Objective To observe and analyze the clinical efficacy of docetaxel and S-1 in treatment of anthracycline-resistant triple-negtive breast cancer(TNBC).Methods 64 cases with TNBC admitted in People' Hospital of Shaoxing City from June 2009 to June 2011were selected as research object.The clinical data of these cases were analyzed retrospectively.Anthracycline had been used to treat the cases, but with no effect or recurrence.Then docetaxel combined with S-1 was applied to the cases.Clinical efficacy and adverse reactions of the chemotherapy were observed and analyzed. Results After treatment,the efficiency of 64 cases was 54.69%,and the disease control rate was 79.69%.During the treatment,the main adverse reactions were gastrointestinal reactions and bone marrow suppression,without death,and patients could tolerate the adverse event.Follow-up results showed that the median time of progression was 10.5 months.After two years,progression-free survival rate was 0.Conclusion Docetaxel combined with S-1 has good clinical efficacy for anthracycline-resistant triple-negtive breast cancer,with relatively mild side effects,which may be an ideal adjuvant chemotherapy method.

Objective To compare the efficacy and safety of icotinib therapy alone versus icotinib combined with thoracic radiotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with an activating epidermal growth factor receptor (EGFR) gene mutation.Methods A total of 83 patients with advanced NSCLC harboring an activating EGFR gene mutation was enrolled in this study.All the patients were randomly divided into 2 groups.Patients in group A (n =41) received thoracic radiotherapy (prescribed at 60-66 Gy) combined with icotinib (three times per day,125 mg once).Patients in group B (n =42) were given icotinib therapy alone (three times per day,125 mg once).Treatment was continued until disease progression or unacceptable toxicity or death.The primary end points were median progression-free survival (mPFS) and 12 month-PFS rate.The secondary end points included objective response rate (ORR),disease control rate (DCR) and adverse events.Results With a median follow-up of 18.2 months,mPFS was 15.2 months (95％ CI:12.2-17.4) in group A and 13.2 months (95％ CI:10.8-14.9) in group B (x2 =4.29,P=0.036).PFS rates of 12 months for group A and group B were 70.3％ and 61.2％,respectively.The ORR were 78.0％ vs.57.1％ (x2 =5.16,P =0.028),and the DCR were 95.1％ vs.92.9％ (P＞0.05) in groups A and group B,respectively.No grade 3-4 adverse events was observed in both groups except the rashes (4 cases in each group).Besides,10 patients had grade 1-2 radiation-related pneumonitis and 15 patients suffered grade 1-2 radiation-related oesophagitis in group A.Conclusions In advanced NSCLC patients with an activating EGFR gene mutation,the combination of thoracic radiotherapy and icotinib had achieved an improvement on ORR and PFS with good tolerance.Clinical trial registration Chinese clinical trial registry,ChiCTRINR-16010262.

Objective To evaluate the efficacy and safety of paclitaxel plus cisplatin combination in treatment patients with advanced or metastatic squamous-cell carcinoma of the esophagus(ESCC).Methods Twenty-five patients with advanced or metastatic ESCC received paclitaxel 175mg/m2 by 3-hour infusion on day 1 and cisplatin 25mg/m2 by infusion on day 1 ～ 3.3 weeks as one cycle.Results Twenty-four patients were eligible to be evaluated the efficacy and safety.The overall response rate was 45.8％ with complete and partial response rates of 4.1％ and 41.7％,respectively.The median survival time of all patients was 11 months(95％ CI:8.35 ～ 13.65 months).There was significant difference in the median overall survival between the patients who had showed response versus those who had not(P =0.022).Median survival was 12.5 months(95％ CI:9.11 ～ 15.90 months) and 8 months(95％CI:5.50 -9.50 months),respectively.The 1-year survival probability was 37.3％.The most common toxicities were leukopenia,neutropenia,thrombocytopenia and alopecia.Conclusion The effect of paclitaxel and cisplatin which seems beneficial as first-line therapy in advanced squamous-cell carcinoma of the esophagus had a high effective rate with acceptable toxicity.

AIM: To investigate the effect of hypoxia on the expression of MMP-2 and TIMP-1 in pulmonary artery fibroblasts. METHODS: MMP-2 activity was measured by using gelatin zymography. TIMP-1 protein level was determined by immunocytochemistry and Western blotting. mRNA expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The production of MMP-2 mRNA and protein was down-regulated in pulmonary artery fibroblasts exposed to hypoxia for 24 h. Gelatin zymography also demonstrated that lower level of MMP-2 activity was induced after hypoxia. Meanwhile, hypoxia induced the up-regulation of TIMP-1 mRNA and protein in pulmonary artery fibroblasts. CONCLUSION: Hypoxia induces unbalance of MMP-2/TIMP-1 in pulmonary artery fibroblasts, which may contribute to the mechanism of hypoxic pulmonary vascular remodeling.

