Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
Adult ; Humans ; Male ; China ; Cohort Studies ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Genotype ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities* ; East Asian People/genetics*

OBJECTIVE: To investigate the surgical method and short-term effectiveness of arthroscopy edge-to-edge #-shaped suture in the treatment of the complete radial tear of the lateral meniscus body. METHODS: The clinical data of 13 patients with complete radial tear of lateral meniscus body between May 2020 and August 2023 were retrospectively analyzed. There were 10 males and 3 females, aged 15-38 years (mean, 24.2 years). There were 11 cases of acute injury and 2 cases of chronic injury, with time from injury to admission ranging from 2 days to 5 months. All patients had tenderness in the lateral joint space, and 2 patients with chronic injury had positive McMurray's sign. All patients were treated with arthroscopic edge-to-edge #-shaped suture technique. The knee joint activity and tenderness in the lateral joint space were detected, and the healing of the incision and the occurrence of complications were observed. X-ray films and MRI of the knee joint were performed to evaluate joint degeneration and meniscus healing. Lysholm score, International Knee Documentation Committee (IKDC) subjective score, Tegner score, and visual analogue scale (VAS) score were used to evaluate the functional recovery before and after operation. RESULTS: The operation time ranged from 46 to 100 minutes (mean, 80.08 minutes). All the incisions healed by first intention, and no complication such as intraoperative vascular and nerve injury or postoperative infection occurred. All 13 patients were followed up 20-59 months (mean, 29.3 months). All patients had no limitation of knee extension and flexion. One patient with chronic injury continued to have tenderness in the lateral space of the knee joint, while the remaining patients had no tenderness, swelling, and locking in the lateral space. Immediate postoperative MRI of knee joint showed continuous recovery of the lateral meniscus. At last follow-up, no degenerative changes were observed in X-ray films of knee joint. Except for 1 patient with chronic injury, the MRI of the other patients showed the healing performance after lateral meniscus suture. Lysholm score, IKDC subjective score, Tegner score, and VAS score all significantly improved when compared with those before operation (P<0.05). CONCLUSION The edge-to-edge #-shaped suture technique can effectively repair the complete radial tear of the lateral meniscus body, and the short-term effectiveness is satisfactory.
Humans ; Male ; Female ; Adult ; Tibial Meniscus Injuries/surgery* ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Suture Techniques ; Treatment Outcome ; Menisci, Tibial/surgery* ; Sutures ; Knee Joint/surgery* ; Magnetic Resonance Imaging

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.

Objective To explore the effects and potential mechanism of electroacupuncture at acute phase on cognitive dysfunction at later stage in rats with middle cerebral artery occlusion(MCAO).Methods Totally 39 SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 13 rats in each group.MCAO model was established by Zea Longa thread embolism method in model group and electroacupuncture group.The sham-operation group only separated blood vessels.Electroacupuncture group was treated with electroacupuncture at"Baihui"and"Shenting"acupoints at 5 min and 6 h after model establishment respectively,for 30 min.The body mass,modified neuropathy severity scale(mNSS),and percentage of stiff immobility time of rats were monitored weekly,Nissl staining was used to observe the morphology of hippocampal tissue on the 28 d,immunofluorescence staining was used to detect the expression of Ki67,dual cortin(DCX)and neuronal differentiation factor 1(NeuroD1)in dentate gyrus of the hippocampus,the expression of synaptic vesicle protein 2A(SV2A)protein in dentate gyrus of hippocampus was detected by Western blot.Results Compared with the sham-operation group,on the first day after operation,the body mass of the model group rats decreased,then gradually increased,and on the 28th day,the body mass was still lower than that of the sham-operation group(P<0.05);on the first day after operation,the mNSS score significantly increased,gradually decreased thereafter,and remained higher than the sham-operation group until the 28th day(P<0.01);the percentage of stiff immobility time significantly decreased on the first day after operation,gradually stabilized,and remained lower than the sham-operation group on the 28th day(P<0.05);the hippocampal tissue structure was significantly damaged,and the density of Ki67+DCX+NeuroD1 positive cells in the dentate gyrus of hippocampus was significantly increased(P<0.05),the expression of SV2A protein in the dentate gyrus of hippocampal was significantly decreased(P<0.05).Compared with the model group,the body mass of rats in the electroacupuncture group showed an increasing trend(P<0.05),the mNSS score decreased(P<0.01),and the percentage of stiff immobility time increased(P<0.05);the ischemic injury area was significantly reduced,the structure was clearer,and the disordered and irregularly cells arrangement were reduced,the density of Ki67+DCX+NeuroD1 positive cells in the dentate gyrus of hippocampus significantly increased(P<0.05),and the expression of SV2A protein in the dentate gyrus of hippocampal significantly increased(P<0.05).Conclusion Electroacupuncture at acute phase at"Baihui"and"Shenting"can promote the recovery of cognitive dysfunction in MCAO rats in the later stage,and its mechanism may be related to enhancing the proliferation and differentiation of neural precursor cells in the dentate gyrus of hippocampus,promoting neurogenesis.

