Objective To explore the correlation between continues glucose monitoring(CGM)parameters and nerve conduction velocity(NCV)in patients with diabetic peripheral neuropathy(DPN).Methods A total of 180 T2DM patients who visited our Endocrinology Department were enrolled in this study from June 2020 to June 2022 and divided into simple type 2 diabetes mellitus(T2DM)group(n=30)and a T2DM combined with DPN group(DPN,n=150)based on whether they had DPN.The DPN group was further divided into mild DPN subgroup(VPT 16～24 V,n=51),moderate DPN subgroup(VPT 25～39 V,n=67),and severe DPN subgroup(VPT≥40 V,n=32)according to the VPT.Results Compared with T2DM group,DM duration,SUA,TBIL,AST,TC,TG,LDL-C and GSP were increased in DPN group(P<0.05 or P<0.01).MAGE,LAGE,MBG,SDBG and FBG-CV in mild,moderate and severe subgroups of DPN increased in turn(P<0.01),while TIR,MNCV and SNCV decreased in turn(P<0.01).Hierarchical regression model analysis showed that MAGE,LAGE,MBG,FBG-CV were the influencing factors for MNCV and SNCV.Logistic regression analysis showed that MAGE,LAGE,MBG,FBG-CV,MNCV and SNCV were all influencing factors for DPN severity.Interaction analysis showed that MNCV,SNCV,MAGE,LAGE,MBG and FBG-CV all had additive and multiplying interactions on the severity of DPN.Conclusions MAGE,LAGE,MBG,FBG-CV,MNCV,and SNCV are factors that affect the severity of DPN,with additive and multiplicative interactions present.

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.

Objective To study the protective effects of vitamin E combined with Rhodiola rosea on the injury in mice skeletal muscle through hypoxia with exercise training and research the mechanism of action.Methods Forty ICR mice were randomly divided into control group and observation group,20 mice in each group.The control group was given Vitamin E (40 mg·kg-1·d-1),and the observation group was given Vitamin E (40 mg·kg-1·d-1)combined with Rhodiola rosea (20 g·kg-1·d-1);the rats in the two groups were treated with hypoxia (11.3%) for 4 weeks (5 ℃,15 m/min,60 min/d) after 15-day drug using.After the last training,all the mice were euthanized and then detected the gene of Bax and Bcl-2 mRNA through the RT-PCR in the skeletal muscle and the activity of GSH-PX,SOD,ROS,the concentration of MDA in the skeletal muscle.During the period (pretrain and 1,2,4 weeks) of hypoxia combined with exercise training,the CK,LDH in the serum were detected.Results The expression of CK and LDH in the observation group were lower than those of the control group (P<0.05).The activity of GSH-PX and SOD in the skeletal muscle of the observation group was significantly higher than that of the control group (P<0.05),while the ROS and MDA were lower than those of the control group(P<0.05);the expression of Bax mRNA and Bax/Bcl-2 of the observation group was significantly lower than that of the control group(P<0.05).While the expression of Bcl-2 mRNA was significantly higher than that of the control group(P<0.05).Conclusion Rhodiola rosea combined with Vitamin E can inhibit the expression of apoptotic genes by correcting the oxidation and hypoxia imbalance under hypoxia.

A colorimetric self-indicating probe for glucose was constructed by self-assembly of MnO2 nanosheets (MnO2 NSs) and glucose oxidase(GOD) in this paper.Under the weak acidic medium,glucose oxidase specifically catalyzes glucose into gluconic acid and hydrogen peroxide.The by-product of hydrogen peroxide could efficiently dissolve the MnO2 nanosheets,resulting into a significant decrease of the characteristic absorbance at 374 nm assigned to MnO2 NSs.Furthermore,the absorbance difference was linearly proportional to the concentration of glucose ranging from 1 to 20 μmol/L The fitted curve could be used for quantification of glucose with a correlation coefficient of 0.990 1.And the detection limit as low as 0.1 μmol/L could be reached based on the definition of three times of the deviation of the blank signal (3σ) and there was negligible interference with other co-existing amino acids,anions,cations and protein,which indicated high sensitivity and selectivity of the hybrid probe.The construction strategy of designated probe is readily generalized in principle for detection of numerous analytes in view of reactive property of MnO2 and the diversity of enzymes.

An acute myocardial infarction rat model was established by ligation of the left ventricular coronary artery.Plasma samples of rats were collected and analyzed by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to study the myocardial protection mechanism of compound Danshen dropping pill (CDDP).After principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), 22 metabolites were identified as potential biomarker of AMI.Furthermore, CDDP had remarkable effect on AMI rats.p-Tolyl sulfate, hippuric acid, equol 7-O-glucuronide, lysoPC(16∶0), cholic acid, oleamide, palmitic amide and SM(d18∶1/16∶0) were significantly changed in treatment group.The results showed that CDDP had a very good myocardial protection effect on AMI rats, and might influence the pathways of phenylalanine metabolism, glycerophospholipid metabolism, fatty acid metabolism, primary bile acid biosynthesis and Sphingolipid metabolism.

Objective To explore the effects of gross saponins of Tribulus terrestris L.on inflammatory reaction and permeability of blood-brain barrier in rats following cerebral ischemia-reperfusion injury and their potential mechanisms. Methods Sixty SD rats were divided into sham operation group,model control group,gross saponins of Tribulus terrestris L.at low-dose (10 mg?kg-1 )and high-dose groups(30 mg?kg-1 ).Cerebral ischemia -reperfusion model was established with suture emboli method in middle cerebral artery of rats.Neural injury scores,the contents of Evans blue ( EB) and myeloperoxidase( MPO) activities in rat brain were measured 24 hours after the cerebral reperfusion post 2 h ischemia.Content of tumor necrosis factor-α (TNF-α) in rat brain was detected by ELISA; expression levels of matrix metalloproteinase-9(MMP-9) in rat brain was determined by Western blot. Results Compared to the model control group,the neurological deficit scores were significantly decreased(P<0.05),MPO activities and EB contents decreased(P< 0.05 or P< 0.01) in the treatment groups.The expression levels of TNF-α were significantly lower in the treatment groups(0.760±0.110) mg?g-1 and (0.670±0.073) mg?g-1 compared to (0.920±0.128) mg?g-1 in the model control group ( P< 0.05 or P< 0.01). The MMP-9 expression levels were (1.770± 0.181)% and(1.480±0.146)%,significantly lower than(2.200±0.186)% in the model control group(P<0.01). Conclusion Gross saponins of Tribulus terrestris L. exert neuroprotective effects on cerebral ischemia-reperfusion injury in rats through inhibiting the inflammatory reaction and decreasing the permeability of blood-brain barrier,which may be associated with the decrease of the TNF-α content and downregulation of the MMP-9 expression.

Objective Toinvestigatetherelationbetweenserumneuron-specificenolase(NSE), bilirubinandcerebraldysfunction,prognosisafterlarge-arteryatheroscleroticstroke.Methods According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST)criteria,all the 73 patients with large artery atherosclerotic stroke were divided into the test group (41 cases ) and control group (32 cases ) according to the elevated or normal levels of serum NSE and total bilirubin. At the first day of their hospitalization,the National Institutes of Health Stroke Scale (NIHSS)score was conducted,their serum NSE,bilirubin (total bilirubin,direct bilirubin,indirect bilirubin)levels were detected,and were compared with the reevaluation of 7 and 14 days of their hospitalization and reexamination results. The modified Rankin Scale (mRS)was use to assess the recovery of their neurological function at day 30 after onset/admission. The prognosis of the patients was followed up at 1 year after onset/admission. The Kaplan-Meier product-limit method was used to conduct the analysis of the good outcome rate,and the good outcomes of both groups/interlayers (different bilirubin and NSE levels)were tested with Log-rank test. Results (1)The NIHSS scores,the levels of serum bilirubin and NSE at day 1,7,and 14 in the test group were significantly higher than those of a control group (all P<0. 01). The levels of serum bilirubin and NSE at day 7 and 14 were lower than those at day 1. (2)The mRS score at day 30 between the test group and the control group was singnificantly different (Z =3. 286,P =0. 001). (3)At day 1,the CT detection rate of large area cerebral infarction of the test group was significantly higher than that of the control group (56. 1%[n=23]vs. 28. 1%[n=9]). There was significant difference (χ2 =5. 712,P=0. 017). (4)The analysis result of Kaplan-Meier showed that there was no significant difference in its good outcome no matter grouped by the test or by serum NSE level stratification of the patients on admission (the accurateχ2valueswere4.063and4.685respectively,P=0.044and0.030respectively).Conclusion Early high-level serum NSE and hyperbilirubinemia can be used as the indexes of early identification of poor prognosis in patients with large-artery atherosclerotic stroke.

