Chronic Hepatitis B in Women of Childbearing Age and Pregnant Women in China: A Cross-Sectional Study.

Pregnant women and women of childbearing age were enrolled in our study and their knowledge about the Hepatitis B virus (HBV) and chronic hepatitis B (CHB) was evaluated. A questionnaire was distributed to every woman in the cross-sectional study. The questionnaire was answered by all participants before they received health education and advice about HBV and CHB from the doctors visited. Data collected from all answers were analyzed using the χ2 test and logistic regression models. A total of 206 pregnant women and women of childbearing age with CHB infection were enrolled in the study during their first visit to the Infectious Diseases Clinic of the Third Affiliated Hospital of Guangzhou Medical University. Some women of childbearing age (40.8%) and pregnant women with CHB infection (30.6%) still believed HBV could be transmitted through diet and/or mosquito bites. Some women of childbearing age and pregnant women with CHB infection had limited knowledge of the prevention of HBV transmission (111 of 206, 53.9%). Women with higher levels of education had more knowledge about HBV (senior middle school, P = 0.02; university, P <0.01). The majority of participants were willing to take antiviral medicine to decrease the mother-to-child transmission (MTCT) rate of HBV. Some women of childbearing age and/or pregnant women with CHB infection have relatively limited knowledge about HBV or CHB. This situation contributes to the timeliness, or lack thereof, of these women with CHB to see a doctor and receive antiviral therapy. As a result, the morbidity and mortality of HBV-related complications could increase along with the rate of MTCT of HBV.

Follow-Up of 108 Patients with Chronic Hepatitis B Virus Infection Treated with Polyethylene Glycol-Conjugated Derivatives of Interferon-Alpha and Monitoring of Off-Treatment Virological Relapse.

BACKGROUND This single center study, which enrolled 108 patients with chronic hepatitis B virus infection treated with pegylated interferon-alpha (PEG-IFN-alpha), aimed to follow up and monitor off-treatment responses, including virological relapse, and analyze predictors of long-term efficacy of the PEG-IFN-alpha regimen. MATERIAL AND METHODS In total, 108 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B who had completed the PEG-IFN-alpha regimen and achieved virological suppression were enrolled. The patients were followed up for 5 years to monitor off-treatment responses. Twenty-eight relevant factors, including the history of antiviral therapy and HBeAg seroconversion, were analyzed using the Cox proportional hazards regression model. RESULTS The cumulative rates of virological suppression were 75.70%, 68.68%, 65.25%, 63.91%, and 63.91% at 1, 2, 3, 4, and 5 years of the follow-up period, respectively. Compared with the rates of virological suppression, the cumulative rates of clinical suppression were 88.41%, 79.83%, 78.59%, 75.65%, and 75.65%, respectively, for the 5 years. Alanine aminotransferase (ALT) normalization at 24 weeks after off-therapy (relative risk [RR]=3.430, P=0.013) was a potential predictor for sustained virological suppression, and the history of anti-viral therapy (RR=0.164, P=0.004), quantitative value of hepatitis B virus surface antigen (HBsAg) at 48 weeks of anti-viral therapy (RR=2.697, P=0.039), and ALT normalization at 24 weeks after off-therapy (RR=5.467, P=0.004) were potential predictors for sustained clinical suppression. CONCLUSIONS Our results suggested that increased HBsAg levels at 48 weeks and normalization of ALT at 24 weeks after off-therapy might be predictive factors for long-term treatment efficacy.[color=red] [/color].

Repeat laboratory testing of SARS-CoV-2 is necessary to diagnose COVID-19.

The pandemic of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 is ravaging the world. Diagnosis and isolation of persons who are infected with SARS-CoV-2 is very important medical emergency to contain the epidemic of COVID-19. To date, the diagnosis of COVID-19 is mainly depending on positive quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) results for SARS-CoV-2. In the present study, we reported that two cases with uncommon symptoms from a family cluster were ultimately diagnosed as COVID-19 after more than twice of collecting samples and qRT-PCR tests were done. It is easily to miss diagnosis of COVID-19 especially for patients with uncommon symptoms. More attention should be paid to observe the clinical characteristics of it and invent more accurate and convenient methods to detect SARS-CoV-2 as soon as possible.

Research on Mechanism of Superparamagnetic Iron Oxide Nanoparticles in Activating Endoplasmic Reticulum and Prompting Apoptosis of Liver Cells Through Mediation of Tumor Necrosis Factor-α/Tumor Necrosis Factor Receptor 1 (TNF-α/TNFR1) Pathway.

