ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.

To summarize the current status in the application of digital and intelligent technologies in the field of pharmacovigilance and to provide reference to the selection and development of methods for pharmacovigilance of rare diseases.

ObjectiveTo construct a group-based trajectory model (GBTM) for early medication adherence check-in, and to analyze the relationship between different trajectories and treatment outcomes in tuberculosis patients using data that were generated from smart tools for monitoring their medication adherence and check-in. MethodsFrom October 1, 2022 to September 30, 2023, a total of 163 pulmonary tuberculosis patients diagnosed in Fengxian District were selected as the study subjects. The GBTM was utilized to analyze the weekly active check-in trajectories of the subjects during the first 4 weeks and establish different trajectory groups. The χ² tests were employed to compare the differences between groups and logistic regression analysis was conducted to explore the relationship between different trajectory groups and treatment outcomes. ResultsA total of four groups were generated by GBTM analyses, of which a low level of punch card was maintained in group A, 6% of the drug users increased rapidly from a low level in group B, 17% of drug users increased gradually from a low level in group C, and 18% of drug users maintained a high level of punch card in group D. The trajectory group was divided into two groups according to homogeneity, namely the low level medication punch card group (group A) and the high level medication punch card group (group B, group C, and group D). The results of multivariate logistic regression analyses revealed that low-level medication check-in (OR=3.250, 95%CI: 1.089‒9.696), increasing age (OR=1.030, 95%CI: 1.004‒1.056), and not undergoing sputum examination at the end of the fifth month (OR=2.746, 95%CI: 1.090‒7.009) were significantly associated with poor treatment outcomes. ConclusionThe medication check-in trajectory of pulmonary tuberculosis patients within the first 4 weeks is correlated with adverse outcomes, or namely consistent low-level medication adherence check-ins are associated with poor treatment outcomes, while high-level medication adherence check-ins are associated with a lower incidence of adverse outcomes.

Objective To investigate the characteristic distribution of traditional Chinese medicine(TCM)syndrome types in gouty arthritis patients complicated with bone erosion,and to analyze the associated factors.Methods A total of 318 gouty arthritis patients hospitalized in the Rheumatology and Immunology Department of Foshan Hospital of Traditional Chinese Medicine between November 2021 and November 2023 were included.The patients were allocated to a bone erosion group(142 cases)and a non-bone erosion group(176 cases)according to the findings of musculoskeletal ultrasound.The clinical data of gender,age,body height,body mass,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),course of gout,findings of musculoskeletal ultrasound,complete blood count[white blood cell count(WBC),platelet count(PLT),hemoglobin(Hb),and red blood cell count(RBC)],blood uric acid(UA),creatinine(Cr),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)of the patients during hospitalization were collected.Differences in general information,laboratory parameters,and distribution of TCM syndrome types were compared between the two groups,and then the potential influencing factors of bone erosion in gouty arthritis patients were explored.Results(1)Analysis of general information showed that the bone erosion group had longer course of gout and slightly lower BMI than that the non-bone erosion group,and the differences were statistically significant(P＜0.05 or P＜0.01).However,there were no statistically significant differences in age,body height,body mass,SBP and DBP among the patients of the two groups(P>0.05).(2)Analysis of laboratory indicators showed that the levels of Cr,UA,ESR and TC in the bone erosion group were significantly higher than those in the non-bone erosion group,and the differences were statistically significant(P＜0.05 or P＜0.01).However,no statistically significant differences in the levels of CRP,WBC,RBC,PLT and LDL-C were presented between the two groups(P＞0.05).(3)Analysis of the distribution of TCM syndromes showed that in the bone erosion group,stagnant-heat obstruction syndrome accounted for the largest proportion(33.10%),followed by phlegm-turbidity obstruction syndrome(29.58%),damp-heat accumulation syndrome(22.54%),and liver-kidney yin deficiency syndrome(14.79%);in the non-bone erosion group,damp-heat accumulation syndrome accounted for the largest proportion(38.07%),followed by liver-kidney yin deficiency syndrome(32.95%),phlegm-turbidity obstruction(14.77%),and stagnant-heat obstruction(14.20%).There was statistically significant difference in the distribution of TCM syndromes between the two groups(P＜0.01).(4)The results of logistic regression analysis suggested that the higher the levels of ESR,UA,and TC,the longer the course of gout.And the TCM syndromes of stagnant-heat obstruction and phlegm-heat obstruction were the risk factors for bone erosion in gouty arthritis(P＜0.05 or P＜0.01).Conclusion Gouty arthritis patients with bone erosion exhibit higher UA,ESR,Cr,and TC levels,longer course of disease,and higher incidence of stagnant-heat obstruction syndrome and phlegm-turbidity obstruction syndrome.Bone erosion in gouty arthritis is closely associated with elevated UA,ESR,TC,and some specific TCM syndrome patterns.

Chronic eczema is clinically characterized by pruritus and skin lesions such as macules,exudation,desquamation,and lichenification.Traditional Chinese medicine(TCM)typically attributes its pathogenesis to wind,dampness,and heat pathogens,and TCM treatment for chronic eczema focused on dispelling wind,eliminating dampness,and clearing heat.However,there were fewer reports about the treatment of accompanying emotional changes and sleep disturbances in chronic eczema patients.This paper integrated the physique-qi-spirit trinity life view with zang-fu organ differentiation,and proposed that the disorder of spleen transportation and transformation contributed to the pathological foundation of chronic eczema,while the dysfunction of heart and liver was the factor that significantly influenced disease progression after analyzing the clinical features of chronic eczema.For the treatment of chronic eczema,the establishment of strategies should consider clinical characteristics,duration of disease,and skin lesion patterns.The combination of physique-qi-spirit regulation with heart-liver-spleen treatment approaches aims to alleviate clinical symptoms,improve quality of life,and enhance therapeutic efficacy for chronic eczema patients.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Objective To evaluate the application of shear wave elastography(SWE)in the diagnosis of peripheral neuropathy in patients with diabetes.Methods Totally 85 patients with type 2 diabetes(T2DM)were selected from the Chengdu Office Hospital of People's Government of Tibetan Autonomous Region,including 46 patients with peripheral neuropathy(DPN)and 39 patients without peripheral neuropathy(NDPN).Compared for clinical data(gender,age,disease duration),cross-sectional area of the median nerve measured by high-frequency ultra-sound(CSA)and shear wave elastography(SWE)parameters(mean Young's modulus value,Emean)and shear wave velocity(SWV)between two groups of patients.Multifactor Logistic regression analysis was carried out on the indicators between the above groups to screen independent predictors in the diagnosis of peripheral neuropathy in diabetes patients,and a combined model was constructed.The area under the operating characteristic curve(AUC),sensitivity and specificity of the subjects were used to evaluate the diagnostic efficacy of the single model and com?bined model of the quantitative parameters(CSA,Emean,SWV)measured by clinical data,high?frequency ultra?sound and SWE in the diagnosis of peripheral neuropathy in diabetes patients.Results Age,course of disease,Emean,SWV and CSA were statistically significant in the diagnosis of peripheral neuropathy in diabetes patients(all P<0.05).AUC was 0.658,0.754,0.839,0.822 and 0.736,respectively.The combination model based on disease course,CSA and SWV showed the highest diagnostic efficiency,with AUC,sensitivity,and specificity of 0.887(0.800-0.946),80.43％,and 84.62％,respectively.Conclusions The combined model based on the course of disease,CSA and SWV have a high diagnostic efficiency in peripheral neuropathy of diabetes patients,and has good clinical application value.