ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

This paper investigated the inhibitory effect of carbonized Scutellariae Radix(Cb-SR) on pyroptosis in endometrial epithelial cells of mice with endometritis and its correlation with the IKBKE/NLRP3 signaling axis. Mice model of endometritis was established by using an intrauterine injection of 10 μL polysaccharides(LPS, 5 mg·mL~(-1)), and the mice were randomly divided into model group(LPS), low-dose group of Cb-SR(L-Cb-SR, 0.55 g·kg~(-1)), medium-dose group of Cb-SR(M-Cb-SR, 1.10 g·kg~(-1)), high-dose group of Cb-SR(H-Cb-SR, 2.20 g·kg~(-1)), crude Scutellariae Radix group(Cr-SR, 1.63 g·kg~(-1)), and Fuke Qianjin Capsule group(FQC, 0.30 g·kg~(-1)), with 10 mice in each group. Ten healthy female mice were selected and injected with PBS of equal volume into the bilateral uterus, and they were set as the sham group. The mice in the drug treatment groups were given the corresponding doses of Cb-SR, Cr-SR, FQC, or physiological saline of equal volume by gavage twice a day for seven days. Thirty minutes after the last administration, each mouse was euthanized by cervical dislocation. Hematoxylin-eosin(HE) staining and transmission electron microscopy were applied to observe the histopathological morphology of the uterine tissue. Immunohistochemistry was used to detect the expression of CD38 and CD138. Myeloperoxidase(MPO) values in neutrophils were measured by the kit; Enzyme-linked immunosorbent assay(ELISA) was used to measure the secretion of interleukin-18(IL-18), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Immunofluorescence and Western blot were used to analyze the expression of the proteins related to the IKBKE/NLRP3 signaling axis. Mouse endometrial epithelial cells(MEECs) were separated and purified from the uterine tissue of pregnant female mice through in vitro experiments and injured by LPS for 24 h, and then they were cultured with Cb-SR-containing serum. The anti-endometritis effect of Cb-SR was investigated by CCK-8 assay, scanning electron microscopy, and Western blot. The results showed that Cb-SR significantly reduced MPO values, attenuated uterine tissue damage, inhibited the expression of CD38 and CD138, decreased the levels of IL-1β, IL-18, and TNF-α, and inhibited the expression of proteins associated with IKBKE/NLRP3 signaling axis in mice with endometritis. In addition, Cb-SR-containing serum reduced swelling of MEECs organelles induced by LPS, decreased the expression of inflammatory factors, and suppressed the expression of IKBKE/NLRP3 signaling axis-related proteins. These results suggest that Cb-SR can inhibit endometrial epithelial cell pyroptosis in endometritis by suppressing the IKBKE/NLRP3 signaling axis.
Animals ; Female ; Mice ; Pyroptosis/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/chemistry* ; Endometritis/chemically induced* ; Lipopolysaccharides/adverse effects* ; Scutellaria baicalensis/chemistry* ; Humans ; Epithelial Cells/drug effects*

