1.Improvement effect of imperatorin on airway remodeling in bronchial asthma mice and its mechanism
Yu YAN ; Dandan HUANG ; Chunling HONG ; Bowen WEI ; Yuanyuan YANG ; Guanghai YAN ; Yilan SONG ; Zhemin XIAN
Journal of Jilin University(Medicine Edition) 2025;51(6):1508-1517
Objective:To explore the effects of imperatorin(IMP)on airway remodeling in the bronchial asthma mice,and to elucidate the possible mechanisms.Methods:Forty SFP male BALB/c mice were randomly divided into control group,model group,low dose of IMP group(IMP-L group),high dose of IMP group(IMP-H group)and dexamethasone group,with 8 mice in each group.Except for contol group,the mice in the other groups were injected with an ovalbumin(OVA)suspension intraperitoneally to induce the asthma models.After one week,the daily asthma symptoms of the mice were observed and scored.After 8 weeks,the enhanced pause(Penh)values of the mice in various groups were detected to evaluate the airway reactivities.The percentages of eosinophils in the bronchoalveolar lavage fluid(BALF)of the mice in various groups were detected by flow cytometry.The levels of serum IgE,interleukin interferon-gamma(IL)-13,IL-5,IL-4 and interferon-gamma(IFN-γ)in BALF of the mice in various groups were measured by enzyme-linked immunosorbent assay(ELISA)method.HE,PAS and Masson staining were applied to observe the pathomorphology,the number of goblet cells and collagen deposition of the lung tissue of the mice in various groups.Immunohisto chemistry method was applied to detect the expressions of α-smooth muscle actin(α-SMA)and mouse mammary tumor virus(MMTV)wingless type MMTV intergration site family member 5A(Wnt5A)proteins in lung tissue of the mice in various groups.The expression levels of Wnt5A,cellular myelocytomatosis oncogene(c-Myc),β-catenin and α-SMA in lung tissue of the mice in various groups were detected by Western blotting method.The expression levels of α-SMA protein in lung tissue of the mice in various groups were detected by immunofluorescence method.Results:Compared with control group,the score of asthma symptoms of the mice in model group was increased(P<0.01);the Penh value was significantly increased(P<0.01);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentage of eosinophils(EOS)in BALF were significantly increased(P<0.05 or P<0.01),and the level of IFN-γ was reduced(P<0.05);the expression levels of α-SMA and Wnt5A proteins in lung tissue were markedly increased(P<0.01);the expression levels of proteins associated with the Wnt/β-catenin signaling pathway in the lung tissue were significantly increased(P<0.01);the immofluorescence method results showed the expression level of α-SMA protein in lung tissue was significantly increased(P<0.01).Compared with model group,the scores of asthma symphtoms of the mice in IMP-L group,IMP-H group,and dexamethasone group were decereased(P<0.01),and the Penh values of the mice in IMP-H group were decreased(P<0.05);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentages of EOS in BALF of the mice in IMP-L group,IMP-H group,and dexamethasone group were decreased(P<0.05 or P<0.01),and the levels of IFN-γ were increased(P<0.05);the expression levels α-SMA and Wnt5A proteins in lung tissue were decreased(P<0.05 or P<0.01);the expression levels of proteins related to the Wnt/β-catenin signaling pathway in the lung tissue were decreased(P<0.05 or P<0.01);the immunofluorescence method results showed that expression levels of the α-SMA protein in the lung tissue were reduced(P<0.05 or P<0.01).Conclusion:IMP has an improving effect on airway remodeling in the asthmatic mice and can inhibit the expression levels of Wnt/β-catenin pathway-related proteins.
2.Associations between parental adherence to healthy lifestyles and cognitive performance in offspring: A prospective cohort study in China
Rongxia LV ; Yuhui HUANG ; Siyi HUANG ; Shiyi WU ; Siwen WANG ; Guangyu HU ; Yanan MA ; Peige SONG ; E. Jorge CHAVARRO ; S.V. SUBRAMANIAN ; Chunling LU ; Zhihui LI ; Changzheng YUAN
Chinese Medical Journal 2024;137(6):683-693
Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.
