1.Mechanism of Chaishao Kaiyu Decoction in ameliorating hippocampal neuroinflammation in depressed rats based on complement component C3/C3aR pathway.
Ying-Juan TANG ; Hai-Peng GUO ; Man-Shu ZOU ; Yuan-Shan HAN ; Jun-Cheng LIU ; Yu-Hong WANG
China Journal of Chinese Materia Medica 2025;50(1):1-9
This study investigated the mechanism of Chaishao Kaiyu Decoction in improving hippocampal neuroinflammation in depressed rats based on complement component 3(C3)/C3 receptor(C3aR). A total of 60 SD rats were randomly divided into a blank group, a model group, high, medium, and low dose groups of Chaishao Kaiyu Decoction, and a positive drug group, with 10 rats in each group. Except for the blank group, chronic unpredictable mild stress(CUMS) was used to construct depression models in other groups. Sucrose preference, open-field experiment, forced swimming, and water maze were used to detect the changes in depression-like behavior in each group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum inflammatory factor level in rats, and hematoxylin-eosin(HE) staining and Nissl staining were employed to observe the pathological damage of hippocampal neurons. Golgi-Cox staining was used to observe the dendritic spine damage of hippocampal neurons, and immunofluorescence and Western blot were utilized to detect the expression of microglial marker Iba-1 and C3/C3aR protein in the hippocampus of rats. The behavioral results showed that compared with the model group, Chaishao Kaiyu Decoction could significantly strengthen the sugar water preference, increase the distance and number of voluntary activities, shorten the immobility time in forced swimming and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant. ELISA results showed that the content of inflammatory factors in the hippocampus of depressed rats was significantly higher than that of the blank group, and the content of inflammatory factors decreased significantly after the intervention of Chaishao Kaiyu Decoction. In addition, Chaishao Kaiyu Decoction could relieve pathological damage such as cell swelling and loose arrangement of hippocampus tissue. In the Western blot experiment, the expression levels of C3 and C3aR proteins in the model group were higher than those in the blank group, while the expression of C3 and C3aR in Chaishao Kaiyu Decoction could be down-regulated. Immunofluorescence results showed that compared with the model group, the fluorescence intensity of microglia marker Iba-1 decreased significantly after the intervention of Chaishao Kaiyu Decoction and positive drugs. The antidepressant effect of Chaishao Kaiyu Decoction may be related to the down-regulation of C3/C3aR signaling pathway-related proteins, thus alleviating hippocampal inflammation.
Animals
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Hippocampus/metabolism*
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Rats, Sprague-Dawley
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Drugs, Chinese Herbal/administration & dosage*
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Rats
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Male
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Depression/metabolism*
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Complement C3/metabolism*
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Receptors, Complement/metabolism*
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Humans
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Neuroinflammatory Diseases/genetics*
2.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
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Rats
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Nucleus Accumbens/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Depression/complications*
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Membrane Glycoproteins/genetics*
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Rats, Sprague-Dawley
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Sleep Initiation and Maintenance Disorders/complications*
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Neurons/metabolism*
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Receptors, Immunologic/genetics*
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Signal Transduction/drug effects*
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Synapses/metabolism*
3.Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency
Chengcheng WANG ; Xing TANG ; Chunmei LI ; Zhongbo WANG ; Yanlin FU ; Min DAI ; Min YANG ; Congcong YU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):163-169
ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome (CFS) with Qi deficiency and its effects on TCM syndromes, fatigue symptoms, serum superoxide dismutase (SOD), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group (100 cases) and an observation group (100 cases). The control group was treated with vitamin B compounds, and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes, fatigue symptoms, levels of serum SOD, MDA, and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment, the total effective rate of the control group was 54.34% (50/92), while that of the observation group was 88.54% (85/96). The total effective rate of the observation group was higher than that of the control group (χ2=27.13,P<0.05). Compared with those in the two groups before treatment, scores of fatigue self-assessment scale (FSAS), physical fatigue and mental fatigue, and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased (P<0.05). After treatment, scores of FSAS, physical fatigue and mental fatigue, and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group (P<0.05). Compared with those in the two groups before treatment, TCM syndrome scores in the two groups after treatment were significantly decreased (P<0.05). After treatment, TCM syndrome scores in the observation group were significantly decreased compared with those in the control group (P<0.05). Compared with those in the two groups before treatment, MDA levels in the two groups were significantly decreased (P<0.05), ox-LDL levels in the observation group were significantly decreased (P<0.05), and SOD levels were significantly increased (P<0.05). After treatment, compared with those in the control group, the serum MDA and ox-LDL levels in the observation group were significantly decreased (P<0.05), and the serum SOD was significantly increased (P<0.05). No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency, which can effectively improve the fatigue symptoms of patients, increase the level of SOD, and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants, inhibiting the production of lipid peroxides, and improving the body's ability to resist oxidative stress.
