ObjectiveTo investigate the potential mechanism of Danggui Buxuetang （DBT） in the treatment of vascular dementia （VAD）. MethodsSixty male SD rats were randomly assigned to the sham-operated group， model group， DBT low-， medium-， and high-dose groups， and the donepezil group. Except for the sham-operated group， rats in all other groups underwent bilateral common carotid artery ligation. After successful modeling， DBT was administered at doses of 9.2， 18.4， 36.8 g·kg^-1 for the low-， medium-， and high-dose groups， respectively， while the donepezil group received 3 mg·kg^-1 donepezil solution by gavage once daily. After 4 consecutive weeks of drug treatment， rats underwent the Morris water maze test， novel object recognition test， Nissl staining to observe hippocampal neurons， and immunofluorescence staining to detect the expression of neuronal nuclear protein （NeuN） in the hippocampus. Western blot was used to assess the expression of PTEN-induced kinase 1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Transmission electron microscopy was used to observe hippocampal neuronal ultrastructure. Real-time PCR was used to detect the expression of NADPH oxidase subunits p22^phox and p47^phox in hippocampal tissues. The levels of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， and total antioxidant capacity were measured to evaluate oxidative stress levels. ResultsIn the Morris water maze test， escape latency changed significantly over time in all groups except the model group. Compared with the sham-operated group， the model group showed significantly prolonged escape latency （P<0.01）. Compared with the model group， rats in the DBT groups and the donepezil group exhibited significantly shorter escape latency （P<0.05， P<0.01）. The number of crossings over the original platform was significantly reduced in the model group compared with the sham-operated group （P<0.01）， whereas rats in the DBT and donepezil groups showed significantly increased platform crossings compared with the model group （P<0.05， P<0.01）. Compared with the sham-operated group， exploration time of new objects was significantly reduced in the model group （P<0.01）. Compared with the model group， exploration time of new objects increased significantly in the medium- and high-dose DBT groups and the donepezil group （P<0.05， P<0.01）， while no significant change was observed in the low-dose DBT group. Compared with the high-dose DBT group， rats in the donepezil group had significantly prolonged escape latency and reduced platform crossings and new-object exploration time （P<0.05）. Nissl staining showed decreased density of healthy neurons in the CA1 and CA3 regions of the hippocampus in the model group， with loss of Nissl bodies and nuclear atrophy or disappearance. In the high-dose DBT group， neuronal density in CA1 and CA3 increased， with neurons arranged closely and displaying normal morphology. Immunofluorescence showed that compared with the sham-operated group， the hippocampal NeuN⁺ cell count in the VAD model group was significantly decreased（P<0.01）， compared with the VAD model group， the hippocampal NeuN⁺ cell count in the high-dose DBT group was significantly increased（P<0.01）. Compared with the sham-operated group， the expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins was significantly increased（P<0.01）， while the expression of Bcl-2 was significantly decreased in the VAD model group（P<0.01）. Compared with the VAD model group， the high-dose DBT group showed significantly decreased expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins（P<0.01）and significantly upregulated Bcl-2 expression（P<0.01）. The medium-dose DBT group exhibited significantly reduced expression of Parkin， LC3Ⅱ， and Bax proteins（P<0.05，P<0.01） and significantly increased Bcl-2 expression（P<0.01）， while no statistically significant differences were observed in the low-dose DBT group. Transmission electron microscopy showed mitochondrial pyknosis， thickened cristae， increased electron density， and the presence of mitochondrial autophagy in the model group. In contrast， hippocampal neurons in the high-dose DBT group contained abundant mitochondria with intact morphology， clear cristae， and uniform matrix. Compared with the sham-operated group， total antioxidant capacity， SOD activity， and GSH levels were significantly decreased， while MDA levels were significantly increased in the model group （P<0.01）. Compared with the model group， total antioxidant capacity and antioxidant levels （SOD， GSH） increased significantly， and MDA decreased significantly in the medium- and high-dose DBT groups （P<0.01）， while no significant changes were observed in the low-dose DBT group. Compared with the sham-operated group， mRNA expression of p22^phox and p47^phox was significantly increased in the model group （P<0.01）. Compared with the model group， expression of p22^phox and p47^phox was significantly decreased in the DBT groups （P<0.05， P<0.01）. ConclusionDBT may exert neuroprotective effects by regulating PINK1/Parkin-mediated mitochondrial autophagy， thereby improving learning and memory abilities and treating VAD.

