1.Correlation of FBXL5 and IREB2 with iron homeostasis and efficacy of neoadju-vant chemotherapy in colorectal cancer
Miaomiao WANG ; Ruizhe ZHANG ; Xiaoyang XU ; Shuang HE ; Feifei WEN ; Yangyang LI ; Shuhua WU
Chinese Journal of Clinical and Experimental Pathology 2025;41(10):1280-1290
Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P<0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P<0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P<0.05)and negatively correlated with the expression of FBXL5 and FTH1(P<0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P<0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P<0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P<0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P<0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P<0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.
2.Correlation of FBXL5 and IREB2 with iron homeostasis and efficacy of neoadju-vant chemotherapy in colorectal cancer
Miaomiao WANG ; Ruizhe ZHANG ; Xiaoyang XU ; Shuang HE ; Feifei WEN ; Yangyang LI ; Shuhua WU
Chinese Journal of Clinical and Experimental Pathology 2025;41(10):1280-1290
Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P<0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P<0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P<0.05)and negatively correlated with the expression of FBXL5 and FTH1(P<0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P<0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P<0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P<0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P<0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P<0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.
3.Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022
Qijun SHAN ; Xudong MA ; Yujie CHEN ; Guanghua ZHOU ; Sifa GAO ; Jialu SUN ; Fuping GUO ; Feng ZHANG ; Dandan MA ; Guoqiang SUN ; Wen ZHU ; Xiaoyang MENG ; Guiren RUAN ; Yuelun ZHANG ; Xutong TAN ; Dawei LIU ; Yi WANG ; Chang YIN ; Xiang ZHOU
Chinese Medical Journal 2025;138(5):562-567
Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.
4.Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022
Qijun SHAN ; Xudong MA ; Yujie CHEN ; Guanghua ZHOU ; Sifa GAO ; Jialu SUN ; Fuping GUO ; Feng ZHANG ; Dandan MA ; Guoqiang SUN ; Wen ZHU ; Xiaoyang MENG ; Guiren RUAN ; Yuelun ZHANG ; Xutong TAN ; Dawei LIU ; Yi WANG ; Chang YIN ; Xiang ZHOU
Chinese Medical Journal 2025;138(5):562-567
Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.
5.Effects of intervention in autophagy regulation of p62-Keap1/Nrf2-GPX4 pathway on ferroptosis and oxaliplatin resistance in colorectal cancer cells
Lei XU ; Han WU ; Miaomiao WANG ; Ruizhe ZHANG ; Feifei WEN ; Xiaoyang XU ; Shuhua WU
Chinese Journal of Clinical and Experimental Pathology 2024;40(2):133-144
Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P<0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P<0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P<0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P<0.05).There was no significant difference between Fer-1 group and con-trol group(P<0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P<0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.
6.Analysis of factors influencing stone recurrence and establishment of risk prediction model after laparoscopic common bile duct exploration combined with laparoscopic cholecystectomy
Xiaoyang ZHANG ; Hanxiang YU ; Junye WEN ; Wenjuan BAO ; Xing XU ; Yige SHI
Chinese Journal of Hepatobiliary Surgery 2024;30(10):766-770
Objective:To explore the risk factors for stone recurrence after laparoscopic common bile duct exploration (LCBDE) combined with laparoscopic cholecystectomy (LC) and to develop a risk prediction model.Methods:Clinical data of 344 patients with bile duct stones who underwent LCBDE combined with LC at Hebei General Hospital from January 2016 to March 2022 were retrospectively analyzed, including 165 males and 179 females, aged (62.72±13.56) years old. Patients were divided into two groups based on whether stones recurred during the follow-up period: recurrence group ( n=37) and non-recurrence group ( n=307). Clinical data such as common bile duct diameter, stone size, number of stones and duration of T-tube drainage were collected from the patients. Logistic regression was used to analyze the risk factors for postoperative stone recurrence, and then developed a logistic regression model. The predictive efficacy of the model was assessed by the area under the receiver operating characteristic (ROC) curve, and the Hosmer-Lemeshow test. Results:The results of multifactorial logistic regression analysis showed that patients with ≥2 choledochal stones had a high risk of stone recurrence after LCBDE combined with LC ( OR=3.094, 95% CI: 1.069-8.954, P=0.037). In contrast, regular postoperative oral choleretic medication was a protective factor for stone recurrence after LCBDE combined with LC ( OR=0.160, 95% CI: 0.072-0.354, P=0.001). A logistic regression model, based on the number of common bile duct stones and regular postoperative oral choleretic medication, was developed to predict the recurrence of bile duct stones in patients who underwent LCBDE combined with LC. The area under the ROC curve for this model was found to be 0.821 (95% CI: 0.758-0.885). The Hosmer-Lemeshow test, χ 2=7.26, P=0.509, suggested that there is good agreement between the model's predicted probabilities and ideal probabilities. Conclusions:The number of stones (≥2) is an independent risk factor for stone recurrence after LCBDE combined with LC in patients with bile duct stones. Regular postoperative oral choleretic medication is a protective factor for stone recurrence after LCBDE combined with LC. Predictive models based on the number of choledochal stones and regular postoperative oral choleretic medication have better efficacy in predicting postoperative stone recurrence.
7.Analysis of five-wind differentiation and treatment system of tic disorder based on the "manifestation-qi transformation" theory
Wenbo LIU ; Wenli SHI ; Bingxiang MA ; Xiaoyang TIAN ; Yudi LI ; Yingying WEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1075-1080
Tic disorder (TD) is a neurodevelopmental disorder. According to the core symptoms,it can be classified as "liver wind","wind syndrome",and "concurrent". The clinical syndrome of TCM is based on wind,and the pathogenesis is based on the liver. However,the clinical symptoms of this disease are relatively complicated. Based on the " manifestation-qi transformation" theory,this study further explores the liver wind,lung wind,heart wind,spleen wind,and kidney wind from the pathological basis of intrinsic wind rash movement and proposes that the liver wind caused by hyperactivity of liver yang is the main cause of intrinsic wind rash movement in TD,and the lung wind caused by lung loss is the main cause. The liver is related to the heart,spleen,and kidney. Together,the five-wind affect the onset,development,and outcome of TD. Based on this understanding of the pathogenesis,it is necessary to identify the specific syndromes of the patients. The five-wind differentiation and treatment system uses the method of calming the liver and dispelling the lungs to treat the root of the internal wind rash movement. Xiaochaihu Decoction,Sangju Decoction,Cang'erzi Powder,and other prescriptions can be used with modification and subtract and use method of controlling heart fire,transporting spleen soil,and nourishing kidney water to treat derived images. Meanwhile,Xieqing Pill,Daochi Powder,Yigong Powder,Erchen Decoction,Liuwei Dihuang Pill,and other prescriptions can be used with modification.
8.Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies.
Zhenan DENG ; Meiling JIN ; Changxing OU ; Wei JIANG ; Jianping ZHAO ; Xiaoxia LIU ; Shenghua SUN ; Huaping TANG ; Bei HE ; Shaoxi CAI ; Ping CHEN ; Penghui WU ; Yujing LIU ; Jian KANG ; Yunhui ZHANG ; Mao HUANG ; Jinfu XU ; Kewu HUANG ; Qiang LI ; Xiangyan ZHANG ; Xiuhua FU ; Changzheng WANG ; Huahao SHEN ; Lei ZHU ; Guochao SHI ; Zhongmin QIU ; Zhongguang WEN ; Xiaoyang WEI ; Wei GU ; Chunhua WEI ; Guangfa WANG ; Ping CHEN ; Lixin XIE ; Jiangtao LIN ; Yuling TANG ; Zhihai HAN ; Kian Fan CHUNG ; Qingling ZHANG ; Nanshan ZHONG
Chinese Medical Journal 2023;136(2):230-232
9.Dosimetric comparison of intensity-modulated photon radiotherapy and intensity-modulated proton radiotherapy for non-small cell lung cancer
Lu LIU ; Yuxiang WANG ; Hefei LIU ; Mei WEN ; Hong NIE ; Xiaoyang LI ; Tengfei LONG
Cancer Research and Clinic 2023;35(6):429-433
Objective:To investigate the difference of dose distribution between intensity-modulated photon radiotherapy (IMRT) and intensity-modulated proton radiotherapy (IMPT) in patients with non-small cell lung cancer.Methods:The clinical data of 8 patients with stage Ⅱ-Ⅲ non-small cell lung cancer who received radiotherapy in Ion Medical center of the First Affiliated Hospital of University of Science and Technology of China from November 2020 to April 2022 were retrospectively analyzed. IMRT and IMPT radiotherapy plans were created for each patient separately, the main evaluation indicators were targeted area dose distribution parameters [homogeneity index (HI), conformity index (CI) and the percent volume of volume wrapped by 95% and 100% of prescription dose profile in the targeted area (V 95% and V 100%)], and the average dose (D mean) to the organ at risk and the percent volume of a certain relative biological effect (RBE) dose exposure [D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of ipsilateral lung, D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of bilateral lung, D mean, V 30 Gy(RBE) and V 40 Gy(RBE) of heart, maximum dose (D max) of spinal cord, and D mean of esophageal]. Results:In comparison with IMRT, IMPT reduced the levels of dose parameters in bilateral lung, ipsilateral lung, spinal cord, esophagus, and heart with statistically significant differences (all P < 0.05), especially in D mean of bilateral lung [(4.1±1.8) Gy (RBE) vs. (6.9±1.9) Gy (RBE)], V 5 Gy(RBE) [(15.9±7.1) % vs. (28.5±8.6)%], V 20 Gy(RBE) [(7.4±3.5)% vs. (10.1±3.5)%], and D mean of ipsilateral lung [(9.1±4.5) Gy (RBE) vs. (11.9±3.3) Gy (RBE)], all decreased significantly (all P < 0.001), but the differences in the levels of targeted area dose distribution parameters between them were not statistically significant (all P > 0.05). Conclusions:For patients with non-small cell lung cancer, IMPT is superior to IMRT in the protection of bilateral lung, ipsilateral lung, spinal cord, esophagus and heart.
10.Evaluation of ICUs and weight of quality control indicators: an exploratory study based on Chinese ICU quality data from 2015 to 2020.
Longxiang SU ; Xudong MA ; Sifa GAO ; Zhi YIN ; Yujie CHEN ; Wenhu WANG ; Huaiwu HE ; Wei DU ; Yaoda HU ; Dandan MA ; Feng ZHANG ; Wen ZHU ; Xiaoyang MENG ; Guoqiang SUN ; Lian MA ; Huizhen JIANG ; Guangliang SHAN ; Dawei LIU ; Xiang ZHOU
Frontiers of Medicine 2023;17(4):675-684
This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans
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China/epidemiology*
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Cross Infection/epidemiology*
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Intensive Care Units/statistics & numerical data*
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Quality Control
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Quality Indicators, Health Care/statistics & numerical data*
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Sepsis/therapy*
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East Asian People/statistics & numerical data*

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