3.Clinical effect of Sijunzi decoction combined with Fangji Huangqi decoction added and decreased in treating chronic heart failure patients with reduced ejection fraction and Qi deficiency,blood stasis and phlegm retention syndrome
Jie LIU ; Chunling LIANG ; Xiaojie CHEN ; Ning LI ; Yuanyuan HUANG
Chongqing Medicine 2024;53(14):2168-2172
Objective To observe the clinical effect of Sijunzi decoction and Fangji Huangqi decoction combined with Sacubitril Valsartan Sodium Tablets in treating chronic heart failure patients with reduced ejec-tion fraction and Qi deficiency,blood stasis and phlegm retention.Methods Ninety-four inpatients with chro-nic heart failure treated in this hospital from January 2021 to December 2022 were selected as the study sub-jects and divided into the Sijunzi Decoction and Fangji Huangqi Decoction combined with Sacubitril Valsartan Sodium Tablets group (the Chinese medicine combined group) and Sacubitril Valsartan Sodium Tablets group (the control group) according to the random number table method.Both groups were treated with standard therapy,and the Chinese medicine combined group added Sijunzi Decoction and Fangji Huangqi Decoction on this basis.Both groups were continuously treated for 8 weeks.The mean systolic blood pressure,left ventricu-lar end diastolic diameter (LVEDD),left ventricular ejection fraction (LVEF),TCM syndrome score and 6 min walking test (6-MWT) results at 24 h before treatment and after treatment were compared between the two groups.Results The average 24 h systolic blood pressure,score of each TCM syndrome and LVEDD after treatment in the two groups were decreased compared with those before treatment (P<0.05),while LVEF and 6-MWT in the two groups were increased,and the differences were statistically significant (P<0.05). Compared with the control group,the average 24 h systolic blood pressure in the Chinese medicine combined group was higher,each score of TCM syndrome score and LVEDD were lower,LVEF and 6-MWT were high-er,and the differences were statistically significant (P<0.05).Conclusion Sijunzi Decoction and Fangji Huangqi Decoction combined with Sacubitril Valsartan Sodium Tablets has a good effect on the patients with chronic heart failure with reduced ejection fraction and Qi deficiency,blood stasis and phlegm retention,which could effectively increase the systolic blood pressure,improve the cardiac coronary arterial perfusion and the quality of life of the patients,and alleviate the left ventricular remodeling status.
4.Evaluation value of IL-6,PCT,IgG in children with hormone-sensitive PNS bacteria infection pneumonia susceptibility and recurrence
Chunling MA ; Zhong HUANG ; Jing ZHOU ; Xin XIE ; Zhixu YE
International Journal of Laboratory Medicine 2024;45(17):2103-2107
Objective To investigate the value of interleukin-6(IL-6),procalcitonin(PCT)and immuno-globulin G(IgG)in evaluating the susceptibility and recurrence of bacterial pneumonia in children with hor-mone-sensitive primary nephrotic syndrome(PNS).Methods A total of 150 children with hormone-sensitive PNS admitted to the hospital from January 2019 to March 2023 were selected as the study objects.The pa-tients were divided into concurrent group and non-concurrent group according to whether bacterial pneumonia was complicated or not within 3 months.The baseline IL-6,PCT and IgG levels of the two groups were com-pared,and the factors affecting susceptibility to bacterial pneumonia were analyzed by Logistic regression.Re-ceiver operating characteristic curve(ROC)was drawn to analyze the value of IL-6,PCT and IgG in assessing susceptibility to PNS bacterial pneumonia and the risk of PNS recurrence.Results IL-6[(7.84±2.49)pg/mL]and PCT[(0.39±0.11)ng/mL]in concurrent group were higher than those in non-concurrent group[(4.75±1.56)pg/mL,(0.29±0.09)ng/mL].IgG[(3.82±1.25)g/L]was lower than that of non-concurrent group[(5.92±1.97)g/L],and the differences were statistically significant(P<0.05).Logistic regression e-quation showed that with the increase of IL-6 and PCT and the decrease of IgG,the susceptibility to bacterial pneumonia gradually