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Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.
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Background Parabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. Objective To analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. Methods A total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. Results The positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L−1. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P<0.001) and waist circumference (b=−0.80, 95%CI: −1.23, −0.37; P<0.001) in boys, but not in girls. The BKMR results also found significant negative correlations of urinary BzP concentrations with BMI-Z score and waist circumference, which were consistent with the GLM results. Conclusion The selected 10-year-old children are extensively exposed to PBs in the study area. Furthermore, childhood PBs exposure may have potential impacts on childhood adiposity measures with sex-specific effects.
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Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg−1 per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L−1 FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L−1 FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg−1 FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg−1 FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg−1 group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L−1 FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L−1, respectively. The Nrf2 protein level in the 40 μmol·L−1 group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L−1 groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L−1 groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L−1 group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L−1 groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.
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Objective To investigate the characteristics and liver function of the population with occupational exposure to hepatotoxicants. Methods A total of 17 093 workers with occupational hepatotoxicants exposure who underwent occupational medical examination during their employment in a occupational medical examination institution of Shanghai in 2021 were selected as the research subjects by judgement sampling method. Occupational medical examination data were collected, and the prevalence of abnormal liver function and fatty liver were analyzed. The association between hepatotoxicants exposure and abnormal liver function were analyzed. Results The median and the 0th-100th percentiles of the duration of exposure to hepatotoxicants was 6.5(1.0-42.0) years. The prevalence of fatty liver was 48.4% and the incidence of abnormal liver function was 23.7%. Among the workers with fatty liver, the prevalence of abnormal liver function was higher in workers exposed to metals, metalloids and their compounds than in unexposed workers (33.9% vs 30.0%, P<0.01). The results of multivariate logistic regression analysis demonstrated that the risk of abnormal liver function increased with the number of different hepatotoxicants mixed exposures (all P<0.01), after correcting for confounding factors including gender, age, years of exposure, marital status, drinking, hypertension, fatty liver and blood sugar. Conclusion Exposure to hepatotoxicants is a risk factor for abnormal liver function. The more diverse types of hepatotoxicants an individual is exposed to, the stronger the association with this risk.
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Functional cure of chronic hepatitis B (CHB), defined as negative hepatitis B surface antigen (HBsAg) with or without the presence of hepatitis B surface antibody (anti-HBs), is considered the optimal endpoint for CHB treatment at present. Studies have shown that HBsAg clearance can reduce the risk of HBV complications such as liver cirrhosis and hepatocellular carcinoma. However, HBsAg clearance rate remains at a relatively low level, which may be associated with the immune tolerance state caused by HBV infection. HBsAg clearance and/or the presence of anti-HBs indicate the partial recovery of HBV-specific immunity. This article discusses the influencing factors for the functional cure of CHB and the underlying mechanisms.
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Objective@#To evaluate the status of dietary diversity and determinants among school age left behind children.@*Methods@#A total of 501 children aged 9-10 years in Sheyang Mini Cohort Study were enrolled from Sheyang City in Jiangsu Province during 2019. A questionnaires survey was administrated to collect left behind and socioeconomic information. Twenty four hour dietary recall survey was conducted, dietary diversity score (DDS 10 and DDS) and food variety score (FVS) were computed according to Food and Agriculture Organization (FAO). Weight and height of children were measured and sex and age standardized body mass index was used to define obesity. Multivariable regression models were preformed to explore the determinants of dietary diversity in school age left behind children.@*Results@#The proportion of left behind children was 40.9%. The mean value and standard deviation of three kinds of dietary diversity score (DDS 10 , DDS, FVS) in left behind children were (5.69±1.31)(6.55±1.44) and (13.48± 4.23 ), respectively. All of these were lower than that in non left behind children (DDS 10 :5.99±1.29; DDS:6.79±1.40; FVS:14.15±4.22). Significant difference in DDS 10 between left behind and non left behind children was observed ( P =0.01). The results of multivariable regression demonstrated that gender, passive smoking, family education level and family economic status were related to dietary diversity scores ( P <0.05).@*Conclusion@#Dietary diversity in school age left behind children was not optimistic and gender, passive smoking, parental education level, family economic status and left behind situation play a critical role in dietary diversity among these children.
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Wuhan is the city with the most serious outbreak of corona virus disease 2019 (COVID-19) in China. The outbreak of community has exhausted the current medical resources. With integrating local and support medical resources from other province, Wuhan City has rapidly rebuilt a new emergency medical system of classified treatment, and effectively responded to the overload medical demand after the outbreak in the community.
