The traditional Chinese medicine Qiangjing tablet prevents blood-testis barrier injury induced by CdCl2 through the PI3K/Akt/Rictor signaling pathway.

OBJECTIVE: Environmental contaminants such as cadmium (Cd) may have a deleterious impact on sperm and reduce male fertility by compromising the blood-testis barrier (BTB). Hence, the effects of the traditional Chinese medicine Qiangjing tablet (QJP) on sperm quality and BTB alterations induced by Cd in mouse testes were examined. METHODS: Adult KM mice challenged with Cd chloride were examined, QJP was administered to mice as an oral drug by gavage, and the experiments lasted 2 weeks. Testicular and epididymal weights, sperm quality, anti-sperm antibodies (AsAb), hormone levels, and histology were evaluated. Changes in the levels of N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin and their mRNAs were evaluated. The effects of QJP on the PI3K/Akt/Rictor pathway were evaluated. RESULTS: CdCl2 decreased reproductive organ weight, sperm quality, and testosterone (T) levels; increased AsAb, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; induced structural damage in testicles with BTB disruption; increased BTB permeability; and decreased N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin expression. After treatment, QJP blocked the effects of Cd on reproductive organ weight, sperm quality, and T; mitigated germinal epithelium compartment alterations; decreased AsAb, FSH, and LH levels; and preserved BTB ultrastructure and function. In addition, QJP induced increases in N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin levels and the expression of their mRNAs through the PI3K/Akt/Rictor pathway. After the application of JRAB2011, the levels of a specific mTORC2 suppressor, Rictor, and the BTB-protective effect of QJP were greatly reduced. CONCLUSIONS: We demonstrated the effect of QJP against Cd-induced damage to the BTB, and the results indicate that QJP may play a significant role in opposing the effects of Cd through the PI3K/Akt/Rictor pathway.

Qiangjing tablets ameliorate asthenozoospermia via mitochondrial ubiquitination and mitophagy mediated by LKB1/AMPK/ULK1 signaling.

CONTEXT: Therapeutic effects of Qiangjing tablets (QJT) on sperm vitality and asthenozoospermia (AZS) have been confirmed. However, the mechanism of action remains unclear. OBJECTIVE: This study investigates the effects of QJT on AZS and the underlying mechanism of action. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into six groups: Control, ORN (ornidazole; 200 mg/kg), ORN + QJT-low (0.17 g/mL), ORN + QJT-middle (0.33 g/mL), ORN + QJT-high (0.67 g/mL), and ORN + QJT + Radicicol (0.67 g/mL QJT and 20 mg/kg radicicol) groups. Pathological evaluation and analysis of mitophagy were conducted by H&E staining and transmission electron microscopy, respectively. Reactive oxygen species were detected by flow cytometry. Protein expression was determined by Western blotting. RESULTS: QJT significantly improved ORN-treated sperm motility and kinematic parameters, as well as the pathological symptoms of testicular and epididymal tissues. In particular, QJT mitigated impaired mitochondrial morphology, and increased the PHB, Beclin-1, LC3-II protein, and ROS levels (p < 0.05), and reduced the protein expression levels of LC3-I and p62 (p < 0.05). Mechanistically, QJT antagonized the downregulation of SCF and Parkin protein levels (p < 0.05). Furthermore, QJT significantly increased the protein expressions levels of LKB1, AMPKα, p-AMPKα, ULK1 and p-ULK1 (p < 0.05). The ameliorative effect of QJT on pathological manifestations, mitochondrial morphology, and the expressions of mitophagy and mitochondrial ubiquitination-related proteins was counteracted by radicicol. DISCUSSION AND CONCLUSIONS: QJT improved AZS via mitochondrial ubiquitination and mitophagy mediated by the LKB1/AMPK/ULK1 signaling pathway. Our study provides a theoretical basis for the treatment of AZS and male infertility.

[Effects of Qilan Prescription on the proliferation and apoptosis of human prostate cancer DU145 cells and its action mechanism].