increased,and the difference was statistically significant(P<0.05).The AUC of IL-6,PCT and IgG for PNS bacterial pneumonia susceptibility was 0.792,0.744 and 0.677,respectively.The AUC of IL-6 and PCT combined IgG for PNS bacterial pneumonia susceptibility was 0.929,which was higher than that of IL-6,PCT and IgG alone(P<0.05).The risk of PNS recurrence in patients with high IL-6 level was 7.054 times that of low IL-6 level,the risk of PNS recurrence in patients with high PCT level was 6.750 times that of low PCT level,and the risk of PNS recurrence in patients with high IgG level was 0.079 times that of low level,the differences were statistically significant(P<0.05).Conclusion IL-6,PCT and IgG are the influencing factors of hormone-sensitive PNS bacterial pneumonia in children,and they are related to the recurrence of PNS.Clinically,IL-6,PCT and IgG levels can be used to evaluate the susceptibility and recur-rence risk of bacterial pneumonia in children,so as to provide guidance for preventive clinical intervention.
5.Application of case-based teaching method based on the Xuexitong learning platform in the online teaching of Digestive System
Bimei JIANG ; Desheng XIAO ; Qiongqiong HE ; Gengqiu LUO ; Xiangping QU ; Fayi LIU ; Junwen LIU ; He HUANG ; Chunling FAN ; Dahua LU ; Qinglan LÜ
Chinese Journal of Medical Education Research 2023;22(3):363-366
This study explores the application effect of the case-based teaching method based on Xuexitong learning platform in the online teaching of Digestive System, and analyzes the learner's emotional experience, learning behavior, and learning effect in the case-based online teaching. The results of the study show that the case-based online teaching model based on Xuexitong learning platform improves students' online learning interest, and the students have good emotional experience, high learning enthusiasm, good classroom interaction, enhanced self-learning ability before and after class, and good learning effect. In addition, precise teaching can be used for individual students who are not enthusiastic about online learning.
6.Comparison of the predictive value of the modified CADILLAC, GRACE and TIMI risk scores for the risk of short-term death in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention
Chunling JI ; Fang SONG ; Xiaomo HUANG ; Xiang QU ; Nan QIU ; Jiaying ZHU
Chinese Critical Care Medicine 2023;35(3):299-304
Objective:To establish a modified controlled abciximab and device investigation to lower late angioplasty complication (CADILLAC) score, and to compare the predictive value of modified CADILLAC score, the global registry of acute coronary event (GRACE) score and the thrombolysis in myocardial infarction (TIMI) score in predicting the risk of short-term death after percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction (STEMI).Methods:A retrospective study was conducted. The clinical data of 169 STEMI patients under going PCI admitted to the department of cardiology of Guizhou Provincial People's Hospital from September 2019 to December 2020 through emergency chest pain fast track were enrolled. A multivariate Logistic regression analysis was used to screen the factors closely related to the mortality risk within 30 days of STEMI, and a modified CADILLAC scoring system was established by referring to CADILLAC scoring settings. The score of modified CADILLAC, GRACE and TIMI scores of patients were calculated after admission, and the number of deaths due to cardiovascular disease (CVD) within 30 days after onset was recorded. The receiver operating characteristic curve (ROC curve) was used to evaluate the predictive value of three scoring systems on the risk of death within 30 days after PCI in patients with STEMI.Results:In 169 STEMI patients, 16 patients died of CVD within 30 days after PCI, and the actual case mortality was 9.47%. Multivariate Logistic regression analysis showed that age > 75 years old, cardiac function Killip ≥ Grade Ⅲ, ventricular arrhythmia, ST segment elevation ≥ 0.2 mV, cardiac troponin I (cTnI) increase, systolic blood pressure (SBP) < 90 mmHg (1 