1.Efficacy analysis of total knee arthroplasty for severe genu varus combined with flexion deformity
Hao PENG ; Long OUYANG ; Dong YIN
Journal of Clinical Surgery 2014;(11):846-848
Objective To analyze the curative effects of total knee arthroplasty(TKA)for severe genu varus combined with flexion deformity.Methods The clinical data of 25 patients(36 knees),who had undergone TKA for severe genu varus combined with flexion deformity from January 2005 to October 2010,were retrospectively analyzed.There were 7 males and 18 females,aged from 55 to 80 years(average 70.5 years).The primary diseases were osteoarthritis in 22 cases and rheumatoid arthritis in 3 cases.HSS knee score was used before and after the operation to assess the efficacy of the TKA.Results All of the patients were followed up for 4 to 9 years(average 6 years).The degree of flexion deformity was reduced from (21 ±63)°to(1.1 ±2.3)°;the degree of the varus decreased from(210 ±4.8)°to(175.6 ±2.1)°;range of motion of the knee joint increased from(70.5 ±20.5)°to(115.1 ±5.3)°;knee score augmen-ted from(33.2 ±10.5)to(90.7 ±8.5);function score added from(35.5 ±14.2)to(85.6 ±10.5);there were 21 cases(8 knees)rated as excellent,2(3 knees)as good and 2(3 knees)as fair,and the excel-lent and good rate was 86%.Most of the patients had normal force line of the knee joint,but 2 patients re-mained varus deformity of 5°~10°.Conclusion Satisfying outcome can be achieved by TKA in treating severe genu varus combined with flexion deformity of the knee.
2.Impact of lymph node micrometastasis for the UICC stage in non-small cell lung carcinoma
Weiwei OUYANG ; Bing LU ; Chang HE ; Yiguo LONG ; Ping WANG
Chinese Journal of Radiation Oncology 1992;0(04):-
Objective To detect cytokeratin in routine pathology negative regional lymph nodes postoperatively in non-small cell lung carcinoma (NSCLC). To investigate the relationship of lymph node micrometastasis in P-TNM stages NSCLC and survival rates. Methods From Jan. 1996 to Dec. 2003, 107 paraffin-embedded specimens of T1-T4N0-N1M0 NSCLC patients were collected. Anti-cytokeratin(CK) an- tibody AE1/AE3 was applied to detect cytokeratin with Envision~(TM) method in routine pathological negative re- gion lymph nodes in NSCLC, and selected negative control, positive control and blank control. The pulmo- nary hilar lymph node micrometastasis was upward regulated with stage pCK-N1, mediastinal lymph node mi- crometastatsis was upward regulated with stage pCK-N2. The result applied to SPSS11.0 software to process. Results The CK positive rate was 29.9% in all the patients. The CK positive rate was 27% (21/78), 30% (7/23), 67% (4/6)in stage p-Ⅰ, p-Ⅱand p-Ⅲ, respectively. All these data showed the tendency by which detectable rate increased and was accompanied by disease progress. Comparing the annual survival rate and median survival time of the non-micrometastasis group with the mierometastasis group in two groups, the survival rate difference was statistically significant. Comparing the annual survival rate and median sur- vival time in pCK-ⅢA stage with p-Ⅰ-Ⅱstage, pCK-ⅢA stage annual survival rate and median survival time was significantly different (P=0.020). Similarly, comparing the survival rate in pCK-ⅡB stage with p-ⅠB stage, pCK-ⅡB stage survival rate was significantly different(P=0.059). Comparing the survival time of pCK-ⅢA stage with p-Ⅲstage, pCK-ⅡB stage, with p-ⅡB stage, euther survival time difference was statistically significant (P=0.838, 0.518). Conclusions The rate of positive cytokeratin increase is ac- companied by the disease progress in NSCLC. Positive cytokeratin has disadvantagious prognosis. It is showed that pCK-N1 may be equal to p-N1 and pCK-N2 which also may be equal to p-N2. Micrometastasis may affect the UICC staging currently in use.
3.Effect of electroacupuncture at Ganshu (BL 18) and Shenshu (BL 23) on the expression of EphB2 protein in cortex around cerebral infracted area of rat
Hongliang LI ; Juan XIANG ; Lizhi OUYANG ; Guo CHEN ; Zhihui XUE ; Kangsheng LONG ; Tielang LI
Journal of Acupuncture and Tuina Science 2017;15(1):14-21
Objective:To observe the effect of electroacupuncture (EA) on the expression of erythropoie-tin-producing hepatocyte receptor B2 (EphB2) in the cortex around the infracted area of middle cerebral artery occlusion (MCAO) rats at different timing, and to reveal the possible mechanism of acupuncture in the treatment of cerebral ischemia.
Methods:A total of 180 male Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, with 45 rats in each group. Rats in each group were further divided into three subgroups: postoperative 3 d, postoperative 14 d and postoperative 21 d groups, with 15 rats in each subgroup. The MCAO model was made by the modified occlusion method. The neurological function score, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, immunohistochemistry assay, immunofluorescence double labeling method and Western blot were used to detect the corresponding indicators.
Results:The neurological impairment of rats was most obvious at postoperative 3 d, and then gradually improved with time, which was more significant in the acupoint group (P<0.05). The change of infarcted volume was consistent with the neurological function impairment. The number of EphB2 positive cells (EphB2+) around the infarcted area was decreased significantly at postoperative 3 d, and then gradually improved with time, which returned to the same level as that in the sham operation group at postoperative 21 d. The increase was most significant in the acupoint group (P<0.05), and the positive cell number was higher than that in the sham operation group (P<0.01). Western blot and immunohistochemistry results were basically consistent. Immunofluorescence displayed that EphB2+ and postsynaptic density-95 positive (PSD-95+) were co-expressed, after the MCAO operation, in the cortical neuron around the infracted area, and the number of co-expressing cells was increased gradually with time, which was most significant in the acupoint group (P<0.05).
Conclusion:Electroacupuncture at Ganshu (BL 18) and Shenshu (BL 23) can significantly improve the neurological function and cerebral infarcted volume ratio of MCAO rats, which may be related to the activation of EphB2 expression in cortex around the infracted area and the promotion of synaptic remodeling.
4.Evaluation of volume overload in critical patients by monitoring change of cardiac output under bed head raising combined with passive leg raising
Long ZHANG ; Luhao WANG ; Weixiong LUO ; Meihua MEI ; Youjuan CHEN ; Bin OUYANG
Chinese Critical Care Medicine 2017;29(8):711-715
Objective To investigate whether the change of cardiac output (CO) with bed head raising (BHR) combined with passive leg raising (PLR) can be used to assess volume overload in critical patients.Methods A prospective observational diagnostic trial was designed. The patients who underwent fluid resuscitation 6 hours or more, and admitted to intensive care unit (ICU) of Meizhou People's Hospital in Guangdong Province from January to December in 2016 were enrolled. Volume overload were identified with the criteria including the increasing of pulmonary rales, the higher levels of N-terminal brain natriuretic peptide (NT-proBNP) and new pulmonary exudates in chest radiograph. CO and heart rate (HR) were monitored with impedance cardiography at supine position and BHR by 30°(BHR30), 60° (BHR60), and PLR in all patients. The changes of CO (?CO30,?CO60,?COPLR) and HR (?HR30,?HR60,?HRPLR) were calculated at different positions. The receiver operating characteristic curve (ROC) was used to evaluate the predictive values of?CO30,?CO60 and combination of?CO60 and?COPLR on volume overload.Results A total of 62 patients were enrolled in this study, with 44 males and 18 females, age of (58.9±15.9) years, a body mass index of (22.7±2.4) kg/m2, and an acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score of 18.7±4.4. The CO of 32 patients with volume overload was significantly increased at BHR30 or BHR60 compared with supine position [?CO30 was (14.5±11.5)%,?CO60 was (26.9±17.5)%, bothP< 0.01], and the?CO60 was increased more than the?CO30 (P < 0.01);while CO was slightly decreased after PLR,?COPLR was (-8.4±11.3)% (P > 0.05). There was no consistent change of CO at BHR30 or BHR60 compared with supine position in 30 patients without volume overload,?CO30 was (-3.4±9.1)% (P < 0.05),?CO60 was (-2.4±14.0)% (P > 0.05), while CO was significantly increased after PLR,?COPLR was (12.4±11.3)% (P < 0.01). There was no significant change of HR after BHR and PLR in patients with volume overload and non volume overload. ROC curve showed that when the cut-off value of ΔCO30≥3.3%, the area under ROC curve (AUC) was 0.903±0.039, the sensitivity was 90.6%, the specificity was 80.0%, and the accuracy was 85.5% for predicting volume overload; when the cut-off value of ΔCO60≥5.6%, the AUC was 0.911±0.036, the sensitivity was 96.9%, the specificity was 73.3%, and the accuracy was 85.5% for predicting volume overload. If volume overload was assessed by the increase of ΔCO60 combining with the decrease of ΔCOPLR, the AUC was 0.928±0.034, the optimal cut-off value for the new combined predictive indicator in predicting volume overload was -0.008, and the sensitivity, specificity, accuracy was 96.9%, 83.3%, 90.3%, respectively, and its evaluation effect is better than the use of ΔCO30 or ΔCO60 alone.Conclusion The change of CO with BHR combined with PLR can be used to accurately evaluate volume overload in patient with critically illness.
5.Efficacy observation of pelvic floor muscle training combined with traditional Chinese medicine in the treatment of mild-moderate pelvic organ prolapse
Jun LUO ; Ziting OUYANG ; Fei WU ; Wei CHENG ; Haiyan ZENG ; Ting LONG
Journal of Chinese Physician 2015;17(6):868-871,875
Objective To explore the rehabilitation effect of pelvic floor muscle training combined with traditional Chinese medicine in the treatment of mild-moderate pelvic organ prolapse.Methods A prospective ease-control study,choosing 103 patients of mild-moderate pelvic organ prolapse from October 2012 to May 2014 in Maternal and Child Health Hospital Outpatient of Hunan Province,which were randomly divided into study group (52 cases) and control group (51 cases).All of the patients underwent two courses of pelvic floor muscle training,including Kegel exercise,biofeedback,electrical stimulation therapy,the study group combined with traditional Chinese medicine (Buzhongyiqitang) at the same time.The efficacy was analyzed before and after treatment of pelvic floor muscle strength,myoelectric potential and indexing of pelvic organ prolapse quantification (POP-Q) changes.Results There werent statistically significant differences in type Ⅰ and Ⅲ muscle fiber muscle strength and myoelectric potential of two groups before treatment,while the shrinkage index improved significantly after treatment,and the study group was significantly higher with statistically significant difference (P < 0.05).The effective rates of POP-Q indexing changes in two groups were 71.2% and 56.9%,respectively.The effective rate of the study group was significantly higher than the control group(P < 0.05).Conclusions The clinical efficacy of pelvic floor muscle training combined with Buzhongyiqitang in the treatment of mild-moderate pelvic organ prolapse was significant,and it had a good clinical value.
6.The study on importance of three-dimensional radiotherapy for elderly patients with stage Ⅳ non small cell lung cancer
Bo ZHANG ; Bing LU ; Shengfa SU ; Yinxiang HU ; Weiwei OUYANG ; Huiqin LI ; Zhu MA ; Jinhua LONG
Chinese Journal of Radiation Oncology 2012;(6):504-507
Objective To evaluate the importance of three-dimensional radiotherapy for elderly patients of stage Ⅳ non-small cell lung cancer (NSCLC).Methods Comparing with treatment outcome of ≥65 years 67 patients and < 65 years 134 patients using concurrent chemotherapy and thoracic threedimensional radiotherapy during 2003 to 2010 years.Survival analysis was taken by Kaplan-Meier method.The multivariate prognosis was analyzed by Cox model.Results The follow-up was 97.8%.The percentage of ≥65 years and < 65 years patients accepted with concurrent 4-5 cycles chemotherapy were 30% and 55%,and with 42% and 49% patients with radiotherapy ≥63 Gy.The median survival time (MST) were 17 months and 14 months (x2 =0.76,P =0.384) for ≥65 years and < 65 years patients accepted with concurrent 4-5 cycles chemotherapy concurrent ≥63 Gy radiotherapy respectively.The MST and 1-,2-,3year overall survival rate were 17 months and 8 months,65% and 23%,30% and 13%,24% and 9%(x2 =7.90,P =0.005) for whole groups patients treated with chemotherapy concurrent ≥63 Gy and < 63 Gy radiotherapy.And the MST of patients ≥ 63 Gy was significantly longer than those with < 63 Gy either concurrent chemotherapy any cycles (x2 =9.54,P =0.023).The MST were 14 months and 8 months (x2 =1.82,P=0.178),17 months and 17 months (x2 =0.47,P=0.492) for ≥ 65 years and ≥ 63 Gy radiotherapy patients accepted with concurrent 4-5 cycles and 2-3 cycles chemotherapy concurrent respectively.Multivariate analysis showed local response (β =0.600,P =0.003) and numbers of tumor metastasis (β =0.670,P =0.040) were independent factors for survival.Conclusions For a part of elderly patients of stage Ⅳ NSCLC,concurrent chemotherapy and thoracic three-dimensional radiotherapy can prolong survival time with acceptable toxicity.Perhaps radiotherapy is more important.
7.Study on serum level of uric acid and on its relation with cognition function in elderly patients with Parkinson's disease
Tao LIU ; Feng CHEN ; Guoqiang WEN ; Feng OUYANG ; Zhigang LONG ; Tianlian LI ; Tao CHEN
Chinese Journal of Geriatrics 2011;30(8):629-631
Objective To explore the relationship between uric acid (UA) level and cognitive function in elderly patients with Parkinson,s disease (PD) and analyze the cognition related factors.Methods The clinical data of 60 elderly PD cases in our hospital from 2001 to 2009 were retrospectively analyzed. The 60 healthy people receiving medical examination in our hospital and matched by gender and age, were as control group. The information including gender, age, illness duration, Hoehn & Yahr stage (H-Y stage), serum UA level and Mini-Mental State Examination (MMSE) scale were recorded. Results The serum UA level was significantly lower in PD group than in control group [(262±53) μmol/L vs. (332±45) μmol/L, t=-6.724, P<0.001]. In PD group, the serum UA level was slightly higher in males than in females [(271 ±48) μmol/L vs.(254±39) μmol/L, t=3. 282, P=0. 058]. The serum UA level was significantly lower in male PD patients than in male controls [(353± 62) μmol/L, t=- 5. 625, P<0. 001], and was lower in female PD patients than in female controls [( 294 ± 59) μmol/L, t = - 4. 721, P = 0. 012]. There were no significant differences in serum UA level among different H-Y stage subgroups (P>0. 05), but the serum UA level was lower in different H-Y stage subgroups than in control group (F=22. 039, P<0. 01 ). There was no correlation between the UA level and the illness duration (r=0. 961, P>0.05).The MMSE score had significant difference between elderly PD group and control group (t= -3. 168,P<0. 001). In PD patients, the MMSE score was positively correlated with serum UA level (r=0. 789, P= 0. 000), and was negatively correlated with H-Y stage (r= - 0. 577, P = 0. 019 ), age (r= -0. 333, P=0. 034), but was not correlated with illness duration (r= -0. 333, P=0. 207) and BMI (t=- 0. 410, P= 0. 115). Conclusions The level of serum UA is lower in elderly patients with PD than in normal controls. There is correlation between the serum UA level and cognitive impairment. Lower serum UA level predicts worse cognitive scores.
8.A prospective study on concurrent chemotherapy and thoracic three - dimensional radiotherapy for stage Ⅳ non - small cell lung cancer ( 2 ) — The impact of different metastasis organs on survival
Gang WANG ; Bing LU ; Shengfa SU ; Weiwei OUYANG ; Yinxiang HU ; Jinhua LONG ; Huiqin LI ; Bo ZHANG
Chinese Journal of Radiation Oncology 2011;20(6):473-477
Objective To prospectively evaluate the survival of different metastasis organs with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC).Methods Two hundred and one patients of stage Ⅳ NSCLC were enrolled from January,2003 to July,2010.Of the 182 patients eligible for analysis,The number of patients with single-organ metastasis or multiple-organ metastasis was 107 and 75,respectively.Patients were treated by platinum-based chemotherapy,the median number of cycle was 4.The median dose to planning target volume of primary tumor (DTPTv) was 63 Gy.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Results The follow-up rate of 201 patients was 97.5%.with 201,170 and 134 patients finished < 1,1 -2 and ≥3 years'follow up.Of 182 patients,the 1-,2-,and 3-year overall survival (OS) rate and median survival time (MST) was 41.0%,17.0%,10.0% and 10.5 months,respectively ;with single-organ metastasis and multi-organ metastasis were 50%,20%,14% and 13 months and 29%,12%,0% and 8.5 months ( x2 =10.10,P =0.001 ),respectively; compared with multi-organ metastasis,the 1-,2-,and 3-year OS arte and MST of patients with bone,lung metastasis only was 58%,25%,16% and 14 months (x2 =10.42,P=0.001 ) and 49%,21%,21% and 11 months (x2 =6.39,P=0.011 ) respectively;patients with brain metastasis only did not show advantage of survival comparing with patients with multi-organ metastasis (49%,8%,0% and 12 months and 29%,12%,0% and 8 months,respectively;x2 =0.71,P =0.401 ) ;the 1-,2-,and 3-year OS rate and MST was 63%,23%,19% and 15 months and 42%,15%,0% and 10 months,respectively for patients with single-organ metastasis and multi-organ metastasis patients who accepted 4 - 5 cycles of chemotherapy ( x2 =6.47,P =0.011 ) ; for patients under the same metastasis and 4 - 5 cycles of chemotherapy,no matter whether single-organ or multiple-organ metastases,the 1 -,2-,3-year OS rate and MST of patients with enough radiotherapy on DTPTV ≥63 Gy were better than patients without enough radiotherapy ( DTPTV < 63 Gy ) ( 71%,25 %,25% and 16.8 months and 33%,17%,0% and 10.5 months,respectively;x2 =4.73,P =0.030 ;54%,21%,0% and 14.3 months and 29%,10%,0% and 7.6 months,respectively,x2 =8.16,P =0.004).The MST of liver metastases was 6 months,there was significantly difference when comparing with non liver matastasis ( x2 =17.21,P =0.000).Conclusions It is very important to treat stage Ⅳ NSCLC with CCTTRT,especially patients with single-organ metastasis.Liver metastases is a unfavorable prognostic factor.
9.A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage Ⅳ non-small cell lung cancer ( 1 )——survival and toxicity
Shengfa SU ; Bing LU ; Bo ZHANG ; Yinxiang HU ; Weiwei OUYANG ; Huiqin LI ; Gang WANG ; Jinhua LONG
Chinese Journal of Radiation Oncology 2011;20(6):467-472
Objective To evaluate the overall survival and safety among patients for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to July 2010,201 patients with stage Ⅳ NSCLC were included.All patients were treated with CCTTRT.Those patients who received only one cycle chemotherapy were not included in survival analysis,but analysis of toxicity.One hundred and eighty-two patients were eligible for survival analysis.All patients received platinum-based two-drug chemotherapy.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV ) was 63 Gy.Treatment-related gastrointestinal and hematological toxicity were scored according to WHO criteria.Radiation-related pneumonitis and esophagitis were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) version 3.0.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Cox regression model was used to examine the effect of CCTTRT on overall survival.Results The follow-up rate of 201 patients was 97.5%.with 201,170 and 134 patients finished < 1,1 -2 and ≥3 years' follow-up,respectively.Of the 182 patients eligible for survival analysis,further stratified analysis showed that the 1-,2-and 3-year overall survival rate and median survival time (MST) was 54%,20%,13% and 14.3 months,respectively for patients treated with concurrent 4 -5 cycles chemotherapy and CCTTRT,and 66%,23%,19% and 16.1 months,respectively for those treated with 4 -5 cycles chemotherapy and DTPTV ≥ 63 Gy.Under similar chemoradiotherapy intensity,the MST of patients with single organ metastasis was significantly longer than that with multiple organ metastases ( 13.0 months versus 8.5 months,x2 =10.10,P =0.001 ).For patients eligible for survival analysis and received 4 - 5 cycles of systemic chemotherapy,MST of patients treated with DTPTV≥63 Gy was significantly longer than those treated with DTPTV <63 Gy[14.9 months vs.8.4 months (x2 =20.48,P =0.000) and 16.1 months vs.8.8 months ( x2 =11.75,P =0.001 )].For patients with single organ metastasis,MST was 16 months for those treated with DTPTV ≥63 Gy and 9 months for those with DTPTV <63 Gy (x2 =10.51,P=0.000) ;for patients with multiple organ metastasis,it was 11 months and 7 months,respectively ( x2 =7.90,P =0.005 ).Multivariate analysis showed that concurrent 4 - 5 cycles chemotherapy and DTPTV ≥63 Gy (β =0.243,P=0.019) and improved KPS (β =1.268,P=0.000) were independent factors for survival.For the whole group,45% patients had Grade 2 -3 gastrointestinal toxicity,35.0% grade 3- 4 leukopenia,18% grade 3- 4 thrombocytopenia.15.0% grade 3- 4 anemia,9.5% Grade 2 - 3 radiation pneumonia and 13.4% radiation esophagitis,respectively.Conclusions For stage Ⅳ NSCLC,CCTTRT can prolong survival time with acceptable toxicity.Radiotherapy to thoracic primary tumor should be under consideration.
10.A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage Ⅳ non-small cell lung cancer (4)-The impact of response on survival
Bo ZHANG ; Bing LU ; Shengfa SU ; Weiwei OUYANG ; Yinxiang HU ; Gang WANG ; Jinhua LONG ; Huiqin LI
Chinese Journal of Radiation Oncology 2012;21(1):29-34
ObjectiveTo prospectively investigate the impact of short-time response on survival of concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC). Methods From Jan.2003 to Oct.2010,201 patients with pathologically or cytologically proven stage Ⅳ NSCLC were included.All patients received platinum-based chemotherapy.Of the 167 patients eligible for analysis,the median number of chemotherapy were 4 cycles.The median dose for planning target volume (PTV) of thoracic primary tumor was 63 Gy.Response was scored according to WHO criteria. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model were used to examine the effect of response on overall survival.ResultsThe follow-up rate of 201 patients was 97.5%.with 201,170 and 134 patients finished < 1,1 -2 and ≥3 years' follow-up.For the 167 patients eligible for analysis,the CR,PR,NC and PD rate of primary tumor was 5.4%,65.9%,21.0% and 7.7%,respectively.The effective group ( CR + PR) and ineffective group ( NC + PD) was 71.3% and 28.7%,respectively.The median survival time (MST) for patients with CR,PR,NC and PD was 22.6,13.4,8.8 and 4.8 months,respectively ( χ2 =44.79,P =0.000).The MST for effective and ineffective group was 13.9 and 7.6 months,respectively in the whole group ( χ2 =8.3 0,P =0.004 ),12.1months and 7.3 months in those treated with 2 - 3 cycles chemotherapy ( χ2 =7.71,P =0.007 ),and 13.9months and 7.9 months in those treated with 2 -5 cycles chemotherapy and radiation dose to PTV ≥36 Gy ( χ2 =4.00,P =0.045 ).No significant MST difference was detected between patients of effective group and ineffective group treated with 4 -5 cycles chemotherapy ( χ2 =0.67,P =0.413),or those treated with 4 -5 cycles of chemotherapy and radiation dose to primary lesion ≥36 Gy (χ2 =0.00,P =0.956).Multivariate analysis showed that 4-5 cycles of chemotherapy and CR and PR achieved in primary tumor (β =0.182,P=0.041 ) were independent favorable factors for survival. Conclusion CCTTRT can improve local control,and prolong the survival time for Stage Ⅳ NSCLC.