Prognostic analysis of uveal melanoma based on the characteristic genes of M2-type macrophages in the tumor microenvironment.

Uveal melanoma arises from stromal melanocytes and is the most prevalent primary intraocular tumor in adults. It poses a significant diagnostic and therapeutic challenge due to its high malignancy and early onset of metastases. In recent years, there has been a growing interest in the role of diverse immune cells in tumor cell development and metastasis. Using The Cancer Genome Atlas and the gene expression omnibus databases, and the CIBERSORT method, we investigated the topography of intra-tumor immune infiltration in uveal melanoma in this research. We evaluated the prognosis of uveal melanoma patients using the M2 macrophage immune cell infiltration score in conjunction with clinical tumor patient data. We built a prognostic model based on the distinctive genes of M2 macrophages and combined it with patients' clinical data in the database; we ran a survival prognostic analysis to authenticate the model's accuracy. The functional study revealed the importance of macrophage-associated genes in the development of uveal melanoma. Moreover, the reliability of our prediction model was verified by combining tumor mutational load, immune checkpoint, and drug sensitivity, respectively. Our study provides a reference for the follow-up study of uveal melanoma.

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.

[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.

The 100 most-cited publications on Peyronie's disease: a bibliometric analysis and visualization study.

This study aimed to summarize the characteristics of the top 100 most-cited publications on Peyronie's disease (PD) research and to analyse past and current research hotspots and trends. The SCI-E database of the Web of Science Core Collection (WoSCC) provided us with the top 100 most-cited publications in PD research, from which we took the following information: general trend of publication, year of publication, nation/region, institution, journal, author, and keywords. VOSviewer (version 1.6.18) and Excel (version 2016) were used for information analysis. Through a standardized search, we ultimately found 1019 papers in the field of PD research, from which we extracted the 100 articles that had received the highest citations. The articles were published between 1949 and 2016. The United States is a major contributor to PD research (n = 67). The University of California, Los Angeles, was the institution with the largest number of articles (n = 11). These articles were published in 16 journals, with the largest number appearing in the Journal of Urology (n = 47). The author with the most articles was Levine LA (n = 9). Gelbard MK's articles had the highest citation frequency (n = 1158). Erectile dysfunction (n = 19) was the keyword with the highest frequency, indicating that PD-related erectile dysfunction was the leading focus of research in this field. Most of the keywords that have appeared in the past decade are related to the clinical treatment of PD. Therefore, we believe that improving patients' erectile function to the greatest extent in clinical treatment is the frontier and hot spot of future research.

The Effect of COVID-19 on Male Sex Hormones: A Meta-Analysis of Prospective Cohort Study.

PURPOSE: To evaluate the possible effects of novel coronavirus disease 2019 (2019-NCOV) on male sex hormones and reproductive ability, and analyze its incidence and risk factors. METHODS: We retrieved from PubMed, Embase, The Cochrane Library, Web of Science, Clinical Trails, CNKI, CBM, Wan Fang Database and VIP to collect research on the effects of COVID-19 on the male sex hormone. Our literature search was conducted until April 2022, and two investigators independently screened articles based on inclusion and exclusion criteria. In strict accordance with the inclusion and exclusion criteria, two researchers independently screened the literature and comprehensively analyzed 8 cohort studies on the impact of COVID-19 on male sex hormone. And We used RevMan5.4.1 and Stata15.0 for statistical analysis. Finally, there were eight cohort studies on the effects of COVID-19 on male sex hormones. RESULTS: T(RR = - 3.94; 95% CI - 6.22, - 1.66; P = 0.0007), testosterone in the COVID-19 group decreased by 3.94 nmol/L compared with the control group, and the difference was statistically significant. LH (RR = 0.85; 95% CI - 0.26, 1.96; P = 0.13), the LH in COVID-19 group was 0.85 mlU/ml higher than that in control group, but the difference was not statistically significant. FSH (RR = 0.25; 95% CI - 0.72, 1.23; P = 0.61), the FSH of COVID-19 group was 0.25 mlU/ml higher than that of the control group, but the difference was not statistically significant. PRL (RR = 2.42; 95% CI 0.52, 4.31; P = 0.01), the PRL in the COVID-19 group was 2.42 ng/ml higher than that in the control group, and the difference was statistically significant. E2(RR = 11.88; 95% CI 9.90, 13.86; P < 0.00001), The level of E2 in the COVID-19 group was 11.88 pg/ml higher than that in the control group, and the difference was statistically significant. T:LH (RR = - 0.39; 95% CI - 076, - 0.02; P = 0.04), the ratio of T:LH in COVID-19 group was lower than that in control group, and the difference was statistically significant. FSH:LH (RR = - 0.38; 95% CI - 0.86, 0.11; P = 0.13), the ratio of FSH:LH decreased in COVID-19 group compared with control group, but the difference was not statistically significant. CONCLUSIONS: COVID-19 can affect the level of sex hormones, especially T, which may further affect male fertility. Due to the limitations of this study, this conclusion needs to be further verified by large-sample, high-quality prospective cohort studies on the long-term effects of COVID-19 on male sex hormones and fertility.

