The clinical phenotype and gene analysis of syndromic deafness with PTPN11 gene mutation / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical phenotype and screen the genetic mutations of hereditary deafness in three deaf families to clarify their molecular biology etiology. Methods: From January 2019 to January 2020, three deaf children and family members were collected for medical history, physical examination, audiology evaluation, electrocardiogram and cardiac color Doppler ultrasound, temporal bone CT examination, and peripheral blood DNA was obtained for high-throughput sequencing of deafness genes. Sanger sequencing was performed to verify the variant sites among family members. The pathogenicity of the variants was evaluated according to the American College of Medical Genetics and Genomics. Results: The probands in the three families had deafness phenotypes. In family 1, proband had multiple lentigines, special facial features, growth retardation, pectus carinatum, abnormal skin elasticity, cryptorchidism and other manifestations. In family 2, proband had special facial features, growth retardation and abnormal heart, and the proband in family 3 had growth retardation and abnormal electrocardiogram. Genetic testing of three families detected three heterozygous mutations in the PTPN11 gene: c.1391G>C (p.Gly464Ala), c.1510A>G (p.Met504Val), c.1502G>A (p.Arg501Lys). All three sites were missense mutations, and the mutation sites were highly conserved among multiple homologous species. Based on clinical manifestations and genetic test results, proband 1 was diagnosed with multiple lentigines Noonan syndrome, and probands 2 and 3 were diagnosed with Noonan syndrome. Conclusion: Missense mutations in the PTPN11 gene may be the cause of the disease in the three deaf families. This study enriches the clinical phenotype and mutation spectrum of the PTPN11 gene in the Chinese population.

Study on quality grade standard of premature Forsythia suspensa / 中国药房

OBJECTIVE To study the quality grade stand ard of the premature Forsythia suspensa . METHODS A total of 138 batches of premature F. suspensa were collected from the main producing areas of F. suspensa in China. According to 2020 edition of Chinese Pharmacopoeia ，the contents of impurities ，moisture，ethanol-soluble extract ，volatile oil ，forsythin and forsythoside A in the premature F. suspense were determined ，and the qualified samples were screened. AHP-PCA mixed weighting method was used to give comprehensive weight to the indicators （except for the limit of impurity ）. The comprehensive score of the samples was calculated. The suggestions on the quality grade division of premature F. suspensa were put forward according to cluster analysis of K-mean value. RESULTS & CONCLUSIONS The contents of impurities ，moisture，ethanol-soluble extract ，volatile oil ，forsythin and forsythoside A in the premature F. suspense were 0-7.80％，1.60％-8.18％，13.13％-61.60％，0.21％-3.47％，0.02％-2.15％ and 0.79％-14.04％，respectively；average contents of them were 1.24％，4.97％，34.88％，2.01％，0.42％，6.86％，respectively. Totally 47 batches of 138 batches were qualified in all indexes. It is suggested that the quality grade of the premature F. suspense can be divided into three grades ：in first grade of F. suspense ，the contents of volatile oil ，forsythin，forsythoside A ， ethanol-soluble extract and moisture were ≥2.40％，≥0.59％，≥8.34％，≥38.66％ and ≤4.99％，respectively；in second grade of F. suspense ，the contents of above indicators were ≥2.26％，≥0.41％，≥7.47％，≥32.58％ and ≤5.33％，respectively；in third grade of F. suspense ，the contents of above indicators were ≥2.15％，≥0.32％，≥4.60％，≥31.52％ and≤7.23％，respectively.

Effects of multicomponent training on nutritional status and muscle function in frail elderly adults / 中国实用护理杂志

