Objective : To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA) by network pharmacology and animal experiments. Methods : Traditional Chinese Medicine Systems Pharmcolog Database(TCMSP) and SwissTargetPrediction database were used to collect puerarin targets, and the targets of RA were obtained from GeneCards database and OMIM database. The PPI network was established by Cytoscape 3.7.2 software. Gene ontology(GO) function and Kyotoencyclopedia of genes(KEGG) enrichment analysis were performed through the Metascape database. RA rat-collagen-induced arthritis(CIA) model was reproduced using type Ⅱ collagen emulsion, 49 Wistar rats were randomly assigned to seven groups: control group, CIA model group, low-dose, medium-dose and high-dose puerarin group, methotrexate group, Tripterysium Glycosides Tablets group. Except for the control group, the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared. The redness and swelling of the joints and ankle joint pathological changes were observed in each group. Western blot was used to detect the expression of Glycogen synthase kinase3β(GSK-3β), beta-catenin(β-catenin) proteins in the synovium. Real-time quantitative polymerase chain reaction(qPCR) was used to detect the expression of GSK-3β, β-catenin and c-Myc mRNA in the synovium. Results : Puerarin had 134 targets genes, RA had 5 821 target genes, and there were 102 overlapping target genes of puerarin and RA. It involved 184 signaling pathways, including JAK-STAT signaling pathway, NF-κB signaling pathway, Wnt signaling pathway, et al. The results of animal experiments showed that after the intervention of M-puerarin and MTX, the symptoms of redness and swelling of the hind foot were alleviated, the inflammatory cell infiltration in the synovium of the joint was significantly reduced, and the damage of cartilage and bone tissue was reduced. Compared with CIA group, the expressions of GSK-3β, β-catenin protein and GSK-3β, β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P<0.05). Conclusion Puerarin has the characteristic of multi-components, multi-targets and multi-pathway intervention in RA. Puerarin may alleviate synovial hyperplasia, reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.

Objective:To understand the prevalence and characteristics of Rhinovirus (HRV) infection in influenza-like Illness (ILIs) patients in Mianyang, Sichuan province, China.Methods:Throat swabs were collected from patients of ILIs in sentinel hospitals in Mianyang during 2021—2022. Real-time fluorescence quantitative PCR was used to detect 16 common pathogens. The VP4/VP2 coding region genes of HRV positive samples were amplified by nest PCR. The phylogeny, consistency and amino acid variation of different serotypes were analyzed and compared with reference sequences from GenBank database.Results:A total of 332 ILIs′ samples were collected with a virus detection rate of 58.73% (195/332) in Mianyang. Among them, 23 samples (23/332) were HRV-positive, and 18 VP4/VP2 sequences of HRV strains were successfully amplified. It was found that 13 HRV serotypes were detected in ILIs samples in Mianyang, which belonged to three genotypes, namely HRV-A (12 strains), HRV-B (5 strains) and HRV-C (1 strain).Conclusions:HRV was one of the pathogens of ILIs cases in Mianyang during 2021—2022, with HRV-A types as the dominant strains.

Objective:To observe the clinical efficacy of Jiechang Qingre pills for dampness-heat syndrome of large intestine at active stage of ulcerative colitis （UC） and investigate its effect on inflammatory factors. Method:One hundred and eight patients with active UC were divided into observation group and control group. Both groups were treated with Mesalazine enteric-coated tablets， 2 g/times， 2 times/day， for 2 weeks. If symptoms were poorly controlled， prednisone acetate tablets would be used instead， 0.75 mg·kg^-1·d^-1 in 3 times by oral administration. Patients in the observation group took Jiechang Qingre pills， 10 g/time， 3 times/day before meals. Patients in the control group took Jiechang Qingre pills simulated drug， 10 g/time， 3 times/day before meals. The course of treatment was 12 weeks in both groups and the patients were followed up for 3 months. The modified Mayo score was used to evaluate disease activity. Before and after treatment， large intestine dampness-heat syndrome score， inflammatory bowel disease questionnaire （IBDQ）， mucosal histology assessment and scores of major symptoms and intestinal mucosal lesion severity were graded. The incidence of non-reactivity， hormone failure， hormone dependence， and early recurrence were recorded 2 weeks after treatment. Tumor necrosis factor-α （TNF-α）， interleukin-6（IL-6） and IL-17 levels were measured before and after treatment. Result:The clinical effective rate in the observation group was 94.00% （47/50）， higher than 77.55% （38/49） in the control group （χ²=5.514，P<0.05）. The clinical remission rate was 82.00%（41/50） in the observation group， higher than 61.22% （30/49） in the control group （χ²=5.266，P<0.05）. The endoscopic response rate was 96.00% （48/50） in the observation group， higher than 79.59% （39/49） in the control group （χ²=6.251，P<0.05）. The rate of mucosal healing in the observation group was 90.00% （45/50）， higher than 79.59% （35/49） in the control group （χ²=5.503，P<0.05）. The scores of diarrhea， purulent stool， abdominal pain， tenesmus， hyperemia， edema， erosion and ulcer in the observation group were lower than those in the control group （P<0.01）. The rate of non-reactivity in the observation group was 16.00% （8/50）， lower than 34.69% （17/49） in the control group（χ²=4.581，P<0.05）. The hormone failure rate in the observation group was 37.50%（3/8）， lower than 64.71%（11/17）in the control group，but the difference was not statistically significant（tested by the exact probaility method）. The hormone dependence rate in the observation group was 12.50%（1/8）， lower than 23.53% （4/17） in the control group，but the difference was not statistically significant（tested by the exact probaility method）. The early recurrence rate in the observation group was 14.00% （7/50）， lower than 32.65%（16/49） in the control group（χ²=4.827，P<0.05）. The scores of Mayo， dampness and heat syndrome and Geboes index in the observation group were lower than those in the control group （P<0.01）， and the IBDQ scores were significantly higher than those in the control group （P<0.01）. The TNF-α， IL-6 and IL-17 levels of the patients in the observation group were lower than those in the control group （P<0.01）. Conclusion:Based on the routine treatment of western medicine， Jiechang Qingre pills treatment for the patients with active UC can effectively induce clinical remission， alleviate inflammatory reaction， promote intestinal mucosal healing， improve clinical symptoms， quality of life and the response of treatment. Its clinical efficacy and enteroscopy efficacy are better than western medicine treatment alone， so it is worthy of clinical use.

