AIM To describe contrast-enhanced ultrasound(CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study ...AIM To describe contrast-enhanced ultrasound(CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as(1) benign,(2) probably benign,(3) probably malignant or(4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared.RESULTS There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS(e.g., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8%and 95.2%, respectively. These were significantly higher than conventional ultrasound(82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer.CONCLUSION CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound.展开更多
BACKGROUND It is important to differentiate benign and malignant focal liver lesions(FLLs)accurately.Despite the wide use and acceptance of shear wave elastography(SWE),its value for assessing the elasticity of FLLs a...BACKGROUND It is important to differentiate benign and malignant focal liver lesions(FLLs)accurately.Despite the wide use and acceptance of shear wave elastography(SWE),its value for assessing the elasticity of FLLs and differentiating benign and malignant FLLs is still investigational.Previous studies of SWE for FLLs used mean elasticity as the parameter to reflect the stiffness of FLLs.Considering the inhomogeneity of tumor stiffness,maximal elasticity(Emax)might be the suitable parameter to reflect the stiffness of FLLs and to differentiate malignant FLLs from benign ones.AIM To explore the value of SWE with Emax in differential diagnosis of solid FLLs.METHODS We included 104 solid FLLs in 95 patients and 50 healthy volunteers.All the subjects were examined using conventional ultrasound(US)and virtual touch tissue quantification(VTQ)imaging.A diagnosis of benign or malignant FLL was made using conventional US.Ten VTQ values were acquired after 10 consecutive measurements for each FLL and each normal liver,and the largest value was recorded as Emax.RESULTS There were 56 cases of malignant FLLs and 48 cases of benign FLLs in this study.Emax of malignant FLLs(3.29±0.88 m/s)was significantly higher than that of benign FLLs(1.30±0.46 m/s,P<0.01)and that of livers in healthy volunteers(1.15±0.17 m/s,P<0.01).The cut-off point of Emax was 1.945,and the area under the curve was 0.978.The sensitivity and specificity of Emax were 92.9%and 91.7%,respectively,higher(but not significantly)than those of conventional US(80.4%for sensitivity and 81.3%for specificity).Combined diagnosis of conventional US and Emax using parallel testing improved the sensitivity to 100%with specificity of 75%.CONCLUSION SWE is a convenient and easy method to obtain accurate stiffness information of solid FLLs.Emax is useful for differential diagnosis of FLLs,especially in combination with conventional US.展开更多
BACKGROUND The clinical management and prognosis differ between benign and malignant solid focal liver lesions(FLLs),as well as among different pathological types of malignant FLLs.Accurate diagnosis of the possible t...BACKGROUND The clinical management and prognosis differ between benign and malignant solid focal liver lesions(FLLs),as well as among different pathological types of malignant FLLs.Accurate diagnosis of the possible types of solid FLLs is important.Our previous study confirmed the value of shear wave elastography(SWE)using maximal elasticity(Emax)as the parameter in the differential diagnosis between benign and malignant FLLs.However,the value of SWE in the differential diagnosis among different pathological types of malignant FLLs has not been proved.AIM To explore the value of two-dimensional SWE(2D-SWE)using Emax in the differential diagnosis of FLLs,especially among different pathological types of malignant FLLs.METHODS All the patients enrolled in this study were diagnosed as benign,malignant or undetermined FLLs by conventional ultrasound.Emax of FLLs and the periphery of FLLs was measured using 2D-SWE and compared between benign and malignant FLLs or among different pathological types of malignant FLLs.RESULTS The study included 32 benign FLLs in 31 patients and 100 malignant FLLs in 96 patients,including 16 cholangiocellular carcinomas(CCCs),72 hepatocellular carcinomas(HCCs)and 12 liver metastases.Thirty-five FLLs were diagnosed as undetermined by conventional ultrasound.There were significant differences between Emax of malignant(2.21±0.57 m/s)and benign(1.59±0.37 m/s)FLLs(P=0.000),and between Emax of the periphery of malignant(1.52±0.39 m/s)and benign(1.36±0.44 m/s)FLLs(P=0.040).Emax of liver metastases(2.73±0.99 m/s)was significantly higher than that of CCCs(2.14±0.34 m/s)and HCCs(2.14±0.46 m/s)(P=0.002).The sensitivity,specificity and accuracy were 71.00%,84.38%and 74.24%respectively,using Emax>1.905 m/s(AUC 0.843)to diagnose as malignant and 23 of 35(65.74%)FLLs with undetermined diagnosis by conventional ultrasound were diagnosed correctly.CONCLUSION Malignant FLLs were stiffer than benign ones and liver metastases were stiffer than primary liver carcinomas.2D-SWE with Emax was a useful complement to conventional ultrasound for the differential diagnosis of FLLs.展开更多
Hydraulic fracturing in the soil core of earth-rockfill dams is a common problem affecting the safety of the dams. Based on fracture tests, a new criterion for hydraulic fracturing in cohesive soil was suggested. Usin...Hydraulic fracturing in the soil core of earth-rockfill dams is a common problem affecting the safety of the dams. Based on fracture tests, a new criterion for hydraulic fracturing in cohesive soil was suggested. Using this criterion, the mechanisms of hydraulic fracturing in cubic soil specimens were investigated. The results indicate that the propagation of the crack in a cubic specimen under water pressure occurs in a mixed mode I-II if the crack face is not perpendicular to any of the principal stresses, and the crack most likely to propagate is the one that is perpendicular to the minor principal stress and propagates in mode I.展开更多
