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*

OBJECTIVES: To investigate the clinical characteristics and drug resistance profile of invasive non-typhoidal Salmonella (NTS) enteritis in children in Chengdu, China, providing a reference for rational drug use and empirical treatment in clinical practice. METHODS: A retrospective analysis was conducted on the clinical data of 130 children with invasive bacterial enteritis due to NTS identified by fecal bacterial culture and the results of drug sensitivity tests for NTS in Chengdu from January 2022 to December 2023. RESULTS: NTS infections were mainly observed from April to September (113 cases, 86.9%), with a peak in August (36 cases, 27.7%). Children aged <36 months accounted for 86.2% (112/130) of all cases, and the main symptoms were diarrhea (130 cases, 100%), fever (123 cases, 94.6%), and hematochezia (112 cases, 86.2%). The 130 NTS isolates exhibited a sensitivity rate of 64.6% to ceftriaxone and 63.8% to cefotaxime, and a sensitivity rate of >90.0% to piperacillin-tazobactam and nitrofurantoin (nitrofurans). The detection rate of multidrug-resistant strains was 48.5% (63/130), and the clinical efficacy of third-generation cephalosporins used in 38 patients (29.2%) was inconsistent with the results of drug sensitivity tests. CONCLUSIONS The peak of invasive NTS enteritis in children aged 0-6 years occurs in August in the Chengdu area, with a relatively high incidence rate in children aged <36 months. The situation of drug resistance is severe for NTS, and piperacillin-tazobactam may be an effective option for treating multidrug-resistant NTS infections in children, while nitrofuran antibiotics might be used to treat such infections.
Humans ; Infant ; Child, Preschool ; Enteritis/microbiology* ; Retrospective Studies ; Male ; Salmonella Infections/microbiology* ; Female ; Child ; Salmonella/drug effects* ; Infant, Newborn ; Microbial Sensitivity Tests ; Anti-Bacterial Agents/therapeutic use*

OBJECTIVES: We propose a multi-feature fusion model based on manually extracted features and deep learning features from endoscopic images for grading rebleeding risk of peptic ulcers. METHODS: Based on the endoscopic appearance of peptic ulcers, color features were extracted to distinguish active bleeding (Forrest I) from non-bleeding ulcers (Forrest II and III). The edge and texture features were used to describe the morphology and appearance of the ulcers in different grades. By integrating deep features extracted from a deep learning network with manually extracted visual features, a multi-feature representation of endoscopic images was created to predict the risk of rebleeding of peptic ulcers. RESULTS: In a dataset consisting of 3573 images from 708 patients with Forrest classification, the proposed multi-feature fusion model achieved an accuracy of 74.94% in the 6-level rebleeding risk classification task, outperforming the experienced physicians who had a classification accuracy of 59.9% (P<0.05). The F1 scores of the model for identifying Forrest Ib, IIa, and III ulcers were 90.16%, 75.44%, and 77.13%, respectively, demonstrating particularly good performance of the model for Forrest Ib ulcers. Compared with the first model for peptic ulcer rebleeding classification, the proposed model had improved F1 scores by 5.8%. In the simplified 3-level risk (high-risk, low-risk, and non-endoscopic treatment) classification task, the model achieved F1 scores of 93.74%, 81.30%, and 73.59%, respectively. CONCLUSIONS The proposed multi-feature fusion model integrating deep features from CNNs with manually extracted visual features effectively improves the accuracy of rebleeding risk classification for peptic ulcers, thus providing an efficient diagnostic tool for clinical assessment of rebleeding risks of peptic ulcers.
Humans ; Deep Learning ; Peptic Ulcer ; Risk Assessment ; Peptic Ulcer Hemorrhage ; Recurrence

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Perimenopausal insomnia is referred to as"syndromes occured before and after amenorrhea","insomnia"and"visceral irritability"in traditional Chinese medicine.It is believed that yin deficiency of the liver and kidney leads to liver constraint transforming into fire,which harassing the upper body of the heart and spirit,as well as qi and blood insufficiency that leads to the dysfunction of liver,which is the main pathogenesis of perimenopausal insomnia.Therefore,the treatment method of soothing the liver and regulating the mind is proposed,and combined with acupuncture,fine moxibustion,pricking collaterals,auricular acupuncture,back-shu point embedding acupuncture and other treatment methods,which together constitute the"firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation"integrated acupuncture and moxibustion program to provide treatment ideas for perimenopausal insomnia.

