Microwave ablation for recurrent primary hyperparathyroidism in four patients with multiple endocrine neoplasia type 1: a case series report.

Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome, is inherited in an autosomal dominant pattern, mainly manifested as primary hyperparathyroidism (PHPT). Surgery is preferred for patients with MEN1 and PHPT. Thermal ablation has been widely applied for PHPT but rarely for postoperative recurrent PHPT in MEN1 patients. Based on a series of cases, we aimed to investigate the clinical efficacy and safety of ultrasound-guided percutaneous microwave ablation in the treatment of MEN1 patients with postoperative recurrence of PHPT.

Update on the STING Signaling Pathway in Developing Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

Exploring Anti-Type 2 Diabetes Mellitus Mechanism of Gegen Qinlian Decoction by Network Pharmacology and Experimental Validation.

Purpose: Gegen Qinlian Decoction (GGQL) has been employed to treat type 2 diabetes mellitus (T2DM) in the clinical practice of traditional Chinese medicine. However, the underlying mechanism of GGQL in the treatment of T2DM remains unknown. This study was aimed at exploring the pharmacological mechanisms of GGQL against T2DM via network pharmacology analysis combined with experimental validation. Methods: The effective components of GGQL were screened, and the target was predicted by using traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). The candidate targets of GGQL were predicted by network pharmacological analysis, and crucial targets were chosen by the protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of GGQL against T2DM. Then, T2DM mice were induced by a high-fat diet combined with streptozotocin. The model and GGQL groups were given normal saline and GGQL aqueous solution (10 and 20 g/kg/d) intragastric administration, respectively, for 8 weeks. The mice in the GGQLT groups were administered with GGQLT at 10 and 20 g/kg/d, respectively. The pathological changes in liver tissues were observed by hematoxylin-eosin staining. The protein expression of TNF-α and NF-κB was verified by western blotting. Results: A total of 204 common targets of GGQL for the treatment of T2DM were obtained from 140 active ingredients and 212 potential targets of T2DM. GO and KEGG enrichment analysis involved 119 signaling pathways, mainly in inflammatory TNF signaling pathways. Animal experiments showed that GGQL significantly reduced the serum levels of body mass, fasting blood glucose, fasting insulin, HOMA-IR, TNF-α, and IL-17. The liver pathological section showed that GGQL could improve the vacuolar degeneration and lipid deposition in the liver of T2DM mice. Mechanistically, GGQL downregulated the mRNA expression of TNF-α and NF-κB. Conclusions: This study demonstrated that GGQL may exert antidiabetic effects against T2DM by suppressing TNF-α signaling pathway activation, thus providing a basis for its potential use in clinical practice and further study in treating T2DM.

Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages.

BACKGROUND: Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingguizhugan decoction (LGZG), a Traditional Chinese herbal decoction, has been applied to treat metabolic disorders for many years. However, whether LGZG can alleviate the progression of NAFLD through inhibiting inflammation remains unclear. This study was to determine the role of STING-mediated inflammation in the HFD-induced hepatic-lipid deposition treated with LGZG. METHODS: The anti-inflammatory and anti-steatotic effects of LGZG in vivo were detected by H&E staining, immunofluorescence and immuno-chemistry. Mice bone-marrow-derived macrophages (BMDMs) and primary liver macrophages were treated with STING-specific agonist (DMXAA), LGZG and its critical components respectively. The treated culture supernatant of BMDMs and primary liver macrophages from each group was co-cultured with palmitic acid-treated mouse primary hepatocytes or mouse liver cell line AML-12 respectively to detect whether the activation of STING-mediated pathway is involved in the anti-steatotic effect of LGZG. The hepatocyte lipid deposition in vivo and in vitro were detected by oil red staining. Mitochondrial DNA release of mouse liver extracts were detected by real time PCR. The expression of proteins and inflammatory cytokines related to STING-TBK1-NF-κB pathway was detected by western blotting and ELISA. RESULTS: LGZG significantly ameliorated HFD induced hepatic steatosis, oxidative stress, hepatic mitochondrial damage and mitochondrial DNA release, which was correlated with reduction of the expression level of STING as well as the infiltration of STING-positive macrophages in the livers of HFD fed mice. The critical components of LGZG directly inhibited the activation of STING-TBK1-NF-κB pathway in liver macrophages induced by DMXAA, LPS, thereby reducing the release of IFNß and TNFα. Co-incubating the culture supernatant of LGZG treated liver macrophages and PA-stimulated hepatocytes significantly inhibited the PA-induced lipid deposition. CONCLUSION: This study demonstrates that LGZG can ameliorate HFD-induced hepatic-lipid deposition through inhibiting STING-TBK1-NF-κB pathway in liver macrophages, which provides novel insight for elucidating the molecular mechanism of LGZG alleviating HFD induced hepatic steatosis.

