Short-term effects of high-resolution (1-km) ambient PM2.5 and PM10 on hospital admission for pulmonary tuberculosis: a case-crossover study in Hainan, China.

Introduction: There is limited evidence regarding particulate matter (PM)'s short-term effects on pulmonary tuberculosis (PTB) hospital admission. Our study aimed to determine the short-term associations of the exposure to ambient PM with aerodynamic diameters <2.5 µm (PM2.5) and < 10 µm (PM10) with hospital admission for PTB in Hainan, a tropical province in China. Methods: We collected individual data on patients hospitalized with PTB, PM2.5, PM10, and meteorological data from 2016 to 2019 in Hainan Province, China. Conditional logistic regression models with a time-stratified case-crossover design were used to assess the short-term effects of PM2.5 and PM10 on hospital admission for PTB at a spatial resolution of 1 km × 1 km. Stratified analyses were performed according to age at admission, sex, marital status, administrative division, and season of admission. Results: Each interquartile range (IQR) increases in the concentrations of PM2.5 and PM10 were associated with 1.155 (95% confidence interval [CI]: 1.041-1.282) and 1.142 (95% CI: 1.033-1.263) hospital admission risks for PTB at lag 0-8 days, respectively. The stratified analyses showed that the effects of PM2.5 and PM10 were statistically significant for patients aged ≥65 years, males, married, and those residing in prefecture-level cities. Regarding seasonal differences, the associations between PM and hospital admission for PTB were statistically significant in the warm season but not in the cold season. The effect of PM2.5 was consistently stronger than that of PM10 in most subgroups. Conclusion: Short-term exposure to PM increases the risk of hospital admission for PTB. The potential impact of PM with smaller aerodynamic diameter is more detrimental. Our findings highlight the importance of reducing ambient PM level to alleviate the burden of PTB.

[Depression and anxiety caused by pegylated interferon treatment in patients with chronic hepatitis B and the therapeutic effects of escitalopram and alprazolam].

OBJECTIVE: To evaluate the incidence of depression and anxiety caused by pegylated interferon α (PegIFN-α) treatment for chronic hepatitis B (CHB) and assess the efficacy of intervention with escitalopram and alprazolam. METHODS: A total of 165 CHB patients receiving PegIFN-α-based treatment for 12 weeks were assessed for moderate to severe depression and anxiety using Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7)]. The patients identified to have moderate to severe depression and anxiety treated with escitalopram or alprazolam and the psychological condition of the patients was assessed at the 2nd, 4th and 8th weeks of the treatments. RESULTS: In the 165 patients receiving PegIFN-α treatment, 51 patients developed moderate to severe psychiatric symptoms, incuding 37 (22.4%) with depression, 31 (18.8%) with anxiety, and 17 (10.3%) with both. The symptoms of depression and anxiety was both significantly improved by intervention with escitalopram (P=0.000); alprazolam was effective for anxiety (P=0.001) but did not produce obvious effects on depression (P=0.904). Nevertheless, alprazolam had a much better therapeutic effect than escitalopram on anxiety in these patients (t=-3.198, P=0.010). CONCLUSION: Psychological symptoms are common in CHB patients receiving PegIFN-α treatment. The symptoms of depression and anxiety can be ameliorated by intervention with escitalopram and alprazolam, respectively.

[Entecavir combined with Fufang Biejia Ruangan tablet in treatment of chronic hepatitis B patients with liver fibrosis: 96-week efficacy analyses].

OBJECTIVE: To evaluate the effect of long-term therapy with entecavir and Fufang Biejia Ruangan tablet in patients with chronic hepatitis B (CHB)-associated fibrosis and explore the synergistic therapy that accelerates the reversion of liver fibrosis. METHODS: A total of 197 patients with CHB-associated fibrosis were recruited from Nanfang Hospital between June, 2010 and June, 2015. The patients were divided into two groups after matching for age, gender and liver stiffness measurement (LSM), namely group A (n=98) treated with Fufang Biejia Ruangan Tablet plus entecavir, and group B (n=99) to receive entecavir only. HBV DNA quantification, HBV serological indicators, blood biochemical indexes, and results of abdominal ultrasound and FibroScan were recorded every 12 weeks. FibroScan values were converted to Metavir staging. RESULTS: Both groups showed significant decreases in serum levels of HBV DNA, alanine aminotransferase (ALT), and LSM value from baseline (all P<0.05). The median time to achieve Metavir fibrosis staging improvement were 72 weeks in group A and 96 weeks in group B (P<0.05), and the median time to achieve ALT and AST normalization were 12 and 24 weeks in Group A, respectively, significantly shorter than the time in group B (P<0.05). No significant difference was found between the two groups in HBV DNA undetectable rate and HBeAg seroconversion rate. CONCLUSION: The combination therapy with Fufang Biejia Ruangan tablet and entecavir produces a stronger efficacy than entecavir alone in the treatment of chronic hepatitis B patients with liver fibrosis, and Fufang Biejia Ruangan tablet shows an obvious hepatoprotective effect in these patients.

Baseline prognostic factors and statistic model to predict early virological response in telbivudine-treated patients with chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) infection is still a worldwide disease, which may cause liver cirrhosis or even hepatocellular carcinoma. Telbivudine is a potent nucleoside analogue used in the treatment of chronic hepatitis B (CHB); however, drug resistance has remained a challenge. As early virological response can predict long-term efficacy of nucleotide analogue treatment, numerous studies have been conducted in this area. OBJECTIVES: The aim of this study was to establish baseline prognostic factors and a statistical model to predict early virological response in telbivudine-treated CHB patients. PATIENTS AND METHODS: One hundred and eight CHB patients without any experience of nucleotide analogue therapy were assigned to receive telbivudine (600 mg, once daily) for at least 24 weeks, and then were followed up every two weeks. Cox proportional hazard regression model analyses were employed to evaluate baseline variables, and further developing a statistical model to predict early virological response. RESULTS: Negative family history of HBV infection (P = 0.000235), baseline higher serum TBIL (P = 0.038714) and AST (P = 0.020684) concentrations, and lower level of HBV-DNA (P = 0.0034784) were identified to be associated with higher possibility of early virological response. A model was established based on these variables to calculate the risk scores (R) for CHB patients. R > -0.38 suggested early virological response to telbivudine. The model was validated among an independent set of 20 patients. CONCLUSIONS: Family history as well as baseline bilirubin, AST and HBV DNA levels can predict early virological response. The model provides a better tool for response prediction based on the four prognostic factors.

A local outbreak of dengue caused by an imported case in Dongguan China.

BACKGROUND: Dengue, a mosquito-borne febrile viral disease, is found in tropical and sub-tropical regions around the world. Since the first occurrence of dengue was confirmed in Guangdong, China in 1978, dengue outbreaks have been reported sequentially in different provinces in South China transmitted by peridomestic Ae. albopictus mosquitoes, diplaying Ae. aegypti, a fully domestic vector that transmits dengue worldwide. Rapid and uncontrolled urbanization is a characteristic change in developing countries, which impacts greatly on vector habitat, human lifestyle and transmission dynamics on dengue epidemics. In September 2010, an outbreak of dengue was detected in Dongguan, a city in Guangdong province characterized by its fast urbanization. An investigation was initiated to identify the cause, to describe the epidemical characteristics of the outbreak, and to implement control measures to stop the outbreak. This is the first report of dengue outbreak in Dongguan, even though dengue cases were documented before in this city. METHODS: Epidemiological data were obtained from local Center of Disease Control and prevention (CDC). Laboratory tests such as real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR), the virus cDNA sequencing, and Enzyme-Linked immunosorbent assay (ELISA) were employed to identify the virus infection and molecular phylogenetic analysis was performed with MEGA5. The febrile cases were reported every day by the fever surveillance system. Vector control measures including insecticidal fogging and elimination of habitats of Ae. albopictus were used to control the dengue outbreak. RESULTS: The epidemiological studies results showed that this dengue outbreak was initiated by an imported case from Southeast Asia. The outbreak was characterized by 31 cases reported with an attack rate of 50.63 out of a population of 100,000. Ae. albopictus was the only vector species responsible for the outbreak. The virus cDNA sequencing analysis showed that the virus responsible for the outbreak was Dengue Virus serotype-1 (DENV-1). CONCLUSIONS: Several characterized points of urbanization contributed to this outbreak of dengue in Dongguan: the residents are highly concentrated; the residents' life habits helped to form the habitats of Ae. albopictus and contributed to the high Breteau Index; the self-constructed houses lacks of mosquito prevention facilities. This report has reaffirmed the importance of a surveillance system for infectious diseases control and aroused the awareness of an imported case causing the epidemic of an infectious disease in urbanized region.

[Relationship between single nucleotide polymorphisms in IL28B gene and response to interferon treatment in chronic hepatitis B patients].

