Adolescent ; Bacteria ; isolation & purification ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Respiratory Tract Infections ; microbiology

To explore new agents of quinolone derivatives with high antibacterial activity, 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones were designed and synthesized, and their activity against gram-positive and gram-negative strains was tested in vitro. Sixteen target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. Compounds 14k and 14m-14o show good antibacterial activity against the tested five gram-positive strains and five gram-negative strains (MIC: 0.25-16 micromg x mL(-1)), of which the most active compound 14o is 8-fold more potent than levofloxacin against S. pneumoniae (MIC: 4 microg x mL(-1)), and comparable to levofloxacin against S. aureus, S. epidermidis, E. faecalis and E. coli (MIC: 0.25-1 microg x mL(-1)), but generally less potent than gemifloxacin.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Gram-Negative Bacteria ; drug effects ; Gram-Positive Bacteria ; drug effects ; Molecular Structure ; Quinolones ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo investigate thiopurine S-methyltransferase (TPMT) activity and gene promoter polymorphism to probe its significance of individual chemotherapy in acute lymphoblastic leukemia (ALL) children.

METHODSHPLC method was carried out to determine TPMT activity (n=100), which activity at newly diagnosed. At the same time determination of TPMT activity in healthy children (n=180), these children come from the health care clinic. Using online primer3 software design primers, PCR products were purified. To sequence TPMT gene of the patients with clinical events(n=30). According to the method to analysis of correlation between TPMT activity and toxicity.

RESULTSThe average TPMT activities were (31.72±10.31) nmol·g⁻¹Hb·h⁻¹ and (30.70±9.67) nmol·g⁻¹Hb·h⁻¹ in ALL and healthy groups respectively, without gender differences of TPMT activities (P=0.45) in both groups. The TPMT activity with clinical events in newly diagnosed ALL patients (n=30) was (24.07±11.43) nmol·g⁻¹Hb·h⁻¹. There are significant differences of TPMT activities between severe bone marrow suppression [(20.96±7.24) nmol·g⁻¹Hb·h⁻¹] and ALL patients with clinical events groups (P<0.05). The TPMT activity of (40.46±8.18) nmol·g⁻¹Hb·h⁻¹ in recurrence children was also significantly different (P<0.05). TPMT activity in severe liver toxicity group was not significantly different (P=0. 930). Of TPMT gene sequencing in ALL patients with clinical events, only 3 children were heterozygosity mutations of TPMT*3C, while others homozygous genotype. There were significant differences of TPMT activities between heterozygosity genotype [(11.99±1.32) nmol·g⁻¹Hb·h⁻¹] and homozygous genotype groups [(24.95±11.32) nmol·g⁻¹Hb·h⁻¹] (P<0.05). There were five kinds of variations at the vicinity of the promoter region of -100 of tandem repeats (VNTR) polymorphism（*V3/*V3、*V3/*V4、*V4/*V4、*V5/*V5、*V4/*V6）without significant differences of TPMT activities among five kinds (P=0.186).

CONCLUSIONTPMT activity was related to the gene polymorphism. TPMT activity determination had prognostic value and guided individualized treatment.

Child ; Child, Preschool ; Female ; Humans ; Male ; Methyltransferases ; genetics ; Mutation ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Prognosis ; Promoter Regions, Genetic

Objective:To explore the learning curve of MAKO-assisted total knee arthroplasty.Methods:From May 2021 to September 2022, 136 patients were conducted MAKO-assisted total knee arthroplasty in the PLA General Hospital, including 37 males and 99 females, 65.53±7.01 years old (range 54-80 years). All cases were patients with unilateral knee osteoarthritis. The operations were performed by three surgeons, respectively. Sixty-one cases were performed by surgeon 1, 47 cases were performed by surgeon 2, and 28 cases were performed by surgeon 3. Record the time of each step during the operation, and measure the limb alignment in X-ray. The statistical difference between the two groups was compared by t test by SPSS. The cumulative sum control chart (CUSUM) learning curve was modeled by curve fitting and R2 was used to testify the goodness. Results:The total operation time of the three surgeons was 114.3±25.1 min, 109.8±10.9 min, and 118.6±15.1 min, respectively. The time of each step in the first 10 cases and the last 10 cases of operator 1-3 was counted. The osteotomy time of surgeons 1, 2 and 3 in the final 10 cases was less than that in the initial 10 cases (surgeon 1: 13.5 ± 3.41 min vs. 8.0±1.58 min, t=4.30, P=0.001; surgeon 2: 13.7±3.02 min vs. 8.0± 2.58 min, t=4.77, P=0.001; surgeon 3: 15.3±3.97 min vs. 11.0±2.38 min, t=2.87, P=0.010), and the difference was statistically significant. The CUSUM of osteotomy was calculated and the curve was fitted. The highest point of the curve of the three surgeons was in the 16th, 18th and 12th patients, respectively, and the time of osteotomy continued to decline after passing the peak. No statistical differences were found in surgery time for the remaining steps. Comparing the lower alignment angles of intraoperative planning and postoperative X-ray films, the overall difference was greater than 1 degree. The difference was 1.41°±1.32° for operator 1, 1.34°±1.22° for operator 2, and 1.04°±0.88° for operator 3. The percentages of fully accurate implant size planning were 85.2%(52/61), 76.7%(36/47), and 85.7%(24/28), respectively. Conclusion:For MAKO-assisted total knee arthroplasty, the operator can decrease the operation time by practice, which is mainly reflected in the shortening of the osteotomy time. The learning curve threshold is around in the 15th case. The increase in the number of surgeries did not bring about changes in the accuracy of lower extremity alignment.

OBJECTIVETo explore the clinical spectrum, geographic location of human H7N9 avian influenza as well as the characteristics of population at high risk of infection, in order to develop strategies for the prevention and control of the infection. Clinical and epidemiological characteristics on the 6 confirmed human cases in Zhejiang were also analyzed.

METHODSReal-time fluorescent quantitative PCR was used to test the nucleic acid of human H7N9 avian influenza infection, from pharyngeal swabs of the patients and their close contacts. Face to face interview and descriptive method were used to collect related clinical and epidemiological data. Statistical analysis was performed by SPSS 17.0.

RESULTSSix confirmed cases were distributed in Hangzhou and Huzhou cities. The 6 confirmed human cases, including 5 males and 1 female were all confirmed with novel influenza A (H7N9) virus infection, with an average age as 60.83 years (with median as 64.50 years). Cough was the most common initial symptom to be noticed. The clinical manifestations would include fever, dizziness, pain of muscles, coughing, expectoration and short of breath. All the X-ray chest films showed severe pneumonia, and 5 of them having had other chronic diseases. None of the cases admitted to have had a history of exposure to ill/death avians. However, all of the cases had been frequently exposed to the agricultural-byproduct-trading-markets where the positive rate of novel influenza A (H7N9) virus in environmental specimens was up to 43.21%. 32 of the 375 close contacts (8.53%) to the 6 cases appeared abnormal symptoms, but no positive result related to novel influenza A (H7N9) virus nucleic acid was detected from their throat swabs.

CONCLUSIONAcute infection on the respiratory system seemed the main clinical manifestation. Elderly men, especially those with chronic diseases were under high risk of human infection with H7N9 avian influenza. The source of infection might be associated with the exposure to poultry. There was still lack of evidence to confirm the route of person to person transmission on H7N9 avian influenza.

Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; epidemiology ; virology ; Male ; Middle Aged

Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.
Animals ; Antioxidants ; pharmacology ; therapeutic use ; Apoptosis ; Cardiomyopathies ; drug therapy ; etiology ; Caspase 3 ; metabolism ; Cytochromes c ; metabolism ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Ventricles ; drug effects ; pathology ; physiopathology ; Hypoxia ; Male ; Mice, Inbred ICR ; Mitochondria ; drug effects ; metabolism ; Myocardium ; pathology ; Oxygen ; metabolism ; Phytotherapy ; Qi ; Up-Regulation ; Ventricular Dysfunction, Left ; drug therapy ; etiology ; bcl-2-Associated X Protein ; metabolism

Apoptosis ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Leukemia, Promyelocytic, Acute ; RNA, Long Noncoding ; Tretinoin