In 2005, a program named "Early Detection and Early Treatment of Esophageal and Cardiac Cancer" (EDETEC) was initiated in China. A total of 8279 residents aged 40-69 years old were recruited into the EDETEC ...In 2005, a program named "Early Detection and Early Treatment of Esophageal and Cardiac Cancer" (EDETEC) was initiated in China. A total of 8279 residents aged 40-69 years old were recruited into the EDETEC program in Linzhou of Henan Province between 2005 and 2008. Howerer, the cost-benefit of the EDETEC program is not very clear yet. We conducted herein a cost-benefit analysis of screening for esophageal and cardiac cancer. The assessed costs of the EDETEC program included screening costs for each subject, as well as direct and indirect treatment costs for esophageal and cardiac severe dysplasia and cancer detected by screening. The assessed benefits of this program included the saved treatment costs, both direct and indirect, on esophageal and cardiac cancer, as well as the value of prolonged life due to screening, as determined by the human capital approach. The results showed the screening cost of finding esophageal and cardiac severe dysplasia or cancer ranged from $2707 to $4512, and the total cost on screening and treatment was $13 115-$14 920. The cost benefit was $58 944-$155 110 (the saved treatment cost, $17 730, plus the value of prolonged life, $41 214-$137 380). The ratio of benefit-to-cost (BCR) was 3.95-11.83. Our results suggest that EDETEC has a high benefit-to-cost ratio in China and could be instituted into high risk areas of China.展开更多
Objective: To evaluate the feasibility of DNA image cytometry (DNA-ICM) as a primary screening method for esophageal squamous cell cancer (ESCC). Methods: A total of 5,382 local residents aged 40-69 years from t...Objective: To evaluate the feasibility of DNA image cytometry (DNA-ICM) as a primary screening method for esophageal squamous cell cancer (ESCC). Methods: A total of 5,382 local residents aged 40-69 years from three high-risk areas in China (Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province) from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol's iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity (SE), specificity (SP), negative predictive values (NPV) and positive predictive values (PPV) as well as their 95% confidence intervals (95% CI) for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic (ROC) curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results: DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions (X2= 18.016, P〈0.001). The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test (cutoff point 5,803) combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance (ASCUS)] were separately 72.1% (95% CI: 70.3%-73.9%), 43.3% (95% CI. 41.3%-45.3%), 22.8% (95% CI: 21.1%-24.5%) and 87.0% (95% CI: 85.7%-88.3%) for LGIN, 85.7% (95% CI: 84.3%-87.1%), 41.3% (95% CI: 39.3%-43.3%), 4.6% (95% CI: 3.8%-5.4%) and 98.9% (95% CI: 98.5%-99.3%) for HGIN, and 96.0% (95% CI: 95.2%-96.8%), 40.8% (95% CI: 38.8%-42.8%), 1.7% (95% CI: 1.2%-2.2%) and 99.9% (95% CI: 99.8%-100.0%) for ESCC. Conclusions: It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.展开更多
Objective: Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods: Costs per hospitalization of all p...Objective: Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods: Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness (ACI)was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars(1 USD:6.6423 RMB).Results: Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions: The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.展开更多
Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relations...Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients.Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival.Results: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.展开更多
Objective: To explore the natural history of severe dysplasia/carcinoma in situ(SD/CIS) patients and to evaluate the efficacy of endoscopic treatment to SD/CIS patients.Methods: Between January 2005 and December 2009,...Objective: To explore the natural history of severe dysplasia/carcinoma in situ(SD/CIS) patients and to evaluate the efficacy of endoscopic treatment to SD/CIS patients.Methods: Between January 2005 and December 2009, a population-based prospective screening program on esophageal squamous cell carcinoma(ESCC) was performed in Linzhou, China, with endoscopic screening plus iodine staining. All the eligible histologically confirmed SD/CIS patients were followed up through the door-todoor follow-up and local cancer registry. The endpoint was diagnosed as ESCC or the December 31 st, 2016.Kaplan-Meier survival analysis and Log-rank test were used to compare the survival rates among treated and untreated patients.Results: A total of 175 SD/CIS patients were enrolled and grouped by whether they received endoscopic treatment. Eleven-year cumulative incidence rates for untreated and treated SD/CIS patients were 10.7% [95%confidence interval(95% CI): 6.9-16.1] and 3.2%(95% CI: 1.4-7.0), respectively. The ESCC incidence free survival rate, and all-cause incidence and mortality free survival rates were all significantly higher in the treated patients vs. untreated patients(P=0.043, P=0.008 and P=0.015, respectively). The ESCC mortality free survival rate showed no significant differences between the two groups(P=0.847).Conclusions: The cumulative incidence rate of SD/CIS patients to ESCC was much lower than previously reported. The Kaplan-Meier survival analysis showed that endoscopic treatment could increase the ESCC and allcause disease-free survival rates of SD/CIS patients significantly.展开更多
AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Unzhou, Henan Province, China. METHODS: A...AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Unzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P〈0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P〈0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.展开更多
Background:Risk-stratified endoscopic screening(RSES),which offers endoscopy to those with a high risk of esophageal cancer,has the potential to increase effectiveness and reduce endoscopic demands compared with the u...Background:Risk-stratified endoscopic screening(RSES),which offers endoscopy to those with a high risk of esophageal cancer,has the potential to increase effectiveness and reduce endoscopic demands compared with the universal screening strategy(i.e.,endoscopic screening for all targets without risk prediction).Evidence of RSES in high-risk areas of China is limited.This study aimed to estimate whether RSES based on a 22-score esophageal squamous cell carcinoma(ESCC)risk prediction model could optimize the universal endoscopic screening strategy for ESCC screening in high-risk areas of China.Methods:Eight epidemiological variables in the ESCC risk prediction model were collected retrospectively from 26,618 individuals aged 40-69 from three high-risk areas of China who underwent endoscopic screening betweenMay 2015 and July 2017.The model’s performance was estimated using the area under the curve(AUC).Participants were categorized into a high-risk group and a low-risk group with a cutoff score having sensitivities of both ESCC and severe dysplasia and above(SDA)at more than 90.0%.Results:The ESCC risk prediction model had an AUC of 0.80(95% confidence interval:0.75-0.84)in this external population.We found that a score of 8(ranging from 0 to 22)had a sensitivity of 94.2% for ESCC and 92.5% for SDA.The RSES strategy using this threshold score would allow 50.6% of endoscopies to be avoided and save approximately US$0.59 million compared to universal endoscopic screening among 26,618 participants.In addition,a higher prevalence of SDA(1.7%vs.0.9%),a lower number need to screen(60 vs.111),and a lower average cost per detected SDA(US$3.22 thousand vs.US$5.45 thousand)could have been obtained by the RSES strategy.Conclusions:The RSES strategy based on individual risk has the potential to optimize the universal endoscopic screening strategy in ESCC high-risk areas of China.展开更多
基金supported by Key Projects in the National Science & Technology Pillar Program (No.2006BAI02 A15)
文摘In 2005, a program named "Early Detection and Early Treatment of Esophageal and Cardiac Cancer" (EDETEC) was initiated in China. A total of 8279 residents aged 40-69 years old were recruited into the EDETEC program in Linzhou of Henan Province between 2005 and 2008. Howerer, the cost-benefit of the EDETEC program is not very clear yet. We conducted herein a cost-benefit analysis of screening for esophageal and cardiac cancer. The assessed costs of the EDETEC program included screening costs for each subject, as well as direct and indirect treatment costs for esophageal and cardiac severe dysplasia and cancer detected by screening. The assessed benefits of this program included the saved treatment costs, both direct and indirect, on esophageal and cardiac cancer, as well as the value of prolonged life due to screening, as determined by the human capital approach. The results showed the screening cost of finding esophageal and cardiac severe dysplasia or cancer ranged from $2707 to $4512, and the total cost on screening and treatment was $13 115-$14 920. The cost benefit was $58 944-$155 110 (the saved treatment cost, $17 730, plus the value of prolonged life, $41 214-$137 380). The ratio of benefit-to-cost (BCR) was 3.95-11.83. Our results suggest that EDETEC has a high benefit-to-cost ratio in China and could be instituted into high risk areas of China.
基金granted by the National Natural Science Foundation of China (No.81241091)
文摘Objective: To evaluate the feasibility of DNA image cytometry (DNA-ICM) as a primary screening method for esophageal squamous cell cancer (ESCC). Methods: A total of 5,382 local residents aged 40-69 years from three high-risk areas in China (Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province) from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol's iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity (SE), specificity (SP), negative predictive values (NPV) and positive predictive values (PPV) as well as their 95% confidence intervals (95% CI) for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic (ROC) curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results: DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions (X2= 18.016, P〈0.001). The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test (cutoff point 5,803) combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance (ASCUS)] were separately 72.1% (95% CI: 70.3%-73.9%), 43.3% (95% CI. 41.3%-45.3%), 22.8% (95% CI: 21.1%-24.5%) and 87.0% (95% CI: 85.7%-88.3%) for LGIN, 85.7% (95% CI: 84.3%-87.1%), 41.3% (95% CI: 39.3%-43.3%), 4.6% (95% CI: 3.8%-5.4%) and 98.9% (95% CI: 98.5%-99.3%) for HGIN, and 96.0% (95% CI: 95.2%-96.8%), 40.8% (95% CI: 38.8%-42.8%), 1.7% (95% CI: 1.2%-2.2%) and 99.9% (95% CI: 99.8%-100.0%) for ESCC. Conclusions: It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.
基金supported by the Special Fund for Health Research in the Public Interest (No. 201502001)
文摘Objective: Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods: Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness (ACI)was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars(1 USD:6.6423 RMB).Results: Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions: The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.
基金supported by the National Key R&D Program “Precision Medicine” of China (Grant No. 2016YFC0901403)the Major Science and Technology Projects of Henan Province (Grant No. 16110031 1300)+2 种基金the Doctoral Team Foundation of the First Affiliated Hospital of Zhengzhou University (Grant No. 2016-BSTDJJ-03)the National Natural Science Foundation of China (Grant No. 81872032, U1804262)the State Key Laboratory of Esophageal Cancer Prevention and Treatment (Grant No. Z2020-0010)。
文摘Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients.Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival.Results: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.
基金supported by the National Key Research and Development Program of China (No. 2016YFC 0901404)the Youth Research Fund by Peking Union Medical College (No. 2017310044)+1 种基金the National Natural Science Foundation of China (No. 81573224)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2017PT32001 and 2016ZX310178)
文摘Objective: To explore the natural history of severe dysplasia/carcinoma in situ(SD/CIS) patients and to evaluate the efficacy of endoscopic treatment to SD/CIS patients.Methods: Between January 2005 and December 2009, a population-based prospective screening program on esophageal squamous cell carcinoma(ESCC) was performed in Linzhou, China, with endoscopic screening plus iodine staining. All the eligible histologically confirmed SD/CIS patients were followed up through the door-todoor follow-up and local cancer registry. The endpoint was diagnosed as ESCC or the December 31 st, 2016.Kaplan-Meier survival analysis and Log-rank test were used to compare the survival rates among treated and untreated patients.Results: A total of 175 SD/CIS patients were enrolled and grouped by whether they received endoscopic treatment. Eleven-year cumulative incidence rates for untreated and treated SD/CIS patients were 10.7% [95%confidence interval(95% CI): 6.9-16.1] and 3.2%(95% CI: 1.4-7.0), respectively. The ESCC incidence free survival rate, and all-cause incidence and mortality free survival rates were all significantly higher in the treated patients vs. untreated patients(P=0.043, P=0.008 and P=0.015, respectively). The ESCC mortality free survival rate showed no significant differences between the two groups(P=0.847).Conclusions: The cumulative incidence rate of SD/CIS patients to ESCC was much lower than previously reported. The Kaplan-Meier survival analysis showed that endoscopic treatment could increase the ESCC and allcause disease-free survival rates of SD/CIS patients significantly.
基金Supported by the National Outstanding Young Scientist Award of China, No. 30025016State Key Project for Basic Research, No. G1998051206Foundation of Henan Education Committee 1999125 the US NIH Grant, No. CA65871
文摘AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Unzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P〈0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P〈0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.
基金National Key R&D Program of China,Grant/Award Number:2018YFC1313100Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation,Grant/Award Number:J200017+2 种基金Sanming Project of Medicine in Shenzhen,Grant/Award Number:SZSM201911015Special Fund for Health Research in the Public Interest,Grant/Award Number:201502001Major State Basic Innovation Program of the Chinese Academy of Medical Sciences,Grant/Award Numbers:2016-12M-2-004,2019-I2M-2-004。
文摘Background:Risk-stratified endoscopic screening(RSES),which offers endoscopy to those with a high risk of esophageal cancer,has the potential to increase effectiveness and reduce endoscopic demands compared with the universal screening strategy(i.e.,endoscopic screening for all targets without risk prediction).Evidence of RSES in high-risk areas of China is limited.This study aimed to estimate whether RSES based on a 22-score esophageal squamous cell carcinoma(ESCC)risk prediction model could optimize the universal endoscopic screening strategy for ESCC screening in high-risk areas of China.Methods:Eight epidemiological variables in the ESCC risk prediction model were collected retrospectively from 26,618 individuals aged 40-69 from three high-risk areas of China who underwent endoscopic screening betweenMay 2015 and July 2017.The model’s performance was estimated using the area under the curve(AUC).Participants were categorized into a high-risk group and a low-risk group with a cutoff score having sensitivities of both ESCC and severe dysplasia and above(SDA)at more than 90.0%.Results:The ESCC risk prediction model had an AUC of 0.80(95% confidence interval:0.75-0.84)in this external population.We found that a score of 8(ranging from 0 to 22)had a sensitivity of 94.2% for ESCC and 92.5% for SDA.The RSES strategy using this threshold score would allow 50.6% of endoscopies to be avoided and save approximately US$0.59 million compared to universal endoscopic screening among 26,618 participants.In addition,a higher prevalence of SDA(1.7%vs.0.9%),a lower number need to screen(60 vs.111),and a lower average cost per detected SDA(US$3.22 thousand vs.US$5.45 thousand)could have been obtained by the RSES strategy.Conclusions:The RSES strategy based on individual risk has the potential to optimize the universal endoscopic screening strategy in ESCC high-risk areas of China.