1.Exploration of the renal protective effect and mechanism of Shenbining granule on IgA nephropathy rats based on the CXCL12/CXCR4/STAT3 signaling pathway
Xu WANG ; Chundong SONG ; Chenchen CHEN ; Haoran JIANG
China Pharmacy 2025;36(23):2912-2917
OBJECTIVE To investigate the renal protective effect and mechanism of Shenbining granule on IgA nephropathy (IgAN) rats by regulating the CXC chemokine motif ligand 12 (CXCL12)/CXC chemokine receptor 4 (CXCR4)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. METHODS A total of 60 rats were randomly assigned into blank group (n=12) and modeling group (n=48). IgAN model of modeling group was induced by using bovine serum albumin, carbon tetrachloride and lipopolysaccharide, followed by model validation. Ultimately, a total of 55 rats (9 in the blank group, 46 in the modeling group) were included in the subsequent study. The rats in the modeling group were randomly divided into model group (n=10), prednisone acetate group [positive control group, 6.25 mg/(kg·d), n=12], Shenbining granule low- and high-dose groups [4.17, 8.33 g/(kg·d), n=12]. They were given relevant medicine/distilled water intragastrically, once a day, for 4 consecutive weeks. After the last medication, biochemical indicators in the urine and serum of rats were measured, and pathological morphological changes in the renal tissues of rats were observed. IgA deposition in the renal tissues, as well as the mRNA expression levels of CXCL12, CXCR4 and STAT3, and the protein expression levels of CXCL12, CXCR4, STAT3 and phosphorylated STAT3 (p-STAT3) were detected. Additionally, the level of interleukin-6 (IL-6) in the renal tissue was measured. RESULTS Compared with the model group, the low-dose and high-dose Shenbining granule groups showed significantly decreased urinary red blood cell count, 24 h total urinary protein, blood urea nitrogen, serum creatinine, and alanine amino-transferase, along with increased Alb levels (P<0.05). Pathological damage in the renal tissues was alleviated, with reduced IgA deposition in the mesangial region (P<0.05); protein and mRNA expressions of CXCL12, CXCR4 and STAT3, as well as phosphorylation level of STAT3 protein and the IL-6 level, were significantly decreased in renal tissue (P<0.05). CONCLUSIONS Shenbining granule may exert its renal protective effects in IgAN rats by inhibiting the activation of the CXCL12/ CXCR4/STAT3 signaling pathway, downregulating the expression of inflammatory factors such as IL-6, alleviating renal inflammation, and thereby improving renal pathological damage.
2.Analysis and suggestions on China′s family bed service policy based on grounded theory
Yaqing LIU ; Sixian DU ; Haoran NIU ; Feng JIANG ; Liwen GONG ; Junfeng PEI
Chinese Journal of Hospital Administration 2024;40(8):613-618
Objective:To analyze the current status and deficiencies of family bed service policies in China, for references for promoting the construction of China′s home health service system.Methods:Key words such as " family bed" and " home health services" were used to search for relevant policies(from January 1, 1984 to May 31, 2023)in Peking University Treasure Database, the State Council′s policy document repository, and official websites of health administrative departments at all levels. NVivo 11.0 software was utilized for a three-level coding process to establish a policy text analysis framework and to identify deficiencies in the construction of policies.Results:A total of 63 policy documents were included, comprising 53 provincial and municipal documents, which were mainly concentrated in economically developed provinces; After three-level coding, 72 third level nodes, 21 second level nodes, and 8 first level nodes(service objects, service providers, service methods, service content, service fees, subsidy policies, hospital bed configuration, and standardized management) were obtained. Among them, the responsibilities of service providers needed to be further clarified, the technical and innovative nature of service content was still insufficient, the charging standards and medical insurance reimbursement policies needed to be improved, the support for subsidy policies was limited, and the use of intelligent devices in bed configuration needed to be strengthened.Conclusions:China′s family bed service policy focused on eight dimensions, covering a comprehensive range of content, but there were still areas that need to be refined and improved. This study suggested that relevant departments should further clarify the responsibilities of service providers, deepen the construction of service connotations, moderately increase government support, promote the intelligent construction of services, and achieve multi-party collaboration to jointly promote the sustainable development of family bed services in China.
