Causal relationships between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers: univariable and multivariable Mendelian randomization.

PURPOSE: Coffee intake and apolipoprotein B levels have been linked to gastric, colorectal, and esophageal cancers in numerous recent studies. However, whether these associations are all causal remains unestablished. This study aimed to assess the potential causal associations of apolipoprotein B and coffee intake with the risk of gastric, colorectal, and esophageal cancers using Mendelian randomization analysis. METHODS: In this study, we utilized a two-sample Mendelian randomization analysis to access the causal effects of coffee intake and apolipoprotein B on gastric, colorectal, and esophageal cancers. The summary statistics of coffee intake (n = 428,860) and apolipoprotein B (n = 439,214) were obtained from the UK Biobank. In addition, the summary statistics of gastric cancer, colorectal cancer, and esophageal cancer were obtained from the FinnGen biobank (n = 218,792). Inverse variance weighted, MR-Egger, weighted median, and weighted mode were applied to examine the causal relationship between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. Steiger filtering and bidirectional mendelian randomization analysis were performed to evaluate the possible reverse causality. RESULTS: The result of the inverse variance weighted method indicated that apolipoprotein B levels were significantly associated with a higher risk of gastric cancer (OR = 1.392, 95% CI 1.027-1.889, P = 0.0333) and colorectal cancer (OR = 1.188, 95% CI 1.001-1.411, P = 0.0491). Furthermore, multivariable Mendelian randomization analysis also revealed a positive association between apolipoprotein B levels and colorectal cancer risk, but the effect of apolipoprotein B on gastric cancer risk disappeared after adjustment of coffee intake, body mass index or lipid-related traits. However, we did not discover any conclusive evidence linking coffee intake to gastric, colorectal, or esophageal cancers. CONCLUSIONS: This study suggested a causal association between genetically increased apolipoprotein B levels and higher risk of colorectal cancer. No causal relationship was observed between coffee intake and gastric, colorectal, or esophageal cancers.

Homeodomain protein DLX4 facilitates nasopharyngeal carcinoma progression via up-regulation of YB-1.

Nasopharyngeal carcinoma (NPC) is a malignant tumor in nasopharynx tissues and lacks effective treatment strategies. Dysregulation of distal-less homeobox 4 (DLX4) participates in the development of tumors. Understanding the regulatory mechanism of DLX4 in NPC progression may address this issue. Here, we first identified an up-regulation of DLX4 in NPC cell lines compared to normal epithelial cells. Data from colony formation and transwell assays showed that knockdown of DLX4 inhibited cell proliferation and invasion of NPC, respectively. Moreover, DLX4 knockdown blocked the cell cycle of NPC at G1 phase, suggesting the antitumor effect of DLX4 knockdown on NPC. The downstream target of DLX4 was identified as Y-box binding protein 1 (YB-1), whose expression was increased by over-expression of DLX4, while decreased by knockdown of DLX4. The binding capacity between DLX4 and YB-1 was verified by chromatin immunoprecipitation (ChIP), and the result showed that DLX4 could not directly bind to the promoter of YB-1. Mechanically, YB-1 over-expression reversed the effects of DLX4 knockdown on cell proliferation, cell cycle arrest and cell invasion of NPC. In conclusion, our findings indicated that DLX4 promoted NPC progression via up-regulation of YB-1, which would shed light on therapeutic schedule in NPC.

MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway.

MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.

Changes in Markers of Mineral and Bone Disorders and Mortality in Incident Hemodialysis Patients.