The aim of this study was to assess mechanism of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in activating endoplasmic reticulum (ER) and prompting apoptosis of liver cells through mediating the TNF-α/TNFR1 pathway. The SPIO-NPs were prepared and identified, and HegG2 cells were cultivated in vitro, and their apoptosis was detected. The specific pathogen-free (SPF)-grade rats were divided into several groups; which included blank group, low concentration group, high concentration group and control group. The enzymatic activity of Caspase-3 in liver tissue was tested, and expressions of Caspase-3, Bax, Bcl-2, TNF-α, p-TNFR1, IRE1α, and eIF2α were tested. The size of prepared SPIO-NPs was 7.5 nm and there was no coagulation. There was good dispersity and electric potential, and appearance was stable. The apoptotic rate in the high concentration group was notably higher than in the other groups. There was notable inflammatory cell infiltration in the high concentration group, where quantity of apoptosis was highest. The quantity of apoptosis and fluorocyte in the high concentration group were notably higher than in the other groups. Moreover, there were over expressions of Caspase-3, Bax, Caspase-3, p-TNFR1, IRE1α, and eIF2α in the high concentration group while the expression of TNF-α was lowest. The apoptosis of HegG2 cells was prompted by SPIO-NPs, and quantity of apoptosis was increased with increased adopted concentration. The active expression of p-TNFR1, IRE1α, and eIF2α could be prompted to reduce the expression of TNF-α and increase the expression of Caspase-3 and Bax for prompting the apoptosis.

Efficacy and safety of continuous antiviral therapy from preconception to prevent perinatal transmission of hepatitis B virus.

Few studies were conducted to assess safety and efficacy of continuous antiviral therapy administrated from preconception. In the present study, 136 eligible women with chronic HBV infection were recruited, and assigned to active chronic hepatitis B (CHB) (Group A, B or C) or chronic HBV carrier (Group D). Antiviral therapy was administrated in preconception (Group A), in early (Group B) or late pregnancy (Group C and Group D). Immunoprophylaxis was administrated to all infants. Mothers' HBV status and ALT were assessed at delivery and 7 months postpartum. Offspring's HBV status was examined at 7 months old. Group A women showed low HBV DNA level and normal ALT throughout pregnancy. All women at delivery had an HBV DNA level of less than 106 IU/ml, but the proportion of patients with lower HBV DNA level in Group A was higher than any of other three groups (P < 0.05). No differences in obstetrical complications were found among the four groups. None of infants who completed follow-up showed positive HBsAg at age of 7 months. Congenital malformation and infant growth indicators were similar among study cohorts. Continuous antiviral therapy from preconception to entire pregnancy is effective and safe for active CHB mothers and their infants.

Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin.

A small population of cells with stem cell-like properties in prostate cancer (PCa), called prostate cancer stem cells (PrCSCs) or prostate stemness-high cancer cells, displays highly tumorigenic and metastatic features and may be responsible for the therapy resistance. A small molecule, napabucasin (BBI608), recently have been identified with suppression of stemness-high cancer cells in a variety of cancers. However, the effects of napabucasin on PCa cells as well as PrCSCs isolated from PCa cells have not yet been defined. The effect of napabucasin on PCa cells in cell proliferation, colony formation, and cell migration in vitro were measured by MTS, colony formation assay, and Transwell, respectively. Flow cytometry was employed to evaluate cell cycle and cell apoptosis, and the effect on tumorigenesis in vivo was examined by tumor growth assays. Furthermore, the role of napabucasin on self-renewal and survival of PrCSCs was evaluated by their ability to grow spheres and cell viability assay, respectively. Western Blot and qRT-PCR were used to determine the effect of napabucasin on the expressions of stemness markers. Decrease in cell viability, colony formation, migration, and survival with cell cycle arrest, higher sensitivity to docetaxel in vitro, and repressed tumorigenesis in vivo was observed upon napabucasin treatment. More importantly, napabucasin can obviously inhibit spherogenesis and even kill PrCSCs in vitro. Downregulation of stemness markers was observed after PrCSCs were treated with napabucasin. This study demonstrates that napabucasin may be a novel approach in the treatment of advanced PCa, specifically for castration-resistant prostate cancer (CRPC).

Association of Fcγ receptor IIB polymorphism with cryptococcal meningitis in HIV-uninfected Chinese patients.

BACKGROUND: As important regulators of the immune system, the human Fcγ receptors (FcγRs) have been demonstrated to play important roles in the pathogenesis of various infectious diseases. The aim of the present study was to identify the association between FCGR polymorphisms and cryptococcal meningitis. METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study, we genotyped four functional polymorphisms in low-affinity FcγRs, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot technology. Among the 117 patients with cryptococcal meningitis, 59 had predisposing factors. In patients with cryptococcal meningitis, the FCGR2B 232I/I genotype was over-presented (OR = 1.652, 95% CI [1.02-2.67]; P = 0.039) and the FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33-0.90]; P = 0.016) in comparison with control group. In cryptococcal meningitis patients without predisposing factors, FCGR2B 232I/I genotype was also more frequently detected (OR = 1.958, 95% CI [1.05-3.66]; P = 0.033), and the FCGR2B 232I/T genotype was also less frequently detected (OR = 0.467, 95% CI [0.24-0.91]; P = 0.023) than in controls. No significant difference was found among FCGR2A 131H/R, FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and controls. CONCLUSION/SIGNIFICANCE: We found for the first time associations between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that FcγRIIB might play an important role in the central nervous system infection by Cryptococcus in HIV-uninfected individuals.