Objective To investigate the mechanism of an inhibitor of NADPH oxidases,diphenylene iodonium (DPI),in preventing radiation-induced lung injury.Methods Totally 48 adult SD male rats were randomly classified into 4 groups:control group (C),radiation group (R),radiation plus DPI group (R + D) and DPI group (D).The radiation induced pulmonary injury model was preformed by using 6 MV X-rays to deliver 8 Gy per day for 5 consecutive days with 40 Gy in total to the thorax of each animal.Rats in R + D group were subcutaneously administered with 0.02％ DPI (1 mg/kg) at 1 h prior to radiation while rats in D group received the same dose of DPI without radiation.DPI was given from 3 d before radiation to 30 d after the first radiation.Rats in C and D groups received the same dose of saline.Animals were sacrificed at 1 month and 6 months after radiation,respectively.The lungs were removed and processed for HE and Masson staining,hydroxyproline content measurement,and TGF-β1 immunohistochemical detection.Results At 1 month post-radiation,rats in R group showed typical alveolitis,the level of hydroxyproline was (0.69 ± 0.05) μg/mg,and the positive area of TGF-β1 expression was (39.97 ± 0.90) ％,while the level of hydroxyproline in R + D group was (0.55 ± 0.03) μg/mg and the positive area of TGF-β1 expression was(33.83 ± 1.55) ％,rats in R + D group showed less severe alveolitis compared with R group(t =5.32,5.93,P ＜0.05).At 6 months post-radiation,rats in R group showed typical lung fibrosis with hydroxyproline level of (1.04 ±-0.02) μg/mg and TGF-β1 expression of (37.80 ± 0.85) ％,whereas the hydroxyproline level in R + D group was (0.85 ± 0.02) μg/ mg,the TGF-β1 expression was(23.93 ± 1.16)％,rats in R + D group showed moderate lung fibrosis(t =15.77,16.68,P ＜ 0.05),rats in C and D group had no noticeable changes.Conclusions Diphenylene iodonium could prevent radiation-induced lung injury by reducing the level of hydroxyproline and the expression of TGF-β1.

AIM: To investigate the expression of FIZZ1/RELM? in lung tissue of chronic cigarette smoking rat,and to determine the relationship between airway inflammation and airway hyperresponsiveness.METHODS: Made rat model of chronic cigarette smoking was used.The expression of FIZZ1/RELM? in lung tissue was determined by immuno-histochemistry and in situ hybridization.RESULTS: In control rats,FIZZ1/RELM? protein and mRNA expressions were observed at low levels.In cigarette smoking rats,FIZZ1/RELM? expression increased in all the cells especially in bronchial smooth muscle cells,vascular wall cells and alveolar epithelial cells.CONCLUSION: FIZZ1/RELM? is a secreted peptide specifically expressed in lung.Cigarette smoking induces its upregulation,which possibly contributes to cigarette smoking-induced airway hyperresponsiveness.

Primary cell culture, techniques of gene transfection, gelatin zymography, and Western blot were used to investigate the effect of hypoxia on the secretion of MMP-2 and MMP-9 in pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC), and the role of HIF-1. Our results showed that (1) after exposure to hypoxia for 24 h, the protein content and activity of MMP-2 in the PAEC medium as well as these of MMP-2 and MMP-9 in PASMC medium (P<0.01) decreased significantly in contrast to those in normoxic group (P<0.05); (2) after transfection of wild type EPO3'-enhancer, a HIF-1 decoy, the content and activity of MMP-2 and MMP-9 in hypoxic mediums became higher than those in normoxic group (P<0.01), while transfection of mutant EPO3'-enhancer didn't affect the hypoxia-induced down-regulation. It is concluded that hypoxia could inhibit the secretion and activity of MMP-2 and MMP-9 in PAEC and PASMC, which could be mitigated by the transfection of EPO3'-enhancer and that HIF-1 pathway might contribute to hypoxia-induced down-regulation of MMP-2 and MMP-9.

OBJECTIVETo investigate the physicochemical constants such as equilibrium solubility and apparent partition coefficients (Papp), and study the effects of temperature, pH value and antioxidants on the stability of breviscapine solution.

