared before and after treatment in patients with DGP. Results： The tl. pylori infection rate was 74.6% in the DGP group, which was significantly higher than that in the simple diabetes （51.1%, P 〈 0.01）, NDG （57.7%, P 〈 0.05）, and normal groups （48.0%, P 〈 0.01）. With increased disease course, the incidence of DGP and the H. pylori infection rate gradually increased （P 〈 0.05）. In the DGP group, the incidences of upper abdominal pain and distention, early satiety, and anorexia were 75.5%, 66.0%, and 67.9%, respectively, before eradication treatment; and 43.4%, 35.8%, and 39.6%, respectively, after eradication treatment, and the difference was statistically significant （P 〈 0.01）. In patients with DGP with successful H. pylori eradication, the number of barium strips discharged after eradication was 5.9 ± 1.0, which was significantly larger than that before treatment （4.1 ± 0.7, P 〈 0.01）. In addition, the number of barium strips discharged was significantly larger in patients with DGP with successful H. pylori eradication than those with failed H. pylori eradication （P 〈 0.01 ）. Conclusions： DGP development might be associated with H. pylori infection. H. pylori eradication can effectively improve dyspepsia-associated symptoms and delayed gastric emptying in patients with DGP.

Screening for Differentially Expressed Genes of Gastric Stromal Tumor Originating from Muscularis Propria

INTRODUCTION Gastric stromal tumor （GST） is a set of gastrointestinal mesenchymal tumors those originate from interstitial cells of Cajal. Its early diagnosis and treatment are critical to prognosis. The occurrence of GST remains obscure; this study used Affymetrix expression spectrum chip to detect the gene expression spectrum of GST and explore new molecular target that is used in the treatment and prognosis of GST.