Mendelian-randomization study revealed causal relationship between nonalcoholic fatty liver disease and osteoporosis/fractures.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. METHODS: Publicly available genome-wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs of NAFLD and fractures were obtained from the FinnGen Consortium. GWASs of bone mineral density (BMD) were derived from a meta-analysis. GWASs of obesity, diabetes, liver function, and serum lipid-related metrics were used to clarify whether the accompanying NAFLD symptoms contributed to fractures. Moreover, two additional GWASs of NAFLD were applied. RESULTS: A causal association was not observed between NAFLD and BMD using GWASs from the FinnGen Consortium. However, a causal relationship between NAFLD and femoral neck-BMD (FN-BMD), a suggestive relationship between fibrosis and FN-BMD, and between NAFLD and osteoporosis were identified in replication GWASs. Genetically proxied body mass index (BMI), high-density lipoprotein (HDL), and hip circumference increased the likelihood of lower limb fractures. The waist-to-hip ratio decreased, whereas glycated hemoglobin (HbA1C) and homeostasis model assessment of ß-cell function (HOMA-B) increased the risk of forearm fractures. Low-density lipoprotein (LDL) reduced, whereas HbA1C increased the incidence of femoral fractures. Alkaline phosphatase (ALP) raised the risk of foot fractures. However, after a multivariate MR analysis (adjusted for BMI), all the relationships became insignificant. CONCLUSIONS: NAFLD caused reduced BMD, and genetically predicted HDL, LDL, HbA1C, HOMA-B, ALP, hip circumference, and waist-to-hip ratio causally increased the risk of fractures. BMI may mediate causal relationships. Larger GWASs are required to verify this finding.

Progressive multifocal leukoencephalopathy in an HIV patient: A case report and literature review.

Key Clinical Message: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the brain caused by reactivation of the JC virus, which can lead to a lytic infection of oligodendrocytes. We report a patient with HIV who developed PML. Abstract: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the brain caused by reactivation of the John Cunningham virus (JCV), which can lead to a lytic infection of oligodendrocytes. Herein, we report the case of a patient with HIV who developed PML that presented as a progressive disturbance of consciousness and movement. The patient's clinical symptoms progressively deteriorated, and positive JC viral DNA in his cerebrospinal fluid (CSF) helped us diagnose him with PML. Magnetic resonance imaging (MRI) showed multiple asymmetric subcortical and deep white-matter lesions. Although we administered immunoreconstructive therapy, the patient's condition gradually worsened. Therefore, we suggest that PML should be considered if such lesions are found in MRIs of HIV patients.

Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy.

Background: Tissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA. We explored the dynamics and the potential role of serum pgRNA in patients receiving long-term NAs treatment. Methods: Serum pgRNA, HBV DNA, HBsAg, HBeAg, and ALT levels were quantified, and the relationships between serum pgRNA and these common clinical indicators before and after the treatment were investigated. Results: Serum pgRNA showed dynamic change during the 96-month NAs therapy, and serum pgRNA levels were positive and detectable in 19 patients with undetectable serum HBV DNA. Serum pgRNA showed strong and positive correlation with serum HBV DNA (r = 0.693, p < 0.001) and serum HBsAg levels (r = 0.621, p < 0.001) at baseline. Patients with HBeAg seroconversion had lower baseline serum pgRNA levels (p = 0.002). The area under the curve (AUC) of baseline serum pgRNA for predicting HBeAg seroconversion was 0.742 (95% CI: 0.606-0.850) with 63.16% sensitivity and 80.56% specificity. The cumulative HBeAg seroconversion rate was higher in patients with low serum pgRNA (p = 0.001). Conclusion: Serum pgRNA of low level at baseline or great decline at month 6 may independently predict the high incidence of undetectable serum pgRNA at year 4 following NAs therapy, and the baseline serum pgRNA may serve as a novel predictor for HBeAg seroconversion during NAs therapy.

Emergomyces orientalis Emergomycosis Diagnosed by Metagenomic Next-Generation Sequencing.

Emergomyces is a newly described dimorphic fungus genus; it may cause fatal infections in immunocompromised patients, but diagnosis is often delayed. We report a case of disseminated emergomycosis caused by the novel species Emergomyces orientalis in a kidney transplant recipient from Tibet. Infection was diagnosed early by metagenomic next-generation sequencing.

