Abstract: Objective To explore and analyze the diagnostic value of multicolor melting curve analysis (MMCA) for the resistance of five anti-tuberculosis drugs, so as to clarify the clinical value of MMCA in detecting drug resistance of Mycobacterium tuberculosis. Methods From April 2021 to May 2022, 200 patients with positive Mycobacterium tuberculosis admitted to the Fourth People's Hospital of Qinghai Province were selected as research objects, and sputum specimens were taken from the patients. Traditional Mycobacterium tuberculosis drug sensitivity test (modified Löwenstein-Jensen medium method) and MMCA analysis were respectively given to detect the resistance of five anti-tuberculosis drugs, including isoniazid, ethambutol, streptomycin, rifampicin and isoniazid, respectively. Those samples with inconsistent results between the two diagnosis methods were subjected to gene sequencing verification, and the diagnosis efficiency of MMCA for the five anti-tuberculosis drugs was compared. Results Using Mycobacterium tuberculosis drug sensitivity as the gold standard for drug resistance diagnosis, the sensitivity of MMCA for detecting drug resistance of rifampicin, ethambutol, streptomycin, isoniazid and levofloxacin were 95.83% (46/48), 93.75% (15/16), 100.00% (15/15), 100.00% (20/20) and 70.00% (7/10), respectively, with statistical differences between groups (P<0.05). There were no statistically significant differences in the specificity, positive predictive value, negative predictive value and accuracy of MMCA for the five anti-tuberculosis drugs (P>0.05). For the 8 samples with inconsistent results between MMCA and modified Löwenstein-Jensen medium method, gene sequencing was performed and compared with the results of gene sequencing. After comparison with gene sequencing results, it was found that the coincidence rate of MMCA and gene sequencing results was 75.00% (6/8). Conclusions In the detection of drug-resistant mutations in TB patients, multi-color probe fusion curve analysis has high diagnostic efficacy for first-line anti-tuberculosis drugs, but is not sensitive to second-line anti-tuberculosis drug levofloxacin. Therefore, for the detection of first-line anti-tuberculosis drugs, MMCA has a good clinical application prospect.

OBJECTIVETo evaluate the effectiveness and safety of hydroxyethyl starch (HES 130/ 0.4, 60 g/L) in resuscitation during shock stage of burns.

METHODSSixty-six burn patients who were admitted to hospital within 2 hours after burn injury requiring fluid resuscitation were enrolled into this study, and they were randomized into HES( n = 33, with HES as a component of fluid resuscitation) and plasma (P, n = 33, with plasma as a component of fluid resuscitation) groups. HES or plasma was given as colloid within 48 postburn hours (PBH), and only albumin [( 111 +/- 4) , ( 105 +/- 5 ) g for each group] were given to the patients during 3 to 7 postburn days (PBD). Heart rate, blood pressure, central venous pressure (CVP) , urine output per hour were measured, gain/loss of body fluid during the first and second 24 PBH were recorded, serum total protein, albumin, hemoglobin( Hb) , prothrombin time (PT) , fibrinogen; platelet ( PLT) , as well as liver and renal function, allergy and bleeding tendency were determined and observed at corresponding time-points.

RESULTSThere were no obvious differences in heart rate, blood pressure, CVP and urine output per hour within 24 PBH between the two groups (P > 0.05). Also there was no difference in gain/loss of body fluid during the first and second 24 PBH. The content of hemoglobin on 1 ,3, 7,14 PBD ,and the PT, the content of fibrinogen, the number of PLT on 1,3,14 PBD also exhibited no difference between the two groups (P > 0.05). The serum contents of total protein and albumin in HES group were [(31 +/- 3) g/L, (30 +/- 3)g/L ] on 1 PBD, and [(20.4 +/- 3.6) g/L, (18.4 +/-2.3) g/L] on 3 PBD, which were obviously lower than those in P group [(45 +/- 4) g/L, (39 +/- 3) g/L on 1 PBD, and 1 (24.5 +/- 4.3) g/L, (21.3 +/- 3.9) g/L) on 3 PBD, (P <0. 01). Though the serum content of albumin on 7 PBD was similar in the two groups (P > 0.05), the serum total protein in HES group (40 +/- 4) g/L was markedly lower than that in P group [(45 +/- 4) g/L, P < 0.01] . Within 7 PBD, no abnormal bleeding was found in the two groups, and the liver function and renal function were similar. There were 4 cases showing allergic reaction in plasma group while none in HES group.

CONCLUSIONNew type of HES can partially substitute plasma and be used in fluid resuscitation for burn patients. However, plasma protein replenishment should still be emphasized.

Adult ; Burns ; therapy ; Female ; Humans ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Male ; Middle Aged ; Resuscitation ; methods ; Shock ; therapy

AIMTo investigate whether mitochondrial calcium uniporter participates in the cardioprotection of tumor necrosis factor alpha (TNFalpha) pretreatment in isolated rat hearts subjected to ischemia/reperfusion.

METHODSIsolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, coronary flow (CF) and lactate dehydrogenase (LDH) release during reperfusion were measured. The mitochondria of the heart were isolated and suspended in the swelling buffer for measurement of absorbance at 520 nm.

RESULTSPretreatment with TNFa at 10 U/ml for 7 min followed by 10 min washout reduced the infarct size and LDH release, and improved the recovery of CF during reperfusion. Administration of spermine (20 micromol/L), an opener of mitochondrial calcium uniporter, for 10 min during early reperfusion attenuated the reduction of infarct size and LDH release, and improvement of CF induced by TNFalpha. In isolated mitochondria of the heart pretreated with TNFalpha, the absorbance at 520 nm decreased less than that of mitochondria without TNFalpha pretreatment. Administration of spermine (50 micromol/L) attenuated the change of the absorbance induced by TNFalpha.

CONCLUSIONThe findings indicate that TNFalpha protects myocardium against ischemia/reperfusion injury via inhibiting mitochondrial calcium uniporter opening as well as mitochondrial permeability transition pore opening.

Animals ; Calcium Channels ; drug effects ; metabolism ; Cardiotonic Agents ; pharmacology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Mitochondrial Membrane Transport Proteins ; drug effects ; Myocardial Reperfusion Injury ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Spermine ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo explore whether the inhibitory effect of Genipin on uncoupling protein-2 (UCP-2) in mitochondria is involved in energy metabolism of androgen-independent PC3 prostate cancer cells.

METHODSPC3 prostate cancer cells were cultured and treated with Genipin at the concentrations of 40, 80, and 160 μmol/L for 48 hours. Then the proliferation of the cells was detected by MTT assay, the expression of UCP-2 mRNA determined by RT-PCR, and the content of intracellular pyruvic acid (PA) and the activity of succinate dehydrogenase (SDH) in the mitochondria measured by visible spectrophotometry.

RESULTSWith the increased concentration of Genipin, the proliferative activity of the PC-3 cells, the expression level of UCP-2 mRNA, the content of intracellular PA and the activity of SDH in the cells were all decreased, namely, with the enhanced inhibitory effect of Genipin on UCP-2, a trend of reduction was observed in the proliferation of the cells, intracellular PA content, and SDH activity in the mitochondria.

CONCLUSIONGenipin is involved in the energy metabolism of androgen-independent PC3 prostate cancer cells by reducing the content of intracellular PA and the activity of SDH in the mitochondria, which may be associated with its inhibitory effect on UCP-2.

Cell Line, Tumor ; drug effects ; Energy Metabolism ; Humans ; Ion Channels ; metabolism ; Iridoids ; pharmacology ; Male ; Mitochondria ; metabolism ; Mitochondrial Proteins ; metabolism ; Prostatic Neoplasms ; metabolism ; Pyruvic Acid ; metabolism ; RNA, Messenger ; Succinate Dehydrogenase ; metabolism ; Uncoupling Protein 2

With the wide application of electronic data management (EDC), the data management is shifting to a new mode. In order to recognize the advantages of EDC, we choose 20 representative registered clinical trials, which involve 5 404 subjects and 321 sites. We found that EDC has many beneficial impacts on the course of clinical trial data management, including the process of data collection, data cleaning, data quality control and clinical trial decision-making. The result also provides a reference for the adoption of EDC in clinical trials.
Clinical Trials as Topic ; Data Collection ; standards ; Information Storage and Retrieval ; standards ; Quality Control

The crude extracts of the fermentation broth from a marine sediment-derived actinomycete strain, Saccharothrix sp. 10-10, showed significant antibacterial activities against drug-resistant pathogens. A genome-mining PCR-based experiment targeting the genes encoding key enzymes involved in the biosynthesis of secondary metabolites indicated that the strain 10-10 showed the potential to produce tetracenomycin-like compounds. Further chemical investigation of the cultures of this strain led to the identification of two antibiotics, including a tetracenomycin (Tcm) analogs, Tcm X (1), and a tomaymycin derivative, oxotomaymycin (2). Their structures were identified by spectroscopic data analysis, including UV, 1D-NMR, 2D-NMR and MS spectra. Tcm X (1) showed moderate antibacterial activities against a number of drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) pathogens, with the MIC values in the range of 32-64 microg x mL(-1). In addition, 1 also displayed significant cytotoxic activities against human cancer cell lines, including HL60 (leukemia), HepG2 (liver), and MCF-7 (breast) with the IC 50 values of 5.1, 9.7 and 18.0 micromol x L(-1), respectively. Guided by the PCR-based gene sequence analysis, Tcm X (1) and oxotomaymycin (2) were identified from the genus of Saccharothrix and their 13C NMR data were correctly assigned on the basis of 2D NMR spectroscopic data analysis for the first time.
Actinomycetales ; chemistry ; genetics ; Anti-Bacterial Agents ; chemistry ; isolation & purification ; pharmacology ; Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; Benzodiazepinones ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Data Mining ; methods ; Drug Resistance, Bacterial ; Enterococcus faecalis ; drug effects ; Fermentation ; Genomics ; Humans ; Inhibitory Concentration 50 ; Marine Biology ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Naphthacenes ; chemistry ; isolation & purification ; pharmacology ; Phylogeny ; Staphylococcus epidermidis ; drug effects