4.The value of diagnostic nomogram based on CT radiomics for the preoperative differentiation between benign and malignant thyroid follicular neoplasms
Pengzhou TANG ; Caiyue REN ; Yueming WANG ; Zhengrong ZHOU
Chinese Journal of Radiology 2022;56(2):136-141
Objective:To investigate the value of nomogram constructed by CT-based radiomics for differentiating benign and malignant thyroid follicular neoplasms.Methods:Totally 200 post-surgery patients with pathologically confirmed thyroid follicular neoplasms in Fudan University Shanghai Cancer Center from January 2016 to December 2018 were retrospectively analyzed. Among the patients, 46 were follicular thyroid carcinoma (FTC) and 154 patients were follicular thyroid adenoma (FTA). The patients were randomly divided into a training set ( n=140) and validation set ( n=60) using a random number table. CT signs and radiomics features of each patient were analyzed within the LIFEx package. A predictive model was developed by the least absolute shrinkage and selection operator regression to build a nomogram based on selected parameters. The predictive effectiveness of differentiating benign and malignant thyroid follicular neoplasms was evaluated by the area under receiver operating characteristic curve (AUC). Calibration plots were formulated to evaluate the reliability and accuracy of the nomogram based on internal (training set) and external (validation set) validity. The clinical value of the nomogram was estimated through the decision curve analysis. Results:The prediction nomogram was built with 4 selected parameters, including grey level zone length matrix (GLZLM)-gray-level zone length matrix_zone length non-uniformity, GLZLM-gray-level zone length matrix_low gray-level zone emphasis, CONVENTIONAL_HUQ3, CONVENTIONAL_HUmean. In training and validation sets, the AUCs for differentiating FTC and FTA were 0.863 (95%CI 0.746-0.932), 0.792 (95%CI 0.658-0.917), accuracy were 87.9% and 75.0%, sensitivity were 67.9% and 66.7%, specificity were 91.1% and 90.5%, respectively. The calibration curves indicated good consistency between actual observation and prediction for differentiating the malignancy. Decision curve analysis demonstrated the nomogram was clinically useful.Conclusions:The CT radiomics mode shows the certain value and great potential to identify benign or malignant thyroid follicular neoplasms and the nomogram can accurately and intuitively predict the malignancy potential in patients with thyroid follicular neoplasms.
5.Effects of bariatric metabolic surgery on body composition
Beibei CUI ; Liyong ZHU ; Pengzhou LI ; Weizheng LI ; Guohui WANG ; Xulong SUN ; Guangnian JI ; Zhaomei YU ; Haibo TANG ; Xianhao YI ; Jiapu LING ; Shaihong ZHU
Chinese Journal of Digestive Surgery 2020;19(11):1173-1182
Objective:To explore the effects of bariatric metabolic surgery on body composition.Methods:The retrospective cohort study was conducted. The clinicopathological data of 66 patients with metabolic diseases who were admitted to the Third Xiangya Hospital of Central South University from January 2013 to December 2014 were collected. There were 42 males and 24 females, aged (40±11)years, with a range from 17 to 63 years. Of the 66 patients, 27 undergoing laparoscopic sleeve gastrectomy (LSG) and 39 undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) were allocated into LSG group and LRYGB group, respectively. The body composition of all patients was determined by dual-energy X-ray absorptiometry at preoperation and postoperative 6 months. Observation indicators: (1) the changes of anthropometric parameters, glucolipid metabolism, body fat mass percentage (BF%) and the ratio of Android BF% and Gynoid BF% (A/G ratio) from preoperation to postoperative 6 months; (2) the changes of whole and local body composition from preoperation to postoperative 6 months; (3) analysis of the correlation between BF% and anthropometric parameters, glucolipid metabolism. (4) Follow-up. Follow-up was conducted using outpatient or hospitalization examination to detect the changes of body composition at the time of postoperative 6 month. The follow-up time was up to July 2015. Measurement data with normal distribution were represented as Mean± SD, paired-samples t test was used for intra-group comparison, and independent-samples t test when baseline data were consistency or covariance analysis when baseline data were not consistency was used for inter-group comparison. Measurement data with skewed distribution were represented as M ( P25, P75), and comparison between groups was analyzed using Wilcoxon signed rank test. The correlation test was undertaken with the Pearson bivariate analysis. Results:(1) The changes of anthropometric parameters, glucolipid metabolism, BF% and A/G ratio from preoperation to postoperative 6 months: for patients in the LSG group, the body mass, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), diastolic blood pressure (DBP), systolic blood pressure (SBP), fasting plasma glucose (FPG), HbA1c, high density lipoprotein cholesterol (HDL-C), triglyceride (TG), whole BF%, arms BF%, legs BF%, trunk BF%, Android BF%, Gynoid BF% and A/G ratio at preoperation and postoperative 6 months were (102±17)kg, (37±5)kg/m 2, (118±14)cm, 1.01±0.06, (94±14)mmHg(1 mmHg=0.133 kPa), (137±15)mmHg, (8.1±4.2)mmol/L, 7.3%±2.4%, (1.11±0.26)mmol/L, 2.14 mmol/L(1.73 mmol/L, 2.59 mmol/L), 40%±6%, 46%±10%, 36%±8%, 42%±6%, 45%±6%, 37%±7%, 1.23±0.18 and (82±15)kg, (29±4)kg/m 2, (101±13)cm, 0.95±0.08, (76±10)mmHg, (118±16)mmHg, (7.2±1.2)mmol/L, 5.4%±0.8%, (1.26±0.32)mmol/L, 1.21 mmol/L(0.88 mmol/L, 1.55 mmol/L), 36%±8%, 41%±9%, 34%±10%, 38%±8%, 41%±8%, 35%±10%, 1.20±0.17, respectively. There was no significant difference in the intra-group comparison of the Gynoid BF% and A/G ratio ( t=1.903, 1.730, P>0.05) and there were significant differences in the intra-group comparison of the rest of above indicators ( t=12.748, 13.283, 9.013, 3.804, 6.031, 6.226, 2.393, 4.287, -2.900, 3.193, 2.932, 5.198, 2.167, 3.357, 3.116, P<0.05). For patients in the LRYGB group, the body mass, BMI, WC, WHR, DBP, SBP, FPG, HbA1c, HDL-C, TG, whole BF%, arms BF%, legs BF%, trunk BF%, Android BF%, Gynoid BF% and A/G ratio at preoperation and postoperative 6 months were (80±12)kg, (28±4)kg/m 2, (98±9)cm, 0.96±0.05, (85±10)mmHg, (134±17)mmHg, (8.6±2.8)mmol/L, 8.3%±1.7%, (1.13±0.26)mmol/L, 2.06 mmol/L(1.15 mmol/L, 3.30 mmol/L), 30%±8%, 29%±11%, 23%±9%, 37%±7%, 40%±7%, 29%±8%, 1.42±0.26 and (69±9)kg, (24±3)kg/m 2, (91±8)cm, 0.93±0.05, (80±9)mmHg, (129±18)mmHg, (7.4±1.8)mmol/L, 7.0%±1.5%, (1.18±0.29)mmol/L, 1.29 mmol/L(0.85 mmol/L, 2.02 mmol/L), 25%±8%, 23%±12%, 20%±9%, 29%±9%, 32%±10%, 25%±9%, 1.29±0.25, respectively. There was no significant difference in the intra-group comparison of the SBP and HDL-C ( t=1.733, -1.073, P>0.05) and there were significant differences in the intra-group comparison of the rest of above indicators ( t=10.525, 10.200, 7.129, 2.887, 2.805, 2.517, 3.699, 2.608, 7.997, 8.018, 6.029, 8.342, 8.069, 5.813, 6.391, P<0.05). There were significant differences in DBP, SBP, HbA1c, trunk BF%, Android BF% and A/G ratio at postoperative 6 months between LSG group and LRYGB group ( F=6.408, t=2.641, F=20.673, 5.140, 5.735, 4.714, P<0.05). (2) The changes of whole and local body composition from preoperation to postoperative 6 months: for patients in the LSG group, the whole fat mass, muscle mass, fat-free mass at preoperation and postoperative 6 months were (38.74±9.68)kg, (57.71±11.62)kg, (60.14±11.95)kg and (26.64±8.29)kg, (48.65±13.80)kg, (51.00±14.27)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=5.256, 5.413, 5.315, P<0.05); the arms fat mass, muscle mass, fat-free mass were (5.19±1.67)kg, (5.78±1.58)kg, (6.10±1.64)kg and (3.73±1.19)kg, (5.10±1.53)kg, (5.43±1.57)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=7.564, 5.405, 5.363, P<0.05); the legs muscle mass and fat-free mass were (19.05±4.19)kg, (19.93±4.35)kg and (15.93±4.71)kg, (16.81±4.87)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=5.623, 5.568, P<0.05); the trunk fat mass