mmHg ≈ 0.133 kPa) were all independent predictors of death after PCI in STEMI patients. The improved CADILLAC scoring system was constructed based on the above predictive factors combined with left ventricular ejection fraction (LVEF) less than 0.40. The GRACE, TIMI and modified CADILLAC scores of dead patients were significantly higher than those of survival patients (GRACE score: 197.60±31.83 vs. 149.81±36.72, TIMI score: 11.21±2.13 vs. 7.27±1.97, modified CADILLAC score: 12.60±2.52 vs. 6.96±2.17, all P < 0.05). The higher the risk stratification of the three scores, the higher the mortality of patients with CVD within 30 days after PCI [the mortality of patients with low, medium and high risk in GRACE score were 2.41% (2/83), 9.61% (5/52) and 26.47% (9/34); the mortality of patients with low, medium and high risk in TIMI score were 3.12% (3/96), 12.82% (5/39) and 23.53% (8/34); and the mortality of patients with low, medium and high risk in modified CADILLAC score were 3.19% (3/94), 7.69% (4/52) and 39.13% (9/23), respectively, all P < 0.01]. The area under the ROC curve (AUC) of the GRACE, TIMI and the modified CADILLAC scores predicting the risk of death 30 days after PCI in STEMI patients were 0.855 [95% confidence interval (95% CI) was 0.702-0.923], 0.725 (95% CI was 0.666-0.812) and 0.882 (95% CI was 0.732-0.936), respectively, all P = 0.000; the sensitivity of its prediction accuracy were 81.59%, 78.65% and 89.26%, and the specificity were 78.62%, 57.12% and 75.54%, respectively. Conclusions:The GRACE and the modified CADILLAC scores have predictive value for the short-term mortality risk of STEMI patients after PCI, and the modified CADILLAC score is more accurate. But the TIMI score has a poor predictive effect on the short-term mortality risk of STEMI patients after PCI.
7.Role of extracellular signal-regulated kinase 1/2 in glutamate-induced ferroptosis in PC12 cells
Yan HUANG ; Zhuoyi LIU ; Qian ZHANG ; Wanqing ZHOU ; Pingping XIA ; Zhi YE ; Chunling LI
Chinese Journal of Anesthesiology 2023;43(8):946-950
Objective:To evaluate the role of extracellular signal-regulated kinase (ERK)1/2 in glutamate-induced ferroptosis in PC12 cells.Methods:PC12 cells were divided into 6 groups ( n=21 each) using a random number table method: control group (C group), glutamategroup (Glu group), glutamate+ ERK1/2 over-expression group (Glu+ ERK1/2-OE group), glutamate+ ERK1/2 plasmid empty vector group (Glu+ Vec group), glutamate+ ERK1/2 knockdown group (Glu+ si-ERK1/2 group)and glutamate+ ERK1/2 SiRNA negative control group (Glu+ si-NC group). Cells were treated with glutamate at a final concentration of 6 mmol/L for 72 h in Glu group and with the equal volume of PBS buffer for 72 h in C group. Glu+ ERK1/2-OE group was transfected with ERK1/2 overexpression plasmid, Glu+ Vec group was transfected with plasmid empty vector, and Glu+ si-ERK1/2 group was transfected with ERK1/2 siRNA, Glu+ si-NC group was transfected with siRNA negative control for 48 h, and then glutamate at a final concentration of 6 mmol/L was added and cells were treated for 72 h. The cell viability, lactic dehydrogenase (LDH)activity and contents of glutathione (GSH), ferrous ions and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Mitochondrial membrane potential (MMP) and lipid reactive oxygen species (Lip-ROS) were measured by flow cytometry. Results:Compared with C group, the cell viability, GSH content and MMP were significantly decreased, and the LDH activity, ferrous ions content, MDA content and Lip-ROS levels were increased in Glu group ( P<0.05). Compared with Glu+ Vec group, the cell viability, GSH content and MMP were significantly increased, and the activity of LDH, contents of ferrous ions and MDA, and Lip-ROS levels were decreased in Glu+ ERK1/2-OE group( P<0.05). Compared with Glu+ si-NC group, the cell viability, GSH content and MMP were significantly decreased, and the LDH activity, contents of ferrous ions and MDA, and Lip-ROS level were increased in Glu+ si-ERK1/2 group ( P<0.05). Conclusions:ERK1/2 is involved in glutamate-induced ferroptosis in PC12 cells.