Drimary fetal hydrothorax(DPHT)is an uncommon congenital disease. Petal hydrothorax is thought to be due to leakage of lymphatic fluid in the pleural space either caused by direct leakage of lymphatic fluid from the thoracic duct,overproduction or impaired drainage of lymph. The outcome of fetal hydrothorax may vary from spon_taneous resolution without postnatal morbidity to severe fetal hydrops and perinatal death. At present,there is no consen_sus on the treatment of DPHT. Now,the latest researches progress on prenatal ultrasonographic characteristics,prenatal diagnostic procedures,prenatal intervention,and prognosis in DPHT,were reviewed combined with the diagnosis and treatment principle of single center in Guangdong Women and Childrenˊs Hospital,which would provide useful guidance for clinical treatment of DPHT.

Objective： The current study was designed to investigate the effect of heat shock protein 70(HSP70) on stability of mutant p53 protein. Methods： Retroviral recombinant expressing antisense HSP70 RNA was constructed and transfected into MCF7/Adr breast cancer cells. The existence of foreign DNA was identified by PCR method and the HSP70 protein level was determined by Western blot analysis. The half-life of mutant p53 protein(mtp53) was measured by p53 stability assay. Results： The stable expressing strain(MAp70) from transfected cells was obtained through G418 selection. The foreign DNA in transfectant cells were confirmed by PCR, and the repression rate of HSP70 protein was 42％ . The half-life of mutant p53 in MAp70 cell was 12 hours, significantly lower than that of the control cells. Conclusion： Antisense HSP70 RNA can decrease the HSP70 protein level and significantly increase instability of mutant p53 protein in MCF7/Adr breast cancer cell.

Objective To study the effects of ubenimex on immunocyte functions of mice.Methods Antitumor activity of ubenimex was observed in implanted H22 mice.The killing activity of NK cells to target cell YAC-1, phagocytosis of peritoneal macrophage and the secretion of mac -rophage NO effect were carried out with CCK method , neutral red colori-metric method and Griess method , respectively.Lymphocyte proliferation test was done by stimulating methods in vitro and in vivo.Tumor associated macrophages(TAMs)and myeloid derived suppressor cells (MDSCs) in pe-ripheral blood and T lymphocytes , B lymphocytes and NK cell in spleen were determined by flow cytometry method.Results The 20 mg· kg-1 of ubenimex could depress the growth of H 22 and its tumor inhibitory rate was 41.71%.The killing activity of NK cells was increased by 56.5%.The 10μg· mL-1 of ubenimex significantly enhanced secretion of macrophage NO effect (P<0.01) and it also enhanced phagocytosis of peritoneal mac-rophage (P<0.05) at concentration of 100μg· mL-1.Besides the lym-phocyte proliferation was also strengthened (P<0.05).The number of T lymphocytes and CD 8+T cell in spleen was increased obviously ( P<0.01 or P<0.05).Ubenimex could adjust the number of TAMs and MDSCs in peripheral blood to normal level.Conclusion Ubenimex has antitumor growth activity through enhances non -specific immunity and specific immunity and suppresses the tumor associated cell.

PURPOSE: To evaluate social adjustment and related factors among Chinese children with Down syndrome (DS). PATIENTS AND METHODS: A structured interview and Peabody Picture Vocabulary Test (PPVT) were conducted with a group of 36 DS children with a mean age of 106.28 months, a group of 30 normally-developing children matched for mental age (MA) and a group of 40 normally-developing children matched for chronological age (CA). Mean scores of social adjustment were compared between the three groups, and partial correlations and stepwise multiple regression models were used to further explore related factors. RESULTS: There was no difference between the DS group and the MA group in terms of communication skills. However, the DS group scored much better than the MA group in self-dependence, locomotion, work skills, socialization and self-management. Children in the CA group achieved significantly higher scores in all aspects of social adjustment than the DS children. Partial correlations indicate a relationship between social adjustment and the PPVT raw score and also between social adjustment and age (significant r ranging between 0.24 and 0.92). A stepwise linear regression analysis showed that family structure was the main predictor of social adjustment. Newborn history was also a predictor of work skills, communication, socialization and self-management. Parental education was found to account for 8% of self-dependence. Maternal education explained 6% of the variation in locomotion. CONCLUSION: Although limited by the small sample size, these results indicate that Chinese DS children have better social adjustment skills when compared to their mental-age-matched normally-developing peers, but that the Chinese DS children showed aspects of adaptive development that differed from Western DS children. Analyses of factors related to social adjustment suggest that effective early intervention may improve social adaptability.
Adolescent ; Asian Continental Ancestry Group/*psychology ; Child ; Child, Preschool ; China ; Communication ; Down Syndrome/ethnology/*psychology ; Female ; Humans ; Male ; *Social Adjustment ; Socioeconomic Factors