1.Cost-effectiveness analysis of insulin degludec and insulin aspart in Chinese patients with type 2 diabetes mellitus
Jiali QIN ; Yawen ZHANG ; Lei ZHANG ; Shan JIANG ; Xiaoyan YOU ; Xiaomei WANG ; Xianying WANG
China Pharmacy 2025;36(22):2809-2814
OBJECTIVE To evaluate the long-term cost-effectiveness of insulin degludec and insulin aspart (IDegAsp) in patients with type 2 diabetes mellitus (T2DM) in China. METHODS A cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system, using the CORE diabetes model to simulate long-term (20-year) health and economic outcomes. Baseline cohort characteristics and treatment effect data were derived from the CREATE study. The prices of glucose- lowering drugs were obtained from medical insurance payment standards and the average winning bid prices in the follow-up round of the specialized centralized procurement for insulin, while the daily dosages were derived from the CREATE study. The costs of complications and utility values were obtained from published literature, with a discount rate of 5%. One-way sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis were performed to verify the robustness of the results. RESULTS Patients switching from previous once-daily basal insulin regimens to IDegAsp therapy gained an incremental 0.190 quality-adjusted life year (QALY) with direct medical cost savings of 42 163.58 yuan. For those switching from premixed insulin therapies, IDegAsp treatment provided 0.130 incremental QALY and reduced direct healthcare costs by 41 129.11 yuan. The outcome was significantly influenced by the discount rate and the cost of complications. Probabilistic sensitivity analysis and scenario analysis confirmed the robustness of these findings. CONCLUSIONS Switching from previous daily basal insulin or premixed insulin regimens to IDegAsp in Chinese patients with T2DM can improve patients’ long-term health outcomes and achieve cost savings, making it a more cost-effective treatment option.
2.Association of physical activity level and all-cause mortality among stroke survivors: evidence from NHANES 2007-2018.
Fude LIU ; Xiangning HAN ; Yawen CHENG ; Ning ZHU ; Shiliang JIANG ; Jiahao LI ; Jin ZHAO ; Guogang LUO
Environmental Health and Preventive Medicine 2025;30():27-27
BACKGROUND:
Post-stroke disability diminishes the physical activity (PA) level of survivors, potentially affecting their long-term prognosis. This study endeavors to explore the correlation between daily PA level and the all-cause mortality in patients with a history of stoke in the United States.
METHODS:
Data of stroke survivors were sourced from the National Health and Nutritional Examination Survey (NHANES) 2007-2018. The population was stratified into three groups based on their PA level. Kaplan-Meier method with log-rank tests for significance was used for survival analysis. Weighted Cox proportional hazards regression models were employed to estimate the hazard ratios (HRs) for all-cause mortality. Subgroup analysis was conducted to strengthen the results.
RESULTS:
A total of 1395 participants were recruited, comprising 679 males and 716 females, with a median age of 68 years. Based on their PA levels, 779 individuals were classified as inactive, 156 as insufficiently active, and 460 as sufficiently active. Following a median observation period of 59 months, there were 476 recorded deaths, with 349, 47, and 80 cases in the three respective groups. Compared to the inactive group, the HRs and 95% confidence intervals (CIs) for all-cause mortality in participants who were insufficiently active and sufficiently active were 0.58 (0.40, 0.84) and 0.47 (0.33, 0.67), respectively. The Kaplan-Meier curve revealed a significant difference in overall survival between the three groups, as confirmed by the log-rank test (P < 0.0001). Subgroup analysis further validated our results and demonstrated that the protective impact of PA on stroke prognosis varies according to distinct characteristics.
CONCLUSIONS
The results indicate that increased levels of PA are associated with a protective effect on long-term mortality among stroke survivors. Further prospective longitudinal studies are necessary to elucidate the optional PA level and special exercise guideline targeting this population.
Humans
;
Male
;
Female
;
Aged
;
Exercise
;
Middle Aged
;
Nutrition Surveys
;
Stroke/mortality*
;
United States/epidemiology*
;
Survivors/statistics & numerical data*
;
Aged, 80 and over
;
Mortality
3.An empirical study on the effect of influenza vaccination on the prevention of school absence among primary and secondary school students
LI Wu, LIU Lanlan, TAN Huiling, JIANG Yawen, CHEN Wanyi, ZHUANG Chunyan, XIE Yuanna, XIE Xu, LI Gang
Chinese Journal of School Health 2024;45(12):1775-1779
Objective:
To evaluate the preventive effect of implementing the free influenza vaccination policy on school absence among primary and secondary school students, so as to provide a reference for formulating and adjusting vaccination strategies.
Methods:
Among primary and secondary school students aged 6 to 18 in Longgang District, Shenzhen, they were divided into a vaccinated group (265 996 students) and an unvaccinated group (122 513 students) according to their influenza vaccination history during November 2023. Propensity score matching was used to conduct a 1∶1 match between the two groups to balance covariates. The number of absences per month was set as the dependent variable to construct a difference in differences model, and Poisson regression was employed to analyze the overall and multi time point effects.
Results:
Vaccination against influenza was associated with low rate of absenteeism among primary and secondary school students, with an overall preventive effect of 26.52% (95% CI = 23.47% -29.45%). The preventive effects in November (the month of vaccination) and December 2023, January and March 2024 were 42.12%, 40.12%, 30.33% and 20.91%, respectively. The preventive effect of the influenza vaccine on absenteeism among primary school students (26.39%) was not significantly different from that among secondary school students ( 27.97% ) ( P >0.05). The regression coefficient for class vaccination rates ranged from 0.998 to 0.999 ( P <0.01), indicating that for every 10% increase in influenza vaccination rates, absenteeism could be reduced by 1.5% to 2.2%.
Conclusion
Implementing free influenza vaccination for primary and secondary school students might help to reduce the risk of absenteeism, yielding significant socioeconomic benefits.
4.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
5.Correlation between neutrophil/lymphocyte ratio and carotid atherosclerosis in pa-tients with hypertension in the morning
Qian SHU ; Cui ZHAO ; Yumei FENG ; Haisen JIANG ; Yawen CAO ; Wei LI ; Qiuping XIN ; Xiangyu GUO
Chinese Journal of Arteriosclerosis 2024;32(11):979-984,993
Aim To explore the correlation between carotid atherosclerosis(CAS)and neutrophil/lymphocyte ratio(NLR)in patients with early morning hypertension,and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning.Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected,and their basic data,blood routine and blood biochemical indexes were collected.All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection.According to the presence or absence of CAS,all selected patients were divided into morning hypertension with CAS group(n=197)and morning hypertension without CAS group(n=58).Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS,and to construct and verify an individual line chart model to predict the risk of early morning hypertension pa-tients with CAS.Results The age,NLR,neutrophils(NE),monocytes(MO),white blood cell(WBC),total cho-lesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDLC)increased in the early morning hyperten-sion with CAS group compared with those in the morning hypertension group without CAS,while the HDLC decreased(P<0.05).The results of multivariate Logistic regression analysis showed that the age,NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group,while HDLC was lower;Age,NLR and TC were independent risk factors of early morning hypertension with CAS,while HDLC was inde-pendent protective factors of morning hypertension with CAS.Based on the results of multivariate Logistic regression anal-ysis,an individualized line chart model for predicting early morning hypertension with CAS was constructed.The area un-der the ROC curve of the line chart model was 0.853(95%CI:0.802-0.904,P<0.01).The result of Hosmer Leme-show fit test was x2=1.665(P>0.05).Conclusions There was a positive correlation between NLR and morning hy-pertension with CAS,and NLR was an independent risk factor for morning hypertension with CAS.The individualized line chart model based on age,NLR,TC and HDLC can effectively predict the risk of hypertension with CAS in the early morn-ing,which provides a theoretical basis for early detection and prevention of atherosclerosis.
6.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
7.Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia
Guochang XUE ; Huali ZHANG ; Xuexing DING ; Fu XIONG ; Yanhong LIU ; Hui PENG ; Changlin WANG ; Yi ZHAO ; Huili YAN ; Mingxing REN ; Chaoying MA ; Hanming LU ; Yanli LI ; Ruifeng MENG ; Lingjun XIE ; Na CHEN ; Xiufang CHENG ; Jiaojiao WANG ; Xiaohong XIN ; Ruifen WANG ; Qi JIANG ; Yong ZHANG ; Guijuan LIANG ; Yuanzheng LI ; Jianing KANG ; Huimin ZHANG ; Yinying ZHANG ; Yuan YUAN ; Yawen LI ; Yinglin SU ; Junping LIU ; Shengjie DUAN ; Qingsheng LIU ; Jing WEI
Chinese Journal of Pediatrics 2024;62(6):535-541
Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).
8.Evaluation on professional competencies and development of teachers for health in primary and secondary schools in Shanghai
HOU Xiaojing, JIANG Xingwen, SUN Yawen
Chinese Journal of School Health 2022;43(6):941-945
Objective:
To evaluate the self awareness of professional competencies and its development of teachers for health in primary and secondary schools in Shanghai, so as to provide a reference for development of professional competencies and future specialized development.
Methods:
A survey was conducted among 1 722 teachers for health in primary and secondary school by the professional competency questionnaire.
Results:
Most of the teachers for health had bachelor s degrees (65.6%) and junior professional titles (43.4%), the full time teachers accounted for 66.5%, the percentage of teaching health education courses was 69.8 %, 7.7% took part in the formal class of schedule; the two top scorers were the dimension of "professional ethic as a teacher" and "school public health prevention and control" (4.68±0.43, 4.55±0.47); the two lowest scorers dimensions were related to school health education with increasing standard deviation (3.96±0.66, 3.91±0.65); the mean of self rated competency of the 6-14 years working experience group was slightly higher in all dimensions, that of 15 years or above group was lower than 6-14 years group in the total system and the dimensions of professional ethic as a teacher and emergency handling of accidents, and in responsing specific health problems dimension, the mean of 15 years or above group lower than that of 1-5 years group ( P <0.05).
Conclusion
The entry threshold of teachers for health in primary and secondary school is a critical consideration; Teachers competency preparations are satisfying in professional ethics and school public health prevention/control; meanwhile, the overall health education competencies were insufficient, and noticeable differences in the competency level among teachers are observed. It suggest drawing up entry qualifications and professional standards for health education teachers to guide the teacher s learning and improvement, calling for facilitating the professional promotion of teachers at the government s policy level.
9.Characterization of highly active tyrosine ammonia lyase and its application in biosynthesis of p-coumaric acid.
Yawen HUANG ; Xiaolong JIANG ; Wujiu CHEN ; Guimin ZHANG ; Qinhong WANG
Chinese Journal of Biotechnology 2022;38(12):4553-4566
p-coumaric acid is one of the aromatic compounds that are widely used in food, cosmetics and medicine due to its properties of antibacterium, antioxidation and cardiovascular disease prevention. Tyrosine ammonia-lyase (TAL) catalyzes the deamination of tyrosine to p-coumaric acid. However, the lack of highly active and specific tyrosine ammonia lyase limits cost-effective microbial production of p-coumaric acid. In order to improve biosynthesis efficiency of p-coumaric acid, two tyrosine ammonia-lyases, namely Fc-TAL2 derived from Flavobacterium columnare and Fs-TAL derived from Flavobacterium suncheonense, were selected and characterized. The optimum temperature (55 ℃) and pH (9.5) for Fs-TAL and Fc-TAL2 are the same. Under optimal conditions, the specific enzyme activity of Fs-TAL and Fc-TAL2 were 82.47 U/mg and 13.27 U/mg, respectively. Structural simulation and alignment analysis showed that the orientation of the phenolic hydroxyl group of the conserved Y50 residue on the inner lid loop and its distance to the substrate were the main reasons accounting for the higher activity of Fs-TAL than that of Fc-TAL2. The higher activity and specificity of Fs-TAL were further confirmed via whole-cell catalysis using recombinant Escherichia coli, which could convert 10 g/L tyrosine into 6.2 g/L p-coumaric acid with a yield of 67.9%. This study provides alternative tyrosine ammonia-lyases and may facilitate the microbial production of p-coumaric acid and its derivatives.
Ammonia-Lyases/chemistry*
;
Coumaric Acids
;
Escherichia coli/genetics*
;
Tyrosine
10.Based on a Markov model, cost-effectiveness analysis of influenza vaccination among people aged 60 years and older in Shenzhen
Xiaoliang WU ; Zhaojia YE ; Xu XIE ; Fang HUANG ; Dongfeng KONG ; Tiejian FENG ; Shunxiang ZHANG ; Yawen JIANG
Chinese Journal of Epidemiology 2022;43(7):1140-1146
Objective:To assess the cost-effectiveness of influenza vaccination among people aged 60 years and older in Shenzhen.Methods:A Markov state transition model was constructed to evaluate the cost-effectiveness of annual influenza vaccination for preventing influenza infection compared with no vaccination among the elderly from the social perspective. Allowing seasonal variation of influenza activity, the model followed a five-year cohort using weekly cycles. We employed once the Chinese gross domestic product (GDP) per capita in 2019 (70 892 yuan) as the willingness-to-pay (WTP) threshold and calculated the net monetary benefit (NMB) with costs and quality-adjusted life-years (QALYs) discounted at 5% annually. The impact of parameter uncertainty on the results was examined using one-way and probabilistic sensitivity analyses (PSA).Results:The base case amounted to approximately 35 yuan of cost-saving and a net gain of 0.007 QALYs. Correspondingly, the NMB was 529 yuan per vaccinated person. One-way sensitivity analyses showed that the NMB was relatively sensitive to changes in the attack rate of influenza and vaccine effectiveness. Based on the results of PSA with 1 000 Monte Carlo simulations, influenza vaccination had a probability of being cost-effective in 100% of the repetitions.Conclusions:The present study provides evidence that influenza vaccination is a cost-saving disease prevention strategy for people aged 60 years and older in Shenzhen.


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