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.

Objective To investigate the effects of Sini Powder on serum hypothalamic-pituitary-adrenal(HPA)axis-related hormones and inflammatory factors in liver cancer mice with comorbid depression,and to evaluate its effect on depressive behavior and tumor proliferation activity.Methods Forty-eight specific pathogen-free female C57BL/6 mice were randomly assigned to either a blank(n=8)or model group(n=40).The modeling group was subjected to chronic unpredictable mild stress(CUMS)for six weeks.Both groups underwent orthotopically transplanted liver tumor surgery at the end of the fourth week of CUMS treatment.At the end of the sixth week of CUMS treatment,color Doppler ultrasonography was used to observe tumor formation in the orthotopic transplantation liver tumors,and the tail suspension test was used to assess depressive behavior.Non-tumor-bearing and deceased mice were excluded.The remaining model group mice were stratified by tail suspension immobility time and randomly assigned to the following groups:model group(distilled water),Fluoxetine group(5.0 mg/kg),and Sini Powder low-dose,medium-dose,and high-dose groups(5.2,10.4,and 20.8 g/kg,respectively),with six mice per group.The treatments were administered once daily for 21 consecutive days.After treatment,depressive behaviors were assessed using the open field,tail suspension,and forced swimming tests.The proliferation status of the orthotopic liver transplantation tumor was evaluated by measuring the size of the tumor,observing pathological changes in the tumor tissue through hematoxylin and eosin staining,and detecting the positive cell rate of proliferating cell nuclear antigen(Ki-67)in the tumor tissue using immunohistochemistry.The levels of HPA axis-related hormones in serum,such as corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),as well as inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an enzyme-linked immunosorbent assay.Western blotting was used to assess mitogen-activated protein kinase(MAPKs)phosphorylation and the expression of nuclear factor-κB(NF-κB),NOD-like receptor family pyrin domain-containing receptor 3(NLRP3),and cysteine aspartic protease-1(Caspase-1)in orthotopic tumors.Results Compared with the blank group,the model group showed reduced total distance traveled in open field test,prolonged immobility times in the tail suspension and forced swimming tests(P<0.05,P<0.01),indicating successful establishment of the liver cancer with comorbid depression mice model.Also,the model group showed increased orthotopic tumor volume(P<0.01),and elevated serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.01).The phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),while NF-κB,NLRP3,and Caspase-1 expression levels were downregulated(P<0.01).Compared with the model group,Sini Powder medium-and high-dose groups exhibited increased total distance traveled in the open field test(P<0.05),reduced forced swimming test and prolonged total distance traveled in open field test(P<0.01),while Sini Powder high-dose group showed reduced immobility times in the tail suspension test(P<0.05).Also,Sini Powder low-dose,medium-dose,and high-dose groups showed slower tumor growth,histological changes,including vacuolization and necrosis,decreased Ki-67 positive cell rate(P<0.01),and reduced serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.05).Additionally,the phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),and NF-κB,NLRP3,and caspase-1 expression levels were downregulated(P<0.01).Conclusion Sini Powder may alleviate depressive behaviors and suppress tumor proliferation activity in liver cancer mice with comorbid depression by modulating MAPKs activation,inhibiting NF-κB,NLRP3,and Caspase-1 expressions,and reducing serum inflammatory factors and HPA axis-related hormones levels.