Case Report: A Novel Homozygous Variant Identified in a Chinese Patient With Benign Recurrent Intrahepatic Cholestasis-Type 1.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare hereditary cholestatic liver disorder. Accurate diagnosis and timely interventions are important in determining outcomes. Besides clinical and pathologic diagnosis, genetic study of BRIC remains limited. Here, we report a young man enduring recurrent jaundice and severe pruritus for 15 years. The increased level of direct bilirubin was the main biochemical abnormality, and the work-up for common causes of jaundice were unremarkable. Liver biopsy showed extensive cholestasis of hepatocytes in zone 3. The novel homozygous variant including c.1817T > C and p.I606T was detected on his ATP8B1gene. The patient was finally diagnosed with BRIC-1. His symptoms were relieved, and liver function tests returned to normal after taking ursodeoxycholic acid. This case provides a different perspective to the methodology employed when dealing with cases of jaundice and helping diagnose rare diseases.

TRAIL inhibits HBV replication and expression by down-regulating liver-enriched transcription factors.

BACKGROUND AND STUDY AIMS: To investigate the role of low-concentration TRAIL on HBV replication and expression. MATERIAL AND METHODS: MTT assay was performed to determine the minimum concentrations of TRAIL protein in HepG2 cell apoptosis. HepG2 cells were transfected by HBV replication plasmid pHBV4.1. After the treatment with low concentration of TRAIL, the culture supernatant was collected to detect HBsAg and HBeAg by ELISA. Proteins were extracted from the resulted cells, followed by total RNA and HBV DNA intermediate replication. Southern Blot and Northern Blot were carried out to detect HBV RNA and HBV DNA replication intermediates, respectively. RT-PCR and Western Blot were carried out to detect gene and protein expressions for HNF4α, PPARα, and RXRα, respectively. RESULTS: 50 ng/ml of TRAIL protein led to significant decline on the secretions of HBsAg and HBeAg. Expression levels of HBV RNA and HBV DNA replication intermediates were significantly decreased too. In addition, gene and protein expressions of HNF4α, PPARα and RXRα also dropped, especially for PPARα whose expressions significantly decreased. CONCLUSION: TRAIL could inhibit HBV replication and expression by downregulating the expressions of liver-enriched transcription factors HNF4α, PPARα, and RXRα.

A novel predictive score for citrate accumulation among patients receiving artificial liver support system therapy with regional citrate anticoagulation.

Patients with liver failure may suffer citrate accumulation when using regional citrate anticoagulation for artificial liver support system therapy (RCA-ALSS therapy). This study aimed to develop a predictive scoring system to stratify the risk of citrate accumulation. A total of 338 patients treated with RCA-ALSS therapy were retrospectively enrolled and randomly divided into derivation and validation cohorts. Longer duration of citrate accumulation (LDCA) was defined as the presence of citrate accumulation 2 h after RCA-ALSS therapy. Four baseline variables were found to be independently associated with LDCA: gender, international normalized ratio of prothrombin time, serum creatinine, and serum chloride. A predictive R-CA model and its simplified R-CA score were developed. The R-CA model (AUROC = 0.848) was found to be superior to the MELD score (AUROC = 0.725; p = 0.022) and other univariate predictors (AUROCs < 0.700; all p ≤ 0.001) in predicting LDCA. The R-CA score (AUROC = 0.803) was as capable as the R-CA model (p = 0.369) and the MELD score (p = 0.174), and was superior to other univariate predictors (all p < 0.05) in predicting LDCA. An R-CA score of 0-2 had a negative predictive value of 90.2% for LDCA. Our R-CA score reliably predicts LDCA in patients with RCA-ALSS therapy, and it is easy to use. Patients with R-CA score of 0-2 can safely receive RCA-ALSS therapy, while others should be carefully evaluated before treatment.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029179. Registered 17 January 2020, https://www.chictr.org.cn/showproj.aspx?proj=48084.

Leprosy in a low-incidence setting : Case report relevant to metagenomic next generation sequencing applications.

