Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study.

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

Clinical characteristics of different subtypes and risk factors for the severity of illness in patients with COVID-19 in Zhejiang, China.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment. METHODS: In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19. RESULTS: A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2-2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1-6.3, P <  0.001), cough (OR = 1.7, 95% CI: 1.0-2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1-10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0-3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2-5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19-40 years [OR = 12.7, 95% CI: 4.5-36.0, P < 0.001], 41-65 years [OR = 14.8, 95% CI: 5.2-42.1, P <  0.001], ≥ 66 years [OR = 56.5, 95% CI: 17.1-186.5, P < 0.001]). CONCLUSIONS: Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China.

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS: From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

Switching Lamivudine with Adefovir Dipivoxil Combination Therapy to Entecavir Monotherapy Provides Better Viral Suppression and Kidney Safety.

Introduction: Most chronic hepatitis B (CHB) patients in China are primitively treated with a combination of lamivudine (LAM) and adefovir dipivoxil (ADV). Although antiviral resistance can be avoided with this combination therapy, using it can have harmful side effects related to ADV, specifically kidney and bone injury. This study was designed to compare viral suppression and kidney safety when switching LAM and ADV combination therapy de novo to entecavir (ETV) monotherapy in patients with CHB and compensated hepatic cirrhosis. Materials and methods: In total, 360 CHB and compensated liver cirrhosis patients who received treatment of LAM and ADV combination therapy for more than 1 year were included in this study. One hundred and eighty patients continued combination therapy to serve as a control group and the other 180 patients were switched to ETV monotherapy to serve as the experimental group. The total course of therapy was 3 years. Laboratory studies were done every 3 months to measure liver and kidney function. Studies included glomerular filtration rate (eGFR), HBV-DNA, urine ß2-microglobulin (ß2-M) and retinol binding protein (RBP). Results: In the experimental group, an HBV-DNA level below 20 IU/ml was found in 77.65%, 85.88%, and 94.77% in years 1, 2, and 3, respectively. In the control group, HBV-DNA levels were below 20 IU/ml in 69.66%, 75.42%, and 85.80% in years 1, 2, and 3, respectively. Low HBV-DNA levels in the experimental group were significantly less common than in the control group on the second and third year; P values were 0.009 and 0.006 for years 2 and 3, respectively. The cumulative genetic mutation rate was 3.49% in the experimental group and 8.88% in the control group (P=0.044). Decreases in eGFR more than 30% from baseline were found in 0%, 0.56%, and 1.74% of patients in the experimental group and 4.49%, 9.14% and 14.79% in patients in the control group in the first, second, and third year, respectively. Serum creatinine more than 50 µmol/L above baseline was found in 0%, 0% and 1.74% of patients in the experimental group and 1.12%, 4.00% and 5.32% of patients in the control group in years 1, 2, and 3, respectively. The urine ß2-M and RBP levels were abnormal more often in the experimental group than in the control group. Conclusion: Switching to ETV monotherapy can decrease HBV-DNA levels, reduce the genetic mutation rate, and prevent renal damage caused by LAM and ADV combination therapy in patients with CHB and compensated liver cirrhosis. Patients receiving LAM and ADV combination therapy de novo should be switched to ETV monotherapy immediately.

Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells.

Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy-associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)-3 by adenovirus infection with a green fluorescent protein (FP)-red FP-LC3 reporter construction and confirmed that DCA treatment induced significant autophagy. Furthermore, the inhibition of DCA-induced autophagy facilitated cell apoptosis and improved the drug sensitivity of esophageal squamous carcinoma cells to DCA and 5-FU (5-fluorouracil). The proliferation of TE-1 cells was markedly inhibited at low concentrations of DCA and 5-FU treatment when subjected to Atg5 mRNA interference, indicating that autophagy performed a protective role in cell survival upon DCA treatment. To determine the underlying mechanism of DCA-induced autophagy, the present study measured alterations in autophagy-associated signaling pathways. Notably, the protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) signaling pathway, an important negative regulator of autophagy, was demonstrated to be suppressed by DCA treatment. These results may direct the development of novel strategies for the treatment of esophageal squamous carcinoma based on the combined use of DCA and autophagy inhibitors.