Objective To investigate the effects of Sini Powder on serum hypothalamic-pituitary-adrenal(HPA)axis-related hormones and inflammatory factors in liver cancer mice with comorbid depression,and to evaluate its effect on depressive behavior and tumor proliferation activity.Methods Forty-eight specific pathogen-free female C57BL/6 mice were randomly assigned to either a blank(n=8)or model group(n=40).The modeling group was subjected to chronic unpredictable mild stress(CUMS)for six weeks.Both groups underwent orthotopically transplanted liver tumor surgery at the end of the fourth week of CUMS treatment.At the end of the sixth week of CUMS treatment,color Doppler ultrasonography was used to observe tumor formation in the orthotopic transplantation liver tumors,and the tail suspension test was used to assess depressive behavior.Non-tumor-bearing and deceased mice were excluded.The remaining model group mice were stratified by tail suspension immobility time and randomly assigned to the following groups:model group(distilled water),Fluoxetine group(5.0 mg/kg),and Sini Powder low-dose,medium-dose,and high-dose groups(5.2,10.4,and 20.8 g/kg,respectively),with six mice per group.The treatments were administered once daily for 21 consecutive days.After treatment,depressive behaviors were assessed using the open field,tail suspension,and forced swimming tests.The proliferation status of the orthotopic liver transplantation tumor was evaluated by measuring the size of the tumor,observing pathological changes in the tumor tissue through hematoxylin and eosin staining,and detecting the positive cell rate of proliferating cell nuclear antigen(Ki-67)in the tumor tissue using immunohistochemistry.The levels of HPA axis-related hormones in serum,such as corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),as well as inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an enzyme-linked immunosorbent assay.Western blotting was used to assess mitogen-activated protein kinase(MAPKs)phosphorylation and the expression of nuclear factor-κB(NF-κB),NOD-like receptor family pyrin domain-containing receptor 3(NLRP3),and cysteine aspartic protease-1(Caspase-1)in orthotopic tumors.Results Compared with the blank group,the model group showed reduced total distance traveled in open field test,prolonged immobility times in the tail suspension and forced swimming tests(P<0.05,P<0.01),indicating successful establishment of the liver cancer with comorbid depression mice model.Also,the model group showed increased orthotopic tumor volume(P<0.01),and elevated serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.01).The phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),while NF-κB,NLRP3,and Caspase-1 expression levels were downregulated(P<0.01).Compared with the model group,Sini Powder medium-and high-dose groups exhibited increased total distance traveled in the open field test(P<0.05),reduced forced swimming test and prolonged total distance traveled in open field test(P<0.01),while Sini Powder high-dose group showed reduced immobility times in the tail suspension test(P<0.05).Also,Sini Powder low-dose,medium-dose,and high-dose groups showed slower tumor growth,histological changes,including vacuolization and necrosis,decreased Ki-67 positive cell rate(P<0.01),and reduced serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.05).Additionally,the phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),and NF-κB,NLRP3,and caspase-1 expression levels were downregulated(P<0.01).Conclusion Sini Powder may alleviate depressive behaviors and suppress tumor proliferation activity in liver cancer mice with comorbid depression by modulating MAPKs activation,inhibiting NF-κB,NLRP3,and Caspase-1 expressions,and reducing serum inflammatory factors and HPA axis-related hormones levels.

Objective To explore the effects and potential mechanism of electroacupuncture at acute phase on cognitive dysfunction at later stage in rats with middle cerebral artery occlusion(MCAO).Methods Totally 39 SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 13 rats in each group.MCAO model was established by Zea Longa thread embolism method in model group and electroacupuncture group.The sham-operation group only separated blood vessels.Electroacupuncture group was treated with electroacupuncture at"Baihui"and"Shenting"acupoints at 5 min and 6 h after model establishment respectively,for 30 min.The body mass,modified neuropathy severity scale(mNSS),and percentage of stiff immobility time of rats were monitored weekly,Nissl staining was used to observe the morphology of hippocampal tissue on the 28 d,immunofluorescence staining was used to detect the expression of Ki67,dual cortin(DCX)and neuronal differentiation factor 1(NeuroD1)in dentate gyrus of the hippocampus,the expression of synaptic vesicle protein 2A(SV2A)protein in dentate gyrus of hippocampus was detected by Western blot.Results Compared with the sham-operation group,on the first day after operation,the body mass of the model group rats decreased,then gradually increased,and on the 28th day,the body mass was still lower than that of the sham-operation group(P<0.05);on the first day after operation,the mNSS score significantly increased,gradually decreased thereafter,and remained higher than the sham-operation group until the 28th day(P<0.01);the percentage of stiff immobility time significantly decreased on the first day after operation,gradually stabilized,and remained lower than the sham-operation group on the 28th day(P<0.05);the hippocampal tissue structure was significantly damaged,and the density of Ki67+DCX+NeuroD1 positive cells in the dentate gyrus of hippocampus was significantly increased(P<0.05),the expression of SV2A protein in the dentate gyrus of hippocampal was significantly decreased(P<0.05).Compared with the model group,the body mass of rats in the electroacupuncture group showed an increasing trend(P<0.05),the mNSS score decreased(P<0.01),and the percentage of stiff immobility time increased(P<0.05);the ischemic injury area was significantly reduced,the structure was clearer,and the disordered and irregularly cells arrangement were reduced,the density of Ki67+DCX+NeuroD1 positive cells in the dentate gyrus of hippocampus significantly increased(P<0.05),and the expression of SV2A protein in the dentate gyrus of hippocampal significantly increased(P<0.05).Conclusion Electroacupuncture at acute phase at"Baihui"and"Shenting"can promote the recovery of cognitive dysfunction in MCAO rats in the later stage,and its mechanism may be related to enhancing the proliferation and differentiation of neural precursor cells in the dentate gyrus of hippocampus,promoting neurogenesis.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.