ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

Objective To investigate the impact of holiday effects and prevention/control measures on the development characteristics and incidence trends of influenza in Hefei City using a Prophet-LSTM hybrid model, and to validate the applicability of the Prophet-LSTM model in influenza prediction by comparing the performance of different forecasting models. Methods Influenza incidence data from Hefei City (2016–2024) were collected to construct a Prophet-LSTM feature analysis and prediction model to analyze the impact of holiday effects and intervention measures on influenza incidence trends. Comparative models (ARIMA, GRU, and TimeGPT) were established and evaluated on the same test set. Results The data analysis revealed significantly increased influenza incidence during holidays (e.g., New Year's Day, Spring Festival, and National Day), while prevention and control measures led to declining trends. The Prophet-LSTM model demonstrated high consistency between the predicted and actual values, outperforming the comparative models with superior MAE (0.209), MSE (0.195), and IA (0.914), indicating higher prediction accuracy and trend-fitting capability. Conclusion The Prophet-LSTM model effectively captures spatiotemporal characteristics of influenza incidence, exhibits enhanced predictive performance when incorporating holiday effects and intervention measures, and demonstrates significant advantages and application value in influenza forecasting.

ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

Objective To analyze the epidemiological and etiological characteristics of hand,foot and mouth disease(HFMD)in Nanning City,Liangqing District from 2012 to 2023.Methods Descriptive epidemiological methods were used to describe the three distribution characteristics of HFMD,and to predict the incidence trend of HFMD.Results From 2012 to 2023,Liangqing District of Nanning City reported a total of 19 715 cases of HFMD.The incidence rates varied significantly across different years,with statistically significant differences(P＜0.01).The urban area reported the highest number of cases.The disease primarily occurred from April to October,with the highest incidence among children aged 6 months to 5 years,mainly among children in daycare and preschools.From 2012 to 2023,a total of 588 cases were diagnosed through laboratory tests,with the highest detection rate of other enteroviruses,and a relatively lower detection rate of EV71.Predictions indicate that the incidence of HFMD in Liangqing District of Nanning City will decrease in 2025 compared to 2023.Conclusion Incidence of HFMD in Liangqing District,Nanning is high,especially among children aged 6 months to 5 years.It is suggested to strengthen the epidemic surveillance,continue to carry out pathogen surveillance.

Objective To investigate the correlation between hemoglobin A1c(HbA1c)levels and excessive daytime sleepiness(EDS)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 132 T2DM patients and 40 healthy people(NC group)who were treated in the outpatient department of Nanjing Meishan Hospital from December 2020 to December 2022 were selected.General clinical data of the subjects were collected,and their Epworth sleepiness scale(ESS)scores,Pittsburgh sleep quality index(PSQI),and apnea-hypopnea index(AHI)were measured.Based on ESS scores,T2DM patients were divided into simple T2DM group(ESS score<9,n=99)and EDS group(ESS score≥9,n=33)according to ESS score.The baseline data were compared for each group.Spearman correlation analysis and multivariate logistic regression model were used to evaluate the correlation between HbA1c levels and EDS.The receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)to evaluate the predictive value of HbA1c levels for EDS.Results HbA1c,fasting plasma glucose,AHI index and PSQI score in EDS group were higher than those in T2DM and NC group(P<0.05).Spearman correlation analysis showed that ESS score was positively correlated with HbA1c in T2DM patients(P<0.05).Multivariate logistic regression analysis revealed that elevated HbA1c levels emerged as a significant and independent risk factor for the onset of EDS.The ROC curve indicated that the AUC of HbA1c for predicting EDS was 0.736.Conclusions There is an independent positive correlation between HbA1c levels and EDS in T2DM patients,which provides clues for early identification and treatment of EDS in clinical practice.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

Objective To explore the value of preoperative amide proton transfer(APT)imaging combined with diffusion kurtosis imaging(DKI)in predicting lymphovascular space invasion(LVSI)in cervical cancer.Methods Fifty-one patients with cervical cancer who underwent preoperative MRI examination and had complete postoperative pathology were retrospectively selected.Pelvic MRI scans were performed 1-2 weeks preoperatively,and the corresponding APT values,mean kurtosis(MK)and mean diffusivity(MD)values were obtained respectively,and the occurrence of LVSI was determined based on postoperative pathology results.The predictive effects of APT-and DKI-derived parameters alone or in combination on the LVSI status of cervical cancer were compared.Results Among 51 cases of cervical cancer,36 cases had pathologically confirmed LVSI and 15 cases did not had LVSI.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve for the preoperative APT values,MK and MD values alone and in combination to predict the LVSI status of cervical cancer were 0.820,0.788,0.762,0.894,0.885,and 0.896,respectively.APT values combined with DKI-derived parameters predicted LVSI better than when they were used separately,in which APT values combined with MK and MD values predicted LVSI of cervical cancer with the largest AUC,sensitivity of 91.7％,specificity of 80.0％,and Youden's index of 0.717.Conclusion Preoperative APT imaging and DKI have important value in predicting LVSI of cervical cancer,and the combined application of the two can improve the prediction efficacy,which has certain clinical application value.

