Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases / 中国热带医学

@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

Preparation and evaluation of reference of enterohemorrhagic Escherichia coli strains and genomic DNA / 中国生物制品学杂志

@#Objective To screen enterohemorrhagic Escherichia coli(EHEC) strain and declare it as a standard strain of China Medical Bacterial Species Conservation and Management Center(CMCC).On the base,to prepare strain reference and genomic DNA reference of EHECand declare them as national drug reference with independent intellectual property rights in our country.Methods According to GB4789.6-2016 National Food Safety Standards-Food Microbiology TestDiarrheagenic Escherichia coil Test,the EHEC strain was screened from 160 Escherichia coli strains from patients with diarrhea and declared as a standard strain of CMCC according to management regulations.EHEC bacterial solution and genomic DNA solution were prepared,and freeze-drying technology was used to prepare 600 strain(10~3 CFU/sample) and genomic DNA(20 ng/sample) samples respectively.20 strain and 20 genomic DNA samples were randomly selected for uniformity test.Samples storing at 25 ℃ and 37 ℃ for 1,3,5 and 7 d were taken respectively to test the transportation stability.Then the samples were tested for the short-term storage stability by storing at 4 ℃ for 7,14 and 28 d,and for the long-term storage stability by storing at 20 ℃ for 14,28 and 60 d.Three laboratories were organized for collaborative calibration.20 food products were chosen as the substrate to evaluate the application effect of strain samples.Results The one EHEC strain selected from 160 Escherichia coli strains from patients was finally declared as the CMCC(B) 43207standard strain.In the uniformity test,F_(strainsample)=0.662 0.05,and eae,stxl and stx2 of 20genomic samples were all positive.After storage at 25 and 37 ℃ for 7 d,-20 ℃ for 60 d and 4 ℃ for 28 d,the viable bacteria content of the strain samples was still 103 CFU/sample,and eae,stxl and stx2 of the genomic samples were positive.EHEC strains and genomic DNA samples selected randomly were identified as EHEC by three laboratories,the viable bacteria content was 10~3 CFU/sample,and eae, stxl and stx2 were all positive.It was detected in 20 kinds of food substrates after adding samples,but not in the background control.EHEC strain and the genomic DNA sample were included in drug standard materials in our country,numbered 80024 and 80056,respectively.Conclusion The prepared EHEC strain and genomic DNA standard materials with independent intellectual property rights can improve the timeliness of EHEC testing and make up for the gap in our country.

Meta-Analysis of Pulmonary Artery Denervation for Treatment of Pulmonary Hypertension

ABSTRACT Introduction: Pulmonary artery denervation (PADN) can reduce the sympathetic nervous system (SNS) activity, reduce pulmonary artery pressure (PAP), and improve the quality of life in patients with pulmonary hypertension (PH). We conducted a systematic meta-analysis of the effectiveness of PADN in the treatment of PH patients. Methods: This is a comprehensive literature search including all public clinical trials investigating the effects of PADN on PH. Outcomes were mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), right ventricular (RV) Tei index, 6-minute walk distance (6MWD), and New York Heart Association (NYHA) cardiac function grading. Results: A total of eight clinical studies with 213 PH patients who underwent PADN were included. Meta-analysis showed that after PADN, mPAP (mean difference [MD] -12.51, 95% confidence interval [CI] -17.74 to -7.27, P<0.00001) (mmHg) and PVR (MD -5.17, 95% CI -7.70 to -2.65, P<0.0001) (Wood unit) decreased significantly, CO (MD 0.59, 95% CI 0.32 to 0.86, P<0.0001) (L/min) and 6MWD (MD 107.75, 95% CI 65.64 to 149.86, P<0.00001) (meter) increased significantly, and RV Tei index (MD -0.05, 95% CI -0.28 to 0.17, P=0.63) did not change significantly. Also after PADN, the proportion of NYHA cardiac function grading (risk ratio 0.23, 95% CI 0.14 to 0.37, P<0.00001) III and IV decreased significantly. Conclusion: This meta-analysis supports PADN as a potential new treatment for PH. Further high-quality randomized controlled studies are needed.