Leprosy is a disease caused by Mycobacterium leprae that results in disability. In 2000 the World Health Organization announced that leprosy had been eradicated. In nonendemic areas diagnosing leprosy is becoming a challenge for inexperienced clinicians. This case involves a male patient suffering from chronic numbness, hand deformity and recurrent erythema. Skin biopsy revealed granuloma and acid-fast staining of short-rod bacteria. Peripheral venous blood was subjected to metagenomic next generation sequencing and bioinformatics analysis, which revealed 3 unique sequence reads of M. leprae. Paraffin-embedded tissue and fresh samples scraped from skin lesions were subjected to in-house PCR targeting 16S rRNA, hsp65, rpoB, rpoT, ribF-rpsO, and mmaA. Sanger sequencing of amplicons from fresh samples and paraffin-embedded tissue verified the presence of M. leprae. For inexperienced clinicians in nonendemic areas nucleic acid amplification tests, such as in-house PCR, are helpful for diagnosing leprosy but sequence reads from metagenomic next generation sequencing may also provide evidence when interpreted cautiously.

[The Application of Estrogen Receptor Aptamer in Immunohistochemical Detection of Breast Cancer].

OBJECTIVE: To synthesize and select an estrogen receptors aptamer that can be used in immunostaining of breast cancer tissues. METHODS: ER protein was purified. ER aptamer that showed a high affinity and specificity for ER was synthesized and selected and by SELEX. Ligand -receptor interactions assay was adopted to measure the affinity of the aptamer-ER complex. Both the biotinylated aptamer and the anti-ER monoclonal antibody were tested for immunohistochemical staining of ER status on 105 breast cancer samples. Agreement on the detection of ER expression was determined by Kappa statistics. RESULTS: The dissociation contant (Kd) of the biotinylated aptamer-ER complex, as calculated by a linear regression analysis, was determined to be (0.34±0.05) nmol/L ( n=3, r=0.989). The binding capacity (B max) was 769.23 fmol/(mg prot·nmol -1·L -1). The ER aptamer and the anti-ER antibody both exhibited identical specificity to ER-expressing breast cancer cells. There was a high agreement between the two methods ( n=105, Kappa value=0.943, 95% confident interval=0.879-1.006, P<0.05 for the ER positive and negtive samples; n=75, Kappa value=0.805, 95% confident interval=0.642-0.967, P<0.05 for the ER weak and moderate/strong expression samples). Both the anti-ER antibody and the ER aptamer can also recognized breast cancer cells at the same sites. There was no expression in the negative controls. There were also positive expressions in the 2 endometrial cancer tissues by using biotinylated aptamer. CONCLUSIONS: Our results indicated that the synthesized ER aptamer has a high affinity to bind ER. ER aptamer and the anti-ER antibody can both be used for immunohistochemical staining of ER status in breast cancer tissue.

Safety and Efficacy of Regional Citrate Anticoagulation during Plasma Adsorption Plus Plasma Exchange Therapy for Patients with Acute-on-Chronic Liver Failure: A Pilot Study.

BACKGROUND: Patients with acute-on-chronic liver failure (ACLF) might be at risk for citrate accumulation during plasma adsorption plus plasma exchange (PE) therapy with regional citrate anticoagulation (RCA). OBJECTIVES: To assess the safety and efficacy of RCA during double plasma molecular adsorption system (DPMAS) plus PE therapy for patients with ACLF. METHOD: A prospective nonrandomized controlled pilot study was conducted at West China Hospital of Sichuan University. Patients with ACLF were enrolled to heparin anticoagulation (HA) group and RCA group. Serial blood samples were taken. Patients were followed up for 3 months. RESULTS: Twenty-four patients with 94 sessions of HA and 28 patients with 106 sessions of RCA were enrolled. RCA method did not affect the therapeutic efficacy, the function of extracorporeal circulation, and the prognosis of these patients. The occurrences of citrate accumulation in RCA group were 0.0, 67.0, 100.0, 34.0, and 0.0% before DPMAS therapy, at the end of DPMAS therapy, immediately after PE therapy, 2 h after PE therapy, and the next morning, while that in HA group were 0.0, 0.0, 100.0, 7.4, and 0.0%, respectively. The occurrences of citrate accumulation at the end of DPMAS therapy and at 2 h after PE therapy in RCA group were much higher than that in HA group (67.0 vs. 0.0%, p = 0.000; 34.0 vs. 7.4%, p = 0.000, respectively). Although the trend of citrate accumulation in RCA group was much more obvious than that in HA group during and after DPMAS plus PE therapy (p = 0.000), the values on the next morning were similar between the 2 groups (p > 0.05). The main alteration of acid-base status was metabolic alkalosis with no difference between the 2 groups. CONCLUSIONS: RCA might be safe and effective in patients with ACLF receiving plasma adsorption plus PE therapy. RCA method might offer an alternative anticoagulation method for them.

