Development and Validation of a Hypoxia-related Prognostic Model for Ovarian Cancer.

BACKGROUND: The high heterogeneity of ovarian cancer (OC) brings great difficulties to its early diagnosis and prognostic forecast. There is an urgent need to establish a prognostic model of OC based on clinicopathological features and genomics. METHODS: We identified hypoxia-related differentially expressed genes (DEGs) between OC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression (GTEx). LASSO Cox regression analysis was applied for building a prognostic model in the TCGA-GTEx cohorts, and its predictive value was validated in the GEO-OC cohort. Functional enrichment analysis was performed to investigate the underlying mechanisms. By constructing a hypoxia model of the SKOV3 cell line and applying qRT-PCR, we investigated the relationship between hypoxia with two novel genes in the prognostic model (ISG20 and ANGPTL4). RESULTS: Twelve prognostic hypoxia-related DEGs were identified, and nine of them were selected to establish a prognostic model. OC patients were stratified into two risk groups, and the high-risk group showed reduced survival time compared to the low-risk group upon survival analysis. Univariate and multivariate Cox regression analysis demonstrated that the risk score was an independent risk factor for overall survival. The biological function of the identified prognostic hypoxia-related gene signature was involved in immune cell infiltration. Low expression of ISG20 was observed in the CoCl2-mimicked hypoxic SKOV3 cell line and negatively correlated with HIF-1α. CONCLUSION: Our findings showed that this hypoxia-related gene signature could serve as a satisfactory prognostic classifier for OC and will be beneficial to the research and development of targeted therapeutic strategies.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study.

Background: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P < 0.001) and critical illness (4.4% vs. 0.5%, P = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Antecedentes: Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta. Métodos: Se incluyó de forma retrospectiva a 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu (China). Se describieron sus características clínicas y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística. Resultados: De los 233 pacientes, 45 (19,3%) tenían EM. La mediana de edad de estos pacientes con EM fue significativamente mayor que la de los pacientes sin él (53,0 años frente a 46,0 años; p = 0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los 2 grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%; p < 0,001) y críticas (4,4% frente a 0,5%; p = 0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome de dificultad respiratoria aguda en los pacientes con EM también fueron mayores que en los pacientes sin EM durante la hospitalización. El análisis multivariante mostró que la EM concurrente (odds ratio [OR] 7,668; intervalo de confianza [IC] del 95%: 3,062-19,201; p < 0,001) y la linfopenia (OR 3,315; IC del 95%: 1,306-8,411; p = 0,012) eran factores de riesgo independientes de COVID-19 grave. En una mediana de seguimiento de 28 días tras el alta, se encontró neumonía bilateral en el 95,2% de los pacientes con EM, mientras que solo la presentaron el 54,7% de los pacientes sin EM. Conclusiones: El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes con COVID-19 y EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes con COVID-19 y EM.

Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B.