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.

Comparison of two different size needles in endoscopic ultrasound-guided fine-needle aspiration for diagnosing solid pancreatic lesions: A meta-analysis of prospective controlled trials.

BACKGROUND: This meta-analysis aimed to provide a pooled analysis of prospective controlled trials comparing the diagnostic accuracy of 22-G and 25-G needles on endoscopic ultrasonography (EUS-FNA) of the solid pancreatic mass. METHODS: We established a rigorous study protocol according to Cochrane Collaboration recommendations. We systematically searched the PubMed and Embase databases to identify articles to include in the meta-analysis. Sensitivity, specificity, and corresponding 95% confidence intervals were calculated for 22-G and 25-G needles of individual studies from the contingency tables. RESULTS: Eleven prospective controlled trials included a total of 837 patients (412 with 22-G vs 425 with 25-G). Our outcomes revealed that 25-G needles (92% [95% CI, 89%-95%]) have higher sensitivity than 22-G needles (88% [95% CI, 84%-91%]) on solid pancreatic mass EUS-FNA (P = 0.046). However, there were no significant differences between the 2 groups in overall diagnostic specificity (P = 0.842). The pooled positive and negative likelihood ratio of the 22-G needle were 12.61 (95% CI, 5.65-28.14) and 0.16 (95% CI, 0.12-0.21), respectively. The pooled positive likelihood ratio was 12.61 (95% CI, 5.65-28.14), and the negative likelihood ratio was 0.16 (95% CI, 0.12-0.21) for the 22-G needle. The pooled positive likelihood ratio was 8.44 (95% CI, 3.87-18.42), and the negative likelihood ratio was 0.13 (95% CI, 0.09-0.18) for the 25-G needle. The area under the summary receiver operating characteristic curve was 0.97 for the 22-G needle and 0.96 for the 25-G needle. CONCLUSION: Compared to the study of 22-G EUS-FNA needles, our study showed that 25-G needles have superior sensitivity in the evaluation of solid pancreatic lesions by EUS-FNA.

[Clinical study of titanium mesh in conjunction with concentrate growth factors to rebuild severe bone defect of anterior maxilla].

PURPOSE: To evaluate the effect of overlaying titanium mesh with concentrate growth factors(CGF) for rebuilding severe buccal bone defect of anterior maxilla when used in association with dental implantation. METHODS: Twenty patients with severe buccal bone defect of maxilla were selected. A total of 25 dental implants were placed, including 5 cases in bilateral central incisor area and 15 cases in unilateral central incisor area. After implantation, the defects were treated with Bio-oss and Bio-guid in conjunction with fixation of titanium mesh and then CGF technology was used. Two-stage surgery was carried out after 6 months of submerged healing, and permanent prosthesis was used 3 months after temporary restoration. The repairs of the defect were observed at the second stage surgery. The height of margin bone around implants and the thickness of bone at implants lingual side were measured, at the time of the second stage operation, and 3, 6, 12, 18 months after permanent restoration. The differences were analyzed by SPSS 19.0 software package with multi-sample nonparametric test and Fierdman test. RESULTS: At the time of second operation, the bone plate at lingual side was completely reconstructed, and new bone was formed at the top of implants. Clinical measurements showed that the averaged thickness of bone at lingual side was (2.69±0.154) mm at that time. Three, 6, 12, 18 months after restoration, the values were (2.67±0.152) mm, (2.66±0.153) mm, (2.65±0.153) mm, (2.65±0.151) mm, respectively. Implant-abutment junction was used as a base line to assess vertical bone absorption, the marginal bone of implant neck at lingual side was all inferior to the base line, the distance was (0.02±0.048) mm, (0.69±0.085) mm，(0.87±0.019) mm, (0.87±0.013) mm, respectively. Statistical analysis showed the thickness of bone of labial side decreased significantly over time after permanent restoration (P<0.01). Likewise, the height of marginal bone was also decreased significantly (P<0.01). However, the difference between them at 12 months and 18 months was not statistically significant (P>0.05). CONCLUSIONS: The results indicate that bone augmentation at maxilla can be achieved using titanium mesh in conjunction with CGF. The height and thickness of newly formed bone at the implant neck margin will be stabilized after 1 year. This method is worthy of wide clinical application.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis.