OBJECTIVE: To investigate the effects of different concentrations of Qilan Prescription (QLP) on the proliferation and apoptosis of human PCa DU145 cells and its underlying mechanism. METHODS: We treated human PCa DU145 cells with QLP at 400, 200, 100, 50, 25, 12.5, 6.25, 3.125 or 1.56 µg/ml for 24, 48 and 72 hours respectively. Then we observed the morphological changes of the cells, examined their viability by CCK-8 assay, detected their cell cycle and apoptosis by flow cytometry, and determined the protein expressions of cyclin D1, Bax, Bcl-2 and cleaved-caspase 3 in the DU145 cells by Western blot, followed by comparison of the parameters with those obtained from the blank control group. RESULTS: QLP significantly inhibited the growth, reduced the contour clarity and adhesion ability of the DU145 cells at the concentrations of 100, 200 and 400 µg/ml, and markedly decreased the activity of the cells at 200 and 400 µg/ml, most significantly at 400 µg/ml. The number of the G2-phase DU145 cells was dramatically increased in all the concentration groups (P < 0.01), so was the total number of apoptotic DU145 cells (P < 0.01), while that of the S-phase cells remarkably decreased in the 400 µg/ml QLP (P < 0.01) and 200 µg/ml QLP (P < 0.05) groups. The expression of the cyclin D1 protein was significantly down-regulated in the 400 µg/ml QLP group (P < 0.01). That of Bcl-2 was also down-regulated (P < 0.01) while those of Bax and cleaved-caspase 3 up-regulated in the 400 and 200 µg/ml QLP groups (P < 0.01). CONCLUSION: QLP can inhibit the proliferation and promote the apoptosis of human PCa DU145 cells, which may be associated with its effects of down-regulating the expression of the cell cycle-related protein cyclin D1, disrupting the Bax-Bcl-2 balance, and up-regulating the expression of cleaved-caspase 3.

[Roles of highly expressed bone-specific genes in bone metastatic prostate cancer PC3 cells: Advances in studies].

Prostate cancer (PCa) is a maligmancy with high morbidity and mortality. Bone metastasis is the main cause of short survival time and difficulties in the treatment and prevention of PCa. Previous findings of our team showed 155 bone-specific genes highly expressed in bone metastatic PC3 cells, which is considered to be the key to their adaptation to the bone micro-environment, proliferation and formation of metastatic tumor, and extensively exists in cancer metastasis in multiple systems. This review summarizes the published literature on the highly expressed bone-specific genes, focusing on the roles and values of these genes in the metastasis, progression, clinical diagnosis, treatment and prognosis of PCa, offering a prospect of the direction and targets in the studies of PCa bone metastasis so as to enrich the bone metastatic theories and clinical treatment principles of this disease in the future.

[Inhibitory effect of Qiangjing Tablets on the secretion of IL-1ß and TNF-ɑ from mouse Sertoli cells: A study based on the microenvironment of spermatogenesis].

OBJECTIVE: To study the effect of Qiangjing Tablets (QJT) on the secretion of the inflammatory cytokines IL-1ß and TNF-ɑ from Sertoli cells in infertile mice based on the microenvironment of spermatogenesis. METHODS: We isolated and cultured mouse Sertoli cells, established the model of Ureaplasma urealyticum (UU) infection in the cells, and treated the cells with QJT at the concentrations of 2.5%, 5% and 10% in the serum. After modeling, we determined the contents of IL-1ß and TNF-ɑ in the supernatant of the cells by ELISA and examined the effect of QJT on the secretion of the inflammatory factors from the Sertoli cells by analyzing the dose-effect and time-effect relationships of the drug. RESULTS: In comparison with the blank control, the UU-infected Sertoli cells showed significantly increased secretion of IL-1ß and TNF-ɑ (P < 0.05), the former reaching the peak value in 12 hours and the latter in 24 hours, followed by a downward trend. The secretion of IL-1ß was remarkably inhibited in the 5% and 10% QJT groups (P < 0.05) and that of TNF- ɑ in the 10% QJT group compared with those in the UU infection model group (P < 0.05). CONCLUSIONS: The secretion of IL-1ß and TNF-ɑ is significantly increased in the UU-infected Sertoli cells, and that of IL-1ß negatively correlated with time. QJT-containing serum can inhibit the secretion of IL-1ß and TNF-ɑ from Sertoli cells, and the inhibitory effect of IL-1 ß is most significant at 5% and 10% and that of TNF- ɑ at 10%.

