OBJECTIVE: To design and synthesize a series of oleanolic acid analogs posessing anti-tumor activity based on survivin target. METHODS: Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through using the natural product, oleanolic acid, as a lead compound, the active groups were introduced onto its A-ring, and the carboxyl group at the C-28 position was modified using amidation. SGC-7901 and A549 cells were used to screen the antitumor activity in vitro through the standard MTT method. RESULTS: Ten new oleanolic acid derivatives were designed and synthesized,and their structures were confirmed by MS and NMR. The compounds 5 and Ⅱ5 exhibited more potent cytotoxicity than the positive control drugs. CONCLUSION: The novel oleanolic acid analogues have better antitumor activity than the parent compound, which are worthy of further study.

objective To evaluate the diagnostic efficiency of magnetic resonance imaging(MRI)for rheumatoid arthritis(RA).Methods The major international databases was searched by computer and Other methods to collect control studies about MRI for the diagnosis of RA,the searching deadline was December 2009.Data were screened and extracted by inclusion criteria.Meta-disc software Was used for statistics,including sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio(OR)and heterogeneity analysis.Results Twelve random control tests were included.Meta-analysis indicated that sensitivities of vities of synovitis,bone-erosion and tendenosynovitis were 81%~100%,48%～100%and 67%～96%while specificities of them were 64%～89%,16%~100%and 21%-74%respectively for RA patients(≤2vears).Sensitivities of synovitis and bone-erosion were 91%and 84%while specificities of them were 70%and 81%for RA Datients (>2 years).Conclusion Synovitis shown by MRI is helpful for the diagnosis of earlv and med-to-late RA.Diagnostic values of bone-erosion and tendonosynovitis demonstrated by MRI for earlv RA were not clear.The sample size of the included studies is small and some studies lack of control groupsput the conclusion of this meta-analysis liable for bias.We suggest that better designed and larger sample clinical studies are necessary.

OBJECTIVETo assess the response in THP-1 treated with Rv3671c protein in Mycobacterium tuberculosis (M.tuberculosis).

METHODSThe gene encoding Rv3671c protein of M.tuberculosis was cloned into pET-28a vector and then expressed in Escherichia coli. The Rv3671c was purified with Ni-NTA affinity and ion exchange chromatography. The detection of protein concentration was by Lowry method.THP-1 cell was stimulated with Rv3671c protein and cells were analyzed by Hochest staining under fluorescence microscopy to assay cell death (apoptosis and necrosis). TNF-α and IL-1β were detected by ELISA at each stimulating time.

RESULTSThe Rv3671c protein of M.tuberculosis was successfully expressed in Escherichia coli. The purity of recombinant Rv3671c protein was 95%, and the protein concentration was up to 0.4 mg/ml. The nucleus of THP-1 was isolated and necrosis-like under fluorescence when cells were stimulated by Rv3671c protein. The levels of TNF-α and IL-1β in supernatant were 19 000 and 16 500 pg/ml respectively, and were significantly higher than control cells with the levels of 2100 and 3800 pg/ml separately.

CONCLUSIONThe necrosis of THP-1 cells could be stimulated by Rv3671c protein of M.tuberculosis and it was probably associated with high cytokines TNF-α and IL-1β levels.

Bacterial Proteins ; pharmacology ; Cell Death ; Cell Line ; Humans ; Interleukin-1beta ; metabolism ; Macrophages ; cytology ; metabolism ; Mycobacterium tuberculosis ; genetics ; Tumor Necrosis Factor-alpha ; metabolism