BACKGROUND: Because of the diversity of the clinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS: Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis. RESULTS: The partial least squares discrimination analysis model (R2Y=0.991, Q2=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and specificity of 100%. Five groups of biomarkers were identified, including bile acids, free fatty acids, phosphatidylcholines, lysolecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy control group. The other biomarkers decreased in the AIH and PBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS: The biomarkers identified revealed the pathophysiological changes in AILD and helped to discriminate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B.

AIM: To evaluate urine ß2-microglobulin (ß2-M), retinol-binding protein (RBP) excretion, and renal impairment with adefovir dipivoxil (ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy (n = 90) or ADV plus lamivudine combination therapy (n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine ß2-M, and RBP levels, and estimated the glomerular filtration rate (eGFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine ß2-M abnormalities were observed in patients during the first (n = 3), second (n = 7), third (n = 11), fourth (n = 16), and fifth (n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first (n = 2), second (n = 8), third (n = 12), fourth (n = 15), and fifth (n = 22) year of ADV treatment. eGFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in eGFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and ß2-M abnormalities. In contrast, both serum creatinine and eGFR remained stable in patients treated with entecavir, and only one of these patients developed a urine ß2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and ß2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: a Chinese perspective study.

AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China. METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined. RESULTS: Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log10 IU/mL), IC (4.36 log10 IU/mL), ENH (2.95 log10 IU/mL), LR (3.18 log10 IU/mL) and LC (2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed. CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy.

MicroRNA expression profiles related to early stage murine concanavalin A-induced hepatitis.

BACKGROUND: Fulminant hepatitis is a severe liver disease characterized by massive hepatocyte necrosis and clinical signs of liver failure. This study explores the expression profile of microRNAs, which are regulators of a number of pathophysiological processes, during the early stage of concanavalin A (Con A)-induced hepatitis. METHODS: Balb/c mice were given ConA injections to induce fulminant hepatitis. miRNA expression profiling in liver tissues was carried out by microarray analysis. The differentially expressed miRNAs were subjected to time sequence profile analysis, gene-miRNA regulatory network analysis, and gene ontology-miRNA regulatory network analysis. RESULTS: Eleven miRNAs among multiClass were found to be significantly differentially expressed between liver tissue in early stage fulminant hepatitis and normal control liver tissue. Mmu-miR-133a was the most differentially expressed with the strongest regulatory ability, regulating 47 mRNAs. Mmu-miR-10a was the most highly expressed in the microRNA-GO-Network and also exerted a strong regulatory ability. The expression profiles of miR-133a and miR-10a were verified by RT-PCR. CONCLUSIONS: These results show that, in the early stage, ConA-induced fulminant hepatitis induces a distinct miRNA expression profile. This differential miRNA expression profile may provide pathogenic clues and potential diagnostic and prognostic markers in acute and severe liver disease.

HBsAg levels in HBeAg-positive chronic hepatitis B patients with different immune conditions.

