Objective To investigate the chemical constituents of Epimedium multiflorum T. S. Ying. Methods The ethanol extract of E. multiflorum was separated and purified by silica gel column chromatography, preparative thin-layer chromatography, and semi-preparative reversed-phase high-performance liquid chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy and comparison with literature data. Results Ten compounds were isolated and purified, which structures were identified as baohuoside Ⅱ（1），2′′-O-rhamnosyl-icariside Ⅱ（2）, icariin（3）, epimedoside A（4）, ikarisoside B（5）, epimedin C（6）, baohuoside Ⅴ（7）, epimedin A（8）, epimedin B（9）, and ikarisoside C（10）. Conclusion All the isolated flavonoid compounds were obtained from E. multiflorum for the first time.

Objective To explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P＜0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P＜0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.

Objective To investigate the effect of intravenous flurbiprofen axetil on the incidence and severity of catheter-related bladder discomfort(CRBD)after transurethral resection of the prostate(TURP).Methods The elderly patients undergoing TURP under general anesthesia were enrolled,and randomly divided into two groups:flurbiprofen axetil group(group F)and control group(group C).Ten minutes before the end of surgery,group F was given 50 mg of flurbiprofen axetil intravenously,group C was given an equal amount of 0.9％sodium chloride injection.The primary outcome indicator was the incidence of moderate to severe CRBD immediately after entering the resuscitation room(T0).Secondary indicators included the incidence and severity of CRBD at 1 h(T1),2 h(T2),and 6 h(T3)after entering the resuscitation room,the amount of sufentanil used within 24 hours after surgery,postoperative NRS score,flurbiprofen axetil-related and analgesic adverse reactions 24 hours after surgery,and patient satisfaction.Results A total of 90 patients were included and each group was 45 patients.The incidence of moderate to severe CRBD at T0 was significantly lower in group F than that in group C(8.9％vs.33.3％,P=0.004).The incidence of CRBD in T1,T2,and T3 was lower in group F than in group C(P＜0.05).The incidence of mild CRBD at T3 in group F was lower than that in group C(P＜0.05).The incidence of moderate to severe CRBD at T1 and T2 in groups F was lower than that in group C(P＜0.05).The amount of sufentanil used in group F at 24 hours after surgery was significantly lower than that in group C(P=0.001).The pain scores in group F at T0,T1,T2,and T3 were lower than those in group C(P＜0.05);The postoperative patient satisfaction score in group F was higher than that in group C(P=0.001).However,there were no significant differences between the two groups in postoperative anesthesia resuscitation time and 24-hour adverse reactions incidence(P＞0.05).Conclusion Intravenous flurbiprofen axetil can safely and effectively reduce the incidence and severity of CRBD after TURP.It can significantly relieve pain,reduce sufentanil use,and have high clinical application value.

Objective Aimed at investigating the effect and molecular mechanism of artemisinin on hemo-dynamics and vascular remodeling in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)rats.Methods 30 male SD rats were randomly divided into 3 groups(n=10):control group,MCT-induced PAH group(MCT group,60 mg/kg)and artemisinin intervention group(50 mg/kg).At 28 days after modeling,the right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),heart rate and right ventricular hypertrophy index(RVHI)were measured to evaluate the development of PAH.HE staining and α-SMA immuno-histochemistry were used to observe the morphology and assess muscularization of pulmonary arterioles,and the percentage of medial wall thickness(WT%),the percentage of vascular wall area(WA%)and the proportion of muscular vessels were calculated to evaluate the degree of pulmonary vascular remodeling.The mRNA and protein levels of HIF-1α and LDHA were detected by real-time PCR and Western blot,respectively.Pyruvate and lactate concentration in lung tissue was measured using pyruvate and lactateassay kit.Results Compared with the control group,the RVSP,mPAP,heart rate and RVHI were significantly increased in MCT-induced PAH rats(all P<0.05).Histological analysis showed that the increasedmedial wall thickness of small pulmonary arteries and vascular muscularization were observed in MCT-treated rats compared with control rats.WT%,WA%and muscularization degrees of pulmonary arterioles were higher in MCT-treated rats than those in the control group(all P<0.05),suggesting successful construction of PAH model.Compared with the MCT group,the RVSP,mPAP,heart rate and RVHI decreased in the rats treated with artemisinin(all P<0.05),accompanied with lower WT%and WA%(P<0.05),and muscularization of pulmonary arterioles was improved(P<0.05).Further study showed the mRNA and protein levels ofHIF-1α and LDHA in lung tissue of MCT-induced PAH rats were higher than those in the control group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were higher than that in the control group(all P<0.05).However,the mRNA and protein levels of HIF-1α and LDHA in lung tissue of rats treated with artemisinin were lower than those in the MCT group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were lower than that in the MCT group(all P<0.05).Conclusion Artemisinin improves hemodynamic and pulmonary vascular remodeling in PAH rats through inhibiting HIF-1α/LDHA signaling pathway-mediated glycolysis.