[Effect of Qiangjing Tablets on the MAPK signaling pathway in SD rats with asthenospermia].

OBJECTIVE: To investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS). METHODS: A total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-ß1 in the semen measured by ELISA. RESULTS: The AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue (ï¼»9.20 ± 3.07ï¼½ vs ï¼»42.20 ± 9.17ï¼½ %, P<0.01), but decreased level of TGF-ß1 in the semen (ï¼»627.67 ± 26.07ï¼½ vs ï¼»566.73 ± 68.44ï¼½ ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis (ï¼»42.20 ± 9.17ï¼½ vs ï¼»21.60 ± 5.94ï¼½ %, P<0.01; ï¼»42.20 ± 9.17ï¼½ vs ï¼»33.95 ± 6.39ï¼½ %, P<0.05). The concentration of TGF-ß1 in the semen was markedly lower in the high-dose QJT than in the AS model control group (ï¼»621.78 ± 30.80ï¼½ vs ï¼»566.73 ± 68.44ï¼½ ng/ml, P < 0.05). CONCLUSIONS: Qiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.

[Inhibitory effect of Qiangjing Tablets on the Fas/FasL pathway of cell apoptosis in male SD rats with infertility].

OBJECTIVE: To observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility. METHODS: Models of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue. RESULTS: Compared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 106/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 106/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 106/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01). CONCLUSION: By upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.

[Longbishu Capsule combined with mesylate doxazosin: an efficacious therapy for benign prostatic hyperplasia].

OBJECTIVE: To assess the clinical effect and safety of the Chinese medicine Longbishu Capsule combined with mesylate doxazosin in the treatment of benign prostatic hyperplasia (BPH) of the kidney deficiency and blood stagnation type. METHODS: This was a randomized, double-blind, double-simulation control study. We equally assigned 60 men diagnosed with BPH of the kidney deficiency and blood stagnation type to an experimental and a control group, the former treated with mesylate doxazosin plus Longbishu Capsule and the latter with mesylate doxazosin plus placebo. We compared the International Prostate Symptom Score (IPSS), quality of life (QOL), Chinese symptom score (CSS), maximal urinary flow rate (Qmax), and prostate volume between the two groups of patients before and after 6 months of medication. RESULTS: After treatment, there were 5 cured cases, 13 markedly effective cases, 9 effective cases, 1 ineffective case, and 2 eliminated cases in the experimental group, as compared with 2 cured cases, 8 markedly effective cases, 10 effective cases, 7 ineffective cases, and 3 eliminated cases in the control group. The total effectiveness rate was obviously higher in the former (96.4%) than in the latter (74.1%). IPSS, Qmax, and CSS were improved in both of the groups after medication, even more significantly in the experimental than in the control group (IPSS: 15.22 ± 2.98 vs 18.15 ± 5.88, P <0.05; Qmax: [13.56 ± 2.26] ml/s vs [11.78 ± 2.97] ml/s, P <0.05; CSS: 6.18 ± 2.13 vs 9.52 ± 3.15, P <0.05). Because of the difference in the QOL score between the two groups at the baseline (P = 0.038 <0.05), no more comparison was made in this aspect after treatment. CONCLUSION: The combination of Longbishu Capsule with mesylate doxazosin is safe and effective for the treatment of BPH.

Silk Fibroin Encapsulated Icariin Nanoparticles Mitigate Bisphenol A-Induced Spermatogenesis Dysfunction.

