Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I² = 0; P = 0.003), total sperm count (I² = 46.3%; P = 0.043), progressive motility (I² = 50.0%; P < 0.001), total sperm motility (I² = 76.1%; P = 0.047), and normal sperm morphology (I² = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.
Pregnancy ; Female ; Humans ; Male ; Semen Analysis ; Semen ; Infertility, Male ; Sperm Motility ; COVID-19 ; Sperm Count ; Spermatozoa ; Testosterone ; Gonadal Steroid Hormones

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.
Humans ; Male ; Fluorides/adverse effects* ; Semen ; Polymorphism, Genetic ; Glutathione Transferase/genetics* ; Glutathione S-Transferase pi/genetics* ; Infertility, Male/genetics* ; Genotype ; Biomarkers ; Genetic Predisposition to Disease ; Case-Control Studies

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

According to the 2020 world cancer data report， the prevalence of prostate cancer ranks second in male malignant tumors and the mortality fifth. In China， due to the poor living and eating habits， the prevalence of prostate cancer is still rising， and advanced prostate cancer can adapt to and tolerate androgen castration related drugs through a variety of mechanisms， which often indicates poor therapeutic outcomes in the late stage. Houttuyniae Herba， a medicinal plant of family Saururaceae， has been officially identified both as food and medicine by the National Health Commission. The existing studies have shown that Houttuyniae Herba inhibits the proliferation， migration， and invasion of prostate cancer and induces its apoptosis and cell cycle arrest via multiple targets， links， and pathways. These anti-tumor activities can also be observed in breast cancer， leukemia， gastric cancer， colorectal cancer， and other tumor cells. Such activities are mainly related to the inhibited expression of cyclin and cyclin-dependent kinase， regulation of apoptosis-related proteins， activation of apoptosis-related pathways， reduced secretion of matrix metalloproteinase， inhibition of activator of transcription 3 （STAT3）/Zinc finger protein （Snail） / transcription factor twist signaling pathway， and antagonization of growth factor receptor， androgen， inflammation， and oxidative stress in promoting the occurrence and development of prostate cancer. In addition， Houttuyniae Herba is able to alleviate diabetes， regulate blood glucose-lowering pathways， and boost immunity by inhibiting the protein kinase B （Akt）/mammalian target of rapamycin （mTOR） and mitogen-activated protein kinase （MAPK） signaling pathways， thus suppressing the occurrence and progression of prostatic cancer. In conclusion，Houttuyniae Herba can be used as a potential drug against prostate cancer.

Objective:To explore the effect of Duanteng Yimu decoction （DTYM） on the activation of the human umbilical vein endothelial cell （HUVEC） model and the effect on related activated proteins and vascular endothelial growth factor （VEGF） signaling pathway. Method:After DTYM （200， 400 g·mL^-1） treatment of HUVEC induced by VEGF and tumor necrosis factor-α （TNF-α）， cell proliferation， migration， and tubulogenesis were detected by cell counting kit-8 （CCK-8） assay， 5-ethynyl-2'-deoxyuridine （EdU） assay， transwell migration assay， phalloidin staining， and matrix gel card method. The mRNA expression of adhesion factors， including E-selectin， intercellular adhesion molecule-1 （ICAM-1）， and vascular cell adhesion molecule-1 （VCAM-1） was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of von Willebrand factor （VWF）， platelet-endothelial cell adhesion molecule-31 （CD31）， angiogenic factor cysteine-rich-61 （CYR61）， angiopoietin-1 （ANG-1）， VEGF， and VEGF receptor-2 （VEGFR2） was detected by Western blot. Immunofluorescence was used to determine CD31 expression. Result:Compared with the normal group， the model group showed potentiated proliferation， migration， and tubulogenesis of HUVEC （P<0.05， P<0.01）， elevated mRNA expression of E-selectin， ICAM-1， and VCAM-1 （P<0.01）， up-regulated protein expression of VWF， CD31， ANG-1， CYR61， VEGF-α， and phospho （p）-VEGFR2 （P<0.05， P<0.01）， and increased CD31 immunofluorescence intensity （P<0.01）. Compared with the model group， the DTYM groups displayed blunted proliferation， migration， and tubulogenesis of HUVEC （P<0.05， P<0.01）， decreased mRNA expression of E-selectin， ICAM-1， and VCAM-1 （P<0.05， P<0.01）， down-regulated protein expression of VWF， CD31， ANG-1， CYR61， VEGF-α， and p-VEGFR2 （P<0.05， P<0.01）， and weakened CD31 immunofluorescence intensity （P<0.01）. Conclusion:DTYM inhibits HUVEC proliferation， migration， adhesion， and tubulogenesis， which is associated with the regulation of CD31， VWF， CYR61， and ANG-1 expression in HUVEC and the VEGF signaling pathway.

