Honeybee symbiont Bombella apis could restore larval-to-pupal transition disrupted by antibiotic treatment.

Numerous studies have demonstrated the vital roles of gut microbes in the health, immunity, nutrient metabolism, and behavior of adult worker honeybees. However, a few studies have been conducted on gut microbiota associated with the larval stage of honeybees. In the present study, we explored the role of a gut bacterium in larval development and larval-pupal transition in the Asian honeybee, Apis cerana. First, our examination of gut microbial profiling showed that Bombella apis, a larvae-associated bacterium, was the most dominant bacterium colonized in the fifth instar larvae. Second, we demonstrated that tetracycline, an antibiotic used to treat a honeybee bacterial brood disease, could cause the complete depletion of gut bacteria. This antibiotic-induced gut microbiome depletion in turn, significantly impacted the survivorship, pupation rate and emergence rate of the treated larvae. Furthermore, our analysis of gene expression pattens revealed noteworthy changes in key genes. The expression of genes responsible for encoding storage proteins vitellogenin (vg) and major royal jelly protein 1 (mrjp1) was significantly down-regulated in the tetracycline-treated larvae. Concurrently, the expression of krüppel homolog 1(kr-h1), a pivotal gene in endocrine signaling, increased, whilethe expression of broad-complex (br-c) gene that plays a key role in the ecdysone regulation decreased. These alterations indicated a disruption in the coordination of juvenile hormone and ecdysteroid synthesis. Finally, we cultivated B. apis isolated from the fifth instar worker larval of A. cerana and fed tetracycline-treated larvae with a diet replenished by B. apis. This intervention resulted in a significant improvement in the pupation rate, emergence rate, and overall survival rate of the treated larvae. Our findings demonstrate the positive impact of B. apis on honeybee larvae development, providing new evidence of the functional capacities of gut microbes in honeybee growth and development.

An end-end arrhythmia diagnosis model based on deep learning neural network with multi-scale feature extraction.

This study presents an innovative end-to-end deep learning arrhythmia diagnosis model that aims to address the problems in arrhythmia diagnosis. The model performs pre-processing of the heartbeat signal by automatically and efficiently extracting time-domain, time-frequency-domain and multi-scale features at different scales. These features are imported into an adaptive online convolutional network-based classification inference module for arrhythmia diagnosis. Experimental results show that the AOCT-based deep learning neural network diagnostic module has excellent parallel computing and classification inference capabilities, and the overall performance of the model improves with increasing scales. In particular, when multi-scale features are used as inputs, the model is able to learn both time-frequency domain information and other rich information, thus significantly improving the performance of the end-to-end diagnostic model. The final results show that the AOCT-based deep learning neural network model has an average accuracy of 99.72%, a recall of 99.62%, and an F1 score of 99.3% in diagnosing four common heart diseases.

Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

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.

Establishment of A Mouse Model of Obesity and Depression Comorbidity and Its Application in Pharmacological Study of Tripterine / 中国实验方剂学杂志

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.

Effects of resistance training on insulin sensitivity in the elderly: A meta-analysis of randomized controlled trials.

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of resistance training in older adults on insulin sensitivity. METHODS: Cochrane, Embase, PubMed, Web of Science and EBSCO were searched from inception to April 2021. We integrated randomized controlled trials published in English, and participants were non-athletic and aged ≥60 years. The outcome of interest was the change in insulin sensitivity, derived from the homeostatic model of insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c). RESULTS: 12 RCTs were included in this meta-analysis comparing resistance training (n = 232) with control (n = 209). Resistance exercise significantly reduced HOMA-IR level (d = -0.25, 95% CI, -0.43 to -0.06; P < 0.05) and HbA1c levels of (d = -0.51, 95% CI, -0.84 to -0.18; P < 0.05). Subgroup analysis of HOMA-IR revealed that the variables "population", "training intensity" and "period" had significant effects on HOMA-IR, with the largest effect sizes for high-intensity (d = -0.43, 95%CI, -0.85 to -0.22, P < 0.05) and long-term (more than 12 weeks) (d = -0.43, 95%CI, -0.85 to -0.22, P < 0.05) training programs in older adults without type 2 diabetes (T2D) (d = -0.23, 95%CI, -0.42 to -0.04, P < 0.05). Subgroup analysis of HbA1c suggested that resistance training programs with moderate intensity (d = -0.51, 95%CI, -0.90 to -0.12, P < 0.05) and short term (less than or equal to 12 weeks) (d = -0.49, 95%CI, -0.84 to -0.14, P < 0.05) have greater effects on HbA1c. CONCLUSION: The findings of this meta-analysis suggest that resistance training is effective for inducing improvement in insulin sensitivity for elderly. Subgroup analysis showed that high intensity and long period of resistance exercise improve HOMA-IR in healthy old adults, and that resistance training with moderate intensity and short period improve HbA1c in T2D old people. More studies with high methodological qualities and large sample sizes need to be done to further confirm our conclusion.

Relationship Between the Incidence of Deep Vein Thrombosis During Hospitalization and the Energy of Injury in Tibial Plateau Fractures.

This study aimed to investigate the relationship between the incidence of deep vein thrombosis (DVT) during hospitalization and the energy of injury in tibial plateau fractures (TPFs). One hundred and forty patients were enrolled between September 1, 2014, and October 1, 2017. According to Schatzker's classification, they were classified into the low-energy (type I-III) and high-energy (type IV-VI) groups. For DVT evaluation, duplex ultrasonography was performed in the lower extremities preoperatively and postoperatively. The location and changes of DVT were recorded. All patients underwent mechanical and chemical thromboprophylaxis. The incidence of DVT in TPFs was 36.43% and 46.43% preoperatively and postoperatively, respectively. The DVT incidence was 31.75% (20/63) in the low-energy group and 40.26% (31/77) in the high-energy group preoperatively, and 44.44% (28/63) in the low-energy group and 48.05% (37/77) in the high-energy group postoperatively. There was no significant difference between the 2 groups preoperatively (P = .298) and postoperatively (P = .785). The days between operation and discharge (P = .016), blood loss during surgery (P = .016), and preoperative d-dimer level (P = .02) showed differences between the 2 groups. Additionally, 29 new thrombi (14 [48.28%] in the high-energy group and 15 [51.72%] in the low-energy group) appeared and 16 preoperative thrombi disappeared postoperatively. Despite mechanical and chemical thromboprophylaxis, the DVT risk in patients with TPFs remains high. Although the DVT incidence is not significantly different between high-energy and low-energy injuries, the occurrence of DVT should be carefully monitored.

Incidence and risk factors of deep venous thrombosis in lower extremity in patients with tibial plateau fracture / 中华创伤骨科杂志

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.

Incidence of and risk factors for deep vein thrombosis at uninjured limb in patients with lower ex-tremity fracture / 中华创伤骨科杂志

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.

Relationship between the incidence of deep vein thrombosis during hospitalization and the energy of injury in tibial plateau fractures / 国际外科学杂志

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.

A prospective study on the time course and outcome of perioperative deep venous thrombosis in hip fracture patients / 国际外科学杂志

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.