Objective:To investigate the levels of chemokine 2 (CCL2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X3-C motif) ligand 1 (CX3CL1), and chemokine (C-X-C motif) ligand 10 (CXCL10) in the cerebrospinal fluid of patients with acute and chronic herpes zoster (HZ), and their correlation with the severity of neuropathic pain.Methods:A total of 60 patients with acute herpes zoster and postherpetic neuralgia (PHN) treated at the First Affiliated Hospital of Zhengzhou University from November 2022 to November 2023 were selected for a case-control study. These patients were divided into a HZ group ( n = 25) and a PHN group ( n = 35). The pressure pain threshold in the affected area was measured on the day of admission for all patients. The Visual Analogue Scale scores were evaluated in both groups. After lumbar puncture, 2 mL of cerebrospinal fluid was collected, and the levels of related chemokines in the cerebrospinal fluid were detected using the enzyme-linked immunosorbent assay. Results:In the HZ group, the levels of chemokines CXCL1 and CXCL10 were (24.84 ± 6.97) ng/L and (107.46 ± 28.29) μg/L, respectively, while in the PHN group, they were (20.51 ± 3.16) ng/L and (132.98 ± 30.92) μg/L. The differences in the levels of chemokines CXCL1 and CXCL10 between the two groups were statistically significant ( t = 2.91, -3.26, both P < 0.05). There were no statistically significant differences in the levels of chemokines CCL2 and CX3CL1 between the two groups ( t = 1.62, -0.23, both P > 0.05). The levels of CCL2, CXCL1, CX3CL1, and CXCL10 in both groups were negatively correlated with the pressure pain threshold (HZ group: r = -0.84, -0.78, -0.93, -0.86; PHN group: r = -0.71, -0.78, -0.94, -0.76, all P < 0.01). Conclusion:Higher levels of chemokines in the cerebrospinal fluid of patients with acute and chronic HZ are associated with more pronounced neuropathic pain. The neuro-immune inflammation involving chemokines may be correlated with the severity of neuropathic pain in acute and chronic HZ.

Objective:To investigate the mechanism of curcumin affecting HIV-1 infection co-receptor CCR5 by regulating transcription factor FOXP3.Methods:Binding sites of transcription factor FOXP3 on CCR5 promoter were predicted and analyzed by bioinformatics method.AutoDock 4.2 software was used to connect curcumin and FOXP3 flexibly.MTT assay was used to detect cyto-toxcity of curcumin on activity of Jurkat cells.qRT-PCR and Western blot were used to detect expression levels of CCR5 and FOXP3 mRNA and protein in Jurkat cells that were treated with different concentrations of curcumin.pcDNA3.1-FOXP3 expression vector was built and combined with the prediction results of transcription factors.The mutant CCR5 gene fragment was amplified by Overlap PCR,and the mutant CCR5 promoter recombinant vector pFireRluc-Mt-CCR5 was constructed.Binding site between transcription fac-tor FOXP3 and CCR5 promoter was verified by double luciferase reporter gene assay.Results:Results of JASPAR transcription factor prediction showed that there was a binding site between CCR5 promoter and transcription factor FOXP3;molecular docking results showed that curcumin could bind to the active region of FOXP3;MTT results showed that curcumin inhibited the activity of Jurkat cells after 24 hours,and the IC50 was 34.48 μmol/L.qRT-PCR and Western blot showed that expression levels of CCR5 and FOXP3 mRNA and protein were decreased in a dose-dependent manner after different concentrations of curcumin treated Jurkat cells;double luciferase reporter gene confirmed that FOXP3 could bind to CCR5 promoter,and the transcription factor FOXP3 could regulate the activity of CCR5 promoter;results of the recovery experiment of FOXP3 on curcumin showed that when the curcumin concentration was 60 μmol/L,relative value of luciferase activity in HEK293T cells with pcDNA3.1-FOXP3 and pFireRluc-Wt-CCR5 was signifi-cantly higher than that in pFireRluc-Wt-CCR5+curcumin-60 group(P<0.01).Conclusion:FOXP3 can regulate the activity of CCR5 promoter,and the mechanism may be that curcumin affects activity of CCR5 promoter by acting on binding site of FOXP3 and CCR5 promoter.