Objective The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.Methods We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg·day) and 50 μg/(kg·day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing. Results Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment. Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.

Objective To observe the clinical efficacy of Lingnan Traditional Vesiculating Moxibustion No.4 Recipe(mainly composed of Brassicae Junceae Semen,Euodiae Fructus,and Curcumae Radix)in the treatment of mild depressive disorder(DD),and to provide a novel approach to the treatment of mild DD population.Methods Sixty-one patients with mild DD were randomly divided into 31 cases in the trial group and 30 cases in the control group.The trial group was given medicinal vesiculation treatment with Lingnan Traditional Vesiculating Moxibustion No.4 Recipe,and the control group was given medicinal vesiculation treatment with the placebo of Lingnan Traditional Vesiculating Moxibustion No.4 Recipe.The treatment was performed twice a week and with an interval of 3-4 days between the treatment,and the course of treatment covered 6 weeks.The changes of Hamilton Depression Scale-17(HAMD-17)scores and Patient Health Questionnaire-9(PHQ-9)scores in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After 6 weeks of treatment,the total efficacy rate of the trial group was 77.42%(24/31),and that of the control group was 26.67%(8/30).The intergroup comparison(tested by rank sum test)showed that the efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.01).(2)After treatment,the HAMD-17 scores and PHQ-9 scores of patients in the two groups were lower than those before treatment(P＜0.01),and the decrease of HAMD-17 and PHQ-9 scores in the trial group was significantly superior to that of the control group,the difference being statistically significant(P＜0.01).(3)During the trial,there were 5 cases of adverse events related to the vesiculating moxibustion treatment,and all 5 cases of adverse events occurred in the trial group,manifested as minor blisters at the acupoint application region.The 5 cases kept on participating in the trial after relevant treatment.Conclusion Lingnan Traditional Vesiculating Moxibustion No.4 Recipe can effectively relieve the clinical symptoms of patients with mild DD,and has high safety.

Objective To explore the public's cognition and attitude towards general medicine,general practitioners,and pre-hospital first-aid knowledge in Ludian County,Yunnan Province,to find out the training and learning methods that are more acceptable to the public for this kind of related knowledge,and to propose targeted solutions.Methods A complete random sampling survey was conducted among the nucleic acid collection office at the gate of the vegetable market from October 15,2022,to December 30,2022,and the outpatient clinic of Wenping Street Health Center from January 1,2023,to February 28,2023,by using electronic questionnaire and paper questionnaire.Results Nearly 50%of the people in Ludian County of Yunnan Province lack the knowledge of general medicine and pre-hospital emergency care,especially the knowledge of electrical defibrillation.People with higher education and the medical profession have a higher understanding of general medicine,and people with a higher understanding of general medicine are more willing to participate in pre-hospital emergency care.The average Ridit value is:very familiar with general medicine(0.774)>Knowledge of some general practices(0.565)>Never heard of general practice(0.400).The higher education level and the more comprehensive understanding of general medicine had a positive impact on participation in pre-hospital emergency care,with B values of 0.624 and 0.619,OR 95%CI of 1.867(1.544～2.257)and 1.857(1.298～2.657),respectively.Taking medical staff as a reference,the B value of medical students was = 0.942,P = 0.234,the difference was not significant,and the B value of non-medical professional population was all less than 0,the effect is negative.In addition,most people have a positive attitude towards learning pre-hospital first aid,and more than 70%of people are willing to learn and train related knowledge of pre-hospital first aid.Conclusions People in urban areas of Ludian County,Yunnan Province have poor understanding of general practice,low recognition of general practitioners,low demand for general practitioners,and lack of awareness of the importance of pre-hospital emergency treatment.Because of the cognitive differences among different groups,it is necessary to conduct specific training for different groups.