Experimental study of the removal of Candida albicans from mouse tongues using photoactivated disinfection / 口腔疾病防治

Objective @#To establish a mouse model of acute pseudomembranous stomatitis and to observe the effect of photoactivated disinfection (PAD) on the removal of Candida albicans in vivo, and initially explore the feasibility of this technology in the treatment of acute pseudomembranous stomatitis.@*Methods@#Six-week-old male ICR mice were selected and immunized with 1 × 107CFU/mL Candida albicans solution on the backs of the tongues of immunosuppressed mice. Thirty model mice with acute pseudomembranous stomatitis were successfully established and randomly divided into a control group and a photoactivated disinfection group, with 15 mice in each group. Mice in the photoactivated disinfection group were coated with 1 mg/mL toluidine blue solution on the back of the tongue, incubated for 1 min and irradiated with 750 mW LED red light for 1 min. Immediately after treatment, the tongue fungal load was measured in the photoactivated disinfection group and the control group. Tongue fungal load was measured again 48 h later, and tongue histopathological examination was performed in both groups. @*Results @# Forty-eight hours after PAD treatment, the white pseudomembrane on the back of the tongue in the photoactivated group was significantly less than the control group. The fungal load on the dorsum of the tongue in the treatment group was significantly lower than the control group immediately and 48 h after treatment for PAD, and the difference was statistically significant (P<0.05). Forty-eight hours after PAD treatment, HE staining showed that the epithelial structure of the PAD group was more regular than the control group, and no microabscesses were observed. PAS staining showed that the number of mycelia in the PAD group was significantly less than the control group. Mycelia occasionally invaded the keratinized layer but did not penetrate into the upper cortex.@*Conclusion@#PAD significantly removed Candida albicans from the tongues of mice with acute pseudomembranous Candida stomatitis.

Azeliragon ameliorates Alzheimer's disease via the Janus tyrosine kinase and signal transducer and activator of transcription signaling pathway

OBJECTIVES: TTP488, an antagonist of the receptor for advanced glycation end-products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). However, the mechanism underlying the protective action of TTP488 against AD has not yet been fully explored. METHODS: Healthy male rats were exposed to aberrant amyloid β (Aβ) 1-42. Lipopolysaccharide (LPS) and the NOD-like receptor family pyrin domain containing 1 (NLRP1) overexpression lentivirus were injected to activate the NLRP1 inflammasome and exacerbate AD. TTP488 was administered to reverse AD injury. Finally, tofacitinib and fludarabine were used to inhibit the activity of Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) to prove the relationship between the JAK/STAT signaling pathway and TTP488. RESULTS: LPS and NLRP1 overexpression significantly increased the NLRP1 levels, reduced neurological function, and aggravated neuronal damage, as demonstrated by the impact latency time of, time spent by, and length of the platform covered by, the mice in the Morris water maze assay, Nissl staining, and immunofluorescence staining in rats with AD. CONCLUSIONS: TTP488 administration successfully reduced AD injury and reversed the aforementioned processes. Additionally, tofacitinib and fludarabine administration could further reverse AD injury after the TTP488 intervention. These results suggest a new potential mechanism underlying the TTP488-mediated alleviation of AD injury.

Next generation sequencing in early diagnosis of pneumocystis jirovecii pneumonia after chemotherapy: a case report

The incidence of Pneumocystis pneumonia is increasing in immunosuppressive patients. How to diagnose and treat Pneumocystis pneumonia in the early stage has become an important issue for clinicians. The development of Next-generation Sequencing (NGS) provides technical support for the diagnosis of Pneumocystis pneumonia. Case report: A 14-year-old male patient was diagnosed with T lymphoblastoma and treated with chemotherapy. After chemotherapy, the patient developed bone marrow suppression and was complicated with severe pneumonia. He was given endotracheal intubation and ventilator assisted respiration. Samples of patients' alveolar lavage fluid were obtained, and Next-generation Sequencing (NGS) was used for diagnosis, confirming the pathogen as Pneumocystis jiroveci, which was treated by TMP/SMX. The patient's condition gradually improved, and was finally removed from ventilator and endotracheal tube. Pneumocystis jiroveci is a common opportunistic pathogen in immunosuppressive patients, and Next-generation Sequencing (NGS) can be used for rapid diagnosis of Pneumocystis pneumonia, thus improving the clinical therapeutic effect.