Genotypes coding for mannose-binding lectin deficiency correlated with cryptococcal meningitis in HIV-uninfected Chinese patients.

BACKGROUND: There is increasing evidence that mannose-binding lectin (MBL) has a complex role in many diseases, particularly in infectious diseases. However, the relationship between MBL deficiency and cryptococcal meningitis has not been clarified. The purpose of this study was to investigate the correlation between MBL polymorphism and non-HIV cryptococcal meningitis. METHODS: A case-controlled genetic association study was conducted. Patients with cryptococcal meningitis and control subjects were genotyped for 6 alleles of MBL2 gene (H/L, Y/X, P/Q, A/D, A/B, and A/C). The distributions in allele frequency, genotypes, haplotypes, and genotype groups were compared between patients and control subjects. RESULTS: Study participants included 103 HIV-uninfected patients with cryptococcal meningitis and 208 healthy control subjects, all of Chinese Han ethnicity. The homozygous mutative genotypes (O/O) of the coding region were associated with cryptococcal meningitis (P = .023; odds ratio [OR], 4.29; 95% confidence interval [CI], 1.11-19.88), the correlation more overt in immunocompetent patients (P = .005; OR, 6.65; 95% CI, 1.49-33.05). MBL-deficient participant group was associated with cryptococcal meningitis (P = .039; OR, 2.09; 95% CI, .96-4.51), particularly in immunocompetent patients (P = .028; OR, 2.51; 95% CI, .96-6.22). CONCLUSIONS: This is the first to show genotypes coding for MBL deficiency are associated with cryptococcal meningitis in nonimmunocompromised hosts.

Epidemiology and risk factors for non-Candida albicans candidemia in non-neutropenic patients at a Chinese teaching hospital.

The purpose of this study was to describe the epidemiology of nosocomial candidemia and identify risk factors involved in infections caused by non-C. albicans Candida species in a Chinese tertiary care center over a 10-year period. A total of 102 cases of nosocomial candidemia in non-neutropenic patients admitted from 1998 through 2007 were included in the study. Candida albicans remained the most common causative agent, accounting for 57.8% of all cases, followed by C. tropicalis (12.8%), C. parapsilosis (10.8%) and C. glabrata (10.8%). Comparison of C. albicans and non-C. albicans candidemia by multivariate logistic regression showed that factors independently associated with non-C. albicans candidemia included head trauma (OR, 5.34; 95% CI, 1.18-24.17; P = 0.029) and bacterial sepsis (OR, 3.58; 95% CI, 1.17-10.98; P = 0.026). Factors independently associated with C. albicans candidemia included tracheal intubation (OR, 0.26; 95% CI, 0.08-0.92; P = 0.037), and increased peripheral WBC count (OR, 0.84; 95% CI, 0.74-0.95; P = 0.006).

[The polymorphism of cytochrome P(450) 2C19 gene in patients with invasive fungal infections.].

OBJECTIVE: To investigate the polymorphism profile of cytochrome P(450) 2C19 (CYP2C19) in Chinese patients with invasive fungal infections. METHODS: Two major single nucleotide polymorphism loci of the CYP2C19 gene (CYP2C19*2 and CYP2C19*3) were genotyped with PCR and restriction fragment length polymorphism (PCR-RFLP) in 134 patients with invasive fungal infections and 134 healthy volunteers. Allele frequencies and the proportions of metabolizer phenotypes were compared. RESULTS: In patients with invasive fungal infections, CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles showed frequencies of 58.2%, 36.6% and 5.2%. In healthy volunteers, the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 63.4%, 34.3% and 2.2%. There was no significant difference in allele frequencies between the two groups. Of the patients with invasive fungal infections, 33.6% were homozygous extensive metabolizers, 50.0% heterozygous extensive metabolizers and 16.4% poor metabolizers. Of the healthy volunteers, 40.3% were homozygous extensive metabolizers, 48.5% heterozygous extensive metabolizers and 11.2% poor metabolizers. The proportions of metabolizer phenotypes were similar between the two groups. CONCLUSIONS: Significant CYP2C19 polymorphism was detected in both groups. Approximately two thirds of the Chinese patients were either heterozygous extensive metabolizers or poor metabolizers. The genetic polymorphism may have important effect on drug metabolism in these patients.

[Factors associated with mortality in cryptococcal meningitis].