[Testosterone replacement therapy improves metabolic indexes of the patients with hypogonadism: A meta-analysis].

OBJECTIVE: To systematically evaluate the effect of testosterone replacement therapy (TRT) on metabolic indexes in patients with hypogonadism. METHODS: We searched the databases of CNKI, CBM, Wanfang Data, VIP, PubMed, Medline, Embase and Cochrane Library from the establishment to May 2021 for clinical randomized controlled trials (RCT) on the improvement of metabolic indexes of the patients with hypogonadism treated by TRT. According to the inclusion and excretion criteria, we screened the literature, extracted the data and evaluated the quality of the included RCTs, followed by statistical analysis with the STATA15.1 software. RESULTS: Totally 19 RCTs with 1 553 cases were included. Compared with placebo, TRT effectively reduced the levels of fasting plasma glucose (FPG) and fasting insulin (FINS), improved Homeostatic Model Assessment-insulin resistance (HOMA-IR), decreased total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), increased the body mass index (BMI), lowered the waist circumference (WC), but elevated the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients. No statistically significant differences were observed in the improvement of glycosylated hemoglobin (HbA1c) and triglyceride (TG) between the TRT-treated patients and placebo controls. The results of Egger's and Begg's tests showed no significant publication bias among the studies. CONCLUSION: TRT can significantly improve metabolic indexes in patients with hypogonadism, though further studies are needed to confirm its long-term efficacy and safety in patients with metabolic disorders.

Berberine Ameliorates Hepatic Insulin Resistance by Regulating microRNA-146b/SIRT1 Pathway.

OBJECTIVE: Hepatic insulin resistance is a major initiating factor for type 2 diabetes mellitus. In previous study, Gegen Qinlian Decoction containing berberine could enhance hepatic insulin sensitivity by SIRT1-dependent deacetylation of FOXO1. However, it is not clear whether berberine also can improve hepatic insulin sensitivity by SIRT1/FOXO1 pathway. This study aimed to evaluate the efficacy of berberine for improving hepatic insulin resistance and the possible molecular mechanisms involved. METHODS: In vitro, HepG2 cells were induced with palmitic acid, and glycogen synthesis was examined. In vivo, a high-fat diet (HFD)-fed mouse model was established, and metabolic parameters were assessed. The expressions of miR-146b and sirtuin 1 (SIRT1) in liver were also examined. The relationship between miR-146b and SIRT1 was examined by the dual-luciferase reporter gene assay. RESULTS: Serum biochemical parameters, such as glucose and HOMA-IR index, were increased in HFD mice; miR-146b and SIRT1 were abnormally expressed in HFD mice and palmitic acid-treated HepG2 cells. Interestingly, berberine reduced body weight and caused a significant improvement in glucose tolerance and HOMA-IR index without altering food intake in mice. Overexpression of miR-146b abolished the protective effect of berberine on palmitic acid-induced impaired glycogen synthesis in HepG2 cells. Luciferase assay showed that miR-146b directly targeted SIRT1. CONCLUSION: The present findings suggest that berberine could attenuate hepatic insulin resistance through the miR-146b/SIRT1 pathway, which may represent a potential therapeutic target for the prevention and treatment of metabolic diseases, particularly diabetes.

The effects of bone metabolism in different methylprednisolone pulse treatments for Graves' ophthalmopathy.

