Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P＜0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P＜0.05 or P＜0.01),significantly lower spontaneous alternation percentage in Y-maze test(P＜0.05),and significantly elevated hippocampal Aβ1-42 level(P＜0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P＜0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P＜0.05),significantly higher spontaneous alternation percentage in Y-maze test(P＜0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P＜0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P＞0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P＞0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

The clinical data of a case of paroxysmal extreme pain disorder(PEPD) in Guangdong 999 Brain Hospital were retrospectively analyzed.The male patient, age of first examination was 7 months, began to have recurrent tonic accompanied by facial redness or cyanosis at 5 months after birth.The patient was diagnosed with epilepsy.The oral solution of sodium valproate and Levetiracetam were not effective.The video electroencephalogram examination displayed that, when the patient had tonic and bradycardia, the synchro electroencephalogram did not show epileptic discharge, so the patient was considered to have non-epileptic tonic.Genetic examination suggested that SCN9A gene mutation of c. 5240T >C resulted in amino acid changes: Val1747Ala.Combined with the skin changes, the patient was diagnosed as PEPD caused by SCN9A gene mutation.After the treatment with Carbamazepine, the patient′s abnormal skin changed and his-epileptic tonic disappeared, and his condition improved significantly.The early stage of PEPD can be mainly manifested as non-epileptic tonic.It is easy to be misdiagnosed as epilepsy, so the patient′s characteristic skin changes should be noticed, and genetic examination is also helpful in the diagnosis of the disease.

Objective To explore the relationship between radiomics signatures based on DWI and dynamic contrast-enhanced MRI (DCE-MRI) and molecular subtypes of breast cancer.Methods A retrospective analysis of 79 female breast cancer patients, with single mass, clear molecular subtypes and preoperative breast MRI scanning (obtaining DCE-MRI and ADC images), of Guangdong General Hospital from June 2015 to June 2016,were performed.Traditional quantitative parameters,including ADC value and initial enhancement rate(IER),were recorded.Texture analysis were performed on ADC map and DCE map, with manual segmentation and extraction of radiomic features,and Manual segmentation was performed on ADC map and DCE map, radiomics features were extracted and 10 radiomics signatures were finally selected after dimension reduction. Four molecular subtypes of breast cancer were classified by immunohistochemical detection of pathological specimens, including Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple negative (TN). Univariate logistic regression analysis was used for assessing the performance of ADC values, IER values and radiomics signatures to independently predict molecular subtypes groups.Multivariate logistic regression analysis was performed to establish predicting models, then receiver operating characteristic curves (ROC) were drawn and areas under ROC curve were calculated to compare the diagnostic performance of each model. The Hosmer-Lemeshow test was performed to test the goodness of model fitness. Results There were 29 cases of Luminal A, 39 cases of Luminal B, 5 cases of HER2 overexpression and 6 cases of TN breast cancer patients.Univariate logistic regression analysis was used to assess the ability of traditonal MRI parameters of ADC and IER values and ten of the radiomics siganitures in classifying molecular subtypes,results showed that the AUC values of ADC and IER values, were both less than 0.70 (range 0.516 to 0.605), which indicated valueless;at least one radiomic signature had AUC greater than 0.70 when identifying each molecular subtype, and AUC of DCE_L_G_2.5_autocorrelation achieved the highest value of 0.941 in identifying TN and non-TN subtypes.Multivariate logistic regression analysis were performed to obtain the best model, results showed that the AUCs for classifying Luminal A and non-Luminal A, Luminal B and non-Luminal B, TN and non-TN subtypes were 0.786 and 0.733 And 0.941, respectively. The Hosmer-Lemeshow test showed that the P values of all models were larger than 0.10 (0.156, 0.204 and 0.820,respectively),indicating that there was no significant difference between the predicted and observed values of each model established, these models were all fitted good. Conclusion The radiomics features based on ADC map and DCE map can help to identify the molecular subtypes of breast cancer,especially for the identification of TN type breast cancer.

The expert system is an important field of the artificial intelligence. The traditional interface of the expert system is the command, menu and window at present. It limits the application of the expert system and embarrasses the enthusiasm of using expert system. Combining with the study on the expert system of network fault diagnosis, the natural language interface of the expert system has been discussed in this article. This interface can understand and generate Chinese sentences. Using this interface, the user and field experts can use the expert system to diagnose the fault of network conveniently. In the article, first, the extended production rule has been proposed. Then the methods of Chinese sentence generation from conceptual graphs and the model of expert system are introduced in detail. Using this model, the network fault diagnosis expert system and its natural language interface have been developed with Prolog.

Aim To investigate the effects of monocrotaline pyrrole on production of nitric oxide and expression of eNOS protein of cultured pulmonary artery endothelial cells and on contractility of cultured pulmonary artery smooth muscle cells.Methods DAF-2 fluorescence technique was used to determine NO level,Western blot analysis was performed to determine the level of eNOS protein,and collagen gel contraction system was adopted to analyze muscle contractility.Results NO production induced by ACh and expression of eNOS protein were obviously inhibited by monocrotaline pyrrole compared with those of control group and gel contraction area in MCTP-treated cells induced by Thapsigargin obviously decreased.Conclusions monocrotaline pyrrole could inhibit the level of the ACh-induced production of NO and expression of eNOS protein,and enhance the contractility of pulmonary artery smooth muscle cells,which may be one of the possible mechanisms of MCTP-induced pulmonary artery hypertension.

Objective To assess the effects of cyclic stretch on fibroblast orientation in order to find the appropriate cyclic stretch to cause maximum fibroblast orientation and to explore the mechanism of cell signalling since cells are known to orient in response to the application of mechanical forces. Methods Human forehead dermal fibroblasts were seeded onto collagen coated flexible membranes. Membranes were then deformed at 10 cycles per minute by the application of 135 mmHg subatmospheric pressure. This corresponded to strain levels of 0% to 24% from the center to extremity of the flexible membrane. Cells orientation angles were studied by inverted microscopy. Integrin ?1 distribution were studied with immunocytochemical staining and confocal microscopy. Integrin ?1 expression and focal adhesion kinase ( FAK) phosphorylation were analyzed with Western blot analysis. Results A minimum of 15% cell stretch was required to significantly stimulate the fibroblast orientation response. Cyclic stretch induced integrin ?1 redistribution and FAK phosphorylation. Incubation of cells with anti-integrin ?1 prior to the application of stretch abrogated fibroblast orientation and FAK phosphorylation. Conclusion Fibroblast orientation in response to cyclic stretch is mediated at least in part by integrin ?1 through phosphorylation of FAK.