Association of Monocyte Count on Admission with the Angiographic Thrombus Burden in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention / Associação da Contagem de Monócitos na Internação com a Carga Trombótica Angiográfica em Pacientes com Infarto com Supradesnivelamento do Segmento ST Submetidos à Intervenção Coronária Percutânea Primária

Abstract Background: The intracoronary high-thrombus burden during the primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI) can lead to poor outcomes. Monocytes have been described to play an important role in thrombotic disorders. Objectives: This study aimed to investigate the relationship between admission monocyte count and angiographic intracoronary thrombus burden in patients receiving primary percutaneous coronary intervention (PPCI). Methods: A total of 273 patients with acute STEMI who underwent PPCI were enrolled. The patients were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) thrombus grade: low-thrombus burden group with a grade of 0-2 and high-thrombus burden group with a grade of 3-4. The monocyte count and other laboratory parameters were measured on admission before PPCI. P-value < 0.05 was considered significant. Results: There were 95 patients (34.8%) in the high-thrombus burden group, and 178 patients (65.2%) in the low-thrombus burden group. Patients with high-thrombus burden had significantly higher admission monocyte count (0.61 ± 0.29×109/L vs. 0.53 ± 0.24×109/L, p = 0.021). In multivariate analysis, monocyte count was the independent predictor of angiographic high-thrombus burden (odds ratio 3.107, 95% confidence interval [CI] 1.199-7.052, p = 0.020). For the prediction of angiographic high-thrombus burden, admission monocyte count at a cut-off value of 0.48×109/L yielded 0.59 ROC-AUC (71.9% sensitivity, 46.9% specificity). Conclusions: Monocyte count on admission was an independent clinical predictor of high-thrombus burden in patients with STEMI undergoing PPCI. Our findings suggest that admission monocyte count may be available for early risk stratification of high-thrombus burden in acute STEMI patients and might allow the optimization of antithrombotic therapy to improve the outcomes of PPCI.

Resumo Fundamento: A carga trombótica intracoronária durante a intervenção coronária percutânea primária em pacientes com Infarto com Supradesnivelamento do Segmento ST (STEMI) pode levar a resultados negativos.Os monócitos foram descritos para desempenhar um papel importante nos distúrbios trombóticos. Objetivos: Este estudo investigou a relação entre a contagem de monócitos no momento da internação e a carga trombótica angiográfica intracoronária em pacientes submetidos à intervenção coronária percutânea primária (ICPP). Métodos: Um total de 273 pacientes com STEMI agudo submetidos à ICPP participaram. Os pacientes se dividiram em dois grupos de acordo com o grau trombótico na trombólise do infarto do miocárdio (TIMI): grupo baixa carga trombótica, com graus de 0-2, e grupo alta carga trombótica, com graus de 3-4. A contagem de monócitos e outros parâmetros laboratoriais foram medidos na internação antes da ICPP. Consideramos o valor de p < 0,05 significativo. Resultados: Havia 95 pacientes (34,8%) no grupo alta carga trombótica, e 178 pacientes (65,2%) no grupo baixa carga trombótica. Pacientes com alta carga trombótica apresentaram contagem de monócitos no momento da internação mais alta (0,61 ± 0,29×109/L vs. 0,53 ± 0,24×109/L, p = 0,021). Na análise multivariada, a contagem de monócitos foi o indicador independente da alta carga trombótica angiográfica (odds ratio 3,107, intervalo de confiança de 95% [IC] 1,199-7,052, p = 0,020). Para a previsão da alta carga trombótica angiográfica, a contagem de monócitos na internação tinha ponto de corte de 0,48×109/L, chegou a 0.59 ROC-AUC (71,9% sensibilidade, 46,9% especificidade). Conclusões: a contagem de monócitos na internação foi um indicador clínico independente da alta carga trombótica em pacientes com STEMI submetidos à ICPP. Nossos achados sugerem que a contagem de monócitos na internação pode estar disponível para a estratificação de risco precoce da alta carga trombótica em pacientes com STEMI agudo, e podem levar à otimização da terapia antitrombótica para melhorar os resultados da ICPP.