Bisphenol A (BPA) is a prevalent endocrine disruptor found in natural environments. Exposure to BPA has been associated with male infertility. The natural phytochemical icariin (ICA) has demonstrated significant promise for the treatment of male infertility. However, its effectiveness is limited due to its low bioavailability, poor water solubility, and insufficient targeting abilities. Herein, novel nanoparticles are generated from the natural silk fibroin, which are used to load ICA. The efficient drug delivery system (ICA-SNPs) result in significantly focused drug distribution to spermatogonium, enhancing the anti-infertility properties of ICA, and can effectively mitigate spermatogenesis dysfunction induced by BPA, control serum sex hormone levels, and enhance testicular ultrastructure. Additionally, the ICA-SNPs restore spermatogenesis dysfunction primarily via the hormone biosynthesis, spermatogonium meiosis process, and glycerophospholipid metabolism.

Progress in the development of TRPV1 small-molecule antagonists: Novel Strategies for pain management.

Transient receptor potential vanilloid 1 (TRPV1) channels are widely distributed in sensory nerve endings, the central nervous system, and other tissues, functioning as ion channel proteins responsive to thermal pain and chemical stimuli. In recent years, the TRPV1 receptor has garnered significant interest as a potential therapeutic approach for various pain-related disorders, particularly TRPV1 antagonists. The present review offers a comprehensive, systematic exploration of both first- and second-generation TRPV1 antagonists in the context of pain management. Antagonists are categorized and explicated according to their structural characteristics. Detailed examination of binding modes, structural features, and pharmacological activities, alongside a critical appraisal of the advantages and limitations inherent to typical compounds within each structural category, are undertaken. Detailed discussions of the binding modes, structural features, pharmacological activities, advantages, and limitations of typical compounds within each structural category offer valuable insights and guidance for the future research and development of safer, more effective, and more targeted TRPV1 antagonists.

A systematic review evaluating the effectiveness of exercise training on physical condition in prostate cancer patients undergoing androgen deprivation therapy.

Background: Androgen deprivation therapy (ADT) is an effective prostate cancer (PCa) treatment strategy that can curb the development or progression of the disease. This review aimed to examine and summarize available systematic reviews/meta-analyses (SRs/MAs) of exercise training on physical condition of PCa patients undergoing ADT. Methods: A comprehensive search of 8 databases was conducted for relevant literature published before April 25, 2022 with the language restrictions of Chinese and English. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs using a range of evaluation tools, including A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE). Results: This review included 8 SRs/MAs which included a total of 94 studies. Ultimately, A total of 51 outcomes was included, regarding 11 different outcome categories. The AMSTAR-2 tool showed that 3 SRs/MAs had moderate methodological quality, 4 SRs/MAs had very low quality, and the remaining 1 had low quality. According to the ROBIS scale, 3 SRs/MAs had a high risk of bias. The PRISMA checklist showed that the primary reporting faults were protocol registration and funding source. The GRADE system was used to analyze the evidence quality of the 51 outcomes, and no high-quality evidence was found. However, moderate-quality evidence indicated that exercise training may improve body composition [by lowering body fat mass (BFM) and body fat rate (BFR)], muscular strength, and quality of life (QoL) in PCa patients undergoing ADT. Low-quality evidence demonstrated that exercise training could improve such symptoms as fatigue, depression, sexual function, and cardiometabolic changes. Conclusions: Available evidence suggests that exercise training may be used as an adjuvant treatment for PCa patients undergoing ADT to improve several aspects of general health. Studies with more rigorous designs and larger sample sizes are needed to support our findings with more robust evidence.

Identification of potential core genes and miRNAs in pediatric ACC via bioinformatics analysis.

