An anoikis-related lncRNA signature is a useful tool for predicting the prognosis of patients with lung adenocarcinoma.

Background: Anoikis-related long non-coding RNAs (ARLs) play a critical role in tumor metastasis and progression, suggesting that they may serve as risk markers for cancer. This study aimed to investigate the prognostic value of ARLs in patients with lung adenocarcinoma (LUAD). Methods: Clinical data, RNA sequencing (RNA-seq) data, and mutation data from the LUAD project were obtained from The Cancer Genome Atlas (TCGA) database. The Molecular Signatures Database (MSigDB) and the GeneCard database were used to collect an anoikis-related gene (ARG) set. Pearson correlation analysis was performed to identify ARLs. LASSO and Cox regression were then used to establish a prognostic risk signature for ARLs. The median risk score served as the basis for categorizing patients into high and low-risk groups. Kaplan-Meier analysis was utilized to compare the prognosis between these two groups. The study also examined the associations between risk scores and prognosis, clinicopathological characteristics, immune status, tumor mutation burden (TMB), and chemotherapeutic agents. LncRNA expression was assessed using quantitative real-time PCR (qRT-PCR). Results: A total of 480 RNA expression profiles, 501 ARGs, and 2698 ARLs were obtained from the database. A prognostic ARL signature for LUAD was established, consisting of 9 lncRNAs. Patients in the low-risk group exhibited significantly better prognosis compared to those in the high-risk group (P < 0.001). The 9 lncRNAs from the ARL signature were identified as independent prognostic factors (P < 0.001). The signature demonstrated high accuracy in predicting LUAD prognosis, with area under the curve values exceeding 0.7. The risk scores for ARLs showed strong negative correlations with stroma score (P = 5.9E-07, R = -0.23), immune score (P = 9.7E-09, R = -0.26), and microenvironment score (P = 8E-11, R = -0.29). Additionally, the low-risk group exhibited significantly higher TMB compared to the high-risk group (P = 4.6E-05). High-risk status was significantly associated with lower half-maximal inhibitory concentrations for most chemotherapeutic drugs. Conclusion: This newly constructed signature based on nine ARLs is a useful instrument for the risk stratification of LUAD patients. The signature has potential clinical significance for predicting the prognosis of LUAD patients and guiding personalized immunotherapy.

Appraisal of evidence reliability and applicability of Paxlovid as treatment for SARS-COV-2 infection: A systematic review.

This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and ClinicalTrials.gov were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS-COV-2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780-109,254. Based on the randomised controlled trial data, the risk of all-cause mortality, all-cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID-19 (moderate certainty) and improve in-hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged <65 years. As per the economic utility analysis, the economic cost of reducing one death dramatically decreased with increasing age. Early use of Paxlovid in the older adult population with COVID-19 is beneficial. However, in the setting of limited resources, Paxlovid should be prioritised for older patients.

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.

Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19).

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.

Suitable hepatitis B vaccine for adult immunization in China: a systematic review and meta-analysis.

Hepatitis B virus (HBV) infection remains an important public health problem in China, and adults need to be vaccinated. This systematic review and meta-analysis assessed the appropriate immunization of adults in China. Only randomized controlled trials (RCTs) were eligible, and seroprotection was defined as anti-HBs≥ 10 mIU/ml; 18,308 participants in 27 studies were included. Relative risk (RR) and random effects models were used. Twenty micrograms of HBV vaccine resulted in a better response than 10 µg (RR: 1.05, 95% confidence interval (CI): 1.02 to 1.08), and the 0-, 1-, and 6-month schedule was more effective than the 0-, 1-, and 2 - or 3-month schedule (RR: 0.98, 95% CI: 0.96 to 1.00). No significant differences were observed between 10 µg and 5 µg (RR: 1.05, 95% CI: 0.88 to 1.01); (yeast-derived hepatitis B vaccines) YDV and recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine (RR: 1.01, 95% CI: 0.98 to 1.04); domestic and imported (RR: 1.02, 95% CI: 0.99 to 1.05); or 0-, 1-, and 6-month and 0-, 1-, and 12-month schedules (RR: 1.02, 95% CI: 0.89 to 1.08). In conclusion, 20 µg of vaccine is recommended for adults in China, and the 0-, 1-, and 12-month immunization program schedule is also worth choosing when it is not possible to complete the 0-, 1-, and 6-month schedule.

