1.Formulation Characteristics and Efficacy Classification of Chinese Patent Medicines for Cardiovascular and Cerebrovascular Diseases Based on Diagram of Tangye Jingfa Tu
Yuguang WANG ; Runtao ZHUANG ; Yanqing LIU ; Shen LI ; Xiaolan LIN ; Rui JIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):224-233
ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article, based on the formulation compatibility analysis technology of "Tangye Jingfa Tu", clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases, providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines, covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue (2023) (more than 50% of the total), were selected for the study. Within the knowledge system of "Tangye Jingfa Tu", the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally, the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills, Danshen tablets, Qili Qiangxin capsules, Breviscapine tablets, etc., covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines, salty flavor was the most common (48), followed by pungent (33), and sweet (26). According to the dominant herbal flavor, salty flavor was the most common (37), followed by pungent (9), and sour (5). According to the dominant herbal quantity, salty flavor was the most common (27), followed by sour (7), and pungent (5). Furthermore, Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example, most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen (9/10), most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver (7/8), and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys (6/6). However, the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas, as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty, sour, and pungent flavors, which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart, heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.
2.Formulation Characteristics and Efficacy Classification of Chinese Patent Medicines for Cardiovascular and Cerebrovascular Diseases Based on Diagram of Tangye Jingfa Tu
Yuguang WANG ; Runtao ZHUANG ; Yanqing LIU ; Shen LI ; Xiaolan LIN ; Rui JIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):224-233
ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article, based on the formulation compatibility analysis technology of "Tangye Jingfa Tu", clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases, providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines, covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue (2023) (more than 50% of the total), were selected for the study. Within the knowledge system of "Tangye Jingfa Tu", the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally, the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills, Danshen tablets, Qili Qiangxin capsules, Breviscapine tablets, etc., covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines, salty flavor was the most common (48), followed by pungent (33), and sweet (26). According to the dominant herbal flavor, salty flavor was the most common (37), followed by pungent (9), and sour (5). According to the dominant herbal quantity, salty flavor was the most common (27), followed by sour (7), and pungent (5). Furthermore, Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example, most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen (9/10), most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver (7/8), and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys (6/6). However, the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas, as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty, sour, and pungent flavors, which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart, heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.
3.Advances in Lipid-Lowering Therapy for Homozygous Familial Hypercholesterolemia
Rui LI ; Zhuang TIAN ; Shuyang ZHANG
JOURNAL OF RARE DISEASES 2025;4(3):361-369
Homozygous familial hypercholesterolemia (HoFH) is an extremely rare and severe hereditary lipid metabolism disorder, characterized by markedly elevated levels of plasma low-density lipoprotein cholesterol (LDL-C), significantly increasing the risk of atherosclerotic cardiovascular diseases. Among traditional lipid-lowering therapies, the combination of statins and ezetimibe is the basic treatment approach, but its efficacy is limited. In recent years, notable progress has been made in lipid-lowering therapy for HoFH. New drugs such as proprotein convertase subtilisin/kexin type 9 inhibitors and angiopoietin-like protein 3 inhibitors have demonstrated favorable LDL-C-lowering effects and play an active role in treatment. Lipoprotein apheresis can rapidly reduce LDL-C levels and has become an important adjuvant treatment modality. Although approaches like gene therapy and liver transplantation face many challenges, they offer hope for radical cure. Further research is still needed to optimize treatment strategies and regimens for more effective blood lipid management in patients with HoFH.
4.A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey
Chiyu XU ; Yanshu ZHANG ; Ning LUAN ; Xiangyi LIU ; Dayang QIN ; Hongmin WANG ; Xuping XIAO ; Shuihong ZHOU ; Jie ZHANG ; Ping ZHANG ; Yuqing BAI ; Pengpeng WANG ; Yan QI ; Zhongwu SUN ; Zhuang LIU ; Luo BA ; Wenchao WANG ; Xing LU ; Min WANG ; Rui GUO ; Deyi SUN ; Liyuan TAO ; Li ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):2-11
Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.
