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 After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated.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.

Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

Objective To analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Shanxi Province from 2012 to 2024, and predict the incidence trend for 2025, and to provide a scientific basis for the formulation of prevention and control strategies. Methods Based on the surveillance data of HFMD in Shanxi Province from 2012 to 2024, the spatial and temporal distribution characteristics and time trends of the disease were analyzed. The ARIMA model was constructed and used to predict the incidence trend in 2025. Results From 2012 to 2024, a total of 254 028 HFMD cases were reported in Shanxi Province, with an average annual incidence rate of 54.17 per 100 000 population, a severe case rate of 0.56%, and a case fatality rate (CFR) of 12.60 per 100 000 population. Joinpoint regression analysis showed that the incidence rate, severe case rate, mortality rate, and case fatality rate all presented a downward trend. The epidemic exhibited obvious seasonal distribution characteristics, with the peak period from April to November, and two incidence peaks in June-July and October-November. The male-to-female incidence ratio was 1.41:1. Children aged 1-5 years accounted for 89.24% of the total cases, among which scattered children (58.48%) and nursery children (33.54%) were the high-risk groups. Linfen City (96.06 /100 000) and Taiyuan City (88.54 /100 000) had relatively high incidence rates. After 2017, the proportion of enterovirus A71 (EV-A71) decreased, while coxsackievirus A16 (Cox-A16) and other enteroviruses became the main epidemic strains. The ARIMA(1,0,1)(0,1,1)₁₂ model predicted that the incidence of HFMD in 2025 would remain at the level of 2023-2024, and the dual-peak characteristic would continue. Conclusion From 2012 to 2024, the overall HFMD epidemic in Shanxi Province generally shows a significant downward trend. The high-risk population includes scattered children and nursery children under 5 years old, with high-incidence areas concentrated in the central and southern regions, requiring focused attention. The seasonal ARIMA model can effectively fit the evolutionary trend of HFMD incidence in Shanxi Province and possesses short-term predictive capability.

Objective:This study aimed to analyze the genetic subtypes and drug resistance transmission characteristics of HIV-1 among the preoperative population in Ningxia from 2018 to 2023, to provide a scientific basis for the prevention and control of the AIDS epidemic.Methods:Plasma samples and demographic information of HIV/AIDS patients receiving antiviral treatment in Ningxia from 2018 to 2023 were collected. Blood samples with a viral loads >200 copies/ml from preoperative testing were amplified, sequenced, and subjected to genotypic resistance testing to analyze their genetic subtypes and drug resistance characteristics. The TN93 model in MEGA11 software was used to calculate the genetic distance between each pair of all sequences, and a molecular transmission network was constructed in Cytoscape 3.10.0 with 1.9% as the genetic threshold.Results:Among 101 preoperative HIV/AIDS patients, CRF07_BC and CRF01_AE were the predominant subtypes. The majority were male (85.15%, 86/101), aged 41-60 years (45.54%, 46/101), residing in Yinchuan city (61.39%, 62/101), and infected via heterosexual transmission (71.29%, 72/101), with most cases being late-detected. Of 39 drug-resistant sequences, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) alone (18.81%, 19/101) and dual resistance to nucleoside reverse transcriptase inhibitors (NRTIs)-NNRTIs (13.86%, 14/101) were most common. Among 44 sequences forming 13 transmission clusters, nine clusters harbored drug-resistant mutations. Four subtypes entered the molecular network, primarily involving heterosexual transmission, individuals with junior high school education or below, and men aged≥50 years.Conclusions:From 2018 to 2023, the preoperative HIV/AIDS patients had diversified genetic subtypes, with higher rates of overall drug resistance and late detection, stronger drug resistance and higher mortality rate. Strengthening molecular epidemiological research and developing targeted screening strategies are critical to improve early detection and reduce transmission risks.

