OBJECTIVE: To explore the genetic basis for a patient with repeated fertilization failure during assisted reproductive therapy, and to identify the source and mode of mutation. METHODS: A couple treated at the Center for Reproductive Medicine, Gansu Provincial Maternal and Child Health Care Hospital in January 2024 for infertility with incomplete left tube obstruction was selected as the study subject. Relevant clinical data was collected. The couple was subjected to whole exome sequencing (WES), and the candidate variant was verified by Sanger sequencing of their family members and bioinformatic analysis. RESULTS: WES has identified a homozygous c.495del frameshifting mutation of the WEE2 gene in the female partner, whilst no relevant variant was suspected in the male partner. The elder brother of the female partner was homozygous for the above variant, while her parents, maternal and paternal aunts, uncle, grandmother, and grandmother were heterozygous for it. Based on the guidelines from the American College of Medical Genetics and Genomics, above variant was rated to be pathogenic. CONCLUSION The homozygous c.495del frameshifting mutation of the WEE2 gene probably underlay the oocyte fertilization disorder in this couple, which has conformed to an autosomal recessive inheritance.
Adult ; Female ; Humans ; Male ; Cell Cycle Proteins/genetics* ; East Asian People/genetics* ; Exome Sequencing ; Frameshift Mutation ; Homozygote ; Infertility, Female/genetics* ; Pedigree ; Protein-Tyrosine Kinases/genetics*

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

Objective:To investigate the relevant situation of the emergency departments (ED) of general hospitals at all levels in Zhejiang Province participating in the prevention and control of Corona Virus Disease 2019 (COVID-19), and to provide a reference for further improving the capacity of emergency services.Methods:A multi-center cross-sectional investigation study was jointly initiated by the Zhejiang Provincial Emergency Medicine Quality Control Center, the Emergency Medicine Branch of Zhejiang Medical Association, and the Emergency Physicians Branch of Zhejiang Medical Doctors Association. Before investigation, experts were organized to develop a special questionnaire. Then the ED of general people's hospitals or Chinese Medicine hospitals at the county/district-level or above were included and their participations in the prevention and control of COVID-19 epidemic between March 9, 2020 and March 15, 2020 were investigated. The collected information included: basic information of the hospitals; participation of ED in fever clinics; the number of COVID-19 patients admitted to ED; the situation of ED support to the anti-epidemic front-line; and the epidemic prevention facilities of ED, and the early supply of medical protective equipments.Results:A total of 181 hospitals from 11 prefectures and cities across the province were finally included, including 52 (28.7%) Grade-A tertiary hospitals, 45 (24.9%) Grade-B tertiary hospitals, 64(35.4%) Grade-A secondary hospitals, and 20 (11.0%) Grade-B secondary or lower hospitals. Among them, 93 (51.4%) were COVID-19 designated hospitals, and 49 (27.1%) had the ability to detect COVID-19 nucleic acid; 177 (97.8%) set up independent fever clinics and 33 (18.6%) were managed by ED alone or mainly. The medical staffs of 65 (36.7%) fever clinics were all or mainly from ED. A total of 213 cases of COVID-19 were received/treated in 40.3% ED, accounting for 17.3% of the total number of cases in Zhejiang Province. A total of 3 848 doctors and nurses supported the front-line of epidemic prevention, of them, 253 supported Hubei Province (accounting for 12.5% ??of the total number). There were 68.5% and 76.8% ED having spare separate clinic and ordinary rescue single room to deal with the COVID-19. In addition, at the early days of anti-epidemic, more than 50% ED were in short supply or even had no medical protective equipment.Conclusions:The ED of Zhejiang Province plays an important role and has made a great contribution to the prevention and control of the COVID-19 epidemic. It is necessary to improve the conditions of ED to effectively respond to the prevention and control of daily infectious diseases.

Objective: To explore the changes of helper T lymphocytes 17 (Th17) and regulatory T lymphocytes (Tregs) in peripheral blood of patients with extensive burn at early stage in August 2nd aluminum dust explosion accident in Kunshan factory (hereinafter referred to as Kunshan explosion accident) and the significance. Methods: Twenty patients with extensive burn in Kunshan explosion accident admitted to our department of burns and plastic surgery were enrolled in burn group, and 10 healthy adult volunteers with no history of smoking were enrolled in healthy control group. Five mL of peripheral venous blood samples were collected from patients in burn group at admission (≤post injury hour 6, PIH 6) and PIH 24, and on post injury day (PID) 7, and from volunteers in healthy control group respectively. The percentages of CD64⁺ T lymphocytes, human leukocyte antigen-DR positive (HLA-DR⁺ ) T lymphocytes, CD3⁺ CD8^- Th17, and CD4⁺ CD25⁺ Tregs in peripheral blood T lymphocytes were determined by flow cytometer. Results: (1) The percentages of CD64⁺ T lymphocytes in peripheral blood T lymphocytes of patients in burn group at admission and PIH 24 [(2.35±0.32)% and (4.02±0.15)%] were higher than (0.67±0.11)% of healthy volunteers in healthy control group. The percentage of CD64⁺ T lymphocytes in peripheral blood T lymphocytes of patients in burn group on PID 7 [(0.39±0.25)% ] was lower than that of healthy volunteers in healthy control group. The percentages of HLA-DR⁺ T lymphocytes in peripheral blood T lymphocytes of patients in burn group at admission and PIH 24 [(54±18)% and (72±17)%] were higher than (38±14)% of healthy volunteers in healthy control group. The percentage of HLA-DR⁺ T lymphocytes in peripheral blood T lymphocytes of patients in burn group on PID 7 [(28±15)% ] was lower than that of healthy volunteers in healthy control group. (2) The percentages of CD3⁺ CD8^-Th17 in peripheral blood T lymphocytes of patients in burn group at admission and PIH 24 [(4.21±0.46)% and (7.38±0.39)%] were higher than (0.98±0.09)% of healthy volunteers in healthy control group. The percentage of CD3⁺ CD8^-Th17 in peripheral blood T lymphocytes of patients in burn group on PID 7 [(0.81±0.05)% ] was lower than that of healthy volunteers in healthy control group. (3) The percentages of CD4⁺ CD25⁺ Tregs in peripheral blood T lymphocytes of patients in burn group at admission and PIH 24, and on PID 7 [(1.78±0.26)%, (1.26±0.37)%, and (0.38±0.03)%] were lower than (3.24±0.52)% of healthy volunteers in healthy control group. Conclusions The percentage of Th17 in peripheral blood T lymphocytes of patients with extensive burn at early stage in Kunshan explosion accident increased at first and then decreased compared with that of healthy volunteers, indicating that the patients′ immune function increased first and then weakened. The percentages of Tregs in peripheral blood T lymphocytes at each time point were lower than the percentage of healthy volunteers, indicating that the patients′ immunomodulation gradually weakened after extensive burns.

Objective To investigate if immunological factors associated with the false HIV screening test results in RA.Methods Subjects who attended the Rheumatology Outpatient Clinic -Internal Medicine Unit of Guanghua Integrative Hospital , from October 2013 to October 2014, who met the American College of Rheumatology /European League Against Rheumatism Criteria for RA were recruited for the study . 100 subjects with RA were recruited.Each patient underwent clinical examination and blood sampling for assessment of serum HIV screening test and Rheumatoid factors ( RF-IgA, -IgG, -IgM) and anti-cyclic citrullinated protein antibodies (anti-CCP) were purified from the plasma and detected by ELISA , Samples were collected and processed using standard protocols and were stored in the same freezer before analysis . RA patients were divided into two groups based on the titters of RF and anti -CCP:RF <18 U/ml/anti-CCP <25 U/ml group and RF >300 U/ml /anti-CCP >500 U/ml group.HIV screening tests were determined by three methods: ELISA、Immuno-colloidal Golden Method and ECLIA.The positive results were confirmed by the Changning Centers for Disease Control , Shanghai through western -blotting test.Results 100 samples detected by ELISA and Immuno-colloidal Golden Method were given negative results , 16 positive results existed in ECLIA group.There were1,12,3 positive cases in RF-IgM <18 U/ml, RF-IgM and RF-IgG >300 U/ml group(2.7%,32.4%,13.6%;P <0.01).In anti-CCP <25 RU/ml and >500 RU/ml groups there were 2 and 4 positive results(4.7%,24.6%;P <0.01).Conclusions Different HIV screening test methods would give different results , according to operation requirement using second method to determine the HIV screening result.HIV False-positivity was associated with the titers of anti -CCP and RF in RA.

Objective To investigate the change of AQP1 and AQP2 before and after the release of obstruction and explore the relationship between reabsorption dysfunction of renal tubule and the change of AQPs. Methods The model of unilateral ureter obstruction (UUO) was established by surgery. Western blot and immunohistochemistry were used to study the expression of AQPs before and after obstruction. Results In UUO model, both AQPs began to down-regulate one day after obstruction, the expression of both AQPs became lower one day after the release of obstruction. And they started to up-regulate 7 day after the release of obstruction. AQP2 became normal since 14 days after the release of obstruction, and AQP1 became normal since 21 days after the release of obstruction. Conclusion The expression of AQP1 and AQP2 were descended in hydronephrosis. The dysfunction of renal tubule and the osmotic-dependent polyuria after the release of obstruction in UUO were caused by the down - regulation of AQPs.