Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Objective To establish an ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry method for the determination of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ) in human plasma and urine. Methods Plasma and urine samples (0.3 mL each) were mixed with 0.9 mL acetonitrile and dichloromethane, vortexed, and subjected to ultrasonic treatment to facilitate extraction. After centrifugation, the extract was collected, evaporated to dry powder under nitrogen, and reconstituted. Separation was performed on a C18 column, and detection was carried out using ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry with external standard quantification. Results 6PPDQ showed good linearity in the range of 0.01-25.00 μg/L in both human plasma and urine, with correlation coefficients of 0.999 5 and 0.999 7, respectively. The detection limits for plasma and urine were 8 and 6 ng/L, and the lower limits of quantification were 27 and 19 ng/L, respectively. The average recovery rates were 97.00%-100.00% for plasma and 90.00%-96.50% for urine. The within-run relative standard deviations (RSDs) were 4.35%-10.00% for plasma and 2.34%-11.11% for urine, while the between-run RSDs were 6.80%-8.46% and 2.60%-10.00%, respectively. Samples can be stored for seven days at 4 ℃ or -20 ℃. respectively. Samples can be stored for seven days at 4 ℃ or -20 ℃. Matrix effects ranged from 87.12%-99.27% for plasma and 91.00%-97.56% for urine. Conclusion The proposed method is simple, highly sensitive, and reproducible, and is suitable for the determination of 6PPDQ in human plasma and urine samples.

Objective:To screen for regulatory cell death and senescence genes with differential prognostic significances in the gastric cancer through bioinformatics methods,and to analyze the effect of phosphodiesterase 1B(PDE1B)on the survival prognosis of the gastric cancer patients.Methods:The gastric cancer gene expression data and clinical data were downloaded from the TCGA Public Database.Fifty gastric cancer patients were randomly selected from the local database,and their clinical informations and paraffin samples,including gastric cancer tissue and adjacent normal tissue,were collected.The R software"limma"package was used to screen differentially expressed genes(DEGs);univariate COX analysis and Kaplan-Meier survival analysis were used to screen DEGs with predictive survival value.The intersection genes affecting the survival prognosis of gastric cancer patients were obtained,and the gene most associated with clinical pathological features PDE1B was screened.The TCGA Database and Kaplan-Meier survival analysis were used to detect the expression levels of PDE1B mRNA in adjacent normal and gastric cancer tissues and their relationships with survival period of the gastric cancer patients.Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were used to enrich the biological functions of PDE1B.The CIBERSORT algorithm,Tumor Immunity Database(TISIDB),and GSCA online website were used to analyze the correlation between PDE1B and tumor microenvironment,immune characteristic molecules,and drug sensitivity.The real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the PDE1B mRNA expression levels in gastric cancer tissue and adjacent normal tissue of the gastric cancer patients.Results:A total of 716 DEGs were screened,among which 505 DEGs were upregulated(P<0.05),and 211 DEGs were downregulated(P<0.05).There were 10 intersection genes affecting survival prognosis.The PDE1B mRNA expression level was most closely related to the clinical pathological characteristics of the gastric cancer patients,being associated with age,tumor grade,tumor stage,and tumor T,N,and M stages(P<0.05).Compared with G1-G2,stage Ⅰ,T1-T2,N0,and M0 stage gastric cancer patients,the PDE1B mRNA expression levels in G3-G4,stage Ⅱ-Ⅳ,T3-T4,N1-N3,and M1 stage gastric cancer patients were significantly increased(P<0.05).Compared with adjacent normal tissue,the PDE1B mRNA expression level in gastric cancer tissue was significantly decreased(P<0.05).Compared with the patients with low PDE1B expression,the patients with high PDE1B expression had a significantly lower overall survival rate(P<0.01).PDE1B expression,age,and tumor stage were the risk factors for the prognosis of gastric cancer patients(P<0.05).After adjusting for gender,age,tumor grade,and tumor stage,PDE1B expression was an independent risk factor affecting the prognosis of the gastric cancer patients(P<0.05).PDE1B was mainly enriched in the biological process(BP),such as immunoglobilin production,second-messenger,mediated signaling transduction and calcium ion transport,cellular component(CC),such as Tlymplocytes receptor complex,plasma membrance signaling receptor complex and collagen-containing extracellular matrix,and molecular function(MF),such as antigen binding,glycosaminoglycan binding,and extracellular matrix structural constituents.PDE1B was mainly involved in the pathways such as neuroactive ligand-receptor interaction,calcium signaling pathway,cGMP-PKG signaling pathway,and cytokine-cytokine receptor interaction.PDE1B was positively correlated with regulatory T lymphocytes(r=0.488),myeloid-derived suppressor cells(r=0.474),and macrophages(r=0.617)(P<0.01).Compared with the patients with low PDE1B expression,the patients with high PDE1B expression promoted the significant increase of infiltration of regulatory T lymphocytes,monocytes,and M2 macrophages(P<0.05).The PDE1B mRNA expression levels were positively correlated with the immunosuppressive agents transforming growth factor-β1(TGF-β1)(r=0.535),colony-stimulating factor 1 receptor(CSF1R)(r=0.519),immune activator ectonucleoside triphosphate diphosphohydrolase 1(ENTPD1)(r=0.593),and CXC chemokine ligand 12(CXCL12)(r=0.646)(P<0.01).The gastric cancer tissue with high PDE1B expression was more sensitive to the drugs such as fluorouracil(-0.3