Objective To explore the anti-inflammatory mechanism of the active ingredients of Gubi Formula in treating osteoarthritis.Methods Normal human chondrocytes were cultured in vitro,and lipopolysaccharide(LPS)stimulated inflammation.The cells were divided into control group(normal culture),model group(10 μg·mL-1 LPS),quercetin group(10 μg·mL-1 LPS+8 μmol·L-1 quercetin),formononetin group(10 μg·mL-1 LPS+50 μmol·L-1 formononetin),naringin group(10 μg·mL-1 LPS+10 μmol·L-1 naringin),asperosaponin Ⅵ group(10 μg·mL-1 LPS+50 pmol·L-1 asperosaponin Ⅵ),β-ecdysterone group(10 μg·mL-1 LPS+50 μmol·L-1β-ecdysterone).Cell counting kit-8(CCK8)was used to detect the viability of chondrocytes.Western blot was used to detect the expression of nuclear factor NF-kappa-B p65 subunit(p65),nuclear factor erythroid 2-related factor 2(Nrf2)nuclear protein.Results The cell viability of control group,model group,quercetin group,formononetin group,naringin group,Dipsacoside Ⅵ group,β-ecdysterone group were(103.10±8.55)％,(62.41±2.35)％,(76.92±1.74)％,(77.01±0.60)％,(80.39±3.06)％,(79.43±0.94)％,(55.20±0.99)％;the relative expression of Nrf2 protein were 1.00±0.00,1.01±0.09,1.30±0.15,0.91±0.15,1.23±0.25,0.71±0.19,1.51±0.13,1.26±0.15;the relative expression of P65 protein were 1.00±0.00,2.24±0.85,0.74±0.33,1.49±0.29,0.97±0.06,1.33±0.07,1.67±0.22,1.52±0.17;the relative expression of inflammatory mediators iNOS were 1.00±0.00,1.52±0.27,1.07±0.24,1.25±0.12,1.01±0.30,1.44±0.12,1.07±0.18,1.11±0.16.The above indexes in quercetin group,formononetin group and naringin group were significantly different from those in model group(P＜0.05,P＜0.01 and P＜0.001).Compared with the model group,there was no significant difference in the above indexes between the Asperosaponin Ⅵ group and theβ-ecdysterone group(all P＞0.05).Conclusion The active components of Gubi Formula,including quercetin,mangiferin,and naringin,can activate Nrf2-HO-1 signaling and inhibit the activation of the Nuclear factor-κB(NF-κB)pathway plays an anti-inflammatory role in alleviating osteoarthritis.

Objective:To investigate the role of multiparameter flow cytometry (MFC) in detecting non-neoplastic abnormal phenotypes, including monoclonal gammopathy of undetermined significance (MGUS), monoclonal B-cell lymphocytosis (MBL), Fcγ receptor Ⅲb (FcγRⅢB), and CD36 deficiencies.Methods:A retrospective and observational study was conducted on a total of 24 864 patients who underwent one-step screening for leukemia/lymphoma at Hebei Yanda Ludaopei Hospital from January 3, 2020, to March 31, 2024. Clinical data and MFC results of the patients were collected. Patients were grouped by age, group of <45 years (11 495 cases), group of 45-<60 years (5 322 cases), group of ≥60 years (7 081 cases) and disease nature, benign group (8 336 cases), malignant group (15 562), and other diseases group (966 cases). The incidence of non-neoplastic abnormal phenotypes was analyzed across groups.Results:The incidence rates of MGUS, MBL, FcγRⅢB, and CD36 deficiencies were 0.072% (18/24 864), 0.511% (127/24 864), 0.221% (55/24 864), and 0.004% (1/24 864), respectively. MBL incidence was lower in the malignant group than in the benign group ( P<0.001), while MGUS incidence was higher in the malignant group than in the benign group ( P=0.034). The incidence rate of MBL among subtypes within the benign group varied significantly ( P<0.001 ), with the highest incidence in patients with pancytopenia at 2.72% (48/1 765). In the malignant group, the incidence of MBL differed significantly across various disease types ( P<0.001), among which MDS/MPN exhibited the highest incidence at 1.95% (3/154) and 1.30% (2/154). Conclusion:Utility of multiparameter flow cytometry method for one-step screening of leukemia and lymphoma shows variety in detecting non-neoplastic abnormal phenotypes, facilitating the identification of diseases.