Plasma miRNA-122-5p and miRNA-151a-3p identified as potential biomarkers for liver injury among CHB patients with PNALT.

BACKGROUND: Plasma microRNA (miRNA) levels may be altered during pathological processes; therefore, they may potentially serve as biomarkers for the diagnosis and prognosis of human diseases. This study aimed to explore whether plasma miRNAs may serve as new biomarkers for liver injury among chronic hepatitis B (CHB) patients with normal or nearly normal alanine aminotransferase (ALT) levels. METHODS: Plasma miRNAs from each of three independent groups (no prominent liver injury and persistently normal ALT levels, NPNALT; significant liver injury with persistently normal ALT levels, SPNALT; and healthy) were profiled by miRNA microarray analysis. Differentially expressed miRNAs were then validated by a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. The area under the receiver operating characteristic (AUC) curve was used to analyze the candidate miRNAs validated by qRT-PCR for diagnostic accuracy. RESULTS: Twenty differentially expressed miRNAs were identified by microarray analysis. Seven miRNAs with elevated serum levels were validated by qRT-PCR analysis, and four of them were significantly different between the SPNALT and NPNALT groups. The AUCs of hsa-miR-122-5p and hsa-miR-151-3p were 0.877 (cutoff value = 13.38; 95% CI 0.792-0.963; sensitivity = 83.3%, specificity = 80%) and 0.882 (cutoff value = 7.4; 95% CI 0.797-0.966; sensitivity = 83.3%, specificity = 73.3%), respectively, indicating early liver injury. However, there was no significant correlation of miRNAs with either necroinflammation or fibrosis. CONCLUSION: Serum hsa-miR-122-5p and hsa-miR-151-3p may function as new biomarkers for liver injury in SPNALT patients. With these two biomarkers, we may be able to identify a subset of patients who are experiencing liver injury but have normal ALT levels for further evaluation with a biopsy procedure.

Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE. DATA SOURCES: Seven electronic databases were searched for relevant randomized controlled trials (RCTs) published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated. RESULTS: A total of 14 RCTs (combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test (NCT; week 4: MD = -30.25, 95% CI: -49.85 to -10.66), improve MHE (week 4: OR = 0.18, 95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression (week 4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels (week 4: MD = -0.33 µmol/L, 95% CI: -5.39 to 4.74; week 8: MD = 6.22 µmol/L, 95% CI: -24.04 to 36.48), decrease NCT (week 8: MD = 3.93, 95% CI: -0.72 to 8.58), improve MHE (week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE (week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12: OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics (week 4: MD = 6.7, 95% CI: 0.58 to 12.82). CONCLUSION: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.

The effects of booster vaccination of hepatitis B vaccine on children 5-15 years after primary immunization: A 5-year follow-up study.

The aim of this study was to evaluate changes in hepatitis B surface antibody titers (anti-HBs) after booster vaccinations in children aged 5-15 y and to provide suitable immunization strategies. A total of 2208 children were initially enrolled in screening, and 559 children were finally included. The participants were divided into 2 groups according to their pre-booster anti-HBs levels: Group I, <10 mIU/ml and Group II, ≥10 mIU/ml. Group I was administered 3 doses of booster hepatitis B vaccine (0-1-6 months, 10 µg), and Group II was administered 1 dose of booster hepatitis B vaccine (10 µg). The antibody titer changes were examined at 4 time points: 1 month after dose 1 and dose 3, and 1 year and 5 years after dose 3. The protective seroconversion rates at those points were 95.65%, 99.67%, 97.59% and 91.05% (p < 0.001), respectively, in Group I, and 100.00%, 99.87%, 99.66% and 98.21% (χ2 = 6.04, p = 0.11), respectively, in Group II. The GMT in subjects aged 5-9 y were higher than that in subjects aged 10-15 y in both Group I and Group II at 1 month after dose 1, but no difference was observed at the other three time points. This study demonstrates that booster vaccination has a good medium-term effect. A booster dose for subjects with protective antibodies is not necessary but effective, and 3 doses of hepatitis B vaccination are recommended for those who have lost immunological memory. Receiving booster immunization at the age of 10-15 years may be more appropriate for individuals living in HBV high epidemic areas.

Non-ALT biomarkers for markedly abnormal liver histology among Chinese persistently normal alanine aminotransferase-chronic hepatitis B patients.

AIM: To determine incidence and clinical biomarkers of marked necroinflammation and fibrosis characteristics among chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT). METHODS: Liver biopsy was performed on 115 CHB patients with PNALT. Necroinflammation and fibrosis were graded by the Knodell histologic activity index and the Ishak fibrosis score, respectively. Correlations between the available clinical parameters and necroinflammation and fibrosis were analysed. RESULTS: Marked necroinflammation (Knodell activity index ≥ 7) and fibrosis (Ishak fibrosis score ≥ 3) were found in 36.5% and 15.5% of CHB patients with PNALT, respectively. Following a univariate logistic regression analysis, multiple logistic regression analysis indicated that aspartate transaminase (AST) (AUROC = 0.852, cut-off value = 22.5 U/L) serves as an independent predictor of notable liver inflammation, while platelet (PLT) count (AUROC = 0.905, cut-off value = 171.5 ×109/mL) and gamma-glutamyl transpeptidase (GGT) (AUROC = 0.909, cut-off value = 21.5 U/L) level serve as independent predictors of notable liver fibrosis. CONCLUSION: A considerable proportion of marked histological abnormalities existed in our cohort, who will benefit from optimal therapeutic strategies administered according to predictive indication by AST, PLT and GGT levels.

Effect of low-to-moderate-dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia.

BACKGROUND: The effect of corticosteroids on influenza A(H1N1)pdm09 viral pneumonia patients remains controversial, and the impact of dosage has never been studied. METHODS: Using data of hospitalized adolescent and adult patients with influenza A(H1N1)pdm09 viral pneumonia, prospectively collected from 407 hospitals in mainland China, the effects of low-to-moderate-dose (25-150 mg d-1 ) and high-dose (>150 mg d-1 ) corticosteroids on 30-day mortality, 60-day mortality, and nosocomial infection were assessed with multivariate Cox regression and propensity score-matched case-control analysis. RESULTS: In total, 2141 patients (median age: 34 years; morality rate: 15.9%) were included. Among them, 1160 (54.2%) had PaO2 /FiO2 <300 mm Hg on admission, and 1055 (49.3%) received corticosteroids therapy. Corticosteroids, without consideration of dose, did not influence either 30-day or 60-day mortality. Further analysis revealed that, as compared with the no-corticosteroid group, low-to-moderate-dose corticosteroids were related to reduced 30-day mortality (adjusted hazard ratio [aHR] 0.64 [95% CI 0.43-0.96, P=.033]). In the subgroup analysis among patients with PaO2 /FiO2 <300 mm Hg, low-to-moderate-dose corticosteroid treatment significantly reduced both 30-day mortality (aHR 0.49 [95% CI 0.32-0.77]) and 60-day mortality (aHR 0.51 [95% CI 0.33-0.78]), while high-dose corticosteroid therapy yielded no difference. For patients with PaO2 /FiO2 ≥300 mm Hg, corticosteroids (irrespective of dose) showed no benefit and even increased 60-day mortality (aHR 3.02 [95% CI 1.06-8.58]). Results were similar in the propensity model analysis. CONCLUSIONS: Low-to-moderate-dose corticosteroids might reduce mortality of influenza A(H1N1)pdm09 viral pneumonia patients with PaO2 /FiO2 <300 mm Hg. Mild patients with PaO2 /FiO2 ≥300 mm Hg could not benefit from corticosteroid therapy.

Suitable hepatitis B vaccine for adult immunization in China.