8.Effects of psychological education based on timing theory in caregivers of epileptic patients
Chunling WANG ; Yuanyuan CAI ; Dan HUANG
Chinese Journal of Modern Nursing 2023;29(4):478-481
Objective:To explore the effect of psychological education based on timing theory in caregivers of epileptic patients.Methods:From April 2018 to April 2020, 160 caregivers of epilepsy patients from China-Japan Union Hospital of Jilin University were selected as the study subject by convenience sampling. Caregivers were divided into observation group and control group according to random number table, 80 in each group. The control group received routine intervention, while the observation group received psychological education based on timing theory on the basis of the control group. The Chinese version of the Depression Anxiety Stress Scale-21 (DASS-21) and the World Health Organization Quality of Life Measurement Scale-Brief Version (WHOQOL-BREF) were used to compare the psychological status and quality of life of the caregivers of epilepsy patients in the two groups before and after the intervention.Results:Finally, 77 subjects in the observation group and 75 subjects in the control group completed the study. After intervention, the scores of anxiety, stress and depression in DASS-21 in the observation group were lower than those in the control group, with a statistically significant difference ( P<0.01) . The scores of WHOQOL-BREF in physiology, psychology and social relations in the observation group were higher than those in the control group, and the difference was statistically significant ( P<0.01) . Conclusions:The application of psychological education based on timing theory in the caregivers of epileptic patients can reduce their unhealthy psychological state and improve their quality of life.
9.Epidemiological features and antiviral response of genotype 6 chronic hepatitis C
Jinni HUANG ; Jianning JIANG ; Dandan LIANG ; Shiyu LONG ; Guozhen DONG ; Man SU ; Jijiao LI ; Chunling TENG ; Ping ZHANG ; Minghua SU
Journal of Clinical Hepatology 2022;38(4):793-797
Objective To investigate the epidemiological features and antiviral response of patients with genotype 6 chronic hepatitis C (CHC) in Guangxi, China. Methods A total of 97 patients with genotype 6 CHC who were admitted to The First Affiliated Hospital of Guangxi Medical University from December 2012 to December 2020 were enrolled, among whom 62 patients were given antiviral therapy. The 62 patients receiving antiviral therapy were divided into interferon group with 22 patients and direct-acting antiviral agent (DAA) group with 40 patients. Related data were collected, including general demographic data, HCV RNA, liver function, routine blood test results, and renal function. The chi-square test was used for comparison of categorical data between groups. Results Among the 97 patients, there were 69 male patients (71.1%) and 28 female patients (28.9%), with a mean age of 41.97±10.12 years, and the patients aged 30-40 years accounted for 47.4% (46/97). Of all 97 patients, 95 (97.9%) had genotype 6a, 1 had genotype 6e, and 1 had genotype 6xa. Among the 65 patients with a definite route of infection, 41 (63.1%) had intravenous drug use, 14 had medical-related operations, 9 had blood transfusion, and 4 had sexual contact as the route of infection. For the interferon group, the rapid virologic response (RVR) rate at week 4 was 81.8% (18/22), the rate of undetectable virus at the time of drug withdrawal (Epoint) was 86.4% (19/22), the rate of sustained virologic response at 12 weeks after drug withdrawal (SVR12) was 81.8%, and the rate of sustained virological response at 24 weeks after drug withdrawal (SVR24) was 81.8%; 1 patient in this group experienced recurrence. All 40 patients in the DAA group were previously untreated patients (33 patients without liver cirrhosis and 7 patients with compensated liver cirrhosis), with an overall RVR rate of 87.5%(35/40), an Epoint rate of 100%, and an SVR12 rate of 100%, and there was no treatment failure or recurrence. Although different DAA regimens had different RVR rates, they all had a SVR12 rate of 100%. The patients with compensated liver cirrhosis and other diseases had a SVR12 rate of 100%. Conclusion Intravenous drug addiction is the main route of infection for patients with genotype 6 CHC in Guangxi, and CHC is more common in men, with genotype 6a as the main subtype. DAA treatment has a higher virologic response rate than interferon treatment, with an SVR12 rate of 100%. There is no significant difference in SVR12 rate between the patients with compensated liver cirrhosis and those without liver cirrhosis.
