Search

Compared with HLA-DQB1*05:02:01:01, the alleles HLA-DQB1*05:239 and HLA-DQB1*05:250 each show one single nucleotide substitution. This article is protected by copyright. All rights reserved.

Compared with HLA-A*24:02:01:01, the alleles HLA-A*24:02:129 and HLA-A*24:02:135 each show one nucleotide substitution, respectively.

The distributions of HLA allele and haplotype are various in the populations. Currently, the data for HLA alleles and haplotypes at three fields resolution level in Chinese Han population is rare. Here, the HLA alleles and haplotypes of the 1734 cord blood samples from Zhejiang Han population, China were reported at three fields resolution. All samples were randomly collected from the Zhejiang Cord Blood Bank, China. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci was genotyped using next generation sequencing method. The genotypes of the samples were assigned using the HLA TypeStream Visual Software version 1.2.0. The frequency of alleles, haplotype estimation and linkage disequilibrium analysis were performed with the Arlequin software 3.5.2.2. It was found that the top three frequent alleles of HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci were A*11:01:01 (25.81%), A*24:02:01 (16.70%), A*02:01:01 (10.61%); B*40:01:02 (15.97%), B*46:01:01 (11.48%), B*58:01:01 (7.96%); C*07:02:01 (19.03%), C*01:02:01 (17.65%), C*03:04:01 (10.41%); DRB1*09:01:02G (17.96%), DRB1*12:02:01 (9.57%), DRB1*08:03:02 (9.54%); DQB1*03:01:01G (21.05%), DQB1*03:03:02 (19.15%), DQB1*06:01:01G (12.08%); DRB4*01:03:01 (25.72%), DRB3*02:02:01 (20.27%), DRB5*01:01:01 (10.96%), respectively. A total of 1528 distinct A∼C∼B∼DRB3/4/5∼DRB1∼DQB1 haplotypes were estimated, and the top three most common haplotypes were A*33:03:01∼C*03:02:02∼B*58:01:01∼DRB3*02:02:01∼DRB1*03:01:01∼ DQB1*02:01:01 (4.02%), A*30:01:01∼C*06:02:01∼B*13:02:01∼DRB4*01:03:01∼ DRB1*07:01:01 ∼DQB1*02:02:01 (3.11%) and A*02:07:01∼C*01:02:01∼B*46:01:01 ∼DRB4*01:03:01∼DRB1*09:01:02G∼DQB1*03:03:02 (3.05%). Some alleles of different HLA loci were shown strong linkage disequilibrium. In conclusion, the data of allele and haplotype of HLA-A, -B, -C, -DRB1, -DQB1 and -DRB3/4/5 loci at three fields resolution level were obtained in Zhejiang Han population, thus contributing to analyze the HLA ploymorphism in the populations.

HLA-DRB1*09:40 differs from HLA-DRB1*09:01:02:01 by one nucleotide substitution at position 214(G>A).

OBJECTIVE: To make a retrospective analysis of the injuries of skiing population in a large ski resort in Chongli, China and provide a basis for predicting the rapidly increasing medical needs for ski injuries in the context of the 2022 Winter Olympic Games. METHODS: The basic data of all injured skiers who were treated in a medical station of a large ski resort in Chongli during the snow season from November 2017 to March 2018 and from November 2018 to March 2019 were collected. The number of skiers, the number of injuries, the causes of injuries, the types of injuries and the locations of injuries were compared. RESULTS: A total of 753 skiers were injured in two snow seasons, and the estimated average incidence of injury was 4.53 and 4.46 per 1 000 skier days at the resort respectively. The average daily injury rate per 1 000 skiers in November of the two snow seasons was relatively low, with 2.20 and 1.38 cases respectively. The difference of injury rate in different months might have little to do with snowfall and more to do with passenger flow. In both the snow seasons, men accounted for more injuries than women, and injured skiers aged between 21 and 30 accounted for the largest proportion, reaching 36.8%. The main causes of injuries were falls (76.6%). The highest rate of injury was in the head and neck (17.9%), followed by the knee (17.4%) and wrist and fingers (13.3%). The most common types of injuries were contusion and trauma (29.5%) and joint and/or ligament injuries (22.2%). Children (2-12 years old) accounted for 12.7% of all the injured skiers. The rate of moderate to severe injuries (including fractures, concussions, etc.) was 34.8% among the injured patients over 50 years of age. CONCLUSION: The snow resort should focus on injuries to children and elderly skiers and carry out targeted guidance and rescue work. In order to better ensure the medical safety of skiers, the ski resort medical station and nearby treatment hospitals should be equipped with a corresponding number of medical personnel and equipment, and the ski resort should further improve its safety management and rescue system.

