ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

The innate immune system employs diverse pattern recognition receptors (PRRs) to monitor pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), thereby initiating innate immune responses against pathogenic invasions. This review focuses on RNA, double-stranded DNA (dsDNA), and non-canonical conformational nucleic acid as structural triggers, comprehensively analyzing the immune recognition mechanisms of nucleic acid-sensing PRRs, their disease relevance, and therapeutic advancements. Key receptors highlighted include Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), cyclic GMP-AMP synthase (cGAS), and Z-DNA-binding protein 1 (ZBP1). We elucidate their pivotal roles in antiviral defense, antitumor immunity, and immune homeostasis maintenance, aiming to provide insights for the development of novel PRR-targeted drugs.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

Objective To investigate the expression levels of LINC02009 and LOC107984895 in peripheral lymphocytes of patients with atrial fibrillation and their clinical significance.Methods A total of 75 hospitalized patients with atrial fibrillation(50 with persistent atrial fibrillation and 25 with paroxysmal atrial fibrillation)from Kunming First People's Hospital between January 2023 and December 2023 were selected as study subjects,along with 50 normal control patients.Real-time quantitative PCR was used to detect the expression levels of LINC02009 and LOC107984895 in peripheral blood leukocytes of patients with atrial fibrillation.Logistic regression analysis was employed to assess the relationship between expression levels and risk factors for atrial fibrillation,and ROC curves were used to predict the diagnostic cut-off values for LINC02009 and LOC107984895 in diagnosing atrial fibrillation.Results There were statistically significant differences in baseline diseases such as hypertension and coronary heart disease,biochemical indicators such as Cr and BNP,and myocardial remodeling indicators such as LAd and LVEF between the AF(paroxysmal atrial fibrillation and persistent atrial fibrillation)group and the Normal group(P＜0.05).The expression levels of LINC02009 and LOC 107984895 in the plasma of the atrial fibrillation group were significantly higher than those in the control group(P＜0.05)and were negatively correlated with LVEF(P＜0.05).The areas under the curve(AUC)of LINC02009 and LOC 107984895 in predicting atrial fibrillation were 0.967(95％CI:0.938～0.995)and 0.900(95％CI:0.838～0.963),respectively.The optimal cut-off values were 1.985 and 0.915,with sensitivities of 88％and 76％,respectively,and specificities of 94％and 90％,respectively.Conclusion LINC02009 and LOC 107984895 are independent risk factors for atrial fibrillation and have certain predictive value for the occurrence of atrial fibrillation.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Objective:To evaluate whether there is a difference between the lesion volumes detected by 18F-FDG PET/CT imaging and 11C-choline PET/CT imaging based on different threshold delineation methods in patients with nasopharyngeal carcinoma, and to recommend a more clinically appropriate threshold method with reference to lesion volume detected by enhanced MRI. Methods:A retrospective study was conducted on 37 patients(27 males, 10 females, age (51.2±11.9) years) with nasopharyngeal carcinoma diagnosed in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between October 2015 and May 2017. All patients underwent nasopharyngeal enhanced MRI, 18F-FDG PET/CT and 11C-choline PET/CT scans. Advantage Workstation 4.6 software was used to fuse images of the 3 imaging examinations. The lesion contour was sketched manually based on enhanced MRI sequences to obtain VMRI, and the lesion was sketched in PET images to obtain the corresponding metabolic tumor volume (MTV) by absolute threshold method, relative threshold method and background threshold method respectively. The correlation between ROIs sketched by different threshold methods and ROI in MRI was evaluated by using the Dice similarity coefficient (DSC). Friedman test or repeated measures analysis of variance (corrected by Greenhouse-Geisser) was employed to analyze the differences of MTV or DSC obtained by using 3 threshold methods. Wilcoxon signed-rank test or paired t-test was used to compare the data of different imaging methods. Results:In 18F-FDG PET/CT results, MTVs obtained by using the absolute threshold method, relative threshold method, and background threshold method were 13.21(5.47, 23.16), 10.13(5.67, 16.81), and 13.68(5.77, 25.52)mm 3, respectively, with significant differences ( χ2=17.89, P<0.001). The corresponding DSC differences for the 3 methods were also significant (0.43±0.19, 0.38±0.17 and 0.44±0.17; F=16.35, P<0.001). In 11C-choline PET/CT results, MTV differences based on the 3 threshold methods were significantly different (14.96(6.80, 32.27), 16.28(12.23, 32.47) and 18.97(14.38, 37.02)mm 3;χ2=10.45, P=0.005), and the DSC differences were also significant (0.52±0.21, 0.58±0.13 and 0.62±0.13; F=16.37, P<0.001). The differences in MTV and DSC between FDG and choline groups were also significant ( Z=-3.87, t=-5.57, both P<0.001). The differences between MTVs of 18F-FDG imaging/ 11C-choline imaging and VMRI (24.35(14.48, 36.89)mm 3) were all significantly different ( Z values: from -5.03 to -2.59, all P<0.05). Conclusions:Compared with 18F-FDG PET/CT, the preoperative 11C-choline PET/CT imaging in patients with nasopharyngeal carcinoma is closer to enhanced MRI (gold standard) in the lesion delineation. Compared with ROIs of the other 2 threshold delineation methods, the ROI obtained by the background threshold method is closer to that in enhanced MRI.