This study was designed to evaluate the effects of testosterone supplementation(TS)on body composition in patients with HIV and the side effects of TS.A comprehensive literature search strategy was used to retrieve re...This study was designed to evaluate the effects of testosterone supplementation(TS)on body composition in patients with HIV and the side effects of TS.A comprehensive literature search strategy was used to retrieve relevant randomized controlled trials(RCTs)examining the effects of TS on body composition.A total of 14 eligible studies were included,enrolling 388 and 349 randomized patients in TS and control groups,respectively.The quality of studies included was assessed,and data on total body weight(BW),lean body mass(LBM),fat mass(FM),serum total testosterone(TT),free testosterone(FT)levels,and adverse events were extracted and analyzed using Review Manager software 5.3.Meta-analysis results showed that TS was associated with a small but significant modification in total BW,serum TT,and FT levels in HIV-infected patients and in patients given various drug administrations.TS also significantly increased LBM in male patients,but no significant difference in LBM was observed between female counterparts treated with TS or not.Conversely,TS relative to placebo did not lead to a significant reduction in FM.No significant difference was observed between the two groups in terms of adverse effects.Our findings suggested that TS may be recommended to improve body composition in patients with HIV-related weight loss.However,owing to the high heterogeneity across included trials,further evaluations using large-scale,multi-center,blinded RCTs are needed.展开更多
Eight of three different kinds of long absorption wavelength dyes with typical structures have been chosen for studying the relation between structure and stability. The three kinds of dyes are quincoyanine. naphthoth...Eight of three different kinds of long absorption wavelength dyes with typical structures have been chosen for studying the relation between structure and stability. The three kinds of dyes are quincoyanine. naphthothiacarbocyanine and carbocyanines. The environmental effect, such as light.oxygen and water, has been investigated. Results show that quinocyanine dyes prefer to hydrolytic reaction. while naphthothiacarbocyanine dyes tend to oxidizing reaction and photo-oxidation reaction process in singlet oxygen mechanism.展开更多
Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%,primarily affecting testicular and epididymal function and ultimately compromising...Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%,primarily affecting testicular and epididymal function and ultimately compromising sperm quality.However,most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked.Traditional indicators,including white blood cells,elastase,and other components in semen,can reflect inflammation of the genital tract,but there is still a lack of a uniform standard method of detection.Therefore,it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract.Using the experimental autoimmune orchitis(EAO)model to simulate noninfectious chronic orchitis,we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices.Proteomic analysis was performed using isobaric tags for relative and absolute quantification(iTRAQ).Compared to the control group,55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group.In a preliminary screening,the inflammation-related protein S100A8/A9 was upregulated.We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model.In patients with oligoasthenospermia and genital tract infections,we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages.S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation.Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.展开更多
Male reproductive infections are known to shape the immunological homeostasis of the testes,leading to male infertility.However,the specific pathogenesis of these changes remains poorly understood.Exosomes released in...Male reproductive infections are known to shape the immunological homeostasis of the testes,leading to male infertility.However,the specific pathogenesis of these changes remains poorly understood.Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells.Here,we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes(IT-exos)and explore their underlying mechanisms in orchitis.IT-exos were isolated using a uropathogenic Escherichia coli(UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in vitro.We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages(TMs)from normal and UPEC-infected testes,respectively,and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes.Further study of bone marrow derived macrophages(BMDMs)transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype.In addition,the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages;however,IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses.Overall,we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis.Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.展开更多
Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen ...Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.展开更多
基金Supported by the National Natural Science Foundation of China,No.81301232
文摘AIM To describe contrast-enhanced ultrasound(CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as(1) benign,(2) probably benign,(3) probably malignant or(4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared.RESULTS There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS(e.g., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8%and 95.2%, respectively. These were significantly higher than conventional ultrasound(82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer.CONCLUSION CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound.