Performance of serum HBcrAg in chronic hepatitis B patients with 8-year nucleos(t)ide analogs therapy.

AIM: This study aimed to investigate long-term kinetics of serum hepatitis B core-related antigen (HBcrAg) and its correlation with serum hepatitis B surface antigen (HBsAg) in a real-world cohort of patients who had received over 8 years of nucleos(t)ide analogs(NAs) therapy. METHODS: This was a retrospective study. All patients were recruited from our previous published study, who started therapy with NAs between 2007 and 2008. Serum HBcrAg and HBsAg levels were quantitatively measured at baseline, the sixth month and each year of follow-up, using the stored serum samples. RESULTS: Among the 94 patients, serum HBcrAg presented a gradually decreasing trend from baseline to year 8, either in HBeAg-negative or HBeAg-positive patients. After 8 years of NAs treatment, 21.3% of patients achieved serum HBcrAg < 3 log 10 U/mL, and only baseline HBcrAg was an independent predictor. Additionally, good correlation of HBcrAg and HBsAg was observed at baseline, but this correlation weakened remarkably during treatment. CONCLUSION: Serum HBcrAg is decreasing gradually with the duration of antiviral therapy, and baseline HBcrAg level is an independent predictor of long-term HBcrAg below the limit of detection.

Insight into the role of TRAIL in liver diseases.

TNF-related apoptosis inducing ligand (TRAIL) is a potential antitumor protein known for its ability to selectively eliminate various types of tumor cells without exerting toxic effects in normal cells and tissues. TRAIL has recently been suggested as a potential therapeutic target in hepatocellular carcinoma (HCC) because it promotes apoptosis in cancer cells. Furthermore, studies on the role of TRAIL in liver injury have reported that TRAIL plays an essential role in viral hepatitis, fatty liver diseases, etc. However, several contradictory and confounding effects of TRAIL in these liver diseases have not been fully elucidated or placed into perspective. Hence, this review summarizes recent progress in studies on TRAIL, including its role in apoptotic signaling, potential therapeutic applications of TRAIL in HCC, hepatitis virus infection, and liver fibrosis and cirrhosis.

Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives.

Drug-induced liver injury (DILI) is one among the common adverse drug reactions and the leading causes of drug development attritions, black box warnings, and post-marketing withdrawals. Despite having relatively low clinical incidence, its potentially severe adverse events should be considered in the individual patients due to the high risk of acute liver failure. Although traditional liver parameters have been applied to the diagnosis of DILI, the lack of specific and sensitive biomarkers poses a major limitation, and thus accurate prediction of the subsequent clinical course remains a significant challenge. These drawbacks prompt the investigation and discovery of more effective biomarkers, which could lead to early detection of DILI, and improve its diagnosis and prognosis. Novel promising biomarkers include glutamate dehydrogenase, keratin 18, sorbitol dehydrogenase, glutathione S-transferase, bile acids, cytochrome P450, osteopontin, high mobility group box-1 protein, fatty acid binding protein 1, cadherin 5, miR-122, genetic testing, and omics technologies, among others. Furthermore, several clinical scoring systems have gradually emerged for the diagnosis of DILI including the Roussel Uclaf Causality Assessment Method (RUCAM), Clinical Diagnostic Scale (CDS), and Digestive Disease Week Japan (DDW-J) systems. However, currently their predictive value is limited with certain inherent deficiencies. Thus, perhaps the greatest benefit would be achieved by simultaneously combining the scoring systems and those biomarkers. Herein, we summarized the recent research progress on molecular biomarkers for DILI to improved approaches for its diagnosis and clinical management.

Pronounced decline of serum HBsAg in chronic hepatitis B patients with long-term effective nucleos(t)ide analogs therapy.