3.Study on the Diagnosis Model of Phlegm-Dampness Obstruction Syndrome in Patients with Stable Angina Pectoris Due to Coronary Heart Disease Based on Machine Learning
Haoran CHEN ; Tong JIANG ; Yi ZHENG ; Weiwei WANG ; Ying LIU ; Kejun WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):142-150
Objective To construct a diagnostic model for the phlegm-dampness obstruction syndrome in patients with coronary heart disease stable angina pectoris(CSAP);To provide a reference for clinical syndrome differentiation.Methods Totally 305 patients'clinical data were collected from the Department of Cardiology,Dongying Hospital Affiliated to Shandong University of Traditional Chinese Medicine,from May 2022 to January 2024.The least absolute shrinkage and selection operator(LASSO)was used to select features,and multiple models were constructed and compared using machine learning(ML)algorithms.The optimal ML model was selected for training,validation,and testing.Finally,the operational logic of the optimal model was explained using Shapley Additive Explanations(SHAP),and two typical examples were provided to help users understand the model's operational logic.Results LASSO regression identified chest pain,body mass index(BMI),limb heaviness,drinking history,age,triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)as features included in the model.After comparing multiple models,the Gaussian Naive Bayes(GNB)model demonstrated the best performance.The final constructed GNB model achieved an average AUC of 0.938(95%CI:0.903-0.972)in the training set,an average AUC of 0.927(95%CI:0.851-0.992)in the validation set,and an AUC of 0.856(95%CI:0.751-0.961)in the test set.The learning curve showed that the error between the training and validation sets in the model converged as the number of training samples increased.The calibration curve showed that the model had good consistency in predicting the probability of observed phlegm-dampness obstruction syndrome patients.The clinical decision curve(DCA)showed that the model could provide clinical benefits for patients at a decision threshold below 0.7.The features ranked by SHAP importance in order were chest pain,BMI,LDL-C,TG,limb heaviness,TC,drinking history and age.Conclusion The diagnostic model for CSAP phlegm-dampness obstruction syndrome constructed in this study can assist physicians in the syndrome differentiation of patients,thereby enabling the formulation of integrated clinical treatment plans combining traditional Chinese and Western medicine,and aiding patients in achieving better clinical therapeutic outcomes.
4.A survey report on the status of emergency radiology in China
Jing WANG ; Zheng MIAO ; Qi YANG ; Lei ZHANG ; Hao WANG ; Huishu YUAN ; Haoran SUN ; Wei JIANG ; Yuan TIAN ; Mingyang LI ; Yaning WANG ; Zhaoyi MA ; Huimao ZHANG
Chinese Journal of Radiology 2024;58(6):661-666
Objective:To investigate the application status of emergency radiology in China, and to provide data support for the standardized development, scientific management and big data research of emergency radiology.Methods:From August 12th to October 19th, 2022, a questionnaire survey was conducted through WeChat"Questionnaire Star"to send targeted questionnaires to investigate the relevant data of the current status of emergency radiology in China, mainly including digital radiography (DR) and computed tomography (CT). This study was initiated by the Chinese Emergency Radiology Database Collaboration Group, and comprehensively investigated emergency imaging personnel, equipment, workload, critical value reporting process, and artificial intelligence (AI) application status.Results:There were 123 hospitals in the study. The survey showed that emergency DR/CT reports were mainly completed by residents and above (69.1%). There were 21 DR brands, 10 CT brands and 8 MR brands used for emergency imaging examinations. The median number of DR examinations in tertiary hospitals and secondary hospitals investigated from January to June 2022 was 4 642 and 2 015 cases respectively, and the median number of CT examinations was 16 512 and 3 762 cases respectively. The average single-shift workload of DR in the emergency radiology department during the day and night shift in tertiary hospitals was mainly ≤20 copies and 21-50 copies, and the average single-shift workload of CT in the emergency radiology department during the day and night shift was mainly 21-50 copies and 51-100 copies, while the average single-shift workload of DR/CT in the emergency radiology department during the day/night shift in secondary hospitals was mainly ≤20 copies. In terms of critical value reporting process, 74.8% of emergency imaging doctors and 84.6% of emergency imaging technicians took the way of phone/text message to notify the clinical doctor or the patients′ family. The overall deployment rate of AI in emergency imaging was about 60.2%. 75% of the respondents believed that in the future, AI can improve emergency radiology work from aspects such as emergency screening, aided diagnosis and process optimization.Conclusions:The emergency medical imaging mainly based on DR and CT has the current situations such as generally low seniority of doctors, diverse brands of imaging equipments, large volume of examinations and intense workload per doctor, especially in tertiary hospitals, and dependence on traditional means for critical value reporting. At present, AI is emerging in the field of emergency imaging, and there is still a long way to go to play the huge potential of AI in the intelligent whole process of emergency imaging in the future.
