Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway / 中国中药杂志

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

Analysis of Nosocomial Infection in a Cancer Hospital from 2019 to 2021 / 中山大学学报(医学科学版)

ObjectiveTo understand the situation of nosocomial infection in cancer hospitals and its changing trend， so as to provide a basis for adjusting the focus of nosocomial infection prevention and control in cancer hospitals. MethodsData of nosocomial infection quality control indices of Sun Yat-sen University Cancer Center from 2019 to 2021 were obtained through the nosocomial infection monitoring system， and the changes of these indices across the three years were analyzed by Chi-square test and Cochran-Armitage trend test. ResultsFrom 2019 to 2021， the incidence rates of nosocomial infection in this hospital were 0.80%， 0.78% and 0.57%， which decreased significantly year by year （P<0.001）. Among them， surgical site and respiratory system infection were more common， accounting for 35.75% and 31.08%， respectively. Gram-negative bacteria and fungi were the main pathogens. The incidence rate of multidrug-resistant bacteria in hospital increased year by year， from 0.08‰ to 0.14‰ （P<0.001）， among which methicillin-resistant staphylococcus aureus， carbapenem-resistant Enterobacter and bacteria producing ultra-broad spectrum β-lactamase （ESBLs） bacteria increased significantly. The incidence rates of three-tube associated infections were no different across 3 years （P>0.05）， which were still at high levels. ConclusionFrom 2019 to 2021， the prevention and control of nonsocomial infection in the cancer hospital has been improved overall. Meanwhile， the infections of respiratory system and surgical sites， ESBLs related multidrug-resistant bacteria and three-tube are weak links in cancer specialized hospitals， which need to be emphasized and improved.

Effect of Compatibility of Alcohol Extract of Magnoliae Officinalis Cortex and Alcohol Extract of Polygalae Radix on Fecal Metabolites of Rats / 中国实验方剂学杂志

Objective:To investigate the effect of alcohol extract of Magnoliae Officinalis Cortex,alcohol extract of Polygalae Radix and their compatibility on fecal metabolites of rats,analyze its potential metabolic pathways,and provide experimental basis for exploring the possible mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix. Method:Forty male SD rats were randomly divided into the normal group,alcohol extract of Magnoliae Officinalis Cortex group(3.50 g·kg-1),alcohol extract of Polygalae Radix group(1.75 g·kg-1) and compatibility group (3.5 g·kg-1 of alcohol extract of Magnoliae Officinalis Cortex+1.75 g·kg-1 of alcohol extract of Polygalae Radix).Fecal samples were collected within 24 h after continuous gavage for 3 days.The fecal metabolites in each group was detected by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),mobile phase was acetonitrile-0.1%formic acid solution for gradient elution,data collection range was m/z 50-1 200 under positive and negative ion mode of electrospray ionization.The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI v2.0,SIMCA-P 14.0,SPSS 20.0,MetaboAnalyst 4.0 and other softwares. Result:A total of 17 characteristic metabolic markers were screened out,including 5-formiminotetrahydrofolic acid,L-3-hydroxykynurenine,7,8-dihydropteroic acid,etc.The main related pathways included biosynthesis of unsaturated fatty acids,linoleic acid metabolism,vitamin B6 metabolism,etc. Conclusion:The mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix may be related to purine metabolism,folate biosynthesis,tryptophan metabolism and primary bile acid biosynthesis.

