1.Development and validation of nomogram and neural network prediction models for stroke-associated pneumonia in patients with acute stroke
Fengchen GAO ; Haimei SUN ; Fuqiang ZHOU ; Weixiang LI ; Siting HUA ; Xuejun LONG ; Ruifei WANG
International Journal of Cerebrovascular Diseases 2025;33(3):173-179
Objectives:To investigate the predictive factors of stroke associated-pneumonia (SAP) in patients with acute stroke, develop nomogram and neural network prediction models and verify their predictive performance.Methods:Patients with acute stroke admitted to the First Affiliated Hospital of Kunming Medical University and Zhenxiong County People's Hospital were included retrospectively. Multivariate logistic regression analysis was used to determine the independent predictive factors of SAP, and develop nomogram and neural network prediction models. Receiver operating characteristic curve (ROC) curves were used to validate and compare the predictive performances. Results:A total of 450 patients with acute stroke were enrolled, including 286 males (63.6%), aged 64.28±13.24 years; 344 patientss (76.4%) had ischemic stroke and 106 (23.6%) had hemorrhagic stroke; 128 patients (28.4%) experienced SAP. According to the random number method, they were divided into a modeling cohort ( n=300) and a validation cohort ( n=150). Multivariate logistic regression analysis in the modeling cohort showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher neutrophil/lymphocyte ratio (NLR) were the independent predictive factors of SAP. ROC curve analysis showed that the area under the ROC curve of the nomogram model for predicting SAP in the modeling cohort and validation cohort was 0.841 (95% confidence interval [ CI] 0.795-0.880) and 0.863 (95% CI 0.798-0.914), respectively. The sensitivity for predicting SAP were 75.00% and 70.45%, respectively, and the specificity was 81.94% and 92.45%, respectively. The area under the ROC curve of the neural network model for predicting SAP in the modeling cohort and validation cohort was 0.847 (95% CI 0.802-0.866) and 0.862 (95% CI 0.796-0.913), respectively. The sensitivity for predicting SAP were 76.19% and 72.73%, and the specificity was 79.17% and 89.62%, respectively. Conclusions:Higher NIHSS score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher NLR are the independent risk factors for SAP in patients with acute stroke. The nomogram and neural network prediction model developed using the above risk factors have higher predictive value for SAP.
2.Clinical Study on Jiangzhi Hugan Soft Extract for Treating Non-Alcoholic Fatty Liver Disease with Internal Dampness-Turbidity Accumulation Syndrome
Siting LI ; Jiangtao ZENG ; Huangbin LI ; Hongmiao WU ; Lingjie LI ; Wanying CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(9):2156-2161
Objective To evaluate the clinical efficacy and safety of Jiangzhi Hugan Soft Extract(composed of stir-fried Dioscoreae Rhizoma,Poria,Ginseng Radix et Rhizoma,Bupleuri Radix,Citri Sarcodactylis Fructus,Persicae Semen,Polygoni Cuspidati Rhizoma,etc.)in treating non-alcoholic fatty liver disease(NAFLD)with internal dampness-turbidity accumulation syndrome.Methods Sixty patients with NAFLD of dampness-turbidity accumulation syndrome treated at the Gastroenterology Department of Maoming Hospital of Guangzhou University of Chinese Medicine(Maoming Hospital of Traditional Chinese Medicine)from November 2023 to December 2024 were enrolled.The patients were divided into trial group and control group using stratified randomization,with 30 patients in each group.Both groups received lifestyle interventions(diet control and exercise),with the trial group additionally receiving Jiangzhi Hugan Soft Extract for 4 weeks.Outcomes included body mass index(BMI),liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT)],lipid profiles[total cholesterol(TC),triglycerides(TG)],traditional Chinese medicine(TCM)syndrome scores,efficacy evaluation,and safety assessment.Results(1)After 4 weeks of treatment,the overall response rate in the trial group was 93.33%(28/30),while that in the control group was 60.00%(18/30).The intergroup comparison(by rank sum test)showed that the efficacy of TCM syndrome in the trial group was significantly superior to that in the control group,with a statistically significant difference(P<0.01).(2)After treatment,the BMI of patients in both groups was improved significantly compared to before treatment(P<0.01).The improvement in BMI was significantly greater in the trial group than in the control group.The difference in the change of BMI between the two groups was statistically significant before and after treatment(P<0.05).(3)After treatment,the levels of ALT,AST,and GGT in both groups decreased compared to before treatment(P<0.01).The trial group showed a significantly greater reduction in ALT,AST,and GGT levels than the control group.The difference between the two groups was statistically significant before and after treatment(P<0.05).(4)After treatment,both groups showed a significant decrease in TC and TG levels compared to pre-treatment levels(P<0.05).The trial group demonstrated a more pronounced reduction in TC levels than the control group.The difference between the two groups was statistically significant before and after treatment(P<0.05).(5)There were no significant adverse reactions occurring in either group during treatment,indicating a high level of safety.Conclusion Jiangzhi Hugan Soft Extract effectively improves BMI,liver function,and lipid profile in NAFLD patients with dampness-turbidity accumulation syndrome,demonstrating good clinical efficacy and high safety,warranting further clinical application.
3.Clinical significance of CD105 and EPHA2 expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on their expressions
Yun GAO ; Haipeng YAO ; Siting XU ; Bo YANG ; Wenhua YU ; Zhongqun WANG ; Lihua LI
Cancer Research and Clinic 2025;37(7):481-487
Objective:To investigate the clinical significance of CD105 and erythropoietin-producing hepatocellular receptor A2 (EPHA2) expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on CD105 and EPHA2 expressions.Methods:A retrospective case series study was conducted. A total of 74 patients with breast invasive ductal carcinoma in Affiliated Hospital of Jiangsu University from June 2019 to June 2024 were selected, and paraffin specimens from the patients after surgery were collected. Immunohistochemistry SP method was used to detect the expressions of CD105 and EPHA2 proteins in specimens. CD105 expression was expressed as the number of CD105 labeled microvessels, and EPHA2 expression was expressed as the proportion of EPHA2 positive expression area. The correlation of CD105 and EPHA2 expressions with the clinicopathological characteristics and diabetes mellitus of patients, as well as the relationship between the expressions of CD105 and EPHA2 were analyzed. Cox proportional hazards model was used to make univariate and multivariate analysis of the factors influencing overall survival of patients.Results:All 74 patients were female. The median age was 60 years old, 44 patients (59.46%) had tumor grade ≥ grade 3, 36 patients (48.65%) had tumor diameter ≥ 2 cm, 28 patients (37.84%) had lymph node metastasis, 30 patients (40.54%) had nerve vessel invasion, and 32 patients (43.24%) had diabetes mellitus. There were statistically significant differences in the proportion of patients with different age, tumor diameter, TNM stage, lymph node metastasis or not and nerve vessel invasion or not between diabetes mellitus group and non-diabetes mellitus group (all P < 0.05). The number of CD105 marking the microvessel was (32±9) and (24±8), respectively in diabetes mellitus group and non-diabetes mellitus group, and the difference was statistically significant ( t = 3.63, P < 0.010); the positive expression area proportion of EPHA2 was (19±5)% and (15±4)%, respectively, and the difference was statistically significant ( t = 3.85, P < 0.010). The expression of CD105 was related to the duration of diabetes mellitus, tumor diameter, TNM stage and lymph node metastasis or not (all P < 0.05), and the expression of EPHA2 was related to tumor diameter and TNM stage (all P < 0.05). Pearson correlation analysis showed a positive correlation between CD105 and EPHA2 expression ( r = 0.75, P < 0.001). The differences in overall survival of patients with or without diabetes mellitus and patients with different CD105 and EPHA2 expressions were statistically significant (all P < 0.05). Multivariate analysis showed that CD105 expression ( HR = 1.10, 95% CI: 1.04-1.16, P = 0.001) and EPHA2 expression ( HR = 1.35, 95% CI: 1.10-1.66, P = 0.005) were independent factors influencing the overall survival of patients with breast invasive ductal carcinoma. Conclusions:The expressions of CD105 and EPHA2 are independent prognostic factors in patients with breast invasive ductal carcinoma, and diabetes mellitus can promote the expressions of CD105 and EPHA2, which may increase the risk of poor prognosis.
4.Clinical characteristics of Pneumocystis carinii pneumonia complicated with acute respiratory failure in 123 immunocompromised patients
Xiuhua LIN ; Jiaping LIN ; Yixian SHI ; Siting ZHANG ; Xin LIN ; Lei CHEN ; Hui LI ; Baosong XIE
Chinese Journal of Infection and Chemotherapy 2025;25(3):248-253
Objective To investigate the risk factors for acute respiratory failure in immunocompromised patients with Pneumocystis jirovecii pneumonia(PJP).Methods Clinical data of 123 immunocompromised patients complicated with PJP hospitalized at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2021 to December 2023 were retrospectively collected and analyzed.SPSS 22.0 statistical software package was used to perform multivariate binary logistic regression analysis to identify risk factors for acute respiratory failure in PJP patients.Results Among the 123 PJP patients,77 were HIV-positive,and 46 were HIV-negative.HIV-negative PJP patients were more likely to have comorbidities such as hypertension(P<0.001),diabetes mellitus(P<0.001),coronary heart disease(P=0.034),chronic kidney disease(P<0.001),chronic liver disease(P=0.019),chronic lung disease(P=0.011),and malignant tumor(P<0.001).They were also more prone to respiratory failure(P<0.001)and ICU admission(P<0.001).The HIV-positive patients had significantly lower CD4+T lymphocyte counts and albumin levels(P<0.001).Forty patients developed acute respiratory failure,and six patients died.Multivariate analysis showed that high neutrophil-to-lymphocyte ratio(NLR)(P=0.031),non-HIV infection(P=0.002),and concomitant infections with other pathogens(P<0.001)were independent risk factors for incidence of respiratory failure.ROC curve analysis revealed that the area under the curve(AUC)was 0.686(0.584,0.789)for non-HIV infection,0.731(0.637,0.826)for concomitant infections with other pathogens,0.648(0.546,0.750)for NLR.The predicted probability was 0.845(0.778,0.912).Conclusions Non-HIV infection,high NLR,and concomitant infections with other pathogens are independent risk factors for incidence of respiratory failure in PJP patients.The panel combining these factors provides a higher predictive value for respiratory failure.Timely assessment of patient condition and early treatment are vital for better outcomes.
5.Sodium tanshinone ⅡA sulfonate inhalation attenuates pulmonary hyper-tension associated with chronic obstructive pulmonary disease in mice
Runhua HOU ; Siting WANG ; Hongping ZHANG ; Ruanyuan YE ; Zeping YANG ; Mengzhu LI ; Guanqing ZHEN ; Jiarui FAN ; Chunyun ZHANG ; Rui CHEN ; Defu LI
Chinese Journal of Pathophysiology 2025;41(9):1713-1720
AIM:To investigate the effects of nebulized sodium tanshinone ⅡA sulfonate(STS)in a mouse model of pulmonary hypertension associated with chronic obstructive pulmonary disease(COPD-PH).METHODS:A to-tal of 32 healthy SPF-grade male C57BL/6 mice were randomly divided into 4 groups:control(CTL,n=8)group,COPD-PH(CS+LPS,n=8)group,STS-treated COPD-PH(CS+LPS+STS,n=8)group,and STS(n=8)group.The COPD-PH model was established through whole-body exposure to cigarette smoke(CS)combined with lipopolysaccharide(LPS)in-halation.Mice were subjected to cigarette smoke exposure in a chamber(9 cigarettes/h,2 h/session,2 sessions/d,6 d/week)for 60 d,except on days of LPS inhalation.On days 1 and 14,COPD-PH model mice received LPS(7.5 μg/mouse in 50 μL saline)via intranasal inhalation,while the CTL and STS groups received an equivalent volume of saline.STS was administered via nebulized inhalation(5 mg/kg,30 min per session,twice daily)immediately before CS exposure.At the end of the modeling period,lung function and right heart pressure were assessed.Bronchoalveolar lavage fluid(BALF)was collected for inflammatory cell counting.Levels of interleukin-6(IL-6)in BALF supernatants and plasma were measured using ELISA.Pathological changes in the airway and lung tissues were evaluated.RESULTS:(1)Com-pared to CTL mice,those exposed to CS and LPS exhibited lesions characteristic of COPD-PH,including emphysema,lung inflammation,decreased lung function,and increased right ventricular systolic pressure(RVSP)and right ventricu-lar hypertrophy index(RVHI)(P<0.05);(2)COPD-PH mice showed significantly elevated IL-6 levels in both BALF and plasma(P<0.05);(3)STS treatment alleviated emphysema and lung inflammation,improved lung function,prevent-ed increases in RVSP and the RV/(LV+S)ratio,and reduced IL-6 levels in both BALF and plasma(P<0.05).CON-CLUSION:The results indicate that nebulized inhalation of STS significantly slows the progression of COPD-PH,likely due to its ability to inhibit lung inflammation and reduce IL-6 expression in the lungs.
6.Quality of life of early esophageal cancer patients after endoscopic mucosal dissection and its influencing factors analysis
Xiaoping LYU ; Yina YANG ; Qingtian LI ; Siting GAO ; Peng CHEN ; Tongjun DONG
Chinese Journal of Modern Nursing 2025;31(8):1089-1093
Objective:To analyze the factors affecting quality of life in patients with early esophageal cancer after endoscopic submucosal dissection (ESD) .Methods:Convenience sampling was used to select 162 early esophageal cancer patients with ESD in Cangzhou Central Hospital from August 2021 to July 2023 who had an on-time follow-up six months as study subjects. General Information Questionnaire and Quality of Life Instruments for Cancer Patients-Esophageal Cancer (QLICP-ES) were used to investigate the patients. Factors affecting the quality of life of patients after ESD for early esophageal cancer were analyzed using univariate analysis and multiple linear regression analysis.Results:Univariate analysis showed statistically significant differences in QLICP-ES scores among patients with different gender, age, marital status, annual income, medical payment method, concomitant diseases, degree of infiltration, vascular invasion, surgical complications, and positive margins ( P<0.05). Multiple linear regression analysis showed that age, marital status, concomitant diseases, vascular invasion, surgical complications, and positive margins were the factors influencing the QLICP-ES scores of patients with ESD for early esophageal cancer, and the differences were statistically significant ( P<0.05) . Conclusions:Quality of life at six months after ESD in patients with early esophageal cancer is at an intermediate to high level. Patients of advanced age, unmarried/divorced/widowed, concomitant diseases, vascular invasion, surgical complications and positive margins have low QLICP-ES scores after ESD for early esophageal cancer. It is recommended that clinical attention be focused on these factors and that targeted nursing measures be taken when necessary.
7.Clinical characteristics of Pneumocystis carinii pneumonia complicated with acute respiratory failure in 123 immunocompromised patients
Xiuhua LIN ; Jiaping LIN ; Yixian SHI ; Siting ZHANG ; Xin LIN ; Lei CHEN ; Hui LI ; Baosong XIE
Chinese Journal of Infection and Chemotherapy 2025;25(3):248-253
Objective To investigate the risk factors for acute respiratory failure in immunocompromised patients with Pneumocystis jirovecii pneumonia(PJP).Methods Clinical data of 123 immunocompromised patients complicated with PJP hospitalized at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2021 to December 2023 were retrospectively collected and analyzed.SPSS 22.0 statistical software package was used to perform multivariate binary logistic regression analysis to identify risk factors for acute respiratory failure in PJP patients.Results Among the 123 PJP patients,77 were HIV-positive,and 46 were HIV-negative.HIV-negative PJP patients were more likely to have comorbidities such as hypertension(P<0.001),diabetes mellitus(P<0.001),coronary heart disease(P=0.034),chronic kidney disease(P<0.001),chronic liver disease(P=0.019),chronic lung disease(P=0.011),and malignant tumor(P<0.001).They were also more prone to respiratory failure(P<0.001)and ICU admission(P<0.001).The HIV-positive patients had significantly lower CD4+T lymphocyte counts and albumin levels(P<0.001).Forty patients developed acute respiratory failure,and six patients died.Multivariate analysis showed that high neutrophil-to-lymphocyte ratio(NLR)(P=0.031),non-HIV infection(P=0.002),and concomitant infections with other pathogens(P<0.001)were independent risk factors for incidence of respiratory failure.ROC curve analysis revealed that the area under the curve(AUC)was 0.686(0.584,0.789)for non-HIV infection,0.731(0.637,0.826)for concomitant infections with other pathogens,0.648(0.546,0.750)for NLR.The predicted probability was 0.845(0.778,0.912).Conclusions Non-HIV infection,high NLR,and concomitant infections with other pathogens are independent risk factors for incidence of respiratory failure in PJP patients.The panel combining these factors provides a higher predictive value for respiratory failure.Timely assessment of patient condition and early treatment are vital for better outcomes.
8.Sodium tanshinone ⅡA sulfonate inhalation attenuates pulmonary hyper-tension associated with chronic obstructive pulmonary disease in mice
Runhua HOU ; Siting WANG ; Hongping ZHANG ; Ruanyuan YE ; Zeping YANG ; Mengzhu LI ; Guanqing ZHEN ; Jiarui FAN ; Chunyun ZHANG ; Rui CHEN ; Defu LI
Chinese Journal of Pathophysiology 2025;41(9):1713-1720
AIM:To investigate the effects of nebulized sodium tanshinone ⅡA sulfonate(STS)in a mouse model of pulmonary hypertension associated with chronic obstructive pulmonary disease(COPD-PH).METHODS:A to-tal of 32 healthy SPF-grade male C57BL/6 mice were randomly divided into 4 groups:control(CTL,n=8)group,COPD-PH(CS+LPS,n=8)group,STS-treated COPD-PH(CS+LPS+STS,n=8)group,and STS(n=8)group.The COPD-PH model was established through whole-body exposure to cigarette smoke(CS)combined with lipopolysaccharide(LPS)in-halation.Mice were subjected to cigarette smoke exposure in a chamber(9 cigarettes/h,2 h/session,2 sessions/d,6 d/week)for 60 d,except on days of LPS inhalation.On days 1 and 14,COPD-PH model mice received LPS(7.5 μg/mouse in 50 μL saline)via intranasal inhalation,while the CTL and STS groups received an equivalent volume of saline.STS was administered via nebulized inhalation(5 mg/kg,30 min per session,twice daily)immediately before CS exposure.At the end of the modeling period,lung function and right heart pressure were assessed.Bronchoalveolar lavage fluid(BALF)was collected for inflammatory cell counting.Levels of interleukin-6(IL-6)in BALF supernatants and plasma were measured using ELISA.Pathological changes in the airway and lung tissues were evaluated.RESULTS:(1)Com-pared to CTL mice,those exposed to CS and LPS exhibited lesions characteristic of COPD-PH,including emphysema,lung inflammation,decreased lung function,and increased right ventricular systolic pressure(RVSP)and right ventricu-lar hypertrophy index(RVHI)(P<0.05);(2)COPD-PH mice showed significantly elevated IL-6 levels in both BALF and plasma(P<0.05);(3)STS treatment alleviated emphysema and lung inflammation,improved lung function,prevent-ed increases in RVSP and the RV/(LV+S)ratio,and reduced IL-6 levels in both BALF and plasma(P<0.05).CON-CLUSION:The results indicate that nebulized inhalation of STS significantly slows the progression of COPD-PH,likely due to its ability to inhibit lung inflammation and reduce IL-6 expression in the lungs.
9.Quality of life of early esophageal cancer patients after endoscopic mucosal dissection and its influencing factors analysis
Xiaoping LYU ; Yina YANG ; Qingtian LI ; Siting GAO ; Peng CHEN ; Tongjun DONG
Chinese Journal of Modern Nursing 2025;31(8):1089-1093
Objective:To analyze the factors affecting quality of life in patients with early esophageal cancer after endoscopic submucosal dissection (ESD) .Methods:Convenience sampling was used to select 162 early esophageal cancer patients with ESD in Cangzhou Central Hospital from August 2021 to July 2023 who had an on-time follow-up six months as study subjects. General Information Questionnaire and Quality of Life Instruments for Cancer Patients-Esophageal Cancer (QLICP-ES) were used to investigate the patients. Factors affecting the quality of life of patients after ESD for early esophageal cancer were analyzed using univariate analysis and multiple linear regression analysis.Results:Univariate analysis showed statistically significant differences in QLICP-ES scores among patients with different gender, age, marital status, annual income, medical payment method, concomitant diseases, degree of infiltration, vascular invasion, surgical complications, and positive margins ( P<0.05). Multiple linear regression analysis showed that age, marital status, concomitant diseases, vascular invasion, surgical complications, and positive margins were the factors influencing the QLICP-ES scores of patients with ESD for early esophageal cancer, and the differences were statistically significant ( P<0.05) . Conclusions:Quality of life at six months after ESD in patients with early esophageal cancer is at an intermediate to high level. Patients of advanced age, unmarried/divorced/widowed, concomitant diseases, vascular invasion, surgical complications and positive margins have low QLICP-ES scores after ESD for early esophageal cancer. It is recommended that clinical attention be focused on these factors and that targeted nursing measures be taken when necessary.
10.Clinical significance of CD105 and EPHA2 expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on their expressions
Yun GAO ; Haipeng YAO ; Siting XU ; Bo YANG ; Wenhua YU ; Zhongqun WANG ; Lihua LI
Cancer Research and Clinic 2025;37(7):481-487
Objective:To investigate the clinical significance of CD105 and erythropoietin-producing hepatocellular receptor A2 (EPHA2) expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on CD105 and EPHA2 expressions.Methods:A retrospective case series study was conducted. A total of 74 patients with breast invasive ductal carcinoma in Affiliated Hospital of Jiangsu University from June 2019 to June 2024 were selected, and paraffin specimens from the patients after surgery were collected. Immunohistochemistry SP method was used to detect the expressions of CD105 and EPHA2 proteins in specimens. CD105 expression was expressed as the number of CD105 labeled microvessels, and EPHA2 expression was expressed as the proportion of EPHA2 positive expression area. The correlation of CD105 and EPHA2 expressions with the clinicopathological characteristics and diabetes mellitus of patients, as well as the relationship between the expressions of CD105 and EPHA2 were analyzed. Cox proportional hazards model was used to make univariate and multivariate analysis of the factors influencing overall survival of patients.Results:All 74 patients were female. The median age was 60 years old, 44 patients (59.46%) had tumor grade ≥ grade 3, 36 patients (48.65%) had tumor diameter ≥ 2 cm, 28 patients (37.84%) had lymph node metastasis, 30 patients (40.54%) had nerve vessel invasion, and 32 patients (43.24%) had diabetes mellitus. There were statistically significant differences in the proportion of patients with different age, tumor diameter, TNM stage, lymph node metastasis or not and nerve vessel invasion or not between diabetes mellitus group and non-diabetes mellitus group (all P < 0.05). The number of CD105 marking the microvessel was (32±9) and (24±8), respectively in diabetes mellitus group and non-diabetes mellitus group, and the difference was statistically significant ( t = 3.63, P < 0.010); the positive expression area proportion of EPHA2 was (19±5)% and (15±4)%, respectively, and the difference was statistically significant ( t = 3.85, P < 0.010). The expression of CD105 was related to the duration of diabetes mellitus, tumor diameter, TNM stage and lymph node metastasis or not (all P < 0.05), and the expression of EPHA2 was related to tumor diameter and TNM stage (all P < 0.05). Pearson correlation analysis showed a positive correlation between CD105 and EPHA2 expression ( r = 0.75, P < 0.001). The differences in overall survival of patients with or without diabetes mellitus and patients with different CD105 and EPHA2 expressions were statistically significant (all P < 0.05). Multivariate analysis showed that CD105 expression ( HR = 1.10, 95% CI: 1.04-1.16, P = 0.001) and EPHA2 expression ( HR = 1.35, 95% CI: 1.10-1.66, P = 0.005) were independent factors influencing the overall survival of patients with breast invasive ductal carcinoma. Conclusions:The expressions of CD105 and EPHA2 are independent prognostic factors in patients with breast invasive ductal carcinoma, and diabetes mellitus can promote the expressions of CD105 and EPHA2, which may increase the risk of poor prognosis.

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