Pediatric adrenocortical carcinomas (ACC) are rare aggressive neoplasms with heterogeneous prognosis, and often produce a most lethal malignant tumor, whereas its aetiology is still unclear. The aim of the present study was to identify the factors responsible for the development of pediatric ACC, a better understanding of the disease, and investigate new molecular biomarkers and therapeutic targets. To identify the key genes and miRNAs linked to pediatric ACC, as well as their potential molecular mechanisms, the GSEGSE75415 and GSE169253 microarray datasets were analyzed. A total of 329 differentially produced genes (DEGs) and 187 differentially produced miRNAs (DEMs) were obtained after analyzing the GSEGSE75415 and GSE169253 datasets, respectively. Next, 3,359 genes were obtained by overlapping the target mRNAs of DEMs. Following protein-protein interaction network and Gene Ontology analysis, the ten nodes with the highest degrees were screened as hub genes. Among them, the highly expressed hub genes, MAPK1 and EP300, were associated with a worse overall survival. Additionally, hsa-miR-376, hsa-miR-148, hsa-miR-139, and hsa-miR-1305 were strongly associated with poorer survival. We proposed that the hub genes (MAPK1, EP300, hsa-miR-376, hsa-miR-148, hsa-miR-139, and hsa-miR-1305) may have a definite impact on cellular proliferation and migration in adrenocortical tumors. The roles of these hub genes in adrenocortical tumors may provide novel insight to improve the diagnosis and treatment of patients with pediatric ACC.

Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway.

BACKGROUND: The blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats. METHODS: BTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues. RESULTS: QJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB. CONCLUSION: These results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice.

The alkylating antineoplastic agent cyclophosphamide (CP) is known to be toxic to the male reproductive system, but there are no effective prevention or treatment options. The flavonoid icariin (ICA), which is used in Chinese medicine, has been shown to have a number of biological functions, including testicular protection. The current study looked into the protective effects of ICA in preventing CP-induced spermatogenesis dysfunction. The current study looked into the role of ICA in preventing testicular dysfunction caused by CP. For 5 days, healthy adult mice were given saline or a single dose of CP (50 mg/kg) intraperitoneally (i.p). For the next 30 days, mice were given ICA (80 mg/kg) by gavage. Animals were euthanized 12 h after receiving ICA, and testes were removed for biochemical, histopathological, sperm evaluation, and transmission electron microscope analysis (TEM). We also investigated the potential biological effects of ICA on CP-induced spermatogenesis dysfunction in mice using an integrated proteomic and metabolomic approach. The levels of 8309 proteins and 600 metabolites were measured. The majority of the differential proteins and metabolites were found to be enriched in a variety of metabolic pathways, including the PI3K-Akt signaling pathway, necroptosis, the mTOR signaling pathway, glycerophospholipid metabolism, and ABC transporters, implying that ICA may have molecular mechanisms that contribute to CP-induced spermatogenesis dysfunction in the testis. Taken together, these findings show that ICA effectively reduces testis injury, implying that ICA may have a role in male infertility preservation.

Bibliometric and visual analysis of blood-testis barrier research.

Background: Extensive research on the blood-testis barrier has been undertaken in recent years. However, no systematic bibliometric study has been conducted on this subject. Our research aimed to identify the hotspots and frontiers of blood-testis barrier research and to serve as a guide for future scientific research and decision-making in the field. Methods: Studies on the blood-testis barrier were found in the Web of Science Core Collection. VOSviewer, CiteSpace, and Microsoft Excel were used to conduct the bibliometric and visual analyses. Results: We found 942 blood-testis barrier studies published in English between 1992 and 2022. The number of annual publications and citations increased significantly between 2011 and 2022, notably in the United States. China and the United States, the US Population Council, Endocrinology, and Cheng C. Yan were the most productive countries, institution, journal, and author, respectively. The study keywords indicated that blood-testis barrier research involves a variety of compositional features (tight junctions, cytoskeleton, adherens junctions), cell types (Sertoli cells, germ cells, Leydig cells, stem cells), reproductive toxicity (cadmium, nanoparticles, bisphenol-a), and relevant mechanisms (spermatogenesis, apoptosis, oxidative stress, dynamics, inflammation, immune privilege). Conclusion: The composition and molecular processes of the blood-testis barrier as well as the blood-testis barrier in male infertility patients are the primary research hotspots in this field. In addition, future research will likely focus on treatment and the development of novel medications that target signal pathways in oxidative stress and apoptosis to preserve the blood-testis barrier. Further studies must extend to clinical diagnosis and therapy.

Exosomes in the f ield of reproduction: A scientometric study and visualization analysis.