Impact of maternal gestation combined exposure to lead and mental stress on offspring's fear-conditioning memory / 上海交通大学学报（医学版）

Objective: To explore whether prenatal stress can enhance the accumulation of blood/bone lead in the offspring on the basis of prenatal lead exposure, and to compare the effects of prenatal single exposures to stress/lead and prenatal combined exposure to lead and stress on fear-conditioning memory in the offspring. Methods: Pregnant rats were randomly divided into control group, stress exposure group, lead exposure group and combined lead-stress exposure group. After delivery, each group contained twelve pups (male:female=1:1). The extinction process of fear-conditioning memory was evaluated by the fear-conditioning test in the offspring at 3 weeks old. The offspring were then sacrificed at 4 weeks old. Blood and tibia samples were collected, blood lead was measured by using the atomic absorption spectrometer, and tibia lead was measured by using the inductively coupled plasma-mass spectrometry. The levels of blood lead, bone lead and fear memory were compared by analysis of variance, and the relationship between blood lead, bone lead and fear memory were analyzed by Logistic regression model. Results: The levels of blood and bone lead in the lead exposure group (P blood lead=0.013, P bone lead=0.000) and combined exposure group (P blood lead=0.000, P bone lead=0.000) were significantly higher than those in the control group; the level of blood lead in the stress group was higher but not significantly different from that in the control group (P blood lead=0.056) and the level of bone lead in the stress group was significantly higher than that in the control group (P bone lead=0.004); the levels of blood and bone lead in combined exposure group were higher than those in the lead exposure group, but the differences didn’t reach statistical significance (P blood lead=0.682, P bone lead=0.124). Compared with young rats in the lowest blood lead/bone lead groups, young rats in the groups of higher blood/bone lead levels had higher odds ratios of high fear reaction during the second (P=0.008/P=0.016) and the third (P=0.019/P=0.005) time periods. The ratios of freezing time in the first [(83.73±25.47)%] and the second [(92.97±15.75)%] periods of the fear-conditioning test in the combined exposure group were significantly higher than those in the control group [the first period, (65.35±28.80)%, P1=0.048; the second period, (68.78±27.22)%, P2=0.021]. Conclusion: Compared with the single exposure to lead during pregnancy, maternal gestation combined exposure to lead and stress may induce more increases in the blood and bone lead levels in the offspring. Lead exposure during pregnancy may inhibit the process of the extinction of fear memory in the offspring, and this effect may be aggravated by prenatal concurrent exposure to stress.

Screening indices and their cut-off values for full-term neonates carrying β-thalassemia gene / 中国当代儿科杂志

OBJECTIVE@#To investigate the screening indices and their cut-off values for full-term neonates carrying β-thalassemia gene.@*METHODS@#A retrospective analysis was performed for the clinical data of 1 193 full-term neonates who underwent β-thalassemia screening (hemoglobin analysis with dried blood spots on neonatal heel blood filter paper and mutation detection of 17 β-globin genes). A multivariate logistic regression analysis was used to investigate the association between screening indices and β-thalassemia gene, and the receiver operating characteristic (ROC) curve was used to analyze the value of screening indices in determining the presence or absence of β-thalassemia gene.@*RESULTS@#Of the 1 193 neonates, 638 carried β-thalassemia gene. Of the 1 193 neonates, 637 (53.39%) had no HbA, among whom 310 carried β-thalassemia gene and 327 did not carry this gene; 556 (46.61%) had HbA, among whom 328 carried β-thalassemia gene and 228 did not carry this gene. As for the neonates without HbA, the β-thalassemia gene group had a significantly lower HbA level and a significantly higher HbF level than the β-thalassemia gene-negative group (P1.4 had the largest AUC in determining the presence or absence of β-thalassemia gene, with a sensitivity of 91.38% and a specificity of 91.89%.@*CONCLUSIONS@#HbA and HbA/HbA ratio are effective indices for screening out full-term neonates carrying β-thalassemia gene.