Objective:To investigate the mechanism of Duanteng Yimu decoction （DTYM） in the inhibition of pannus formation in collagen-induced arthritis （CIA） mice. Method:Twenty-four SPF-grade DBA/1 male mice were randomly divided into the following four groups： a blank group （NC group）， a model group （CIA group）， a methotrexate group （MTX group）， and a DTYM group， with six mice in each group. The mice， except for those in the NC group， were modeled. From the second immunization， the medium， MTX （1 mg·kg^-1）， and DTYM （15.4 g·kg^-1） were administered at an equal volume by gavage for 35 days. Mice were observed for general condition and the arthritis index. The knee and ankle joints were scanned by microcomputed tomography （micro CT）. Hematoxylin-eosin （HE） and safranin O/fast green staining were performed to observe pathological changes. Immunohistochemistry was performed to detect the expression of platelet/endothelial cell adhesion molecule-1 （CD31）， vascular endothelial growth factor-α （VEGF-α）， vascular endothelial growth factor receptor 2 （VEGFR2）， and phosphorylated（p）-VEGFR2. Result:Compared with the NC group， the CIA group showed red and swollen ankle joints， increased arthritis index scores （P<0.05， P<0.01）， manifest injury in the knee and ankle joints， reduced cartilage thickness， elevated Micro CT bone destruction scores of knee and ankle joints （P<0.01）， and up-regulated absorbance values of synovial CD31， VEGF-α， VEGFR2， and p-VEGFR2 （P<0.01）. Compared with the CIA group， the DTYM group showed relieved ankle joint redness and swelling， reduced arthritis index scores of mice three weeks after administration （P<0.05， P<0.01）， intact joint surfaces of the knee and ankle joints， thickened cartilage， declining Micro CT bone destruction scores in both the knee and ankle joints （P<0.05， P<0.01）， and lowered absorbance values of CD31， VEGF-α， VEGFR2， and p-VEGFR2 in the synovium （P<0.01）. Conclusion:DTYM can inhibit the pannus formation in CIA mice presumedly by regulating the VEGF pathway.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective To analyze the genetic phenotypes of Y-chromosome STR and SNP in Han male population of Wujiang area, Suzhou City and explore the genetic structure of population of Wujiang area for further examination of regional-specific Y-SNP genetic markers ancestor haplogroups. Methods Blood samples of 472 Wujiang area Han males were randomly collected and genotyped by Yfiler^TM Plus PCR Amplification Kit. The allele frequencies and haplotype frequencies of each locus were obtained using the direct calculation method. Y-SNP haplogroups of each sample were estimated using Y-Predictor software and verified through experiments by amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results A total of 453 haplotypes were found in the 27 Y-STR genetic markers in 472 Han males of Wujiang area. The haplotype diversity （HD） was 0.997 696 93, among which, the highest gene diversity （GD） value was DYF387S1a/b （GD=0.953 1） and the lowest was DYS438 （GD=0.321 8）. Based on genotyping data of 27 Y-STRs and 472 samples, 132 haplogroups from C, D, N, O and Q, etc downstream Y-SNP haplogroups were estimated and then verified through experiments. Conclusion This study is based on Y-chromosome STR haplotypes, and predicts Y-SNP haplogroups by Y-Predictor software, then uses ARMS-PCR to verify. Y-SNP genetic markers were introduced to achieve precise analysis of the genetic structure of male families in population of three towns in Wujiang area.
China ; Chromosomes, Human, Y/genetics* ; Cities ; Gene Frequency ; Genetics, Population ; Haplotypes ; Humans ; Male ; Microsatellite Repeats ; Polymorphism, Single Nucleotide

Objective To compare the subjective and objective outcomes of flexible ureterorenoscopy (F-URS) and extracorporeal shock wave lithotripsy (ESWL) for the treatment of inferior calyceal calculi between 10 to 20 mm. Method A retrospective analysis was performed for inferior calyceal calculi between 10 to 20 mm at our institution on a total of 112 patients treated with holmium laser lithotripsy or ESWL from September 2013 to September 2016. Retreatment rate, complications, stone clearance rate and subjective patient-reported outcomes were compared. Result Stone clearance rate was significantly higher in F-URS group compared with ESWL group (86.1% vs 61.8%, P < 0.05). Retreatment rate (44.7% vs 8.3%, P < 0.05) was higher in ESWL. There was no significant difference in complication (11.1% vs 7.9%, P > 0.05). Overall satisfaction score [(2.92 ± 1.24) vs (2.07 ± 1.35), P < 0.05] and voiding symptom score [(3.87 ± 0.64) vs (2.23 ± 0.73), P < 0.05)] were significantly higher in F-URS than ESWL. More patients in F-URS were willing to undergo the procedure again (83.3% vs 55.3%, P<0.05). Conclusion For the treatment of intermediate size inferior calyceal calculi,F-URS is superior to ESWL in terms of stone clearance rate, retreatment rate and subjective satisfaction.

The pathogenesis of male infertility involves the interactions between environmental and genetic factors. An individual's susceptibility to male infertility is influenced by his internal abilities of metabolizing and detoxicating endogenous and exogenous chemicals. Glutathione-S-transferases (GSTs), such as enzymes, are involved in the cellular detoxication of various physiological and xenobiotic substances. Studies show that the polymorphism of the GSTs gene is correlated with male infertility. GSTs polymorphism-related susceptibilities to male infertility were found similar but with some inconsistencies within the same community, and inconsistent with some similarities among different communities. Therefore, further studies are to be done on the differences in GSTs polymorphism-related susceptibility to male infertility in different communities.
Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Genetic