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 investigate the effect of daratumumab, lenalidomide and dexamethasone on quality of life in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). METHODS: The clinical data of 93 TIE NDMM patients in our hospital from January 2020 to December 2022 were retrospectively analyzed. The patients were divided into D-Rd group (48 cases) and Rd group (45 cases) according to treatment regimen. The patients in Rd group were treated with lenalidomide and dexamethasone, while those in D-Rd group were treated with daratumumab on the basis of Rd group. The QLQ-C30 and EQ-5D VAS scores of the two groups were compared at baseline and after 3, 6 and 12 treatment cycles. The last follow-up date was June 30, 2023, and overall survival (OS) was compared between the two groups. RESULTS: The median follow-up period in the D-Rd group was 21 (7-38) months, and the median OS was 34 months, while that in the Rd group was 16 (5-35) months, and the median OS was 28 months. There was significant difference in OS between the two groups ( P <0.05). After 3, 6 and 12 treatment cycles, the QLQ-C30 score and EQ-5D VAS score of the two groups were significantly improved (all P <0.05). After 3 and 12 treatment cycles, the QLQ-C30 score and EQ-5D VAS score of D-Rd group were significantly higher than those of Rd group (all P <0.05). There were no significant differences in the improvement of QLQ-C30 GHS and pain scores between the two groups of patients with age <75 years and ECOG 0-1 score after 3, 6 and 12 treatment cycles (P >0.05). In D-Rd group of patients with age≥75 years, the improvement of QLQ-C30 GHS scores after 3 and 12 treatment cycles and QLQ-C30 pain scores after 3, 6 and 12 treatment cycles was significantly superior to that in Rd group (all P <0.05). In D-Rd group of patients with ECOG 2 scores, the improvement of QLQ-C30 GHS and pain scores after 3, 6 and 12 treatment cycles was significantly superior to that in Rd group (all P <0.05). CONCLUSION Daratumumab, lenalidomide, and dexamethasone can significantly improve OS in TIE NDMM patients without decrease of quality of life, especially in those with age≥75 years or ECOG 2 scores.
Humans ; Multiple Myeloma/drug therapy* ; Lenalidomide/therapeutic use* ; Quality of Life ; Dexamethasone/therapeutic use* ; Retrospective Studies ; Antibodies, Monoclonal/therapeutic use* ; Female ; Male ; Middle Aged ; Aged ; Stem Cell Transplantation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

OBJECTIVE: To investigate the effect of miR-483-5p on hepatocellular carcinoma (HCC) cells proliferation and stemness, as well as the attenuating effect of Pien Tze Huang (PZH). METHODS: Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells (HCSCs) were identified by a miRNA microarray assay. miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness. HepG2 cells and HCSCs were treated with PZH (0, 0.25, 0.50 and 0.75 mg/mL) to explore the effects of PZH on the proliferation and stemness, both in non-induced state and the state induced by miR-483-5p mimics. RESULTS: miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells (P<0.05). PZH not only significantly inhibited proliferation in HepG2 cells, but also significantly suppressed the cell proliferation and self-renewal of HCSCs (P<0.05). The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH. CONCLUSIONS miR-483-5p promotes proliferation and enhances stemness of HepG2 cells, which were attenuated by PZH, demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.
Humans ; MicroRNAs/metabolism* ; Cell Proliferation/drug effects* ; Liver Neoplasms/drug therapy* ; Carcinoma, Hepatocellular/drug therapy* ; Hep G2 Cells ; Neoplastic Stem Cells/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