Objective To evaluate the values of the quantitative parameters obtained from 18F-fluorodeoxyglucose (FDG) PET/CT imaging and MRI in prediction of lymph node metastasis (LNM) in patients with rectal cancer.Methods From May 2013 to October 2015,80 patients with rectal cancer (63 males,17 females,age range:37-85 years) that underwent preoperative MRI-diffusion weighted imaging (DWI) and 18 F-FDG PET/CT were enrolled.All patients had pathological results.Auto-segmentation methods of various thresholds were selected to determine the FDG metabolic parameters and whole volume region of interest (ROI) method was performed to measure apparent diffusion coefficient (ADC) in lymph node.Maximum standardized uptake value (SUVmax) =2.5,20％ SUVmax,30％ SUVmax,40％ SUVmax and 50％ SUVmax were selected as the cut-off values (COV),and named as COV1,COV2,COV3,COV4 and COV5,respectively.ROI was drawn automatically and the corresponding mean standardized uptake value (SUVmean) 1-SUVmean5,metabolic tumor volume (MTV) 1-MTV5 and total lesion glycolysis (TLG) 1-TLG5 were calculated.x2 test and logistic regression analysis were used to analyze the associations between the LNM and pathological factors,as well as 18F-FDG metabolic parameters and ADC.Results LNM was found in 55％ (44/80) of the patients.The metabolic parameters of primary tumor in patients with LNM were significantly higher than those in patients without LNM (u values:152.0-555.0,all P＜0.05);the ADC was significantly lower in LNM positive cases than that in LNM negative cases:0.96 (0.93,1.02) × 10-3 mm2/s vs 1.07(1.01,1.11) ×10-3 mm2/s,u=249.0,P＜0.05.Univariate analysis showed that T stage,SUVmax,SUVmean 1-SUVmean 5,MTV1-MTV5,TLG1-TLG5,ADC value were associated with pathologic lymph node involvement (x2 values:7.730-48.198,all P＜0.05).Multivariate analysis indicated that MTV1 (odds ratio (OR)=0.110,95％ CI:0.014-0.840),MTV2 (OR=0.075,95％ CI:0.007-0.852) and ADC (OR=0.034,95％ CI:0.003-0.381) of tumor were significant risk factors associated with LNM (all P＜0.05).The optimal COV of MTV1,MTV2 and ADC were 20.26 cm3,18.47 cm3 and 1.00× 10-3 mm2/s.Conclusion MTV1,MTV2 measured by 18F-FDG PET/CT and ADC measured by MRI-DWI of the primary tumor are risk factors of LNM from rectal cancer,and they may be useful to predict LNM in patients with rectal cancer.

AIM To observe the effects of Sangtongjian Mixture (STJ) on glucose and lipid metabolism,insulin resistance and fat cytokines in type 2 diabetic rats,and their mechanisms of action.METHODS One hundred and forty rats fed on the combination of STZ and high fat diet were established as the type 2 diabetic models.Fasting blood glucose (FBG) level reached more than 16.7 mmol/L and then the rats were randomly divided into model group,metformin (180 mg/kg) group,STJ (73.5,147 and 294 mg/kg) groups.Ten rats were set as the blank group.Each treatment group was intragastrically given the corresponding agents for twelve weeks.The fasting blood glucose levels of rats were measured once every two weeks after the administration.After a 12-week administration period,glycosylated serum protein (GSP),glycosylated hemoglobin (GHb) and lipid profile indices (TC,TG,HDL-C and LDL-C) were determined.The serum insulin level was measured by radioimmunoassay,and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated.The levels of serum adiponectin and leptin were detected by ELISA.RESULTS STJ remarkably decreased the levels of FBG,GSP,GHb,TC,TG,LDL-C,leptin and HOMR-IR in type 2 diabetic rats.Furthermore,STJ also significantly increased the levels of HDL-C,adiponectin and ISI.CONCLUSION STJ can improve glucose and lipid metabolism in type 2 diabetic rats by ameliorating insulin resistance and regulating fat cytokine levels.

By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, ¹³C NMR and ¹H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I₁ has a certain inhibitory effect on human HepG-2 cells, which is worth further study.

The computer-aided design was used to simulate the docking of PDGF receptor with known active compounds, and the active groups that can bind to key sites were identified by analyzing the key amino acid residue fragments that exerted active effects on the target proteins. The natural product oleanolic acid was used as the parent, and the active group was introduced into the 2-position, and the C-28 carboxyl group was esterified and amidated. A series of oleanolic acid analogues targeting PDGF receptor inhibitors were designed and synthesized. Their structures were confirmed by MS and NMR. Through MTT assay, SGC-7901 and A549 cells were selected for preliminary in vitro anti-tumor activity screening. PDGF receptor protein inhibition test was performed on I₃ and Ⅱ₅ by FPIA. The activity tests showed that I₃ and Ⅱ₅, compared with the positive control drug, had stronger inhibition. FPIA test showed that Ⅱ₅ and PDGF receptor protein had good binding ability. The newly synthesized oleanolic acid analogues have significantly higher antitumor activity than the parent compound and deserve further study.

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ²=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.
Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Acute Kidney Injury/epidemiology* ; Cohort Studies ; Critical Illness ; Prospective Studies ; Risk Factors