10.Construction and validation of a risk prediction model for work-related musculoskeletal disorders among nurses
Na XU ; Chunling YANG ; Dong DONG ; Lili TAN ; Aizheng JIANG ; Lining QIN ; Jing HUANG
Chinese Journal of Modern Nursing 2022;28(14):1876-1883
Objective:To construct and validate a risk prediction model for work-related musculoskeletal disorders (WMSDs) among nurses, so as to provide a scientific and objective reference tool for the screening of high-risk groups of WMSDs among nurses.Methods:This study was a cross-sectional study. From March to July 2021, convenience sampling was used to select 1 050 nurses from 25 hospitals in Beijing as the research subject. The risk factors for WMSDs were evaluated by issuing the Musculoskeletal Disease Questionnaire. All survey subjects were randomly divided into the training set ( n=715) and the validation set ( n=304) according to the ratio of 7∶3, and the training set was used to build the model. The predictive ability of the risk model was evaluated using the area under receiver operating characteristic curve (AUC) and the validation set was used for validation. A total of 1 050 questionnaires were distributed and 1 019 valid questionnaires were recovered, with a valid recovery rate of 97.05%. Results:Among 1 019 nurses, the weekly incidence of WMSDs was 84.0% (856/1 019) and the annual incidence was 86.7% (883/1 019) . The neck was the site with the highest incidence of WMSDs, the weekly incidence and annual incidence were 70.3% (716/1 019) and 70.1% (714/1 019) , respectively. The results of multivariate Logistic regression analysis showed that the risk factors of the weekly incidence of WMSDs among nurses included age ≥40 years old ( P<0.001) , tense work atmosphere ( P<0.001) , forward neck posture ( P=0.002) , doing the same job daily ( P=0.039) , needing to dealing with patients ( P=0.012) and keeping the back in the same posture for a long time ( P=0.002) , and the risk factors of the annual incidence of WMSDs among nurses included age ≥40 years old ( P=0.001) , did not participation in safety protection training ( P=0.003) , high education ( P=0.041) , stressful work atmosphere ( P=0.005) , significantly forward neck posture ( P=0.008) , needing to dealing with patients frequently ( P=0.001) , work involving cold or temperature changes ( P=0.017) , insufficient rest time ( P=0.019) , frequent shift change ( P=0.035) , frequent repetition of the same action of the trunk at work ( P=0.025) , hand bending ( P=0.006) . Based on the above screening variables, a nomogram model was established to predict the risk of weekly and annual incidence of WMSDs among nurses, and the AUC values of the model in the training set were 0.794 [95% CI: (0.750-0.838) ] and 0.789 [95% CI: (0.718-0.860) ], respectively. The validation set further confirmed the predictive ability of the nomogram model. The AUC values for predicting the risk of weekly and annual incidence of WMSDs among nurses were 0.782 [95% CI: (0.729-0.835) ] and 0.794 [95% CI: (0.721-0.868) ], respectively. Conclusions:The nomogram model has good predictive ability for the occurrence risk of WMSDs among nurses, which can help to screen high-risk groups and give effective intervention in time.

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