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 A visualized analysis of the relevant literature on the application of Wuling San(Five-Ingredient Powder Containing Poria)in China in the recent 10 years was conducted to explore the application of Wuling San.Methods The applied research of Wuling San issued in the academic journals of CNKI from January 1,2013 to December 31,2022 were retrieved.The corresponding knowledge graphs were drawn with CiteSpace software,and the keywords of the literature were visualized and analyzed.Results A total of 1 121 articles related to the applied research of Wuling San were obtained after preliminary retrieval,and 1 104 articles were included for visual analysis after screening.The results of keyword co-occurrence analysis showed that Wuling San was usually used for treating cirrhosis ascites,chronic heart failure,diabetic nephropathy and other multi-system diseases,and it was mostly used by the compatibility of Taohong Siwu Decoction,Zhenwu Decoction,Xiaochaihu Decoction,Shenqi Pills and Linggui Zhugan Decoction.Wuling San was indicated for the symptoms of edema,dysuria and urinary retention.The commonly-used research methods for Wuling San included network pharmacology,molecular docking,etc.The results of keyword burst analysis showed that the hotspots of Wuling San applied research were as follows:cirrhosis in 2013,Yinchenhao Decoction in 2015,cerebral edema in 2018,and network pharmacology,novel coronavirus-infected pneumonia and cardiac function since 2020.Conclusion Wuling San is widely used in the clinic,and is indicated for water metabolism disorders.Wuling San in the treatment of cirrhotic ascites,chronic heart failure and diabetic nephropathy becomes the research hotspots in recent years.The applied researches of Wuling San on novel coronavirus-infected pneumonia and on improving cardiac function have become the trend and focus of current research.

Objective To observe the regulatory effects of Yitangkang on neuroinflammation and polarization of microglia and astrocytes in db/db mice;To explore the its mechanism in the treatment of cognitive impairment in diabetes.Methods Totally 32 db/db mice were randomly divided into model group,liraglutide group,and Yitangkang low-and high-dosage group.Another C57BL/6 mice were taken as blank group,with 8 mice in each group.Yitangkang low-and high-dosage group were given Yitangkang Decoction 15,30 g/kg respectively,the liraglutide group was intraperitoneally injected with liraglutide 200 μg/kg,the blank group and model group were given the same volume of distilled water by gavage,for 5 weeks.FJC staining was used to observe the damage of hippocampal neurons,ELISA was used to detect the content of IL-6 and IL-1β in hippocampal tissue,immunohistochemistry was used to detect the expressions of IL-6,IL-1β,Iba1 and GFAP in hippocampal tissue,the expressions of CD86,CD206,C3,S100A10,NLRP3,Iba1 and GFAP were detected by immunofluorescence,the protein expressions of CD86,CD206,C3,S100A10 and NLRP3 in hippocampal tissue were detected by Western blot.Results Compared with the blank group,the FJC positive cells in the model group significantly increased,and the contents of IL-6 and IL-1β significantly increased,the expressions of Iba1,CD86,GFAP and C3 significantly increased,CD206 and S100A10 expressions significantly decreased,NLRP3 protein expression and co-expression with Iba1 and GFAP significantly increased,with statistical significance(P<0.05,P<0.01).Compared with the model group,the FJC positive cells in hippocampal tissue of liraglutide group and Yitangkang low-and high-dosage group significantly decreased,the contents of IL-6 and IL-1β significantly decreased,the expressions of Iba1,CD86,GFAP and C3 significantly decreased,the expressions of CD206 and S100A10 significantly increased,the expression of NLRP3 protein and co-expression with Iba1 and GFAP were significantly decreased,the differences were statistically significant(P<0.05,P<0.01)except for CD206 in Yitangkang low-dosage group.Conclusion Yitangkang can effectively regulate the expression of NLRP3 in db/db mice,promote the transformation of microglia/astrocytes from M1/A1 type to M2/A2 type,inhibit the inflammatory response,and exert neuroprotective effects.

Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-β-glucopyranoside(3),(-)-isolariciresinol 3α-O-β-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-β-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) μmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 μmol·L~(-1) was 96.09%±1.77%.
Cornus ; Wine ; Naphthols ; Lignin

Objective:To develop a short-term prognostic model of spontaneous cerebral hemorrhage based on eXtreme Gradient Boosting (XGBoost) machine learning, and to compare its predictive performance with a Logistic regression model.Methods:Patients with sICH admitted to Department of Neurology, Second People's Hospital of Hefei from January 2018 to March 2022 were chosen; their general demographic characteristics, medical history, laboratory indices and cranial imaging data were retrospectively collected. The prognoses of patients 90 d after discharge were evaluated according to modified Rankin Scale (mRS) scores (good prognosis: mRS scores<3; poor prognosis: mRS scores≥3). XGboost and multiple Logistic regression models were used to screen out the factors for prognoses of patients 90 d after discharge, and area under receiver operating characteristic (ROC) curves, sensitivity, specificity and prediction accuracy of the 2 models were analyzed and compared.Results:A total of 413 patients with sICH were included; 180 patients(43.6 %) had poor prognosis and 233 (56.4%) had good prognosis 90 d after discharge. Multivariate Logistic regression results showed that age≥65 years, hemorrhage into the ventricle, hematoma volume of 20-40 mL, hematoma volume>40 mL and National Institutes of Health Stroke Scale (NIHSS) scores were independent influencing factors for short-term prognoses of sICH ( P<0.05). The variables in the XGBoost model were ranked in order of importance: NIHSS scores, systolic blood pressure at admission, Glasgow coma scale (GCS) scores, age≥65 years, hemorrhage into the ventricle, hematoma volume of 20-40 mL, and hematoma volume>40 mL. AUC of XGBoost model in predicting the prognosis was 0.895 (95% CI: 0.820-0.947), enjoying sensitivity of 68.89%, specificity of 94.83%, and prediction accuracy of 83.5%. AUC of Logistic regression model in predicting the prognosis was 0.894 (95% CI: 0.818-0.946), enjoying sensitivity of 93.33%, specificity of 70.69%, and prediction accuracy of 80.58%. Conclusion:The short-term prognostic model based on XGboost for sICH patients has high predictive efficacy, whose predictive accuracy is better than traditional Logistic regression.

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Self Efficacy ; Self-Management ; Blood Glucose Self-Monitoring ; Blood Glucose ; Self Care

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.
Acupuncture Points ; Acupuncture Therapy ; COVID-19/therapy* ; Humans ; Lung ; Vascular Surgical Procedures

ObjectiveTo retrospectively analyze the clinical data of 52 patients with coronavirus disease-2019 （COVID-19） and explore the clinical efficacy of modified Sanxiaoyin on mild/moderate COVID-19 patients. MethodThe propensity score matching method was used to collect the clinical data of mild or moderate COVID-19 patients enrolled in the designated hospital of the Second Hospital of Jingzhou from December 2019 to May 2020. A total of 26 eligible patients who were treated with modified Sanxiaoyin were included in the observation group， and the 26 patients treated with conventional method were the regarded as the control. The disappearance of clinical symptoms， disappearance time of main symptoms， efficacy on traditional Chinese medicine （TCM） symptoms， hospitalization duration， laboratory test indicators， and CT imaging changes in the two groups were compared. ResultThe general data in the two groups were insignificantly different and thus they were comparable. After 7 days of treatment， the disappearance rate of fever， cough， fatigue， dry throat， anorexia， poor mental state， and poor sleep quality in the observation group was higher than that in the control group （P<0.05）， and the difference in the disappearance rate of expectoration and chest distress was insignificant. For the cases with the disappearance of symptoms， the main symptoms （fever， cough， fatigue， dry throat， anorexia， chest distress） disappeared earlier in the observation group than in the control group （P<0.01）. After 7 days of treatment， the scores of the TCM symptom scale of both groups decreased （P<0.01）， and the decrease of the observation group was larger that of the control group （P<0.01）. All patients in the two groups were cured and discharged. The average hospitalization duration in the observation group ［（12.79±2.68） d］ was shorter than that in the control group ［（15.27±3.11） d］ （P<0.01）. The effective rate in the observation group （92.31%， 24/26） was higher than that in the control group （76.92%， 20/26） . After 7 days of treatment， the lymphocyte （LYM） count increased （P<0.05）， and white blood cell （WBC） count and neutrophil （NEUT） count decreased insignificantly in the two groups. Moreover， levels of C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， and procalcitonin （PCT） reduced in the two groups after treatment （P<0.01） and the reduction in the observation group was larger than that in the control group （P<0.01）. Through 7 days of treatment， the total effective rate on pulmonary shadow in the observation group （90.00%， 18/20） was higher than that in the control group （77.27%， 17/22） （P>0.05） and the improvement of lung shadow in the observation group was better than that in the control group （P<0.01）. ConclusionModified Sanxiaoyin can significantly alleviate fever， cough， fatigue， anorexia， chest distress， poor sleep quality， and other symptoms of patients with mild or moderate COVID-19， improve biochemical indicators， and promote the recovery of lung function. This paper provides clinical evidence for the application of modified Sanxiaoyin in the treatment of mild or moderate COVID-19.

