1.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
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Drugs, Chinese Herbal/therapeutic use*
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Hypertension/pathology*
;
Renin-Angiotensin System/drug effects*
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Rats, Inbred SHR
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Oxidative Stress/drug effects*
;
Male
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Rats, Inbred WKY
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Blood Pressure/drug effects*
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Myocardium/pathology*
;
Rats
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Inflammation/pathology*
2.Observation on the Therapeutic Effect of Jianpi Shuyan Decoction Combined with Thumbtack Needling Therapy for Chronic Sore Throat of Spleen-Qi Weakness Type
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2054-2061
Objective To explore the clinical efficacy of Jianpi Shuyan Decoction(mainly composed of Astragali Radix,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Angelicae Sinensis Radix,Pinelliae Rhizoma Praeparatum,Cortex Magnoliae Officinalis,Bombyx Batryticatus,and Platycodonis Radix)combined with thumbtack needling therapy(treated with thumbtack-type needle for subcutaneous embedding)in the treatment of chronic sore throat,i.e.,chronic pharyngitis,of spleen-qi weakness type.Methods Sixty-eight patients with chronic pharyngitis of spleen-qi weakness type were randomly divided into the control group and the trial group,with 34 patients in each group.The two groups were given buccal use of Cydiodine Buccal Tablets,and additionally,the trial group was treated with Jianpi Shuyan Decoction combined with thumbtack needling therapy at the six acupoints for pharyngeal disease,i.e.,Futu(LI18),Yamen(GV15),Lianquan(CV23),Tiantu(CV22),Lieque(LU7),and Zhaohai(KI6).Seven days constituted one course of treatment,and the two groups were treated for a total of two courses of treatment.One month and three months after the completion of treatment,the long-term follow-up of the patients was carried out.Before and after the treatment,the changes in visual analogue scale(VAS)score of the illness,inflammatory indicators of C-reactive protein(CRP)and interleukin 2(IL-2),and traditional Chinese medicine(TCM)syndrome scores in the two groups were observed.Moreover,the clinical efficacy,recurrence rate and clinical safety of the two groups were evaluated.Results(1)During the study,2 patients in each of the two groups fell off,and finally 32 patients in each group completed the whole course of treatment.(2)After 2 weeks of treatment,the total effective rate of the trial group was 90.63%(29/32),and that of the control group was 75.00%(24/32).The total effective rate(tested by chi-square test)and overall efficacy(tested by rank sum test)of the trial group were significantly superior to those of the control group(P<0.05).(2)After 2 weeks of treatment,the VAS score of the illness in the two groups was improved compared with that before treatment(P<0.05),and the improvement of the VAS scores in the trial group was significantly superior to that in the control group(P<0.05).(3)After 2 weeks of treatment,the levels of serum inflammatory indicators of CRP and IL-2 in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of serum CRP and IL-2 levels in the trial group was significantly superior to that in the control group(P<0.05).(4)After 2 weeks of treatment and one month and three months after the completion of treatment,the TCM syndrome scores of the two groups were lower than those before treatment(P<0.05),but the scores in the two groups one month after the completion of treatment did not differ from those three months after the completion of treatment(P>0.05).The intergroup comparison showed that the decrease of the scores in the trial group was significantly superior to that in the control group after two weeks of treatment and one month and three months after the completion of treatment(P<0.05).(5)During the treatment,there were no obvious adverse reactions occurring in the two groups and there were no obvious abnormalities in the safety indexes of blood routine test and liver and kidney function,with high safety.(6)The results of long-term follow-up showed that the recurrence rate of the trial group was 9.38%(3/32)and that of the control group was 18.75%(6/32),and the difference between the two groups was statistically significant(P<0.05).With the consideration of the changes of TCM syndrome scores in the two groups,it is indicated that the long-term efficacy of the trial group was significantly superior to that of the control group.Conclusion On the basis of buccal use of Cydiodine Buccal Tablets,the application of Jianpi Shuyan Decoction combined with thumbtack needling therapy at the six acupoints for pharyngeal disease exerts certain effectin the treatment of patients with chronic pharyngitis of spleen-qi weakness type.The combined therapy is more effective on relieving clinical symptoms,inhibiting inflammatory response and maintaining long-term efficacy than Cydiodine Buccal Tablets alone.
3.Approach to chronic cough in children.
Zai Ru CHENG ; Ying Xian CHUA ; Choon How HOW ; Yi Hua TAN
Singapore medical journal 2021;62(10):513-519
4.Studies on chemical constituents of Valeriana plants and their biological activities.
Ru-Jing WANG ; Qing HUANG ; Yan YONG ; Hong-Xiang LI ; Shi-Jing ZHANG ; Bao-Hua CHEN ; Li-Xia ZHU ; Yin CHEN ; Xin TANG ; Shan-Shan SONG ; Xiao-Ping DONG ; Yu-Zhu TAN ; Hai ZHANG
China Journal of Chinese Materia Medica 2016;41(8):1405-1414
The recent progresses on chemical components and pharmacological activities of the genus Valerianawere summarized.Besides-essential oil, the chemical composition of Valerianais mainly focused on monoterpenoids,sesquiterpenoids,lignans, flavonoids, alkaloids, etc. Iridoids are the main chemical components ofmonoterpenoids. There are two types ofiridoidson the basis of the cyclopentane open or not. The Valerianahas been drawmuch attention for their significant sedation,spasmolysis,antidepression,antitumor, against adenosine A1 receptors and cytotoxicityactivity,and had certain function for cardiovascular disease treatment. Given to the fact of the lack of systematic review and summary of studies on the Valeriana, we summarized and analyze the study literatures on the pharmacological activity of Valerianain recent years, and providedsome basisfor further study.
5.Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients.
Ying ZHENG ; Guang-Yan CAI ; Xiang-Mei CHEN ; Ping FU ; Jiang-Hua CHEN ; Xiao-Qiang DING ; Xue-Qing YU ; Hong-Li LIN ; Jian LIU ; Ru-Juan XIE ; Li-Ning WANG ; Zhao-Hui NI ; Fu-You LIU ; Ai-Ping YIN ; Chang-Ying XING ; Li WANG ; Wei SHI ; Jian-She LIU ; Ya-Ni HE ; Guo-Hua DING ; Wen-Ge LI ; Guang-Li WU ; Li-Ning MIAO ; Nan CHEN ; Zhen SU ; Chang-Lin MEI ; Jiu-Yang ZHAO ; Yong GU ; Yun-Kai BAI ; Hui-Min LUO ; Shan LIN ; Meng-Hua CHEN ; Li GONG ; Yi-Bin YANG ; Xiao-Ping YANG ; Ying LI ; Jian-Xin WAN ; Nian-Song WANG ; Hai-Ying LI ; Chun-Sheng XI ; Li HAO ; Yan XU ; Jing-Ai FANG ; Bi-Cheng LIU ; Rong-Shan LI ; Rong WANG ; Jing-Hong ZHANG ; Jian-Qin WANG ; Tan-Qi LOU ; Feng-Min SHAO ; Feng MEI ; Zhi-Hong LIU ; Wei-Jie YUAN ; Shi-Ren SUN ; Ling ZHANG ; Chun-Hua ZHOU ; Qin-Kai CHEN ; Shun-Lian JIA ; Zhi-Feng GONG ; Guang-Ju GUAN ; Tian XIA ; Liang-Bao ZHONG ; null
Chinese Medical Journal 2013;126(12):2276-2280
BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.
METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.
RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).
CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.
Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications
6.Emergency use of extracorporeal membrane oxygenation in pediatric critically ill patients.
Ru LIN ; Chen-mei ZHANG ; Lin-hua TAN ; Li-ping SHI ; Qi-xing XIONG ; Ee-wei ZHANG ; Qiang SHU ; Li-zhong DU
Chinese Journal of Pediatrics 2012;50(9):649-652
OBJECTIVEThe history of clinical application of extracorporeal membrane oxygenation (ECMO) has been more than 30 years. But in China, there were only a few ECMO centers with limited successful cases reported by the end of twentieth century. The high morbidities and mortalities in current pediatric ECMO practice are noted in China. Therefore, it is necessary to review the experience on rescue use of ECMO in critically ill pediatric patients.
METHODA retrospective analysis was done for patients who had been receiving ECMO treatment to rescue refractory cardiorespiratory failure from different causes in a hospital between July 2007 and May 2011.
RESULTA total of 12 patients were treated with ECMO; 7 of them were male and 5 female, they aged 6 days to 11 years, weighed 2.8 - 35 (17.21 ± 11.64) kg. The underlying causes of cardiorespiratory failure were as follows: two cases with acute respiratory distress syndrome (ARDS) leading to respiratory failure, 4 with failure of weaning from cardiopulmonary bypass, 3 with fulminant myocarditis, 1 with right ventricular cardiomyopathy leading to repeated cardiac arrest, 1 with preoperative severe hypoxemia, and 1 with anaphylactic shock complicated with massive pulmonary hemorrhage and severe hypoxemia. Of the 12 cases, 3 were established ECMO (E-CPR) while underwent chest compression cardiopulmonary resuscitation (CPR). The mean ECMO support time was 151.75 (15 - 572) h. Seven patients (58.33%) were weaned from ECMO, 6 patients (50.00%) were successfully discharged. Six cases had bleeding from sutures, 2 cases with severe bleeding underwent thoracotomy hemostasis, 2 presented with acute renal failure. Infection was documented in 3 cases, hyperbilirubinemia in 2 cases, lower limb ischemia in 1 case, hyperglycemia in 3 cases, disseminated intravascular coagulation in 1 case, membrane lung leakage in 2 cases, systemic hemolysis in 3 cases, oxygenator failure in 2 cases and oxygenator thrombosis in one case. During the follow-up between 6 months and 4.5 years, 5 patients survived with good quality of life, without any documented central nervous system disorders. One case survived with the right lower extremity disorder from ischemic damage. His motor function has been improved following orthopedic operation at one year after discharge.
CONCLUSIONECMO is a justifiable alternative treatment for reversible severe cardiopulmonary failure in critically ill children.
Cardiac Output, Low ; etiology ; therapy ; Cause of Death ; Child ; Child, Preschool ; Critical Illness ; mortality ; therapy ; Extracorporeal Membrane Oxygenation ; adverse effects ; Female ; Heart Failure ; etiology ; mortality ; therapy ; Hemorrhage ; epidemiology ; etiology ; Humans ; Infant ; Infant, Newborn ; Male ; Postoperative Complications ; mortality ; therapy ; Respiratory Insufficiency ; etiology ; mortality ; therapy ; Retrospective Studies ; Survival Analysis ; Thrombosis ; epidemiology ; etiology ; Treatment Outcome
7.Bicyclol protects rat thoracic aorta from superoxide anion-induced inhibition of vascular relaxation.
Xiao-Chen RU ; Ke-Yong LIANG ; Wen-Hua LEI ; Yi-Nuo TAN ; Qiang XIA
Chinese Journal of Applied Physiology 2011;27(1):81-85
OBJECTIVETo investigate the effect of bicyclol on vascular oxidative stress injury induced by superoxide anion.
METHODSRat thoracic aortic rings were isolated for isometric tension recording using organ bath technique. Superoxide arterial injury was induced by pyrogallol exposure, and the effect of bicyclol on endothelium-dependent relaxation was evaluated.
RESULTSBicyclol (10(-8) - 10(-5) mol/L) relaxed endothelium-intact aortic rings precontracted by phenylephrine. This effect was abolished by L-NAME, an inhibitor of nitric oxide synthase and indomethacin, an inhibitor of cyclooxygenase. Exposure to pyrogallol (500 micromol/L) resulted in decrease of acetylcholine(ACh)-induced endothelium-dependent relaxation in aortic rings, and pre-incubation of bicyclol (10(-5) mol/L) for 45 min improved the relaxation attenuated by pyrogallol. In aortic rings pre-treated with indomethacin, bicyclol increased the ACh-induced relaxation that was inhibited by pyrogallol (500 micromol/L). This effect was not found in aortic rings pre-treated with L-NAME.
CONCLUSIONBicyclol has endothelium-dependent vasodilating effect on rat thoracic aorta and improves vascular function by attenuating oxidative stress. Nitric oxide from endothelium is involved in the anti-oxidative effect of bicyclol.
Animals ; Antioxidants ; pharmacology ; Aorta, Thoracic ; metabolism ; physiology ; Biphenyl Compounds ; pharmacology ; Endothelium, Vascular ; physiology ; In Vitro Techniques ; Male ; Oxidative Stress ; drug effects ; Pyrogallol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxides ; pharmacology ; Vasodilation ; drug effects ; physiology
9.Extracorporeal membrane oxygenation treatment of a neonate with severe low cardiac output syndrome following open heart surgery.
Ru LIN ; Lin-hua TAN ; Ze-wei ZHANG ; Mei-yue SUN ; Li-zhong DU
Chinese Journal of Pediatrics 2008;46(1):26-29
OBJECTIVETo summarize the experience of extracorporeal membrane oxygenation (ECMO) to rescue a neonate with severe low cardiac output syndrome following open heart surgery.
METHODSThe patient was a male, 2 d, 2.8 kg, G3P2 full-term neonate with gestational age 40 weeks, born by Cesarean-section with Apgar score of 10 at 1 min. He was admitted due to severe dyspnea with oxygen desaturation and heart murmur on the second day after birth. Physical examination showed clear consciousness, cyanosis, dyspnea, RR 70 bpm and a grade II/6 heart murmur. Bp was 56/45 mm Hg (1 mm Hg = 0.133 kPa) and SpO2 around 65%. Blood WBC 13.1 x 10(9)/L, N 46.1%, Hb 238 g/L, Plt 283 x 10(9)/L, CRP < 1 mg/L. Echocardiographic findings: TGA + ASD + PDA with left ventricular ejection fraction (LVEF) of 60%. After supportive care and prostaglandin E1 (5 ng/kg/min) treatment, his condition became stable with SpO2 85 - 90%. On the 6(th) day of life, the baby underwent an arterial switch procedure + ASD closing and PDA ligation. The time of aorta clamp was 72 mins. The cool 4:1 blood cardioplegia was given for 2 times during aortal clamp. Ultrafiltration was used. The internal and external volumes were almost equal and the electrolytes and blood gas and hematocrit (36%) were normal during extracorporeal bypass. Due to a failure (severe low cardiac output) to wean from cardiopulmonary bypass (263 min) with acidosis (lactate 8.8 mmol/L), low blood pressure (< 39/30 mm Hg), increased LAP (> 20 mmHg), bloody phlegm, decreased urine output [< 1 ml/(kg.h)], a V-A ECMO was used for cardio-pulmonary support. ECMO setup: Medtronic pediatric ECMO package (CB2503R1), carmeda membrane oxygenator and centrifugal pump (bio-console 560) were chosen. Direct cannulation of the ascending aorta (Edward FEM008A) and right atrium (TF018090) was performed using techniques that were standard for cardiopulmanory bypass. The ECMO system was primed with 400 ml blood, 5% CaCl(2)1g, 5% sodium bicarbonate 1.5 g, 20% mannitol 2 g, albumin 10 g, and heparin 5 mg. The blood was re-circulated until the temperature was 37 degrees C and blood gases and the electrolytes were in normal range. The patient was weaned from bypass and connected to V-A ECMO. Management of ECMO: the blood flow was set at 150 - 200 ml/kg/min. Venous saturation (SvO2) was maintained at the desired level (75%) by increasing and decreasing extracorporeal blood flow. Systemic blood pressure was maintained at 76/55 - 80/59 mm Hg by adjusting blood volume. Hemoglobin was maintained between 120 - 130 g/L. Platelet count was maintained at > 75,000/mm3 and ACT was maintained at 120 - 190 s. The mechanical ventilation was reduced to lung rest settings (FiO2 35%, RR 10 bpm, PIP 16 cm H(2)O, PEEP 5 cm H2O) to prevent alveolar collapse. Inotropic drug dosages were kept at a low level.
RESULTSThe patient was successfully weaned from ECMO following 87 hours treatment. LVEF on day 1, 2 and 3 following ECMO were 20%, 34% and 43% respectively. The circulation was stable after weaning from ECMO with Bp 75/55 mm Hg, HR 160 bpm and LAP 11 mm Hg under inotropic drug suppor with epinephrine [(0.2 microg/(kg.min)], dopamine [(8 microg/(kg.min)], milrinone [(0.56 microg/(kg.min)]. The blood gases after 1 h off-ECMO showed: pH 7.39, PaO2 104 mm Hg, PaCO2 45 mm Hg, lactate 3.8 mmol/L, Hct 35%, K(+) 3.8 mmol/L, Ca(++) 1.31 mmol/L. The serum lactate was normal after 24 h off-ECMO. On day 22 off-ECMO, the baby was successfully extubated and weaned from conventional ventilator. On day 58, the patient was discharged. Serial ultrasound imaging studies revealed no cerebral infarction or intracranial hemorrhage during and after ECMO. At the time of hospital discharge, the patient demonstrated clear consciousness with good activity, normal function of heart, lung, liver and kidney. However, more subtle morbidities, such as behavior problems, learning disabilities should be observed ria long term follow-up. The main ECMO complications were pulmonary hemorrhage, bleeding on the sternal wound, tamponade, hemolysis and hyperbilirubinemia.
CONCLUSIONECMO is an effective option of cardio-pulmonary support for neonate with low cardiac output syndrome following open heart surgery.
Cardiac Output, Low ; etiology ; therapy ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; methods ; Extracorporeal Membrane Oxygenation ; methods ; Heart ; physiopathology ; Heart Septal Defects, Atrial ; therapy ; Hemodynamics ; Humans ; Infant ; Infant, Newborn ; Oxygenators, Membrane ; utilization ; Thoracic Surgery ; methods
10.XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.
Peng YUAN ; Xiao-ping MIAO ; Xue-mei ZHANG ; Zhong-hua WANG ; Wen TAN ; Yan SUN ; Xiang-ru ZHANG ; Bing-he XU ; Dong-xin LIN
Chinese Journal of Oncology 2006;28(3):196-199
OBJECTIVEDNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).
METHODSXRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.
RESULTSThe overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).
CONCLUSIONThose results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Cisplatin ; administration & dosage ; DNA Repair ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genotype ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; Polymorphism, Genetic ; Remission Induction ; Vinblastine ; administration & dosage ; analogs & derivatives ; X-ray Repair Cross Complementing Protein 1 ; Xeroderma Pigmentosum Group D Protein ; genetics

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