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Teprotumumab-trbw,a monoclonal antibody that acts on the insulin growth factor-Ⅰ receptor, was approved in 2020 for the treatment of thyroid-associated ophthalmopathy, but little is known about it in China. It is hoped to provide guidance for clinical use through the review of its molecular structure, pharmacokinetics, therapeutic mechanism, clinical research and safety. It inhibits immune inflammation by blocking thyroid-stimulating hormone receptor /insulin growth factor-Ⅰ receptor crosstalk signaling, so as to reduce the production of hyaluronic acid and inflammatory factors in response. It can also promote the apoptosis of retro-orbital fibroblasts/adipocytes and inhibit the expression of genes related to the synthesis of thyroid hormones, thereby significantly improving the clinical symptoms such as exophthalmos and diplopia. The common adverse reactions of Teprotumumab-trbw are muscle spasm, hyperglycemia, hearing loss and so on. Teprotumumab-trbw is effective and durable in the treatment of thyroid-associated ophthalmopathy, and patients with secondary treatment can also benefit from it, which provides a new way and hope for the treatment of thyroid-associated ophthalmopathy.
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Thyroid-associated ophthalmopathy(TAO)is an organ-specific autoimmune disease, which will cause a series of symptoms to significantly reduce the health level and life quality of patients. The pathogenesis of TAO has not been fully clarified. At present, there is a lack of unified and mature treatment scheme of it. Indeed, T-helper 17 lymphocyte(Th17)cells, regulatory T(Treg)cells and their imbalance are closely related to the immunological pathogenesis of TAO. It is currently believed that the cytokines secreted by Th17 cells can not only promote the inflammatory response of TAO and the fibrosis of orbital connective tissue, but also inhibit the adipogenic differentiation of TAO orbital connective tissue. In addition, Treg cells mainly exert immunosuppressive effect on TAO and delay the disease progression. At the same time, there is a dynamic balance relationship between Th17 and Treg cells, the imbalance of Th17/Treg cells can trigger the occurrence and development of TAO. This paper mainly expounds the influence mechanism of Th17, Treg cells and their balance on TAO, and analyzes the reasons for the differences between different research results, so as to provide some reference for the study of the pathogenesis and clinical treatment of TAO.
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OBJECTIVE@#To explore the therapeutic effect and safety of acupoint thread embedding therapy in treatment of simple obesity of stomach heat and damp obstruction.@*METHODS@#A total of 144 patients with simple obesity of stomach heat and damp obstruction were randomized into an acupoint thread embedding group (72 cases, 3 cases dropped off and 1 case removed) and a sham-embedding group (72 cases, 6 cases dropped off and 3 cases removed). On the base of the lifestyle adjustment, the acupoint thread embedding therapy with PGLA thread was applied to Tianshu (ST 25), Zhongwan (CV 12), Ganshu (BL 18), Shuidao (ST 28), etc. in the acupoint thread embedding group, while in the sham-embedding group, the acupoint selection and operation were all same as the acupoint thread embedding group, but without PGLA thread embedded. In either group, the treatment was given once every 2 weeks, consecutively for 12 weeks and the follow-up was conducted for 3 months after treatment. Separately, before and after treatment as well as in follow-up, the obesity indices (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR] and fat percentage [F%]) were observed in the two groups. Before and after treatment, the indices of blood glucose and insulin (fasting blood glucose [FBG], fasting insulin [FINS] and insulin resistance index [HOMA-IR]), adipocyte factor indices (adiponectin, leptin [LP] and serine protease inhibitor [Vaspin]) and inflammatory factor indices (tumor nercosis factor [TNF-α], interleukin-1β [IL-1β] and interleukin-6 [IL-6]) were observed separately in the two groups. The therapeutic effect and safety were compared between the two groups.@*RESULTS@#After treatment and in follow-up, except WC and WHR in the sham-embedding group, BMI, WC, WHR and F% were all reduced as compared with those before treatment in the two groups (P<0.01, P<0.05), and the values in the acupoint thread embedding group were lower than the sham-embedding group (P<0.01). After treatment, except FBG, LP and Vaspin in the sham-embedding group, FBG, FINS, HOMA-IR, LP and Vaspin were all reduced as compared with those before treatment in the two groups (P<0.01, P<0.05), and adiponectin was increased as compared with that before treatment (P<0.01, P<0.05); the improvements in the acupoint thread embedding group were more significant than the sham-embedding group (P<0.01). After treatment, the levels of serum TNF-α, IL-1β and IL-6 in the acupoint thread embedding group were reduced as compared with the values before treatment and those in the sham-embedding group separately (P<0.01). The total effective rate was 89.7% (61/68) in the acupoint thread embedding group, higher than 19.0% (12/63) in the sham-embedding group (P<0.01). There was no severe adverse reaction reported in the two groups.@*CONCLUSION@#Acupoint thread embedding therapy with PGLA thread can alleviate obesity, regulate glucose metabolism and adipocyte factors activity, improve insulin resistance and inhibit the expression of pro-inflammatory factors in the patients with simple obesity with stomach heat and damp obstruction, and this therapy presents a satisfactory safety in treatment.