Outcomes in patients with non-ST-elevation acute coronary syndrome randomly assigned to invasive versus conservative treatment strategies: A meta-analysis

OBJECTIVE: The goal of the present study was to compare the prognoses of patients with non-ST-elevation acute coronary syndromes who were treated with invasive or conservative treatment strategies. METHODS: We performed a meta-analysis of studies of patients with non-ST-elevation acute coronary syndromes to assess the benefits of an invasive strategy vs. a conservative strategy for short- and long-term survival. We searched PubMed for studies published from 1990 to November 2012 that investigated the effects of an invasive vs. conservative strategy in patients with non-ST-elevation acute coronary syndromes. The following search terms were used: “non-ST-elevation myocardial infarction”, “unstable angina”, “acute coronary syndromes”, “invasive strategy”, and “conservative strategy”. The primary endpoints were all-cause mortality at 30 days and 1 year. RESULTS: Seven published studies were included in the present meta-analysis. The pooled analyses show that an invasive strategy decreased the risk of death (risk ratio [0.839] [95% confidence interval {0.648-1.086}; I 2, 86.46%] compared to a conservative strategy over a 30-day-period. Furthermore, invasive treatment also decreased patient mortality (risk ratio [0.276] [95% confidence interval {0.259-0.294}; I 2, 94.58%]) compared to a conservative strategy for one year. CONCLUSION: In non-ST-elevation acute coronary syndromes, an invasive strategy is comparable to a conservative strategy for decreasing short- and long-term mortality rates. .

Comparing percutaneous coronary intervention and thrombolysis in patients with return of spontaneous circulation after cardiac arrest

OBJECTIVE: To evaluate the effects of percutaneous coronary intervention and thrombolysis after restoration of spontaneous circulation in cardiac arrest patients with ST-elevation myocardial infarction using meta-analysis. METHODS: We performed a meta-analysis of clinical studies indexed in the PUBMED, MEDLINE and EMBASE databases and published between January 1995 and October 2012. In addition, we compared the hospital discharge and neurological recovery rates between the patients who received percutaneous coronary intervention and those who received thrombolysis. RESULTS: Twenty-four studies evaluating the effects of percutaneous coronary intervention or thrombolysis after restoration of spontaneous circulation in cardiac arrest patients with ST-elevation myocardial infarction were included. Seventeen of the 24 studies were used in this meta-analysis. All studies were used to compare percutaneous coronary intervention and thrombolysis. The meta-analysis showed that the rate of hospital discharge improved with both percutaneous coronary intervention (p<0.001) and thrombolysis (p<0.001). We also found that cardiac arrest patients with ST-elevation myocardial infarction who received thrombolysis after restoration of spontaneous circulation did not have decreased hospital discharge (p = 0.543) or neurological recovery rates (p = 0.165) compared with those who received percutaneous coronary intervention. CONCLUSION: In cardiac arrest patients with ST-elevation myocardial infarction who achieved restoration of spontaneous circulation, both percutaneous coronary intervention and thrombolysis improved the hospital discharge rate. Furthermore, there were no significant differences in the hospital discharge and neurological recovery rates between the percutaneous coronary intervention-treated group and the thrombolysis-treated group. .

Influences of antenatal administration of taurine on cerebral neurogenesis of fetal rats with intrauterine growth restriction / 中华围产医学杂志