Objective To analyze characteristics of high altitude pulmonary edema (HAPE) in Chinese patients.Methods We performed a retrospective study of 98 patients with HAPE. We reviewed the medical records and summarized the clinical, laboratory and imaging characteristics of these cases, and compared the results on admission with those determined before discharge.Results Forty-eight (49.0%) patients developed HAPE at the altitude of 2800 m to 3000 m. Ninty-five (96.9%) patients were man. Moist rales were audible from the both lungs, and moist rales over the right lung were clearer than those over the left lung in fourteen patients. The white blood cells [(12.83±5.55) versus (8.95±3.23) ×10 /L, P=0.001)] as well as neutrophil counts [(11.34±3.81) versus (7.49±2.83)×10 /L, P=0.001)] were higher, whereas the counts of other subsets of white blood cells were lower on admission than those after recovery (all P<0.05). Serum levels of alkaline phosphatase (115.8±37.6 versus 85.7±32.4 mmol/L, P=0.020), cholinesterase (7226.2±1631.8 versus 6285.3±1693.3 mmol/L, P=0.040), creatinine (85.2±17.1 versus75.1±12.8 mmol/L, P=0.021), uric acid (401.9±114.2 versus 326.0±154.3 mmol/L, P=0.041), and uric glucose (7.20±1.10 versus 5.51±1.11 mmol/L, P=0.001) were higher, but carbondioxide combining power (COCP, 26.7±4.4 versus 28.9±4.5 mmol/L, P=0.042) and serous calcium (2.32±0.13 versus 2.41±0.10 mmol/L, P=0.006) were lower on admission. Arterial blood gas results showed hypoxemia and respiratory alkalosis on admission. Conclusions In the present research, men were more susceptible to HAPE than women, and in the process of HAPE, the lesions of the right lung were more serious than those of the left lung. Some indicators of routine blood test and blood biochemistry of HAPE patients changed.

Because of their physiological similarity to humans, pigs provide an excellent model for the study of obesity. This study evaluated diet-induced adiposity in genetically lean pigs and found that body weight and energy intake did not differ between controls and pigs fed the high-fat (HF) diet for three months. However, fat mass percentage, adipocyte size, concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), insulin, and leptin in plasma were significantly higher in HF pigs than in controls. The HF diet increased the expression in backfat tissue of genes responsible for cholesterol synthesis such as Insig-1 and Insig-2. Lipid metabolism-related genes including sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase 1 (FASN1), diacylglycerol O-acyltransferase 2 (DGAT2), and fatty acid binding protein 4 (FABP4) were significantly up-regulated in backfat tissue, while the expression of proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase 2 (CPT2), both involved in fatty acid oxidation, was reduced. In liver tissue, HF feeding significantly elevated the expression of SREBP-1c, FASN1, DGAT2, and hepatocyte nuclear factor-4α (HNF-4α) mRNAs. Microarray analysis further showed that the HF diet had a significant effect on the expression of 576 genes. Among these, 108 genes were related to 21 pathways, with 20 genes involved in adiposity deposition and 26 related to immune response. Our results suggest that an HF diet can induce genetically lean pigs into obesity with body fat mass expansion and adipose-related inflammation.
Adipocytes/cytology* ; Adipogenesis/genetics* ; Adipose Tissue/metabolism* ; Adiposity ; Animals ; Body Weight ; Cholesterol/blood* ; Cholesterol, HDL/blood* ; Cholesterol, LDL/blood* ; Diet, High-Fat ; Inflammation/genetics* ; Insulin/blood* ; Leptin/blood* ; Lipid Metabolism ; Male ; Obesity/genetics* ; Random Allocation ; Swine ; Triglycerides/blood*