The aim of the present study was to analyze the effects of methylprednisolone pulse therapy (MPPT) courses on bone metabolism in patients with Graves' ophthalmopathy (GO). A retrospective analysis of 45 patients with moderate-to-severe active GO who received 1 or 2 courses of MPPT was performed. Of these, 16 patients underwent 2 courses of treatment. Bone metabolic markers and the density of the lumbar spine (L1-4), femoral neck and total hip were measured using a dual-energy X-ray bone density instrument, and the differences in bone metabolism prior to and after treatment were determined for each group and compared. The results indicated that serum I collagen N-terminal peptide (P1NP) and serum ß-collagen crosslinked C-terminal peptide (CTX) were markedly decreased after the first pulse of treatment. In those patients who received a second course of MPPT, CTX levels were significantly decreased, but P1NP was not significantly different from the baseline value. CTX and P1NP levels remained unchanged between the first and second course of MPPT; similarly, there were no changes from baseline in 25(OH) vitamin D3 and bone mineral density after the first and second course of MPPT. However, the level of 25(OH) vitamin D3 was significantly elevated after the second course compared with the first course. In conclusion, the side effects of MPPT on bone metabolism were marginal and a second course of MPPT did not worsen bone metabolism. These MPPT regimens may therefore be considered to be a safe and effective treatment option for patients with moderate-to-severe active GO.

Gegen Qinlian Decoction Ameliorates Hepatic Insulin Resistance by Silent Information Regulator1 (SIRT1)-Dependent Deacetylation of Forkhead Box O1 (FOXO1).

BACKGROUND Gegen qinlian decoction (GGQLD) is a form of traditional Chinese medicine used for hundreds of years for its efficacy in treating diabetes. However, the mechanisms underlying the therapeutic effects of GGQLD on diabetes are still not clear. We aimed to evaluate the effect of GGQLD on hepatic insulin resistance (IR) through silent information regulator1 (SIRT1)/forkhead box O1 (FOXO1) in an IR mouse model. MATERIAL AND METHODS A high-fat diet (HFD) mouse model was established and GGQLD was administrated by oral gavage. Metabolic parameters were detected, including body weights, triglyceride, fasting glucose, fasting insulin and HOMA-IR index, glucose intolerance, and insulin resistance. HE-stained sections were used to observe the histopathology of liver tissue. For in vitro study, GGQLD-medicated serum was used to treat palmitic acid-stimulated HepG2 cells. The glycogen synthesis and downstream SIRT1/FOXO1 signaling pathways were examined. Specific siRNAs were used to knock down SIRT1 in HepG2 cells. RESULTS GGQLD administration significantly decreased body weights, triglyceride level, fasting glucose level, fasting insulin level, and HOMA-IR index, and improved IR in HFD mice. GGQLD enhanced SIRT1 expression and suppressed the expression of Ac-FOXO1 in liver tissues. Further, GGQLD-medicated serum promoted SIRT1 upregulation and suppressed Ac-FOXO1 levels in palmitate-stimulated HepG2 cells. GGQLD-medicated serum also increased the protein expression of PPARγ and reduced the expression of FABP4 in palmitate-stimulated HepG2 cells. CONCLUSIONS We found that GGQLD alleviates insulin resistance through SIRT1-dependent deacetylation of FOXO1.

Efficacy of Metformin for Benign Thyroid Nodules in Subjects With Insulin Resistance: A Systematic Review and Meta-Analysis.

Background: To evaluate the effect of metformin therapy on decreasing benign thyroid nodule volume in subjects with insulin resistance (IR). Method: Randomized controlled trials (RCTs) and self-controlled trials for the meta-analysis published, before January 31, 2018 were selected from the PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, National Knowledge Infrastructure, WANFANG and VIP Database. Pooled standard mean difference with 95% confidence interval was estimated by fixed- or random-effects model depending on heterogeneity. The risk of bias using the Cochrane Collaboration's tool was used to assess the quality of the RCTs contained. The quality of self-controlled studies was evaluated using the Methodological index for non-randomized studies (MINORS) method. Results: 7 studies (3 RCTs and 4 prospective self-controlled studies) with 240 patients were considered to be appropriate for the meta-analysis. The results of the meta-analysis indicated that the volume of thyroid nodule decreased significantly after metformin therapy (SMD -0.62, 95% CI -0.98 ~ -0.27). 6 studies reported the changes of the level of TSH. TSH levels decreased significantly after metformin therapy (SMD -0.27, 95% CI -0.47 ~ -0.07). The pooled data indicated an increase in FT3 level, and an unchanged FT4 level after metformin therapy (FT3, SMD 0.25, 95% CI 0.05 ~ 0.45; FT4, SMD -0.07, 95% CI -0.27 ~ 0.13). HOMA-IR levels decreased significantly after metformin therapy based on the pooled results of 3 RCTs and 3 prospective self-controlled studies (SMD -1.08, 95% CI -1.69 ~ -0.47). Conclusion: The meta-analysis demonstrated that metformin was safe and useful in shrinking benign thyroid nodules volume, improving thyroid function and IR. A large number of high-quality prospective studies still need to be carried out.

[Correlation Between Testosterone and Metabolic Index in Male Patients with Type 2 Diabetes Mellitus].

OBJECTIVE: To determine the effect of testosterone on serum glucose,lipid,uric acid and insulin metabolism in male patients with type 2 diabetes mellitus. METHODS: A total of 205 male patients with type 2 diabetes participated in this study. They were divided into two groups: those with normal testosterone (TT) (TT≥12 nmol/L,n=135) and those with low TT (TT<12 nmol/L,n=70). Their body mass,waist circumference (WC),body mass index (BMI),blood glucose, total cholesterol (TC), triglycerides (TG), serum uric acid (SUA),insulin,testosterone,luteinizing hormone (LH),follicle stimulating hormone (FSH),estradiol (E2),and sex hormone binding globulin (SHBG) were measured. The insulin resistance index (HOMA-IR) of the participants was calculated using a homeostasis model. Sex hormone levels were compared across the four groups divided by HOMA-IR and SUA in quartiles. RESULTS: The participants with low TT had higher age,SUA,BMI,WC,and HOMA-IR (P<0.05). TT and SHBG decreased with increased HOMA-IR index (P<0.05). TT,LH,FSH and SHBG decreased with increased SUA (P<0.05). The logistic regression model showed that SUA and BMI were predictors of hypogonadism. CONCLUSION: Male patients with type 2 diabetes who are prone to hypogonadism, are possibly related to increased SUA and obesity.

Association between Sex Hormone and Blood Uric Acid in Male Patients with Type 2 Diabetes.

The association between serum uric acid (SUA) level and sexual dysfunction in patients with diabetes is not well characterized. Type 2 diabetes mellitus (T2DM) causes metabolic disorders, including abnormal serum uric acid (SUA) levels. In this study, we enrolled 205 male patients with T2DM and investigated the relationship between sex hormone levels and SUA. Patients were divided into four groups based on SUA quartiles. On the other hand, based on the total testosterone (TT) level, patients were divided into three groups; SUA and other laboratory indices were determined. Increase in SUA level was significantly associated with decreased levels of TT, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, and increased levels of dehydroepiandrosterone, age, body mass index (BMI), waist circumference, glycated hemoglobin, serum creatinine, and HOMA-IR levels. SUA, waist circumference, BMI, and HOMA-IR showed a negative correlation with TT level, while age showed a positive correlation with TT level. SUA and body mass index were found to be risk factors for gonadal dysfunction. Therefore, we conclude that hypogonadism of male patients with T2DM is related to SUA level.

[Testosterone Undecanoate Pills improves insulin resistance in type-2 diabetes men with hypogonadism].

OBJECTIVE: To evaluate the effects of Testosterone Undecanoate Pills (TUP) on insulin resistance (IR) in type-2 diabetes men with hypogonadism. METHODS: We randomly divided 82 type-2 diabetes patients with hypogonadism into a treatment (n = 42) and a control group (n = 40), both maintaining their glucose- and lipid-reducing therapies, while the former treated orally with TUP in addition. After 6 months of medication, we compared the body mass index (BMI), waist circumference (WC), blood glucose level, HbA1c, lipid profile, IR index obtained by homeostatic model assessment (HOMA-IR), insulin sensitivity index (ISI), sex hormone levels, and sexual function scores between the two groups of patients. RESULTS: Compared with the baseline, the patients in the treatment group showed significant decreases after medication in BMI (ï¼»26.71 ± 2.39ï¼½ vs ï¼»25.15 ± 2.28ï¼½ kg/m2, P <0.05), WC (ï¼»89.96 ± 9.13ï¼½ vs ï¼»85.03 ± 9.58ï¼½ cm, P <0.05), HbA1C (ï¼»7.73 ± 1.31ï¼½ vs ï¼»7.01 ± 1.25ï¼½ %, P <0.05), and triglyeride (ï¼»1.97 ± 0.83ï¼½ vs ï¼»1.41 ± 0.69ï¼½ mmol/L, P <0.05), a markedly elevated level of total testosterone (ï¼»7.16 ± 2.21ï¼½ vs ï¼»14.22 ± 2.63ï¼½ nmol/L, P <0.05), and remarkable improvement in HOMA-IR (3.76 ± 1.18 vs 2.55 ± 1.03, P <0.05), ISI (96 ± 51 vs 138 ± 53, P <0.05) and total scores of the Aging Males' Symptoms (P <0.05). But no significant changes were observed in the scores of the International Index of Erectile Function (IIEF) after treatment (13.28 ± 6.38 vs 14.95 ± 6.08, P >0.05). CONCLUSIONS: TUP can significantly improve insulin resistance in type-2 diabetes men with hypogonadism.

Elevated serum gamma-glutamyltransferase predicts advanced histological liver damage in chronic hepatitis B.

Recently, several studies have demonstrated that serum gamma-glutamyltransferase (GGT) is associated with some diseases, such as chronic hepatitis B (CHB). This study investigates the association between GGT levels and liver pathological grading in patients with CHB. 300 patients with CHB who underwent liver biopsy were enrolled. Histological assessment was based on the Scheuer scoring system. Univariate and multivariate analyses were performed to evaluate the independent predicting factors for the presence of liver pathological grade in patients with CHB. In patients with CHB, the mean GGT level was 44.14±3.69 (U/L) in low activity group and 114.87±15.75 (U/L) in the high activity group (p<0.001). Also, there was significant difference between the low and high fibrosis group with regard to GGT levels [45.32±4.64 (U/L) vs. 90.41±11.06 (U/L), p<0.001, respectively]. The variables that were significant in the univariate analysis were evaluated in multivariate logistic regression analysis, and GGT was an independent predicting factor of necroinflammation and fibrosis (OR=1.007, 95%CI: 1.001-1.014, p=0.030; OR=1.009, 95%CI: 1.003-1.014, p=0.003, respectively). Results of this study suggest that GGT is a new non-invasive marker that can be used to predict advanced histological liver damage.

TLR4 polymorphisms associated with developing gastric pre-cancer lesions in a Chinese Han population.

Helicobacter pylori infection is a risk factor for gastric cancer. In addition, toll-like receptor 4 (TLR4) plays a fundamental role in pathogen recognition and activation of innate immunity. This study investigated the association of TLR4 polymorphisms with a risk of intestinal metaplasia (IM) and intraepithelial neoplasia (IN) in a Chinese Han population. This study analyzed TLR4 gene polymorphisms in 333 patients (IM, 193 cases; IN, 140 cases) and 312 atypia-free controls in a Chinese Han population using a Taqman allelic discrimination assay. The TLR4 single nucleotide polymorphisms +896A/G and +1196C/T were not associated with the risk of IM or IN. However, the single-locus analysis showed that the C allele of TLR4+2856T/C had significantly reduced risk of IM and IN [adjusted odds ratio (OR)=0.42; 95%CI=0.29-0.62 and OR=0.62; 95%CI=0.41-0.93, respectively] compared with the wild-type homozygote (TT). The frequencies of TLR4+2856T/C TC and T carrier were significantly lower in patients with Sydney's slight IM and low grade IN (P<0.01 and P=0.01, respectively), while the TC genotype showed a lower risk of moderate IM compared to healthy controls (P=0.045). In addition, the data revealed that H. pylori infection, heavy alcohol consumption and high salt uptake were associated with a higher susceptibility for developing this neoplasm. TLR4 rs10759932 TC and C carriers were associated with a lower risk in developing precancerous lesions in the stomach in a Chinese Han population.