Objective:To investigate the effect of multicomponent training on nutritional status and muscle function in older adults with frailty syndrome.Methods:A total of 120 elderly patients with frailty syndrome of Elderly Diagnosis and Treatment and Physical Examination Center,Jiangsu Provincial People′s Hospital from June 2018 to December 2019 were randomly divided into observation group and control group, each contained 60 cases. The control group received routine nursing care. On the basis of these, the observation group was given multicomponent training. The nutritional status, frailty status and muscle function were compared between two groups before and after 12 weeks of intervention.Results:Before intervention, there was no significant difference in the nutritional status, degree of frailty and muscle function between the two groups ( P>0.05). After intervention, the protein, skeletal muscle and total plasma protein, serum albumin, serum prealbumin and transferrin were (7.55 ± 1.34) kg, (21.37 ± 2.41) kg, (61.97 ± 5.69) g/L, (229.05 ± 17.67)mg/L, (42.14 ± 4.83) g/L, (2 364.29 ± 296.31) mg/L in the observation group, significantly higher than those in the control group (6.92 ± 0.97) kg, (20.31 ± 2.04) kg, (57.96 ± 5.22) g/L, (210.15 ± 27.99) mg/L, (37.66 ± 5.75) g/L, (2 247.42 ± 267.39) mg/L, the differences were statistically significant ( t values were 2.19-4.47, P<0.05). After intervention, the scores of physical, psychological and total frailty were 6.03 ± 0.71, 2.46 ± 0.73, 9.63 ± 0.99 in the observation group, significantly higher than in the control group (6.45 ± 0.95) pionts, (2.71 ± 0.52) pionts, (10.34 ± 1.20) pionts, the differences were statistically significant ( t=2.67, 2.02, 3.39, P<0.05). After intervention, the side-by-side, full-tandem, 4-m walk, repeated chair stands scores and total Short Physical Performance Battery (SPPB) scores were (0.87 ± 0.28) pionts, (1.65 ± 0.29) pionts, (2.09 ± 0.47) pionts, (1.93 ± 0.49) pionts, (7.36 ± 0.75) pionts, those socres were (0.72 ± 0.31) pionts, (1.50 ± 0.31) pionts, (1.87 ± 0.61) pionts, (1.70 ± 0.62) pionts, (6.55 ± 0.89) pionts in the control group, the differences were statistically significant ( t values were 2.16-5.18, P<0.05). Conclusions:Multicomponent training can improve the nutritional status and muscle function and delay the progress of frailty in elderly in elderly patients.

The predictive potential of genetic single nucleotide polymorphisms in CBX4 for hepatocellular carcinoma survival.

Background: Our previous studies have reported that polycomb chromobox 4 (CBX4) has a potential promoting hepatocellular carcinoma (HCC) angiogenesis and tumor progression. However, it is unclear whether genetic single-nucleotide polymorphisms (SNPs) in this gene are associated with HCC prognosis. Methods: We conducted a hospital-based two-phase study, including 598 patients with pathologically diagnosed HCC for the SNPs screening phase and 328 HCC patients for clinic significance validating phase, to elucidate the association between SNPs of CBX4 and the survival of HCC. The genotypes of CBX4 were tested using the SNaPshot method and the effects of CBX4 SNPs on HCC prognosis were analyzed using Kaplan-Meier survival model and Cox regression model. Results: A total of 33 SNPs were selected and genotyped in this study. We found the rs77447679 SNP was significantly related to survival in individuals with HCC. Specifically, survival was noticeably decreased in HCC patients who have mutant homozygote AA of this SNP (rs77447679-AA) compared with these with wild type (rs77447679-CC). An additive effect of rs77447679 polymorphism and aflatoxin B1 exposure level was also observed in the survival analyses of HCC cases. Furthermore, this SNP was positively correlated not only with tumor size, grade, stage, and microvessel density (correlation coefficient r = 0.17, 0.23, 0.23, and 0.42, respectively), but also with increasing CBX4 expression (r = 0.57). Interestingly, the mutant genotypes of rs77447679 can significantly improve the therapeutic response of HCC cases on post-operative adjuvant transarterial chemoembolization (pa-TACE), but wild type not. Conclusions: These data suggest that genetic polymorphisms in the CBX4 may be a prognostic biomarker for HCC, and the rs77447679 SNP is such a potential candidate.

Advance of Energy Metabolism in Post-stroke Fatigue (review) / 中国康复理论与实践

Physical fatigue often appears after stroke, which may influence rehabilitation training and recovery. This paper introduced the causes, clinical manifestations and related factors of physical fatigue after stroke. Energy metabolism increases after stroke, which may play a role in physical fatigue after stroke, and can be managed in some ways. It is needed to research the application of energy metabolism measure in physical fatigue after stroke further.

Single-nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case-control study.