HLA-DQB1*03:282N differs from HLA-DQB1*03:03:02:01 by a single nucleotide deletion at position 258.

The metabotropic glutamate receptor 2 (mGlu2) is a transmembrane-spanning class C G protein-coupled receptor that is an attractive therapeutic target for multiple psychiatric and neurological disorders. A key challenge has been deciphering the contribution of mGlu2 relative to other closely related mGlu receptors in mediating different physiological responses, which could be achieved through the utilization of subtype selective pharmacological tools. In this respect, allosteric modulators that recognize ligand-binding sites distinct from the endogenous neurotransmitter glutamate offer the promise of higher receptor-subtype selectivity. We hypothesized that mGlu2-selective positive allosteric modulators could be derivatized to generate bifunctional pharmacological tools. Here we developed clickable photoaffinity probes for mGlu2 based on two different positive allosteric modulator scaffolds that retained similar pharmacological activity to parent compounds. We demonstrate successful probe-dependent incorporation of a commercially available clickable fluorophore using bioorthogonal conjugation. Importantly, we also show the limitations of using these probes to assess in situ fluorescence of mGlu2 in intact cells where significant nonspecific membrane binding is evident.

The new allele HLA-B*13:109 differs from HLA-B*13:01:01:01 by one nucleotide substitution in exon 4.

Numerous positive and negative allosteric modulators (PAMs and NAMs) of Class C G protein-coupled receptors (GPCRs) have been developed as valuable preclinical pharmacological tools and therapeutic agents. While many Class C GPCR allosteric modulators have undergone subtype selectivity screening, most assay paradigms have failed to perform rigorous pharmacological assessment. Utilizing mGlu5 as a representative Class C GPCR, we tested the hypothesis that allosteric modulator selectivity was based on cooperativity rather than affinity. Specifically, we aimed to identify ligands that bound to mGlu5 but exhibited neutral cooperativity with mGlu5 agonists. We additionally evaluated the potential for these ligands to exhibit biased pharmacology. Radioligand binding, intracellular calcium (iCa2+) mobilization and inositol monophosphate (IP1) accumulation assays were undertaken in HEK293A cells expressing low levels of rat mGlu5 (HEK293A-mGlu5-low) for diverse allosteric chemotypes. Numerous "non-mGlu5" Class C GPCR allosteric modulators incompletely displaced allosteric mGlu5 radioligand [3H]methoxy-PEPy binding, consistent with a negative allosteric interaction. Affinity estimates for CPCCOEt (mGlu1 ligand), PHCCC (mGlu4 ligand), GS39783 (GABAB ligand), AZ012216052 (mGlu8 ligand), and CGP7930 (GABAB ligand) at mGlu5 were within 10-fold of their target receptor. The majority of Class C GPCR allosteric modulators had neutral cooperativity with both orthosteric and allosteric mGlu5 agonists in functional assays. However, NPS2143 (CaSR NAM), cinacalcet (CaSR PAM), CGP7930 and AZ012216052 were partial mGlu5 agonists for IP1 accumulation, but not iCa2+ mobilization. By employing mGlu5 as a model Class C GPCR, we find that for many Class C GPCR allosteric modulators, subtype selectivity is driven by cooperativity, and misinterpreted due to unappreciated bias.