In recent years,psoriatic arthritis has become a major problem in the medical field,with cases gradually increasing in China,and it is still incurable.Here,we summarize the pathogenesis and clinical characteristics of currently available animal models of psoriatic arthritis based on Chinese and Western medical evidence.Literature in line with this topic was collated and summarized.The etiology and pathogenesis according to Chinese and Western medicine of existing psoriatic arthritis models were given agreement scores;the diagnostic criteria of Chinese and Western medicine were compared;and the models'characteristics and degree of agreement with clinical observations were assessed.This study found that the human leukocyte antigen transgenic mouse model,the multiple hybridization transgenic mouse model,and the mannan-induced mouse model had the highest agreement scores.As psoriatic arthritis is more common in Europe,methods for the preparation of animal models have been mostly imported from abroad,and very few animal models have the characteristics of Chinese medicine;therefore,the model fitness scores of Western diagnoses were higher than those of Chinese diagnoses as a whole.We hope to leverage the unique diagnosis and treatment method of Chinese medicine further to improve the types of psoriatic arthritis animal models available.This study provides a basis for the construction of improved animal models of psoriatic arthritis with combined traditional Chinese and Western medicine characteristics.

Ketosis in dairy cows is often accompanied by apoptotic and inflammatory responses in adipose tissue.In order to investigate the effect of pro-apoptotic protein Bid on adipocyte apoptosis in cows with ketosis,the adipose tissue was stained by TUNEL staining technique in this study to observe the apoptotic changes in adipose tissue of cows with ketosis.In the in vivo test,protein ex-pression of apoptosis-related factors Bid,Bax,C-Caspase-3,Bcl-2 and inflammation marker factors C1q,IL-1β,IL-10 and IL-6 in adipose tissues of healthy cows and ketosis cows were detected by Western blot.In the in vitro assay,the adipocyte lipolysis model was constructed by culturing pri-mary bovine adipocytes in vitro to inhibit Bid and adding isoproterenol(ISO),and the protein ex-pression levels of apoptosis-related molecules and inflammation-related molecules in adipocytes were detected by Western blot technique.The results of TUNEL staining showed that the protein expression of pro-apoptotic factors Bid,Bax and C-Caspase-3,and pro-inflammatory markers TNF-a,IL-1β,and IL-6 were significantly higher,and the protein expression of complement C1q,anti-ap-optotic factor Bcl-2,and anti-inflammatory factor IL-10 were significantly lower in adipose tissues of ketosis cows compared with that of healthy cows.The in vitro results showed that the protein expression levels of apoptosis and inflammation-related factors in adipocytes treated with the ISO group were significantly higher compared with those in the control group,while the protein ex-pression levels of apoptosis and inflammation-related factors in adipocytes treated with the addi-tion of the Bid inhibitor group were significantly lower.The above results showed that inhibition of Bid could alleviate the apoptotic and inflammatory responses of ISO on adipocytes.This will fur-ther clarify the role of Bid/C1q in the regulation of adipose tissue and cell apoptosis and inflamma-tion in ketosis cows.

Traditional Chinese medicine dispensing granules（TCMDGs）is the new type of decoction pieces with the development of modernization of TCM， which has received mixed opinions since its practical application. In 2021， the national departments issued Announcement on Ending the Pilot Work of TCMDGs， marking the end of the 28-year pilot work of TCMDGs， and eligible TCM enterprises can produce TCMDGs after filing. However， this does not mean that the preparation process， quality standard and efficacy research of TCMDGs have been developed and matured， on the contrary， there are still some problems that need to be solved and gradually improved. For example， in the production process， there are problems such as unclear， unified and non-standardized preparation parameters. In terms of quality control， there are some problems such as lack of producing area regulation， variety selection and processing specification. In terms of consistency evaluation with traditional decoction， there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore， in view of some prominent problems of TCMDGs at present， this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia， Publicity of the Unified Standard on the Varieties of TCMDGs， Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs， the origin and variety of raw materials， the processing of decoction pieces， the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining， data analysis and list comparison. Based on the analysis results， the following suggestions were made. In terms of preparation process， the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation， attention should be paid to the relationship between the authenticity， variety， processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction， the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine， quality marker（Q-Marker） theory and physicochemical characterization， so as to provide reference for the application and development of TCMDGs.