Previous studies have shown that single-nucleotide polymorphisms (SNPs) of a disintegrin and metalloproteinase with thrombospondin type 1 motif 4 (ADAMTS4) may involve in the pathogenesis of some diseases. However, it is not clear whether they are associated with hepatocellular carcinoma (HCC). A hospital-based case-control study, including 862 cases with HCC and 1120 controls, was conducted to assess the effects of 258 SNPs in the coding regions of ADAMTS4 on HCC risk and prognosis. We found that six SNPs in ADAMTS4 were differential distribution between cases and controls via the primary screening analyses; however, only rs538321148 and rs1014509103 polymorphisms were further identified to modify the risk of HCC (odds ratio: 2.73 and 2.95; 95% confidence interval, 2.28-3.29 and 2.43-3.58; P-value, 5.73 × 10-27 and 1.36 × 10-27 , respectively). Significant interaction between these two SNPs and two known causes of hepatitis B virus and aflatoxin B1 were also observed. Furthermore, rs538321148 and rs1014509103 polymorphisms were associated not only with clinicopathological features of tumor such as tumor stage and grade, microvessel density, and vessel metastasis, but with poor overall survival. Additionally, these SNPs significantly downregulated ADATMS4 expression in tumor tissues. These data suggest that SNPs in the coding region of ADAMTS4, such as rs538321148 and rs1014509103, may be potential biomarkers for predicting HCC risk and prognosis.

Global and Chinese perspectives on adolescent health and development / 中国学校卫生

Abstract@#Through a review of the current state and risks of adolescent health in the world and in China, the main health issues faced by adolescents are summarized. The importance of promoting adolescent health and the importance of effective adolescent health services are highlighted. The past 30 years important documents of international adolescent health and development have been sorted out. The history of the development of adolescent health care in China has been reviewed. It was pointed out that the health and development of adolescents has become a hot spot and focus of international attention, and it has received more and more attention in China. The adolescent health care has ushered in a new opportunity for development, which will help the health and development of adolescents in China.

Micro RNA-4651 Serves as a Potential Biomarker for Prognosis When Selecting Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial Chemoembolization Therapy.

Our previous reports have shown that microRNA-4651 is a potential early diagnostic and prognostic marker for hepatocellular carcinoma. We aimed to investigate whether microRNA-4651 modified postoperative adjuvant transarterial chemoembolization (pa-TACE) to improve the prognosis of hepatocellular carcinoma. A hospital-based retrospective study, including 302 patients with advanced-stage hepatocellular carcinoma who received tumor resection or tumor resection plus pa-TACE as an initial therapy, was conducted to assess the effects of microRNA-4651 on pa-TACE treatment. MicroRNA-4651 expression in tumor tissues was tested using the TaqMan-PCR technique. The sensitivity of tumor cells to doxorubicin (an anticancer drug used in pa-TACE procedure) was analyzed by the half-maximal inhibitory concentration (IC50). Upregulated microRNA-4651 expression in tumor tissues can improve the therapeutic response of patients with hepatocellular carcinoma on pa-TACE (hazard ratios [95% confidence intervals] = 0.32 [0.22-0.46] for death risk and 0.39 [0.28-0.56] for tumor-recurrence risk, respectively), but downregulated expression cannot. Functional analyses-displayed microRNA-4651 mimics decreased while its inhibitor increased the IC50 of tumor cells to doxorubicin (0.65 [0.61-0.69] versus 2.17 [1.98-2.37] µM). Cytochrome P450 2W1 was shown as a possible target of microRNA-4651. Additionally, dysregulation of microRNA-4651 also affected the clinical pathological features of hepatocellular carcinoma and was an independent prognostic factor for this cancer. Conclusion: These results indicate that increasing microRNA-4651 expression may be beneficial for pa-TACE in improving hepatocellular carcinoma prognosis.

Genetic polymorphisms in ataxin-3 and liver cirrhosis risk related to aflatoxin B1.

