Objective: To investigate the effects of glucagon-like peptide-1(GLP-1)on high glucose-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Methods: HUVECs were cultured under varying conditions for 48 h, and the cell viability was spectrophotometrically measured by MTT assay. Flow cytometry detected the ratio of cell apoptosis. Western blot detected the protein levels of p-Akt and p-eNOS, while NO assay kit detected the NO concentration.
Results: Treatment of high glucose (33 mmol/L) for 48 h signiifcantly decreased the HUVECs viability and induced the apoptosis of HUVECs, concomitant with decreased Akt and eNOS phosphorylation leves and subsequent NO production. Treatment with GLP-1 (3 nmol/L) for 48 h in the high glucose group increased the HUVECs viability (P<0.01), decreased the ratio of HUVECs early apoptosis (P<0.05), ameliorated the reduced protein levels of p-Akt and p-eNOS caused by high glucose, and increased the NO production (P<0.05). The anti-apoptotic effect and the increased NO production of GLP-1were inhibited by PI3K inhibitor wortmannine (100 nmol/L) or eNOS inhibitor L-NAME (100μmol/L). The effect on p-Akt, p-eNOS of GLP-1 was inhibited by wortmannine (100 nmol/L) while L-NAME (100μmol/L) did not have any influence on the expression of p-Akt.
Conclusion: GLP-1 can ameliorate high glucose-induced HUVECs apoptosis, which is probably related to the up-regulation of PI3K/Akt/eNOS pathway.

Objective To investigate the executive function features of different subtypes of vascular cognitive impairment (VCI). Methods Sixty-four subjects with subcortical ischaemic vascular disease (SIVD) presumed by medical history and neuroimaging (cranial MRI) were recruited. The clinical and neuropsychological features of the 4 groups were compared: cognitive normal control (n=25), simple executive impairment of VCI-ND (s-VCI-ND, n=16), multi-domain impairment of VCI-ND (m-VCI-ND, n=26) and vascular dementia (VaD) patients (n=22). All participants underwent neuropsychological tests covering global cognitive function, executive function, memory function, language function and visual spatial skills. The executive tests included 15 independent subtest reflect set shifting, inhibition of prepotent responses, working memory, concept formation and fluency. Results Tower of Hanoi, self ordered pointing test and paced auditory serial addition test were not suitable for identification of VCI-ND because their finish rates were less 50%. Performance of trail making test (216.5±69.3 vs 137.4±37.9), Stroop color words test (115.4±30.1 vs 72.9±17.5), California cards sorting test-Chinese version (1.9±1.4 vs 2.7±1.2)and animal category fluency test(14.2±2.3 vs 17.7±4.4) had significant difference between s-VCI-ND group and cognitive normal control group (t=4.73, 5.72, 2.04 and 3.53, all P<0.05) and these tests were applicable and sensitive assessment tools in all executive tests. Time-consuming index showed more sensitivity than correct index in executive function. Neuropsychological deficits of m-VCI-ND patients showed lower than that of s-VCI-ND group and better than that of VaD patients. It was likely that the m-VCI-ND was a transition state between normal aging and VaD. Conclusion Executive dysfunction of VCI caused by SIVD is short of specificity. Some tests may appear earlier in screening of VCI-ND.

Objective To analyze the clinical characteristic of spontaneous bacterial peritonitis (SBP) in patients with severe viral hepatitis, and explore its clinical classification and significance. Methods A retrospective research of 120 cases of SBP associated with severe viral hepatitis was performed, and main clinical symptoms and physical signs appeared at the early onset were classified and explored. Results Clinical manifestations of SBP in patients with severe viral hepatitis included 5 types, which were conventional type(41.7%, 50/120), symptomless type(15.8%, 19/120), hepatic coma type(13.3%, 16/120), refractory aacites type (17.5%, 21/120), and shock type (11.7%, 14/120). The germieuhure positive rate of SBP with hepatic coma type and shock type were relatively high, and the survival rate of these patients were low. Conclusions Clinical manifestations of SBP in patients with severe viral hepatitis may be atypical, and its classification help to enhancing the understanding and early diagnosis of SBP, and decreasing missed diagnosis. The prognosis of SBP in patients with hepatic coma type and shock type was poor, and then it must be taken high into account more than ever before in the clinical practice.