BACKGROUND: Abnormalities in mineral and bone disorder (MBD) markers are common in patients with chronic kidney disease. However, previous studies have not accounted for their changes over time, and it is unclear whether these changes are associated with survival. METHODS: We examined the association of change in MBD markers (serum phosphorus (Phos), albumin-corrected calcium (Ca(Alb)), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP)) during the first 6 months of hemodialysis (HD) with all-cause mortality across baseline MBD strata using survival models adjusted for clinical characteristics and laboratory measurements in 102,754 incident HD patients treated in a large dialysis organization between 2007 and 2011. RESULTS: Across all MBD markers (Phos, Ca(Alb), iPTH and ALP), among patients whose baseline MBD levels were higher than the reference range, increase in MBD levels was associated with higher mortality (reference group: MBD level within reference range at baseline and no change at 6 months follow-up). Conversely, decrease in Phos and iPTH, among baseline Phos and iPTH levels lower than the reference range, respectively, were associated with higher mortality. An increase in ALP was associated with higher mortality across baseline strata of ALP ≥80 U/l. However, patients with baseline ALP <80 U/l trended towards a lower risk of mortality irrespective of the direction of change at 6 months follow-up. CONCLUSIONS: There is a differential association between changes in MBD markers with mortality across varying baseline levels in HD patients. Further study is needed to determine if consideration of both baseline and longitudinal changes in the management of MBD derangements improves outcomes in this population.

Lean Body Mass and Survival in Hemodialysis Patients and the Roles of Race and Ethnicity.

BACKGROUND: Lean body mass (LBM) represents the "fat-free" muscle mass in hemodialysis (HD) patients and is an important nutritional measure. Previous studies have found that both higher LBM and body mass index (BMI) were related to greater survival in HD patients. Additional studies have shown differences in survival across racial-ethnic groups of HD patients. However, the association of LBM and mortality across racial-ethnic subgroups has not been examined. OBJECTIVE: We hypothesize that racial differences in LBM affect the mortality in HD patients. SETTING AND SUBJECTS: Chronic HD patients from a large dialysis organization in the United States. PREDICTORS: Estimated LBM (eLBM), self-identified racial subgroups. MAIN OUTCOME MEASURE: 5-year survival. STUDY DESIGN: We examined the association between baseline eLBM and survival using Cox proportional hazard models adjusted for demographics, comorbidities, and laboratory measures. Associations were examined across subgroups of race-ethnicity (non-Hispanic white, African American, and Hispanic) and BMI. RESULTS: The final cohort included 117,683 HD patients, who were 62 ± 15 (mean ± standard deviation) years old, 43% women and 59% with diabetes mellitus. Higher eLBM was linearly associated with lower mortality. Compared with the reference group (48.4-<50.5 kg), patients with the lowest eLBM (<41.3 kg) had a 1.4-fold higher risk of mortality (hazard ratio: 1.37; 95% confidence interval: 1.30-1.44) in the fully adjusted model. A similar linear association was seen among patients with BMI < 35 kg/m(2) and in non-Hispanic whites and African American subgroups. However, higher eLBM was not associated with improved survival in Hispanic patients or patients with BMI ≥ 35 kg/m(2). LIMITATION: Potential residual confounding. CONCLUSIONS: Higher eLBM is associated with a lower mortality risk in HD patients, especially among non-Hispanic white and African American groups. Hispanic patients do not demonstrate a similar inverse relationship. The association between LBM and mortality among different racial groups of HD patients deserves additional study.

Mechanism of ELL-associated factor 2 and vasohibin 1 regulating invasion, migration, and angiogenesis in colorectal cancer.

BACKGROUND: As a novel endogenous anti-angiogenic molecule, vasohibin 1 (VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer (CRC). Knockdown of VASH1 enhanced transforming growth factor-ß1 (TGF-ß1)/Smad3 pathway activity and type I/III collagen production. Our previous findings suggest that ELL-associated factor 2 (EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3 (STAT3)/TGF-ß1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-ß1 related pathway in CRC has not been elucidated. AIM: To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro. METHODS: We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection. RESULTS: Our findings indicated that EAF2 was down-regulated and VASH1 was up-regulated in advanced CRC tissue compared to normal colorectal tissue. Kaplan-Meier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-ß1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells. CONCLUSION: This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cell-derived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-ß1 pathway.

Regulatory mechanisms and therapeutic implications of insulin-like growth factor 2 mRNA-binding proteins, the emerging crucial m6A regulators of tumors.

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) serve essential biological functions as post-transcriptional performers, participating in the acquisition or maintenance of tumor hallmarks due to their distinct protein structures. Emerging evidence indicates that IGF2BPs belong to the class III type of RNA N6-methyladenosine (m6A) modification readers, controlling RNA stability, storage, localization, metabolism, and translation in multiple vital bioprocesses, particularly tumorigenesis and tumor progression. Here, we discuss the underlying regulatory mechanisms and pathological functions of IGF2BPs which act as m6A readers in the context of tumor pathogenesis and multidrug resistance. Furthermore, we highlight the potential of IGF2BPs as drug targets in clinical tumor treatment. Hence, precise and novel tumor therapeutic approaches could be uncovered by targeting epigenetic heterogeneity.

Clinical and prognostic significance of expression of phosphoglycerate mutase family member 5 and Parkin in advanced colorectal cancer.

BACKGROUND: Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer (CRC) cells. Phosphoglycerate mutase family member 5 (PGAM5) activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy. However, there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients. AIM: To assess the clinical significance of PGAM5 and Parkin proteins, as biomarkers for diagnosis and prognosis of CRC, by studying their expression in advanced CRC tissues and their association with clinicopathological parameters. METHODS: The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry. Each case was evaluated by using a combined scoring method based on signal intensity staining (scored 0-3) and the proportion of positively stained cancer cells (scored 0-4). The final staining score was calculated as the intensity score multiplied by the proportion score. Specimens were categorized as either high or low expression according to the Youden index, and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained. Additionally, we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues. RESULTS: Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues: PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells. PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues. Moreover, reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis. CONCLUSION: The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers. Parkin may be a potential marker for the survival of CRC patients.

LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the ß-catenin pathway.

LIM domain only 3 (LMO3) interacts with transcription factors to regulate target genes involved in embryonic development. The oncogenic role of LMO3 in hepatocellular carcinoma, gastric cancer, and neuroblastoma has been reported recently. However, little is known about the biological function of LMO3 in papillary thyroid carcinoma (PTC). First, expression of LMO3 was dramatically enhanced in the PTC tissues and cell lines. Second, knockdown of LMO3 in PTC cells repressed cell proliferation and promoted cell apoptosis with downregulated Bcl-2 and upregulated cleaved caspase-3/PARP. In vitro cell migration and invasion of PTC were also retarded by siRNA-mediated silence of LMO3. Third, protein expression of LIM kinase (LIMK) 1-mediated phosphorylation of cofilin and nuclear translocation of ß-catenin were reduced by the knockdown of LMO3. pcDNA-mediated overexpression of LIMK1 promoted cofilin phosphorylation and attenuated LMO3 silence-induced decrease of cofilin phosphorylation. Last, enhanced LIMK1 expression promoted PTC cell proliferation and metastasis and counteracted the suppressive effects of LMO3 silence on PTC cell proliferation and metastasis. In conclusion, LMO3 promoted PTC cell proliferation and metastasis by regulating LIMK1-mediated cofilin and the ß-catenin pathway.

RBMS1 promotes gastric cancer metastasis through autocrine IL-6/JAK2/STAT3 signaling.

Metastasis is the most important reason for the poor prognosis of gastric cancer (GC) patients, and the mechanism urgently needs to be clarified. Here, we explored a prognostic model for the estimation of tumor-associated mortality in GC patients and revealed the RNA-binding protein RBMS1 as a candidate promoter gene for GC metastasis by analyzing GOBO and Oncomine high-throughput sequencing datasets for 408 GC patients. Additionally, RBMS1 was observed with overexpression in 85 GC patient clinical specimens by IHC staining and further be verified its role in GC metastasis via inducing EMT process both in in vitro and in vivo experiments. Moreover, we identified that IL-6 was predicted to be one of the most significant upstream cytokines in the RBMS1 overexpression gene set based on the Ingenuity Pathway Analysis (IPA) algorithm. Most importantly, we also revealed that RBMS1 could promote migration and invasion through IL6 transactivation and JAK2/STAT3 downstream signaling pathway activation by influencing histone modification in the promoter regions after binding with the transcription factor MYC in the HGC-27 and SGC-7901 GC cell lines. Hence, we shed light on the potential molecular mechanisms of RBMS1 in the promotion of GC metastasis, which suggests that RBMS1 may be a potential therapeutic target for GC patients.