Objective:To explore the correlation of neutrophil-to-lymphocyte ratio(NLR) and platelet-to-lymphocyte ratio (PLR) with lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM).Methods:A total of 314 T2DM patients hospitalized in Tengzhou Central People′s Hospital from January 2018 to December 2019 were collected and divided into LEAD group (168 cases) and control group (146 cases) according to the results of color Doppler ultrasound of lower extremity arteries. General clinical data were collected. Fasting venous blood samples were collected to detect blood routine and biochemical indicators. NLR and PLR values were calculated. Patients were divided into 4 groups according to the NLR and PLR quartiles. The differences of data in each group were analyzed; Spearman correlation was used to analyze the correlation between NLR, PLR and each index; The risk factors of LEAD in T2DM patients were analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to determine the efficiency of the model predicting LEAD in T2DM patients.Results:The age, white blood cells count (WBC), neutrophil count, NLR, PLR and C-reactive protein (CRP) in LEAD group were significantly higher than those in control group (all P<0.05). With the increase of NLR and PLR quartiles, the age, body mass index, WBC, neutrophils and platelets increased gradually ( P<0.05), and the lymphocytes decreased gradually ( P<0.05). Spearman correlation analysis showed that NLR and PLR were positively correlated with age, neutrophils and platelets (all P<0.01), but negatively correlated with lymphocytes (all P<0.01). Logistic regression analysis showed that age, NLR, PLR, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and CRP were the risk factors of LEAD in T2DM patients (all P<0.01). The area under the curve (AUC) of NLR, PLR, CRP and age were 0.813, 0.683, 0.668 and 0.630, respectively; The sensitivity was 82.49%, 84.37%, 72.58% and 62.87%, respectively. Conclusions:NLR and PLR are closely related to LEAD in T2DM patients. NLR is superior to PLR and CRP in the diagnosis of LEAD.

OBJECTIVE To study the improvement effects and mechan ism of thalidomide on Alzheimer ’s disease （AD）model of Caenorhabditis elegans . METHODS In this study ，the BR 5270 strain of C. elegans was used as AD model and BR 5271 strain as the control. The effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the motility of BR 5270 strains of C. elegans were studied by the basal slowing response assay ；the effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the survival time of BR 5270 strain of C. elegans were studied by life assay ；the effects of thalidomide （0.5，2.0，6.0 mg/mL）on learning and memory ability of BR 5270 strain of C. elegans were studied by short-term and long-term learning and memory assay. RT-PCR technology was used to study the effects of thalidomide （0.5，2.0，6.0 mg/mL）on mRNA expression of phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）signal pathway related genes （Age-1，Akt-1，Gsk-3）and calpain homologous gene （Clp-1）in BR 5270 strain of C. elegans . RESULTS After the intervention of thalidomide ，oscillation times of BR 5270 strain of C. elegans increased significantly within 30 s （except for 0.5 mg/mL group ），and the 10％ of maximum life span was prolonged significantly （only 0.5 mg/mL group ）；the short-term and long-term learning indexes were improved significantly （only 6.0 mg/mL group ）；mRNA expression of Age-1 and Akt-1（except for 0.5，2.0 mg/mL groups ）were increased significantly ，mRNA expression of Gsk-3（except for 0.5 mg/mL group ） and Clp-1 were decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Thalidomide can ameliorate the dyskinesia of AD model of C. elegans，prolong the lifespan of this strain ，and enhance its learning and memory ability. Its mechanism of action may be related to activation of PI 3K/Akt signaling pathway and inhibition of calpain.

