It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The a...It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.展开更多
Poly(2-hydroxyethyl methacrylate)(PHEMA)and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) [P(HEMA-co-SMA)]hydrogels with different compositions were prepared to be used as intravaginal rings,and their gelat...Poly(2-hydroxyethyl methacrylate)(PHEMA)and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) [P(HEMA-co-SMA)]hydrogels with different compositions were prepared to be used as intravaginal rings,and their gelation time,water content,mechanical properties and morphology were investigated.The water content of PHEMA and P(HEMA-co-SMA) hydrogels decreased as the concentration of the monomer and the degree of crosslinking increased,while the water content significantly increased as the content of SMA,the hydrophilic monomer,increased.The increasing of the concentration of the crosslinking agent affected the tensile and flexural properties highly.The presence of a proper small amount of SMA also led the tensile and flexural modulus to move to a higher level.The results showed that P(HEMA-co-SMA) hydrogel with high drug load and good mechanical properties at optimum preparation conditions can be prepared for intravaginal rings to deliver nonhormonal contraceptives.These results may be applied to prepare better intravaginal drug delivery devices.展开更多
Ejaculation is regulated by the central nervous system.However,the central pathophysiology of primary intravaginal anejaculation(PIAJ)is unclear.The present study aimed to examine the changes in regional brain activit...Ejaculation is regulated by the central nervous system.However,the central pathophysiology of primary intravaginal anejaculation(PIAJ)is unclear.The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ.A total of 20 PIAJ patients and 16 healthy controls(HCs)were enrolled from September 2020 to September 2022 in the Department of Andrology,Nanjing Drum Tower Hospital(Nanjing,China).Magnetic resonance imaging data were acquired from all participants and then were preprocessed.The measures of fractional amplitude of low-frequency fluctuation(fALFF),regional homogeneity(ReHo),and functional connectivity(FC)were calculated and compared between the groups.PIAJ patients showed increased fALFF values in the left precuneus compared with HCs.Additionally,PIAJ patients showed increased ReHo values in the left precuneus,left postcentral gyrus,left superior occipital gyrus,left calcarine fissure,right precuneus,and right middle temporal gyrus,and decreased ReHo values in the left inferior parietal gyrus,compared with HCs.Finally,brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions,which included the frontal,parietal,temporal,and occipital regions,compared with HCs.In conclusion,increased regional brain activity in the parietal,temporal,and occipital regions,and increased FC between these brain regions,may be associated with PIAJ occurrence.展开更多
Identifying relevant animal challenge models adds to the complexity of human vaccine development. Murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The que...Identifying relevant animal challenge models adds to the complexity of human vaccine development. Murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The question arises as to whether the C. trachomatis or C. muridarum pre-clinical model is optimal. We compared C. muridarum and C. trachomatis intravaginal challenge models in a combined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. muridarum studies, mice immunized with Chlamydia elementary bodies (EB) demonstrated a significant reduction in urogenital bacterial shedding as measured by qPCR (p C. trachomatis studies. We have evaluated proposed vaccine antigens in both models and observed immunization with Chlamydia major outer membrane protein (MOMP) vaccine formulations to be protective (p C. trachomatis model, and immunization with PmpD p82 translocator domain was not protective in either model. We also observed in both models that depletion of CD4+ T-cells in MOMP-immunized mice resulted in diminished protective immunity but animals were still able to reduce the infection level. In contrast, mice immunized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from intravaginal challenge in either model. Overall, we have found the C. muridarum model to be a more robust, reliable, and reproducible model for vaccine antigen discovery.展开更多
文摘It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
文摘Poly(2-hydroxyethyl methacrylate)(PHEMA)and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) [P(HEMA-co-SMA)]hydrogels with different compositions were prepared to be used as intravaginal rings,and their gelation time,water content,mechanical properties and morphology were investigated.The water content of PHEMA and P(HEMA-co-SMA) hydrogels decreased as the concentration of the monomer and the degree of crosslinking increased,while the water content significantly increased as the content of SMA,the hydrophilic monomer,increased.The increasing of the concentration of the crosslinking agent affected the tensile and flexural properties highly.The presence of a proper small amount of SMA also led the tensile and flexural modulus to move to a higher level.The results showed that P(HEMA-co-SMA) hydrogel with high drug load and good mechanical properties at optimum preparation conditions can be prepared for intravaginal rings to deliver nonhormonal contraceptives.These results may be applied to prepare better intravaginal drug delivery devices.
基金supported by grants from the Nanjing Medical Technology Development Project(No.YKK19059)Excellent Young Doctor Training Program of Jiangsu Province Hospital of Chinese Medicine(No.2023QB0126)+1 种基金Jiangsu Province Graduate Research and Practice Innovation Program Project-School Assisted General Project(No.SJCX23_0804)the General project of Natural Science Foundat。
文摘Ejaculation is regulated by the central nervous system.However,the central pathophysiology of primary intravaginal anejaculation(PIAJ)is unclear.The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ.A total of 20 PIAJ patients and 16 healthy controls(HCs)were enrolled from September 2020 to September 2022 in the Department of Andrology,Nanjing Drum Tower Hospital(Nanjing,China).Magnetic resonance imaging data were acquired from all participants and then were preprocessed.The measures of fractional amplitude of low-frequency fluctuation(fALFF),regional homogeneity(ReHo),and functional connectivity(FC)were calculated and compared between the groups.PIAJ patients showed increased fALFF values in the left precuneus compared with HCs.Additionally,PIAJ patients showed increased ReHo values in the left precuneus,left postcentral gyrus,left superior occipital gyrus,left calcarine fissure,right precuneus,and right middle temporal gyrus,and decreased ReHo values in the left inferior parietal gyrus,compared with HCs.Finally,brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions,which included the frontal,parietal,temporal,and occipital regions,compared with HCs.In conclusion,increased regional brain activity in the parietal,temporal,and occipital regions,and increased FC between these brain regions,may be associated with PIAJ occurrence.
文摘Identifying relevant animal challenge models adds to the complexity of human vaccine development. Murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The question arises as to whether the C. trachomatis or C. muridarum pre-clinical model is optimal. We compared C. muridarum and C. trachomatis intravaginal challenge models in a combined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. muridarum studies, mice immunized with Chlamydia elementary bodies (EB) demonstrated a significant reduction in urogenital bacterial shedding as measured by qPCR (p C. trachomatis studies. We have evaluated proposed vaccine antigens in both models and observed immunization with Chlamydia major outer membrane protein (MOMP) vaccine formulations to be protective (p C. trachomatis model, and immunization with PmpD p82 translocator domain was not protective in either model. We also observed in both models that depletion of CD4+ T-cells in MOMP-immunized mice resulted in diminished protective immunity but animals were still able to reduce the infection level. In contrast, mice immunized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from intravaginal challenge in either model. Overall, we have found the C. muridarum model to be a more robust, reliable, and reproducible model for vaccine antigen discovery.