Overexpression of ELL-associated factor 2 suppresses invasion, migration, and angiogenesis in colorectal cancer.

BACKGROUND: The androgen responsive gene, ELL-associated factor 2 (EAF2), expressed in benign prostate tissues, has been shown to play an important role in tumor suppression in a variety of malignant tumors. In addition, some scholars found that EAF2 frameshift mutations are associated with intratumor heterogeneity in colorectal cancer (CRC) and inactivation of EAF2 in microsatellite instability-high CRC. However, the molecular mechanism by which EAF2 is involved in CRC invasion and metastasis remains unclear. AIM: To determine the clinical value of expression of EAF2 protein in CRC, and to study the effects of EAF2 on the invasion, migration, and angiogenesis of CRC cells in vitro. METHODS: In this study, we collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein in patients with advanced CRC. Subsequently, we investigated the effect of EAF2 on the invasion, migration, and angiogenesis of CRC cells in vitro using plasmid transfection. RESULTS: EAF2 protein was lowly expressed in cancer tissues of patients with advanced CRC. Kaplan-Meier survival analysis showed that the survival rate of the high EAF2 level group was higher than that of the low EAF2 level group. CONCLUSION: Our results demonstrated that EAF2, as a tumor suppressor, may inhibit the invasion, metastasis, and angiogenesis of CRC cells by regulating the signal transducer and activator of transcription 3/transforming growth factor-ß1 crosstalk pathway, and play a cancer suppressive and protective role in the occurrence and development of CRC. Our findings are of great significance to provide a new idea and theoretical basis for the targeted diagnosis and treatment of CRC.

Impaired TGF-beta signalling enhances peritoneal inflammation induced by E. coli in rats.

BACKGROUND: Peritonitis is a common and severe complication of peritoneal dialysis (PD). Although TGF-beta is a key mediator in peritoneal fibrosis with chronic PD, its role in acute peritoneal inflammation remains unclear. METHODS: Potential role of TGF-beta signalling in acute peritonitis was investigated in a rat model by infecting peritoneum with E. coli and in primary culture of peritoneal mesothelial cells (PMC) by LPS. RESULTS: We found that a single infection of E. coli caused an acute, but transient peritonitis by a significant increase in ascites white blood cells (WBC), peritoneal CD45+ leukocytes, upregulation of TNFalpha, activation of NF-kappaB/p65 and impaired peritoneal function (all P < 0.01). Interestingly, spontaneous recovery of acute peritonitis occurred with upregulation of TGF-beta1 and activation of Smad2/3, suggesting a protective role of TGF-beta signalling in acute peritonitis. This was demonstrated by the finding that blockade of the TGF-beta signalling pathway with gene transfer of Smad7 inactivated peritoneal Smad2/3 but worsened E. coli-induced, NF-kappaB-dependent peritoneal inflammation and peritoneal dysfunction (all P < 0.01). Furthermore, studies in vitro also found that impaired TGF-beta signalling by overexpressing Smad7 in PMC were able to overcome the inhibitory effect of TGF-beta on LPS-induced, NF-kappaB-mediated peritoneal inflammation. CONCLUSION: Results from this study demonstrate that TGF-beta signalling is essential in protection against acute peritoneal inflammation induced by bacterial infection.

Renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion: an adult case report and literature review.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion is a rare and independent subtype of RCC included in the classification of MiT (microphthalmia-associated transcriptional factor) family translocation RCC. Herein, we report an adult case of Xp11.2 translocation RCC, and review the relevant literature to improve our understanding of the pathogenesis, epidemiology, clinical manifestations, diagnosis, differential diagnosis, treatment, and other aspects of the disease.

Autophagy modulation in bladder cancer development and treatment (Review).