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Elimination of HBV cccDNA from hepatocytes infected with chronic HBV virus is considered to be the key to eradicating HBV. Monitoring HBV cccDNA before, during, and after viral treatment is essential for routine treatment of patients with chronic hepatitis B. With the introduction of new anti-HBV treatment technologies and new drugs targeting HBV cccDNA, Accurate and sensitive HBV cccDNA assays are urgently needed to evaluate efficacy. In recent years, HBV cccDNA detection methods have achieved gratifying results in both traditional PCR methods and digital PCR methods popular in recent years. In this paper, the advances in HBV cccDNA quantitative detection by qPCR, Magnetic bead capture hybridization, rolling circle amplification combined with in situ PCR, digital PCR and digital PCR assay in single cells were reviewed.
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Current antiviral treatment regimens seldom clear hepatitis B virus (HBV) infection and achieve complete cure, and therefore, many patients need long-term or even life-long antiviral therapy with nucleos(t)ide analogues. The root cause is the presence of covalently closed circular DNA (cccDNA) with transcriptional activity within hepatocytes. In order to help readers understand the research advances in HBV cccDNA, this issue invites leading experts in China to introduce the research advances from the following six aspects: anti-HBV treatment and functional cure of chronic hepatitis B, drugs and biotechniques targeting HBV cccDNA, transcriptional regulation of HBV cccDNA and prospects of anti-HBV treatment, in vitro cell models and experimental mouse models of HBV cccDNA, application of in situ hybridization in detection of HBV nucleic acid and cccDNA, and quantification of HBV cccDNA.
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Objective@#To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C.@*Methods@#Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded.@*Results@#108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin.@*Conclusion@#Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.
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Objective To analyze the clinical characteristics of brucellosis cases with fever of unknown origin (FUO) as initial manifestation,and to further raise awareness of doctors in non-epidemic areas.Methods Clinical data of 19 brucellosis cases with FUO as initial manifestation in Huashan Hospital,Fudan University and Jing'an branch from June 2005 to July 2016 were collected.The epidemiological,clinical,assistant examination,imaging,treatment and prognosis data of these patients were retrospectively analyzed.Results The average age of the 19 cases was 48 years old,of whom 3 were female and 16 were male.Seventeen cases had the history of contact with sick livestock or epidemic areas.The main clinical manifestations were hepatomegaly or splenomegaly or lymphadenectasis (14 cases),bone,joint and spine involvement (9 cases),orchitis (3 cases),encephalopathy and peripheral neuropathy (1 case),infectious myelitis (1 case) and sequelae of infectious transverse myelitis (1 case).Brucella was detected in 7 patients by blood culture.The agglutination test of serum antibody were 100％ positive.All patients got improvement after anti-Brucella therapeutic regimen based on doxycycline.Conclusion Brucellosis should be considered for patients with FUO from non-epidemic areas according to clinical and epidemic features.
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Objective@#To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control.@*Methods@#This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data.@*Results@#A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events.@*Conclusion@#In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.
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Objective To explore the correlation between serum homocysteine (Hcy) level and diabetes mellitus combined with cerebral infarction (DMCI) in patients. Methods A total of 144 patients with type 2 diabetes mellitus (T2DM) were selected and divided into two groups, patients without cerebral infaction (group A, n=64) and patients with cerebral infaction (group B, n=80). Thirty healthy people were used as control group (group C). The serum Hcy level was detected by enzymatic cycling assay in three groups. The serum levels of cholesterol (TC) and triglyceride cholesterol (TG) were detected by enzymatic determination. The serum levels of high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were detected by homogeneous phase method. The serum level of creatinine (Cr) was detected by creatine oxidase method. The level of uric acid (UA) was detected by urinary enzyme peroxidase coupling method. Glycosylated hemoglobin (HbA1c) was detected by high performance liquid chromatography. The carotid artery intima media thickness (IMT) was examined by color Doppler ultrasound, and patients were divided into mild and no stenosis group, moderate stenosis group and severe stenosis group according to the results. The levels of Hcy were compared between all groups. The correlation of Hcy level and other indicators was analyzed. Results The levels of Hcy and HbA1c were group C0.05). There were no significant differences in UA and Cr levels between the three groups (P>0.05). The level of Hcy was positively correlated with age (rs=0.411), HbA1c (rs=0.219) and Cr (rs=0.242), and negatively correlated with gender (rs=-0.202) and HDL-C (rs=-0.278, P0.05). With the increased degree of carotid artery stenosis, the Hcy level and the proportion of HHcy showed a rising trend in patients (P<0.01). The level of Hcy was positively correlated with IMT(rs=0.781, P<0.001). Conclusion Hcy is a risk factor for the onset of DMCI. The high level of Hcy is closely related to the occurrence and progression of atherosclerosis. Hcy has great value for early screening and prevention of DMCI.