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective:To explore the trend of influenza positive rate in Beijing by using classic autoregressive integrated moving average (ARIMA) model, autoregressive integrated moving average model with exogenous variables (ARIMAX) and vector autoregression model (VAR) to compare the performance of three models in influenza prediction and select the most suitable one for Beijing.Methods:The weekly positive rate of influenza virus nucleic acid test and meteorological data in Beijing from week 1 of 2013 to week 40 of 2024 were collected. The data were divided into four groups with expanding training sets and corresponding testing sets. The training set of the first group was from week 1 of 2013 to week 40 of 2016, and the testing set was from week 41 of 2016 to week 40 of 2017. Subsequent groups extended the training set by one year each time. Data from 2020 to 2023 were excluded due to COVID-19 pandemic. The fourth group used data from the week 1 of 2013 to week 40 of 2023 for training and from the week 41 of 2023 to week 40 of 2024 for testing.Results:The incidence of influenza had seasonality in Beijing with higher incidence in winter and spring. The positive rate of influenza virus was positively correlated with the weekly average atmospheric pressure ( r=0.482, P<0.001) and weekly average wind speed ( r=0.003, P=0.034), and negatively correlated with the weekly average temperature ( r=-0.541, P<0.001). The ARIMAX model incorporating meteorological factors had the best prediction performance, with test set's root mean square error ( RMSE) of 0.115 3 and mean absolute error ( MAE) of 0.076 7 (the RMSE and MAE values for ARIMA and VAR models were 0.117 1 and 0.163 8, and 0.078 6 and 0.122 3, respectively). The prediction results of the optimal model showed that the positive rate of influenza virus would continue to rise in Beijing after October 2024 and reach peak in the second week of 2025, but the peak positive rate would be lower than that of previous influenza season. Conclusions:Compared with the ARIMA model and the VAR model,the ARIMAX model which used meteorological parameters is more suitable for prediction of long-term influenza trend in Beijing. The influenza trend peak was predicted to occur in the second week of 2025, but lower than that in previous influenza season.

Objective:To identify and summarize the best evidence for pelvic floor muscle exercises (PFME) in preventing pelvic floor dysfunction (PFD) during pregnancy.Methods:A systematic search was conducted in databases including UpToData, Cochrane Library, PubMed, Web of Science, Embase, China National Knowledge Infrastructure, VIP, Wanfang Data, SinoMed, Yiigle, and Joanna Briggs Institute Evidence Based Healthcare Center Database and so on. The search spanned from January 1, 2018, to March 16, 2023. Two researchers independently evaluated the quality of clinical decision-making articles, expert consensus, and systematic reviews, while four researchers appraised the quality of guidelines. Evidence extraction and grading were performed independently by two researchers.Results:A total of nine documents were included: three guidelines, two clinical decision-making articles, one expert consensus, and three systematic reviews. A total of 20 evidence-based recommendations were summarized in six categories: indications and contraindications, assessment, implementation plans, supervision and follow-up, management, and outcome evaluation.Conclusions:PFME during pregnancy is effective in preventing PFD. Healthcare providers should integrate best evidence into clinical practice to develop tailored PFME plans for pregnant women, aiming to prevent PFD.