[Correlation of IPSS with IL-8 and COX-2 levels in patients with benign prostatic hyperplasia and prostatitis].

OBJECTIVE: To investigate the correlation of International Prostate Symptom Score (IPSS) with the levels of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the prostate tissue and expressed prostatic secretion (EPS) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. METHODS: We divided 80 BPH patients to be treated by transurethral resection of the prostate (TURP) into a simple BPH group (n = 30) and a BPH with prostatitis group (n = 50) based on the pathologic features. We statistically analyzed IPSS and the levels of IL-8 and COX-2 in EPS before surgery and the IL-8 and COX-2 levels in the prostate tissue after surgery. RESULTS: IPSS was positively correlated with the IL-8 and COX-2 levels in the prostate tissue and EPS of the BPH patients, moderately in the simple hyperplasia group (r > 0.5) and highly in the other (r > 0.8). The levels of IL-8 and COX-2 in the prostate tissue and EPS were significantly higher in the BPH with prostatitis group than in the simple BPH group (P < 0.05). CONCLUSION: The levels of IL-8 and COX-2 in EPS indirectly reflect those in the prostate tissue. IPSS and the levels of IL-8 and COX-2 in EPS can help determine whether BPH is complicated by histological prostatic inflammation.

Integrative analysis illustrates the role of PCDH7 in lung cancer development, cisplatin resistance, and immunotherapy resistance: an underlying target.

Background: Cisplatin resistance is a common clinical problem in lung cancer. However, the underlying mechanisms have not yet been fully elucidated, highlighting the importance of searching for biological targets. Methods: Bioinformatics analysis is completed through downloaded public data (GSE21656, GSE108214, and TCGA) and specific R packages. The evaluation of cell proliferation ability is completed through CCK8 assay, colony formation, and EdU assay. The evaluation of cell invasion and migration ability is completed through transwell and wound-healing assays. In addition, we evaluated cell cisplatin sensitivity by calculating IC50. Results: Here, we found that PCDH7 may be involved in cisplatin resistance in lung cancer through public database analysis (GSE21656 and GSE108214). Then, a series of in vitro experiments was performed, which verified the cancer-promoting role of PCDH7 in NSCLC. Moreover, the results of IC50 detection showed that PCDH7 might be associated with cisplatin resistance of NSCLC. Next, we investigated the single-cell pattern, biological function, and immune analysis of PCDH7. Importantly, we noticed PCDH7 may regulate epithelial-mesenchymal transition activity, and the local infiltration of CD8+ T and activated NK cells. Furthermore, we noticed that patients with high PCDH7 expression might be more sensitive to bortezomib, docetaxel, and gemcitabine, and resistant to immunotherapy. Finally, a prognosis model based on three PCDH7-derived genes (GPX8, BCAR3, and TNS4) was constructed through a machine learning algorithm, which has good prediction ability on NSCLC patients' survival. Conclusion: Our research has improved the regulatory framework for cisplatin resistance in NSCLC and can provide direction for subsequent related research, especially regarding PCDH7.

Histone ubiquitination-related gene CUL4B promotes lung adenocarcinoma progression and cisplatin resistance.

Background: The role of the histone ubiquitination-related gene in the cisplatin resistance of lung adenocarcinoma (LUAD) remains an intricate subject. Methods: We accessed transcriptome data of both wild type and cisplatin-resistant cells from the GSE108214 dataset, and garnered transcriptome and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) database. Utilizing the R software, we analyzed these public datasets in depth. Real-time Quantitative PCR (qPCR) was used to detect the RNA level of CUL4B. Effect of CUL4B on cell proliferation was evaluated using CCK8 and colony formation assay. Effect of CUL4B on cell invasion was evaluated using transwell assay. Cisplatin sensitivity was evaluated by calculating IC50. Results: Our analysis shed light on the significance of the histone ubiquitination-related gene, CUL4B, in relation to cisplatin resistance and the overall survival rates of LUAD patients. Notably, CUL4B was found to be overexpressed in both lung cancer tissues and cells. Meanwhile, in vitro experiments indicated can CUL4B significantly promote the proliferation, invasion and migration of lung cancer cells. Furthermore, suppressing CUL4B expression led to a noticeable reduction in the IC50 value of cisplatin in lung cancer cells. A deep dive into biological enrichment analysis revealed that among patients exhibiting high CUL4B expression, there was a pronounced activation of the G2M checkpoint and the PI3K/AKT/mTOR signaling pathways. Immune microenvironment analysis has revealed that patients with elevated CUL4B expression may exhibit increased infiltration of M2 macrophages, coupled with a reduced infiltration of CD8+ T cells and activated NK cells. Notably, we observed higher CUL4B expression among those who responded positively to immunotherapy. Conclusion: These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target.

