Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Objective To investigate the technical capacity and service quality of occupational health technical service institutions (hereinafter referred to as "occupational health institutions") in Guangdong Province. Methods All occupational health institutions in Guangdong Province that had valid occupational health service qualifications and within the validity period were included for analysis. Data on basic information, employed personnel, and results of professional technical capacity assessments across occupational health institutions were obtained through the Guangdong Provincial Occupational Health Technical Quality Control Center. Results A total of 99 institutions with 2 732 technical staff were included in this study. Occupational health institutions in Guangdong Province were mainly distributed in the Pearl River Delta region, accounting for 87.9% (87/99) of the total. The number of public and private health institutions was 23 and 76, accounted for 23.2% and 76.8% respectively. In terms of technical personnel, the percentage of individuals worked in public or private health institutions was 24.1% and 75.9%, respectively. Personnel titles were predominantly intermediate level and no title, accounting for 38.7% and 26.4%, respectively. Individuals with a bachelor′s degree or above accounted for 67.4%. Engineering and other professionals accounted for 35.4% and 30.5%, respectively. Private institutions undertook 97.3% of testing and evaluation workload related to occupational hazard in the province. The number of occupational health institutes acquiring category Ⅰ and Ⅱ service license were 97 and 13. Among institutions participating in inter-laboratory comparisons, the overall pass rates for quantitative items were 95.5% in public and 70.3% in private institutions, while the pass rates for qualitative items were 100.0% and 94.5%, respectively. Conclusion Occupational health institutions in Guangdong Province face issues such as imbalanced regional distribution, uneven development, and insufficient technical competence and testing capacity of professional personnel. Health authorities at all levels should continue to strengthen supervision and quality control to solidify the technical foundation and comprehensively enhance service capacity and quality.

Objective To summarize the key precautions in the determination of nitrogen oxides (nitric oxide and nitrogen dioxide) in the workplace air and to explore potential optimization items in the national standard analytical method. Methods According to GBZ/T 160.29-2004 Methods for Determination of Inorganic Nitrogen Compounds in the Air Workplace, comparative experiments were conducted to evaluate and optimize critical technical parameters of the standardized method, including the oxidation efficiency of oxidation tubes and the preparation and storage of absorption solutions. The application details of the standard method were refined. Results The concentrations of nitrogen oxides (nitric oxide and nitrogen dioxide) were expressed as nitrogen dioxide equivalents. During calibration, the flow calibrator should be connected to the upstream of the air sampler, and the sampling system should undergo an air tightness check. Each batch of oxidation tubes should be validated before use. Before sampling, both end caps should be removed and the tube should be equilibrated for one hour in a clean environment with 30.00%-70.00% relative humidity. The prepared absorption stock solution in this method can be stored at 4 ℃ for up to 96 days. Commercial porous plate absorption tubes must be batch-validated before use. The sampling flow rate during sampling should be consistent with that specified in the standard method. After sampling, collected samples should be sealed in 10.00 mL amber glass bottles with screw caps and stored at 4 ℃ for up to 120 hours. Conclusion This study summarizes precautions for the sampling, detection, and calculation of nitrogen oxides (nitric oxide and nitrogen dioxide)in workplace air to strengthen quality control. Experimental optimizations of oxidation tube conditioning, absorption stock solution preparation and preservation, and sample storage conditions and durations may provide references for diversifying and simplifying the detection process, which facilitate the practical application in actual work.

The current situation of tumor radiotherapy teaching is far behind the development of radiotherapy technologies. The construction of a teaching system based on an artificial intelligence-powered automatic target delineation system and a standardized cancer radiotherapy case library is operable and practical for realizing the standardization and homogenization of clinical target volume delineation teaching, improving students' precision and speed of target volume delineation, and promoting students' learning interest, initiative, and efficiency, which can bring new vitality to the development of radiotherapy education and is worthy of further exploration and promotion.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus(SLE)and lupus nephritis(LN)in children,as well as their diagnostic value for active SLE and LN.Methods A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital,Central South University from January 2016 to March 2019 as the SLE group,all of whom were tested for anti-C1q antibodies.A control group was formed by collecting 70 hospitalized children with other autoimmune diseases(OAD)during the same period.The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed,and the diagnostic value of anti-C1q in SLE and LN was evaluated.Results The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group(P<0.05).The SLE disease activity index score was positively correlated with anti-C1q antibodies(rs=0.371,P<0.001)and positively correlated with anti-double-stranded DNA antibodies(rs=0.370,P<0.001).The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90%and 53.90%,respectively,with an area under the curve of 0.720(P<0.05)and a critical value of 5.45 U/mL.The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50%and 85.00%,respectively,with an area under the curve of 0.675(P<0.05)and a critical value of 22.05 U/mL.Conclusions Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Objective To analyze the problems and differences in workplace on-site sampling and testing skills in external quality assessment in laboratory among occupational health technical service institutions. Methods A total of 108 occupational health technical service institutions nationwide, participated in the external quality assessment in laboratory of the on-site individual sampling operation skills for silica dust (hereinafter refer to as "silica dust sampling assessment") and on-site detection operation skills for carbon monoxide (hereinafter refer to as " carbon monoxide sampling assessment") in 2023, were selected as the research subjects. The result of the assessment was analyzed. Results The qualification rate of the institutions for the silica dust sampling assessment was 98.1%. The unqualified rate of institutions in the Pearl River Delta region was lower than that in non-Pearl River Delta regions (0.0% vs 11.1%, P<0.017). The excellence rate was higher in public institutions than that in private enterprises (73.5% vs 40.0%, P<0.017). The unqualified rate of institutions with permit was lower than that of institutions without permit (0.0% vs 13.3%, P<0.05). The qualification rate of the institutions for the carbon monoxide sampling assessment was 79.4%. The proportion of the institutes, whose results of carbon monoxide standard gas (gas bag) deviation was >±20.0% was higher in private enterprises than that in public institutions (32.8% vs 7.1%, P<0.017). In terms of the normativity of on-site individual sampling for silica dust, the rates of conducting air tightness checks before sampling, correct disassembly and installation and correct placement direction of dust sampling heads, and correct flow for calibration based on the provided dust sampling heads were low, at 53.7%, 33.3%, and 14.8%, respectively. In terms of the normativity of on-site detection of carbon monoxide, the accuracy rate of converting results by on-site detection individuals was low, at only 57.8%. ConclusionIt is necessary to further strengthen the training of theoretical knowledge and practical skills of individuals in occupational health technical service institutions in Guangdong Province, especially to enhance the capacity of occupational health technical services in non-Pearl River Delta regions of the province.