BACKGROUND: Altered expression of ataxin-3 (AT3) can modify DNA repair capacity and is observed in human diseases. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related liver cirrhosis (LC) have not yet been elucidated. MATERIALS AND METHODS: We conducted a hospital-based case-control study, including 384 patients with LC and 851 controls without any liver diseases, to assess the association between 264 polymorphisms in AT3 and AFB1-related LC risk. Genotype were tested using TaqMan-PCR or sequencing technique. RESULTS: We found three differentially distributed SNPs (rs8021276, rs7158733, and rs10146249) via the screening analysis; however, only rs8021276 polymorphism was further identified to modify the risk of LC. Compared with the homozygote of rs8021276 A alleles (rs8021276-AA), the genotypes of rs8021276 G alleles (rs8021276-AG or -GG) increased LC risk (OR: 2.48 and 6.98; 95% CI: 1.84-3.33 and 4.35-11.22, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Additionally, rs8021276 polymorphism was also associated with down-regulation of AT3 mRNA expression and increasing AFB1-DNA adducts in liver tissues with cirrhosis. CONCLUSIONS: These results suggest AT3 polymorphisms may be risk biomarkers of AFB1-related LC, and rs8021276 is a potential candidate.

Prognostic significance of XRCC4 expression in hepatocellular carcinoma.

BACKGROUND: Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. MATERIALS AND METHODS: We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50). RESULTS: XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin. CONCLUSIONS: These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma.

Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1.

BACKGROUND: The serum microRNAs have been reported as potential biomarkers for hepatitis virus-related hepatocellular carcinoma (HCC); however, their role in aflatoxin B1 (AFB1)-related HCC to has not yet been evaluated. MATERIALS AND METHODS: We conducted a case-control study, including 366 HCC cases and 662 controls without any evidence of tumors, to identify and assess diagnostic and prognostic potential of serum microRNAs for AFB1-related HCC. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to elucidate diagnostic performance, and to compare the microRNAs with α-fetoprotein (AFP) at a cutoff of 20 ng/mL (AFP20) and 400 ng/mL (AFP400). RESULTS: We found 8 differentially expressed microRNAs via the microRNA array analysis; however, only microRNA-4651 was further identified to detect AFB1-positive HCC but not AFB1-negative HCC. For AFB1-positive HCC, microRNA-4651 showed higher accuracy and sensitivity than AFP400 (AUC, 0.85 vs. 0.72; Sensitivity, 78.1% vs. 43.0%). Compared to AFP20, microRNA-4651 exhibited higher potential in identifying small-size (0.68 vs. 0.84 for AUC and 36.7% vs. 75.5% for sensitivity, respectively) and early-stage HCC (0.69 vs. 0.84 for AUC and 38.7% vs. 75.7% for sensitivity, respectively). Additionally, miR-4651 was also associated with HCC prognosis (hazard risk value, 2.67 for overall survival and 3.62 for tumor recurrence analysis). CONCLUSIONS: These data suggest that serum microRNA-4651 may be a useful marker for HCC diagnosis and prognosis, especially AFB1-positive cases.

Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma.

Our recent investigation has shown that the variables of microRNA-1268a may involve in hepatocellular carcinoma (HCC) tumorigenesis. Here, we attempted to identify the prognostic significance of microRNA-1268a expression in tumor tissues by a retrospective analysis in 411 patients with HCC, and analyze its effects on post-operative adjuvant transarterial chemoembolization (TACE) improving HCC prognosis. All cases received tumor resection or tumor resection plus post-operative adjuvant TACE as an initial treatment. Logistical regression analysis exhibited that microRNA-1268a expression was significantly correlated with tumor stage, tumor grade, tumor size, and microvessel density. Cox regression analysis showed that microRNA-1268a expression was an independent prognostic factor for HCC, and TACE treatment had no effects on prognosis of HCC patients with high microRNA-1268a expression. More intriguingly, TACE improved the prognosis of HCC patients with low microRNA-1268a expression. Functionally, overexpression of microRNA-1268a inhibited while its inhibitor enhanced doxorubicin-induced the death of cancer cells. These results suggest that microRNA-1268a may be an independent prognostic factor for HCC patients, and that decreasing microRNA-1268a expression may be beneficial for post-operative adjuvant TACE treatment in HCC.

Spautin-1 Ameliorates Acute Pancreatitis via Inhibiting Impaired Autophagy and Alleviating Calcium Overload.