Objective To provide the experimental evidence for clinical application of taurine,rat model of intrauterine growth restriction (FGR) was made to investigate influence of prenatal administration of taurine on neurogenesis.Methods Fifteen pregnant rats were divided into control,FGR model and taurine groups,5 rats for each group.Rats in the control group were supplied with unlimited food and drink while the other two groups were fed by 40％ food intake of the control group throughout pregnancy.Since gestational day 12,taurine (100 mg/kg) was added into diet of taurine group every day until term delivery.Brain tissues were obtained immediately after baby rats were born.Expression of proliferating cell nuclear antigen (PCNA),neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) of brain tissue was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry; meanwhile,numbers of PCNA-immunoreactive cells in subventricular zone,subgranular zone and cerebral cortex were compared with ANOVA test or q test.Results Levels of PCNA mRNA and GFAP mRNA expression in FGR group were significantly higher than those of control group (PCNA mRNA:1.002±0.011 vs 0.894 ± 0.040,P＜0.01; GFAP-mRNA:1.012±0.013 vs 0.913±0.012,P＜0.01).Compared to FGR model group,mRNA expressions of PCNA and GFAP in taurine groups were higher (1.090±0.029,P＜0.01 ; 1.034±0.011,P＞0.05).There was a significant decrease in the expression of NSE mRNA in FGR group compared with control group (0.796±0.036 vs 1.582±0.057,P＜0.01),while the expression in taurine group (0.933±0.027) was significantly higher than that in FGR model group (P ＜ 0.01).PCNA immunoreactive cells were mostly distributed in subventricular zone,followed by subgranular zone and cerebral cortex.Conclusions Prenatal application of taurine could enhance neurogenesis of FGR newborn rats and improve survival of neurons to ameliorate FGR brain damage.

Avoiding the internet addiction disorder- from the self-regulated circle theory / 中华医学教育探索杂志

The internet addiction disorder is an important problem under the internet circumstance.Improving self-regulated ability is a good method to avoid the problem.The article uses the selfregulated circle theory to gain the self-regulating strategy in three phases:forethought,performance or volitional control,self-reflection.These strategies include making goal,planning strategy,self-observation and self-record,attribution.

Neurogenesis of Adipose-derived Stem Cells in Hydrogel / 华中科技大学学报（医学）（英德文版）

Adipose tissue is a readily available source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications.Peptide hydrogel is a novel biomaterial which provides three-dimensional microenvironments for a variety of cells for tissue grafting.In this study,adipose-derived stem cells (ADSCs) were isolated from rats,seeded into the peptide hydrogel polymer scaffolds and cultured in Neurobasal (NB) media supplemented with B27,basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF).Ten days after the culture,some cells were expanded into clonal populations in which the expression of both Nestin and Brdu was detected but only Brdu expression was detected in the cells that were not expanded into clonal populations.Our results suggested that ADSCs in peptide hydrogel polymer scaffolds can be induced to differentiate into cells capable of expressing the neuron-associated markers,self-renewal and self-propagation.

Ellagic acid-induced hypercoagulable state in animals: a potentially useful animal hypercoagulable model for evaluation of anticoagulants / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To establish and evaluate a hypercoagulable animal model for the assessment of anticoagulants.</p><p><b>METHODS</b>Forty mice, thirty-two rats, and twenty-four rabbits were randomly and equally divided into control group (saline) and three ellagic acid (EA)-treated groups (low, middle, and high doses). In the mice, bleeding time (BT) was estimated with tail transaction, and clotting time (CT) with template method. Prothrombin time (PT) and the activated partial thromboplastin time (APTT) in rats and rabbits were measured by means of Quick's one-stage assay and modified APTT assay respectively. In addition, thrombin activity was estimated in rats with PT assay using a hemagglutination analyzer. The circulating platelet aggregates were detected in rabbits through platelet counting and presented as the circulating platelet aggregate ratio (CPAR).</p><p><b>RESULTS</b>EA shortened BT and CT in mice, PT and APTT in rats, and increased thrombin activity and CPAR, all in a dose-dependent manner. EA also brought reduction of PT and APTT in rabbits in dose- and time-dependent manners.</p><p><b>CONCLUSION</b>EA could induce hypercoagulable state through activating coagulation system and platelets in mice, rats, and rabbits.</p>

Risk Factors and Prognostic Evaluation of Transient Ischemic Attack / 国际脑血管病杂志

Transient ischemic attack (TIA) is the most important early warning signal of cerebral infarction, and it is also the critical period for the prevention of cerebral infarction. If we effectively control the risk factors of TIA, the onset and the progress of TIA can be prevented and controlled, This article reviews the correlation between the risk factors of TIA and prognosis.