1.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
2.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
3.Distribution of Traditional Chinese Medicine Syndrome Elements in Different Risk Populations of Heart Failure Complicated with Type 2 Diabetes: A Retrospective Study Based on Nomogram Model and Factor Analysis
Tingting LI ; Zhipeng YAN ; Yajie FAN ; Wenxiu LI ; Wenyu SHANG ; Yongchun LIANG ; Yiming ZUO ; Yuxin KANG ; Boyu ZHU ; Junping ZHANG
Journal of Traditional Chinese Medicine 2025;66(11):1140-1146
ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this, 441 non-heart failure patients were divided into a low-risk group (325 cases) and a high-risk group (116 cases) according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information (four diagnostic methods) was collected for both groups, and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age, disease duration, coronary heart disease, old myocardial infarction, arrhythmia, absolute neutrophil count, activated partial thromboplastin time, and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the modeling group and validation group were 0.934 and 0.935, respectively. The Hosmer-Lemeshow test (modeling group P = 0.996, validation group P = 0.121) indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner, indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency (175 cases, 53.85%), dampness (118 cases, 36.31%), and heat (118 cases, 36.31%), with the primary locations in the spleen (125 cases, 38.46%) and lungs (99 cases, 30.46%). In the high-risk group, the main disease elements were yang deficiency (73 cases, 62.93%), blood stasis (68 cases, 58.62%), and heat (49 cases, 42.24%), with the primary locations in the kidney (84 cases, 72.41%) and heart (70 cases, 60.34%). ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess, with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat, related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat, related to the kidneys and heart.
4.Efficacy and safety of a domestic hair follicle extraction system in extracting hair follicles from patients with androgenetic alopecia: a multicenter, prospective, randomized, self-controlled clinical trial
Kai YANG ; Jinran LIN ; Fei ZHU ; Suyun FENG ; Zheng LI ; Yue ZHANG ; Ruiming HU ; Hanxiao CHENG ; Zhentao ZHOU ; Yatong WU ; Dingquan YANG ; Jufang ZHANG ; Wenyu WU
Chinese Journal of Dermatology 2025;58(7):603-607
Objective:To compare the efficacy and safety of a domestic hair follicle extraction system versus traditional follicular unit excision (FUE) in extracting hair follicles for the treatment of androgenetic alopecia (AGA) .Methods:A multicenter, randomized, self-controlled clinical trial was conducted on AGA patients aged 18 - 59 years who were recruited from the Huashan Hospital, Fudan University, the Affiliated Hangzhou First People's Hospital, and the China-Japan Friendship Hospital between June 2023 and September 2024. Each patient's scalp was randomly divided into two sides (experimental side vs. control side) using an envelope method. The experimental side underwent robotic hair transplantation with a domestic hair follicle extraction system, and the control side underwent traditional FUE. Hair follicles were extracted from the safe donor area in the occipital region, and implanted into the ipsilateral hair loss area. The primary outcome was the hair transection rate which was calculated immediately after follicular extraction. The secondary outcomes included the hair follicle unit loss rate and the change in hair density at the recipient site on postoperative day 14. Safety was evaluated by assessing the incidence of folliculitis at the donor site on postoperative day 14 and the overall incidence of adverse events. Surgical outcomes were evaluated at 9 months after surgery. Comparisons of evaluation indicators among groups were performed by using a paired t test or Wilcoxon signed-rank test. Results:A total of 55 patients with AGA (51 males and 4 females, aged 32.71 ± 5.75 years) completed the hair follicle transplantation and postoperative follow-up. The hair transection rate ( M[ Q1, Q3]) was 6.65% (4.56%, 10.16%) in the experimental group and 5.28% (3.04%, 8.89%) in the control group (difference = 1.24%, 95% CI: -0.24%, 2.65%) . The hair follicle unit loss rate was 2.00% (1.00%, 3.50%) in the experimental group and 0.50% (0, 2.00%) in the control group, with a significant difference between the two groups ( P = 0.008) . On postoperative day 14, there was no significant difference in the hair density between the experimental group and control group (72.20 ± 25.95 per cm 2vs. 76.49 ± 30.84 per cm 2, P = 0.173) . At 9-month follow-up, both groups showed improvement in the investigator's overall score in the recipient areas. Seven adverse events occurred in 7 subjects (12.72%) in each group, and all were mild folliculitis. Conclusion:The domestic hair follicle extraction system demonstrated comparable efficacy and safety to the traditional FUE in hair transplantation.