Acute pancreatitis is characterized by zymogen pre-activation. Severe inflammation caused by zymogen activation can eventually lead to multiple organ dysfunctions, which contributes to the high mortality rate of severe acute pancreatitis. However, there is no specific treatment available for acute pancreatitis therapy. Here, we show that spautin-1, which effectively inhibits autophagy flux, ameliorated the pathogenesis of acute pancreatitis induced by cerulein or L-Arginine. CaMKII phosphorylation due to cytosolic calcium oeverload was revealed in this paper. It was also demonstrated that autophagic protein aggregates degradation blockade accompanying with impaired autophagy correlated positively to intra acinar cells digestive aymogen activation sitimulated by cerulein or L-Arginine. The role of spautin-1 in ameliorating acute pancreatitis was shown here to be associated with impaired autophagy inhibition and Ca2+ overload alleviation. We provided a promising therapy for acute pancreatitis here through targeting both impaired autophagy and increased cytosolic calcium.

Polymorphisms of a Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 and Aflatoxin B1-Related Hepatocellular Carcinoma.

BACKGROUND: Altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is observed in hepatocellular carcinoma. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related hepatocellular carcinoma have not yet been elucidated. METHODS: We conducted a hospital-based case-control study, including 1,706 hepatocellular carcinoma cases and 2,270 controls without any liver diseases or tumors, to assess the association between 74 polymorphisms in ADAMTS5 and AFB1-related hepatocellular carcinoma risk and prognosis. Genotype, mRNA levels, and TP53 gene mutation (TP53M) related to AFB1 exposure were tested using TaqMan-PCR or sequencing technique. ADAMTS5 protein level and microvessel density were analyzed by IHC. RESULTS: Among these 74 polymorphisms, only rs2830581 affected hepatocellular carcinoma risk. Compared with the homozygote of rs2830581 G alleles (rs2830581-GG), the genotypes of rs2830581 A alleles (rs2830581-GA or -AA) increased hepatocellular carcinoma risk (OR: 1.85 and 4.40; 95% CI: 1.57-2.19 and 3.43-5.64, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Furthermore, the rs2830581 polymorphism modified the tumor recurrence-free survival and overall survival of patients. This polymorphism not only affected pathologic features of hepatocellular carcinoma such as tumor dedifferentiation and microvessel density, but also modified ADAMTS5 expression and the effects of transarterial chemoembolization treatment on hepatocellular carcinoma. CONCLUSIONS: These results suggest ADAMTS5 polymorphisms may be risk and prognostic biomarkers of AFB1-related hepatocellular carcinoma, and rs2830581 is a potential candidate. IMPACT: Our findings support the hypothesis that ADAMTS5 rs2830581 polymorphism modifies AFB1-related hepatocellular carcinoma risk and prognosis.

Polymorphisms in the precursor microRNAs and aflatoxin B1-related hepatocellular carcinoma.

The altered expression of some microRNAs (miRNAs) is observed in hepatocellular carcinoma (HCC); however, the genetic polymorphisms in the precursor miRNAs (pre-miRNAs) in aflatoxin B1 (AFB1)-related HCC have not yet been investigated. A hospital-based case-control study, including 1,706 HCC cases and 2,270 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area of China to assess the relationship between 48 polymorphisms in the pre-miRNAs and AFB1-related HCC risk and prognosis. Among 48 polymorphisms, only rs28599926 (in the miRNA 1268a) affected HCC risk. Compared with the homozygote of rs28599926C alleles (rs28599926-CC), the genotypes of rs28599926 T alleles (namely rs28599926-CT or -TT) increased HCC risk (odds ratio [OR]: 1.63 and 5.52, 95% confidence interval [CI]: 1.40-1.90 and 4.27-7.14, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. This polymorphism was associated not only with larger tumor size, higher portal vein tumor risk, and tumor dedifferentiation, but also with higher AFB1 adducts levels and increasing the mutation risk of TP53 gene. Furthermore, rs28599926 modified the tumor recurrence-free survival (hazard ratio [HR]: 2.86, 95% CI: 2.36-3.43) and overall survival (HR: 2.12, 95% CI: 1.86-2.41) of cases. Additionally, one target of miR-1268a was show to be the ADAMTS4 mRNA and rs28599926 polymorphism might modify ADAMTS4 expression. These findings indicate that polymorphisms in the pre-miRNAs may be risk and prognostic biomarkers of AFB1-related HCC, and rs28599926 in miR-1268a is such a potential candidate. © 2015 Wiley Periodicals, Inc.