AIMS: This study aims to investigate the kinetics of serum HBsAg levels in chronic hepatitis B patients with long-term nucleos(t)ide analogs (NAs) therapy. METHODS: This was a retrospective clinical study. Serum HBsAg in serial samples of 94 patients, who received at least 8 years of NAs therapy, were measured using Elecsys® HBsAg II Quant Assay. RESULTS: In this cohort, serum HBsAg levels reduced from 3.80 log10 IU/mL at baseline to 2.72 log10 IU/mL at year 8 (p < .001), and the percentage of patients with HBsAg <1000 IU/mL increased from 14.9% at baseline to 55.3% at year 8 (p < .001). The reduction of serum HBsAg did not differ significantly between patients stratified by baseline virological parameters and type of antiviral agents. But as compared to patients without HBeAg seroconversion, HBsAg levels were significant lower in patients with HBeAg seroconversion (3.19 vs. 2.47 log10 IU/mL at year 8, p = .001). As compared to patients with slow (0-1 log10 IU/mL) or steady HBsAg(≤0 log10 IU/mL) decline at year 1, patients with a rapid HBsAg (≥1 log10 IU/mL) decline had a significantly lower HBsAg levels from year 2 to 8. However, Cox regression analysis showed that only absolute HBsAg levels at year 1 was an independent predictor of subsequent HBsAg <1000 IU/mL at year 8 of antiviral therapy(HR 0.242, p = .004). CONCLUSION: Pronounced HBsAg declines could be achieved in patients after long-term effective therapy with NAs, and on-treatment low serum HBsAg level at year 1 might be a predictor of serum HBsAg <1000 IU/mL at year 8.

The Prevalence and Replication Capacity of a Tibetan Dominant HBV Strain, C/D Recombinant.

This study aimed to estimate the distribution of hepatitis B virus (HBV) C/D recombinant in Han and Tibet patients with chronic hepatitis B (CHB) and then learn such strain's replication capacity in vivo. A total of 331 serum samples were collected from Han outpatients from Sichuan Province and Tibetan outpatients from Tibet. Viral genotypes in these samples were identified. An HBV replicative plasmid of C/D recombinant was constructed with selected genome. Sequentially, HBV replicative mouse models were established and the replication capacity of the viral strain was studied in vivo. In the 314 Han patients, 66% (207) were infected by genotype B strain while 31% (96) were by genotype C strain. Only 1% (3) were by C/D recombinant. In the 17 Tibetan patients, 41% (7) were by genotype D and 35% (6) by C/D recombinant. A plasmid with 1.3 copies of C/D recombinant genome was constructed. And its replication intermediates were found at similar levels to that of genotype D strain. Thus, C/D recombinant, the dominant viral strain in Tibet, was rather rare in the genotype B predominated Han patients from Sichuan Province. And the C/D recombinant replicated at a similar level to viral strain of genotype D in vivo.

Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study.

BACKGROUND: The incidence of cryptococcal meningitis (CM) and tuberculous meningitis (TBM) have gradually increased in recent years. These two types of meningitis are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences of clinical features and prognostic factors in non-HIV adults with CM and TBM. METHODS: We retrospectively reviewed the medical records of CM and TBM patients from January 2008 to December 2015 in our university hospital in China. The data included demographic characteristics, laboratory results, imaging findings, clinical outcomes. RESULTS: A total of 126 CM and 105 TBM patients were included. CM patients were more likely to present with headache, abnormal vision and hearing, and they might be less prone to fever and cough than TBM patients (P < 0.05). Higher percentage of CM patients presented with cerebral ischemia/infarction and demyelination in brain MRI than TBM patients (P < 0.05). CM patients had lower counts of WBC in CSF, lower total protein in CSF and serum CD4/CD8 ratio than TBM patients (P < 0.05). After three months of treatment, CM group have worse outcome than TBM group (P < 0.05). Multivariate analysis showed that age more than 60y (OR = 4.981, 95% CI: 1.955-12.692, P = 0.001), altered mentation (OR = 5.054, 95% CI: 1.592-16.046, P = 0.006), CD4/CD8 ratios < 1 (OR = 8.782, 95% CI: 2.436-31.661, P = 0.001) and CSF CrAg ≥ 1:1024 (OR = 4.853, 95% CI: 1.377-17.098, P = 0.014) were independent risk factors for poor prognosis for CM patients. For TBM patients, hydrocephalus (OR = 7.290, 95% CI: 1.630-32.606, P = 0.009) and no less than three underlying diseases (OR = 6.899, 95% CI: 1.766-26.949, P = 0.005) were independent risk factors, headache was a protective factor of prognosis. CONCLUSIONS: Our study provided some helpful clues in the differential diagnosis of non-HIV patients with CM or TBM and identified some risk factors for the poor prognosis of these two meningitis which could help to improve the treatment outcome. Further studies are worth to be done.

The Serum Anti-HBs Level Among Children Who Received Routine Hepatitis B Vaccination During Infancy in Mianyang City, China: A Cross-Sectional Study.