The aim of this study was to evaluate, in adults, the immunogenicity of six hepatitis B vaccines with different doses or different manufacturers in the Chinese market and to provide evidence to support adult hepatitis B vaccination. Participants were randomly divided into six groups (I-VI). Six vaccines (4 at 10 µg/dose and 2 at 20 µg/dose) were administered intramuscularly to healthy adults at 0, 1 and 6 month intervals. All participants (16-50 years) who were negative for any hepatitis B virus serological markers were vaccinated. Anti-HBs levels were assessed 1 month and 1 year after the third vaccination. The anti-HBs seroconversion rate (anti-HBs >10 mIU/ml) was 99.4 % (99.9 % for 10 µg dose groups and 97.9 % for 20 µg dose groups) 1 month after the third vaccination, and the anti-HBs seroreversion rate was 77.0 % (75.3 and 82.6 %) 1 year after the third vaccination (n = 1036). One month after completing the vaccinations, the seroconversion rates were not significantly different (100.0, 100.0, 99.6, 100.0 %) for the four 10 µg dose and two 20 µg dose groups (99.1, 96.9 %). One year after the third vaccination, the group II positive rate was significantly higher than the other three 10 µg dose groups, and the group VI positive rate was significantly higher than the other 20 µg dose group. Groups II and VI showed a significantly higher positive rate and anti-HBs geometric mean titer (GMT) than the other groups. The anti-HBs level declined with increasing age, and the seroreversion rate and GMT decreased over time. All six vaccines had high anti-HBs seroconversion rates and good immunization effects. The 10 µg dose vaccine (Dalian High-Tech) and the 20 µg dose vaccine (GlaxoSmithKline) are recommended for adults.

The one year effects of three doses of hepatitis B vaccine as a booster in anti-HBs-negative children 11-15 years after primary immunization; China, 2009-2011.

The aim of this study was to evaluate hepatitis B surface antibody (anti-HBs) levels one year after hepatitis B booster vaccination in anti-HBs-negative (<10 mIU/mL) children 11-15 y after primary vaccination. Anti-HBs titers were examined in 235 children who were negative for hepatitis B surface antigen (HBsAg), anti-HBs, and hepatitis B core antibody (anti-HBc). The children were then divided into 3 groups based on their anti-HBs levels pre-booster: Group I, <0 .1 mIU/mL; Group II, 0.1 to <1 .0 mIU/mL; and Group III, 1.0 to <10 .0 mIU/mL. They were vaccinated with 3 doses of hepatitis B vaccine (0-1-6 month, 20 ug), and anti-HBs levels were measured. One month after the first dose, the anti-HBs positive rates (≥ 10 mIU/mL) in Groups I-III were 56.14%, 83.61% and 100%. One month after the third dose, the anti-HBs-positive rates in Groups I-III were 96.49%, 98.36% and 100%. One year after the third dose, the anti-HBs-positive rates in Groups I-III were 73.68%, 75.41% and 98.29%, respectively. Protective levels declined more rapidly for those with lower titers. Children with pre-booster anti-HBs titers of 1-9.9 mIU/mL might not need any booster dose, and the children with pre-booster titers of 0.1-0.9 and <0 .1 mIU/mL might need more than one dose booster vaccination.

Comparison of the effect of two different doses of recombinant hepatitis B vaccine on immunogenicity in healthy adults.

The aim of this study was to evaluate the one-month immune response to 2 different doses (10 and 20 µg) of recombinant hepatitis B vaccine in adults aged 20-46 y. Subjects who were negative for hepatitis B surface antigen (HBsAg), hepatitis B antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) were recruited. The participants were divided into 2 groups: group I received 3 doses of 10 µg hepatitis B vaccine at 0, 1 and 3 months, and group II received 3 doses of 20 µg at the same time points. The anti-HBs levels were measured one month after the third vaccination. Among 739 subjects, 62 (9.70%) were positive for HBsAg, and 317 subjects were eligible. The anti-HBs seroprotection rates (anti-HBs ≥ 10 mIU/mL was considered to indicate seroprotection) after the third vaccination were 88.05% and 94.06% in group I and group II respectively, and the geometric mean titers were 91.69 and 290.23 mIU/mL respectively. The difference in the seroprotection rate was not significant (χ(2) = 2.566, P > 0.05), but the GMT after the third dose was significantly lower for group I than for group II (F = 20.587, P < 0.05). Better responses were observed in young adults, especially in group I. In group I, the seroprotection rate and GMT were significantly higher in the 20-35 y group than in the 36-46 y group (P < 0.05); there was no significant difference compared to group II (P > 0.05). The hepatitis B vaccine has good immunological effect; the 20 µg dose can be used in adults aged 20-46 y and the 10 µg dose can be used in subjects aged 20-35 years, and it should be tested on a larger number of subjects before recommending it for adult routine vaccination.

The response of hepatitis B vaccination on seronegative adults with different vaccination schedules.

The purpose of this study was to compare the response of hepatitis B vaccination with different vaccination schedules among seronegative adults, and to provide suitable vaccination schedules for floating and fixed population. The study included adults aged 20 to 39 y without prior history of vaccination with hepatitis B vaccine. The serum samples were collected and tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels. Out of all, 686 adults who were negative for anti-HBs, anti-HBc and HBsAg were vaccinated with 10 ug hepatitis B vaccine at 0, 1 and 3, 6 or 12 month schedules, and their antibody titers were monitored. The rates of completion of the vaccination in floating and fixed population were 90.4% and 94.1% respectively (p = 0.061). The anti-HBs positive rates in adults vaccinated at 0, 1 and 3 ,6 or 12 month were 83.9%, 88.2% and 94.2% respectively (P = 0.0003). The corresponding geometric mean titers (GMTs) were 61.19 (95%CI:47.10-81.23) mIU/mL, 214.04(95%CI:157.14-291.61) mIU/mL and 345.78(95%CI:251.25-475.77) mIU/mL, respectively ( P < 0.0001). Vaccination of hepatitis B with both 0-1-6 and 0-1-12 month schedules in adults result in better level of immune responses. Also, a longer vaccination schedule (0-1-12 month) may be more suitable for floating population and 0-1-6 month schedule is recommended for the fixed population.

Viral genome and antiviral drug sensitivity analysis of two patients from a family cluster caused by the influenza A(H7N9) virus in Zhejiang, China, 2013.

OBJECTIVES: In the winter of 2013, people were facing the risk of human-to-human transmission of the re-emerging influenza A(H7N9) virus. We report herein information on the clinical features of two patients from the same family infected with this virus, the genomic sequences of the viruses harbored, and antiviral drug sensitivity. METHODS: Clinical and epidemiological data of two patients from the same family were collected and analyzed. Sequencing was done for the viruses isolated from these two patients and one epidemiologically related chicken, and the sequences of the eight gene segments of the viruses were analyzed phylogenetically. The sensitivity of the viruses to antiviral drug treatment was determined by neuraminidase inhibitor susceptibility test. RESULTS: The two patients from one family cluster shared the same symptoms but had different outcomes, and had a strong epidemiological link. Three strains, two from these two patients and one from the chicken, were isolated. Genome sequencing and analyses of phylogenetic trees demonstrated that the two viruses were almost identical. We noted the presence of the PB2 E627K amino acid substitution that was not present in isolates from the first wave, as well as two new mutations in the NA gene and six in the PB2 gene. Drug sensitivity testing showed that the new isolates were resistant to oseltamivir but sensitive to peramivir. CONCLUSIONS: The two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir.

Role of general practitioners in prevention and treatment of hepatitis B in China.

BACKGROUND: Hepatitis B virus (HBV) infection may impose an economic burden to patients or their families. The prevention and control of HBV could effectively reduce the burden. However, the management of HBV-related patients has not been well controlled in China. With the development of general practitioner (GP) system in this country, GPs may greatly improve the management of the patients with HBV infection. However, the role of GPs in controlling HBV infection has been rarely studied. DATA SOURCES: A literature search of PubMed, CNKI, Wanfang data and VIP was performed with the following key words: "general practitioner", "family physician", "community management", "community health care workers", "family practice", "hepatitis B virus", "HBV", "HBV vaccination", "HBV prevention", "HBV management", "HBV treatment", "antiviral therapy" and "chronic hepatitis B (CHB)". The information about the GPs-involved prevention, diagnosis and treatment of CHB was reviewed. RESULTS: The reports on the role of GPs in the prevention, diagnosis and treatment of HBV infection are few. But the experiences from Western countries demonstrated that GPs could play a significant role in the management of patients with CHB. The importance of GPs is obvious although there are some difficulties in China. GPs and health officials at different levels should work together in the management of patients with CHB. CONCLUSIONS: The involvement of GPs in the management of patients with HBV infection is effective in China. But GPs' knowledge and skills for the control of HBV infection have to be improved currently. GPs' involvement will enforce the management of CHB in China in the near future.