Objective:To evaluate the role of spinal cord mitochondrial autophagy in alleviation of diabetic neuropathic pain (DNP) by curcumin in mice.Methods:SPF healthy male C57BL/6 mice, aged 2 months, weighing 20-25 g, in which DNP model was established by intraperitoneal injection of streptozotocin (STZ) 130 mg/kg, were used in this study.A total of 36 mice with successfully established DNP model were divided into 3 groups ( n=12 each) using the random number table method: DNP group, DNP + curcumin group (DPR group), and DNP + curcumin + cyclosporine A group (DRC group). Another 12 C57BL/6 mice were selected and served as normal control group (NC group), and the equal volume of normal saline was intraperitoneally injected.In group DPR, curcumin 200 mg/kg was administered by intragastric gavage, once a day, for 7 consecutive days.In group DRC, the mitochondrial autophagy inhibitor cyclosporine A 10 mg/kg was intrathecally injected once a day for 7 consecutive days before each administration of curcumin.The equal volume of normal saline was administered by intragastric gavage at the same time point, once a day, for 7 consecutive days in group NC and group DNP.The mechanical paw withdrawal threshold (MWT) was measured before intragastric gavage and at 1, 3, 5 and 7 days after intragastric gavage.After the last behavioral testing, the L 4-6 spinal cord tissues were removed for determination of the mitochondrial membrane potential and ROS content (by JC-1 and DCFH-DA combined with flow cytometry), expression of microtubule-associated protein light chain 3 (LC3), Beclin1 and P62 (by Western blot), and mitochondrial autophagosomes (by transmission electron microscopy) and for microscopic examination of the co-expression of LC3-Ⅱwith mitochondrial translocase outer membrane protein 20 (TOM20) (using immunofluorescence double-labeling technique). Results:Compared with group NC, the MWT and mitochondrial membrane potential were significantly decreased, the ROS content and LC3-Ⅱ/Ⅰ ratio were increased, the expression of Beclin1 was up-regulated, the expression of P62 was down-regulated ( P<0.05), the number of mitophagosomes developed was increased, and the co-expression of LC3-Ⅱwith TOM20 was increased in group DNP.Compared with group DNP, the MWT and mitochondrial membrane potential were significantly increased, the ROS content was decreased, and LC3-Ⅱ/Ⅰ ratio was increased, the expression of Beclin1 was up-regulated, the expression of P62 was down-regulated ( P<0.05), the number of mitophagosomes developed was increased, and the co-expression of LC3-Ⅱwith TOM20 was increased in group DPR.Compared with group DPR, the MWT and mitochondrial membrane potential were significantly decreased, the ROS content was increased, LC3-Ⅱ/Ⅰ ratio was decreased, the expression of Beclin1 was down-regulated, the expression of P62 was up-regulated ( P<0.05), the number of mitophagosomes developed was decreased, and the co-expression of LC3-Ⅱ with TOM20 was decreased in group DRC. Conclusions:The mechanism by which curcumin reduces DNP may be related to the up-regulation of mitochondrial autophagy in the spinal cord and improvement in mitochondrial function in mice.

To solve the problem of stent malapposition of intravascular stents, explore the design method of intravascular body-fitted stent structure and to establish an objective apposition evaluation method, the support and apposition performance of body-fitted stent in the stenotic vessels with different degrees of calcified plaque were simulated and analyzed. The traditional tube-mesh-like stent model was constructed by using computational aided design tool SolidWorks, and based on this model, the body-fitted stent model was designed by means of projection algorithm. Abaqus was used to simulate the crimping-expansion-recoil process of the two stents in the stenotic vessel with incompletely calcified plaque and completely calcified plaque respectively. A comprehensive method for apposition evaluation was proposed considering three aspects such as separation distance, fraction of non-contact area and residual volume. Compared with the traditional stent, the separation distances of the body-fitted stent in the incompletely calcified plaque model and the completely calcified plaque model were decreased by 21.5% and 22.0% respectively, the fractions of non-contact areas were decreased by 11.3% and 11.1% respectively, and the residual volumes were decreased by 93.1% and 92.5% respectively. The body-fitted stent improved the apposition performance and was effective in both incompletely and completely calcified plaque models. The established apposition performance evaluation method of stent considered more geometric factors, and the results were more comprehensive and objective.
Constriction, Pathologic/surgery* ; Humans ; Plaque, Atherosclerotic ; Stents

Shortcomings have been inherited in the traditional influenza early warning system, often expressed through the scope, accuracy on prediction and real-time performance of the monitor related programs. With the new round of scientific and technological revolution and the increasingly maturity of modern information system, related technology on influenza early warning has become the focus of research in this field, based on big data analysis technology. Using the traditional influenza surveillance and early warning system as reference, this paper summarizes the progress of influenza early warning research, based on the Internet, influencing factors, time and space trends, and risk assessment etc., to summarize the trends on the advantages, shortcomings and future development of big data, used in the early warning system on influenza.