Hepatitis B virus (HBV) prevalence has declined remarkably in children due to nationwide universal vaccination program for HBV in China. However, the persistence of immune response against HBV infection and the optimal time point when a booster vaccination should be performed remain to be elucidated. To assess the persistence and level of antibody against hepatitis B surface antigen (anti-HBs) in a representative population of age 15 and younger who received routine hepatitis B vaccination in Mianyang City, China. A cross-sectional study was conducted in 2011. One thousand five hundred twenty-six children of age 15 and younger who received three doses of 5 µg hepatitis B vaccine series during infancy but did not receive a booster vaccination later were enrolled. Of the 1,526 children, the mean age was 8.2 ± 4.1 and 739 children were male. The median anti-HBs level was 23.0 mIU/mL, and the total percentage of anti-HBs levels ≥10 mIU/mL was 60.9%. With an increase of age, median anti-HBs level, percentage of anti-HBs levels ≥10 mIU/mL, and percentage of anti-HBs levels ≥100 mIU/mL declined remarkably in the early period and reached the lowest level at the age of 3 and then remained relatively stable. The median anti-HBs level, the percentage of anti-HBs levels ≥10 mIU/mL, and the percentage of anti-HBs levels ≥100 mIU/mL in 1- and 2-year-old children were much higher than that in children aged 3-15 (p < 0.05, respectively). Immunity against HBV infection gradually decreased in early ages of children of 15 and younger who received three doses of 5 µg hepatitis B vaccine series during infancy in China. Three dosages of 10 µg hepatitis B vaccine for infants and repeated vaccination or additional booster vaccination for some children at or before age 3 should be provided to get much more powerful immunity to HBV.

Sustained suppression of viral replication in improving vitamin D serum concentrations in patients with chronic hepatitis B.

Recently, the role of vitamin D in chronic hepatitis B (CHB) has attracted a lot attention. In this study, 128 naïve CHB patients (91 with positive HBeAg, 37 with negative-HBeAg) were enrolled, and 128 volunteers without liver diseases were enrolled as controls. Compared to that of healthy controls, the mean level of 25(OH)D3 in CHB patients was significantly lower; and the percent of patients with sufficient 25(OH)D3 (≥20 ng/mL) was also significantly lower than that of healthy controls. Among those CHB patients, the level of 25(OH)D3 was negatively correlated with the serum HBV-DNA level. Additionally, the level of 25(OH)D3 was significantly lower in HBeAg-positive patients than that in HBeAg-negative patients. After the patients went through the long-term antiviral treatments, both the mean level of 25(OH)D3 and the percent of patients with sufficient 25(OH)D3 increased significantly. Additionally, patients who were HBeAg free after the treatment also had much higher 25(OH)D3 level than those with persistent positive HBeAg. All those data suggested that the low vitamin D serum level was dangerous for CHB patients, and the level of 25(OH)D3 was highly negatively correlated with HBV-DNA levels. Effective antiviral therapy might increase the level of vitamin D in CHB patients.

Association of the miRNA146a rs2910164 C>G Polymorphism with Head and Neck Cancer Risk: A Meta-analysis.

OBJECTIVE: To investigate any association of the miRNA146a rs2910164 C>G polymorphism with head and neck cancer risk. MATERIALS AND METHODS: The Medline, PubMed, PUBMED, EMBASE, Web of Science, WanFang and CNKI databases were searched and a meta-analysis was conducted using RevMan 5.2 software. RESULTS: After searching and evaluating the literature, a total seven papers involving 2,766 patients with head and neck cancer and 6,603 healthy controls were included into this meta analysis. The results showed that there were no significant differences between patients and healthy controls overall for the miRNA rs2910164 C>G gene polymorphism (dominant model:OR=0.78, 95%CI:0.58-1.04, P=0.09; recessive model:OR=0.86, 95%CI:0.67-1.12, P=0.27;GG:CC:OR=0.75, 95%CI:0.52-1.08, P=0.12;GC:CC:OR=0.79, 95%CI:0.60-1.04, P=0.10). However, a significant association of miRNA rs2910164 C>G gene polymorphism with Chinese head and neck cancer risk was noted, limited to the dominant model (OR=0.68, 95%CI:0.50-0.95, P=0.02;GG:CC:OR=0.62, 95%CI:0.42-0.92, P=0.02;GC:CC:OR=0.72, 95%CI:0.520.99, P=0.04). CONCLUSIONS: miRNA146a rs2910164 C>G polymorphism is not associated with head and neck cancer risk in general, but tehre may be link in Chinese.