Objective To study the clinical value of esophageal stent placement with radiation therapy for the middle-late pa-tients with esophageal cancer.Methods To perform esophageal stent placement and radiation therapy for the middle-late 35 pa-tients,and to perform radiation therapy for the middle-late 37 patients,then observe the clinical curative effects.Results The treat-ment group were significantly alleviated with dysphagia symptom after operation,which 32 cases sticked the entire radiation,ac-counting for 91.4%,no one can′t complete the treatment because of nutritional status reason.Survival time of one month after ra-diotherapy was up to 100.0%,and survival time of six months was 85.7% (30/35).But the contrast group with dysphagia symp-tom were aggravated or no relief,and needed parenteral nutrition.There were 23 cases to complete the entire radiation,accounting for 62.2%,and 5 cases happened esophageal tracheal fistula.Survival time of one month after radiotherapy was 83.8%(31/37),and survival time of six months was 62.2% (23/37).Two groups of cases in radiotherapy resistance difference was statistically signifi-cant,one month and six months of survival time were statistically significant (all P <0.05 ).Conclusion Esophageal stent place-ment with radiotherapy is more efficient than only radiation therapy to the middle-late patients with esophageal cancer.

Objective To investigate the infectious rates of 9 common pathogens and epidemiology in children with acute respira‐tory tract infections(ARI) in Maoming district .Methods The serum were collected from 6 241 children with acute respiratory in‐fection .IgM of 9 common pathogen including Mycoplasma pneumoniae (MP) ,Legionella pneumophila (LP) ,Coxiella burnetii (C .burnetii) ,Chlamydophila pneumoniae(CP) ,adenovirus(ADV) ,respiratory syncytial virus(RSV) ,type A and type B influenza virus(INFA and INFB) ,and parainfluenza virus(PIVS) ,were detected using immunofluorescence assay .Results Among 6 241 ca‐ses ,1 320 showed atypical pathogens infection ,and infection rate was 21% .The positive rate of MP was 15 .12% ,the highest infec‐tious pathogen;followed by the positive rate of INFB ,LP ,ADV and PIVS were 3 .03% ,1 .92% ,0 .54% and 0 .22% respectively . The pathogens with the lowest positive rate were RSV ,COX ,INFA and CP ,their infectious rates were 0 .14% ,0 .11% ,0 .048%and 0 .016% respectively .Conclusion The infection rate of atypical pathogen among children is high in this area ,which should be taken seriously .MP is the most common pathogen in children with ARI in Maoming district .The pathogen positive rate has rela‐tionship with season .

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88(MyD88)/extracellular signal-regulated kinase(ERK)pathway and nuclear factor-κB(NF-κB)nuclear translocation.Methods SD rats were randomly divided into sham operation group,model group and emodin group,with six rats in each group.The rat model of transient middle cerebral artery occlusion(tMCAO)was established by middle cerebral artery embolization.Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72,48 and 24 hours before modeling.At 24 hours after modeling,the neurological function of rats was scored.TTC staining was used to detect the area of cerebral infarction.HE staining was used to observe the morphological changes of brain tissue.The mRNA expression levels of MyD88 and tumor necrosis factor-α(TNF-α)in brain tissue were detected by RT-qPCR.The expression levels of MyD88,ERK,p-ERK and TNF-α in brain tissue were detected by Western Blot.The protein expression of NF-κB in brain tissue was detected by immunofluorescence.Results Compared with the sham operation group,the neurological function score of the model group was significantly increased(P＜0.01),and the cerebral infarction area was significantly increased(P＜0.01).In the cortical area of the ischemic penumbra,cell necrosis,abnormal cell morphology,nuclear fragmentation and atrophy,and the number of cells decreased significantly;the mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly increased(P＜0.01,P＜0.001),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the proportion of NF-κB into nuclear cells was significantly increased(P＜0.001).Compared with the model group,the neurological function score of rats in the emodin group was significantly decreased(P＜0.05),and the area of cerebral infarction was significantly reduced(P＜0.05).The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent.The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased(P＜0.05,P＜0.01),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly decreased(P＜0.05),and the proportion of NF-κB into nuclear cells was significantly decreased(P＜0.001).Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia,which may be related to its inhibition of MyD88 activation,ERK phosphorylation and NF-κB nuclear translocation,and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α,thereby exerting anti-inflammatory effects.