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Objective To investigate the assessments from family member and nurse for nursing care needs of critical patients based on the Maslow's hierarchy of needs. Methods Questionnaires regarding nursing care needs of critical patients were designed according to the Maslow′s hierarchy of needs; these questionnaires were performed to family members and nurses, and the results were analyzed. Results There was difference regarding the order of various needs of critical patients between family members and nurses; compared to nurse, family members had significantly higher scores on love and belongingness need [(4.08±0.72) points vs. (3.44±0.63) points, t=5.61, P<0.01], and had obviously lower scores on safety needs [(3.71±0.62) points vs. (3.92±0.69) points, t=2.18, P<0.05]. Conclusions The asymmetry in assessments from family member and nurse for nursing care needs of critical patients exist objectively;during clinical nursing, communication with family members should enhance and provide humanized services and management measures should be adopted to improve family members′satisfaction towards nursing service.
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Objective To establish a novel and convenient method to study the phenotype of drug resistant hepatitis B virus (HBV) isolates,and to analyze the drug susceptibility by replacing the reverse transcriptase (RT) domain of wild-type HBV with that of the drug resistant HBV isolates.Methods Full length of HBV isolates was amplified and cloned from the sera of patients prior to nucleoside/nucleotide analogues (NA) treatment.Wild-type full-length HBV genomes was used to construct the recombinant expression plasmids PHY536207 (genotype B) and PHY97 (genotype C).The restriction enzyme sites were introduced in the upstream and downstream region of reverse transeription (RT) domain to construct plasmid,which were named as mPHY536207 and mPHY97,respectively.Lamivudine (LAM) resistant mutant and adefovir (ADV) resistant mutant were isolated and cloned to construct recombinant expression plasmids PHY634 and PHY6923,respectively.Subsequently,the RT domain of mPHY536207 was replaced by that of drug resistant mutant to construct the plasmids RT634 (LAM-resistant) and RT6923 (ADVresistant).The HBV constructs were transfected into Huh7 cells.The HBsAg levels in supernatant were determined by enzyme-linked immunosobent assay (ELISA),and the amount of intracellular HBV DNA was assayed by real-time polymerase chain reaction and Southern blot analysis.Results The plasmids PHY536207 and PHY97 containing genotype B and genotype C wild-type fulllength HBV genomes were constructed successfully,both of which could replicate in Huh7 cells.Intracellular HBV DNA extracted from cells in each of six-well culture plates was more than 1 × 107 copy/ mL,and the introduction of Pst Ⅰ restriction enzyme site did not affect the viral replication and HBsAg secretion.PHY634 and RT634,in which mutant RT domain was replaced into a wild type HBV expressing vector,exhibited the same HBV DNA replication under the treatment with different doses of LAM,the value of 50％ inhibitory concentration (IC50) was ＞100 μmol/L,while the IC50 of mPHY536207 was 0.18μmol/L.Moreover,wild-type isolate was sensitive to ADV (IC50 =1.2 μmol/L),while PHY6923 and RT6923 were resistant to ADV treatment (IC50 ＞100 μmol/L).Conclusion The phenotypic assay is successfully developed in this study based on replacing RT domain of wild-type HBV strains with that of clinical isolated drug resistant strain.
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Objective To describe the clinical feature ,therapeutic approach and prognosis of histoplasmosis for improving clinicians’ awareness of this disease .Methods The clinical data of 7 cases of histoplasmosis treated in Shanghai Huashan Hospital from 2001 to 2014 were reviewed retrospectively .Relevant reports about histoplasmosis from 2001 to 2014 in Chinese mainland were comprehensively reviewed .Results The major clinical manifestations of progressive disseminated histoplasmosis included fever ,hepatosplenomegaly ,lymphadenopathy ,and pancytopenia .Skin lesions and pancytopenia were more common in the patients complicated with HIV/AIDS .The patients with local infection were lack of systemic symptoms or signs . Histological examination found Histoplasmacapsulatum in macrophages in bone marrow or biopsy tissues .Amphotericin B was used most frequently to treat histoplasmosis .Itraconazole was appropriate in mild patients .Conclusions Histoplasmosis is caused by H .capsulatum .The golden standard of diagnosis is any culture positive for H .capsulatum .Antifungal treatments such as amphotericin B and itraconazole are very important .
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Objective To understand the epidemiology and clinical features of avian influenza,improve the prophylaxis and treatment.Methods Clinical data of a fatal case caused by H7N9 avian influenza A virus in Shanghai was retrospectively reported and analyzed,literature on avian influenza A virus infection in human was reviewed.Results A severe case of H7N9 avian influenza was reported,with typical clinical characteristics.The epidemiology history of the patient was unclear,all the contacts were tested negative for H7N9 avian influenza A virus.Literature search,H7 subtype of avian influenza in 2012 was only sporadic,the majority of patients with mild symptoms.People did not have immunity against avian influenza.Conclusions Severe case of H7N9 avian influenza progress quickly and its infection pattern is not clear up-to the time point.It needs further exploration and discovery.