AIM: To investigate hepatitis B surface antigen (HBsAg) levels in patients with HBeAg-positive chronic hepatitis B (CHB) and different immune conditions. METHODS: HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study. These patients were grouped according to the following criteria: immune-tolerant patients, IT group; patients with a mild immune response in the immune clearance phase, IC-Mild group; and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure (ACLF), ACLF group. All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of 2:2:1. Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus (HBV) DNA level were evaluated in these groups. RESULTS: In total, 180 HBeAg-positive CHB patients [IT group (n = 72), IC-Mild group (n = 72), and ACLF group (n = 36)] were enrolled in this study. The median serum HBsAg levels varied among the groups (P < 0.001): IT, 4.86 log10 IU/mL; IC-Mild, 3.97 log10 IU/mL; and ACLF, 3.57 log10 IU/mL. Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group (r = 0.60, P < 0.001), but exhibited a weaker correlation in the IT (r = 0.52, P < 0.001) and ACLF groups (r = 0.51, P = 0.001). The ratio of HBsAg/HBV DNA did not differ significantly among the IT, IC-Mild, and ACLF groups (medians: 0.56, 0.55, and 0.56, respectively; P = 0.179). CONCLUSION: Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions. These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients.

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis.

AIM: To compare efficacy of combined lamivudine (LAM) and adefovir dipivoxil (ADV) therapy with that of entecavir (ETV) monotherapy for hepatitis B virus (HBV)-related decompensated liver cirrhosis. METHODS: A total of 120 naïve patients with HBV-related decompensated cirrhosis participated in this study. Sixty patients were treated with combined LAM and ADV therapy (LAM + ADV group), while the other 60 were treated with ETV monotherapy (ETV group) for two years. Tests for liver and kidney function, alpha-fetoprotein, HBV serum markers, HBV DNA load, prothrombin time (PT), and ultrasonography or computed tomography scan of the liver were performed every 1 to 3 mo. Repeated measure ANOVA and the χ(2) test were performed to compare the efficacy, side effects, and the cumulative survival rates at 48 and 96 wk. RESULTS: Forty-five patients in each group were observed for 96 wk. No significant differences in HBV DNA negative rates and alanine aminotransferase (ALT) normalization rates at weeks 48 (χ(2) = 2.12 and 2.88) and 96 (χ(2) = 3.21 and 3.24) between the two groups were observed. Hepatitis B e antigen seroconversion rate in the LAM + ADV group at week 96 was significantly higher in the ETV group (43.5% vs 36.4%, χ(2) = 4.09, P < 0.05). Viral breakthrough occurred in 2 cases (4.4%) by week 48 and in 3 cases (6.7%) by week 96 in the LAM + ADV group, and no viral mutation was detected. In the ETV group, viral breakthrough occurred in 1 case (2.2%) at the end of week 96. An increase in albumin (F = 18.9 and 17.3), decrease in total bilirubin and in ALT (F = 16.5, 17.1 and 23.7, 24.8), reduced PT (F = 22.7 and 24.5), and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores (F = 18.5, 17.8, and 24.2, 23.8) were observed in both groups. The cumulative rates of mortality and liver transplantation were 16.7% (10/60) and 18.3% (11/60) in the LAM + ADV and ETV groups, respectively. CONCLUSION: Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication, improve liver function, and decrease mortality.

Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1) virus.

BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1) pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2%) than those with who received oseltamivir ≤ 2 days (2.9%), between 2-5 days (4.6%) and >5 days after illness onset (4.9%), p<0.01. A similar trend was observed in pediatric patients. Cox regression showed that at 60 days after symptoms onset, 11 patients (10.8%) who did not receive antivirals died versus 4 (1.8%), 18 (3.3%), and 23 (3.7%) patients whose oseltamivir treatment was started ≤ 2 days, between 2-5 days, and >5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2)/FiO(2)<200, oseltamivir administration reduced the mortality risk by 92.1%, 88% and 83.5%, respectively. Higher doses of oseltamivir (>3.8 mg/kg/d) did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05). CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2)/FiO(2)<200.

[Efficacy of lamivudine monotherapy and combination therapy with adefovir dipivoxil for patients with hepatitis B virus-related decompensated cirrhosis].