5.Construction and preparation of human metapneumovirus vaccine based on influenza virus vector
Mengxue GAO ; Xiaoman LIU ; Liru GUO ; Mei KONG ; Zhichao ZHUANG ; Aiping YU ; Rui LI ; Xiaoyan LI
Chinese Journal of Experimental and Clinical Virology 2024;38(1):77-85
Objective:To construct and prepare recombinant virus strains chimeric with human metapneumovirus (HMPV) antigenic epitopes.Methods:Recombinant influenza virus vectors which chimeric with different HMPV antigenic epitopes were rescued by reverse genetics using eight-plasmid system. The recombinant influenza virus strain used the internal genes of A/PR/8/34 (PB1, PB2, PA, NP, NS, M, HA, and NA) as a backbone, with concomitant genetic modifications to insert the B-cell epitopes of HMPV into the HA gene, and the CTL+ Th cell epitopes of HMPV into the NA gene. Preparation of recombinant influenza virus strains using reverse genetics in a " 7+ 1" model. The recombinant virus strains were evaluated by measuring hemagglutinin (HA) titers, half tissue culture infectious dose (TCID 50) and growth curves. Sequencing analysis was conducted to verify whether the rescued viruses carried the chimeric HMPV epitopes. Results:The epitopes of HMPV were inserted into the influenza virus genome and two recombinant influenza virus strains were rescued successfully, named as FLU/HMPV/B and FLU/HMPV/CTL+ Th. HA titers of the recombinant strains were both 2 7, their TCID 50 were 10 5.2/ml and 10 5.0/ml, respectively. After cultured for three passages in chick embryo, these two recombinant strains could proliferate steadily. Whole genome sequencing verified that the FLU/HMPV/B carried the B-cell epitopes of HMPV, the FLU/HMPV/CTL+ Th carried the CTL and Th cell epitopes of HMPV. Growth curve tests also verified that the recombinant strains could proliferate steadily in eggs. Conclusions:Two recombinant influenza virus vector strains carrying the B cell, CTL and Th epitopes of HMPV were rescued successfully. The result of the recombinant virus strains in terms of growth characteristics as well as genetic stability indicate that they meet the requirements for proceeding to the next step of animal experiments. The immunogenicity and immunoprotective effect will be further evaluated by mouse experiments. Ultimately new ideas for the realization of " one vaccine for two uses" or " one vaccine formultiple uses", as well as a new strategy for the development of HMPV vaccine will be proposed.
6.Changes of corneal densitometry in patients with keratoconus after corneal collagen cross-linking
Shuai LI ; Yang GAO ; Limei MA ; Rui LI ; Yixuan QIN ; Caihong SUN ; Yu HAN ; Jinjin ZHANG ; Wenjuan ZHUANG
International Eye Science 2024;24(12):1954-1958
AIM: To observe the changes of corneal densitometry(CD)in patients with keratoconus after corneal cross-linking(CXL).METHODS: Retrospective study. A total of 32 patients(43 eyes)with keratoconus in Ningxia Eye Hospital from April 2020 to April 2022 were selected. Pentacam analysis system divided the cornea into three layers: anterior 120 μm, middle layer and posterior 60 μm, and divides it into five regions with diameters of 0-2, 2-6, 6-10, 10-12 mm and full diameter according to the diameter, and measures the CD in different ranges. The changes of CD were compared before operation and at 1, 3 and 6 mo after operation.RESULTS: There were differences in uncorrected visual acuity, best corrected visual acuity and intraocular pressure before and 6 mo after operation(all P<0.05), and there was no difference in corneal endothelial cells(P=0.477). CD reached its peak at 1 mo after operation, and decreased at 3 mo and 6 mo after operation, but it was still higher than that before operation. There is a significant positive correlation between CD and Kmax in the anterior layer and the whole layer(r=0.164, P=0.016; r=0.152, P=0.023).CONCLUSION: The values of CD peaked at 1 mo after CXL, then it gradually decreased, tending to become stable at 6 mo postoperatively.