For the treatment of atrial fibrillation,Professor WU Wei innovatively put forward the theory of heart-blood-vessels trinity and the theory of stasis-toxin causing palpitation.It is believed that atrial fibrillation is caused by stasis and toxin,and affects the heart,blood and vessels.The core pathogenesis of atrial fibrillation is due to qi stagnation,blood stasis and toxin.The treatment for atrial fibrillation should be closely based on the pathogenesis,the therapeutic principles of treating from the perspective of stasis and together by removing toxin gradually is advocated.And the therapy of regulating qi,activating blood and removing stasis is also the way to remove toxin.The medication is based on the modified Taoren Honghua Decoction,which is mainly composed of Persicae Semen,Carthami Flos,Chuanxiong Rhizoma,Corydalis Rhizoma,Rehmanniae Radix,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Jujubae Fructus,Puerariae Lobatae Radix,Nardostachyos Radix et Rhizoma,Ostreae Concha,Poria,and Polygonati Odorati Rhizoma.According to the characteristics of Lingnan climate and atrial fibrillation mostly being easy to affect the emotions,the pungent drugs in the prescription are usually removed,and the specific herbal pair of Puerariae Lobatae Radix-Nardostachyos Radix et Rhizoma is added to remove toxin according to the differentiation of disease.Moreover,for the treatment of atrial fibrillation,Professor WU Wei also adopts traditional Chinese medicine(TCM)external treatment such as foot bath,acupuncture and moxibustion,and physical-breathing exercise as well as health-care methods for comprehensive regulation,relieving the toxin and restoring the original qi.During the treatment atrial fibrillation,Professor WU Wei follows the principle of precise intervention and comprehensive regulation with Chinese medicine,so as to achieve the purpose of eliminating symptoms,restoring sinus rhythm and improving physical constitution.The thoughts of Professor WU Wei for the syndrome differentiation and treatment of atrial fibrillation will provide reference for the treatment of atrial fibrillation with TCM.

Deep vein thrombosis(DVT)is a common complication after surgery for lower limb fracture.It has the features of high morbidity,high disability rate and high mortality.At present,the measures for clinical prevention and treatment of post-operative DVT in lower limb fracture mainly include perioperative nursing,intervention with medical auxiliary instruments,western medicine prevention and treatment,traditional Chinese medicine(TCM)intervention,and patients'self-cooperation.The patients'self-cooperation is the basis for the smooth implementation of other measures for prevention and treatment,and the patients'active cooperation is the premise of achieving the efficacy of prevention and treatment.Perioperative nursing is helpful for the patients to understand the risk factors of postoperative DVT and the possible risks after the occurrence of DVT,guides the patients to choose the food,assists the patients to do postoperative exercises,improves the level of patients'hemorheological indexes,and reduce the incidence of postoperative DVT.Medical devices are helpful for assisting patients to do postoperative rehabilitation exercises,improving the levels of hemodynamic indicators,promoting patients'rehabilitation and reducing the incidence of postoperative DVT.Western medicines such as low molecular weight heparin,Rivaroxaban,Enoxaparin and other anticoagulant drugs can reduce the aggregation of coagulation factors and blood viscosity,and reduce the incidence of postoperative DVT.TCM interventions mainly include oral administration of Chinese medicine and external treatment such as acupuncture,moxibustion and massage.Oral administration of Chinese medicine is helpful for improving blood flow status.Acupuncture,moxibustion and massage are beneficial to the activation of the function of zang-fu organs,and can stimulate the healthy qi to improve the qi-blood state of the whole body.Each method of prevention and treatment has its advantages and disadvantages.In clinical application,reasonable prevention and treatment methods should be selected according to the specific conditions and individual conditions of the patients.TCM intervention of DVT can be performed in patients with lower limb fracture before and after surgery,and has the advantages of low cost and definite efficacy,which is worthy of continuous research and inheritance and innovation.

Objective To investigate the efficacy and safety of Chinese herbal compound modified Huanglian Wendan Decoction in the treatment of hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.Methods A total of 70 patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type were randomly divided into a control group and an observation group,35 cases in each group.The patients in the control group were treated with conventional western medicine,and the patients in the observation group were treated with modified Huanglian Wendan Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The Clinical Global Impression(CGI)score,traditional Chinese medicine(TCM)syndrome score,Pittsburgh Sleep Quality Index(PSQI)score,blood pressure,and serum levels of homocysteine(Hey),interleukin 6(IL-6),interleukin 10(IL-10)and interleukin 8(IL-8)levels in the two groups were observed before and after treatment.Moreover,the safety of medication was evaluated in the two groups.Results(1)After four weeks of treatment,the CGI score of the observation group was(1.63±0.60)points,which was significantly lower than that of the control group[(2.74±0.82)points],and the difference was statistically significant(P＜0.01).(2)After treatment,the TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score of the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease of TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the levels of serum Hcy,IL-6 and IL-8 in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum IL-10 level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum Hcy,IL-6 and IL-8 levels and the increase of serum IL-10 level in the observation group were significantly superior to those in the control group(P＜0.01).(4)During the treatment,no treatment-related adverse reactions or complications occurred in the two groups.Conclusion Modified Huanglian Wendan Decoction has certain efficacy on patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.The decoction can not only reduce the blood pressure and serum Hcy level of the patients,but also regulate the level of inflammatory factors with high safety.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.