Effect of full-time infection control nurses' supervision on the compliance to comprehensive intervention measures and incidence of ventilator-associated pneumonia / 中国感染控制杂志

Objective To evaluate the effect of full-time infection control nurses' supervision on the compliance to implementation of comprehensive intervention measures and incidence of ventilator-associated pneumonia (VAP).Methods Full-time infection control nurses in the general intensive care unit(ICU) of a hospital were assigned,compliance to comprehensive intervention measures among all patients who were admitted to ICU was monitored.September 2012-April 2014 was pre-intervention stage,May 2014-December 2015 was post-intervention stage.Utilization of ventilator and occurrence of VAP before and after implementing intervention measures were analyzed statistically.Results A total of 1 373 patients were monitored before intervention,1 477 were monitored after intervention.Utilization rates of ventilator before and after intervention were 31.89％ and 40.95％ respectively.Incidence of VAP before and after intervention were 31.97‰ and 17.82‰ respectively,incidence of MDRO infection were 11.99‰ and 6.41‰ respectively.Microbial monitoring results of environmental object surface after intervention were all qualified (all≤5 CFU/cm2).Fluorescence labeling clearance rate and hand hygiene compliance rate increased gradually in each quarter,reached more than 80％ in the latter period;compliance to semireclining position was all 100％ from the fourth quarter of 2014 to the fourth quarter of 2015.Conclusion Through implementation of comprehensive intervention measures by full time infection control nurses,incidence of VAP can be decreased significantly,quality of medical treatment is improved,and safety of patients is ensured.

Neodymium Oxide Induces Cytotoxicity and Activates NF-κB and Caspase-3 in NR8383 Cells / 生物医学与环境科学（英文）

We investigated whether Nd2O3 treatment results in cytotoxicity and other underlying effects in rat NR8383 alveolar macrophages. Cell viability assessed by the MTT assay revealed that Nd2O3 was toxic in a dose-dependent manner, but not in a time-dependent manner. An ELISA analysis indicated that exposure to Nd2O3 caused cell damage and enhanced synthesis and release of inflammatory chemokines. A Western blot analysis showed that protein expression levels of caspase-3, nuclear factor-κB (NF-κB) and its inhibitor IκB increased significantly in response to Nd2O3 treatment. Both NF-κB and caspase-3 signaling were activated, suggesting that both pathways are involved in Nd2O3 cytotoxicity.

An investigation and analysis on the implementation situation of the performance salary system of primary healthcare institutions in Zhejiang Province / 预防医学

Objective To learn the main problems of performance salary system in primary healthcare institutions after the implement of recent performance salary system guiding opinion in Zhejiang Province.Methods Purposive sampling method was used to separately select 2 counties from high,average and poor economic level regions in Zhejiang Province. Questionnaire survey was conducted among 100 leaders of 84 primary healthcare institutions which the number of staffs is larger than 20.The survey contents included demographic characteristics and the assessment of performance appraisal and performance salary system,which embraced workload,the change of work income and enthusiasm,the incentive function, component ratio and existing problem of performance salary system.Results The average income general increased, however,the staffs working enthusiasm should be further improved.Some problems still exist,such as the public health funds were brought into the total performance salary,and the gross payroll levels were low as well as the performance salary was lack of increasing mechanism.The TCM was the prior development business and contribute most to the revenue and expenditure surplus of primary healthcare institutions.Conclusion The performance salary system should be further improved and the operating effect evaluation in phases and stages should be developed.The decoction pieces should be selled without added profit,and the service ability of primary traditional Chinese medicine should be further strengthened.

Preparation of SUN5-specific polyclonal antibody for detection of SUN5 expression in human germ cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare a specific polyclonal antibody against full-length SUN5 for detecting the expression of SUN5 in human germ cells.</p><p><b>METHODS</b>Bioinformatic methods were used to compare the full-length SUN5 and its variant SUN5β, and a short peptide was designed based on the differential region to prepare SUN5 antibody. The prepared antibody was used to detect the expression of SUN5 in Ntera-2 cells and in human germ cells by Western blotting and immunofluorescence assay.</p><p><b>RESULTS</b>The short peptide was correctly synthesized and SUN5 antibody was obtained and purified. Western blotting showed that the prepared antibody was capable of recognizing full-length SUN5 in Ntera-2 cells, and SUN5 expression was localized on the nuclear membrane and in the cytoplasm as shown by immunofluorescence assay. Using this antibody, we detected SUN5 expression in the spermatocytes, round spermatids and sperms in human germ cells.</p><p><b>CONCLUSION</b>We successfully prepared SUN5-specific antibody. SUN5 is expressed in the spermatocytes, round spermatids and sperms in human germ cells, suggesting its important role in spermatogenesis.</p>

Role of miR-511 in the Regulation of OATP1B1 Expression by Free Fatty Acid

MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATP-binding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.

ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients

Objective: To investigate the azole susceptibility of Candida albicans ( C. albicans) from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance. Methods: Three hundred and two clinical isolates of Candida species were collected. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans (2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced. Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and 4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total, 27 missense mutations were detected in ERG11 genes from resistant/susceptible dose-dependent isolates. Among them, Y132H, A114S, and Y257H substitutions were most prevalent and were known to cause fluconazole resistance. G464S and F72S also have been proved to cause fluconazole resistance. Two novel substitutions (T285A, S457P) in hotspot regions were identified. Conclusions: Twenty seven mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions (T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.

Effect of pitavastatin in different SLCO1B1 backgrounds on repaglinide pharmacokinetics and pharmacodynamics in healthy Chinese males

The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry [LC/MS/MS] and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration [C[max]] of repaglinide [P=0.003] in SLCO1B1[asterisk]1b homozygotes [P=0.015] and SLCO1B1[asterisk]15 carriers [P=0.031]. Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity [AUC[0][rightwards arrow][infinity]] of repaglinide [P=0.091]. There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the C[max] of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported

Effect of HeLa cells infected with Coxsackie virus B3 on mTOR and p70S6K mRNA expression under different nutritional conditions / 中华实用儿科临床杂志

Objective To explore the effect of HeLa cells infected with Coxsackie virus B3 (CVB3) on the changes of mTOR signal pathway under different nutritional conditions.Methods The HeLa cells were cultured under conventional culture and serum starvation culture.(1) For the conventional method,the medium with 10 g/L fetal bovine serum was added for 24 h after the Hela cells were fused into 40％ to 50％,and the medium was changed on the next day,then the virus group was infected with CVB3 of 50％ tissue culture infective dose (TCID50).However,the control group was cultured by 2 g/L fetal bovine serum.(2) For the serum starvation method,HeLa cells were cultured with the medium without fetal bovine serum for 24 h.Then the virus group was infected with CVB3 of TCID50.The cells in control group were cultured by 2 g/L fetal bovine serum.Cell morphology changes were observed by inverted microscope,and the expressions of the mTOR,p70S6K mRNA were detected with Real-time PCR at 3 h,6 h,9 h,12 h,24 h respectively in both conventional culture and serum starvation groups.Results The expressions of mTOR and p70S6K mRNA were lower in the virus group than those in control group at 12 h and the 24 h (all P ＜0.05) in the conventional culture group.And the expressions of mTOR and p70S6K mRNA in the virus group were lower than those in the control group at every time points (all P ＜ 0.05) in serum starvation group.The expressions of mTOR and p70S6K mRNA in group with serum starvation virus and the control groups were higher than those in conventional culture group in all time points,but only the expressions of mTOR mRNA were significantly different between the 2 groups (all P ＜0.05),however,the expressions of p70S6K mRNA had no significant difference between the 2 groups (all P ＞ 0.05).Conclusion CVB3 may be able to down-regulate the expressions of mTOR and p70S6K mRNA.

