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.

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.

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.

Objective To explore the efficacy of blunt separation method in midline catheter intubation in elderly patients with coagulation dysfunction.Methods A total of 80 elderly patients with coagulation dysfunction were selected in the convenience sampling method from October 2022 to April 2023 in our hospital,and they were randomly divided into an experimental(blunt)group and a control(routine)group,with 40 patients in each group.The differences in the degree of bleeding and exudation at the puncture site,the pain score and the incidence of complications(including bleeding and exudation,phlebitis,symptomatic catheter-related thrombus,catheter blockage,catheter pulling-off)were compared between 2 groups.Results In the experimental group,the degree of bleeding and exudation at the puncture point immediately after the operation,degree of bleeding and exudation at the puncture point 24 hours after the operation,pain score 1 day after the catheterization,pain score 3 days after the catheterization,incidence of bleeding and exudation,total incidence of complications and maintenance times were significantly lower than these in the control group(P＜0.05).In terms of the pain score immediately after the operation,pain score 5 days after the operation,incidence of phlebitis,incidence of symptomatic catheter-related thrombosis,incidence of catheter blockage,incidence of catheter pulling-off,incidence of catheter related skin injury,incidence of unplanned extubation,success rate of one-time sheath delivery and the indwelling time,the differences between the experimental group and control group were not significant(P＜0.05).Conclusion The application of blunt separation method in midline catheter indwelling can significantly reduce the incidence and degree of bleeding at the puncture point,decrease the maintenance times and relieve the pain in elderly patients with coagulation dysfunction.

Objective To develop and validate a prediction model for severe disability or death(SDD)in acute ischemic stroke(AIS)patients who underwent endovascular treatment(EVT).Methods Based on the dataset of ANGEL-ACT study who received EVT for AIS between november 2017 and march 2019,a retrospective analysis was performed on 1 677 patients,including 1 111 males and 566 females,aged ≥ 18 years.Patients were divided into two groups according to whether SDD occurred(mRS 5-6 scores 90 days after surgery):SDD group(n=478)and non-SDD group(n=1 199).Risk factors that might influence SDD after EVT in AIS patients were screened and analyzed by multifactorial analysis,LAS-SO regression,and RF-RFE methods.A nomogram was developed after evaluating the model performance and the execution of internal validation.Results SDD occurred in 380(28.1％)patients in the develop-ment cohort and 98(30.2％)patients in the validation cohort.Combining the three variable screening meth-ods,10 risk factors were selected for inclusion in the final model:age,NIHSS score,whether successful re-canalization,glucose level,hemoglobin,hematocrit,onset to puncture time,systolic blood pressure,AS-PECT score,and whether have treatment-related serious adverse events.A two-stage model means that model 1 contains pre-treatment variables(7 in total)and model 2 contains pre-treatment and post-treatment variables(10 in total).The area under the curve(AUC)of model 1 in the development cohort was 0.705(95％CI 0.674-0.736)and 0.731(95％CI 0.701-0.760)in model 2.Both models had good calibration with aslope of 1.000,and the decision curve analysis showed good clinical applicability.The results of the validation cohort were similar to those of the development cohort.Conclusion Age,admission NIHSS score,whether successful recanalization,admission glucose level,hemoglobin content,erythrocyte pressure volume,onset to puncture time,admission systolic blood pressure,ASPECT score,and whether have treat-ment-related serious adverse events are risk factors for SDD in patients with acute ischemic stroke.The two prediction models based on the above factors were used before and after endovascular treatment to predict SDD occurrence better.

Objective:To explore the clinical and genetic characteristics of asparagine synthase deficiency.Methods:Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed.Results:All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor.Conclusions:Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Objective To investigate the predictive value of the inflammation scoring system based on the blood routine for complicated acute pancreatitis(CAP).Methods The clinical data of 630 patients with a-cute pancreatitis(AP)receiving the treatment in the People's Hospital of Chongqing Liang Jiang New Area from January 2021 to January 2024 were retrospectively analyzed.The patients were divided into the mild a-cute pancreatitis(MAP)group and CAP group according to the disease severity degree.The propensity score matching was used to balance the baseline characteristics of the cases in the two groups,the differences be-tween the inflammatory scoring system based on the blood routine[neutrophile granulocyte/lymphocyte ratio(NLR),derived neutrophile granulocyte/lymphocyte ratio(dNLR),platelet/lymphocyte ratio(PLR),system-ic immune inflammatory index(SII)and systemic inflammatory response index(SIRI)]and the clinical out-come indexes within 24 h of admission were analyzed,and the logistic regression was used to analyze the risk factors of CAP.Results A total of 404 patients were included in the study by the propensity score matching,each 202 cases in the two groups.In the CAP group,there were 35 cases(16.7％)receiving intensive care unit(ICU)treatment and 4 cases(1.9％)of death.Compared with the MAP group,WBC,neutrophile granulo-cyte,CRP,BUN,amylase and lipase levels and NLR,dNLR,SII and SIRI scores in the CAP group were high-er,serum calcium and albumin levels were lower,and the differences were statistically significant(P＜0.05).The stepwise logistics regression analysis showed that CRP,albumin,lipase,serum calcium and SIRI were the independent influencing factors of CAP occurrence(P＜0.05).Conclusion The inflammation scoring system based on the blood routine could predict the CAP occurrence.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram（aEEG）in small for gestational age（SGA）preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested，and aEEG was monitored at 6h and 72 h after birth，corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants，SGA preterm infants were divided into brain injury group（45 cases）and non-brain injury group（61 cases），and compared the differences of S100β protein，lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group（28 cases）and non-symmetrical group（15 cases）. The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared，and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein［（0.826±0.218）μg/L vs（0.397±0.196）μg/L， t=8.316， P<0.05］and lactate［（8.5±1.3）mmol/L vs（3.8±0.9）mmol/L， t=3.281， P<0.05］than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group［（0.924±0.205）μg/L vs（0.438±0.196）μg/L， t=5.734， P<0.05］.But there was no statistically significant difference in lactate levels［（5.6±1.4）mmol/L vs（3.9±1.2）mmol/L， t=0.932， P>0.05］between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%（45/45）vs 22.95%（14/61）at 6 h after birth，95.56%（43/45）vs 16.39%（10/61）at 72 h after birth，62.22%（28/45）vs 6.56%（4/61）at 32 weeks of corrected gestational age，22.22%（10/45）vs 3.28%（2/61）at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time，and the differences were statistically significant（ χ 2 value respectively 62.292，64.913，38.074，9.257，all P<0.05）. Conclusion:There were significant value in umbilical cord blood S100β protein，lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.