Many studies have investigated the relationship between KIR, HLA and acute myeloid leukemia (AML), but the results were different in different laboratories, and the data in Chinese population were limited. In this study, the distribution of KIR gene, KIR genotypes, HLA-C groups, HLA-Bw4, and KIR-HLA interaction from 273 healthy participants and 253 AML patients (M0-M6) in southern Chinese Han were determined to investigate the relationships among KIR, HLA and AML. The results showed that the frequencies of 2DS4del in M5 patients were significantly higher than those of the controls (65.0% vs 46.5%, P=0.0104, OR=2.135, P

Three new HLA class I alleles were described in the Chinese population. HLA-B*46:68,-B*46:71,-B*46:72 alleles differ from HLA-B*46:01:01 by a single nucleotide substitution at position 485C>T, 484A>G, 299T>A respectively.

Allosteric modulators bind sites distinct from orthosteric ligands, allowing for improved spatiotemporal control of receptors and greater subtype selectivity. However, we recently showed that allosteric ligands previously classified as selective for select Class C G protein-coupled receptors (GPCRs) had unappreciated activity at other off-target receptors, in some cases higher affinity, within the class. Here, we extended our investigation of off-target activity of "selective" allosteric ligands for the sweet taste receptor. Using metabotropic glutamate receptor 5 (mGlu5 ) as a representative of Class C GPCR, we assessed the sweet protein, monellin and the small-molecule artificial sweetener, NHDC. We found that monellin, but not NHDC, is an agonist for mGlu5 . Radioligand binding and functional assays performed in cells expressing N-terminally truncated mGlu5 demonstrated that monellin agonism was not mediated via the "common" allosteric binding site in the transmembrane domain but required the presence of the large extracellular N-terminal domain of mGlu5 . Monellin displayed neutral functional cooperativity with orthosteric ligands. However, monellin positively modulated the mGlu5 PAM-agonist, VU0424465, activity in intracellular calcium assays, but the interaction was neutral in inositol phosphate accumulation assays. Furthermore, monellin mGlu5 agonism was positively modulated by the mGlu5 pure PAM, VU0360172. Taken together, these data indicate that monellin is an allosteric agonist for mGlu5 , binding to an allosteric binding site on the N-terminus that is functionally linked to the common Class C GPCR allosteric site in a biased manner. This is the first evidence of a naturally derived proteinaceous allosteric ligand for the mGlu receptor family.

HLA-A*31:124 differs from HLA-A*31:01:02:01 by a single-nucleotide substitution at position 491 C>G.

Based on the integration of existing programming languages and framework technologies, this paper designs and implements a Web-based situational plotting system. This system combines Web-oriented and map services, it uses Leaflet framework and SVG (Scalable Vector Graphics) technology design and implementation, classify the symbols and generate corresponding situational symbol frameworks, which can be extended to different areas such as emergency rescue, logistics coordination, communication planning, and realize the situational symbol mapping and editing, map browsing, and plotting Sample set saving and uploading functions have good real-time, cross-platform and interactive features. At the same time, aiming at the problem of generating linear plotting symbols, a plotting algorithm based on Centripetal Catmull–Rom curve is proposed, which avoids sharp angle and self-intersections in the process of plotting linear symbols. The experimental results prove that compared with the traditional curve plotting algorithm, the proposed algorithm has the characteristics of fewer control points and good fitting effects, which improves the plotting efficiency.

HLA-C*03:365 shows a substitution G to A at position 257 when compared to HLA-C*03:02:01.

Numerous positive and negative allosteric modulators (PAMs and NAMs) of class C G protein-coupled receptors (GPCRs) have been developed as valuable preclinical pharmacologic tools and therapeutic agents. Although many class C GPCR allosteric modulators have undergone subtype selectivity screening, most assay paradigms have failed to perform rigorous pharmacologic assessment. Using mGlu

Killer cell immunoglobulin like receptor (KIR) 3DS1 is one of the most important activating receptors and some studies revealed that KIR3DS1 combined with HLA ligand was not related to acute myeloid leukemia (AML), but rare data was reported in Chinese population. In this study, KIR3DS1 gene polymorphisms and HLA-Bw4 were investigated in 189 Chinese AML patients compared with 166 healthy individuals. The results showed that the distributions of KIR3DS1, Bw4, 3DS1/Bw4 and 3DS1/Bw4-80I were insignificantly different between AML and healthy individuals. This study suggests that the presence of 3DS1 and HLA-Bw4 ligands have no effect on AML disease.