Selenium supplementation for autoimmune thyroiditis: a systematic review and meta-analysis.

Many studies have reported that selenium (Se) has a close relationship with autoimmune thyroiditis (AIT). The therapeutic effect of Se supplementation in AIT treatment remains unclear. The objective of the present study was to determine the efficacy of Se supplementation for the treatment of AIT. A structured literature search was undertaken to identify all randomized controlled trials conducted in patients with AIT receiving Se supplementation or placebo. Nine studies enrolling a total of 787 patients were included. The results showed that Se supplementation with duration 6 months significantly dropped the TPOAb titers but did not decrease the TgAb titers. Patients assigned to Se supplementation for 12-month duration showed significantly lower TPOAb titers and TgAb titers. Patients after Se supplementation had a higher chance to improve the mood or well-being compared with controls. Se supplementation is associated with a significant decrease in TPOAb titers at 6 and 12 months; meanwhile, the TgAb titers can be dropped at 12 months. After Se supplementation treatment, patients had a higher chance to improve the mood without significant adverse events.

Association between ADIPOQ +45T>G polymorphism and type 2 diabetes: a systematic review and meta-analysis.

Recently, a number of studies have reported the association between the single nucleotide polymorphisms (SNPs) +45 T>G polymorphism in the adiponectin (ADIPOQ) gene and type 2 diabetes mellitus (T2DM) risk, though the results are inconsistent. In order to obtain a more precise estimation of the relationship, a meta-analysis was performed. In this current study, the Medline, Embase, Pubmed, ISI Web of Knowledge, Ovid, Science Citation Index Expanded Database, Wanfang Database, and China National Knowledge Infrastructure were searched for eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. Forty-five publications were included in the final meta-analysis with 9986 T2DM patients and 16,222 controls for ADIPOQ +45 T>G polymorphism according to our inclusion and exclusion criteria. The +45 T>G polymorphism was associated with an overall significantly increased risk of T2DM (G vs. T: OR = 1.18, 95% CI = 1.06-1.32; The dominant model: OR = 1.18, 95% CI = 1.03-1.33; The recessive model: OR = 1.47, 95% CI = 1.20-1.78; The homozygous model: OR = 1.62, 95% CI = 1.25-2.09; Except the heterozygous model: OR = 1.11, 95% CI = 0.98-1.24). Subgroup analysis revealed a significant association between the +45 T>G polymorphism and T2D in an Asian population. Thus, this meta-analysis indicates that the G allele of the ADIPOQ +45 T>G polymorphisms associated with a significantly increased risk of T2DM in the Asian population.

Association between cytotoxic T-lymphocyte-associated antigen 4 +49A/G polymorphism and persistent hepatitis B virus infection in the Asian population: evidence from the current studies.

AIMS: A number of studies assessed the association between cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) +49A/G polymorphism and persistent hepatitis B virus (HBV) infection risk. However, the results are quite contradictory. In order to obtain a more precise estimation of the relationship, a meta-analysis was performed. METHODS: Pubmed, ISI Web of Knowledge, HuGE Navigator, Wanfang Database, and China National Knowledge Infrastructure were searched. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the strength of this association. RESULTS: Six publications were included in the final meta-analysis with 1075 cases and 1321 controls for CTLA-4 +49A/G polymorphism according to our inclusion and exclusion criteria. We observed that the CTLA-4 +49A/G polymorphism was significantly correlated with chronic HBV infection risk (the homozygote codominant model: OR 1.67, 95% CI 1.30-2.15; the dominant model: OR 1.34, 95% CI 1.01-1.78; the recessive model: OR 1.56, 95% CI 1.24-1.96; the allele contrast model: OR 1.32, 95% CI 1.10-1.59). No publication bias was observed in this study according to Begg's funnel plot and Egger's test. CONCLUSION: CTLA-4 +49A/G polymorphism is assumed to confer a higher risk for persistent HBV infection in the Asian population.