PURPOSE:Studying the multidrug resistance(MDR) phenotype occurring in retinoblastoma and its mechanism. METHODS:Using the procedure of stepwise increase in drug concentrations to obtain a retinoblastoma subline which resistant to 600ng/ml vincristine (HXO-RB/VCR). Characteristics of this drug-resistant cell line were investigated by cell counting,drugcontents determinatin,drug sensitivity evaluation and radiation sensitivity test. RESULTS:This cell line was cross-resistant to VDS,MMC VP16，ADM ,DDP,CBP,but not resistant to BCNU and 5-Fu. It was proved to be collaterally sensitive to MTX,and the response to 60Co gamma;-ray was modified slightly in HXO-RB/VCR cell line. Intracellular levels of VCR was much higher in HXO-RB44 cells than in the resistant subline. Those cross-resistances can be reversed by verapamil partly. CONCLUSIONS:MDR and radiation resistance of retinoblastoma can be induced by exposing to VCR and reversed by verapamil partly. （Chin J Ocul Fundus Dis,1997,13: 6-9）
Objective To investigate the correlation between pectoralis muscle CT attenuation value (PMT) and cross-sectional area (PMA) with clinical characteristics, exercise tolerance, and respiratory failure in patients with chronic obstructive pulmonary disease (COPD), providing a new perspective for COPD assessment. Methods A total of 120 COPD patients (67 in stable phase, 53 in acute exacerbation phase) admitted between January 2020 and December 2023 and 60 healthy controls in the same period were included. All participants underwent chest CT scans for the measurement of PMA and PMT. Pulmonary function indices, 6-minute walk distance (6MWD), and quality of life scores were also collected from COPD patients. Statistical analysis was conducted to explore the relationship between PMA and PMT with clinical characteristics of COPD patients, and their predictive value for exercise tolerance in stable COPD patients and respiratory failure in acute exacerbation COPD patients was evaluated. Results Both PMA and PMT were significantly lower in the COPD patients compared with the control group (P<0.05) and were significantly correlated with pulmonary function, exercise capacity, and quality of life (P<0.05). PMA was identified as an independent risk factor for exercise intolerance in stable COPD patients (OR=1.261, 95%CI 1.075-1.496, P=0.004). Receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.849 with a cut-off value of 23.72 cm² for PMA. Both PMA (OR=1.141, 95%CI 1.002-1.299, P=0.046) and PMT (OR=1.178, 95%CI 1.085-1.293, P<0.001) were independent risk factors for respiratory failure in acute exacerbation COPD patients. The ROC curve analysis showed an AUC of 0.804 with a cut-off value of 24.15 cm² for PMA and an AUC of 0.831 with a cut-off value of 37.65 Hu for PMT. Conclusions Pectoralis muscle PMA and PMT can serve as effective indicators for assessing the severity and prognosis of COPD. A lower pectoralis muscle PMA is a risk factor for exercise intolerance in patients with stable COPD, while lower pectoralis muscle PMA and PMT are risk factors for the development of respiratory failure in patients with acute exacerbations of COPD.
目的 评价健康志愿受试者对通栓救心片的耐受性和安全性，为Ⅱ期临床试验给药方案提供依据。 方法 2009年1月－4月，选择健康受试者38例，随机进入5个单次给药组和2个连续给药组。单次给药组分别口服通栓救心片3、6、8、10、15片；连续给药组口服通栓救心片2片/次和3片/次，3次/d，服药7 d。观察生命体征、实验室检查指标、临床症状和不良反应。 结果 单次给药8片和15片组各有1例有轻微头痛、头昏；连续给药组有轻微头昏或恶心的不良反应，均未经处理自动消失。 结论 健康人体对通栓救心片耐受性较好，临床应用较安全，仅见轻微头昏、头痛或恶心。推荐Ⅱ期临床试验给药剂量范围是（2～3）片/次，3次/d 。
Objective To review the recent studies on the multidrug resistance of breast cancer. Methods The literatures of recent years on the studies of multidrug resistance, multidrug resistance protein and breast cancer resistance protein were reviewed. Results Multidrug resistance resulted from multiple factors. How to identify the sensibility of chemotherapy drugs and select individual therapeutic regime early were important to improve the survival rate and life quality of breast cancer patients. Conclusion These studies on multidrug resistance of breast cancer are helpful to predicting the effect and outcome of chemotherapy and overcoming the barrier of drug resistance.
ObjectiveTo evaluate the treatment retention rate of five new types of antiepileptic drugs:lamotrigine (LTG), topiramate (TPM), oxcarbazepine (OXC), levetiracetam (LEV) and gabapentin (GBP) and their tolerability. MethodsA total of 216 patients diagnosed as epilepsy by receiving the long-term video electroencephalography monitoring between October 2012 and October 2014 were randomized into five drug treatment groups (LTG, n=57; TPM, n=42; OXC, n=49; LEV, n=47; GBP, n=21) and received corresponding dose of drug therapy. The seizure frequency, adverse events and number of patients giving up therapy were collected and recorded via phone or interview every 4 weeks. Every follow-up retention rate of every drug group equals current patient number continuing therapy/initial patient number of this drug group×100%. When the trial ended, Kaplan-Meier curve and Cox proportional risk model were applied for statistical analysis. ResultsThe trial lasted for 106 weeks. The final retention rate of LTG was the highest (85.9%), and GBP was the lowest (14.3%). Most patients could continue the therapy until the end of the trial after 24 weeks. The leading causes of discontinuing therapy included:no efficacy, rash, sedation and aggressive behavior. ConclusionThe retention rate of new types of antiepileptic drugs is associated with these elements:drug efficacy, adverse events, individual tolerability of drug, drug accessibility and the patients' individual preference of drug administration.
Objective To analyze the distribution of pathogens, drug susceptibility and multi-drug resistant bacteria (MDRB) in elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pneumonia. Methods The clinical data of patients whose discharge diagnosis included AECOPD with pneumonia or pulmonary infection from January 2012 to December 2015 were retrospectively analyzed. Strain identification and drug sensitivity analysis were performed in the pathogenic bacterias isolated from sputum culture. Results A total of 1 978 patients were enrolled in this study, and pathogenic bacterias were isolated from the sputum of 708 patients, including 485 cases of community-acquired pneumonia (CAP) and 223 cases of hospital-acquired pneumonia (HAP); and 786 strains of pathogens were isolated (501 strains from CAP cases, 285 strains from HAP cases), including 448 strains of Gram-negative (G–) bacilli (57.0%), 117 strains of Gram-positive (G+) cocci (14.9%), and 221 strains of fungi (28.1%). Susceptibility testing results showed that G– bacilli were highly resistant to penicillins, third generation cephalosporins, ciprofloxacin, gentamicin, etc., and G+ cocci were highly resistant to penicillin, clindamycin and erythromycin. There were 238 strains of MDRB, mainly including 69 strains of Acinetobacter baumanii [multiple drug resistance rate (MDRR)=67.6%], 27 strains of Escherichia coli (MDRR=52.9%), 25 strains of Klebsiella pneumoniae (MDRR=34.2%), 33 strains of Pseudomonas aeruginosa (MDRR=33.0%) and 24 strains of Stenotrophomonas maltophilia (MDRR=100.0%). MDRR of Enterococcus genus and methicillin-resistant Staphylococcus aureus was 50.0% and 48.0%, respectively. Conclusions The pathogenic bacterias in elderly AECOPD patients complicated with pneumonia are mainly G– bacterias, and the proportion of fungal infection tends to increase. Bacterial drug resistance is serious and the MDRB tends to increase, especially in patients with HAP. Physicians should early find out the characteristics of local pathogenic bacteria and drug sensitivity, rationally select antibiotics, reduce the occurrence of drug-resistant strains and superinfection when treating the elderly patients with AECOPD complicated with pneumonia.
Objective To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 mg, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 mg Yinhuang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher’s exact test were used for categorical variables.Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild adverse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after administration of single-doses (40-560 mg) and multi-doses (240-400 mg once a day for consecutive 7 days). The maximum-tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recommended for phase II study.
Objective To probe the relationship between the patients′prognosis and the gene of multidrugs and drug resistance in uveal melanoma.Methods The gene expression of cyclin D1, epithelial growth factor receptor (EGFR), non-metastasis gene 23 (nm 23), P glucose protein (P-gp ) , multidrug resistance relation protein (MRP) and lung resistance protein (LRP) expression in 96 cases of uveal melanoma were detected by depigment immunohistochemistry. The patients with complete anamnesis data were observed continuously, and the follow-up results were classified. Results Among the 96 cases of uveal melanoma, the epithelioid cell type was in 21, the mixed cell type in 56, and the spindle cell type in 19 ; including 76 at intraocular stage and 20 at extraocular stage. As the level of metastasis suppress gene nm 23 expression decreased and the level of cyclin D1 and EGFR expression increased, the expression level of drug resistance genes increased. The levels of LRP and MRP had negative correlation to the expressions of nm 23 and postive correlation to the expressions of nm 23, Cyclin D1 and EGFR. In 58 patients′who were observed continuously, 19 died in 5 years and 26 survived over 5 years.Conclusion There are significant as sociation between patients′prognosis and multidrug and drug resistance gene in uveal melanoma.(Chin J Ocul Fundus Dis，2003，19：1-4)
目的 总结静脉制剂Ⅰ期临床耐受性试验中的护理要点。方法 2011年10月－12月，采用随机、盲法、安慰剂平行对照试验设计，在健康志愿者中按剂量递增原则，逐组完成8个剂量单次静脉滴注给药耐受性试验。 结果 试验顺利完成。静脉制剂的Ⅰ期耐受性试验中，研究护士在临床试验前需认真学习试验方案，做好试验病房、监护急救设施设备的充分准备，针对可能出现的不良反应制定切实可行的处理预案，试验过程中密切监测，对出现的不良反应做好救治工作。特别针对静脉制剂，须做好受试者的心理疏导，保证静脉穿刺一次成功，减少受试者因情绪紧张、穿刺疼痛等因素干扰对试验药物耐受性的评价。 结论 Ⅰ期临床耐受性试验实施前准备充分，试验过程中为受试者提供良好的试验环境和心理护理，提高静脉穿刺一次成功率，密切监测，可使试验过程顺利，并获得客观、准确的试验结果。