Objective:To investigate the efficacy of neostigmine combined with raw rhubarb enema on severe acute pancreatitis (SAP) patients with intra-abdominal hypertension (IAH).Methods:The clinical data of 89 SAP patients, who were admitted and underwent continuous renal replacement treatment (CRRT) in intensive care unit (ICU) department of the First Affiliated Hospital of Hebei North University from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into control group ( n=44) and experimental group ( n=45) according to the treatment mode. Raw rhubarb enema plus sodium sulfate topical application were administrated twice a day for 7 days in control group; besides the treatment above, intramuscular injection of neostigmine 0.5 mg twice a day for 7 days was given in experimental group. Intra-abdominal pressure was monitored, acute physiology and chronic health evaluation (APACHE)Ⅱ, kidney disease: improving global outcome stage (KDIGO), lung injury score (LIS) were recorded, and serum leukocyte, CRP, procalcitonin (PCT), IL-6, IL-8 and tumor necrosis factor (TNF)-ɑ level were examined before and after treatment in both groups. The primary endpoint was the amount change of intra-abdominal pressure within 24 hours, and secondary endpoints included increased fecal volume within 7 days after treatment, new abdominal compartment syndrome (ACS), new organ dysfunction, vascular complications, length of ICU stay, total length of stay, survival rate and treatment intervention and occurrence of complications within 6 months after the end of treatment. Results:Intra-abdominal pressure began to decrease at 9 hours after treatment both in control group and experimental group. Compared with that before treatment, the intra-abdominal pressure of the two groups decreased significantly after 7 days of treatment, and the decrease rate of the experimental group within 7 days was obviously higher than that of the control group, with statistical significance (all P values <0.05). Compared with those before treatment, APACHEⅡ, KDIGO and LIS in both groups were significantly decreased, but the decreases in experimental group were more remarkable than those in control group (all P values <0.05). After treatment, the serum WBC count and the levels of inflammatory factors CRP, PCT, IL-6, IL-8, TNF-ɑ in experimental group were obviously lower than those in control group with statistical significance (all P values <0.05). Compared with control group, the change of intra-abdominal pressure in experimental group was significantly increased after 24-hour treatment, and the fecal volume was also obviously increased on day 1, 2, 3, 5 and 7 after treatment (all P values <0.05). However, there were no significantly statistical differences on the severity of intra-abdominal pressure, new occurrence of ACS and organ failure, vascular complication, ICU hospitalization and total length of stay and survival rate between two groups. After 6-month follow-up, the recurrence of pancreatitis and its treatment intervention between two groups were not statistically significant. Conclusions:The adjuvant treatment of neostigmine could reduce intra-abdominal pressure, increase defecation volume in SAP patients and alleviate SAP condition, which might be related to reducing the release of inflammatory cytokines.

【Objective】 To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). 【Methods】 Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4⁺ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. 【Results】 CD4⁺ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4⁺ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/10⁶ CD4⁺ T cell′s respectively. 【Conclusion】 The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

Along with the develoipment of high-throughput sequencing technologies, both sample size and SNP number are increasing rapidly in genome-wide association studies (GWAS), and the associated computation is more challenging than ever. Here, we present a memory-efficient, visualization-enhanced, and parallel-accelerated R package called"rMVP"to address the need for improved GWAS computation. rMVP can 1) effectively process large GWAS data, 2) rapidly evaluate population structure, 3) efficiently estimate variance components by Efficient Mixed-Model Association eX-pedited (EMMAX), Factored Spectrally Transformed Linear Mixed Models (FaST-LMM), and Haseman-Elston (HE) regression algorithms, 4) implement parallel-accelerated association tests of markers using general linear model (GLM), mixed linear model (MLM), and fixed and random model circulating probability unification (FarmCPU) methods, 5) compute fast with a globally efficient design in the GWAS processes, and 6) generate various visualizations of GWAS-related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are significantly faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

【Objective】 To analyze the viability of 2 different blood screening strategies against SARS-CoV-2 in low risk populations, so as to provide references for the formulation of blood screening strategy. 【Methods】 Two screening strategies for antibodies against SARS-CoV-2 were adopted: 1) the total antibody were initially screened for all samples, and the antibody IgG and IgM were retested in those primary positive samples; 2) only antibody test of IgG and IgM for all samples. And SARS-CoV-2 nucleic acid was detected in parallel. Reactive samples was confirmed by neutralization test. The sensitivity, specificity and true positive rate of two strategies were calculated. 【Results】 None was positive for SARS-CoV-2 nucleic acid among 880 samples. Four truly positive samples were implicated in 9 (1.02%, 9/880) initially reactive samples in total antibody test; 3 in 26 (2.95%, 26/880) initially IgG or IgM reactive samples. 【Conclusion】 The first strategy is superior to the second strategy in the sensitivity and specificity, and is recommended for the detection of SARS-CoV-2 antibody in low risk populations.