Relationship between effect of lamivudine in the treatment of cirrhotic patients with uncompensated hepatitis B with HBV genotypes and cytotoxic T lymphocyte / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore relationship between effect of Lamivudine in the treatment of cirrhotic patients with uncompensated hepatitis B with hepatitis B virus (HBV)genotypes and HBV specific cytotoxic T lymphocytes (CTL).</p><p><b>METHODS</b>80 cases of uncompensated cirrhotic hepatitis B (40 cases with genotype B and 40 with genotype C), HBV DNA positive, HBeAg positive and human leukocyte antigen (HLA)-A2 positive,were treated with Lamivudine 100 mg/d, one year later, its effect and relationship with HBV genotypes and HBV specific CTL were observed.</p><p><b>RESULTS</b>HBV DNA turned negative:40 cases with genotype B turned negative (100%). In the 9th and 10th month of treatment, there was one case with genotype C had YMDD variation respectively and Adefovir dipivoxil was used for treatment, of the rest 38 cases, HBV DNA of 26 cases (68.42%) turned negative,HBV DNA negative rate of patients with genotype is lower than that of patients with genotype B, chi2 = 14.91, P < 0.01. HBeAg turned negative: 18 cases with genotype B (45%) turned negative, more than that of patients with genotype C (7 cases, 18.42%), chi2 = 6.32, P < 0.05. Peripheral blood HBV specific CTL level: before treatment, it was (0.33 +/- 0.03)% of patients with genotype B,higher than that of patients with genotype C [(0.11 +/- 0.02)%], t = 8.12, P < 0.001. 1 year after treatment: it was (0.44 +/- 0.04)% of patients with genotype B, higher than that before treatment, t = 4.01, P < 0.001, it was also higher than that of patients with genotype C 1 year after treatment [(0.23 +/- 0.03)%], t = 5.63, P < 0.01, alanine amino-transferase (ALT) returned to normal: 38 cases with genotype B (95%) returned to normal, more than that of patients with genotype C (28 cases, 73.68%), X2 = 6.79, P < 0.01.</p><p><b>CONCLUSION</b>Effect of Lamivudinein the treatment of cirrhotic patients with uncompensated hepatitis B is better in patients with genotype B than patients with genotype C, its mechanism may be related to lower level of HBV specific CTL in patients with genotype C than patients with genotype B.</p>

Gene expression patterns of offsprings' hepatocytes induced by prenatal Benzoapyrene exposure / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the gene expression patterns in livers of infant rats after Benzo[a]pyrene (BaP) exposure during pregnancy and explore the important gene and signaling pathways in the toxic mechanism of BaP.</p><p><b>METHODS</b>Thirty-two pregnant SD rats were randomly divided into four groups: vehicle control (corn oil) and treatment groups (0.75, 1.50 and 3.00 mg/kg BaP in corn oil). BaP solutions were given by gastric infusion from the 3rd to the 17th day of pregnancy. After delivery the offspring's liver were taken to detect the gene expression by RatRef-12 gene chip. The stability of gene chip was tested by repeated experiments.</p><p><b>RESULTS</b>After prenatal BaP exposure 1232 genes with different expression variations in hepatocytes of offsprings were identified. Three expression patterns of genes related to the dose of prenatal BaP exposure were identified with significant difference (P < 0.05). As the dose of prenatal BaP exposure increased, the gene expression patterns were downregulated, upregulated, and fluctuated. Twenty-six signaling pathways with differently expressed genes mainly focused on: growth and development, toxicant metabolism and inflammation (P < 0.05). The data from gene network analysis demonstrated that CYP2C13, GSTO1, Rela, MAPK8 and Plcg1 were the key genes in the gene network.</p><p><b>CONCLUSION</b>Gene expression patterns of offsprings' hepatocytes were influenced by prenatal BaP exposure. Some key genes and signal pathways were also found. The study provides an important clue for the toxicity and mechanisms of the prenatal BaP exposure on the growth and development of offspring.</p>

Cell death of THP-1 induced by puried Rv3671c protein of tuberculosis and the detection of TNF-α and IL-1β in Mycobacterium tuberculosis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess the response in THP-1 treated with Rv3671c protein in Mycobacterium tuberculosis (M.tuberculosis).</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>The 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.</p>