Importance: Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) constitutes an atypical serological profile in chronic hepatitis B virus infection, and the association between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) remains unclear. Objective: To investigate the association of coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with CHB. Design, Setting, and Participants: Consecutive treatment-naive patients with CHB from 2 medical institutions in China were enrolled between January 10, 2015, and March 31, 2021. Severe liver fibrosis and cirrhosis were identified using the aspartate transaminase (AST) to platelet ratio index (APRI), the fibrosis index based on 4 factors (FIB-4; factors comprise age, AST level, alanine aminotransferase [ALT] level, and platelet count), transient elastography, or ultrasonography. Data were analyzed from August 1, 2021, to April 15, 2022. Main Outcomes and Measures: The primary outcomes were rates of severe liver fibrosis and cirrhosis among patients with vs patients without coexistant HBsAg and anti-HBs. Severe liver fibrosis was defined as an APRI score of 1.5 or higher, a FIB-4 score of 3.25 or higher, or a liver stiffness measurement of 8 kPa or higher; cirrhosis was defined as an APRI score of 2.0 or higher, a FIB-4 score of 6.5 or higher, a liver stiffness measurement of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis. Results: Of 6534 enrolled patients, 4033 patients (61.7%) were male, and the median (IQR) age was 41.0 (33.0-52.0) years. A total of 277 patients (4.2%) had coexistent HBsAg and anti-HBs. Patients with vs without anti-HBs were older (median [IQR], 46.0 [33.0-55.5] years vs 41.0 [33.0-52.0] years) and had a higher proportion of hepatitis B e antigen (HBeAg) positivity (123 of 277 patients [44.4%] vs 2115 of 6257 patients [33.8%]; P < .001), higher ALT levels (median [IQR], 45.1 [24.6-119.0] U/L vs 36.7 [22.0-77.0] U/L; P = .001) and AST levels (median [IQR], 35.0 [23.5-68.4] U/L vs 28.3 [21.6-51.0] U/L; P < .001), and lower platelet counts (median [IQR], 173.0 × 103/µL [129.0-212.5 × 103/µL] vs 185.0 × 103/µL [141.0-224.0 × 103/µL]; P = .004), albumin levels (median [IQR], 4.37 [4.11-4.56] g/dL vs 4.43 [4.17-4.61] g/dL; P = .02), and HBsAg levels (median [IQR], 2.8 log10 [1.6-3.4 log10] IU/mL vs 3.3 log10 [2.6-3.9 log10] IU/mL; P < .001). Compared with patients without anti-HBs, those with anti-HBs had higher APRI scores (median [IQR], 0.5 [0.3-1.4] vs 0.4 [0.3-0.9]; P < .001), FIB-4 scores (median [IQR], 1.4 [0.9-2.6] vs 1.1 [0.7-2.1]; P < .001), and liver stiffness values (median [IQR], 7.5 [6.2-9.8] kPa vs 6.3 [5.2-8.1] kPa; P = .003). Patients with anti-HBs also had higher proportions of severe liver fibrosis (102 of 277 patients [36.8%] vs 1397 of 6207 patients [22.5%]; P < .001) and cirrhosis (87 of 277 patients [31.4%] vs 1194 of 6213 patients [19.2%]; P < .001) compared with patients without anti-HBs. The coexistence of HBsAg and anti-HBs was independently associated with severe liver fibrosis (odds ratio [OR], 2.29; 95% CI, 1.56-3.38; P < .001) and cirrhosis (OR, 1.73; 95% CI, 1.12-2.68; P = .01) in the multivariate analysis. However, the association of coexistent HBsAg and anti-HBs with cirrhosis was only observed in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in patients with HBeAg positivity (OR, 1.45; 95% CI, 0.87-2.43; P = .16). Conclusions and Relevance: In this cross-sectional study, the coexistence of HBsAg and anti-HBs was unusual in hepatitis B virus infection and was associated with more advanced liver diseases, such as severe liver fibrosis and cirrhosis, especially among patients with HBeAg negativity. These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.

Zuogui pills maintain the stemness of oogonial stem cells and alleviate cyclophosphamide-induced ovarian aging through Notch signaling pathway.

BACKGROUND: Zuogui pills (ZGP), a classical prescription of traditional Chinese medicine, have been widely used in the treatment of ovarian aging. Previous studies have demonstrated its efficacy on protecting ovarian aging, and the mechanisms were mostly relevant to inhibiting the apoptosis of follicles and activating the primordial follicles. However, whether ZGP could stimulate the oogonial stem cells (OSCs) to refresh the follicle pool remains poorly understood. PURPOSE: To investigate the effects of ZGP on the stemness of OSCs in cyclophosphamide (Cy)-induced ovarian aging. STUDY DESIGN AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into 8 groups: control group, model group, ZGP groups (low / high dose groups), estradiol valerate (EV) groups (low / high dose groups), DAPT group and DAPT+ZGP-L group. After modeling with Cy, the ZGP groups and EV groups were treated with ZGP and EV for 8 weeks respectively. Meanwhile, the DAPT groups were treated with DAPT twice a week. Additionally, OSCs were also isolated after modeling, and then treated with drug serum containing ZGP or EV. Ovarian volume and the ratio of weight of total ovaries to the body weight were measured. The serum hormones were measured by ELISA. Quantities and location of OSCs in ovaries were detected by flow cytometry and immunofluorescence. Cell viability was measured by CCK8. And OSCs were identified by immunofluorescence. Biomarkers of germ cells, stem cells and associated to differentiation and meiosis were detected by qPCR and western blot. Proteins in Notch signaling pathway were detected by western blot and immunofluorescence. RESULTS: After treating with ZGP, ovarian volume and the ratio of weight of total ovaries to the body weight increased. ZGP could increase serum AMH and E2 level and decrease serum FSH level. Quantities and cell viability of OSCs increased after ZGP treatment in vivo and in vitro. In addition, treatment with ZGP could increase not only the expression of MVH, Oct4 and DAZL, but also the expression of ZP1 and ZP2. Furthermore, ZGP could up-regulate the expression of Notch intracellular domain (NICD), HES1 and HES5. After blocking the Notch signaling pathway, ZGP could increase not only the expression of NICD, HES1 and HES5, but also the expression of MVH, Oct4, DAZL, ZP1 and ZP3. CONCLUSION: In conclusion, the mechanism of ZGP on treating ovarian aging may be relevant to maintain the stemness of OSCs by up-regulating Notch signaling pathway, which added the mechanism of ZGP on the perspective of OSCs at first time.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study.