By referring to the relevant ancient herbal literature， medical records and prescription books， the textual research of Violae Herba has been conducted to verify the name， origin， producing area， quality evaluation and processing method changes. The results showed that the name of Zihua Diding originated from its flower color and plant morphological characteristics. The primitive plant of Violae Herba is Viola genus of Violaceae， V. yedoensis， as stipulated in the 2020 edition of Chinese Pharmacopoeia， has been the mainstream in past dynasties of China. Violae Herba is mainly wild， and it is widely distributed throughout the country. Since modern times， the quality of Violae Herba is better with integrity， green color and yellow root. There are few records on the harvesting and processing methods of Violae Herba in ancient times， most of which are directly used after drying. It is suggested that the collection and processing methods of Violae Herba in the famous classical formulas can be implemented in accordance with the provisions of the 2020 edition of Chinese Pharmacopoeia.

Objective: To explore current vitamin D status and influential factors of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China. Methods: According to the "province-city-hospital" sampling technical route, a total of 1 531 healthy children under 7 years of age were sampled from 11 provinces, autonomous regions or municipalities in China by the cluster random sampling method from November 2020 to November 2021. The demographic information, family conditions, behavior and living habits and feeding behaviors were collected using unified questionnaire. Serum 25-hydroxyvitamin D(25(OH)D) levels were measured by liquid chromatography-tandem mass spectrometry. Serum 25(OH)D<30 nmol/L was considered deficient and 30-50 nmol/L was considered insufficient. With 25(OH)D≤50 nmol/L as the dependent variable, multivariate Logistic regression was applied to analyze the association between vitamin D deficiency and insufficiency and potential influential factors. Results: The prevalence of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China was 14.0% (215/1 531), 3.8% (25/664) and 21.9% (190/867) in 0-<3 and 3-<7 of age years, respectively. Compared to children aged 0-<3 years, children aged 3-<7 years had a 2.6-fold increased risk of vitamin D deficiency and insufficiency (OR=3.60, 95%CI 1.93-6.72, P<0.001). Frequent sunlight exposure (OR=0.46, 95%CI 0.29-0.73, P=0.001), vitamin D supplementation (sometimes, OR=0.33, 95%CI 0.21-0.51, P<0.001; daily, OR=0.20, 95%CI 0.11-0.36, P<0.001) and infant formula intake(4-7 times per weeks, OR=0.43, 95%CI 0.28-0.68, P<0.001) were protective factors for vitamin D deficiency and insufficiency. Conclusion: Vitamin D deficiency and insufficiency are common among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China, which is affected by age, sunlight exposure, vitamin D supplementation and infant formula intake.
Child ; China/epidemiology* ; Cross-Sectional Studies ; Humans ; Infant ; Vitamin D ; Vitamin D Deficiency/epidemiology* ; Vitamins