HLA-B*52:42 is different from HLA-B*52:01:01:01 by a single nucleotide substitution at position 343G>C.

HLA-B*55:70 has one base substitution at position 199 C>T in exon 2 compared to HLA-B*55:02:01.

HLA-B*40:01:41 differs from HLA-B*40:01:01 by a single nucleotide substitution at position 195 GA.

HLA-C*01:109N differs from HLA-C*01:02:01 by a single nucleotide substitution at position 683 G > A.

HLA-B*13:98 differs from HLA-B*13:02:01 by a single nucleotide substitution at position 193 A>G.

HLA-A*02:07:06 shows 285 A>C and HLA-A*02:426 has 763 G>A change compared with HLA-A*02:07:01.

HLA-B*39:01:23 differs from HLA-B*39:01:01 by a single nucleotide substitution at position 153 CT.

To evaluate the influence of overweight/obesity on the incidence of hypertension among adults in China.The subjects of this prospective study were 13 739 Chinese adults aged 35-74 years recruited at the baseline surveys of China Multicenter Collaborative Study of Cardiovascular Disease Epidemiology and International Collaborative Study of Cardiovascular Disease in Asian. Baseline surveys were conducted in 1998 and during 2000-2001, respectively, and the follow-up was conducted during 2007-2008. According to the body mass index, the subjects were divided into four groups: underweight group(18.5 kg/m(2)), normal weight group(18.5-23.9 kg/m(2)), overweight group(24.0-27.9 kg/m(2))and obesity group(≥28.0 kg/m(2)). Age-standardized cumulative incidence of hypertension was calculated for each group, respectively. The relative risks(RRs)and 95% confidence intervals(CIs)for the incidence of hypertension of underweight, overweight and obesity groups were estimated by using generalized linear regression model with normal weight group as reference.During 8.1 years of follow-up, 4 271 hypertension cases were detected(2 012 in men and 2 259 in women). Age-standardized cumulative incidence of hypertension for the underweight, normal weight, overweight and obesity groups were 20.3%, 30.9%, 43.6% and 50.8% in men, respectively; and 22.9%, 30.4%, 41.1% and 50.8% in women, respectively. Compared with the normal weight group, multivariate-adjusted RR(95% CI)for the incidence of hypertension in underweight, overweight and obesity groups were 0.78(0.64-0.95), 1.22(1.13-1.30)and 1.28(1.16-1.42)in men, respectively; and 0.89(0.77-1.03), 1.16(1.09-1.23)and 1.28(1.18-1.38)in women, respectively. The overweight and obese subjects had higher risk for the incidence of hypertension, with the population attributable risk proportion of 7.4% in men and 8.8% in women, respectively.Overweight or obese people are at an increased risk of developing hypertension, thus prevention and control of overweight/obesity are needed to reduce hypertension incidence among adults in China.

HLA-DRB1*12:50 is different from HLA-DRB1*12:02:01 by a single nucleotide substitution at position 320 AC.

HLA-B*52:42 is different from HLA-B*52:01:01:01 by a single nucleotide substitution at position 343GC.

HLA-A*02:543 differ from HLA-A*02:12 by two nucleotide substitutions.

HLA-B*55:70 has one base substitution at position 199 CT in exon 2 compared to HLA-B*55:02:01.

HLA-A*03:181 and HLA-A*03:229 differ from HLA-A*03:01:01:01 by one and three nucleotide substitutions, respectively.

Both HLA-A*24:258 and HLA-A*24:305 differ from HLA-A*24:01:01:01 by single nucleotide substitutions.

HLA-B*15:326 has one base substitution at position 176GA in exon 2 compared with HLA-B*15:01:01:01.