7.Summary of the best evidence on health education for patients with temporary enterostomies
Danyang LI ; Jiayuan ZHUANG ; Huayan LIN ; Na LIN ; Rui ZHU ; Yan WANG
Chinese Journal of Nursing 2024;59(12):1454-1461
Objective To systematically retrieve and summarize high-quality evidence on health education for patients with temporary enterostomies to provide an evidence-based basis for clinical practice.Methods We searched UpToDate,BMJ Best Practice,AHRQ,NICE,RNAO,MEDLIVE,WCET,UOAA,NSWOCC,NHMRC,CAN,CNKI,Wanfang,VIP,CBM,PubMed,Web of Science,CINAHL,JBI,and Cochrane Collaboration databases of evidence related to health education for patients with temporary enterostomies,including clinical decisions,guidelines,expert consensuses,evidence summaries,and systematic reviews.The search time limit was from January 1,2013 to August 1,2023.2 researchers who were trained in systematic evidence-based knowledge independently conducted literature screening,quality assessment,extraction and summarization of evidence based on inclusion and exclusion criteria.Results A total of 16 articles were included,including 5 guidelines,2 clinical decisions,4 evidence summaries,2 systematic reviews,2 expert consensuses,and 1 standard.The 24 pieces of the best evidences were summarized in 7 aspects:qualification of health educators,subjects of health education,opportunity of health education,mode and evaluation index of health education,preoperative health education,postoperative health education and home follow-up management.Conclusion The best evidence of health education for patients with temporary enterostomies summarized in this study is scientific and practical,providing evidence-based basis for healthcare professionals to implement health education for patients with temporary enterostomies.
8.Clinical value of high frequency ultrasound in the diagnosis of hip joint involvement in patients with ankylosing spondylitis
Guo-Yan XUE ; Ying-Qi LI ; Rui WANG ; Wen-Xing WANG ; Zhuang DONG ; Jian-Feng DING
China Journal of Orthopaedics and Traumatology 2024;37(4):374-380
Objective To analyze the correlation between hip joint musculoskeletal ultrasound score and ankylosing spondylitis(AS)disease activity,as well as to investigate the value of high frequency ultrasound in the assessment of hip joint involvement in AS.Methods The clinical data of 244 patients with AS who were treated in the rheumatology department of from March 2019 to March 2022 were retrospectively analyzed.Among them,there 174 males and 70 females,aged from 19 to 58 years old with an average of(34.22±9.49)years old;the disease duration of AS patients ranged from 8 months to 26 years,with an average of(13.68±4.04)years.The 244 patients were divided into disease group(83 cases)and control group(161 cases)based in the presence of hip joint involuement.According to the the disease activity,patients in the disease group were further categorezed into active phase(45 cases)and stable phase(38 cases).The ultrasound scores of patients in the active and stable phases of the disease group and the control group were compared.Relevant factors of hip joint involvement in AS patients were analyzed,and analyze the correlation between ultrasound score and Bath ankylosing spondylitis disease activity score index(BASD AI),Bath ankylosing spondylitis functional index(BASFI),visual analogue score of pain(VAS),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and the correlation between hip joint capsule score and tendon attach-ment end score and BASDAI,BASFI,VAS,CRP and ESR.Results The hip joint capsule score(3.06±1.12),femoral head score(1.45±0.43),tendon attachment end score(3.28±1.30)and total ultrasound score(6.65±2.31)of the disease group were higher than those of the control group(1.51±0.48)、(0.66±0.27)、(1.61±0.53)、(3.81±1.44)scores(P<0.05).Multifactor Logstic re-gression analysis showed that the course of disease,hip joint capsule score and total ultrasound score were independent risk factors for hip involvement in AS patients.The hip capsule score(3.65±1.22)and total ultrasound score(8.28±2.33)in the ac-tive phase of the disease group were higher than those in the stable phase(2.48±1.04)、(6.82±1.96)scores(P<0.05).The hip joint capsule score and total ultrasonic score of AS patients were positively correlated with BASDAI,BASFI,VAS,CRP,and ESR(P<0.05,P<0.01).The score of tendon attachment end was positively correlated with CRP(P<0.05).The score of joint capsule effusion in AS patients was positively correlated with BASDAI,BASFI and VAS(P<0.05,P<0.01).The synovial blood flow score was positively correlated with BASDAI,VAS,CRP and ESR(P<0.05,P<0.01).The synovial thickening score was positively correlated with BASDAI,BASFI,VAS,CRP and ESR(P<0.05,P<0.01).There was no correlation between the score of tendon attachment end and BASDAI,BASFI,VAS,CRP and ESR.Conclusion There is a correlation between hip joint ul-trasonic score of hip joint and clinical indexes in AS patients.Hip joint capsule score and total ultrasonic score were indepen-dent risk factors for hip involvement in AS patients.High frequency ultrasound exhibits clinical value in the diagnosis of hip joint involvement in AS patients.
9.Atypical memory B cells in children with frequently relapsing nephrotic syndrome
Ting YANG ; Wenjun YUAN ; Nana LI ; Rui SUN ; Yafei ZHUANG ; Jin CHENG ; Fengjun GUAN
International Journal of Laboratory Medicine 2024;45(19):2415-2419
Objective To observe the distribution of atypical memory B cells in peripheral blood of children with frequently relapsing nephrotic syndrome(FRNS).Methods A total of 60 children with primary ne-phrotic syndrome(PNS)admitted to the hospital from October 2020 to March 2023 were selected as the re-search objects.According to the response to glucocorticoid(GC),they were divided into non-frequently relap-sing nephrotic syndrome(NFRNS)group(25 cases)and FRNS group(35 cases).A total of 20 age-and gen-der-matched healthy children were enrolled as the control group.The changes of atypical memory B cells in each group before and after GC treatment were compared,and the correlation between the changes and clinical data was analyzed.Results Before GC treatment,The percentages of total B cells(CD19+CD20+),total memory B cells(CD19+CD20+CD27+),resting memory B cells(CD19+CD20+CD21+CD27+)and atypical memory B cells(CD19+CD20+CD21-CD27-)in FRNS group and NFRNS group were significantly higher than those in control group.And the FRNS group was significantly higher than the NFRNS group(P<0.05).After GC treatment,the percentages of total B cells,total memory B cells,resting memory B cells,acti-vated memory B cells(CD19+CD20+CD21-CD27+)and atypical memory B cells in FRNS group and NFRNS group were lower than those before GC treatment(P<0.05).The FRNS group had a significantly higher pro-portion of atypical memory B cells than the NFRNS group and the control group(P<0.05).Before GC treat-ment,the 24 h urinary protein in FRNS group and NFRNS group were higher than those in control group,and the levels of immunoglobulin G and albumin were lower than those in control group.The 24 h urinary protein in FRNS group was significantly higher than that in NFRNS group(P<0.05).Before GC treatment,there was a positive correlation between 24 h urinary protein and the proportion of atypical memory B cells in FRNS group(P<0.05).Conclusion There is abnormal distribution of atypical memory B cells in peripheral blood of FRNS children.The increase of atypical memory B cells can be used as a marker of recurrence of FRNS af-ter GC treatment.
10.Effects of electroacupuncture on the glucose-lipid metabolism and the expression of ZAG and GLUT4 in the femoral quadriceps and adipose tissue in the rats with type 2 diabetes mellitus.
Cai-Feng GUO ; Rui LI ; Shan-Shan SONG ; Hao-Ru DUAN ; Rong-Yuan ZHANG ; Shu-Ting ZHUANG ; Wei-Xing GUO ; Ying DONG
Chinese Acupuncture & Moxibustion 2023;43(12):1425-1430
OBJECTIVES:
To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM.
METHODS:
Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined.
RESULTS:
After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05).
CONCLUSIONS
Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.
Rats
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Male
;
Animals
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Glucose/metabolism*
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Electroacupuncture
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Rats, Sprague-Dawley
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Diabetes Mellitus, Type 2/therapy*
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Lipid Metabolism
;
Triglycerides
;
Adipose Tissue/metabolism*
;
Acupuncture Points

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