OBJECTIVE: To explore the relationship between the single nucleotide polymorphisms (SNPs) of rs12979860 and rs8099917 in IL28B gene and the response to interferon treatment in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B patients. METHODS: Peripheral blood samples were collected from 82 HBeAg-positive patients with chronic hepatitis B receiving interferon treatment, including 38 with favorable response to the treatment and 44 without response. IL28B gene was amplified from the chromosomal DNA, and rs8099917 SNP was genotyped based on PCR-RLFP and rs12979860 SNP by sequencing. RESULTS: In the responsive patients, the distribution frequencies of TT and TG+GG genotypes and allele G in SNPrs8099917 were 81.6% (31/38), 18.4% (7/38), and 9.2% (7/76), as compared to the frequencies of 97.7% (43/44), 2.3% (1/44), and 1.1% (1/88) in nonresponsive patients, respectively. The frequencies showed significant differences between the responsive and nonresponsive patients (P=0.014 for genotypes and P=0.025 for allele G). The distribution frequencies of CT genotypes and allele T in SNPrs12979860 showed no differences between the responsive and nonresponsive patients (P<0.05). CONCLUSION: rs8099917 SNP is probably associated with the response to interferon treatment in HBeAg-positive patients with chronic hepatitis B, and Allele G may be predictive of the treatment success.

[Study on genetic aberrations of ocular mucosa-associated lymphoid tissue lymphomas occurring in southern China].

OBJECTIVE: To study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China. METHODS: Fifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations. RESULTS: Amongst the 57 cases studied, 9 cases (15.8%) showed chromosome translocations, including 4 cases (7.0%) of t(11;18)(q21;q21)/API2-MALT1, 1 case (1.8%) of t(14;18) (q32;q21)/IgH-MALT1, 1 case (1.8%) of bcl-6 gene-related chromosome translocation and 3 cases (5.3%) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%) with 3 copies of bcl-6 gene, 21 cases (36.8%) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes. CONCLUSIONS: The MALT lymphoma-associated chromosome translocations t(11;18)(q21;q21)/API2-MALT1 and t(14;18) (q32;q21)/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.

[A novel method for hepatitis C virus genotyping using RT-PCR reverse dot blot hybridization technique].

OBJECTIVE: To develop a rapid and specific method for hepatitis C virus ( HCV) genotyping using reverse dot blot hybridization technique and investigate the distribution of HCV genotypes and subtypes in Guangdong. METHODS: The primers and the probes targeting the 5'untranslated region (5'UTR) and core region of HCV genotypes 1b, 2a, 3a, 3b and 6a were designed, and the RT-PCR reverse dot blot hybridization (PCR-RDH) method for HCV genotyping was established. A total of 115 patients with hepatitis C were genotyped using this method, and 38 of them were also genotyped by sequencing and phylogenetic analysis to evaluate the accuracy and specificity of the method. RESULTS: Of the 115 patients, 111 were successfully genotyped to be 1b, 2a, 3a, 3b, 6a and mix-infection of 1b/2a at frequencies of 56.8%, 8.1 %, 3.6%, 5.4%, 25.2% and 0.9% respectively, and all the 15 healthy control samples showed negative results. The accuracy and reliability of the genotyping method of PCR-RDH was confirmed in 38 cases by amplification of HCV core and NS5B regions followed by DNA sequencing and phylogenetic analysis. CONCLUSION: This method for HCV genotyping, with high reliability and specificity, is suitable for clinical and epidemiological investigations. The prevalence of HCV genotypes 1b and 2a decreases while 1b remains the dominant genotype in Guangdong, where the prevalence of 6a significantly increases as compared with that 10 years ago.

[Preparation of human anti-HBs from volunteers with hepatitis B vaccine boost vaccination by modified B-cell immortalization technique].

OBJECTIVE: To establish immortalized B lymphoblast cell lines (B-LCLs) from healthy anti-HBs antibody (anti-HBs)-positive volunteers and screen for human anti-HBs and the antibody-secreting cells. METHODS: The peripheral blood mononuclear cells (PBMC) isolated from 3 healthy volunteers positive for anti-HBs with hepatitis B vaccine boost vaccination were infected with Epstein-Barr virus (EBV) and incubated in the presence of CpG DNA motifs and cyclosporin A (CyA). The anti-HBs in the culture supernatant of the immortalized B-cells was quantified by Architect anti-HBs assay with chemiluminescent microparticle technique. Immunocytochemistry was performed to identify the differentiation of the cell clones expressing anti-HBs. RESULTS: Immortalized B-cell culture was successfully established from the cell clones secreting anti-HBs with EBV infection and CpG DNA stimulation. The titer of anti-HBs in the culture supernatant was at its peak at 3 weeks of cell culture and then decreased gradually. At 3 months of cell culture, the cells still retained the capacity of anti-HBs production as verified by the results of immunocytochemistry for CD20 and CD138. CONCLUSION: Immortalized B-cell culture secreting anti-HBs from volunteers receiving boost hepatitis B vaccination has been successfully established by modified EBV immortalization technique.