BACKGROUND: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. METHODS: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. RESULTS: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P=0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P<0.001) and critical illness (4.4% vs. 0.5%, P=0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P<0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P=0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. CONCLUSIONS: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Can large doses of glucocorticoids lead to Perthes? a case report and review of the literature.

BACKGROUND: Perthes disease (Legg-Calvé-Perthes, LCP) is a self-limited and non-systemic disease occurring in the femoral heads of children, which is mainly manifested as an ischemic necrosis of the femoral head epiphysis, leading to subchondral ossification injury of the femoral head. CASE PRESENTATION: Here we report a case of 11-year-old child with long-term use of high-dose glucocorticoids. With MRI examination finding the epiphyseal necrosis of right humeral head, femur and tibia, and X-ray examination finding bilateral femoral head necrosis, the child was diagnosed as Perthes disease based on his clinical and imaging data. CONCLUSIONS: Long-term and high-dose glucocorticoids may be one of the causes of Perthes disease.

Baseline serum hepatitis B core antibody level predicts HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B after antiviral treatment.

Antibody to hepatitis B core antigen (anti-HBc) is one of the most classical serological markers of HBV infection. This study aimed to investigate the association of serum anti-HBc and HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after antiviral treatment. Two hundred and seventeen HBeAg-positive CHB patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) for 48 weeks were retrospectively enrolled. Serological response (SR) is defined as HBeAg seroconversion at 48 weeks of antiviral treatment. Serum anti-HBc level was measured using the Abbott ARCHITECT assay. After 48 weeks of antiviral treatment, twenty-two (10.1 %) patients achieved SR. Baseline level of serum anti-HBc in the SR patients (11.8 S/CO) was significantly higher than patients with non-SR (9.6 S/CO, P < 0.001). The median anti-HBc level was significantly declined after 48 weeks of antiviral therapy (9.9 vs. 8.9 S/CO, P < 0.001). Multivariate logistic regression analysis showed baseline of serum anti-HBc was an independent predictor of SR (odds ratio [OR]: 1.462, 95 % confidence interval [CI] 1.170-1.825, P = 0.001). The area under receiver operating characteristic curve (AUROC) of baseline anti-HBc level for predicting SR was 0.781 with the cut-off of 11.1 S/CO, with a sensitivity of 77.27 % and a specificity of 72.82 %. Our findings highlighted that baseline serum anti-HBc level is a promising indictor for predicting HBeAg seroconversion in HBeAg-positive CHB patients after antiviral treatment.

Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone.

A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the 'grey zone (GZ)'. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty-nine consecutive treatment-naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106  IU/ml (GZ-A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2 × 104  IU/ml (GZ-B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2 × 103  IU/ml (GZ-C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2 × 103  IU/ml (GZ-D). The distributions of different immune states were: 233 (4.90%) patients in immune-tolerant phase, 941 (19.77%) patients in HBeAg-positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg-negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ-B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg-positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ-B had advanced fibrosis or even cirrhosis.

Risk Factors of Fatal Outcome of Hospitalized Patients with COVID-19.