Objective To explore the clinical value of subcutaneous tunneling in the management of chronic subdural hematoma.Methods A retrospective analysis was conducted on 279 cases of unilateral chronic subdural hematoma treated at the Neurosurgery Department of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019.The patients were randomly assigned to subcutaneous tunnel group(n=164)and control group(n=115)through double-blind randomization.In the subcutaneous tunnel group,the intraoperative drainage tube was extracted through a subcutaneous tunnel,while in the control group,the drainage tube was removed directly from the incision.We analyzed the hematoma clearance rate,complications,and hematoma recurrence rate after 6 months.Results There was no statistical significance in age,sex,comorbidities,hematoma side or hematoma volume between the two groups(P＞0.05).Subcutaneous tunnel group and control group did not significantly differ in operation time[(27.68±4.1)min vs.(27.50±4.02)min],hospital stay[(7.39±1.04)d vs.(7.42±1.04)d],tube removal time[(24.30±4.82)h vs.25.37±5.02)h],or other clinical features(all P＞0.05).The clearance rate of hematoma was significantly higher in subcutaneous tunnel group than in control group(97.6％vs.95.7％,Z=-3.897,P＜0.001).There were 6 cases(3.7％)of hematoma recurrence in the subcutaneous tunnel group and 11 cases(9.6％)in the control group.The subcutaneous tunnel group had significantly lower recurrence of hematoma than the control group(x2=4.122,P=0.042).Conclusion Subcutaneous tunneling for drainage in the treatment of chronic subdural hematoma can increase the hematoma clearance rate and reduce the rates of complications and recurrence.This technique is simple and worthy of broad clinical application.

Objective To explore the clinical value of subcutaneous tunneling in the management of chronic subdural hematoma.Methods A retrospective analysis was conducted on 279 cases of unilateral chronic subdural hematoma treated at the Neurosurgery Department of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019.The patients were randomly assigned to subcutaneous tunnel group(n=164)and control group(n=115)through double-blind randomization.In the subcutaneous tunnel group,the intraoperative drainage tube was extracted through a subcutaneous tunnel,while in the control group,the drainage tube was removed directly from the incision.We analyzed the hematoma clearance rate,complications,and hematoma recurrence rate after 6 months.Results There was no statistical significance in age,sex,comorbidities,hematoma side or hematoma volume between the two groups(P＞0.05).Subcutaneous tunnel group and control group did not significantly differ in operation time[(27.68±4.1)min vs.(27.50±4.02)min],hospital stay[(7.39±1.04)d vs.(7.42±1.04)d],tube removal time[(24.30±4.82)h vs.25.37±5.02)h],or other clinical features(all P＞0.05).The clearance rate of hematoma was significantly higher in subcutaneous tunnel group than in control group(97.6％vs.95.7％,Z=-3.897,P＜0.001).There were 6 cases(3.7％)of hematoma recurrence in the subcutaneous tunnel group and 11 cases(9.6％)in the control group.The subcutaneous tunnel group had significantly lower recurrence of hematoma than the control group(x2=4.122,P=0.042).Conclusion Subcutaneous tunneling for drainage in the treatment of chronic subdural hematoma can increase the hematoma clearance rate and reduce the rates of complications and recurrence.This technique is simple and worthy of broad clinical application.

Objective: Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated favorable therapeutic responses in patients with chemorefractory gestational trophoblastic neoplasia.The need for combined surgery to remove resistant foci in patients treated with anti-PD-1 therapy after complete remission (CR), however, has not been investigated. We therefore compared the prognosis of patients with high-risk chemorefractory or relapsed choriocarcinoma who underwent anti-PD-1 therapy with or without surgery. Methods: Patients with high-risk chemorefractory or relapsed choriocarcinoma who experienced CR following immunotherapy in conjunction with either surgical or non-surgical interventions were selected at Peking Union Medical College Hospital (PUMCH) between August 2018 and December 2023. Study endpoints included progression-free survival (PFS) and overall survival (OS). The results were analyzed using Mann–Whitney U tests and Kaplan–Meier analysis. Results: Forty-three patients who received andi-PD-1 therapy were enrolled in this study, including 18 patients with surgery and 25 without. Most of the foci in the surgery group were solitary (77.8%). The median maximum diameters of resistant foci before immunotherapy were 2.9 (0.7–7.3) cm and 1.4 (0.8–11.2) cm in the surgery and non-surgery groups, respectively (p=0.184). The 2-year PFS rate was both 91.5% in the non-surgery group and 90.9% in the surgery group. The 2-year and 3-year OS rates were 100.0% in both groups.There was no significant difference in PFS (p=0.849) or OS (p=0.371) between the 2 groups. Conclusion These results suggest that surgical resection of drug-resistant lesions may not be necessary in patients with high-risk chemorefractory or relapsed choriocarcinoma who achieve CR after anti-PD-1 therapy.