[The detection of anti-nuclear antibody and IL-21 in patients infected with hepatitis C virus].

AIM: To detect the serum anti-nuclear antibody (ANA) and interleukin-21 (IL-21) levels in patients infected with hepatitis C virus (HCV), and study their impact on the liver function of HCV patients. METHODS: Enzyme-linked immunosorbent(ELISA) assays were used to detect the serum ANA and IL-21 levels in 96 cases of HCV-IgG positive sera, as well as 30 cases of HCV-IgG negative sera. Hitachi 7600 biochemical analyzer was used to test the ALT, AST and ALB of all sera samples. RESULTS: HCV patients have abnormal liver function significantly and their average IL-21 level was much lower than the control group. While the liver function of most ANA positive HCV patients was well-balanced. The IL-21 level of HCV patients with ALT < or = 40 U/L or ALT > 40 U/L were markedly reduced. CONCLUSION: The production of ANA and IL-21 do help to control the progress of hepatitis and reduce the damage to liver cells in HCV patients.

[Influence of chronic HBV infection in the husband on the outcome of IVF-ET treatment].

OBJECTIVE: To investigate the outcome of in vitro fertilization and embryo transfer (IVF-ET) in couples with the husband positive for chronic infection of hepatitis B virus (HBV). METHODS: This study involved 102 infertile couples receiving IVF-ET with the husbands(but not the wives) positive for hepatitis B surface antigen (HBsAg), and another 204 couples negative for HBsAg receiving the treatment served as the control group. The cumulative embryo score, fertilization rate, cleavage rate, rate of good quality embryos, implantation rate, clinical pregnancy rate, first trimester and late miscarriage rates, delivery rate, and neonatal malformation rate were recorded and compared between the two groups. RESULTS: Between the HBsAg-positive and the control groups, the cumulative embryo score (52.8-/+18.7 vs 55.4-/+16.9), insemination rate (66.9% vs 66.1%), cleavage rate (97.6% vs 97.2%), rate of good quality embryos (34.0% vs 37.1%), implantation rate (40.9% vs 34.6%), clinical pregnancy rate (56.9% vs 50%), first trimester miscarriage rate (6.9% vs 5.9%) and late pregnancy miscarriage rate (8.6% vs 4.9%), delivery rate (40.2% vs 43.6%) and neonatal malformation rate (0 vs 0) were all similar (P>0.05;). CONCLUSION: Chronic HBV infection in the husband might not affect the outcome of IVF-ET treatment.

[Therapy effect of lamivudine combination with alpha interferon on patients with chronic hepatitis B].

OBJECTIVE: To evaluate the short-term therapeutic efficacy and safety of lamivudine (LAM) combining with alpha interferon (IFNalpha) on patients with chronic hepatitis B. METHODS: 90 chronic hepatitis B patients with HBV DNA and HBeAg positive were subdivided by 1:1:1 proportion into three groups: (1) LAM+IFN group: 6 months therapy of IFNalpha plus lamivudine followed by 6 months of lamivudine; (2) LAM group: lamivudine alone for 12 months; (3)IFN group: IFNalpha alone for 6 months. RESULTS: At the end of treatment, the HBV DNA undetectable rate in LAM+IFN group (90.0%) was much higher than that in LAM group (80.0%) and IFN group (46.7%) (chi2 = 13.017, P < 0.001). ALT normalization occurred 90.0%, 80.0%, and 53.3% in LAM+IFN group, LAM group, and IFN group, respectively (chi2 = 9.932, P = 0.002). HBeAg/anti-HBe seroconversion rates achieved 46.7%, 13.3%, and 33.3% in LAM+IFN group, LAM group, and IFN group, respectively (chi2 = 7.937, P = 0.005). YMDD mutation was not detected in serum samples from LAM+IFN group patients. CONCLUSIONS: LAM+IFN therapy for chronic hepatitis B is tolerated and more effective than IFN monotherapy in inhibiting viral replication and getting ALT normalization. The HBeAg/anti-HBe seroconversion rate with LAM+IFN therapy is higher than that with lamivudine monotherapy. LAM+IFN combination therapy seems to inhibit or postpone YMDD variants appearing in patients with chronic hepatitis B.