To compare the efficacy of Lamivudine (LAM) monotherapy and combination therapy with Adefovir Dipivoxil (ADV) for patients with hepatitis B virus (HBV) -related decompensated cirrhosis for 2 years. A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study, among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM. The liver and kidney functions, HBV DNA, HBV-M, AFP, Ultrasond or CT scan of liver were tested every 1-3months. the treatment efficacy was evaluated by month 12 and 24. By month 12, the HBV DNA negative rates of combination therapy group and LAM monotherapy group were 51.1% (45 cases) and 47.5% (40 cases) respectively, by month 24 the rates were 86.7% and 60.0% respectively. By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0% respectively, with significant difference existed between the two therapy groups (P values is less than 0.05). By month 24, the ALT normalization rates of the two groups were 88.9% and 72.5% respectively. Viral breakthrough happened in 2 cases (4.4%) by month 12 and 3 cases (6.7%) by month 24 in LAM and ADV combination group, but no viral resistance observed. Viral breakthrough happened in 9 cases (22.5%) by month 12 and 15 cases (37.5%) by month 24 in LAM monotherapy group with viral resistance observed in 7 cases (17.5%) by month 12 and 13 cases (32.5) by month 24. Significant difference existed between the two groups (P is less than 0.05). Improvement of liver function was more obviously in the combination group. The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group. No renal dysfunction observed in both groups. LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.

[Adjuvant effect of co-stimulatory molecule CD137L on cellular responses to HBsAg DNA vaccination in mice].

OBJECTIVE: To investigate the adjuvant effect of co-stimulatory molecule CD137L on cellular responses to HBsAg DNA vaccination in mice. METHODS: Eukaryotic expression vector containing the full length of mouse CD137L cDNA sequence (pcD137L) was transfected into NIH3T3 cells, and then the expression of CD137L mRNA and protein in the transfected cells were detected by RT-PCR, flow cytometry and immunofluorescence method, respectively. The BALB/c mice were co-immunized with pcD137L and HBsAg DNA vaccine (pcDS) by intramuscular injection. HBsAg-specific activity of splenic cytotoxic T lymphocyte (CTL) in the immunized mice was measured by LDH release assay. The splenic memory CD8+ T cells, and intracellular IFN-gamma and IL-4 of splenic lymphocytes and CD8+ T cells after immunization were detected by flow cytometry. RESULTS: The NIH3T3 cells transfected with pcD137L efficiently expressed mouse CD137L mRNA and protein. HBsAg-specific CTL responses induced by the pcDS plus pcD137L group were much stronger than those induced by pcDS alone at a week after immunization (P<0.05). Compared to mice immunized with pcDS alone, CD44high and CD127(IL-7R) were all significantly up-regulated in memory CD8+ T cells from the mice immunized with pcDS combined CD137L both at a week and 12 weeks after immunization (P<0.05 and P<0.01). The pcDS plus CD137L group also elicited higher levels of IFN-gamma secreted by CD8+ T cells and splenic lymphocytes than pcDS alone at a week, 12 and 13 weeks after immunization, respectively (all P<0.01). CONCLUSION: DNA, viral/immunol; Co-stimulatory molecule CD137L can enhance the Tc1 (type I) cell-mediated immunity, HBsAg-specific CTL and memory responses induced by HBsAg DNA vaccine, and may be an efficient adjuvant in priming HBV-specific T cell response.

[Current situation and impact factors of acid deposition in main cites of Shandong Province].

Based on the monitoring data for years in Shandong Province, current situation of acid rain in every city was assessed, and the temporal distribution of the dry, wet and total sulfur deposition in Jinan and Qingdao were studied. The results showed that Qingdao which had the largest precipitation acidity was the single city whose annul average precipitation pH was below 5. 60. The precipitation acidities in the main cities of Shandong Province were in a descent tendency. The total sulfur desposition in Jinan and Qingdao was basically stable or in a descent tendency, but also reached 10 t/(km(2)x a) or so. Among the total sulfur deposition flux, the dry deposition of sulfur had the greater contribution, and the contribution of SO2 dry deposition was higher than that of SO42- dry deposition. By analyzing the relation between the precipitation acidity and the SO2 discharge intensity, soil acidity and meteorological condition, the impact factors of acid precipitation in the cities of Shandong Province were revealed.