Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

Objective:To investigate the clinical efficacy and safety of needle-free and needle-based injections of recombinant human interferon (IFN) -α2a in the treatment of palmoplantar warts.Methods:Patients aged 6 to 75 years with palmoplantar warts were prospectively enrolled from the Department of Dermatology, Zhongda Hospital, Southeast University between March and September 2023, and baseline data were collected. The patients were randomly and equally divided into a needle-free injection group and a needle-based injection group by using a random number table method, and received needle-free and needle-based injections of recombinant human IFN-α2a once every 2 to 3 weeks, respectively, with a maximum of 4 treatment sessions. Efficacy was assessed based on changes in wart size and skin lines under a dermoscope. Pain degrees and adverse reactions were recorded, and patients were followed up for 6 months after the end of treatment. Chi-square test was used to compare the cure rates, recurrence rates, and incidence rates of adverse reactions between the two groups. Logistic regression analysis was employed to identify factors related to the clearance of palmoplantar warts.Results:A total of 160 patients with palmoplantar warts were included, with 80 patients in each group. In the needle-free injection group, there were 45 females (56.2%) and 35 males (43.8%) ; their ages ( M[ Q1, Q3]) were 27 (23, 40) years, and the duration of disease ( M[ Q1, Q3]) was 12 (3, 24) months; warts were located on the hands in 12 cases (15.0%), on the feet in 60 cases (75.0%), and on both sites in 8 cases (10.0%) ; warts measuring ≤ 1 cm in diameter were observed in 71 cases (88.8%), and those measuring > 1 cm were observed in 9 cases (11.3%). In the needle-based injection group, there were 37 females (46.2%) and 43 males (53.8%) ; their ages were 28 (22, 39) years, and the duration of disease was 6 (2, 12) months; warts were located on the hands in 23 cases (28.7%), on the feet in 55 cases (68.8%), and on both sites in 2 cases (2.5%) ; warts measuring ≤ 1 cm in diameter were observed in 67 cases (83.8%), and those measuring > 1 cm in diameter were observed in 13 cases (16.3%). There were no significant differences in gender distribution, age, wart diameters, prior treatment status, or number of warts between the two groups (all P > 0.05). The duration of disease was longer in the needle-free injection group than in the needle-based injection group ( P = 0.041), and the dose of interferon was lower in the needle-free injection group than in the needle-based injection group ( P < 0.001). After treatment, 44 patients (55.0%) were cured in the needle-free injection group, and 39 (48.8%) in the needle-based injection group, with no significant difference in the cure rates between the two groups ( χ2 = 0.63, P = 0.429). Among patients with multiple warts, 54.8% (23/42) were cured in the needle-free injection group, and 47.4% (18/38) in the needle-based injection group, with no significant difference in cure rates between the two groups ( χ2 = 1.28, P = 0.509). The most common adverse reaction was fever or flu-like symptoms (186 instances), which resolved spontaneously in 141 instances and resolved after treatment with oral ibuprofen in 45 instances; the incidence rate of flu-like symptoms was significantly lower in the needle-free injection group (57 instances, 21.6%) than in the needle-based injection group (129 instances, 53.3%; χ2 = 54.63, P < 0.001). The pain score was significantly lower in the needle-free injection group (3.65 ± 1.25 points) than in the needle-based injection group (5.16 ± 1.17 points, t = -7.90, P < 0.001). The logistic regression analysis showed that the duration of disease, lesion sites, patient age, and previous treatment history had no impact on the efficacy in either the needle-free injection group or the needle-based injection group (all P > 0.05) . Conclusions:The efficacy of needle-free and needle-based injections of interferon was similar in the treatment of palmoplantar warts, whereas needle-free injections resulted in less pain and a lower incidence of interferon-related adverse reactions. None of the duration of disease, lesion sites, patient age, or prior treatment status showed significant impact on the efficacy in the two groups.

A novel epileptic seizure prediction prediction model based on multichannel temporal and spatial feature extractions is presented.The model applies Stockwell transform to the original multichannel electroencephalogram(EEG)signals for extracting time-frequency components.To address the issue of insignificant difference between preseizure and interseizure time-frequency features,an adaptive feature module composing of ConvNeXt,SENet and pyramid pooling module is designed to enhance the ability of capturing key time-frequency features in each EEG channel.Meanwhile,a prediction model based on Bi-NLSTM is constructed to improve the spatiotemporal dependence between the time-frequency features of multichannel high-order EEG for further promoting the epilepsy classification performance.On the CHB-MIT dataset,the model has an accuracy,sensitivity,specificity and AUC of 96.0%,97.8%,96.8%and 0.987,respectively,and the false positive rate per hour decreased to 0.038,outperforming the existing mainstream methods.In addition,the effect of each component on the model performance is verified by ablation study.The proposed method improves the overall performance for seizure prediction effectively by optimizing local time-frequency feature extraction and enhancing multichannel spatiotemporal dependence.