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Body Mass Index , Hot Temperature , Obesity/therapy , StomachABSTRACT
Objective:To evaluate the efficacy of modified Xiaoji Baozhong granules combined with scraping in the treatment of abdominal obesity with gastric heat and dampness syndrome and its effect on adipocytokines. Method:One hundred and forty-four patients were randomly divided into the control group and the observation group， 72 cases in each group. The lifestyle adjustments were conducted in both groups. The observation group was given a comprehensive traditional Chinese medicine regimen of modified Xiaoji Baozhong granules combined with scraping. The control group was given modified Xiaoji Baozhong granules combined with scraping. The course of treatment was three months. The body mass index （BMI）， body fat percentage （FP）， waist circumference （WC）， waist to hip ratio （WHR）， obesity and abdominal fat thickness of the two groups were compared before and after treatment. The levels of fasting blood glucose （FBG）， insulin resistance index （HOMA-IR）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， triglyceride （TG）， total cholesterol （TC）， adiponectin， leptin， resistin， endolipid and tumor necrosis factor-α （TNF-α） were compared between the two groups before and after treatment. The clinical efficacy and safety were evaluated. Result:After treatment， the BMI， FP， obesity， WC and WHR of the observation group were lower than those of the control group （<italic>P</italic><0.01）. After treatment， the abdominal wall fat thickness and intra-abdominal fat thickness of patients in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The FBG， HOMA-IR， TG， TC and LDL of the observation group were lower than those of the control group （<italic>P</italic><0.01）， while the HDL level was higher than the control group （<italic>P</italic><0.01）. Adiponectin in the observation group was higher than the control group after treatment （<italic>P</italic><0.01）. The leptin， resistin， visfatin and TNF-α were lower than those in the control group （<italic>P</italic><0.01）. The total clinical efficacy rate of patients in the observation group was 88.24% （60/68）， which was better than 73.53% （50/68） in the control group （<italic>χ</italic><sup>2</sup>=4.755， <italic>P</italic><0.05）. Conclusion:In addition to lifestyle adjustments， modified Xiaoji Baozhong granules combined with scraping treatment can reduce the degree of obesity and fat thickness in patients with abdominal obesity， and regulate lipid， carbohydrate metabolism and adipocytokines， with a better clinical efficacy than simple scraping therapy and the safety in practice.
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Background Graves ophthalmopathy is generally considered to be an organ-speeifie autoimmune disease.It was reported that 99Tc-methylenediphosphonate (99Tc-M)P) has therapeutic effect on Graves ophthalmopathy,though the mechanism has not been completely delineated.Objective This study was to explore the effects of 99Tc-MDP on the proliferation of retrooeular fihrohlasts (RFs) hyaluronic acid (HA) synthesis,and the expression rate of human leucocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1) in cultured RFs.Methods Retroocular connective tissue was obtained from 2 eyes with Graves ophthalmopathy during the orbital decompression surgery.RFs were cultured with explant culture method in DMEM medium with 20％fetal bovine serum.The cells of 2-7 generations were used in the study.Interferon γ (IEN-γ),interleukin-1 (IL-1),tumor necrosis factor-α (TNF-α) was added in medium for 72 hours to stimulate the growth of the RFs,and then 10,100 and 1000 mg/L 99Tc-MDP was respectively used to co-culture the cells with IFN-γ,IL-1 or TNF-α.3H-TdR incorporation was used to detect the proliferation of RFs,and synthesis of HA,expression rate of HLA-DR and ICAM-1 in RFs were assayed by radio-immunoassay and flow cytometry,respeetively.Results Cultured cells showed the fibrous shape under the inverted microseope with the positive response for vimentin and absent response for cytokeratine.After addition of TNF-α,IFN-γ and IL-1,the proliferation value of RFs,HA level,the expression rate of HLA-DR and ICMA-1 in RFs was (4918.33±297.91) counts/min,(505.83±41.29)mg/L,(56.88±14.67)％ and (63.57± 14.11)％ respectively,showing significant differenee in comparison with normal control group(P＜0.01).However,after co-culture of ＞100 mg/L 99Tc-MDP with TNF-α,IFN-γ and IL-1,the proliferation value of RFs,HA level,the expressing rates of HLA-DR and ICMA-1 were significantly lower than those in the TNF-α,IFN-γ and IL-1 only culture groups(P＜0.01),but were still higher than those in the normal group.Conclusions 99Tc-MDP can suppress cytonike-induced activation and growth of RFs derived from Graves ophthalmopathy in vitro at a dosedependent manner.