HLA-B*13:83 differs from HLA-B*13:01:01 by 2 nucleotide substitutions at positions 103 and 106.

HLA-B*39:01:23 differs from HLA-B*39:01:01 by a single nucleotide substitution at position 153 C > T.

HLA-B*46:01:11 has 219 GA compared with HLA-B*46:01:01, and HLA-B*51:01:39 shows 561 GA with HLA-B*51:01:01.

HLA-A*02:07:06 shows 285 AC and HLA-A*02:426 has 763 GA change compared with HLA-A*02:07:01.

HLA*02:06:14 differs from HLA-A*02:06:01 by a single nucleotide substitution G > A at position 246.

HLA-A*33:97 has one base substitution at position 287 A>T in exon 2 compared to HLA-A*33:03:01.

HLA-DRB1*12:50 is different from HLA-DRB1*12:02:01 by a single nucleotide substitution at position 320 A>C.

HLA-A*03:181 and HLA-A*03:229 differ from HLA-A*03:01:01:01 by one and three nucleotide substitutions, respectively.

HLA-B*15:326 has one base substitution at position 176G>A in exon 2 compared with HLA-B*15:01:01:01.

Both HLA-A*24:258 and HLA-A*24:305 differ from HLA-A*24:01:01:01 by single nucleotide substitutions.

Allosteric modulators of G protein-coupled receptors have the potential to achieve greater receptor subtype selectivity compared with ligands targeting the orthosteric site of this receptor family. However, the high attrition rate in GPCR drug discovery programs has highlighted the need to better characterize lead compounds in terms of their allosteric action, as well as the signals they elicit. Recently, the use of label-free technologies has been proposed as an approach to overcome some limitations of endpoint-based assays and detect global changes in the ligand-stimulated cell. In this study, we assessed the ability of an impedance-based label-free technology, xCELLigence, to detect allosteric modulation in a neuronal cell line natively expressing rodent M4 muscarinic acetylcholine receptors. We were able to demonstrate that positive allosteric modulation of the endogenous M4 muscarinic acetylcholine receptor can be detected using this technology. Importantly, the allosteric parameters estimated from the label-free approach are comparable to those estimated from endpoint-based assays.

HLA-B*35:227 differs from HLA-B*35:01:01:01 by a single nucleotide substitution at position 746 C>T.

HLA-B*46:01:11 has 219 G>A compared with HLA-B*46:01:01, and HLA-B*51:01:39 shows 561 G>A with HLA-B*51:01:01.

HLA-B*39:01:01:03 allele differs from HLA-B*39:01:01:01 allele by a single nucleotide substitution.

The polymorphism of major histocompatibility complex class I chain-related gene B (MICB) and variations in MICB alleles in a variety of populations have been characterized using several genotyping approaches. In the present study, a novel polymerase chain reaction sequence-based typing (PCR-SBT) method was established for the genotyping of MICB exons 2-6, and the allelic frequency of MICB in the Zhejiang Han population was investigated. Among 400 unrelated healthy Han individuals from Zhejiang Province, China, a total of 20 MICB alleles were identified, of which MICB*005:02:01, MICB*002:01:01, and MICB*004:01:01 were the most predominant alleles, with frequencies of 0.57375, 0.1225, and 0.08375, respectively. Nine MICB alleles were detected on only one occasion, giving a frequency of 0.00125. Of the 118 distinct MICB ∼ HLA-B haplotypes identified, 42 showed significant linkage disequilibrium (P 0.05). Haplotypes MICB*005:02:01 ∼ B*46:01, MICB*005:02:01 ∼ B*40:01, and MICB*008 ∼ B*58:01 were the most common haplotypes, with frequencies of 0.0978, 0.0761, and 0.0616, respectively. Five novel alleles, MICB*005:07, MICB*005:08, MICB*027, MICB*028, and MICB*029 were identified. Compared with the MICB*005:02:01 sequence, a GA substitution was observed at nucleotide position 210 in MICB*005:07, and a 1,134 TC substitution in MICB*005:08 and an 862 GA substitution in MICB*027 were detected. In addition, it appears that MICB*028 probably arose from MICB*004:01:01 with an A to G substitution at position 1,147 in exon 6. MICB*029 had a GT transversion at nucleotide position 730 in exon 4, compared with that of MICB*002:01:01. On the basis of the new PCR-SBT assay, these observed results demonstrated MICB allelic variations in the Zhejiang Han population.