OBJECTIVE: To investigate factors associated with mortality in non-AIDS patients with cryptococcal meningitis. METHODS: We retrospectively reviewed 154 cases of non-HIV cryptococcal meningitis in a tertiary care hospital in China, from 1997 through 2007. RESULTS: The 1-year attributable mortality was 19.6% (28/143), and overall mortality was 28.7% (41/143). Advanced age (> or = 60 years), delay in diagnosis (> 4 months), hematologic malignancy, solid malignancy, altered mental status (coma, seizure, herniation), and CSF drainage or shunting were factors associated with increased death; factors associated with increased survival were amphotericin B based initial therapy and flucytosine containing therapy. In multivariate analysis, age > or = 60 years, the time from symptom onset to diagnosis > 4 months, coma, cerebral herniation, and non-amphotericin B based initial therapy were independently associated with increased overall mortality; factors independently associated with cause-specific mortality were time from symptom onset to diagnosis > 4 months, cerebral herniation and non-amphotericin B based initial therapy. CONCLUSION: A variety of factors were associated with mortality in non-AIDS cryptococcal meningitis. Amphotericin B based initial treatment was independently correlated to improved 1-year survival.

[Evaluation of low-dose amphotericin B and flucytosine in the treatment of cryptococcal meningitis].

OBJECTIVE: To evaluate the efficacy and safety of low-dose amphotericin B (< 0.7 mg x kg(-1) x d(-1)) and flucytosine in patients with non-AIDS-associated cryptococcal meningitis. METHODS: In non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital, Fudan University in Shanghai from January 1998 to December 2007, 31 were initially treated with low-dose amphotericin B and flucytosine for more than 1 week. The clinical characteristics, clinical responses, drug-related adverse reactions and outcome of these patients were retrospectively evaluated. RESULTS: Among the 31 patients enrolled in this study, 8 patients had one or more predisposing factors. Headache, fever, meningeal irritation and vomiting were common clinical symptoms and signs when cryptococcal meningitis was diagnosed. The result of cranial CT scan and/or MRI showed abnormality in 22 cases (78.6%). When the therapy of low-dose amphotericin B and flucytosine ended, the complete response rate was 19.4% (6/31), partial response rate was 54.8% (17/31), and total effective rate was 74.2%. Except for 1 patient lost to follow-up, the 1-year attributable and all-cause mortality among the remaining 30 patients were 0 (0/30) and 10.0% (3/30) respectively. On the other hand, 26 (83.9%) patients had amphotericin B-related adverse reactions, including renal impairment, liver injury, arrhythmia, and anemia, etc. However, most of these reactions were tolerable. CONCLUSION: Low-dose amphotericin B and flucytosine can be used in non-AIDS-associated cryptococcal meningitis with both acceptable efficacy and safety.

Cryptococcal meningitis in non-HIV-infected patients in a Chinese tertiary care hospital, 1997-2007.

Information remains sparse about non-HIV patients with cryptococcal meningitis in the era of triazole therapy. Particularly of interest are the clinical manifestations and prognosis of the infection in these previously healthy patients. We retrospectively reviewed 154 non-HIV-infected patients with cryptococcal meningitis who presented in our hospital from 1997 to 2007. We compared the clinical features and outcomes between predisposed and otherwise healthy hosts. The number of cases per year showed a steady increase over time. The majority of patients were otherwise apparently healthy (103 patients, 66.9%) and predisposing factors were identified in only 51 (33.1%) patients. Corticosteroid medication accounted for the most common underlying factor in these cases (n = 21). Morbidity was appallingly high, with seizures in 28.6%, cranial nerves palsies in 51.5% and cerebral herniation in 19.5%. Despite these complications, overall mortality during 1 year was 28.7% (41/143), close to that reported from other centers with non-HIV patients. Death attributed to cryptococcosis occurred in 19.6% (28/143) patients with most receiving amphotericin B as a component of their initial therapy. Among surviving patients who had lumbar punctures at weeks 2 and 10, those given amphotericin B for initial therapy achieved higher rates of overall response than those receiving initial fluconazole therapy at either week 2 (84.4% of 96 patients vs. 33.3% of 24 patients, P <0.001) or week 10 (85.0% of 93 patients vs. 66.7% of 24 patients, P = 0.041). In multivariate analysis, coma, cerebral herniation, and initial antifungal therapy without amphotericin B were independently correlated with both increased overall and attributable mortality, while advanced age (>/= 60 years) was correlated with increased overall mortality only. Patients with apparently normal immune status were overall younger than those who were immunocompromised. In addition, previously healthy patients for whom diagnosis was delayed had more severe disease, experiencing more brain herniation, coma, seizures, hydrocephalus and more surgical shunt procedures. On the other hand, immunocompromised patients were more commonly found to have high fever and brain parenchymal involvement. However, both groups had a similar treatment response and 1-year survival.