Objective:To investigate the magnetic resonance imaging (MRI) features of pediatric and adolescent mediastinal T-lymphoblastic lymphoma (T-LBL) and to evaluate their predictive value for early treatment response.Methods:A retrospective, multicenter case series study was conducted on 49 pediatric and adolescent patients diagnosed with mediastinal T-LBL between September 2020 and May 2024 at the Fifth Affiliated Hospital of Zhengzhou University, Beijing Gaobo Boren Hospital, and Henan Cancer Hospital.All patients underwent chest MRI, including conventional MRI sequences and diffusion-weighted imaging.Tumor imaging characteristics were analyzed, and quantitative parameters such as minimum apparent diffusion coefficient (ADCmin), maximum ADC (ADCmax), and mean ADC (ADCmean) were measured.Treatment response was evaluated 15 days post-treatment.The patients were divided into a response group (complete or partial response, 26 cases) and a non-response group (progressive disease or minor response, 23 cases).The relationship between MRI features and treatment response was analyzed.The intraclass correlation coefficient was used to assess inter-reader agreement, and independent sample t-tests and chi-square tests were employed to compare differences between groups.Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of imaging parameters. Results:Significant differences were observed between the response and non-response groups in ADC values [ADCmin (0.80±0.41)×10 -3 mm 2/s vs.(1.23±0.70)×10 -3 mm 2/s, ADCmax (1.14±0.48)×10 -3 mm 2/s vs.(1.92±0.77)×10 -3 mm 2/s, ADCmean (0.98±0.42)×10 -3 mm 2/s vs.(1.56±0.74)×10 -3 mm 2/s] and the maximum tumor diameter was [(11.92±3.61) cm vs.(8.17±2.46) cm] (all P<0.05).ROC curve analysis showed that ADCmax had the highest predictive efficiency for treatment response, with an area under the curve (AUC) of 0.853 (95% CI: 0.790-0.910), sensitivity of 92.3%, and specificity of 65.2%.The AUC for the maximum tumor diameter was 0.814, demonstrating its excellent predictive performance. Conclusions:MRI features, particularly ADC values and the maximum tumor diameter, can effectively predict treatment response in pediatric and adolescent mediastinal T-LBL.

Objective:To assess the risk of hearing impairment caused by Gentamicin in Chinese children.Methods:A retrospective analysis.Related literature was retrieved and selected according to inclusion and exclusion criteria, and relevant data was extracted.An evidence-based analysis was conducted on the relationship between hearing impairment and the application of Gentamicin in children.Results:A total of 150 literature reports in Chinese and 483 in English were retrieved.After screening according to inclusion and exclusion criteria, 33 studies in Chinese and 20 in English were included for analysis.There were 13 clinical case reports, 17 retrospective studies and 4 prospective studies on hearing impairment after the application of the Gentamicin in Chinese children.There were 19 international clinical studies.In the 13 clinical case reports including 21 cases who had a history of Gentamicin, no relationship between hearing impairment and Gentamicin was described.A total of 13 419 patients with hearing impairment were included in 17 retrospective studies, and 3 063 (22.8%) of them had Gentamicin exposure in childhood.Among 19 international studies on the application of Gentamicin in children, 13 reported cases with hearing impairment.The incidence of hearing impairment in Gentamicin-treated patients ranged from 0.9% to 30.9%, and the reasons were family history of hearing impairment, otitis media, and sequelae of nervous system injuries.No children with hearing impairment were proved related to Gentamicin.Five studies with a control group (not the Gentamicin-treated group) showed no difference in the incidence of hearing impairment between the Gentamicin-treated group(0-30.9%) and the control group (0-31.4%).Conclusions:All the retrospective reports of hearing impairment caused by Gentamicin in Chinese children do not describe the causal relationship between hearing impairment and Gentamicin.In international studies, the incidence of hearing impairment is not higher in Gentamicin-treated children.Cohort and randomized controlled studies are needed to further assess the risk of hearing impairment in Chinese children.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6～8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85％～90％Smax)combined with 1 min low-speed(50％～55％Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P＜0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P＜0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P＜0.05,P＜0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P＜0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P＜0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|＞0.75,P＜0.01;|r|＞0.75,P＜0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|＜0.75,P＜0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.