Meta-Analysis of Matrix Metalloproteinases in the Risk of Cardiovascular and Neurodegenerative Diseases.

Objective: To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis. Methods: Relevant literature was searched from Wanfang Medical Center, CNQI, VIP, PubMed, and other domestic and foreign literature databases for the research direction, and the risk of cardiovascular and neurodegenerative diseases induced by MMPs was meta-analyzed using the fixed-effect model and random-effect model. Results: MMP-1 and MMP-9 were risk factors for cardiovascular diseases by fixed and random-effect model analysis, respectively, while MMP-2 and MMP-9 were risk factors for increased neurodegenerative diseases by random-effect model analysis. Conclusion: MMP-1 and MMP-9 are risk factors for cardiovascular diseases, and MMP-2 and MMP-9 are major factors for increased risk of neurodegenerative diseases. MMP-1, MMP-2, and MMP-9 can be used as new targets for clinical diagnosis, treatment, and research of subsequent cardiovascular and neurodegenerative diseases.

Machine learning identifies characteristics molecules of cancer associated fibroblasts significantly correlated with the prognosis, immunotherapy response and immune microenvironment in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a highly lethal disease with a dramatic pro-fibrocytic response. Cancer-associated fibroblasts (CAFs) have been reported to play a key role in lung adenocarcinoma. Methods: Marker genes of CAFs were obtained from the Cell Marker website. Single sample gene set enrichment analysis (ssGSEA) was used for CAFs quantification. R and GraphPad Prism software were utilized for all analysis. Quantitative real-time PCR (qRT-PCR) was utilized to detect the RNA level of specific molecules. Results: Based on the ssGSEA algorithm and obtained CAFs markers, the LUAD patients with low- and high-CAFs infiltration were successfully identified, which had different response patterns to immunotherapy. Through the machine learning algorithm - LASSO logistic regression, we identified 44 characteristic molecules of CAFs. Furthermore, a prognosis signature consisting of seven characteristic genes was established, which showed great prognosis prediction ability. Additionally, we found that patients in the low-risk group might have better outcomes when receiving immunotherapy of PD-1, but not CTLA4. Also, the biological enrichment analysis revealed that immune response-related pathways were significantly associated with CAFs infiltration. Meanwhile, we investigated the underlying biological and microenvironment difference in patients with high- and low-risk groups. Finally, we identified that AMPD1 might be a novel target for LUAD immunotherapy. Patients with a high level of AMPD1 were correlated with worse responses to immunotherapy. Moreover, immunohistochemistry showed that the protein level of AMPD1 was higher in lung cancer. Results of qRT-PCR demonstrated that AMPD1 was upregulated in A549 cells compared with BEAS-2B. Meanwhile, we found that the knockdown of AMPD4 can significantly reduce the expression of CTLA4 and PDCD1, but not CD274 and PDCD1LG2. Conclusion: We comprehensively explored the role of CAFs and its characteristics molecules in LUAD immunotherapy and developed an effective signature to indicate patients prognosis and immunotherapy response. Moreover, AMPD1 was identified as a novel target for lung cancer immunotherapy.

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies.

Background: Common vaccinations may have impacts on dementia risk, but current evidence is inconsistent. We therefore investigated the association between vaccinations and dementia risk by systematic review and meta-analysis approach. Methods: We conducted an extensive search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared the risk of dementia in vaccinated versus unvaccinated populations. The adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were pooled as measures. Results: Of the 9124 records initially retrieved, 17 studies with 1857134 participants were included in our analysis. The overall pooled results showed that vaccinations were associated with a 35% lower dementia risk (HR=0.65, 95% CI: 0.60-0.71, Poverall effect < 0.001; I2 = 91.8%, Pheterogeneity<0.001). All types of vaccination were associated with a trend toward reduced dementia risk, with rabies (HR=0.43), tetanus & diphtheria & pertussis (Tdap) (HR=0.69), herpes zoster (HR=0.69), influenza (HR=0.74), hepatitis A (HR=0.78), typhoid (HR=0.80), and hepatitis B (HR=0.82) vaccinations being significant. Individuals with more full vaccination types and more annual influenza vaccinations were less likely to develop dementia. Gender and age had no effect on this association. Conclusion: Routine adult vaccinations are associated with a significant reduction in dementia risk and may be an effective strategy for dementia prevention. Further research is needed to elucidate the causal effects of this association and the underlying mechanisms.