OBJECTIVETo study the application of serodiagnosis of human bocavirus (HBoV) lower respiratory tract infection in children.

METHODFrom January to April, 2013, samples including serum, sputum and bronchoalveolar lavage fluids (BALFs) were obtained from 714 children hospitalized with ALRI. Serums were tested for HBoV-specific IgG and IgM antibodies by ELISA and all kinds of samples were tested for HBoV DNA by quantitative real-time fluorescent PCR. The results of HBoV serologic tests, viral DNA in sputum and their combination were compared with those of HBoV DNA in serums and/or BALFs, which was considered as the "standard". Their consistence and differences were evaluated, and the diagnostic parameters including sensitivity, specificity, positive predictive value, negative predictive value, consistency rate, Kappa value and J value were calculated. Age distributions of the HBoV positive patients tested by the latter two methods were also compared.

RESULTThe positive rate of HBoV serology was 13.2% (94/714) . The results of HBoV serology, its DNA in sputum and their combination were all consistent with those of HBoV DNA in serums and/or BALFs (χ(2) = 91.834, 124.662, 138.643, P < 0.001 for all comparisons) . Differences were significant by McNemar test (χ(2) = 23.547, 33.440, 12.410, P all <0.001) . All the diagnostic parameters for single HBoV serologic test or single viral DNA test in sputa were approximate. However, they were improved to 70.4%, 94.8%, 38.0%, 98.6%, 93.7%, 0.463(P < 0.001), 0.65 for sensitivity, specificity, positive predictive value, negative predictive value, consistency rate, Kappa value and J value, respectively, when the methods were combined. HBoV was found positive mainly in children under 3 years of age, especially in the 1 year group. The positive rates were the highest in both group -1 year, and group -3 years was the next. However, the rate was the lowest in group >3 years and in the group -6 months.

CONCLUSIONDiagnostic power can be improved and age distribution can be demonstrated when serologic tests were combined with traditional sputum DNA detection in children with HBoV lower respiratory tract infection.

Acute Disease ; Adolescent ; Age Distribution ; Antibodies, Viral ; analysis ; blood ; Antigens, Viral ; analysis ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Human bocavirus ; genetics ; isolation & purification ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Infant ; Male ; Parvoviridae Infections ; diagnosis ; virology ; Real-Time Polymerase Chain Reaction ; Respiratory Tract Infections ; diagnosis ; virology ; Sensitivity and Specificity

BACKGROUND: Cellulose is natural material, which has good chemical stability and biocompatibility. The modified material from cellulose has new properties besides its inherent properties.OBJECTIVE: Based on cytocompatibility evaluation tests, this study is designed to evaluate the cytocompatibiUty of materials synthesized from cellulose to make sure its reliability.DESIGN: Contrast study.SETTING: Department of High Polymer, Material Science and Engineering College, Beijing University of Technology.MATERIALS: This study was performed in the Material Science and Engineering College, Beijing University of Technology between March 2003 and June 2004. The material from cellulose prepared by Beijing University of Technology was white, granules, no taste, and no volatilization (density: 1.2 g/cm3, pH: 6-7). L-929 vigorous cells were provided by Chinese Military Academy of Medical Science. Ten male New Zealand rabbits were provided by Animal Center of Chinese Military Academy of Medical Science.METHODS: Based on GB/T16175-1996 standard, cytotoxicity of the materials from cellulose on L-929 cells was evaluated by growth suppression technique (MTr chromatometry). In addition, based on GB-T14233.2-1993 standard, hemolysis in vitro was evaluated through measuring erythrocyte lysis and ferrohemoglobin freeing degree with indirect contact method.MAIN OUTCOME MEASURES: Cytotoxicity test and hemolysis test.RESULTS: Cytotoxicity test showed that the materials from cellulose did not have obvious toxicity on L-929 cells, and the cytotoxicity graduation of the materials from cellulose was 1 or 0. Hemolysis test suggested that the materials from cellulose did not have obvious hemolysis reaction, and the hemolysis rate in vitro was 1.5 %, which was less than the national standard (5%).CONCLUSION: The materials from cellulose do not have obvious cytotoxicity but have great cytocompatibility.