[Objective] To study the inter-allelic recombination event occurring in the HLA-B locus, and to evaluate the molecular genetic mechanisms of a novel HLA allele, predict and analyze the impact of its amino acid residue changes on the three-dimensional structure. [Methods] HLA typing was taken with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) by Luminex. Sequence-based typing (SBT) and gene clone were used to analyze exons 1-4 sequences of HLA-B allele. In order to determine the exact site of inter-allelic recombination event occurring in the HLA-B locus, sequences of the HLA-B alleles were compared with the IMGT/HLA database by the program “Alignment”. After homology modeling using the Swiss-Model software, the three-dimensional structure of the molecules was simulated using the Swiss Pdb Viewer software, and the FATCAT online software was used to compare the differences in the three-dimensional structures of the molecules. [Results] HLA typing indicated the PCR-SSOP pattern did not match with any known HLA-B alleles, suspected to be a new HLA allele. The genetic clone sequencing results showed HLA-B alleles of the proband were B^*13∶02 and a novel allele. The HLA-B exon2 nucleotide sequence of the novel allele was different from any other known alleles. The novel allele has 12 nucleotides replaced when compared with the closest matching B^*35∶01∶01∶01 allele from c.259 to c.299, which result in 8 amino acids changes. The sequence was identical in B^*35∶01∶01∶01 in exon 1, exon 3, exon 4, intron 1, intron 2, intron 3 and at c.74 to c.258 in exon 2, and c.259 to c.343 sequence in exon 2 was identical in B^*46∶01∶01 by blast search. The structure of the mutant alleles was similar to that of B^*35∶01∶01∶01 and B^*46∶01∶01, and the local hydrogen bonds of amino acids p.63-p.79 were changed at the recombination site. [Conclusion] This study demonstrates a rare inter-allelic recombination event occurring in the HLA-B locus. It has been officially designated as HLA-B^*35∶186 by WHO Nomenclature Committee for Factors of the HLA System. It illustrates the process of novel allele, and provides new evidence for the further studying mechanisms of gene recombination and HLA polymorphism.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective:To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity.Methods:A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE.Results:(1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference ( F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant ( F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure ( r=0.279), mean arterial pressure ( r=0.212), and urinary protein quantification ( r=0.277), while the severe PE manifestations negatively correlated include HSA levels ( r=-0.644) and newborn birth weight ( r=-0.305), all of which were significantly correlated ( P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95% CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95% CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions:The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.
Female ; Humans ; Infant ; Male ; Benserazide/therapeutic use* ; Dystonia/genetics* ; Hypokinesia/drug therapy* ; Levodopa/pharmacology* ; Muscle Hypotonia ; Retrospective Studies ; Tyrosine 3-Monooxygenase/genetics*

Lonicerae Japonicae Flos(LJF), a bulk medicinal material, has long been used in clinical settings. The main/Dao-di production areas are Shandong, Henan, and Hebei. However, no systematic study on the difference in volatile components of LJF from different areas is available at the moment. In this study, gas chromatography-mass spectrometry(GC-MS) was used to detect the volatile components in 30 batches of LJF from 3 main production areas. Based on the relative odor activity value(ROAV), the key aroma components were analyzed. Multivariate statistical analysis was performed to analyze the differential components and characteristic aroma components in the samples from the 3 areas. Finally, 113 volatiles were identified from the samples, which were mainly alcohols, esters, acids, aldehydes, ketones, and alkenes. Among the common components of the three areas, linalool, myristic acid, and α-linolenic acid methyl ester had high content. A total of 15 key and 9 modifying aroma components in LJF were determined based on ROAV. The 15 differential components can be used for origin identification. Among them,(E, E)-2,4-decadienal and hexanal contributed a lot to the aroma of LJF from Henan and α-nerol was a characteristic aroma component of LJF in Hebei. In addition, lauryl aldehyde was a biomarker of LJF from Shandong. This study can provide a reference for the origin identification and quality evaluation of LJF.
Lonicera ; Gas Chromatography-Mass Spectrometry ; Chromatography, High Pressure Liquid ; Multivariate Analysis

OBJECTIVE: To study rare para-Bombay blood type Bm METHODS: ABO and H phenotype of the proband and her pedigree were determined with serological methods. The ABO genotype was analyzed by polymerase chain reaction-sequence specific primer(PCR-SSP). The full coding region of alpha-l,2 fucosyltransferase (FUT1) gene of the pedigree was analyzed by polymerase chain reaction and direct sequencing of the amplified fragments. The haplotype of the FUT1 gene were analyzed by cloning sequencing. RESULTS: The rare para-Bombay blood type Bm CONCLUSION Two new alleles of FUT1 gene (h
ABO Blood-Group System/genetics* ; China ; Female ; Fucosyltransferases/genetics* ; Genotype ; Humans ; Phenotype