ObjectiveTo systematically sort out the knowledge framework and conceptual logic relationship of "disease-syndrome-treatment-prescription-medicine" in the existing literature on traditional Chinese medicine（TCM） treatment of diabetic peripheral neuropathy（DPN）， to construct of the knowledge map of TCM treatment of DPN， and to promote the explicitation of the implicit knowledge in the literature on the treatment of DPN with TCM. MethodTaking the literature of China National Knowledge Infrastructure about TCM treatment of DPN as the main data source， TCM-related concepts and entities were constructed by manual citation， and the corresponding relationships between the entities were established. Structured data were formed by processing with Python 3.7， and the knowledge graph was constructed based on Neo4j 3.5.34 graph database. ResultThe resulting knowledge graph with TCM diagnosis and treatment logic， defined 12 node labels such as prescriptions， Chinese medicines and syndrome types at the schema layer， as well as 4 types of relationships， such as inclusion， correspondence， selection and composition. It could support the query and discovery of nodes（syndrome elements， syndrome types and treatment methods）， as well as the relationship between each node. ConclusionBased on the literature data， this study constructed a knowledge map for TCM treatment of DPN， which brought together various methods of TCM treatment of DPN， including internal and external treatment. The whole chain knowledge structure of syndrome differentiation and classification for DPN treatment is formed from syndrome element analysis， syndrome type composition to treatment method selection， which can provide new ideas and methods for literature data to serve clinical and scientific research work， as well as reference for visualization of TCM literature knowledge， intellectualization of TCM knowledge services and the standardization of TCM diagnosis and treatment.

Objective:To investigate the clinical characteristics of psoriasis and status quo of medical care for patients in county areas of China.Methods:This study was a cross-sectional investigation. Based on the “Qianxian Wuyin” Project (a national project for upgrating ability for psoriasis care at county level), an online questionnaire survey was conducted in the dermatology departments of 459 county hospitals in 404 pilot administrative counties across China from February to June 2023. The questionnaire included demographic information of patients (gender, ethnicity, age, place of residence, education, marital status), and clinical characteristics of psoriasis (disease course, type, comorbidities, body surface area (BSA) and previous treatment. The Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were applied for assessing the quality of life and disease severity, and completed by patients or guardian and doctors, respectively.Results:A total of 16 935 patients completed the questionnaire. The age of patients was 1-102(44.17±11.58)years, and 71.0% (12 036/16 935) were 30-59 years old. The ratio of male to female was 2.21∶1; 24.3%(4 117/16 935) of patients had high school education; there were 9 940 patients(58.7%) with previous or current smoking and/or alcohol use; 42.8%(7 218/16 855) of patients had a disease course of 1-5 years. There were 15 630 patients(92.3%) with DLQI≥10, 8 346 patients(49.7%) with PASI≥10, 15 017 patients(89.2%) with BSA≥10%. The plaque type was the most common disease type ( n=14 965, 88.7%), and spotting type ranked the second ( n=1 141, 6.8%). The most common initial site was the trunk ( n=12 309, 72.9%). Among the comorbidities, hypertension was the most common one ( n=1 681, 10.0%). There were 7 650 reports of treatment response to conventional topical drug therapy and 3 112 reports of treatment response to systemic drug therapy, with 6 269 (81.9%) and 2 493 (80.1%) reporting poor or no response, respectively. Conclusions:The survey shows that in the county areas of China, the majority of psoriasis patients are severe patients with short course of disease, plaque type is the most common type, and hypertension is the most common comorbidity; and the conventional treatment is less effective for most patients.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To investigate the serotype distribution and phylogenetic analysis of virus complete genome from indigenous dengue patients in Guangzhou in 2019 and provide evidence for the development of prevention and treatment strategies.Methods:Dengue virus serotypes of indigenous dengue cases in 2019 were detected using serotype specific fluorescent PCR kits. Complete genome in the culture was performed on Illumina platform. Phylogenetic analysis was conducted on complete genomes extracted from ViPR and the isolates from this study with MEGA7.0 software.Results:In 2019, three prevalent serotypes of dengue virus were found in Guangzhou, among which serotype 1 accounted for 80.35%, serotype 2 accounted for 12.97% and serotype 3 accounted for 6.68%. There were no significant differences in gender, age and severity among three serotypes. Phylogenetic analysis of virus complete genome showed that serotype 1 belonged to genotypeⅠand had two origins, which was close to the Cambodian strain; serotype 2 belonged to genotype cosmopolitan, which was close to the epidemic strain in Southeast Asia; serotype 3 belonged to genotypeⅢ, which was in the same branch as the Indian strain.Conclusions:The dengue epidemic was caused by dengue virus serotypes 1, 2 and 3 in Guangzhou in 2019. Each serotype belonged to a genotype.