BACKGROUND: Few studies reported the risk factors of fatal outcome of hospitalized patients with coronavirus disease 2019 (COVID-19). We aimed to identify the independent risk factors associated with fatal outcome of hospitalized COVID-19 patients. METHODS: The clinical data of 109 consecutive COVID-19 patients including 40 (36.7%) common cases and 69 (63.3%) severe cases were included and analyzed. RESULTS: Multivariate regression analysis indicated that platelets (PLT, OR, 0.988; 95% CI, 0.978-0.998; P=0.017) and C-reactive protein (CRP) (OR, 1.047; 95% CI, 1.026-1.068; P<0.001) levels were the independent risk factors of fatal outcome in COVID-19 patients. The optimal cut-off value of PLT counts for predicting fatal outcome was 161x109/L with the area under receiver operating characteristic curve (AUROC) of 0.824 (95% CI, 0.739-0.890). The optimal cut-off value of CRP for the prediction of fatal outcome was 46.2 mg/L with the AUROC of 0.954 (95% CI, 0.896-0.985). The CRP levels had higher predictive values for fatal outcome than PLT (P=0.016). The cumulative survival rate was significantly higher in patients with PLT>161x109/L compared with patients with PLT≤161x109/L (89.4% vs. 12.5%, log-rank test X2=72.17; P<0.001). Survival rate of COVID-19 patients was prominently higher in CRP≤46.2 mg/L patients compared with patients with CRP>46.2 mg/L (95.9% vs. 22.9%, log-rank test X2=77.85; P<0.001). CONCLUSIONS: PLT counts and CRP levels could predict fatal outcome of hospitalized COVID-19 patients with relatively high accuracy.

Overweight and Obesity are Risk Factors of Severe Illness in Patients with COVID-19.

OBJECTIVE: This study aimed to observe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with overweight and obesity. METHODS: Consecutive patients with COVID-19 from 10 hospitals of Jiangsu province, China, were enrolled. RESULTS: A total of 297 patients with COVID-19 were included, and 39.39% and 13.47% of patients had overweight and obesity, respectively. The proportions of bilateral pneumonia (92.50% vs. 73.57%, P = 0.033) and type 2 diabetes (17.50% vs. 3.57%, P = 0.006) were higher in patients with obesity than lean patients. The proportions of severe illness in patients with overweight (12.82% vs. 2.86%, P = 0.006) and obesity (25.00% vs. 2.86%, P < 0.001) were significantly higher than lean patients. More patients with obesity developed respiratory failure (20.00% vs. 2.86%, P < 0.001) and acute respiratory distress syndrome (5.00% vs. 0%, P = 0.024) than lean patients. The median days of hospitalization were longer in patients with obesity than lean patients (17.00 days vs. 14.00 days, P = 0.029). Overweight (OR, 4.222; 95% CI: 1.322-13.476; P = 0.015) and obesity (OR, 9.216; 95% CI: 2.581-32.903; P = 0.001) were independent risk factors of severe illness. Obesity (HR, 6.607; 95% CI: 1.955-22.329; P = 0.002) was an independent risk factor of respiratory failure. CONCLUSIONS: Overweight and obesity were independent risk factors of severe illness in COVID-19 patients. More attention should be paid to these patients.

Temporal association between carbapenems usage and antimicrobial resistance in gram-negative bacteria at a tertiary hospital in Nanjing, China.

In this study, we investigated the temporal association between carbapenems usage and antimicrobial resistance among major Gram-negative bacteria, using the data of quarterly carbapenems consumptions and percentages of antibiotic resistance for Gram-negative bacteria from inpatients from 2013 to 2017 in a tertiary hospital from Jiangsu Province, China. First, carbapenems consumption showed an increasing trend in the past 5 years, accompanied with the rising rates of A. baumannii and P. aeruginosa resistance against imipenem. In A. baumannii, we identified correlations between carbapenems consumption and antimicrobial resistance against piperacillin/tazobactam, ceftazidime, ciprofloxacin and imipenem, respectively. Additionally, close correlations were observed between carbapenems consumption and antimicrobial resistance against ceftazidime and ciprofloxacin in E. coli. Our data indicated that a significant positive correlation between the usage of carbapenems and the rate of antimicrobial resistance among A. baumannii and E. coli, respectively. Carbapenems should be cautiously prescribed to prevent antimicrobial resistance outbreak in A. baumannii and E. coli.

Profiles of serum soluble programmed death-1 and programmed death-ligand 1 levels in chronic hepatitis B virus-infected patients with different disease phases and after anti-viral treatment.

