This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

Parkinson's disease(PD)is the second most prevalent neurodegenerative disease and a major cause of movement disorders.Neuroinflammation plays an important role in the pathogenesis of PD.Icilin is a small molecule compound that has been reported to inhibit inflammation.Howev-er,its role in PD has not been reported.This study explored the effects of icilin on motor behavior,nerve damage,microglia activation,and neuroinflammation in MPTP-induced PD Meriones unguic-ulatus by behavioral experiments,immunohistochemistry,Western blot,and fluorescence quantifi-cation.The results showed that Icilin not only ameliorated motor dysfunction and neurological damage in MPTP-induced Meriones unguiculatus,but also inhibited microglia hyperactivation and its mediated neuroinflammation.The present study provides an evidence that icilin attenuates MPTP-induced neurodegenerative lesions in long-pawed gerbils,suggesting that it is a promising candidate for PD.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

Parkinson's disease(PD)is the second most prevalent neurodegenerative disease and a major cause of movement disorders.Neuroinflammation plays an important role in the pathogenesis of PD.Icilin is a small molecule compound that has been reported to inhibit inflammation.Howev-er,its role in PD has not been reported.This study explored the effects of icilin on motor behavior,nerve damage,microglia activation,and neuroinflammation in MPTP-induced PD Meriones unguic-ulatus by behavioral experiments,immunohistochemistry,Western blot,and fluorescence quantifi-cation.The results showed that Icilin not only ameliorated motor dysfunction and neurological damage in MPTP-induced Meriones unguiculatus,but also inhibited microglia hyperactivation and its mediated neuroinflammation.The present study provides an evidence that icilin attenuates MPTP-induced neurodegenerative lesions in long-pawed gerbils,suggesting that it is a promising candidate for PD.

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

Objective To deeply explore the principles of drug combinations in the treatment of vitiligo by traditional Chinese medicine master XUAN Guo-Wei by data mining technology,and to analyze the potential mechanism of action of the core drug pairs by network pharmacology.Methods The original case records of Professor XUAN Guo-Wei in treating vitiligo were compiled,and then TCM inheritance Computing Platform was used to analyze the frequency of drugs in the prescriptions,the association rules between drugs,and the core combinations of drugs by the association rule method,and the core drug pairs of Professor XUAN Guo-Wei's treatment of vitiligo were obtained based on the results of the data mining,additionally,the mechanism of the core pairs of drugs was analyzed by using the method of network pharmacology.Results A total of 243 prescriptions were collected,among which the high-frequency drugs were Glycyrrhizae Radix et Rhizoma,Tribuli Fructus,Ecliptae Herba,Cuscutae Semen,Scrophulariae Radix,Angelicae Dahuricae Radix,etc.,and the core pair was Tribuli Fructus-Ecliptae Herba.The main components of Tribuli Fructus-Ecliptae Herba for the treatment of vitiligo were quercetin,kaempferol,etc.,there were 47 targets for the intersection of the active ingredients with the disease,among which TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,and IL4 may be the core targets for the treatment of vitiligo by Tribuli Fructus-Ecliptae Herba.The main pathways of Tribuli Fructus-Ecliptae Herba drug pairs against the disease were PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.Conclusion The core drug pair of Professor XUAN Guo-Wei in the treatment of vitiligo is Tribuli Fructus-Ecliptae Herba,which involves targets such as TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,IL4,etc.,Tribuli Fructus-Ecliptae Herba drug pair maybe exert an effect in the treatment of vitiligo through PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.

Tripterifordin and neotripterifordin are important ent-kaurane diterpenoids in the Chinese medicinal herb Tripterygium wilfordii, possessing significant anti-HIV(human immunodeficiency virus) activity. On the basis of elucidating the natural biosynthetic pathways of these compounds, heterologous production with microbial cell factories can help to alleviate the reliance on plant resources and provide abundant raw materials for sustainable production. TwKO is the first CYP450 enzyme involved in the biosynthesis of tripterifordin and neotripterifordin. This study aimed to enhance the catalytic activity of TwKO by site-directed mutagenesis to benefit the production of tripterifordin and neotripterifordin in yeast. The AlphaFold DB established based on the AlphaFold 2 was employed to obtain the protein model of TwKO. According to multiple sequence alignments and principles of natural evolution, the key residues influencing the binding of TwKO to the substrate were identified. Subsequently, functional characterization of the mutants were conducted in Saccharomyces cerevisiae. A total of 71 mutants were obtained, among which 11 and 11 mutants had the abilities of enhancing the production of 16α-hydroxy-ent-kaurenol and 16α-hydroxy-ent-kaurenoic acid, respectively. In addition, 10 mutants could increase the proportion of the oxidation product of 16α-hydroxy-ent-kaurenol. In particular, R304 was identified as a key residue affecting the catalytic specificity of TwKO, the mutation of which led to the specific prodiction of 16α-hydroxy-ent-kaurenol. This study was the first to reveal the key residue affecting the catalytic activity of TwKO and obtained the mutants with increased TwKO activity, lay a foundation for the biosynthesis of tripterifordin and neotripterifordin.
Tripterygium/chemistry* ; Mutagenesis, Site-Directed ; Diterpenes, Kaurane/chemistry* ; Plant Proteins/chemistry* ; Cytochrome P-450 Enzyme System/chemistry* ; Saccharomyces cerevisiae/metabolism*

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve