Objective: To study the synthesis, antibacterial activities and structure activity relationship of 7 substituted 1 substituted 6,8 difluoro 1,4 dihydro 4 oxo 3 quinolonecarboxylic acid compounds. Methods: The title compounds were synthesized through the process of condensation, Gould Jacobs cyclization, nucleophilic substitution. Antibacterial activities in vitro were determined with 10 kinds of common pathogenic bacteria. Results: Twenty six compounds of 7 substituted 1 substituted 6,8 difluoro 1,4 dihydro 4 oxo 3 quinolonecarboxylic acids were designed and synthesized. Among them 20 compounds were firstly reported. The chemical structures of all the compounds were determined by IR, 1HNMR and elementary analysis. Especially for type Ⅲ, compound Ⅲ b2 had more potent activity compared with fleroxacin in vitro . Conclusion: Among the 26 kinds of compounds synthesized, some of them have good antibacterial activities, the antibacterial activity of compound Ⅲ b2 is better than fleroracin. The compounds of type Ⅲ should be further studied.

Objective Investigated and analyzed the data of routine coefficient of variation (R CV ) from clinical laboratories of the second and the third grade hospital, we have drawed up Internal Quality Control(IQC) requirement of clinical chemistry in Shanghai Methods In this survey, we defined IQC requirement a quarter of CLIA’88 proficiency testing criteria as acceptable analytical performance From 147 clinical laboratories, we get 3 570 336 IQC data of 23 analytes of clinical chemistry which was analyzed and percentiles were calculated The outcome from the statistical analysis was compared with recommendation from the Ministry of Health in1985 Results 138 clinical laboratories (94 0%) CV results in Shanghai were less than R CV recommendation from the Ministry of Health About 111 clinical laboratories (75 5%) results are according with IQC requirement Conclusion IQC requirement is suitable for the clinical laboratories in Shanghai 75 5% clinical laboratories accorded with IQC requirement and 24 5% clinical laboratories should improve technique to carry out the IQC requirement

Objective To explore the shielding effects of 1-4 layers of lead aprons (LPs) and body shielding devices (BSDs) against stray radiation (SR) outside the electron beam field of 6-15 MeV.Methods JR-115B LiF TLDs were used to measure the stray radiation doses (SRDs) to the patient undergoing treatment,before and after being shielding,for different distances,different energies,different applicators,variable layers of LPs,and different thickness of body shielding devices (BSDs),respectively,along long calculating and comparing the shielding ratios of LPs and BSDs against SR.Results When the applicator (10 cm × 10 cm) is unchanged,the shielding ratio increased with the increased distance from measuring point (r =0.717,P ＜ 0.05) and decreased with the increased electron energy (r =-0.678,P ＜ 0.05);when the energy was constant,there was no correlation between the shielding ratio and the size of applicator (P ＞ 0.05);For lower energy electron beam of 6 and 9 MeV,the shielding ratio for 1 mm Pb-BSD was slightly higher than that for 2 layers of LA (t =2.519,2 662,P ＜ 0.05),ranging from 81.5％ to 95.3％ and 55.4％ to 84.6％,respectively.For 12 and 15 MeV higher energy electron beam,the shielding ratio for 2 mm Pb-BSD was slightly higher than that for 4 layers of LA (t=3.768,7.934,P＜0.05),ranging from 64.6％ to 93.4％ and 51.1％ to 92.4％,respectively.Conclusions LAs or BSDs are availavle for effectively reducing the doses from stray radiation,and may help reduce the secondary risks from stray radiation.BSDs have more obvious advantages than LPs with regard to shielding effect.

The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.

Objective To investigate the late effects induced by ionizing radiation and the rehabilitation treatment of local radiation injury by medical follow-up of the patient exposed to192 Ir at 5.7 accident in Nanjing,and to provide more experience for the treatments in the medical emergency of nuclear or radiological accident.Methods According to the history inquiry and physical examination of the patient in detail and the record of clinical symptoms and signs,the changes of the blood system,immune system,reproductive system,eyes,nervous system were systematically evaluated.The effects of rehabilitation treatment for the patient with lower limb dysfunction were also assessed.Results After the medical treatments of the patient,the hematopoietic immune system was restored,but the bone marrow aspiration still showed low bone marrow hyperplasia in right ilium.Meanwhile,the level of sex hormones was within the normal range,but semen examination showed sperm motility was 0.The radiation damage also occurred in the eye lens,retina and fundus.Howevcr,the psychological evaluation showed that the patient was stable and the right lower limb skin wound healing was well except for dysfunction and pain in some extent,which was relieved after the rehabilitation treatment.Conclusions The physiological function of the exposed victim with mild bone marrow type acute radiation sickness could be completely or partially restored after the clinical treatment in the early stage.

Objective: To explore the treatment technique, occurrence and development patterns of such radiation injuries as in a major radiological accident in which a victim suffered mild bone marrow radiation sickness combined grade degree Ⅲ acute radiation induced skin injury, based on his dose estimation, clinical manifestations and disease treatments. Methods: History inquiry in detail, earlier physical dose estimation and biological dose estimation were conducted in conjunction with analyzing the chromosome aberration of peripheral blood lymphocytes. The physical dose was estimated by Monte Carlo method.The systematic laboratory and imaging examination was performed to evaluate the condition. The comprehensive analysis was conducted to determine the diagnosis and treatment plan. Results: At 3d after the exposure, "Ren" felt mild pain and discomfortable on the skin of the right index finger. The body of the right hand index finger was covered with blister at 21 d after exposure.The estimation of biological dose was 0.43 Gy (95%CI: 0.31-0.58 Gy), and the physical dose was estimated to be 36-164 Gy for each part of the right hand finger. The hematopoietic system, immune system and endocrine system were normal. The liver function index value was transiently increased. The liver damage resulted from the use of antibiotic-induced combined with the patient′s past medical history and admission examination result, and the relevant antibiotics were discontinued. The liver function returned to normal after liver protection treatment. At 22 d after irradiation, a right finger incision and decompression surgery were performed. The stem cells were extracted and implanted into the right index finger. After 59 days of hospitalization, there was no obvious discomfort in the body, and the right index finger recovered well, as well as the pain significantly relieved, and the knuckle activity was basically normal. Conclusions The patient with excessive radiation and grade Ⅲ acute radiation skin injury was successfully treated, and local application of autologous adipose-derived stem cell transplantation achieved good result .

Objective:To explore the effects of Liuwei Dihuang Wan on the behaviors and Toll-like receptor 4/nuclear factor kappa-B(TLR4/NF-κB) signal transduction pathway of amyloid β-precursor protein/presenilin-1(APP/PS1) double transgenic mice.Methods:Forty 3-month-old female APP/PS1 mice were randomly divided into model group, low-dose group(0.59 g/kg), medium-dose group(1.18 g/kg), high-dose group(2.36 g/kg)of Liuwei Dihuang Wan(gavaged according to grouped doses), and ibuprofen group(0.04 g/kg, gavage) using a random number table method, with 8 mice in each group.Eight 3-month-old wild-type female C57BL/6 mice with matched body weight were used as the control group.The mice in control group and model group were given an equal volume of 0.9% sodium chloride solution by gavage.The gavage administration was twice a day for a continuous period of 3 months.Morris water maze test was used to detect the learning and memory abilities of mice. ELISA was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β) and immunohistochemistry was used to detect the levels of amyloid β-protein (Aβ), glial fibrillary acidic protein(GFAP) and NF-κB in hippocampal tissue.Western blot was used to detect the expression levels of TLR4, myeloid differentiation primary response gene 88(MyD88), and phosphorylated NF-κB(p-NF-κB) proteins in hippocampal tissue.The SPSS 20.0 software was used for data analysis. Multiple group comparisons were conducted by repeated measure ANOVA or one-way ANOVA.Results:The results of repeated measure ANOVA showed that as for the escape latency of the 6 groups of mice, the interaction effect between time and group was significant ( Finteraction=117.219, P<0.001). The escape latencies of mice in the 6 groups on the 5th day were all lower than those on the 1st day (all P<0.05). The escape latencies of mice in the ibuprofen group and the medium-dose and high-dose groups of Liuwei Dihuang Wan were lower than that in the model group from 1st day to 5th day(all P<0.05). On the 3rd to 5th day, the escape latencies of mice in the medium-dose and high-dose groups of Liuwei Dihuang Wan were lower than those in the low-dose group of Liuwei Dihuang Wan (all P<0.05). There were statistically significant differences in the percentage of residence time in the platform quadrant and the numbers of crossing platform among the 6 groups of mice ( F=5.451, 4.824, both P<0.05). The percentage of residence time in the platform quadrant (50.77±5.49)%, (54.39±5.71)%, (51.98±6.12)%), and the numbers of crossing platform((5.9±1.1) times, (6.0±1.3) times, (5.1±0.8) times) in the high-dose and medium-dose groups of Liuwei Dihuang Wan and the ibuprofen group were all higher than those in the model group ((27.32±3.22)%, (2.2±1.0) times )(all P<0.05). The immunohistochemical results showed that there were statistically significant differences in the integrated optical density values of Aβ, GFAP and NF-κB in the hippocampal tissues of 6 groups of mice ( F=57.52, 45.37, 79.10, all P<0.05). The integrated optical density values of Aβ, GFAP and NF-κB in the high-dose and medium-dose groups of Liuwei Dihuang Wan and the ibuprofen group were all lower than those in the model group (all P<0.05). And the integrated optical density values of Aβ, GFAP, and NF-κB in the high-dose and medium-dose groups of Liuwei Dihuang Wan were all lower than those in the low-dose group of Liuwei Dihuang Wan (all P<0.05). There were statistically significant differences in the levels of serum TNF-α and IL-1β detected by ELISA ( F=3.996, 6.395, both P<0.05) and the proteins levels of TLR4, MyD88, and p-NF-κB in hippocampal tissue detected by Western blot among the 6 groups( F=15.710, 3.522, 4.119, all P<0.05). The serum TNF-α and IL-1β levels in the high-dose and medium-dose groups of Liuwei Dihuang Wan and ibuprofen group were all lower than those in the model group (all P<0.05). The serum TNF-α ((18.90±2.33) ng/L, (21.56±2.49) ng/L) and IL-1β ((5.88±0.80) ng/L, (6.75±0.83) ng/L) levels in the high-dose and medium-dose groups of Liuwei Dihuang Wan were lower than those in the low-dose group ((30.77±2.89) ng/L, (9.11±1.27) ng/L) (all P<0.05). The protein expression levels of TLR4, MyD88, and p-NF-κB in the hippocampus of the high-dose and medium-dose groups of Liuwei Dihuang Wan and ibuprofen group were lower than those of the model group (all P<0.05). The protein expression levels of TLR4 ((0.254±0.091), (0.318±0.122)), MyD88 ((0.229±0.077), (0.386±0.119)), and p-NF-κB ((0.412±0.188), (0.358±0.119)) in the hippocampus of the high-dose and medium-dose groups of Liuwei Dihuang Wan were lower than those of the low-dose group ((0.617±0.172), (0.672±0.166), (0.799±0.227)) (all P<0.05). Conclusion:Liuwei Dihuang Wan can significantly alleviate learning and memory impairment in Alzheimer's disease model mice, possibly by inhibiting TLR4/NF-κB signal pathway, reducing TNF-α and IL-1β expression, thereby alleviate central immune inflammatory response and exert anti Alzheimer's disease effects.

Objective To study the effect of endovenous laser ablation combined with subfascial endoscopy therapy for venous ulcer of the lower limbs.Methods Clinical data of 112 patients undergoing endovenous laser ablation combined with subfascial endoscopy therapy for venous ulcer of the lower limbs from Oct 2011 to Feb 2016 was retrospectively evaluated.Results Patients had average 2-6 perforating veins in their affected lower limbs.Procedures were successful in all the patients,all the superficial varicose veins disappeared after 1 month and 1 year of ultrasound follow-up,perforating veins closed,ulcer healed,and chromatosis alleviated.Conclusion Endovenous laser ablation combined with subfascial endoscopy therapy for venous ulcer of the lower limbs is effective,safe and quick recovery.

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*