5.A multicenter retrospective clinical study of a simplified comprehensive geriatric assessment system in elderly patients with diffuse large B-cell lymphoma
Jiayan LENG ; Yihong CAI ; Xueping GE ; Nanping ZHAO ; Qianqian SU ; Zhuxia JIA ; Jun QIAN ; Bingzong LI ; Haiying HUA ; Xuzhang LU ; Huayuan ZHU ; Jianyong LI ; Wenyu SHI
Chinese Journal of Hematology 2025;46(2):126-133
Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.
6.Efficacy and safety of a domestic hair follicle extraction system in extracting hair follicles from patients with androgenetic alopecia: a multicenter, prospective, randomized, self-controlled clinical trial
Kai YANG ; Jinran LIN ; Fei ZHU ; Suyun FENG ; Zheng LI ; Yue ZHANG ; Ruiming HU ; Hanxiao CHENG ; Zhentao ZHOU ; Yatong WU ; Dingquan YANG ; Jufang ZHANG ; Wenyu WU
Chinese Journal of Dermatology 2025;58(7):603-607
Objective:To compare the efficacy and safety of a domestic hair follicle extraction system versus traditional follicular unit excision (FUE) in extracting hair follicles for the treatment of androgenetic alopecia (AGA) .Methods:A multicenter, randomized, self-controlled clinical trial was conducted on AGA patients aged 18 - 59 years who were recruited from the Huashan Hospital, Fudan University, the Affiliated Hangzhou First People's Hospital, and the China-Japan Friendship Hospital between June 2023 and September 2024. Each patient's scalp was randomly divided into two sides (experimental side vs. control side) using an envelope method. The experimental side underwent robotic hair transplantation with a domestic hair follicle extraction system, and the control side underwent traditional FUE. Hair follicles were extracted from the safe donor area in the occipital region, and implanted into the ipsilateral hair loss area. The primary outcome was the hair transection rate which was calculated immediately after follicular extraction. The secondary outcomes included the hair follicle unit loss rate and the change in hair density at the recipient site on postoperative day 14. Safety was evaluated by assessing the incidence of folliculitis at the donor site on postoperative day 14 and the overall incidence of adverse events. Surgical outcomes were evaluated at 9 months after surgery. Comparisons of evaluation indicators among groups were performed by using a paired t test or Wilcoxon signed-rank test. Results:A total of 55 patients with AGA (51 males and 4 females, aged 32.71 ± 5.75 years) completed the hair follicle transplantation and postoperative follow-up. The hair transection rate ( M[ Q1, Q3]) was 6.65% (4.56%, 10.16%) in the experimental group and 5.28% (3.04%, 8.89%) in the control group (difference = 1.24%, 95% CI: -0.24%, 2.65%) . The hair follicle unit loss rate was 2.00% (1.00%, 3.50%) in the experimental group and 0.50% (0, 2.00%) in the control group, with a significant difference between the two groups ( P = 0.008) . On postoperative day 14, there was no significant difference in the hair density between the experimental group and control group (72.20 ± 25.95 per cm 2vs. 76.49 ± 30.84 per cm 2, P = 0.173) . At 9-month follow-up, both groups showed improvement in the investigator's overall score in the recipient areas. Seven adverse events occurred in 7 subjects (12.72%) in each group, and all were mild folliculitis. Conclusion:The domestic hair follicle extraction system demonstrated comparable efficacy and safety to the traditional FUE in hair transplantation.
7.Effect of Roujishuncuiyin on the improvement of skeletal muscle insulin resistance in a mouse model of type 2 diabetes mellitus
Zhixing CAI ; Qiufang XIA ; Lili CHEN ; Danyang ZHU ; Huiwen ZHU ; Yanan SUN ; Wenyu LIANG ; Heqian ZHAO
Chinese Journal of Tissue Engineering Research 2025;29(35):7537-7543
BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.The traditional Chinese medicine compound Roujishuncuiyin can effectively improve skeletal muscle insulin resistance,but its mechanism has not been clarified.OBJECTIVE:To explore the mechanism of Roujishuncuiyin on skeletal muscle insulin resistance in type 2 diabetes mice.METHODS:Forty db/db mice with type 2 diabetes mellitus were randomized into a model group,a low-dose Roujishuncuiyin group,a high-dose Roujishuncuiyin group,and a positive drug group,with 10 mice in each group.The latter three administration groups were given 157.5 mg/g and 630 mg/g Roujishuncuiyin and 200 mg/g metformin hydrochloride aqueous solution by gavage once a day,respectively.In addition,10 db/dm mice were selected as the blank control group.Mice in the model and blank control groups were given the same dose of 0.9%NaCl solution by gavage.After 12 weeks of intervention,fasting blood glucose was measured in each group of mice,and oral glucose tolerance test was performed to calculate the area under the blood glucose curve.ELISA was used to detect serum insulin level and calculate the resistance index.Mitochondrial structure of skeletal muscle tissue was observed under transmission electron microscopy.Western blot was used to detect the expression levels and phosphorylation levels of protein kinase B(AKT)and glycogen synthase kinase 3β(GSK-3β)proteins in skeletal muscle.RESULTS AND CONCLUSION:(1)Compared with the blank control group,fasting blood glucose,fasting insulin and insulin resistance index were significantly higher in the model group(P<0.05),the area under the curve of the oral glucose tolerance test was significantly increased(P<0.05),the expression of p-AKT and p-GSK3β proteins in tibialis anterior muscle was significantly decreased(P<0.05),and there was a large amount of mitochondrial damage in tibialis anterior muscle and a large number of lipid droplets in the interstitium.(2)Compared with the model group,fasting blood glucose,fasting insulin,and insulin resistance index were significantly reduced in the low-and high-dose Roujishuncuiyin groups and the positive control group(P<0.05),the area under the curve of the oral glucose tolerance test was reduced(P<0.05),the expression of p-AKT and p-GSK3β proteins in the tibialis anterior muscle was significantly elevated(P<0.05),and mitochondrial damage in the tibialis anterior muscle was significantly ameliorated,with decreased lipid droplets in the interstitium.(3)The above indexes were better in the high-dose Roujishuncuiyin group than the low-dose Roujishuncuiyin group(P<0.05),while there was no significant difference between the high-dose Roujishuncuiyin group and positive control group(P>0.05).To conclude,by upregulating the protein levels of p-AKT and p-GSK3β in skeletal muscle tissue,the traditional Chinese medicine compound Roujishuncuiyin can improve structural disorders and mitochondrial morphology in skeletal muscle tissue,reduce insulin resistance in the skeletal muscle and regulate glucose homeostasis in the body.
8.Quality assurance of artificial intelligence models applied to case-specific radiotherapy
Xiaonan LIU ; Guodong JIN ; Wenyu WANG ; Ji ZHU ; Bining YANG ; Siqi YUAN ; Hong QUAN ; Kuo MEN ; Jianrong DAI
Chinese Journal of Radiation Oncology 2025;34(9):949-953
Artificial intelligence (AI) technologies are being widely applied in radiotherapy. However, the integration of AI into clinical workflows of radiotherapy faces a series of challenges, such as poor model interpretability, domain shifts between clinical application and training data, and the inherent model uncertainties. Therefore, case-specific quality assurance (QA) is essential before deploying AI models in clinical practice. This paper reviews and summarizes QA methodologies for the application of AI models in radiotherapy across four key areas: image registration, image generation, region of interest segmentation, and treatment planning.
9.Differentiation and Treatment of Lipid Turbidity Disease Based on Theory of "Spleen Ascending and Stomach Descending"
Yun HUANG ; Wenyu ZHU ; Wei SONG ; Xiaobo ZHANG ; Xin ZHOU ; Lele YANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):244-252
Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment, diet, and lifestyle, which is closely related to many diseases in modern medicine, such as hyperlipidemia, obesity, fatty liver, atherosclerosis, metabolic syndrome, and cardiovascular and cerebrovascular diseases, with a wide range of influence and far-reaching harm. According to the Huangdi Neijing, lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids, which has the function of nourishing, and it is the initial state and source of important substances in the human body such as brain, marrow, essence, and blood. Once the grease of the human body is abnormal, it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach, which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments, leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity, which accumulates in the body's meridians, blood vessels, skin pores, and organs, forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays, it was divided into four common pathogenesis types: ''inability to distinguish between the clear and turbid, turbid stagnation in the Ying blood'', ''spleen not rising clear, turbid accumulation in the vessels'', ''spleen dysfunction, lipid retention in the pores'', ''spleen failure to transportation and transformation, and grease accumulation in the liver''. According to the pathogenesis, it could be divided into four common syndromes, namely, turbid stagnation in the Ying blood, turbid accumulation in the vessels, lipid retention in the pores, and grease accumulation in the liver, and the corresponding prescriptions were given for syndrome differentiation and treatment, so as to guide clinical differentiation and treatment of the lipid turbidity disease.
10.Association between photodynamic diagnosis and treatment efficacy of 5-aminolevulinic acid photodynamic therapy for cutaneous squamous cell carcinoma in situ
Qinyuan ZHU ; Wenjuan MA ; Jing LUAN ; Wenyu WU ; Shujun CHEN
Journal of Chongqing Medical University 2025;50(8):1115-1121
Objective:To investigate the association between photodynamic diagnosis(PDD)and treatment efficacy of 5-aminolevu-linic acid(ALA)photodynamic therapy(PDT)in patients with cutaneous squamous cell carcinoma in situ(cSCCis).Methods:A pro-spective cohort study was conducted among the patients with cSCCis who underwent ALA-PDT in Department of Dermatology,Huashan Hospital,Fudan University,from January 2020 to November 2024.All patients were diagnosed with cSCCis based on biopsy,and invasive squamous cell carcinoma was excluded.Clinical information was collected and PDD was performed before treatment,and the patients were divided into moderate fluorescence group and strong fluorescence groups based on fluorescence intensity.All patients received six sessions of PDT treatment at an interval of 1-2 weeks.The primary endpoint was the initial complete clearance rate at 3 months after the last treatment session,and secondary endpoints were the sustained complete clearance rate at 12 months after the last treatment session and treatment failure rate.The multivariate regression analysis,the survival curves,and the Cox regression analysis were used to investigate the association between PDD fluorescence intensity and treatment efficacy,as well as other influencing factors for treatment efficacy.Results:Compared with the strong fluorescence group,the moderate fluorescence group had significantly lower initial complete clearance rate[57.14%(8/14)vs.93.33%(28/30),odds ratio OR=0.100,P=0.010]and sustained complete clearance rate[42.86%(6/14)vs.76.67%(23/30),OR=0.230,P=0.030)].The multivariate regression analysis showed that moderate fluores-cence was an independent risk factor for initial complete clearance(OR=0.030,P=0.030).The moderate fluorescence group had a significantly higher treatment failure rate than the strong fluorescence group[57.14%(8/14)vs.23.33%(7/30),P=0.030].The survival analysis and the Cox regression analysis showed that moderate fluo-rescence was an independent risk factor for PDT treatment failure(hazard ratio=3.040,P=0.048).There were no significant differences in adverse reactions between the two groups.Conclusion:PDD fluorescence intensity can predict the efficacy of ALA-PDT in patients with cSCCis.Moderate fluorescence indicates a higher risk of treatment failure,which can help to guide clinicians in develop-ing individualized treatment strategies.

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