Bladder cancer (BC) is a potentially life­threatening malignancy. Due to a high recurrence rate, frequent surveillance strategies and intravesical drug therapies, BC is considered one of the most expensive tumors to treat. As a fundamental evolutionary catabolic process, autophagy plays an important role in the maintenance of cellular environmental homeostasis by degrading and recycling damaged cytoplasmic components, including macromolecules and organelles. Scientific studies in the last two decades have shown that autophagy acts as a double­edged sword with regard to the treatment of cancer. On one hand, autophagy inhibition is able to increase the sensitivity of cancer cells to treatment, a process known as protective autophagy. On the other hand, autophagy overactivation may lead to cell death, referred to as autophagic cell death, similar to apoptosis. Therefore, it is essential to identify the role of autophagy in cancer cells in order to develop novel therapeutic agents. In addition, autophagy may potentially become a novel therapeutic target in human diseases. In this review, the current knowledge on autophagy modulation in BC development and treatment is summarized.

[Estimating genetic distance and phylogenetic tree of HPA-1-3, 5, and 15 in different populations].

According to the human platelet alloantigens (HPA) polymorphisms in five systems, the distributions of HPA-1 -3, 5, and 15 systems in 1 000 Chinese donors were carried out by using a polymerase chain reaction with sequence-specific primers (PCR-SSP) method. The genetic distance and phylogenetic tree between Chinese Hans and other populations were estimated by using DISPAN and PHYLIP software. As presented by the phylogenetic tree, Asian had a convergence with European first, and grouped together with African. Beninese which came from Africa was on the top of dendrogram. Indian was located between Asian and European. Brazilian was converged with other Europe populations. Oceanian Polynexiya had been shown specifically to cluster with Asia populations. These results proved the "out of Africa theory" from one side, and it also confirmed that early migration of Asian is from south to southeast, and east Asia., thus it is probable that Europeans are migrated from south to north, and west Europe. As genetic distance was estimated effectively by HPA systems, HPA systems could serve as the genetic marker in human migration and evolution research.

Submucosal Tunneling Endoscopic Resection for Large and Irregular Submucosal Tumors Originating from Muscularis Propria Layer in Upper Gastrointestinal Tract.

BACKGROUND: The majority of submucosal tumors (SMTs) are benign. However, large SMTs with irregular outer shapes are proved to harbor a higher risk for malignancy. Submucosal tunneling endoscopic resection (STER) has emerged as a feasible technique for resecting SMTs. OBJECTIVE: To evaluate the safety and efficacy of STER for large and irregular SMTs with a diameter no <35 mm originating from the muscularis propria layer, and to share the technical skills of STER for complete and en bloc resection. PATIENTS AND METHODS: We retrospectively reported 10 cases in which the new technique of STER was performed to remove large and irregular SMTs with a diameter no <35 mm of upper gastrointestinal tract in our hospital between April 2014 and April 2017. RESULTS: All 10 (100%) patients underwent STER successfully, with a mean operation time of 156 minutes. Among the 10 SMTs, 3 (30%) were located in the esophagus, 7 (70%) were in the cardia. All the SMTs had a maximum diameter no <35 mm, ranging from 35 to 100 mm. The mean size was 57.2 mm. En bloc resection was achieved in 8 (80%) of the tumors. Only two (20%) of the SMTs were resected into more than one piece. Complication occurred in 1 (10%) of the patients as a representation of pneumothorax. No recurrence was noted during a median follow-up of 15 months. CONCLUSION: In this retrospective study, STER may be an effective and safe technique resecting large and irregular SMTs with a diameter no >40 mm in transverse diameter and no >100 mm in longitudinal diameter.

[Polymorphism of the human platelet alloantigens HPA-3 and HPA-9w in the Chinese Han population].

OBJECTIVE: To study the polymorphism of human platelet alloantigens HPA-3 and HPA-9w in the Chinese Han population. METHODS: A total of 1000 unrelated Chinese Han blood donors from different provinces of China were genotyped for HPA-3 and HPA-9w using PCR-sequence specific primer assay. RESULTS: Gene frequencies of 1000 Chinese Hans for HPA-3a and HPA-3b were 0.5935 and 0.4065 respectively, and all of them were HPA-9a positive. The distributions of HPA-3, HPA-9w of Chinese Hans which detected by chi-square criterion fit Hardy-Weinberg equilibrium. There were significant differences of the HPA-3 alleles gene frequency between Guangdong province and other five investigated provinces which included Shanxi, Heilongjiang, Zhejiang, Yunnan and Jiangsu. In comparison to other ethnic groups, no significant differences were observed in the distributions of HPA-3 except the Vietnamese and Australian. CONCLUSION: The results show that the chance of HPA-3 incompatibility were 0.3661 in random transfusion, and also provide a basis for researching on alloimmune thrombocytopenia and HPA-matched transfusion.

[Case report of a rare platelet-specific antigen HPA-10bw allele found in Chinese mainland].

A total of 1,000 Chinese blood donors were typed for human platelet antigens (HPA) using a sequence specific primers -polymerase chain reaction (PCR-SSP) based HPA genotyping method. An individual with a rare HPA-10w(a+b+) genotype was found. In order to confirm the typing results, a fragment of HPA-10 gene was amplified by PCR and then sequenced. Sequencing data showed that a single G to A substitution at nucleotide 263 occurred, resulting in amino acid change from Arg(CGA) to Gln(CAA) at position 62 of GPa protein. The substitution generated antigenic specificity HPA-10bw. The detection of an HPA-10bw allele in the Chinese population suggests that this rare allele should be considered in platelet alloimmunization, such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion thrombocytopenic purpura (PTP) and post-transfusion refractoriness to platelets (PTR).

Curative effects of interferon-alpha and HLA-DRB1 -DQA1 and -DQB1 alleles in chronic viral hepatitis B.

AIM: To investigate the association between curative effects of interferon-alpha and partial human leucocyte antigen (HLA) II alleles in chronic viral hepatitis B. METHODS: Sixty patients with chronic viral hepatitis B in Shanghai were treated with a standard course of treatment with interferon-alpha for 6 mo. HLA-DRB1, -DQA1, and -DQB1 alleles were detected by polymerase chain reaction-sequence specific primer (PCR-SSP) method. RESULTS: Frequencies of HLA-DRB1*04 (P<0.025) and HLA-DQA1*0303 (P<0.01) in non-responders were significantly higher than those in partial and complete responders. Frequencies of HLA-DQA1*0505 (P<0.025) and HLA-DQB1*0301 (P<0.005) in partial and complete responders were significantly higher than those in non-responders. CONCLUSION: Non-response to interferon-alpha therapy is positively correlated with HLA-DRB1*04 and HLA-DQA1*0303, and negatively correlated with HLA-DQA1*0505 and -DQB1*0301 in patient with chronic viral hepatitis B. HLA II genes of the identification alleles provide a method for evaluating outcome of interferon-alpha treatment.

[Study on HLA haplotypes in Jiangsu-Zhejiang-Shanghai Han population].

This study is to investigate HLA haplotypes in Jiangsu-Zhejiang-Shanghai Han population based on 166 families by serological and molecular biological HLA typing methods and to analyze the distribution characteristic of HLA haplotypes. The results showed that allele frequencies of more than 10% for HLA antigens were A2, A11, A24, B13, B46, B60, DRB1 *04, DRB1 *08, DRB1* 09, DRB1 * 12 and DRB1 * 15. In the analysis of HLA haplotypes, 128 kinds of A-B haplotypes and 182 kinds of B-DRB1 haplotypes were found, comprising 19.28% (128/664) and 27.41%(182/664) of total theoretical haplotypes, respectively. 18 kinds of A-B haplotypes and 23 kinds of B-DRB1 haplotypes occurred at frequencies of more than 0.5% (linkage disequilibrium value, delta > 0) .351 kinds of A-B-DRB1 haplotypes were found, comprising 52.86% (351/664) of total theoretical haplotypes, and 8 kinds of A-B-DRB1 haplotypes occurred at frequencies of more than 0.5% (delta > 0). The common A-B-DRB1 haplotypes were A30-B13-DRB1 * 07(4.22%), A2-B46-DRB1 * 09(3.77%), A33-B58-DRB1 * 17(3.01%), A33-B58-DRB1 * 13.1 (1.81%) and A11-B75-DRB1 * 12(1.51%). The HLA haplotype distribution of Jiangsu-Zhejiang-Shanghai Han population has its own genetic characteristics, so it suggests this population is between southern and northern Han population. The HLA polymorphism of Chinese Han population is more abundant in East Asian populations.