5.β-caryophyllene promotes white fat browning in obese mice through up-regulation of the PPARγ/PGC-1α/UCP1 pathway
Haoran JIANG ; Xiaofei TANG ; Jielin WU ; Jiaoling WANG ; Chengyu HUANG ; Shuguang ZHU ; Linquan ZANG
Acta Universitatis Medicinalis Anhui 2024;59(9):1591-1598
Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05),food intake was decreased(P<0.01),insulin resistance was improved(P<0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P<0.000 1 and P<0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P<0.01 and P<0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05,and P<0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.
6.β-caryophyllene promotes white fat browning in obese mice through up-regulation of the PPARγ/PGC-1α/UCP1 pathway
Haoran JIANG ; Xiaofei TANG ; Jielin WU ; Jiaoling WANG ; Chengyu HUANG ; Shuguang ZHU ; Linquan ZANG
Acta Universitatis Medicinalis Anhui 2024;59(9):1591-1598
Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05),food intake was decreased(P<0.01),insulin resistance was improved(P<0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P<0.000 1 and P<0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P<0.01 and P<0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05,and P<0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.
7.β-caryophyllene promotes white fat browning in obese mice through up-regulation of the PPARγ/PGC-1α/UCP1 pathway
Haoran JIANG ; Xiaofei TANG ; Jielin WU ; Jiaoling WANG ; Chengyu HUANG ; Shuguang ZHU ; Linquan ZANG
Acta Universitatis Medicinalis Anhui 2024;59(9):1591-1598
Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05),food intake was decreased(P<0.01),insulin resistance was improved(P<0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P<0.000 1 and P<0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P<0.01 and P<0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05,and P<0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.
8.Study on the Enhanced Transdermal Permeation of Ketoprofen Gel Induced by Ultrasound
Xiumei JIANG ; Renhua FANG ; Wenxin NIU ; Weiqing WANG ; Yue AN ; Jing YANG ; Haoran WANG ; Changzhao JIANG ; Jincui YE
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1508-1514
OBJECTIVE
To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel.
METHODS
Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process.
RESULTS
Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling.
CONCLUSION
Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.
9.β-caryophyllene promotes white fat browning in obese mice through up-regulation of the PPARγ/PGC-1α/UCP1 pathway
Haoran Jiang ; Xiaofei Tang ; Jielin Wu ; Jiaoling Wang ; Chengyu Huang ; Shuguang Zhu ; Linquan Zang
Acta Universitatis Medicinalis Anhui 2024;59(9):1591-1598
Objective:
To investigate the effects of β-caryophyllene(BCP) on the browning of white adipose tissue in obese mice and the related mechanisms.
Methods:
An obese mouse model was establishedviaintraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution [14.4 mg/(kg·d)] in male Kunming mice. Obesity model mice were randomly divided into a model group(Model group) and a BCP administration group(BCP-50 group); normal diet mice were set up as a control group(Control group), with 8 mice in each group. BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group, while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks. The oral glucose tolerance test was performed at the end of 4-week administration, and mice were executed after overnight fasting at the end of the experiment, and blood samples and adipose tissues were rapidly collected for subsequent experimental tests. The kit was used to detect serological-related indexes; hematoxylin-eosin staining was conducted to observe the morphology of adipose tissue; immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1) in adipose tissue; Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α), peroxisome proliferator-activated receptor γ(PPARγ), UCP1 and cannabinoid receptor 2(CNR2) proteins in epididymal white adipose(eWAT).
Results:
Compared with the model group, the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05), food intake was decreased(P<0.01), insulin resistance was improved(P<0.000 1), and the serum content of low-density lipoprotein cholesterol(LDL-C) and nonesterified fatty acid(NEFA) in the obese mice was significantly reduced(P<0.000 1 andP<0.01). Total cholesterol(TC), triglyceride(TG), and high-density lipoprotein cholesterol(HDL-C) contents did not change significantly. In addition, the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05); the adipocytes in eWAT and BAT were reduced; and the expression of the UCP1 protein was significantly elevated(P<0.01 andP<0.05). In addition to UCP1, the expression levels of PGC1α, PPARγ, and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05, andP<0.001).
Conclusion
β-caryophyllene promotes white adipose tissue browning through up-regulating PPARγ/PGC-1α/UCP1 pathway expression, thus improving obesity.
10.β-caryophyllene promotes white fat browning in obese mice through up-regulation of the PPARγ/PGC-1α/UCP1 pathway
Haoran JIANG ; Xiaofei TANG ; Jielin WU ; Jiaoling WANG ; Chengyu HUANG ; Shuguang ZHU ; Linquan ZANG
Acta Universitatis Medicinalis Anhui 2024;59(9):1591-1598
Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05),food intake was decreased(P<0.01),insulin resistance was improved(P<0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P<0.000 1 and P<0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P<0.01 and P<0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05,and P<0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.


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