CD4+CD25+ cells in multiple myeloma related renal impairment.

CD4(+)CD25(+) cells are critical regulators in almost all of the animal models of human organ-specific autoimmune diseases, transplant rejection and allergic diseases. We aimed to explore the role of CD4(+)CD25(+) cells in the pathogenesis of multiple myeloma (MM) related renal impairment (RI). Thirty patients with MM related RI and 30 healthy volunteers were studied. The number of CD4(+)CD25(+) cells was examined by flow cytometry. Clinical and laboratory data were collected from each subject. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4 and IL-6 were analyzed by ELISA. CD4(+)CD25(+) cells significantly decreased in MM related RI patients compared to the controls (P<0.05). CD4(+)CD25(+) cell number was negatively associated with blood urea nitrogen (BUN), supernatant IL-4, serum IL-6, monoclonal immunoglobulin and ß2-microglobulin, as well as bone marrow plasma cell percentage and proteinuria; whereas positively associated with estimated glomerular filtration rate (eGFR) (all P < 0.05). CD4(+)CD25(+) cells gradually decreased as the Clinic Stage increased. The number of CD4(+)CD25(+) cells reduced in MM related RI patients, and was correlated with disease severity. CD4(+)CD25(+) cells may play an important role in the pathogenesis of MM related RI.

A review of life quality in living donors after liver transplantation.

Living-donor liver transplantation (LDLT) has increasingly performed all around the world. However, LDLT donors achieve no medical benefits and are exposed to the risk of complications, and even death. The potential effects of LDLT on donor safety, donor recovery, and post-donation psychological impairment are essential to be better understood. We searched the MEDLINE database to identify articles about the quality of life (QOL) in adults after LDLT donation. Twenty-eight studies with a total of 1944 donors were included in the review. 14 of the 28 studies (50%) had a cross-sectional design, and the remaining half had a prospective design. The Physical Component Score (PCS) decreased immediately after the donation, then returned to the baseline within 6 to 12 months while the Mental Component Score (MCS) remains comparable to that of normative population throughout the procedure. Compared with the left graft (LG) donors, right graft (RG) donors were significantly older, had longer hospital stays and higher rates of postoperative complications, and a higher recipient mortality rate, while there were no difference in the PCS and MCS between the two groups. Our review clearly indicates that the LDLT donors can endure the donation procedure and return to their normal daily life without major problem in the short term. However, to improve the donor selection criteria and ensure the QOL in donors throughout donation procedure, more studies with longer follow up and larger samples are essential and predictors of poor QOL should be identified in study with sufficient response rate and ideal control groups.

XPC codon 939 polymorphism is associated with susceptibility to DNA damage induced by aflatoxin B1 exposure.

Aflatoxin B1 (AFB1), resulting in the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-repairing genotypes may experience an increased risk of genotoxicity. This study was aimed to investigate whether DNA repair gene xerodermapigmentosum complementation group C codon 939 polymorphism (rs2228001) affected the levels of AFB1-DNA adducts in Guangxi Population (n = 2558), from an AFB1-exposure area. AFB1-DNA adducts were measured by ELISA, and XPC codon 939 genotypes were identified by TaqMan-PCR. We found that longer AFB1-exposure years significantly increased XPC genotypes with codon 939 Gln alleles (namely, XPC-LG and -GG, odds ratios [95% confidence intervals] were 1.37 (1.15-1.63) and 1.99 (1.55-2.55), respectively) was significantly associated with higher levels of AFB1-DNA adducts. Furthermore, there was a positive joint effect between XPC genotypes and long-year AFB1 exposure in the formation of AFB1-DNA adducts. These results suggest that individuals with susceptible genotypes XPC-LG and -GG may experience an increased risk of DNA damage elicited by AFB1 exposure.

Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B.

UNLABELLED: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71) ≤ Pmeta ≤ 9.92 × 10(-7) ). CONCLUSION: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease.