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Acta Pharmaceutica Sinica B ; (6): 4801-4822, 2023.
Article in English | WPRIM | ID: wpr-1011212


Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Chinese Journal of Experimental Traditional Medical Formulae ; (24): 81-91, 2022.
Article in Chinese | WPRIM | ID: wpr-940832


ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity (COM) model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group (Chow), a diet-induced obesity group (DIO), and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group, a COM group, and a tumor necrosis factor-α(TNF-α) knock-down group. In the TNF-α knock-down group, TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis, and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group, a DIO group, a DIO + low-dose tripterine group (0.5 mg·kg-1), a DIO + high-dose tripterine group (1.0 mg·kg-1), a COM group, a COM + low-dose tripterine group (0.5 mg·kg-1), and a COM + high-dose tripterine group (1.0 mg·kg-1). The body weight, food intake, glucose tolerance, white/brown fat ratio, serum total cholesterol (TC), triglyceride (TG), and high-/low-density lipoprotein cholesterol (HDL-C and LDL-C) content were recorded, and obesity of mice in each group was evaluated. Forced swimming test (FST), tail suspension test (TST), and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y, tryptophan hydroxylase 2 (TPH2), and brain-derived neurotrophic factor (BDNF) in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific, obesity was manifested as increased body weight and food intake (P<0.05, P<0.01), as well as increased NPY expression in the central amygdala, and depression was manifested as prolonged immobility time in FST and TST (P<0.01), and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus (DRN) and basolateral nucleus of the amygdala (BLA). The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST (P<0.05, P<0.01), increased TPH2/BDNF-positive neurons in BLA, and showed no significant changes in obesity. In DIO mice, the administration of 0.5 mg·kg-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance (P<0.01) and food intake (P<0.05). In COM mice, 1.0 mg·kg-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance (P<0.01), and food intake (P<0.05), and immobility time in TST (P<0.01), increase TPH2-BDNF double-labeled cells in BLA and DRN, and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity, and its mechanism may be related to the inhibition of central nervous system inflammation.

Chinese Journal of Orthopaedic Trauma ; (12): 102-108, 2019.
Article in Chinese | WPRIM | ID: wpr-745083


Objective To investigate the incidence and risk factors of deep venous thrombosis (DVT) in lower extremity in patients with tibial plateau fracture.Methods The data from 148 patients with tibial plateau fracture were retrospectively analyzed who had been admitted to the Department of Orthopaedic Trauma,Honghui Hospital between September 2014 and December 2017.They were 90 males and 58 females,aged from 19 to 83 years (average,47.2 ± 13.1 years).According to the Schatzker classification of tibial plateau fractures,24 cases belonged to type Ⅰ,17 to type Ⅱ,25 to type Ⅲ,29 to type Ⅳ,34 to type Ⅴ,and 19 to type Ⅵ.The incidence of DVT was detected by venous ultrasound of bilateral lower extremities before and after surgery.The factors related to the occurrence of DVT were statistically analyzed.Univariate analysis was used to determine risk factors,and multivariate logistic regression analysis was used to identify the primary independent risk factors.Results The preoperative DVT incidence was 43.92% (65/148) and the postoperative DVT incidence 52.70% (78/148).Distal thrombus predominated both preoperatively and postoperatively.Age (OR =1.043,95% CI 1.015 ~ 1.072,P =0.002) and D-dimer level upon admission (OR =1.219,95% CI 1.009 ~ 1.473,P =0.040) were independent risk factors for preoperative DVT formation;age (OR =1.075,95% CI 1.042 ~ 1.110,P =0.000),operative time (OR =0.994,95% CI 0.989~0.999,P=0.016),D-dimer level at 1 day postoperatively (OR=1.135,95% CI 1.025~1.258,P =0.015) and at 3 days postoperatively (OR =1.366,95% CI 1.008 ~ 1.853,P =0.044) were independent risk factors for postoperative DVT.Conclusions The incidence of DVT in the lower extremity may be high in patients with tibial plateau fracture.Distal thrombus is the main manifestation.In fracture patients,especially the middle-aged and elderly ones,dynamic monitoring of D-dimer level should be combined with lower extremity venous ultrasound for early diagnosis of DVT.In patients with lower extremity DVT,surgical progress should be accelerated on the basis of good surgical quality to reduce the incidence of postoperative lower extremity DVT.

Chinese Journal of Orthopaedic Trauma ; (12): 1060-1065, 2018.
Article in Chinese | WPRIM | ID: wpr-734187


Objective To investigate the incidence of and risk factors for deep venous thrombosis (DVT) at the uninjured limb during hospitalization in patients with lower extremity fracture. Methods The clinical data were retrospectively analyzed of the 494 patients who had been hospitalized for lower extremity fracture at Department of Orthopedics, Honghui Hospital from September 1, 2014 to October 1, 2017. They were 228 males and 266 females with an average age of 58.9 ± 18.9 years ( from 16 to 94 years ) . 290 fractures occurred proximally to the knee, 101 fractures around the knee and 103 fractures distally to the knee. They received anticoagulant prophylaxis or treatment during hospitalization. After operation, they were examined with Doppler sonography for bilateral lower limbs to detect occurrence of thrombus. The incidence of DVT at the uninjured limb during hospitalization was recorded and its possible risk factors were analyzed statistically. The possible risk factors ( gender, age, fracture type, body mass index, concomitant internal disease, time from injury to surgery, time from surgery to discharge, American Society of Anesthesiologists rating, operation duration, blood loss, fluid infusion volume and D-dimer level ) were screened by single factor logistic regression analysis and the major independent risk factors were determined by multi-factor logistic re-gression analysis.Results DVT occurred at the injured limb during hospitalization in 237 cases ( 47.97%). Of them, 221 ( 44.74%) had peripheral thrombus, 7 central thrombus ( 1.42%) and 9 mixed thrombus ( 1.82%). DVT occurred at the uninjured limb during hospitalization in 98 cases ( 19.84%). Of them, 90 (18.2%) had peripheral thrombus, one central thrombus (0.2%) and 7 mixed thrombus (1.4%). Of the 98 patients with DVT at the uninjured limb, 74 (75.51%) had DVT at both lower limbs and 24 (24.49%) had DVT only at the uninjured limb. Age and D-dimer level one day after surgery were independent risk factors for DVT at the uninjured limb during hospitalization. Conclusions The incidence of actual DVT at the unin-jured limb in patients with lower extremity fracture cannot be ignored in spite of use of anticoagulants for pro-phylaxis or treatment during hospitalization. We should also be aware that age and D-dimer level one day after surgery are independent risk factors for DVT at the uninjured limb during hospitalization.

International Journal of Surgery ; (12): 745-749, 2018.
Article in Chinese | WPRIM | ID: wpr-693312


Objective To investigate the relationship between the incidence of deep vein thrombosis (DVT) during hospitalization and the energy of injury in tibial plateau fractures (TPFs).Methods 140 patients were enrolled in the study between September,2014,and October,2017 in Honghui Hospital,Xi'an Jiaotong University.According to the Schatzker classification,the low-energy group (Schatzker Ⅰ-Ⅲ) X-ray showed a simple or lateral fracture or compression fracture of the lateral plateau (n =63);the high-energy group (Schatzker Ⅳ-Ⅵ) X-ray showed the medial tibia or double of the tibial plateau (n =77).Duplex Ultrasonography was performed in lower extremities before and after surgical intervention for DVT evaluation and record the incidence of DVT,the days during hospitalization,the blood loss during surgery and the level of D-Dimer.All patients received mechanical and chemical thromboprophylaxis.The patient was followed up for one month after surgery,and the lower extremity ultrasound was reviewed and recorded.The measurement data were expressed as ((x) ± s),and the categorical variables were expressed in composition ratio.The measurement data were all in accordance with the normal distribution and the variance was uniform.The t-test was used,and the Chi-square test was used for comparison between groups.Results The incidence of thrombosis of tibial plateau fracture in TPFs was 36.43% and 46.43% pre-operation and post-operation respectively.The thrombosis incidence was 31.75 % (20/63) in the low-energy group and 40.26% (31/77) in the high-energy group pre-operation.The thrombosis incidence was 44.44% (28/63) in the low-energy group and 48.05% (37/77) in the high-energy group post-operation.Statistical analysis showed no significant difference between the two groups pre-operation (P =0.298) and post-operation(P =0.785).The days during hospitalization [(11.94 ± 4.18) d,(9.56 ± 2.54) d],the blood loss during surgery [(208.96 ±224.43) ml,(129.68 ± 142.14) ml] and the level of D-Dimer [(2.39 ± 3.38) mg/L,(1.21 ± 2.32) mg/L] at pre-operation showed differences in the high energy group and the low energy group,respectively.Conclusions The incidence of DVT in TPFs is high during the hospital,but most of DVT is concentrated in the distal to the knee.Although the incidence of high energy injury and low energy injury DVT is not significantly different in TPFs,we should also be alert to the occurrence of DVT.

International Journal of Surgery ; (12): 731-735,封3, 2018.
Article in Chinese | WPRIM | ID: wpr-693309


Objective To investigate the time course and prognosis of perioperative deep venous thrombosis in hip fracture patients.Methods A prospective study was conducted to analyze the clinical data of 88 patients with hip fractures who were injured within 24 h in the Department of Traumatic Orthopedics,Honghui Hospital,Xi'an Jiaotong University from September 2017 to March 2018.The patients were divided into anticoagulant group (n =53) (low molecular weight heparin combined with physical prevention) and non-anticoagulant group (n =35) (physical prevention only).The patients were examined by deep venous examination of the lower limbs every 24 h after they were admitted to hospital.The number and incidence of new thrombosis within 4 d after injury and 7 d after operation were recorded.The histogram was recorded.The prognosis of thrombosis and the occurrence of thrombosis in different fracture sites were also recorded.Counting data were expressed by percentage (%),and x2 test was used for comparison between groups.Results In the anticoagulant group,33 cases of deep venous thrombosis occurred in 53 cases,and the incidence rate was 62.26%.Deep venous thrombosis occurred in 29 of 35 patients in non-anticoagulant group (82.86%).The difference between the two groups was statistically significant (P < 0.05).In anticoagulant group,thrombosis occurred in 10 cases (18.87%),7 cases (13.21 %),1 case (1.89%),5 cases (9.43%),7 cases (13.21%) and 3 cases (5.66%) on the 1st,2nd,3rd and 4th day after injury.In non-anticoagulant group,thrombosis occurred in 7 cases (20.0%),8 cases (22.86%),2 cases (5.71%),1 case (2.86%),4 cases (11.42%),3 cases (8.57%),1 case (2.86%),1 case (2.86%),1 case (2.86%),1 case (2.86%) and 1 case (2.86%) respectively on the 1st,2nd,3rd,4th and 6th days after operation.Of the 62 thrombus cases,22 (35.48%) were changed from unilateral to bilateral,6 (9.68%) disappeared,3 (4.84%) from distal to proximal (1 case of pulmonary embolism),1 (1.61%) from proximal to distal,and 30 (48.38%) remained unchanged.43 cases of femoral neck fracture,27 cases of deep vein thrombosis,the incidence rate was 62.79%,45 cases of intertrochanteric fracture,35 cases of deep vein thrombosis,the incidence rate was 77.78%.There was no significant difference between the two groups (P > 0.05).Conclusions Despite routine prophylactic anticoagulation therapy,the incidence of deep venous thrombosis is still high in hip fracture patients.The peak time of perioperative deep venous thrombosis in hip fracture patients was 2 d after injury and 2 d after operation.There was no significant change in thrombus after conventional anticoagulation therapy in patients with deep venous thrombosis during perioperative period,and even some of the thrombus changed from unilateral to bilateral.