Objective:To compare the levels of cytokines in patients with dengue fever (DF) and severe dengue (SD) at different time points during the course of disease, to seek the cytokines that can be used as early warning signs of SD, and to explore the relationship between the immune response and the pathogenesis of SD.Methods:Plasma samples at different time points were collected from 60 hospitalized patients including 48 mild cases and 12 severe cases in Guangzhou Eighth People′s Hospital during June to December, 2014. Levels of 19 cytokines including TNF-α, IL-6, IL-8, IL-10, IL-15, IL-17A, IFN-α2, IP-10, MCP-1, RANTES, GRO-α, PDGF-AA, PDGF-AB/BB, MIF, VEGF, sVCAM-1, sICAM-1, sFas and sFasL were determined by a multiplex Luminex system.The viral loads were determined by using fluorescence quantitative RT-PCR and the correlation between viral loads and cytokine level were analyzed.Results:The levels of TNF-α, IL-6, IL-8, IL-10, IL-15, IFN-α2, IP-10, MCP-1 and sVCAM-1 increased in dengue patients, while RANTES, GRO-α and PDGF decreased.The levels of IL-17A, MIF, VEGF, sICAM-1, sFas and sFasL did not change. The levels of TNF-α, IL-6, IFN-α2, IP-10 and sVCAM-1 in SD patients were significantly higher than those in DF patients at the early stage (Day 2-5 after disease onset), and the differences were statistically significant. On day 6-10, the levels of TNF-α, IL-6, IL-8, IL-10, IL-15, PDGF, RANTES, IFN-α2, IP-10 and sVCAM-1 were significantly different between DF and SD patients. The results of correlation analysis showed that the level of IL-15 was moderately correlated with viral load, while other cytokines was only weakly correlated or not.Conclusions:TNF-α, IL-6, IFN-α2, IP-10 and sVCAM-1 can be used as early warning signs of SD. The level of cytokines is related to the severity of dengue fever.

Objective To investigate the potential effects and mechanism on peroxisome proliferator-activated receptor γ-toll-like receptor 4-tumor necrosis factor-α (PPARγ-TLR4-TNF-α) targeted pathway on hyperglycemia induced myocardium inflammation and oxidative stress. Methods Thirty-two Japanese healthy adult rabbits were randomly divided into four groups with 8 rabbits in each group: normal control group (NC group), diabetes mellitus group (DM group), diabetes mellitus + pioglitazone 4 mg·kg-1·d-1 and 8 mg·kg-1·d-1 groups (DM+PGZ 4 mg and 8 mg groups). DM model was reproduced by alloxan of 150 mg/kg through auricular vein injection. On the same day of successful DM model reproduction, the diabetic rabbits were fed with corresponding dose of pioglitazone in DM+PGZ 4 mg and 8 mg groups, but the rabbits in NC group were not challenged. After 8 weeks of feeding, venous blood of left jugular vein bifurcation and myocardium tissue were harvested respectively for the determination of inflammation and oxidative stress parameters. TNF-α, interleukin-1 (IL-1), adiponectin (ADP), nitric oxide (NO) and total nitric oxide synthase (NOS) levels were determined by enzyme linked immunosorbent assay (ELISA), myeloperoxidase (MPO) activity was determined by colorimetric method, superoxide dismutase (SOD) activity was determined by hydroxylamine method, malondialdehyde (MDA) was determined by thiobarbituric acid colorimetric method, and catalase (CAT) activity was determined by UV spectrophotometry method. In addition, the mRNA expressions of TNF-α and TLR4 were determined by real-time quantitate reverse transcription-polymerase chain reaction (RT-qPCR). Results ① IL-1 and TNF-α in serum and myocardium of model rabbits were significantly increased, ADP was significantly decreased, and the mRNA expressions of TNF-α and TLR4 in myocardium were significantly increased, indicating a significant inflammatory reaction. The inflammatory reaction in pioglitazone intervention groups was significantly reduced, TNF-αand IL-1 levels in serum and myocardium of DM+PGZ 4 mg and 8 mg groups were significantly decreased as compared with those of DM group [serum: TNF-α(ng/L) was 268.33±46.57, 261.34±33.73 vs. 331.40±69.05, myocardium: TNF-α (ng/L) was 144.72±26.90, 139.59±14.59 vs. 177.48±27.40; serum: IL-1 (ng/L) was 24.40±2.56, 23.35±3.13 vs. 30.08±5.44, myocardium: IL-1 (ng/L) was 21.26±2.85, 20.54±2.75 vs. 24.78±3.60, all P < 0.05], and ADP levels were significantly increased [serum (μg/L): 19.64±8.85, 20.54±7.47 vs. 15.45±3.06, myocardium (μg/L): 10.31±2.22, 11.49±3.42 vs. 7.76±1.77, all P < 0.05], and the mRNA expressions of TNF-α and TLR4 in myocardium were significantly decreased (TNF-αmRNA: 0.15±0.05, 0.14±0.06 vs. 0.25±0.09; TLR4 mRNA: 0.57±0.17, 0.40±0.18 vs. 0.75±0.35, all P < 0.05). ②Oxidative stress in serum and myocardium of model rabbits was significantly increased, SOD, NO, and total NOS levels were significantly decreased while the serum CAT and MDA levels were significantly increased without effect on MPO. Compared with the DM group, SOD and NO levels in serum and myocardium were significantly increased in DM+PGZ 4 mg and 8 mg groups [serum: SOD (U/L) was 571.39±40.85, 609.28±54.47 vs. 535.10±37.08, myocardium:SOD (U/mg) was 55.74±8.12, 53.60±9.87 vs. 42.26±12.34; serum: NO (μmol/L) was 2.95±0.51, 2.99±0.43 vs. 2.03±0.78, myocardium: NO (nmol/mg) was 1.95±0.37, 2.11±0.26 vs. 1.56±0.33, all P < 0.05], the serum MDA levels were significantly decreased (μmol/L: 20.11±2.34, 19.70±2.02 vs. 23.07±3.06, both P < 0.05), while no significant effect on CAT. There was no significant difference in parameter of inflammatory and oxidative stress between the two pioglitazone intervention groups. Conclusion 4 mg·kg-1·d-1 pioglitazone could activate PPARγ-TLR4-TNF-α targeted pathway, thus inhibit inflammatory and oxidative stress factors expression, and down-regulate hyperglycemia induced myocardium inflammatory and oxidative stress level, but the effect did not show a dose dependent manner.

