Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study.

BACKGROUND: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. METHODS: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. RESULTS: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. CONCLUSIONS: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. CLINICAL TRIALS REGISTATION: NCT01401400.

Exonuclease I and III improve the detection efficacy of hepatitis B virus covalently closed circular DNA.

BACKGROUND: Hepatitis B virus covalently closed circular DNA (HBV cccDNA) is an important biomarker of hepatitis B virus infection. However, the current methods are not specific and sensitive. The present study aimed to develop a specific and sensitive assay method for the quantification of HBV cccDNA. METHODS: Exonuclease I (Exo I) & Exonuclease III (Exo III) and specific primer probes are used in real-time PCR. The virus particles isolated from peripheral blood mononuclear cells were used as negative control and HBV1.3 recombinant plasmid 3.2 kb circular DNA fragment was used as positive control. The methods of cccDNA detection were evaluated in cell lines, plasmid, animal model, patient serum and liver biopsies. RESULTS: A linear range of 101-107 copies/assay using specific primers for HBV cccDNA was established. HBV cccDNA were only detected in cell lines, animal model and liver tissue. It cannot be detected in serum samples. Intrahepatic HBV cccDNA level had good correlation with intrahepatic total HBV DNA level (r = 0.765, P < 0.001). CONCLUSIONS: The real-time quantitative PCR is an effective and feasible method for sensitive and specific detection of low copy number of cccDNA. The novel detection method is fast, provides high sensitivity and specificity and can be used in clinical practice.

Dibromidobis{1-[4-(pyridin-4-yl)phen-yl]ethanone-κN}mercury(II).

In the title compound, [HgBr(2)(C(13)H(11)NO)(2)], the Hg(II) atom adopts a four-coordinated HgN(2)Br(2) geometry, formed by two pyridine N atoms from two ligands and two bromide anions. The complex is located on a twofold axis. The coordination geometry is close to forming a see-saw (SS-4) polyhedron, the symmetry-related organic ligands being almost perpendicular; the dihedral angles between the two pyridine rings and between the two benzene rings are 85.5 (4) and 87.7 (4)°, respectively. Within the organic ligand, the pyridine ring is nearly coplanar with the benzene ring [dihedral angle = 13.1 (8)°]. In the crystal, the mol-ecular complexes are connected through weak inter-molecular C-H⋯Br contacts.

Efficacy and safety of moxibustion for benign prostatic hyperplasia: A protocol of systematic review and meta-analysis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate gland that is common in older men. The clinical manifestations of BPH are frequent urination, urgency, incomplete dribbling of urine, and urinary retention. Moxibustion, as a convenient, safe and effective method, has been widely applied in the clinical treatment of BPH. The study aim to assess the efficacy and safety of moxibustion for BPH. METHODS: The following electronic databases will be searched regardless of language and publication status: Pubmed, MEDLINE, EMBASE, China Biomedical Database, China National Knowledge Infrastructure, VIP Database, and Wanfang Database, to select studies that meet the requirements. The study will consist of a prospective randomised controlled clinical trials (RCTs) of moxibustion in the treatment of BPH, language of publication does not have barrier of blinding or restrictions, adverse events will be assessed and reported for safety assessment. Two reviewers will independently conduct and screen all included studies and the meta-analysis will be performed with RevMan V5.3. RESULTS: The study will provide a high-quality convincing assessment of efficacy and safety of moxibustion for BPH. CONCLUSION: The conclusion of this study will provide the latest evidence for judging whether moxibustion is effective and safe in the treatment of BPH. TRIAL REGISTRATION NUMBER: INPLASY2021120021.

[Relationship between Early Treatment Response and Prognosis in Children with Acute Lymphoblastic Leukemia].

OBJECTIVE: To analyze the relationship between the early treatment response and the pregnosis in children with acute lymphoblastic leukemia(ALL). METHODS: Two hundred and Seventy-eight ALL children diagnosed and treated in Hainan general hospital from March 2013 to March 2017 were collected. All ALL children received therapy with CCLg-ALL-2008 regimen. The 3 year event-free survival (EFS) rate of ALL children in different groups was analyzed in terms of 4 indexes including sensitivity response to prednison at day 8 (D8-SRP), bone marrow remission at day 15 (D15-BMR) and at day 33 (D33-BMR), and minimal residual disease at day 33 (D33-BMR), and minimal residual disease at day 33(D33-MRD). These 4 indexes and other indexes possibly affecting the prognosis of ALL children were enrolled in Cox regression model for analysis of independent factors affecting the prognosis of ALL children. RESULTS: The D8-SRP test showed that among 269 ALL children, 240(89.22%) cases displayed prednisone poor response (PPR); the 3-year EFS rate in predrisone good response(PGR) group was significantly higher than that in PPR group(P<0.05). The D15-BMR detection showed that among 262 ALL children, the bone marrow remission(BMR) as M1 was observed in 230 cases (87.79%), M2 in 20 cases (7.63%) and M3 in 9 cases (4.58%); the 3-year EFS rate showed as follows:M1 group >M2 group >M3 group(P<0.05). The D33-BMR detection showed that among 257 ALL children, the BMR as M1 was observed in 227 cases (88.33%), M2 in 21 cses(8.17%) and M3 in 9 caes (3.51%); the 3-year EFS rate in 3 groups showed as follows: M1 group >M2 group >M3 group(P<0.05). The D33-MRD detection showed that among 185 ALL children, MRD<10-10 was found in 128 cases (69.19%), MRD≥10-4-10-2 in 43 cases (23.24%), MRD ≥10-2 in 14 cases (7.57%); the 3-year EFS rate in 3 groups showed as follows: MRD <10-4 group > MRD≥ 10-4-10-2 group>MRD≥10-2 group. The Cox regression analysis showed that PPR in D8-SRP test, M2 and M3 in D15 and D33 BMR detection, and MRD≥10-2 in D33 MRD detection as well as T-ALL typing were independent risk factors affecting the prognosis of ALL children. CONCLUSION: The early treatment response can predict the prognosis of ALL children, which is an independent prognostic factor for ALL children.

Aberrant DNA methylation of P16, MGMT, hMLH1 and hMSH2 genes in combination with the MTHFR C677T genetic polymorphism in gastric cancer.

Associations of P16, MGMT, hMLH1 and hMLH2 with gastric cancer and their relation with MTHFR status in gastric patients who were confirmed with pathological diagnosis were assessed. Aberrant DNA methylation of P16, MGMT, hMLH1 and hMLH2 and polymorphisms of MTHFR C677T were assayed. The proportional DNA hypermethylation in P16, MGMT, hMLH1 and hMLH2 in cancer tissues was significantly higher than in remote normal-appearing tissues. DNA hypermethylation of P16 and MGMT was correlated with the T and N stages. Individuals with homozygotes (TT) of MTHFR C677T had significant risk of hypermethylation of MGMT in cancer tissues [OR (95% CI)= 3.47(1.41-7.93)]. However, we did not find association between polymorphism in MTHFR C677T and risk of hypermethylation in P16, MGMT, hMLH1 and hMLH2 genes either in cancer or remote normal-appearing tissues. Aberrant hypermethylation of P16, MGMT, hMLH1 and hMLH2 could be predictive of gastric cancer.

[Treatment of proximal tibial multi-segment comminuted fractures with closed reduction and less invasive stabilization systems].

OBJECTIVE: To explore the clinical effects of closed reduction and less invasive stablization system for the treatment of proximal tibial multi-segment comminuted fractures, and to discuss the influence of LISS on reduction and bone union. METHODS: From 2003.7 to 2007.12, 19 patients with proximal tibial multi-segment comminuted fractures were treated with closed reduction and LISS fixation. Fourteen patients were male, 5 patients were female, ranging in age from 21 to 49 years, with an average of 39.2 years. Fifteen patients were injured with direct violence, 4 indirect violence. The reasons of the injuries were vehicle crashes for 14 cases and falling from high places for 3 cases and falling to the ground for 2 cases. All the patients were followed up postoperatively. Callus formation and bony union were recorded by X-ray. RESULTS: All the patients were followed up for a period averaged 12.2 months (ranged 8 to 21 months). No failure of fixation and nonunion. No deformation of plates and screws occurred in patients,no superficial wound infection. According to the criteria of Merchan, 14 patients got an excellent result, 3 good, and 2 poor. CONCLUSION: Closed reduction and less invasive stabilization systems can provide rigid internal fixation for proximal tibial multi-segment comminuted fractures. The LISS provides stable fixation, a high rate of union, and a low rate of infection for proximal tibial multi-segment comminuted fractures.