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVE: To investigate the effect of different previous treatments on the efficacy of flumatinib in patients with chronic myeloid leukemia (CML). METHODS: The clinical data of 69 patients with CML treated with flumatinib in the Affiliated Hospital of Xuzhou Medical University from 2019 to 2024 were retrospectively analyzed. The patients were divided into a first-line flumatinib group and a first-line non-flumatinib group according to whether flumatinib was used as first-line treatment. The molecular response (MR) at 3, 6 and 12 months of treatment was compared between the two groups to evaluate the early efficacy. The first-line non-flumatinib group was further divided into imatinib group, nilotinib group, and dasatinib group according to the previous first-line drugs used. The efficacy data of these three groups at 3, 6 and 12 months after switching to flumatinib were collected, and the MR was evaluated to compare efficacy differences. RESULTS: The rate of early molecular response (EMR) in the first-line flumatinib group was significantly higher than that in the first-line non-flumatinib group (P < 0.05). At 6 months and 12 months of treatment, the proportion of patients achieving MR 4.5 in the first-line flumatinib group was significantly higher than that in the first-line non-flumatinib group (P < 0.05). Compared with the imatinib and nilotinib groups, the previous dasatinib group showed a significantly higher proportion of patients achieving MR 5.0 at 3, 6, and 12 months after switching to flumatinib (P < 0.05). CONCLUSION Compared with the previous treatment with other tyrosine kinase inhibitors (TKIs), initial use of flumatinib at diagnosis enable patients to achieve deeper molecular remission more rapidly. Compared with previous use of imatinib or nilotinib, previous use of dasatinib is associated with deeper molecular remission after switching to flumatinib.
Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Retrospective Studies ; Imatinib Mesylate/therapeutic use* ; Dasatinib/therapeutic use* ; Treatment Outcome ; Pyrimidines/therapeutic use* ; Female ; Male ; Protein Kinase Inhibitors/therapeutic use* ; Middle Aged ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: To investigate the clinical effect and adverse reactions of dapoxetine hydrochloride versus paroxetine in the treatment of primary premature ejaculation by cross-comparison. METHODS: Based on the clinic-visit time, we equally randomized 148 patients with primary premature ejaculation into groups A and B for a cross-comparison test, the former treated with paroxetine at 20 mg once nightly and the latter with dapoxetine hydrochloride at 30 mg on demand, both for 6 successive weeks, during which we observed the therapeutic effects and adverse reactions. Following 4 weeks of drug discontinuance, we administered dapoxetine hydrochloride at 30 mg on demand for group A and paroxetine at 20 mg once nightly for group B, both for another 6 successive weeks, followed by observation and comparison of the therapeutic effects and adverse reactions. RESULTS: There were no statistically significant differences in the initial characteristics of the two groups of patients (P > 0.05). Compared with the baseline, the mean intra-vaginal ejaculation latency time (IELT) was dramatically improved after treatment in both groups A (4.43 min) and B (7.12 min), increased by 3.99% and 6.72%, respectively (P<0.001). The patients treated with paroxetine showed significantly longer IELT than those taking dapoxetine hydrochloride in both groups (P<0.001). Findings of the Premature Ejaculation Profile (PEP) and spouses' conditions indicated significant improvement after treatment in the average scores of the four indicators of PEP, that is, perceived control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse and ejaculation-related interpersonal difficulty, as well as in the overall experience and partner's satisfaction and orgasm frequency. Adverse reactions to medication were found in 20.8% of the cases in group A and 9.7% in group B, but none was serious. Preference survey following drug withdrawal revealed a preference for paroxetine (61.9%) over dapoxetine (26.8%), and that only a few of the patients thought of the two drugs as comparable or both ineffective. CONCLUSION In term of overall effectiveness, paroxetine was superior to dapoxetine in the treatment of primary premature ejaculation. And the patients obviously preferred the former to the latter, which might be partly attributed to the higher price of dapoxetine.
Humans ; Benzylamines/therapeutic use* ; Male ; Premature Ejaculation/drug therapy* ; Naphthalenes/therapeutic use* ; Paroxetine/therapeutic use* ; Adult ; Treatment Outcome ; Middle Aged ; Young Adult ; Selective Serotonin Reuptake Inhibitors/therapeutic use*

Aim To study the resistance of SIRT3 ex-pression in dopaminergic neurons against the inflamma-tory damage caused by microglia activation and its re-lated mechanism.Methods Dopaminergic neurons(MN9D cells)and microglia(BV-2 cells)were co-cultured to establish an inflammatory injury model in vitro.MN9D cells were divided into the control group,model group,SIRT3 group and SIRT3+PJ34 group.mRNA levels were analyzed by real-time quantitative polymerase chain reaction,cell apoptosis rate was de-tected by flow cytometry,changes in mitochondrial membrane potential were tested by JC-1 method,and the opening of mitochondrial permeability transport pore(mPTP)was analyzed by co-incubation of calce-in-AM and CoCl2.The protein expression was detected by Western blot.Results Compared to the model group,overexpression of SIRT3 in the SIRT3 group significantly reduced the apoptosis rate of MN9D cells.It also led to a significant increase in the expression of SIRT3 and SOD2 genes,as well as a notable decrease in PARP-1,tumor necrosis factor-α,and interleukin 1β(IL-1β)protein expressions.Moreover,it resulted in a substantial reduction in the p-NF-κB p65/NF-κB p65 ratio.There was an improvement observed in mito-chondrial membrane potential along with decreased mPTP opening and ROS production in the SIRT3 group.These differences among these groups were sta-tistically significant(all P＜0.05).After inhibiting PARP-1 activity of MN9D cells in the SIRT3+PJ34 group,except for the insignificant changes in SIRT3 and IL-1 β protein expression,the changing trend of other indicators was further enhanced on the basis of SIRT3 group.The differences between two groups re-mained statistically significant(all P＜0.05).Con-clusions SIRT3 expression can attenuate the inflam-matory damage of dopaminergic neurons induced by microglia activation,and the mechanism may be relat-ed to improving mitochondrial function,inhibiting PARP-1 activity and NF-κB signaling pathway caused by the reduction of ROS production.