BACKGROUND: Soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) play a role in immune regulation of chronic hepatitis B virus (HBV) infection. AIM: To investigate the profiles of serum sPD-1 and sPD-L1 in chronic HBV-infected patients with different disease phases and after anti-viral treatment. METHODS: A total of 99 chronic HBV-infected patients were enrolled and divided into HBeAg-positive chronic HBV infection (EPI) group, HBeAg-positive chronic hepatitis B (EPH) group, HBeAg-negative chronic hepatitis B (ENH) group and HBeAg-negative chronic HBV infection (ENI) group. Eleven healthy subjects were included as healthy controls (HCs). Thirty-two EPH patients received anti-viral treatment with nucleos(t)ide analogues and were followed up to 5 years. Serum sPD-1 and sPD-L1 levels were detected by Multiplex Immunoassays. RESULTS: Serum sPD-1 and sPD-L1 levels of chronic HBV infected patients were significantly higher than that of HCs (P < 0.01). Patients in EPH, ENH and EPI groups had higher serum sPD-1 and sPD-L1 levels than that in HCs (P < 0.01). After anti-viral treatment, serum sPD-1 and sPD-L1 levels declined rapidly. EPH patients with HBeAg clearance after 2 years of anti-viral treatment showed lower baseline HBeAg and sPD-1 levels compared to those without HBeAg clearance. CONCLUSIONS: Serum sPD-1 and sPD-L1 levels varied among chronic HBV infected patients with different disease phases. Lower baseline sPD-1 levels were associated with HBeAg clearance after 2 years of anti-viral treatment in EPH patients.

Topiramate for hypoxic ischemic encephalopathy: A systematic review protocol.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is brain injury caused by different reasons and the most common diagnosed is neonatal HIE. Most of the existing treatments have their own shortcomings or there are still some unexplained mechanisms in it. Topiramate (TPM) is a new drug for the treatment for seizures in neonates with HIE, but is currently used off-label. Our protocol aims to access the efficiency and safety of TPM for HIE. METHODS AND ANALYSIS: Eight databases will be searched by 2 independent researchers for the article on the topic of using TPM as treatment for HIE, including PubMed, the Cochrane Central Register of Controlled Trials (Cochrane Library), Embase, and Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wang Fang Database and Chinese Science and Technology Periodical database (VIP). The included papers are those published from the established date of the databases to 2019. The therapeutic effects based on the grade of neonatal behavioral neurological assessment will be regarded as the primary outcomes. RevMan V5.3 will be used to compute the data synthesis and carry out meta-analysis. The risk of bias will be appraised by the Cochrane risk of bias tool. Rare ratio for dichotomous outcomes and mean different for continuous data will be expressed with 95% confidence intervals (CI) for analysis. A random effects model or a fixed effects model will be employed, when heterogeneity is found or not. Subgroup analysis and sensitivity analysis will be applied if the heterogeneity is obvious. RESULTS: This study will provide the recent evidence of TPM for HIE from reducing seizure acticity. CONCLUSION: The conclusion of this study will provide proof to evaluate if TPM is effective and safe in the treatment of HIE.PROSPERO registration number: PROSPERO CRD42018117981.

Guizhi Gancao Longgu Muli decoction for insomnia: A protocol for a systematic review.

BACKGROUND: Insomnia is a prevalent and bothersome disorder of sleep initiation and maintenance. Although efficacious treatments for insomnia have been available for decades, they all have their own limitations. Guizhi Gancao Longgu Muli Decoction (GGLMD), a popular complementary and alternative therapy, has been widely applied to treat insomnia in some Asian countries for centuries. Yet no systematic reviews have comprehensively assessed the efficacy and safety of GGLMD as a treatment for insomnia. METHODS: A comprehensive search up to November, 2019 will be conducted in the following electronic databases: the Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database (VIP), and the Wanfang Database. The primary outcomes will be sleep quality including Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG). Stata 15 will be used for data analysis as well. RESULTS: This study will provide the current evidence of insomnia treated with GGLMD from the several points including PSQI and PSG. CONCLUSION: The consequence of this summary will furnish proof to evaluate if GGLMD is effective in the treatment of insomnia. ETHICS AND DISSEMINATION: Without personal information involved, ethical approval and informed consent form is no need. The review will be submitted to a peer-reviewed journal prospectively to spread our findings. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018118336.