Objective:To investigate the status quo of human resources of dentists who deal with periodontal disease in Beijing area through an online survey, which may hopefully provide a preliminary basis for the decision-making of administrative departments and the formulation of periodontal professional development plan.Methods:The dentists who deal with periodontal disease at least half a day per week in Beijing area were investigated. A questionnaire was designed by the chairman of the Periodontology Committee of Beijing Stomatological Association. The questionnaire was sent to and finished by the dentists via "WenJuanXing" online survey software. The contents of the survey included general condition, the property of practice unit, title and position of the dentist, membership of professional society, time and content of periodontal treatment, adoption of new technology and new method of periodontal therapy during the past one year, status of periodontal treatment in the local population and reasons, understanding and influencing factors of periodontal professional development.Results:A total of 1 255 dentists completed the survey, who came from all 16 districts in Beijing, mainly Haidian, Chaoyang, Dongcheng and Xicheng Districts [The total percentage of these four main districts was 70.3% (882/1 255)]. The mean age of the dentists was (36.1±8.3) years. Among the dentists, 71.1% (892/1 255) were females, 88.1% (1 106/1 255) got a Bachelor′s degree or above. It was estimated that 35.4% (444/1 255) of the dentists had received standardized periodontal training ever. The percentage of dentists carrying out new technology in the past one year was as high as 68.1% (855/1 255). There were only 163 periodontal specialists (13.0%) out of the dentists in the survey. Only 15.9% (200/1 255) of the dentists routinely performed periodontal surgery. The majority of the dentists [82.8% (1 039/1 255)] were from the state-owned hospitals. Fifty-four point seven percemt (686/1 255) of the dentists thought that lack of knowledge was the main reason why the general public failed to receive periodontal treatment. As for the biggest bottleneck affecting periodontal professional development, fifty-one point zero percent (640/1 255) of the dentists attributed it to the public neglect.Conclusions:The periodontal practitioners in Beijing are young, highly educated, unevenly distributed in 16 districts and mostly females. State-owned oral health institutions are an important force in periodontal diagnosis and treatment services in Beijing. The number of periodontal specialists need to be improved. Promotion of standardized periodontal surgery and the popularization of healthcare knowledge on periodontal disease should also be the focus in the future.

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography (CT) scan, histopathology and enzyme-linked immune sorbent assay (ELISA) were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth, gingival recession, attachment loss and alveolar bone regeneration values were (3.72 ± 1.18) mm vs. (6.56 ± 1.47) mm, (1.67 ± 0.59) mm vs. (2.38 ± 0.61) mm, (5.56 ± 1.29) mm vs. (8.61 ± 1.72) mm, and (25.65 ± 5.13) mm vs. (9.48 ± 1.78) mm in the icariin group and 0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta (IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.
Animals ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flavonoids ; administration & dosage ; pharmacology ; Gingival Crevicular Fluid ; chemistry ; Inflammation ; drug therapy ; Periodontitis ; diagnostic imaging ; drug therapy ; Swine ; Swine, Miniature ; Tomography, X-Ray Computed

Advanced schistosomiasis is the most serious clinical type of schistosomiasis. Its diagnosis and treatment are relat?ed to many special departments,such as gastroenterology,general surgery,neurology,endocrinology,radiology,traditional Chinese medicine,blood purification,endoscopy,intervention,and ICU. It is necessary to apply a multidisciplinary treatment (MDT)mode. However,the mode has no universal standard and guide in practice. It is very important for the implementation of MDT mode of advanced schistosomiasis to form a treatment expert team,formulate the formal working procedures,and standard?ize the treatment schedules. The standardized implementation of MDT mode will be important to provide a more effective clinical decision on advanced schistosomiasis.

OBJECTIVETo explore the molecular mechanism for a case with para-Bombay phenotype caused by α-1,2-fucosyltransferase (FUT1) gene mutations.

METHODSBlood phenotype of the propositus was determined by standard serological testing. Polymerase chain reaction-sequence specific primer (PCR-SSP) and direct sequencing of PCR product were used to analyze its ABO genotype. The PCR product of FUT1 gene was sequenced and analyzed.

RESULTSThe phenotype of the propositus was initially detected as para-Bombay A type. Direct sequencing of ABO gene showed that the genotype of the proband was A101/O01 (261G/del), which was consistent with the result of PCR-SSP. Two homo-mutations, 35C>T and 658C>T, were detected in the FUT1 gene by sequencing, and the genotype was determined as h(35T+658T)/h(35T+658T).

CONCLUSIONh(35T+658T)/h(35T+658T) is responsible for the para-Bombay phenotype of the propositus. The genotype is rare even in para-Bombay populations.

ABO Blood-Group System ; genetics ; Base Sequence ; DNA Mutational Analysis ; methods ; DNA Primers ; Fucosyltransferases ; genetics ; Genotype ; Homozygote ; Humans ; Male ; Phenotype ; Point Mutation ; Polymerase Chain Reaction