Background: The diagnostic capabilities of exosomes in the field of reproductive biomedicine have attracted much attention. The aim of this scientometric study was to statistically and qualitatively assess the knowledge structure, hot issues, and research trends of papers about exosomes in the field of reproduction using visualization methods. Methods: The Web of Science Core Collection was searched for studies on exosomes in the field of reproduction. We performed bibliometric and visual analyses using VOSviewer, CiteSpace, and Microsoft Excel. Results: After database search, 1,011 articles were included, with number of studies being published every year continually increasing. These publications came from 61 nations or regions, with the US having the highest number. The University of Queensland was the main institution in which the research was conducted. The journal Placenta contained the highest number studies. There were 5,247 authors in total. Carlos Salomon had the highest number of papers with co-citations. Exosomes, extracellular vesicles, pregnancy, microRNAs, preeclampsia, placenta, microvesicles, gene expression, biomarkers, and first trimester were the most frequently used terms. Conclusion: Exosome research is booming in reproductive biomedicine. Future studies will likely focus on exosomes as biomarkers in gamete formation and fertilization, pregnancy, and cancers associated with reproduction. In addition to focusing on fundamental research, we should concentrate on the application of the results and the investigation of exosomes in infertile patients.

Novel DNAH1 Mutation Loci Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Literature Review.

The protein encoded by dynein axonemal heavy chain 1 (DNAH1) is a part of dynein, which regulates the function of cilia and sperm flagella. The mutant of DNAH1 causes the deletion of inner dynein arm 3 in the flagellum, leading to multiple morphological abnormalities of the sperm flagella (MMAF) and severe asthenozoospermia. However, instead of asthenozoospermia and MMAF, the result caused by the mutation of DNAH1 remains unknown. Here we report a male infertility patient with severe asthenozoospermia and teratozoospermia. We found two heterozygous mutations in DNAH1 (c.6912C>A and c.7076G>T) and which were reported to be associated with MMAF for the first time. We next collected and analyzed 65 cases of DNAH1 mutation and found that the proportion of short flagella is the largest, while the bent flagella account for the smallest, and the incidence of head deformity is not high in the sperm of these patients. Finally, we also analyzed 31 DNAH1 mutation patients who were treated with intracytoplasmic sperm injection (ICSI) and achieved beneficial outcomes. We hope our research will be helpful in the diagnosis and treatment of male infertility caused by DNAH1 mutation.

Effectiveness of cognitive behavioural therapy on quality of life in patients with prostate cancer after androgen deprivation therapy: a protocol for systematic review and meta-analysis.

INTRODUCTION: Prostate cancer (PCa), as a malignant tumour with rapid development in recent years, significantly affects men's health, work, life and economy. Androgen deprivation therapy (ADT) plays an important role in the treatment of PCa and can be used as a complementary therapy in the late stage of castration-resistant prostate cancer. Though ADT targeting PCa shows an effective therapeutic effect, the underlying side effects (cognitive disorder, hot flashes, a decrease in sexuality) cannot be ignored. At present, cognitive behavioural therapy (CBT) has been widely used for patients with PCa after ADT due to its confirmed efficacy, fewer side effects and lower economic burden. However, the effectiveness of CBT for patients with PCa after ADT is still controversial. Therefore, we will conduct a systematic review and meta-analysis of the effectiveness of CBT for patients with PCa after ADT. METHODS AND ANALYSIS: Literatures will be searched from establishment of the database to 31 May 2021 with the language restrictions of English and Chinese in eight online databases (PubMed, Embase, the Web of Science, Cochrane Library, VIP, CNKI, CBM, and WAN FANG). This study will include RCTs that performed CBT as the main method of the experimental group for patients with PCa after ADT. Two or more reviewers will independently conduct the selection of studies, data extraction and data analysis. The risk ratios with 95% CIs will be used to present the data synthesis result of dichotomous data, while weighted mean differences or standardised mean differences with 95% CIs will be used to present the data synthesis result of continuous data. Meanwhile, evidence quality of outcome will be assessed by using the Grading of Recommendations Assessment, Development and Evaluation method. Stata V.13.0 and Review Manager software V.5.3 will be used for analysis and synthesis. ETHICS AND DISSEMINATION: This protocol is a second study based on a completed randomised controlled study. Thus, ethical approval is not required, and no additional data are available. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/FUVEA.