The gamma-glutamyl transpeptidase to platelet ratio predicts liver inflammation in chronic hepatitis B with normal or mildly elevated alanine transaminase.

BACKGROUND: The gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR) was proposed as a novel index for predicting liver inflammation in chronic hepatitis B (CHB) patients. We aimed to investigate GPR for predicting significant liver inflammation in CHB patients with normal (≤1×upper limit of normal, ULN) or mildly elevated (≤2×ULN) alanine transaminase (ALT). METHODS AND METHODS: 431 treatment-naïve CHB patients with normal or mildly elevated ALT who underwent liver biopsy were enrolled. Comparision of GPR and other parameters for significant liver inflammation (G≥3). RESULTS: For patients with ALT≤2×ULN, the receiver-operating characteristic curves (AUROCs) of GPR in predicting significant liver inflammation were 0.837 (95%CI 0.796 to 0.878), 0.860 (95%CI 0.809 to 0.910) and 0.809 (95%CI 0.739 to 0.878) in the entire patients, HBeAg positive and HBeAg negative CHB patients, respectively. The diagnostic performance of GPR was higher than ALT (P<0.001, P<0.001, respectively), aspartate transaminase (AST) (P=0.001, P=0.003, respectively) and GGT (P=0.002, P=0.002, respectively) in the entire and HBeAg positive patients, but was comparable with AST (P=0.096) and GGT (P=0.273) in the HBeAg negative CHB patients. For patients with ALT≤1×ULN, the diagnostic accuracy of GPR was significantly higher than ALT, AST and GGT in the entire (P<0.001, P=0.008 and P=0.043, respectively) and HBeAg positive CHB patients (P<0.001, P=0.009 and P=0.024, respectively), while was comparable to AST (P=0.209) and GGT(P=0.555) in the HBeAg negative CHB patients. CONCLUSION: GPR has a better diagnostic value than conventional parameters to predict significant liver inflammation in CHB patients with normal or mildly elevated ALT levels, especially for HBeAg positive CHB.

Red blood cell distribution width: A promising index for evaluating the severity and long-term prognosis of hepatitis B virus-related diseases.

BACKGROUND: We sought to explore the association of red blood cell distribution width (RDW) with the severity and long-term prognosis of chronic hepatitis B (CHB)-related liver diseases. METHODS: 1482 treatment-naïve CHB patients without liver cirrhosis (LC), 485 CHB-related LC (CHB-LC) patients and 325 healthy controls (HCs) were enrolled. The median follow-up time for CHB-LC patients was 33.9 months. RESULTS: RDW was significantly higher in CHB-LC (15.0%) than CHB (12.7%) patients or HCs (12.5%). RDW was slightly higher in CHB patients than HCs (p < 0.001). Among CHB patients, the RDW of immune clearance and HBeAg negative hepatitis patients was significantly higher than immune-tolerant and low-replicative phase patients. RDW was positively correlated with Child-Turcotte-Pugh (r = 0.363; p < 0.001) and the model of end-stage liver disease scores (r = 0.218; p < 0.001). The areas under the receiver operating characteristic curve of RDW in predicting one-year, three-year, five-year and global mortality rates were 0.696, 0.668, 0.628 and 0.660, respectively. Through multivariable Cox regression analysis, RDW (p = 0.048) was identified as an independent predictor of liver-related mortality. Over a median follow-up of 33.9 months, CHB-LC patients with RDW ≥ 15.1% had significantly higher liver-related mortality than RDW < 15.1% patients (18.8% vs. 8.6%; p = 0.002). CONCLUSIONS: RDW is positively associated with the severity of CHB and can independently predict the long-term prognosis of CHB-LC patients.

Selection of the Reference Gene for Expression Normalization in Papaver somniferum L. under Abiotic Stress and Hormone Treatment.