METHODThe equilibrium solubility of breviscapine in various medium and the Papp of breviscapine under different pH conditions were determinated by RP-HPLC, and the effects of temperature, pH value and antioxidants on the stability of solution were investigated by taking change rates of drug content in 10 h as detection index.

RESULTThe equilibrium solubility of breviscapine in saline, distilled water, pH 7.0 PBS, pH 7.5 PBS, Ringer's fluid, methanol and ethanol were (20.68 +/- 1.12), (79.35 +/- 0.68), (7954.62 +/- 34.90), (18,708.17 +/- 253.05), (3670.40 +/- 27.64), (210.71 +/- 0.74), (184.34 +/- 1.47) mg x L(-1) respectively; while in pH value 3.0, 4.0, 5.0, 6.5, 7.0 solution, the Papp were 5.362, 0.542, 0.371, 0.328 and 0.143 respectively. The stability of breviscapine in the Ringer's fluid was the worst and the stability was significantly decreased with the increase of temperature and pH value and it could be improved by EDTA-2Na.

CONCLUSIONThe established HPLC assay was accurate and convenient. The Papp of breviscapine is decreased by increased the pH value, while in the aqueous solution the equilibrium solubility of breviscapine increase with the pH in crese. EDTA-2Na can be used as an antioxidant of breviscapine solution.

Antioxidants ; chemistry ; Chemical Phenomena ; Drug Stability ; Edetic Acid ; chemistry ; Flavonoids ; chemistry ; Hydrogen-Ion Concentration ; Solutions ; Solvents ; chemistry ; Temperature

Objective:To analyze the clinical characteristics and causes of death of 80 dead cases with confirmed coronavirus disease 2019 (COVID-19).Methods:The clinical data of 80 dead patients with COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 11 to February 11, 2020 were retrospectively analyzed.The laboratory examination indexes (including white blood cells, lymphocytes, procalcitonin (PCT), lactic acid, D-dimmer, fibrinogen degradation products, N-terminal pro-brain natriuretic peptide (N-proBNP), ultra sensitive-troponin I, lactate dehydrogenase (LDH) and CD4 + T lymphocyte) of the patients at the time of admission were compared with the indexes at the last time before death. Statistical analysis was conducted by using paired t test or Wilcoxon′s signed rank test. Results:The median age was 72 years old of the 80 patients, and 78.75%(63/80) of them were older than 60 years. Thirty-six cases (45.00%) were severe and 44(55.00%) were critical at admission. Fifty-eight cases (72.50%) had underlying diseases. The common underlying diseases were hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and chronic obstructive pulmonary disease. Comparing the patients′ first laboratory tests at admission with those before death, white blood cells increased (8.01(4.86, 12.29)×10 9/L vs 12.55(8.25, 17.66)×10 9/L), lymphocytes decreased (0.70(0.46, 0.88)×10 9/L vs 0.54(0.39, 0.75)×10 9/L), PCT increased (0.20(0.11, 0.74) μg/L vs 1.00(0.20, 1.99) μg/L), lactic acid increased (2.10(1.40, 3.10) mmol/L vs 3.10(2.60, 4.10) mmol/L), D-dimmer increased (4.33(0.97, 18.98) mg/L vs 15.29(5.17, 53.44) mg/L), fibrinogen degradation products increased (15.90(3.58, 76.60) mg/L vs 63.14(21.23, 110.67) mg/L), N-proBNP increased (1 078.00(347.35, 2 996.50) ng/L vs 3 439.50(1 576.00, 9 281.50) ng/L), ultra-sensitive troponin I increased (0.08(0.03, 0.17) μg/L vs 0.33(0.14, 2.47) μg/L), LDH increased (397.00(327.00, 523.50) U/L vs 624.00(481.00, 854.00) U/L) and CD4 + T lymphocyte decreased (137.00(104.00, 168.00)/μL vs 97.00(67.00, 128.00)/μL). The differences between the two groups were all statistically significant ( W=238.00, 1 053.50, 150.00, 152.00, 192.00, 190.00, 108.00, 57.00, 53.00 and 40.00, respectively, all P<0.05). All patients received antiviral and respiratory-support therapy and the main cause of death was respiratory failure caused by intractable hypoxemia and multiple organ failure. Among them, seven cases died in one day hospitalization, and 66 cases died in seven days hospitalization. Conclusions:Elderly patients with a variety of chronic underlying diseases have poor prognosis. It′s essential to pay more attention and deal with the above clinical characteristics at an early stage to improve the outcome of the COVID-19 patients.

Objective:To analyze the risk factors of fatal outcome in patients with severe COVID-19.Methods:The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression.Results:Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators ( P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient’s clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion:COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.