Evaluation of efficacy and safety of sunitinib regimen in 22 patients with metastatic renal cell carcinoma: at least 12-month follow-up / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sunitinib has been proved an effective new option for treatment of metastatic renal cell carcinoma (mRCC). Analysis of clinical data of 22 patients, who were exposed to sunitinib for at least 1 year, was conducted to evaluate the long-term efficacy and safety of sunitinib for the treatment of mRCC.</p><p><b>METHODS</b>A total of 54 patients with mRCC were treated with sunitinib malate, 50 mg/d orally, on a 4-weeks-on and 2-weeks-off dosing schedule in Peking University First Hospital. Treatment continued until disease progression, unacceptable adverse events (AEs), or death. Among them, 22 patients continued treatment for at least 1 year. The clinical data of these 22 patients were prospectively collected for analysis. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Tumor response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors.</p><p><b>RESULTS</b>Median progression-free survival was 19.5 months until last follow-up. The best efficacy results achieved were complete response, partial response, and stable disease for 2, 9, and 11 patients, respectively. Objective response rate was 50%. The most common AEs were hand-foot syndrome (95%) and hypertension (91%). Other common AEs were thyroid-stimulating hormone elevation (82%), platelet decrease (77%), and loss of appetite (77%). Only one patient withdrew from treatment for cardiac infarction. Another nine patients experienced dose modifications or short-term suspensions.</p><p><b>CONCLUSION</b>Long-term exposure to sunitinib malate showed encouraging efficacy in the treatment of mRCC. At the same time, the tolerability was good.</p>

Myocardial injury and inflammatory response after interventional therapy in children with congenital heart disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study myocardial injury and inflammatory response within 7 days after interventional therapy in children with congenital heart disease (CHD).</p><p><b>METHODS</b>A total of 77 children with CHD, including 12 cases of ventricular septal defect (VSD), 14 cases of atrial septal defect (ASD), 14 cases of pulmonary stenosis (PS) and 37 cases of patent ductus arteriosus (PDA), were enrolled. The levels of myocardial enzyme (AST, CK and CKMB), cardiac troponin I (cTnI) and CRP in serum were measured before operation, immediately after operation, and 6 hrs, 24 hrs, 72 hrs and 7 days after operation.</p><p><b>RESULTS</b>Serum AST levels in the VSD group were significantly higher than the other CHD groups immediately after operation, and 6 hrs and 24 hrs after operation (P<0.05). There were significant differences in serum CK and CKMB levels among the four CHD groups immediately and 6 hrs after operation (P<0.05), and the highest serum CK and CKMB levels were found in the VSD group. Serum CRP levels in the PDA group were significantly higher than the other CHD groups 72 hrs and 7 days after operation (P<0.05). Compared with before operation, serum AST levels increased significantly in all four CHD groups 6 and 24 hrs after operation groups (P<0.05). Serum CK and CKMB levels increased significantly in the VSD group immediately and 6 hrs after operation (P<0.05). Serum cTnI levels increased significantly in the VSD, PDA and PS groups immediately and 6 hrs after operation (P<0.05). The PDA group showed increased CRP levels 24 hrs, 72 hrs and 7 days after operation (P<0.05).</p><p><b>CONCLUSIONS</b>Minor myocardial injury can be noted within 7 days after interventional therapy in children with CHD and mainly occurs between immediately and 24 hrs after operation. The injury is more significant in VSD cases. The interventional therapy does not cause significant inflammation.</p>

Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.</p><p><b>METHODS</b>A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.</p><p><b>RESULTS</b>The median follow-up was 15 months (10 cycles, range 1.5 - 30.0 months (1 - 20 cycles)). Ten patients (29.4%) achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting ≥ 2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0 - 28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7 - 24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival (P = 0.004, 0.000, respectively).</p><p><b>CONCLUSIONS</b>The results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, sunitinib-associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.</p>