Low-intensity extracorporeal shockwave therapy for erectile dysfunction: an overview of systematic reviews.

BACKGROUND: Low-intensity extracorporeal shockwave therapy (LI-ESWT) may be a successful complementary treatment approach for erectile dysfunction (ED). In this study, we aimed to review and summarize the research evidence from systematic reviews (SRs)/meta-analyses (MAs) regarding the clinical effectiveness of LI-ESWT for ED. METHODS: Studies on LI-ESWT for ED were searched using eight electronic databases from establishment of each database to 31 June 2021 with the language restrictions of Chinese and English. All articles were screened, and qualifying data were recorded based on the inclusion criteria. Methods including: the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2); the Risk of Bias in Systematic Reviews (ROBIS); the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); and Grading of Recommendations, Assessment Development, and the Evaluation (GRADE) were used by two independent raters to assess methodological quality, risk of bias, reporting quality, and SR evidence of quality, respectively. RESULTS: Eight SRs/MAs met all inclusion criteria. Seven reviews were rated as critically low on overall confidence and one review was low on confidence based on the AMSTAR-2 appraisal tool. While most PRISMA criteria were met, the major reporting flaws were in relation the financial statements not being included, along with no protocol registrations. Three SRs/MAs were classed as low risk regarding bias as measured by the ROBIS tool. Based on the GRADE method, only one SRs/MAs of high-quality evidence and seven SRs/MAs of moderate-quality evidence were found. The present research results supported LI-ESWT as a complementary therapy for ED patients, but the evidence should be considered carefully due to the methodological flaws identified. DISCUSSION: Our results showed that LI-ESWT as an adjunctive therapy has benefits for ED patients. There were no obvious side effects, and the number of shockwave treatments and energy flux density (EFD) would affect the IIEF-EF, EHS and PSV scores. However, due to the limited sample size and the quality of reporting evidence, our conclusions may not be fully representative.

Qiangjing Tablets Regulate Apoptosis and Oxidative Stress via Keap/Nrf2 Pathway to Improve the Reproductive Function in Asthenospermia Rats.

Asthenozoospermia (AZS), is a common cause of male infertility. Currently, most drugs for azoospermia lack desirable therapeutic efficiency, therefore developing new drug therapy is important. Qiangjing tablets could enhance renal function and improve sperm quality. The purpose of this study was to examine whether Qiangjing tablets could improve the reproductive function in azoospermia rats through activating the Nrf2/ARE pathway, and how to regulate energy metabolism and oxidative stress in this process. Sperm motility, sperm concentration and sperm viability were detected by WLJY-9000 Weili Digital Color Sperm Quality Detection System. HE staining was used to observe the pathological condition of testis in AZS rats. Cell apoptosis was analyzed by Tunnel staining and flow cytometry. The changes of mitochondrial membrane potential were detected by JC-1. The levels of Estradiol, testosterone and luteinizing hormone, activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and content of malondialdehyde (MDA) and glutathione (GSH) were detected by ELISA. The effects of Qiangjing Tablets on GC-1 spgs and Nrf2 protein were investigated through CCK-8 assay and western blot. The expression levels of HO-1, Keap1, and P-Nrf2 were detected by western blot. The results demonstrated that Qiangjing tablets upregulated levels of sperm motility, sperm concentration and sperm viability, which was shown to significantly increase levels of HO-1, Keap1, P-Nrf2, Estradiol and testosterone, along with increasing the activity of SOD, GSH-Px and GSH and suppressing the MDA content, luteinizing hormone and Vimentin level. Qiangjing tablets could significantly inhibit spermatogenic cells apoptosis and promote GC-1 spgs viability, increase PE/FITC ratio, mitochondrial membrane potential and reduc oxidative stress. Qiangjing tablets protected spermatogenic cell to upregulate male sex hormoneto, improved the sperm quality and reproductive function in AZS rats via activating the Keap/Nrf2 signaling pathway.