[Analysis of clinical features among severe or critical pregnant women in different trimesters with 2009 pandemic H1N1 infection].

OBJECTIVE: To explore the disease course and outcomes of severe or critical pregnant women with 2009 pandemic H1N1 (pH1N1) infection in China. METHODS: A retrospective observational study was conducted for 394 severe or critical pregnant women with pH1N1 influenza admitted into hospital in 27 Chinese provinces from September 1, 2009 to December 31, 2009. Their clinical features in different trimesters were analyzed. The viral infection of pH1N1 was verified by real-time reverse transcription (rRT)-PCR. Severe and critical cases were defined according to the 2009 H1N1 clinical guidelines. RESULTS: Among them, 374 (94.9%) were infected in the second or third trimester. Fever and cough were the most common symptoms in all trimesters. However, hemoptysis, dyspnea and associated pneumonia were likely to occur in the second or third trimester. The ratio of required mechanical ventilation in the second or third trimester (44.7%, 167/374) was significantly higher than that in the first trimester (3/20). Among 77 mortality cases, 72.7% (56/77) died in the third trimester. Pregnancy was terminated after the onset of pH1N1 symptoms in 52.5%(207/394) pregnant women. And 57.0%(118/207) of them had delivery < 37 weeks and 29.0%(60/207) fetuses deceased. CONCLUSION: A clinician should be on a high alert for pH1N1 infection in pregnant women, particularly in the second or third trimester.

Risk factors for adult death due to 2009 pandemic influenza A (H1N1) virus infection: a 2151 severe and critical cases analysis.

BACKGROUND: The 2009 pandemic H1N1 (pH1N1) influenza showed that relatively young adults accounted for the highest rates of hospital admission and death. In preparation for pH1N1, the aim of the study is to identify factors associated with the mortality of patients with 2009 pH1N1 infection, especially for young patients without chronic medical conditions. METHODS: Retrospective observational study of 2151 severe or critical adult cases (≥ 14 years old) admitted to a hospital with pH1N1 influenza from September 1, 2009 to December 31, 2009 from 426 hospitals of 27 Chinese provinces. A confirmed case was a person whose pH1N1 virus infection was verified by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Severe and critical cases were defined according to the H1N1 2009 Clinical guidelines (Third Edition, 2009) released by the Ministry of Health of China. RESULTS: Among the 2151 patients, the mean age was 34.0 years. Two hundred and ninty-three (13.6%) died during hospital stay. One thousand four hundred and forty-two patients (67.0%) had no comorbidities and 189 (13.1%) of them died. Pregnancy (OR 8.03), pneumonia (OR 8.91), dyspnea (OR 3.95), central nervous system (CNS) symptom (OR 1.55), higher APACHE (Acute Physiology and Chronic Health Evaluation) II score (OR 1.06), Alanine aminotransferase (ALT) (OR 1.002), and the lactate dehydrogenase (LDH) level (OR 1.001) were independent risk factors for death among adults without chronic medical conditions. Higher APACHE II score (OR 1.08) and age (OR 1.06) were independent risk factors for death among adults with respiratory diseases. A multivariate analysis showed an association between mortality and CNS symptoms (OR 2.66), higher APACHE II score (OR 1.03), ALT (OR 1.006), and LDH level (OR 1.002) in patients with cardiovascular diseases. Dyspnea (OR 11.32) was an independent risk factor for patient death in patients with diabetes mellitus. CONCLUSION: Clinical knowledge of identified prognostic factors for mortality may aid in the management of adult influenza infection.

Effectiveness of HBV vaccination in infants and prediction of HBV prevalence trend under new vaccination plan: findings of a large-scale investigation.

BACKGROUND: Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention. METHODS: To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined. RESULTS: Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%. CONCLUSIONS: The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.