Objective:To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard.Methods:From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation.Results:A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant ( M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items ( rs=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion:GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

Objective:To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard.Methods:From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation.Results:A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant ( M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items ( rs=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion:GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

Objective To observe the value of ultrasound-guided intra-articular injection of hypertonic glucose(HG)for treating knee osteoarthritis in plateau area.Methods Ninety-one patients with knee osteoarthritis in plateau area(124 affected knee joints)were enrolled.The knee joints were divided into 20％HG group(n=67),25％HG group(n=42)or sodium hyaluronate group(n=15)based on the medication.Clinical and ultrasound scores were compared before and after treatment,and the efficacy of injection of HG was evaluated.Results At the 12th and 48th weeks after treatment,visual analog scale(VAS)scores decreased in all 3 groups(all P＜0.05),and Lysholm scores of 20％HG group and 25％HG group increased compared to those before treatment(all P＜0.05).The difference of Lysholm score before and in the 12th week after treatment,and of VAS score before and in the 48th week after treatment of 25％HG group were higher than those of 20％HG group(both P＜0.05).The joint exudation score of 20％HG group decreased in the 48th week after treatment compared to that before treatment(P＜0.05),and the synovial blood flow score decreased in the 12th and 48th weeks after treatment compared to those before treatment(both P＜0.05).The joint exudation score of 25％HG group decreased in the 48th week after treatment compared to that before treatment(P＜0.05),and the synovial hyperplasia and synovial blood flow score decreased in the 12th and 48th weeks after treatment compared to before treatment(all P＜0.05).The joint exudation score of sodium hyaluronate group decreased in the 48th week after treatment compared to that before treatment(P＜0.05),and the synovial hyperplasia score decreased in the 12th and 48th weeks after treatment compared to that before treatment(both P＜0.05).Conclusion Ultrasound-guided intra-articular injection of HG,esp.25％HG,had certain value for treating knee osteoarthritis in plateau area.

Metabolomics, including targeted metabolomics and non-targeted metabolomics, is a method to study endogenous small molecule metabolites in organisms. The process of metabolomics analysis generally includes sample collection and pre-treatment, sample detection, data preprocessing, metabolite identification, data statistical analysis, and others. At present, metabolomics technology has been applied to study toxicological mechanism of occupational hazards, early detection and diagnosis of occupational diseases, screening biomarkers of occupational exposure, and others. The application of metabolomics technology to explore the relationship between workers' metabolites and exposure to occupational hazardous, assess the potential impact of occupational exposure on workers' health, and search for ideal biomarkers or therapeutic targets is conducive to early warning and monitoring of occupational health hazards, and assistance in the early diagnosis and prognosis of occupational diseases.In the future, further research is needed in the field of occupational health using metabolomics to establish more complete and standardized workflows and experimental methods, combine big data technology to explore potential biomarkers, utilize metabolic information to provide precise occupational health services, and use artificial intelligence models for data mining and disease diagnosis in metabolomics.

OBJECTIVE To provide a reference for pharmaceutical care in patients with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. METHODS Clinical pharmacists participated in the treatment practice of a patient with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. Because the patient had a hemorrhagic transformation after cerebral infarction after stent implantation and arterial thrombolysis， the clinical pharmacists recommended stopping antiplatelet drugs and giving plasma and cold precipitation； because D-dimer was significantly elevated， the clinical pharmacists recommended anticoagulant therapy with low-molecular heparin. Due to the patient’s recurrence of hemorrhagic transformation after cerebral infarction， the clinical pharmacists recommended discontinuing rivaroxaban and administering human prothrombin complex concentrate. RESULTS The physician adopted the clinical pharmacists’ recommendation. After treatment， the patient’s condition tended to improve steadily and was allowed to be discharged with medication. CONCLUSIONS The clinical pharmacists assessed the individualized risk and optimized the patient’s medication regimen by suggesting discontinuation of antiplatelet and anticoagulant drugs， carrying out pharmaceutical care such as coagulation index monitoring， determining the time and indications for restarting anticoagulation， and pharmaceutical monitoring， to ensure the safety and efficacy of the patient’s medication.