OBJECTIVETo evaluate the difference of clinical outcomes and radiological outcomes through meta-analysis on the total hip arthroplasty (THA) between hydroxyapatite(HA) coating and non-HA coating femoral stems.

METHODSWe searched the MEDLINE, Embase, Cochrane library and CBM for published randomized controlled trial (RCT) comparing HA coating and non-HA coating femoral stems in primary THA clinical outcomes with Harris hip score and incidence postoperative thigh pain, radiological outcomes with presence of endosteal condensation and radioactive line on the prothesis, heterotopic ossification. Data analysis were performed using RevMan 5.0(the Cochrane Collaboration).

RESULTSTen studies and 917 hips into our analysis, with 464 hips in HA groups and 453 hips in non-HA groups. The combined results of the meta-analysis indicated there was no statistical differences between the two groups on postoperative Harris hip score(WMD = 3.04, 95%CI:-4.47-10.54, P = 0.43) , there was statistical difference on incidence postoperative thigh pain (RR = 0.56, 95%CI:0.33-0.94, P = 0.03) . There were no significant differences between the two groups on presence of endosteal condensation (RR = 1.01, 95%CI:0.91-1.11, P = 0.91), presence of radioactive line (RR = 0.99, 95%CI:0.88-1.11, P = 0.83) and incidence of heterotopic ossification (RR = 0.97, 95%CI:0.77-1.21, P = 0.77).

CONCLUSIONSThere are no clinical and radiological benefits in the use of HA coating femoral stems in Primary THA, there is not enough evidence prove the HA can reduce the incidence postoperative thigh pain.

Arthroplasty, Replacement, Hip ; instrumentation ; Coated Materials, Biocompatible ; Durapatite ; Femur ; Hip Prosthesis ; Humans ; Randomized Controlled Trials as Topic ; Treatment Outcome

Effective biomarkers for clinical usage of osteoarthritis are still limited. It was confirmed that C-terminal crosslinking telopeptide of type I collagen (CTX- II) was a specific marker reflecting degradation of articular cartilage. Detection of CTX- II could promptly reflect level of cartilage injury and degradation ,diagnose OA,predict its progress,monitor effects of drug treatment, thus, reflect the condition of osteoarthritis patient indirectly. Application of CTX- II focused mainly on in the early stage of OA and need together to detect with other biomarkers,in order to more accurately reflection of the pathological changes of OA,but the specific clinical significance of CTX- II results still need to improve further.
Biomarkers ; analysis ; Cartilage, Articular ; pathology ; Collagen Type II ; analysis ; Early Diagnosis ; Humans ; Osteoarthritis ; diagnosis ; Peptide Fragments ; analysis

OBJECTIVETo explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA).

METHODSFrom November 2009 to January 2011,70 patients with KOA combined with knee effusion among outpatient and inpatient were analyzed retrospectively. Among the patients, 12 patients were male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were measured respectively by ELISA. The correlation analyses and multiple linear regression analysis were studied to determine associations among biomarkers, clinical variables and radiographic findings of knee joints.

RESULTSThe average scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45) respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml respectively. Grouped by less than the lowest quartile and more than the highest quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01; respectively); WOMAC was also positively correlated with K-L score (r=0.692, P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01; r=0.917, P<0.01). It was determined by stepwise regression that the KOA was mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as independent variables (F=20.327, P<0.01).

CONCLUSIONWORMS has a better reference value for diagnosis of KOA. The expression of COMP is high in the synovial fluid when WORMS at the high point. The clinical symptoms of knee osteoarthritis are mainly affected by WORMS and K-L score.