and fat-free mass were (21.93±4.90)kg, (29.7±5.94)kg and (14.69±4.79)kg, (24.78±7.02)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.903, 5.421, P<0.05); the Android fat mass and fat-free mass were (4.16±1.19)kg, (5.01±1.12)kg and (2.57±0.90)kg, (3.83±1.20)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.288, 7.637, P<0.05); the Gynoid fat mass and fat-free mass were (5.51±1.42)kg, (9.27±1.86)kg and (3.85±1.16)kg, (7.65±2.31)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=7.461, 5.672, P<0.05); the skeletal muscle index were (8.86±1.38)kg/m 2 and (7.49±1.71)kg/m 2, respectively, showing a significant differences in the intra-group comparison ( t=5.724, P<0.05). For patients in the LRYGB group, the whole fat mass, muscle mass, bone mineral content, fat-free mass at preoperation and postoperative 6 months were (23.58±7.80)kg, (51.76±8.35)kg, (2.55±0.48)kg, (54.31±8.63)kg and (16.88±6.86)kg, (49.41±7.70)kg, (2.47±0.50)kg, (51.88±8.05)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=9.001, 3.974, 4.354, 4.075, P<0.05); the arms fat mass were (2.72±2.37)kg and (1.73±1.02)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=3.470, P<0.05); the legs fat mass, muscle mass, fat-free mass were (5.21±2.46)kg, (16.68±3.50)kg, (17.60±3.66)kg and (4.01±2.12)kg, (15.63±2.90)kg, (16.54±3.05)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=6.592, 3.372, 3.319, P<0.05); the trunk fat mass were (14.87±4.11)kg and (10.38±4.00)kg, respectively, showing a significant difference in the intra-group comparison of the above indicators ( t=8.431, P<0.05); the Android fat mass and fat-free mass were (2.61±0.86)kg, (3.96±0.87)kg and (1.81±0.79)kg, (3.78±0.67)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.032, 2.153, P<0.05); the Gynoid fat mass and fat-free mass were (3.14±1.17)kg, (7.89±1.58)kg and (2.44±0.96)kg, (7.43±1.26)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=6.112, 3.207, P<0.05); the skeletal muscle index were (8.04±1.22)kg/m 2 and (7.43±1.13)kg/m 2, respectively, showing significant differences in the intra-group comparison ( t=4.953, P<0.05). There were significant differences in whole muscle mass, whole fat-free mass, arms fat mass, legs muscle mass, legs fat-free mass, trunk fat-free mass, Android fat-free mass, Gynoid fat-free mass and skeletal muscle index at postoperative 6 months between LSG group and LRYGB group ( F=13.846, 13.614, 23.696, 7.100, 7.127, 15.243, 16.921, 8.625, 5.497, P<0.05). (3) Analysis of the correlation between BF% and anthropometric parameters, glucolipid metabolism: the whole BF% of 66 patients was positively correlated with body mass, BMI, WC and WHR ( r=0.405, 0.663, 0.625, 0.331, P<0.05); the arms BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.432, 0.682, 0.639, 0.309, P<0.05); the legs BF% was positively correlated with body mass, BMI and WC ( r=0.366, 0.646, 0.564, P<0.05); the trunk BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.332, 0.560, 0.554, 0.335, P<0.05); the Android BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.327, 0.537, 0.543, 0.336, P<0.05); the Gynoid BF% was positively correlated with BMI and WC ( r=0.561, 0.488, P<0.05), and negatively correlated with FPG ( r=-0.491, P<0.05); the A/G ratio was negatively correlated with BMI ( r=-0.334, P<0.05), and positively correlated with FPG ( r=0.506, P<0.05); the skeletal muscle index was positively correlated with body mass, BMI, WC and WHR ( r=0.757, 0.641, 0.609, 0.519, P<0.05), and negatively correlated with HDL-C ( r=-0.369, P<0.05). (4) Follow-up: 66 patients were followed up at the time of postoperative 6 month. Conclusions:Both LSG and LRYGB significantly change body composition. LRYGB is superior to LSG in reducing trunk BF% and Android BF%. The effects of the two surgical methods on fat mass and bone mineral content are similar. LSG lead to a more significant decrease in whole muscle mass, and LRYGB lead to a more significant decrease in legs muscle mass and skeletal muscle index.

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