Objective:To investigate the risk factors of cardiovascular diseases(CVD)in patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods:A total of 281 OSAHS patients admitted in Second People's Hospital of Huai'an City between May 2020 and March 2022 were selected and divided into CVD group(n=63)and no CVD group(n=218)according to presence of CVD.The OSAHS general data questionnaire designed by the re-search group was used to investigate the patients and univariate analysis was carried out,and the clinically significant single factors were included in the multivariate Logistic regression analysis.Influencing factors for CVD in OSAHS patients were analyzed.Results:Compared with no CVD group,patients in CVD group had significant higher age,body mass index(BMI),fasting plasma glucose(FPG)level,proportions of CVD family history,dyslipidemia and severe OSAHS(P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated that age,BMI,dyslipi-demia,FPG and severe OSAHS were independent risk factors for CVD in OSAHS patients(OR=2.213～2.482,P＜0.05 or＜0.01).Conclusion:Age,BMI,dyslipidemia,FPG and severe OSAHS are independent risk factors of CVD in OSAHS patients.Individualized prevention and control strategies can be formulated according to above fac-tors in clinic,which is of great significance for prevention of CVD occurrence.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Objective To construct and validate a nomogram prediction model for the high-risk human papilloma-virus(HPV)infection and its natural clearance in professional women.Methods Women with regular professions,who underwent professional medical examination and were confirmed with high-risk HPV infection without cervical cancer and cervical epithelial neoplasia in a hospital from March 2020 to March 2021 were studied.Patients were di-vided into the model group and the validation group in a 7:3 ratio.The model group were subdivided into the natural clearance group and the persistent infection group based on follow-up results.The general information,reproduc-tive-related treatment,sexual partner-related information,and examination results of the two groups of patients were compared.Potential factors for natural clearance of high-risk HPV infection in professional women were screened out by LASSO regression.Independent influencing factors were screened out with multivariate logistic re-gression.Based on multivariate logistic regression results,a nomogram prediction model was constructed and valida-ted using R programming language.Results A total of 329 cases were included,230 in the model group and 99 in the validation group.There was no statistically significant difference in general information between the two groups of patients(all P＞0.05).Among the 230 high-risk HPV infection patients in the model group,165 turned negative at the end of follow-up,with a natural clearance rate of 71.74％.Based on LASSO regression analysis,multivariate logistic regression analysis showed that age,contraceptive method,number of sexual partners,excessive foreskin of sexual partners,initial viral load,HPV infection type,and reproductive tract inflammation were independent influ-encing factors for the natural clearance of high-risk HPV infection in professional women(all P＜0.05).The re-ceiver operating characteristic(ROC)curve analysis showed that the areas under the curve(AUC)of natural clea-rance of high-risk HPV infection in professional women in the model group and validation group were 0.834(95％CI:0.776-0.893)and 0.817(95％CI:0.755-0.879),respectively.H-L goodness-of-fit test result showed that the difference between the nomogram model and the ideal model was not statistically significant(P＞0.05).The cali-bration curve results showed that the predicted curves of the model group and validation group were basically fit with the standard curve,indicating a high predictive accuracy of the model.The decision curve analysis results of the model group showed that when the probability threshold of natural clearance of high-risk HPV infection in profes-sional women predicted by the nomogram model was 0.15-0.95,the net benefit rate of patients was＞0.Conclusion The natural clearance rate of high-risk HPV infection in professional women is high,mainly influenced by factors such as age,contraceptive method,and number of sexual partners.The nomogram model constructed in this study has high accuracy and discrimination in predicting the natural clearance rate of high-risk HPV infection in profes-sional women.

Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1％formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62％-101.24％.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.