Aged ; Cartilage Oligomeric Matrix Protein ; Collagen Type I ; analysis ; Extracellular Matrix Proteins ; analysis ; Female ; Glycoproteins ; analysis ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Matrilin Proteins ; Middle Aged ; Osteoarthritis, Knee ; diagnosis ; metabolism ; physiopathology ; Peptides ; analysis

The aim of this study was to investigate the effect of suppression of nicotinamide phosphoribosyltransferase (NAMPT) expression on imatinib-sensitivity in chronic myelogenous leukemia (CML) cell line K562 and its mechanisms, NAMPT siRNA was synthesized and transfected into K562 cells. PI/Calcein staining technique was used to determine survival rate of transfected K562 cells at 48th hour after exposure to 1 µmol/L imatinib. MTS method was used to determine the proliferation changes of transfected K562 cell at 48th hour after exposure to different doses of imatinib, then half inhibitory concentration (IC(50)) was calculated. Expression of NAMPT at 3rd-48th hour after exposure to 1 µmol/L imatinib was determined by Western blot. To explore the effect of NAMPT-siRNA and imatinib on the expression of apoptosis-related genes, the microarray data from NCBI GEO Data-Sets was analyzed, then the results were confirmed by Western blot. The luciferase reporter assay was used to determine the effect of NAMPT and imatinib on transcriptional activity of NF-κB transcription factors. The results showed that after exposure to 1 µmol/L imatinib for 3 - 48 h, there was no significant change of NAMPT expression in K562 cells. The expression of NAMPT could be effectively inhibited by the NAMPT-siRNA. After exposure to 1 µmol/L of imatinib for 48 h, the survival rate of NAMPT-siRNA interference group was lower than that of negative control group (P < 0.05), indicating that suppression of NAMPT expression can increase the sensitivity of K562 cells to imatinib and enhance the killing effect of imatinib on K562 cells. The IC(50) of imatinib in NAMPT-siRNA interference group was the lowest compared with that of control group (P < 0.05) after exposure to different concentrations of imatinib for 48 h, the fitted survival curves showed that the slope of NAMPT-siRNA interference group was the largest ranging between 0.01 - 0.1 µmol/L of imatinib. Data mining of expression profiling indicated that the anti-apoptotic factor Bcl-2 decreased in K562 cells treated with either NAMPT-siRNA or imatinib, which was confirmed by Western blot. The inhibitory effect was much more significant when both NAMPT-siRNA and imatinib were used. The results of luciferase reporter assay showed that either NAMPT-siRNA or imatinib decreased transcriptional activity of NF-κB. The decreased effect was much more significant when both NAMPT-siRNA and imatinib were used. It is concluded that survival of K562 cells affected by imatinib may not be due to regulation of expression of NAMPT. When expression of NAMPT decreases, the K562 cells are more sensitive to imatinib, this may be related with the decreased transcriptional activity of NF-κB and its downstream effector Bcl-2.
Benzamides ; Cytokines ; antagonists & inhibitors ; metabolism ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; K562 Cells ; NF-kappa B ; metabolism ; Nicotinamide Phosphoribosyltransferase ; antagonists & inhibitors ; metabolism ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pyrimidines ; pharmacology

OBJECTIVETo study the effect of Yidu Recipe (YDR) in treating patients of chronic hepatitis B (CHB) with positive hepatitis B e-antigen (HBeAg) and its influence on the quantity and function of T-cell subsets.

METHODSFifty-seven CHB patients measured up the inclusive criteria were randomly assigned to the control group and the treated group, treated respectively by entecavir alone and entecavir + YDR for 6 months. Changes of alanine a minotransferase (ALT), aspartate a minotransferase (AST), HBV-DNA, HBV-M, interleukin-4 (IL-4) and Chinese medicine syndrome score, as well as amounts of natural killer (NK) T cell, gamma-interferon (gamma-IFN), Th1, Th2, Tc1 and Tc2 cells in peripheral blood (detected by flow cytometry) before and after treatment were observed. And the liver function normalization rate, negative inversion rates of HBV-DNA and HBeAg were estimated at terminal of the trial.

RESULTSSeven cases were dropped out in the observation period. Compared with the control group, levels of ALT, AST, HBV-DNA and Chinese medicine syndrome score were lower after treatment (P < 0.05), and liver function normalization rate was higher in the treated group, while the difference between groups in negative inversion rates HBV-DNA and HBeAg were insignificant (P > 0.05). Amount of IFN-gamma increased, IL-4 reduced, and Tc1 cell raised after treatment, which led to the rise of Tcl/Tc2 ratio in both groups; while in the treated group, in addition to the above-mentioned changes, the Th1 cell was increased also, and thus to make elevation of Th1/Th2 ratio (P < 0.05).

CONCLUSIONThe efficacy of entecavir + YDR in treating HBeAg positive CHB patients is better than that of entecavir alone. YDR can effectively improve patients' liver function, inhibit HBV-DNA replication and improve clinical symptoms, its action may be realized by way of increasing the amount of NKT cells, inducing increase of IFN-gamma and decrease of IL-4 secretions, and regulating the balance between Th1/Th2 and Tc1/Tc2.

Adult ; Antiviral Agents ; therapeutic use ; Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; T-Lymphocyte Subsets ; immunology ; Th1-Th2 Balance ; Yin Deficiency ; drug therapy ; immunology ; Young Adult