基金Natural Science Foundation of Shanghai of China,No.19ZR1441500.
文摘BACKGROUND It is important to differentiate benign and malignant focal liver lesions(FLLs)accurately.Despite the wide use and acceptance of shear wave elastography(SWE),its value for assessing the elasticity of FLLs and differentiating benign and malignant FLLs is still investigational.Previous studies of SWE for FLLs used mean elasticity as the parameter to reflect the stiffness of FLLs.Considering the inhomogeneity of tumor stiffness,maximal elasticity(Emax)might be the suitable parameter to reflect the stiffness of FLLs and to differentiate malignant FLLs from benign ones.AIM To explore the value of SWE with Emax in differential diagnosis of solid FLLs.METHODS We included 104 solid FLLs in 95 patients and 50 healthy volunteers.All the subjects were examined using conventional ultrasound(US)and virtual touch tissue quantification(VTQ)imaging.A diagnosis of benign or malignant FLL was made using conventional US.Ten VTQ values were acquired after 10 consecutive measurements for each FLL and each normal liver,and the largest value was recorded as Emax.RESULTS There were 56 cases of malignant FLLs and 48 cases of benign FLLs in this study.Emax of malignant FLLs(3.29±0.88 m/s)was significantly higher than that of benign FLLs(1.30±0.46 m/s,P<0.01)and that of livers in healthy volunteers(1.15±0.17 m/s,P<0.01).The cut-off point of Emax was 1.945,and the area under the curve was 0.978.The sensitivity and specificity of Emax were 92.9%and 91.7%,respectively,higher(but not significantly)than those of conventional US(80.4%for sensitivity and 81.3%for specificity).Combined diagnosis of conventional US and Emax using parallel testing improved the sensitivity to 100%with specificity of 75%.CONCLUSION SWE is a convenient and easy method to obtain accurate stiffness information of solid FLLs.Emax is useful for differential diagnosis of FLLs,especially in combination with conventional US.
基金Supported by Natural Science Foundation of Shanghai of China,No.19ZR1441500,No.22ZR1458200Science Research Foundation of Shanghai Municipal Health Commission,No.202140378Key Program of Science and Technology Commission Foundation of Changning,Shanghai,China,No.CNKW2020Z04.
文摘BACKGROUND The clinical management and prognosis differ between benign and malignant solid focal liver lesions(FLLs),as well as among different pathological types of malignant FLLs.Accurate diagnosis of the possible types of solid FLLs is important.Our previous study confirmed the value of shear wave elastography(SWE)using maximal elasticity(Emax)as the parameter in the differential diagnosis between benign and malignant FLLs.However,the value of SWE in the differential diagnosis among different pathological types of malignant FLLs has not been proved.AIM To explore the value of two-dimensional SWE(2D-SWE)using Emax in the differential diagnosis of FLLs,especially among different pathological types of malignant FLLs.METHODS All the patients enrolled in this study were diagnosed as benign,malignant or undetermined FLLs by conventional ultrasound.Emax of FLLs and the periphery of FLLs was measured using 2D-SWE and compared between benign and malignant FLLs or among different pathological types of malignant FLLs.RESULTS The study included 32 benign FLLs in 31 patients and 100 malignant FLLs in 96 patients,including 16 cholangiocellular carcinomas(CCCs),72 hepatocellular carcinomas(HCCs)and 12 liver metastases.Thirty-five FLLs were diagnosed as undetermined by conventional ultrasound.There were significant differences between Emax of malignant(2.21±0.57 m/s)and benign(1.59±0.37 m/s)FLLs(P=0.000),and between Emax of the periphery of malignant(1.52±0.39 m/s)and benign(1.36±0.44 m/s)FLLs(P=0.040).Emax of liver metastases(2.73±0.99 m/s)was significantly higher than that of CCCs(2.14±0.34 m/s)and HCCs(2.14±0.46 m/s)(P=0.002).The sensitivity,specificity and accuracy were 71.00%,84.38%and 74.24%respectively,using Emax>1.905 m/s(AUC 0.843)to diagnose as malignant and 23 of 35(65.74%)FLLs with undetermined diagnosis by conventional ultrasound were diagnosed correctly.CONCLUSION Malignant FLLs were stiffer than benign ones and liver metastases were stiffer than primary liver carcinomas.2D-SWE with Emax was a useful complement to conventional ultrasound for the differential diagnosis of FLLs.