The clinical features of pituitary adenomas were retrospectively analyzed, focusing on the factors that contribute to the development of pituitary hemorrhage. Although many causes of pituitary adenoma hemorrhage have been identified, it is difficult to distinguish which conditions are truly causative. We determined the independent variables that contribute to pituitary hemorrhage in pituitary adenoma. Two hundred and eighty-eight consecutive patients diagnosed as pituitary adenoma were enrolled. These patients underwent tumor removal through endoscopic transsphenoidal approach. The subjects were divided into hemorrhagic and non-hemorrhagic groups, based on magnetic resonance images and histological findings. The predisposing factors were reviewed in the medical records for all patients. Univariate and multivariate analyses were performed to assess the relationships between variables of pituitary adenoma hemorrhage. We investigated 81 patients in whom hemorrhage from pituitary adenoma occurred. The incidence of pituitary hemorrhage was 28.1% (81/288). The predisposing factors surveyed for pituitary hemorrhage were significantly associated with macroadenoma, non-functional adenomas, anticoagulation therapy, end-stage renal disease, dopamine agonist treatment, and underlying malignant disease (all P0.05). Sex, age, hypertension, diabetes mellitus, and previous radiation therapy were not related to pituitary hemorrhage. In this pooled cohort, the predisposing factors of pituitary adenoma characteristic for pituitary hemorrhage were macroadenoma and non-functional adenoma. Patients who received dopamine agonist and anticoagulation therapy are implicated as precipitating factors. Underlying end-stage renal disease and malignant disease are also factors that contribute to pituitary adenoma hemorrhage.

Background We aimed to assess the value of induction chemotherapy with cisplatin and fluorouracil plus docetaxel (TPF) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods We did an open-label phase 3 multicentre randomised controlled trial at ten institutions in China. Patients with stage III–IVB (except T3–4N0, UICC/AJCC 7th edition) NPC were randomly assigned to receive induction chemotherapy plus CCRT (investigational group) or CCRT alone (control group). Patients in both groups received cisplatin 100 mg/m 2 every 3 weeks for three cycles, concurrently with intensity-modulated radiotherapy (IMRT). The investigational group received docetaxel (60 mg/m 2 on day 1), cisplatin (60 mg/m 2 on day 1), and fluorouracil (600 mg/m 2 per day by continuous intravenous infusion on days 1–5) every 3 weeks for three cycles before CCRT. Our primary endpoint was failure-free survival (FFS), and the sample size was 476 patients (238 per treatment group). This trial is registered with ClinicalTrials.gov, NCT01245959. Findings 241 patients were assigned to the investigational group and 239 to the control group. After a median follow-up of 18.6 months (range 0.8–34 months), the estimated 2-year FFS was 82.2% in the investigational group and 75.5% in the control group (hazard ratio [HR] = 0.61, 95% confidence interval [CI] 0.39–0.97, p = 0.04). The estimated 2-year distant failure-free survival (D-FFS) was 91.3% in the investigational group and 81.7% in the control group (HR = 0.51, 95% CI 0.28–0.91, p = 0.02). No significant differences in overall survival and locoregional failure-free survival were observed between the two arms. The rates of grade 3–4 neutropenia, diarrhoea, and stomatitis during induction chemotherapy were 35.1%, 7.1%, and 6.3%, respectively. Interpretation The preliminary results suggested that compared with CCRT alone, induction chemotherapy with TPF could significantly improve FFS and D-FFS in locoregionally advanced NPC. Long-term follow-up is needed to establish an eventual efficacy of TPF induction chemotherapy.