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Objective To study the clinical features and antifungal therapeutic effects in nonacquired immune deficiency syndrome(AIDS)patients with cryptococcal meningitis. Methods One hundred and fifty-four non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital, Fudan University from 1997 to 2007 were reviewed retrospectively. Clinical characteristics, initial antifungal therapies and outcome of these patients were analyzed. Continuous variables were analyzed using t test and categorical variables were compared by X~2 test or Fisher's exact test. Kaplan-Meier survival curves of different therapies were compared with log-rank test. Results Fifty-one patients (33.12%)had one or more predisposing factors. Headache, fever, meningeal irritation, vomiting and altered mental status were common clinical symptoms and signs during the course of diseases. The positive rates of cerebrospinal fluid(CSF)smear, CSF culture and detection of CSF cryptococcal capsular polysaccharide antigen were 88.44%,78.95%and 100.00%,respectively.Twelve cases were excluded because treatment durations were less than 7 days, including 9 died,2 discharged against medical advice due to illness exacerbation and 1 lost after against medical advice discharge. The remaining 142 patients were evaluated for therapeutic effects. The effective rates in amphotericin B (AmB)group, fluconazole group and AmB plus fluconazole group were 78.3%(36/46),33.3%(8/24)and 76.0%(38/50),respectively. The therapeutic effects in AmB group and AmB plus fluconazole group were superior to fluconazole group(X~2=13.6354,12.5509;P＜0.01).Eleven patients were lost during 1-year follow-up. The attributable and overall mortality in the remaining 143 patients were 19.58% and 28.67%,respectively.The 1-year survival rates in AmB group and AmB plus fluconazole group were significantly higher than that in fluconazole group. Conclusions The mortality of non-AIDS cryptococcal meningitis is still high,which is closely correlated with initial antifungal therapies. AmB alone or combined with flucytosine is related to both higher successful response and higher survival rate, while the efficacy of initial fluconazole alone or combined with flucytosine is poor.
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Objective To investigate the effects of andrographolide on the expressions of Th1 cytokine [interferon (IFN)-γ] mRNA and Th2 cytokines [interleukin (ID-4, IL-10] mRNA of peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis B (CHB) and its anti-hepatitis B virus (HBV) activity. Methods PBMCs from CHB patients were cultured with 10 mg/L andrographolide (experimental group) or 0.1% DMSO (control group). HepG2. 2. 15 cells were stimulated with andrographolide of different concentrations (experimental group) or adefovir (control group). The expressions of IFN-γ mRNA, IL-4 mRNA and IL-10 mRNA of PBMCs and the replication of HBV DNA in HepG2. 2. 15 cell line were detected by fluorescence quantitative PCR. Results The expression of IFN-γ mRNA in PBMCs cultured with 10 mg/L andrographolide for 16 h was higher than that in control group (Z=-2. 78, P=0. 05), and the expressions of IL-4 and IL-10mRNA in experimental group were lower than control group (Z= -3. 82, P<0. 01), while the ratio of IFN-γ/IL-4 mRNA was higher than control group (Z= - 3. 82, P<0. 01). Andrographolide with different concentrations had no effect on the replication of HBV DNA in HepG2. 2.15 cells ((=11. 88, P>0.05). However, adefovir had inhibitory effect on the replication of HBV DNA (t =15. 95,P< 0. 05). Conclusion Andrographolide can regulate the expressions of IFN-γ mRNA, IL-4 mRNA and IL-10 mRNA in PBMCs from CHB patients and improve Thl/Th2 balance, while it has no effect on the replication of HBV DNA.
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Objective To set up the rolling circle amplification (RCA) system for detecting hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and to evaluate the specificity and sensitivity of this system. Methods Plasmids containing full-length of wild-type HBV genome were treated with restriction enzyme and T4 DNA ligase, and then were concentrated. The DNA fragments were recovered by the nucleic acid purification kit and severed as standard HBV cccDNA. Total DNA was extracted from hepatic tissues of seven chronic hepatitis B patients. RCA method was used to amplify genomes from tissue samples. Standard HBV cccDNA, 3.2 kb liner HBV DNA, normal hepatic tissue samples and 15 serum samples of patients with chronic HBV infection were used as controls to determine the specificity of RCA. Ten-fold serial dilutions of standard HBV cccDNA were used for determining the sensitivity. Results The standard HBV cccDNA was successfully constructed and could be detected by RCA method. HBV cccDNA could be amplified from 2 mg hepatic tissue samples at least of HBV infected patients, and could be detected as low as 1 ×102 copy/μL. cccDNA was not detected in 3.2 kb liner HBV DNA, normal hepatic tissue samples and 15 serum samples of chronic HBV infected patients. Conclusion RCA method can be used for rapid and simple detection of HBV cccDNA with high specificity and sensitivity.