Papaver somniferum L. is an important medical plant that produces analgesic drugs used for the pain caused by cancers and surgeries. Recent studies have focused on the expression genes involved in analgesic drugs biosynthesis, and the real-time quantitative polymerase chain reaction (RT-qPCR) technique is the main strategy. However, no reference genes have been reported for gene expression normalization in P. somniferum. Herein, nine reference genes (actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin 2 (CYP2), elongation factor 1-alpha (EF-1α), glyceraldehyde-3-phosphate dehydrogenase 2, cytosolic (GAPC2), nuclear cap-binding protein subunit 2 (NCBP2), protein phosphatase 2A (PP2A), TIP41-like protein (TIP41), and tubulin beta chain (TUB)) of P.somniferum were selected and analyzed under five different treatments (cold, drought, salt, heavy metal, and hormone stress). Then, BestKeeper, NormFinder, geNorm, and RefFinder were employed to analyze their gene expression stability. The results reveal that NCBP2 is the most stable reference gene under various experimental conditions. The work described here is the first report regarding on reference gene selection in P.somniferum, which could be used for the accurate normalization of the gene expression involved in analgesic drug biosynthesis.

Plateletcrit as a potential index for predicting liver fibrosis in chronic hepatitis B.

Noninvasive tests (NITs) for liver fibrosis are highly needed for chronic hepatitis B (CHB) patients. We aimed to investigate whether plateletcrit (PCT) could be used as a NIT in predicting liver fibrosis for CHB patients. Five hundred and sixty-seven treatment-naïve CHB patients with available liver biopsies were included. Patients were randomly divided into a derivation cohort (n = 378) and a validation cohort (n = 189). The diagnostic accuracy of PCT was evaluated using receiver operating characteristic (ROC) curves. In the derivation cohort, PCT in CHB patients with S2-S4 (0.14%), S3-S4 (0.13%) and S4 (0.12%) was lower than patients with S0-S1 (0.17%, P < .001), S0-S2 (0.17%, P < .001) and S0-S3 (0.16%, P < .001), respectively. PCT was an independent predictor of significant fibrosis (≥S2), advanced fibrosis (≥S3) and cirrhosis (S4). The area under the ROC curve (AUROC) of PCT in predicting significant fibrosis, advanced fibrosis and cirrhosis was 0.645, 0.709 and 0.714, respectively. The AUROC of PCT was higher than the aspartate transaminase to platelet ratio index (APRI) in identifying advanced fibrosis and cirrhosis, while this was comparable with APRI in identifying significant fibrosis. The diagnostic value of PCT was comparable with fibrosis-4 score (FIB-4) in predicting significant fibrosis, advanced fibrosis and cirrhosis. In the validation cohort, PCT could also identify significant fibrosis, advanced fibrosis and cirrhosis with similar diagnostic accuracy as in the derivation cohort. PCT represents a simple and inexpensive indictor for liver fibrosis in CHB patients. PCT is just as good or better than other more complex tools for staging liver fibrosis in CHB patients.

HBeAg Negativity Is Associated With More Advanced Liver Fibrosis in Patients With Chronic Hepatitis B: A Propensity Score-Matching Analysis.

BACKGROUND: Serum hepatitis B e antigen (HBeAg) status is associated with the progression of chronic hepatitis B (CHB). The authors aimed to investigate the relationship between HBeAg status and liver pathology in CHB patients. METHODS: A total of 683 treatment-naive CHB patients who had undergone liver biopsy were retrospectively enrolled from 2 medical centers. Propensity score-matching (PSM) method was performed to adjust the imbalance of baseline confounders between HBeAg-positive and HBeAg-negative CHB patients. RESULTS: HBeAg-negative CHB patients (n=338) exhibited more advanced liver fibrosis than HBeAg-positive CHB patients (n=345) before PSM (P<0.001). However, there were no significant differences in the distribution of inflammation grades between HBeAg-positive and HBeAg-negative CHB patients (P=0.051). Of these 683 CHB patients, 123 patients were included in each group after PSM. HBeAg-negative CHB patients still showed significantly advanced liver fibrosis as compared with HBeAg-positive CHB patients (P=0.03) after PSM. Furthermore, the distribution of liver inflammation grades in the HBeAg-negative CHB patients was also more severe than patients with HBeAg-positive (P=0.037). HBeAg-negative status was identified as an independent risk factor of significant liver fibrosis (P=0.011) by multivariate analysis. CONCLUSIONS: HBeAg negativity is associated with more advanced liver fibrosis in CHB patients.