Objective To observe the clinical and transthoracic echocardiographic manifestations of mitral annular disjunction(MAD).Methods Transthoracic echocardiographic data of 990 individuals were retrospectively analyzed.Based on the distance between the attachment point of posterior mitral valve and posterior wall of left ventricle measured on echocardiography,whether there was MAD was judged,and the subjects were divided into MAD group and non-MAD(NMAD)group,and clinical data and echocardiographic parameters were compared between groups.Taken parameters being significantly different between groups as independent variables and the presence or absence of MAD as dependent variable,multivariate binary logistic regression analysis was used to explore correlations of patients' clinical characteristics and transthoracic echocardiographic parameters of MAD.Results MAD was detected in 186 cases(186/990,18.79％).Patients' age,left atrial diameter(LAD),left ventricle diameter(LVD),late diastolic velocity of mitral valve(A)and early diastolic velocity of mitral valve orifices(E)/A in MAD group were all lower than those in NMAD group,while the proportion of moderate and above mitral regurgitation in MAD group was higher than that in NMAD group(all P＜0.05).Patients' age,A and E/A measured with transthoracic echocardiography were all correlated with MAD(all P＜0.05).Conclusion Clinical and transthoracic echocardiographic manifestations of MAD had certain characteristics.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To study the expression levels and clinical significance of histone H3 trimethylation at lysine 4(H3K4me3),histone H3 trimethylation at lysine 27(H3K27me3)and modifying enzyme in placental tissue of patients with premature rupture of membranes(PROM)with chorioamnionitis.Methods Clinical data of 95 pregnant women treated in the Xi'an Gaoxin Hospital due to PROM from June 2021 to December 2023 were retrospectively collected,and they were divided into infected group and a non-infected group according to whether they were complicated with histological chorioamnionitis(HCA).Another 30 normal pregnant women were selected as the control group.Placental tissues of all subjects were collected and H3K4me3 and H3K27me3 levels were detected,and the expression levels of H3K4me3,H3K27me3 specific methyltransferase[mixed lineage leukemia protein-1(MLL1),Zeste enhancer homolog 2(EZH2)]and demethyltransferase[lysine-specific demethylase 5B(KDM5B),Jumonji domain-containing protein 3(JMJD3)]were detected by quantitative real-time PCR(qRT-PCR).The expression differences of H3K4me3,H3K27me3 and specific modifiers among the three groups and the correlation with the histological stage of HCA were analyzed.The Receiver operating characteristic curve(ROC)was plotted,the Area under curve(AUC)value was calculated,and H3K4me3 was evaluated.Predictive value of H3K27me3 for concurrent HCA infection.Result Compared with the control group,the levels of H3K4me3(0.08%±0.02%,0.12%±0.03%vs 0.25%±0.06%),MLL1 mRNA(1.32±0.16,1.44±0.23 vs 2.02±0.31),and JMJD3 mRNA(0.78±0.13,0.91±0.15 vs 1.53±0.23)in the infected and non-infected groups were significantly decreased(t=10.939～19.062),while the levels of H3K27me39(0.23%±0.05%,0.15%±0.03%vs 0.10%±0.02%),EZH2 mRNA(1.96±0.26,1.85±0.25 vs 1.15±0.29)and KDM5B(1.46±0.15,1.35±0.18 vs 0.94±0.12)were significantly increased(t=6.077～14.974),and the levels in the infected group were lower/higher than those in the non-infected group(t=2.017～10.688),with statistically significant differences(all P<0.05).There was a significant negatively correlation between H3K4me3 and H3K27me3 levels in placenta tissue of PROM(r=-0.604,P<0.05).The levels of H3K4me3,MLL1 and JMJD3 were negatively correlated with the histological stages of HCA(r=-0.646,-0.489,-0.503,all P<0.05).The levels of H3K27me3,EZH2 and KDM5B were positively correlated with the histological stages of HCA(r=0.632,0.515,0.520,all P<0.05).The cutoffvalues of H3K4me3 and H3K27me3 were 0.10%and 0.19%,respectively.The AUC(95%CI)value of the combined prediction of PROM combined with HCA infection was 0.896(0.882～0.947),and the sensitivity and specificity were 92.14%and 86.23%respectively,which was significantly higher than the diagnosis of a single index.Conclusion The levels of H3K4me3,H3K27me3 and modifying enzymes in the placenta tissue of PROM are closely related to HCA infection and histological stage,which has high clinical prediction value for HCA infection and is expected to be a new biomarker for clinical diagnosis.

Objective:To investigate the effect of the embryo cryopreservation duration on pregnancy and obstetric outcome.Methods:A retrospective cohort study of 2 662 frozen-thawed embyro tranfer (FET) cycles was conducted in the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital from January 2016 to December 2020. According to embryo cryopreservation duration, the patients were divided into group A (≤1 year, n=2 115), group B (>1 years and ≤3 years, n=319), group C (>3 years and ≤6 years, n=174), and group D (>6 years, n=54). We used the propensity score matching (PSM) to match the baseline data of oocyte retrieval age of the other three groups according to group D at a ratio of 1∶3. Clinical and obstetric outcomes were compared among the four groups. Multiple logistic regression analysis was used to analyze the effect of oocyte retrieval age, embryo transfer age, the duration of embryo cryopreservation, endometrial preparation scheme, endometrial thickness, the number of transferred embryos and the number of high-quality embryos on pregnancy and live birth outcome. Results:1) Before PSM, there were significant differences in the maternal age at oocyte retrieval and embryo transfer and duration of embryo cryopreservation among the four groups(all P<0.001). 2) After PSM, the baseline characteristics of oocyte retrieval age reached a balance among the four groups. There were no statistical differences in the number of embryos transfer, the number of high-quality embryos, the transferred embryo stage, the endometrial regimen among the groups (all P>0.05). The clinical pregnancy rate [37.04% (20/54)] and the live birth rate [33.33% (18/54)] in group D were lower than those in group A [51.57% (82/159), 40.88% (65/159)], group B [50.00% (65/130), 40.77% (53/130)] and group C [49.59% (61/123), 39.02% (48/123)], but the difference was not statistically significant between the four groups ( P=0.310, P=0.781). There were no statistical differences among the four groups in the ratio of male to female newborns, gestational age, birth weight, preterm delivery rate, low birth weight rate, macrosomia rate, birth defects, and premature repture of membranes (all P>0.05). 3) Multiple logistic regression analysis showed that the number of high-quality embryos transferred affected the clinical pregnancy outcome (before PSM, OR=2.614, 95% CI: 2.168-3.151, P<0.001; after PSM, OR=1.984, 95% CI: 1.406-2.800, P<0.001) and live birth (before PSM, OR=2.708, 95% CI: 2.198-3.336, P<0.001; after PSM, OR=2.122, 95% CI: 1.474-3.053, P<0.001). The duration of embryo cryopreservation does not affect the clinical outcome and live birth (all P>0.05). Conclusion:The duration of embryo cryopreservation does not affect the clinical outcome and live birth, but large sample data are still needed to support this conclusion in the future.