OBJECTIVE: To establish GC-MS fingerprint of volatile oil from Citrus aurantium. METHODS: GC-MS method was adopted. The determination was performed on RTX-5MS capillary column with injector temperature of 250 ℃, high pure helium as carrier gas(≥99. 999％), flow rate of 1. 0 mL/min, split ratio of 10:1,and sample size of 1 μL (temperature programming). Mass spectrum condition included electron bombardment ion source, ion source temperature of 230 ℃, detector temperature of 250 ℃, 3 min solvent delay, scanning range of m/z 35-550. GC-MS chromatograms of 21 batches of volatile oil samples were determined using Laurene as reference. The similarity of them was evaluated by using TCM Chromatographic Fingerprint Similarity Evaluation System (2004 A edition), and common peak was determined. The components of common peak were determined by LC Solution 2 mass database (NIST05. LIB and NIST05s. LIB). Relative content of common peak was determined with area normalization. RESULTS; There were 20 common peaks in GC-MS chromatograms of 21 batches of volatile oil samples, and the similarity was higher than 0. 90. After validation, GC-MS chromatograms of 21 batches of volatile oil samples were in good agreement with control fingerprint. The main constituents of the volatile oil of C. aurantium were Limonene, Terpinene, Laurene and D-Cadinene. CONCLUSIONS: Established fingerprint can provide reference for identification and quality evaluation of volatile oil of C. aurantium.

Objective To investigate the regeneration and differentiation of HOCs in the 2-AAF/PHx rat models. To explore the expression of Cyr61and its mechanism in differentiation of HOCs in vitro. Methods In 2-AAF/PHx rats model,induction and expansion of HOCs were detected by immunochemistry and HE staining. West-ern blot was used for observing the expression of Cyr61. Furthermore,the expression of Cyr61 andβ-catenin were detected by Western blot in differentiation of WB-F344 cells in vitro. Results Cyr61 protein level increased as a re-sult of HOCs in rats livers after 2-AAF/PHx. In addition,the expression of Cyr61 and β-catenin significantly in-creased during WB-F344 cells differentiation in vitro. Conclusions Cyr61 might play an important role as a signal-ing mediator in HOCs response and closely correlate with Cyr61 andβ-catenin in proliferation and differentiation of HOCs.

Objective To observe the clinical effect ofJiedu-Huayu granule for the Dengue Fever (DF).Methods The patients with DF were randomly divided into the treatment group and control group. Both groups received the conventional treatment, and the treatment group addedJiedu-Huayu granule. The clinical effects were detected.Results At the baseline, the ALT and AST in the treatment were significantly higher than those in the control group (t=2.830,P=0.014;t=2.109,P=0.044). But after treatment, there was no difference between groups. The ALT in the treatment group showed a gradual change and AST recovery time showed short. Compared with control group, the concentration of sVCAM-1 in the treatment group was higher at baseline and the third day (t=2.780,P=0.018;t=2.130,P=0.460), but the concentration of MCP-1 desceased significantly on the 6th day (t=-2.164,P=0.042).Conclusions Compared with the western medicine, the treatment of western medicine andJiedu-Huayu granule could alleviate liver injure, shorten the recovery time, and reduce the concentration of sVCAM-1 and MCP-1.