The nursing experience was summarised over a patient who developed an impending myasthenic crisis following immune checkpoint inhibitors(ICIs)therapy after the surgery for stage-Ⅳ liver cancer.Key nursing points included:close monitoring for early signs of impending myasthenic crisis;set up a multi-disciplinary team to improve respiratory,oropharyngeal and ocular function,control respiratory infection,provide psychological support in order to prevent the patient from developing a manifest myasthenia-gravis crisis(MC);combine with medications to relieve myasthenic symptoms and prevent adverse drug reactions;individualised rehabilitation training to promote recovery of muscular strength.Eventually,the patient did not develop into a MC during hospitalisation(20d)and was well at 3-month after discharge.

Objective:To investigate the clinical efficacy and safety of needle-free and needle-based injections of recombinant human interferon (IFN) -α2a in the treatment of palmoplantar warts.Methods:Patients aged 6 to 75 years with palmoplantar warts were prospectively enrolled from the Department of Dermatology, Zhongda Hospital, Southeast University between March and September 2023, and baseline data were collected. The patients were randomly and equally divided into a needle-free injection group and a needle-based injection group by using a random number table method, and received needle-free and needle-based injections of recombinant human IFN-α2a once every 2 to 3 weeks, respectively, with a maximum of 4 treatment sessions. Efficacy was assessed based on changes in wart size and skin lines under a dermoscope. Pain degrees and adverse reactions were recorded, and patients were followed up for 6 months after the end of treatment. Chi-square test was used to compare the cure rates, recurrence rates, and incidence rates of adverse reactions between the two groups. Logistic regression analysis was employed to identify factors related to the clearance of palmoplantar warts.Results:A total of 160 patients with palmoplantar warts were included, with 80 patients in each group. In the needle-free injection group, there were 45 females (56.2%) and 35 males (43.8%) ; their ages ( M[ Q1, Q3]) were 27 (23, 40) years, and the duration of disease ( M[ Q1, Q3]) was 12 (3, 24) months; warts were located on the hands in 12 cases (15.0%), on the feet in 60 cases (75.0%), and on both sites in 8 cases (10.0%) ; warts measuring ≤ 1 cm in diameter were observed in 71 cases (88.8%), and those measuring > 1 cm were observed in 9 cases (11.3%). In the needle-based injection group, there were 37 females (46.2%) and 43 males (53.8%) ; their ages were 28 (22, 39) years, and the duration of disease was 6 (2, 12) months; warts were located on the hands in 23 cases (28.7%), on the feet in 55 cases (68.8%), and on both sites in 2 cases (2.5%) ; warts measuring ≤ 1 cm in diameter were observed in 67 cases (83.8%), and those measuring > 1 cm in diameter were observed in 13 cases (16.3%). There were no significant differences in gender distribution, age, wart diameters, prior treatment status, or number of warts between the two groups (all P > 0.05). The duration of disease was longer in the needle-free injection group than in the needle-based injection group ( P = 0.041), and the dose of interferon was lower in the needle-free injection group than in the needle-based injection group ( P < 0.001). After treatment, 44 patients (55.0%) were cured in the needle-free injection group, and 39 (48.8%) in the needle-based injection group, with no significant difference in the cure rates between the two groups ( χ2 = 0.63, P = 0.429). Among patients with multiple warts, 54.8% (23/42) were cured in the needle-free injection group, and 47.4% (18/38) in the needle-based injection group, with no significant difference in cure rates between the two groups ( χ2 = 1.28, P = 0.509). The most common adverse reaction was fever or flu-like symptoms (186 instances), which resolved spontaneously in 141 instances and resolved after treatment with oral ibuprofen in 45 instances; the incidence rate of flu-like symptoms was significantly lower in the needle-free injection group (57 instances, 21.6%) than in the needle-based injection group (129 instances, 53.3%; χ2 = 54.63, P < 0.001). The pain score was significantly lower in the needle-free injection group (3.65 ± 1.25 points) than in the needle-based injection group (5.16 ± 1.17 points, t = -7.90, P < 0.001). The logistic regression analysis showed that the duration of disease, lesion sites, patient age, and previous treatment history had no impact on the efficacy in either the needle-free injection group or the needle-based injection group (all P > 0.05) . Conclusions:The efficacy of needle-free and needle-based injections of interferon was similar in the treatment of palmoplantar warts, whereas needle-free injections resulted in less pain and a lower incidence of interferon-related adverse reactions. None of the duration of disease, lesion sites, patient age, or prior treatment status showed significant impact on the efficacy in the two groups.

Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.

Objective To evaluate the role of remimazolam in lipopolysaccharide(LPS)-induced M1 microglial polarization and its relationship with Toll-like receptor 4(TLR4).Methods BV2 mi-croglia cells were randomly divided into 5 groups(n=20):control group,LPS group(1 μg/ml for 24 h),remimazolam+LPS group(remimazolam group,pretreated with 100 μg/ml remimazolam for 20 min followed by LPS),remimazolam+LPS+Neoseptin-3 group(agonist group,50 pmol Neoseptin-3 dissolved in DMSO),and remimazolam+LPS+DMSO group(agonist control group).The contents of TNF-α and IL-1β in the supernatant were detected by ELISA.The expres-sion of M1 microglia markers,inducible nitric oxide synthase(iNOS)and TLR4 at mRNA.Immu-nofluorescence staining was employed to identify the location of iNOS.Results When compared to the control group,the contents of TNF-α and IL-1β in the supernatant and the expression of iNOS[(14.757±0.986)％vs(1.561±0.08)％]and TLR4 at mRNA and protein levels were sig-nificantly higher in the other four groups(P＜0.05).Remimazolam treatment reversed the increa-ses of the TNF-α and IL-1β contents in the supernatant and mRNA and protein expression of iNOS[(3.767±0.364)％vs(14.757±0.986)％]and TLR4 induced by LPS(P＜0.05).In addi-tion,remimazolam agonist Neoseptin-3 restored the effects of LPS on above molecules[iNOS:(6.827±0.642)％vs(3.767±0.364)％,all P＜0.05].But,there were no statistical differences in above molecules between the agonist group and agonist control group(P＞0.05).Conclusion The mechanism by which remimazolam inhibits LPS-induced M1 microglial polarization is related to down-regulation of TLR4 expression.

Objective To evaluate the role of remimazolam in lipopolysaccharide(LPS)-induced M1 microglial polarization and its relationship with Toll-like receptor 4(TLR4).Methods BV2 mi-croglia cells were randomly divided into 5 groups(n=20):control group,LPS group(1 μg/ml for 24 h),remimazolam+LPS group(remimazolam group,pretreated with 100 μg/ml remimazolam for 20 min followed by LPS),remimazolam+LPS+Neoseptin-3 group(agonist group,50 pmol Neoseptin-3 dissolved in DMSO),and remimazolam+LPS+DMSO group(agonist control group).The contents of TNF-α and IL-1β in the supernatant were detected by ELISA.The expres-sion of M1 microglia markers,inducible nitric oxide synthase(iNOS)and TLR4 at mRNA.Immu-nofluorescence staining was employed to identify the location of iNOS.Results When compared to the control group,the contents of TNF-α and IL-1β in the supernatant and the expression of iNOS[(14.757±0.986)％vs(1.561±0.08)％]and TLR4 at mRNA and protein levels were sig-nificantly higher in the other four groups(P＜0.05).Remimazolam treatment reversed the increa-ses of the TNF-α and IL-1β contents in the supernatant and mRNA and protein expression of iNOS[(3.767±0.364)％vs(14.757±0.986)％]and TLR4 induced by LPS(P＜0.05).In addi-tion,remimazolam agonist Neoseptin-3 restored the effects of LPS on above molecules[iNOS:(6.827±0.642)％vs(3.767±0.364)％,all P＜0.05].But,there were no statistical differences in above molecules between the agonist group and agonist control group(P＞0.05).Conclusion The mechanism by which remimazolam inhibits LPS-induced M1 microglial polarization is related to down-regulation of TLR4 expression.

The nursing experience was summarised over a patient who developed an impending myasthenic crisis following immune checkpoint inhibitors(ICIs)therapy after the surgery for stage-Ⅳ liver cancer.Key nursing points included:close monitoring for early signs of impending myasthenic crisis;set up a multi-disciplinary team to improve respiratory,oropharyngeal and ocular function,control respiratory infection,provide psychological support in order to prevent the patient from developing a manifest myasthenia-gravis crisis(MC);combine with medications to relieve myasthenic symptoms and prevent adverse drug reactions;individualised rehabilitation training to promote recovery of muscular strength.Eventually,the patient did not develop into a MC during hospitalisation(20d)and was well at 3-month after discharge.