基金supported by the National Natural Science Foundation of China (Grant No. 50779081)the Key Project of the Chinese Ministry of Education (Grant No. 208114)the Science and Technology Project of the Chongqing Municipal Education Commission of China (Grant No. KJ080428)
文摘Hydraulic fracturing in the soil core of earth-rockfill dams is a common problem affecting the safety of the dams. Based on fracture tests, a new criterion for hydraulic fracturing in cohesive soil was suggested. Using this criterion, the mechanisms of hydraulic fracturing in cubic soil specimens were investigated. The results indicate that the propagation of the crack in a cubic specimen under water pressure occurs in a mixed mode I-II if the crack face is not perpendicular to any of the principal stresses, and the crack most likely to propagate is the one that is perpendicular to the minor principal stress and propagates in mode I.
文摘This study was designed to evaluate the effects of testosterone supplementation(TS)on body composition in patients with HIV and the side effects of TS.A comprehensive literature search strategy was used to retrieve relevant randomized controlled trials(RCTs)examining the effects of TS on body composition.A total of 14 eligible studies were included,enrolling 388 and 349 randomized patients in TS and control groups,respectively.The quality of studies included was assessed,and data on total body weight(BW),lean body mass(LBM),fat mass(FM),serum total testosterone(TT),free testosterone(FT)levels,and adverse events were extracted and analyzed using Review Manager software 5.3.Meta-analysis results showed that TS was associated with a small but significant modification in total BW,serum TT,and FT levels in HIV-infected patients and in patients given various drug administrations.TS also significantly increased LBM in male patients,but no significant difference in LBM was observed between female counterparts treated with TS or not.Conversely,TS relative to placebo did not lead to a significant reduction in FM.No significant difference was observed between the two groups in terms of adverse effects.Our findings suggested that TS may be recommended to improve body composition in patients with HIV-related weight loss.However,owing to the high heterogeneity across included trials,further evaluations using large-scale,multi-center,blinded RCTs are needed.
文摘Eight of three different kinds of long absorption wavelength dyes with typical structures have been chosen for studying the relation between structure and stability. The three kinds of dyes are quincoyanine. naphthothiacarbocyanine and carbocyanines. The environmental effect, such as light.oxygen and water, has been investigated. Results show that quinocyanine dyes prefer to hydrolytic reaction. while naphthothiacarbocyanine dyes tend to oxidizing reaction and photo-oxidation reaction process in singlet oxygen mechanism.
基金supported by the National Natural Foundation of China(81871148)the Open Fund of NHC Key Laboratory of Birth Defects Prevention,Henan Key Laboratory of Population Defects Prevention(Henan Institute of Reproduction Health Science and Technology,ZD202201)the Fundamental Research Funds for the Central Universities,HUST(2023JYCXJJ062 and YCJJ202201050).
文摘Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%,primarily affecting testicular and epididymal function and ultimately compromising sperm quality.However,most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked.Traditional indicators,including white blood cells,elastase,and other components in semen,can reflect inflammation of the genital tract,but there is still a lack of a uniform standard method of detection.Therefore,it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract.Using the experimental autoimmune orchitis(EAO)model to simulate noninfectious chronic orchitis,we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices.Proteomic analysis was performed using isobaric tags for relative and absolute quantification(iTRAQ).Compared to the control group,55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group.In a preliminary screening,the inflammation-related protein S100A8/A9 was upregulated.We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model.In patients with oligoasthenospermia and genital tract infections,we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages.S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation.Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.
基金This work was funded by National Key R&D Program of China(2018YFC1004300 and 2018YFC1004304)National Natural Foundation of China(No.81871148 and No.818701539).
文摘Male reproductive infections are known to shape the immunological homeostasis of the testes,leading to male infertility.However,the specific pathogenesis of these changes remains poorly understood.Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells.Here,we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes(IT-exos)and explore their underlying mechanisms in orchitis.IT-exos were isolated using a uropathogenic Escherichia coli(UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in vitro.We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages(TMs)from normal and UPEC-infected testes,respectively,and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes.Further study of bone marrow derived macrophages(BMDMs)transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype.In addition,the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages;however,IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses.Overall,we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis.Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
基金the National Natural Science Foundation of China(Grant No.81871148,No.81701539 and No.81571496).
文摘Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.