Neuroimaging Studies of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Evidence shows that chronic prostatitis/chronic pelvic pain syndrome hugely impacts the body and mind. The central mechanisms in patients with CP/CPPS resulted in increased attention as neuroimaging techniques developed. This review investigated the study design and major neuroimaging findings in CP/CPPS patients to provide comprehensive evidence. Seven databases were searched and screened: PubMed, EMBASE/SCOPUS, Cochrane Library Database, China National Knowledge Infrastructure, VIP, Wanfang, and China Biology Medicine disc. Nine studies were eventually included in the analysis. The results demonstrate that the insula, anterior cingulate gyrus, postcentral gyrus, and precuneus are significantly associated with CP/CPPS patients' pain feelings and cause dysregulation of painful emotions, lowering patients' tolerance to stimulus.

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.

Efficacy of electroacupuncture for the treatment of asthenozoospermia: A protocol for systematic review and meta-analysis.

INTRODUCTION: Infertility has affected millions of couples aged 15 to 44 years worldwide. Recently, some studies suggest that abnormal semen quality is the main cause of male infertility and asthenozoospermia accounts for 19% of the infertility of men. The situation has brought a huge burden to the patient with asthenozoospermia and society. Acupuncture is a part of traditional Chinese medicine. Electroacupuncture (EA) has gained in popularity. Although a positive effect of manual acupuncture and EA on sperm parameters has been documented in several studies, there still a lack of more solid evidence. We hope to provide a convincing study for EA. METHODS AND ANALYSIS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of rESWT for patients with CP/CPPS will be included. We will evaluate the outcomes including NIH-CPSI, VAS, IPSS, IIEF-5, and conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on October 31st, 2021. CONCLUSIONS: EA for asthenospermia is a microtrauma surgery with less pain. EA can effectively improve sperm motility; however, its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the EA in patients with asthenospermia. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. PROTOCOL REGISTRATION NUMBER: INPLASY2020100071.

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.

Selective dorsal neurotomy in the treatment of premature ejaculation: A protocol for systematic review and meta-analysis.

INTRODUCTION: Premature ejaculation (PE) affects 8% to 30% of adult men worldwide. Recently, the incidence of PE is on the rise. A series of prior studies suggested that the incidence of PE is related to various biological factors as low testosterone, low serum vitamin D, diabetes, lower urinary tract symptoms, and other psychological factors. At present, the major treatments include selective serotonin reuptake inhibitors antidepressants (dapoxetine, paroxetine), topical anesthetics, phosphodiesterase-5 inhibitor, circumcision, and selective dorsal neurotomy (SDN). The previous study found that SDN is effective for PE. METHODS AND ANALYSIS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of selective dorsal penile neurotomy for patients with PE will be included. The outcome includes intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on June 30th of 2021. CONCLUSION: SDN can effectively prolong IELT, but its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the SDN treatment in patients with PE. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070084.

Efficacy of radial extracorporeal shock wave therapy for chronic prostatitis/chronic pelvic pain syndrome: A protocol for systematic review.

BACKGROUND: Prostatitis is a common urogenital system disease in men which affects 5% to 9% of adult men worldwide and accounts for approximately 8% of visits to urologists. In the past years, its pathogenesis is complicated and the classification of it is not clear, so the effect of treatment measures is not significant. Recently, the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) includes nonsteroidal anti-inflammatory drugs, phytotherapy, hormonal therapy, alpha-blockers, anti-anxiolytic, and acupuncture, which provide more choice for the urologist. But there still are some limitations. scholars. Many studies suggest radial extracorporeal shock wave therapy may be the better option in the treatment of CP/CPPS. However, the efficacy and safety of it still lack solid evidence. METHODS AND ANALYSIS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials.org, China National Knowledge Infrastructure Database, Wan fang Database, China Biology Medicine Database, VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of radial extracorporeal shock wave therapy (rESWT) for patients with CP/CPPS will be included. We will evaluate the outcomes including National Institutes of Health Chronic Prostatitis Symptom Index, visual analog scale, international prostate symptom score, international index of erectile function-5, and conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The current study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on October 31st of 2021. CONCLUSION: rESWT as a noninvasive treatment with no pain, which will be accepted more easily. Although some studies have suggested that rESWT can relieve the symptoms of patients, the efficacy and safety of it still lack solid evidence. To address this limitation scientifically and systematically, this study will inspect the efficacy and safety of the rESWT treatment in patients with CP/CPPS by integrating various studies. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202090076.