ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. RESULTS: AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). CONCLUSION In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.
Animals ; Rats, Sprague-Dawley ; Rotator Cuff Injuries/surgery* ; Amnion/transplantation* ; Rats ; Wound Healing ; Rotator Cuff/surgery* ; Male ; X-Ray Microtomography ; Tendons/surgery* ; Biomechanical Phenomena

Objective To analyze the cellular and histopathological characteristics of underdiagnosed thyroid nodules of Chinese thyroid imaging reporting and data system(C-TIRADS) categories 3 and 4a,thus improving the understanding of these lesions. Methods The data of ultrasound and fine needle aspiration cytology were collected from 683 nodules diagnosed based on pathological evidence in 549 patients undergoing thyroid surgery.The cellular and histopathological characteristics of C-TIRADS 3 and 4a nodules were analyzed. Results Two hundred and sixty-eight nodules were classified as C-TIRADS category 3,including 236 benign nodules,12 low-risk ones,and 20 (7.46%) malignant ones.Two hundred and twenty-one nodules were classified as C-TIRADS category 4a,including 133 benign nodules,7 low-risk ones,and 81 (36.65%) malignant ones.The malignancy rates differed between C-TIRADS 3 and 4a nodules (χ²=58.93,P<0.001),and both were higher than the recommended malignancy rate in the guidelines for malignancy risk stratification of thyroid nodules (C-TIRADS) (both P<0.001).According to the pathological evidence,the underdiagnosed C-TIRADS 3/4a nodules were mainly papillary thyroid carcinoma,especially in patients with Hashimoto thyroiditis.There was not a consistent one-to-one match between each ultrasound result and each cytological classification of low-risk thyroid nodules.Conclusions When the malignant features in preoprative ultrasound imaging are atypical or absent,papillary thyroid carcinoma (especially with Hashimoto thyroiditis),follicular carcinoma,and medullary carcinoma are likely to be underdiagnosed as C-TIRADS 3 or 4a nodules.Therefore,efforts should be made to fully understand the cellular and pathological characteristics of these lesions.
Humans ; Thyroid Nodule/diagnostic imaging* ; Female ; Male ; Middle Aged ; Adult ; Ultrasonography ; Biopsy, Fine-Needle ; Aged ; Young Adult ; Thyroid Neoplasms/diagnostic imaging* ; Adolescent

Greater trochanteric pain syndrome(GTPS)is a disease caused by structural lesions of the muscles,fascia,ligaments,and bursae near the greater trochanter of the femur.GTPS causes lateral hip joint pain,severely affecting patients' quality of life.Ultrasound has many advantages,such as real-time diagnosis,portable operation,non-radiation,and high resolution,demonstrating a high application value in the diagnosis and interventional therapy of GTPS.This article reviews the current status of ultrasound in the diagnosis and interventional therapy of GTPS and prospects its application.
Humans ; Ultrasonography ; Femur/diagnostic imaging* ; Hip Joint/diagnostic imaging* ; Arthralgia/therapy*

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Heart failure,as a severe consequence or late-stage manifestation of various cardiac conditions,is marked by high morbidity,high mortality,and high rates of readmission,significantly compromising patients' quality of life.Despite ongoing advancements in novel drugs and technologies that have improved the clinical efficacy of heart failure,5％to 10％of patients still progress to end-stage heart failure annually.Heart transplantation stands as an effective approach to enhance both the quality of life and survival rates for patients with end-stage heart failure.However,due to the scarcity of donor organs,it falls short of meeting the needs of a large number of patients.In this scenario,left ventricular assist device(LVAD)implantation emerges as a promising alternative therapeutic option for these patients.Acute kidney injury(AKI)represents one of the common complications encoun-tered after LVAD implantation,with notable morbidity and mortality rates.This article synthesized relevant research findings and literature to investigate the risk factors associated with the development of AKI in patients following LVAD implantation.

Objective To investigate the role of bone marrow mesenchymal stem cells derived from diabetic mice and their paracrine roles in inducing insulin resistance(IR).Methods The mouse model of diabetes mellitus was established,bone marrow mesenchymal stem cells(BMSC)were extracted and cultured,and the culture supernatant(M-BMSC-CS)was collected.(1)Cell experiment:HepG2 hepatocytes were divided into normal low-glycemic culture group[cultured with low-glycemic DMEM(5.55 mmol·L-1)],M-BMSC-CS experimental group(M-BMSC-CS 75 μL),and high-glycemic and high-lipid control group(given 25 mmol·L-1 high-glycemic DMEM+0.25 mmol·L-1 palmitic acid);(2)Animal experiments:Mice were divided into normal mice group(0.9％NaCl by intraperitoneal injection)and M-BMSC-CS-m group(M-BMSC-CS by intraperitoneal injection of normal mice(injection dose 0.2 mL/10 g)].Glucose intake was measured by glucose oxidase method.The fluorescence intensity of Glut2 protein was detected by immunofluorescence.The expression of insulin signaling pathway protein was detected by Western blot.Test oral glucose tolerance(OGTT)and insulin tolerance(ITT).Results The glucose intakes of the normal low-glucose culture group,the M-BMSC-CS experimental group and the high-glucose and high-lipid control group were(2.96±0.05),(1.64±0.28)and(1.42±0.32)mmol·L-1,respectively;the fluorescence expressions of glucose transporter 2(Glut2)were 53.21±2.70,30.95±3.39 and 34.96±7.60,respectively;the protein expression levels of phosphorylated insulin receptor substrate 1-ser307(p-IRS-1ser307)were 0.46±0.21,1.09±0.24 and 0.91±0.16,respectively;phosphorylated protein kinase(p-AKT)protein expression levels were 0.94±0.05,0.59±0.06 and 0.53±0.05;Glut2 protein expression levels were 1.08±0.14,0.58±0.14 and 0.62±0.09,respectively.The above indexes in M-BMSC-CS experimental group were statistically significant compared with those in normal low-glycemic culture group(all P＜0.05).Fasting blood glucose levels in the normal group and M-BMSC-CS-m group were(5.23±0.57)and(9.30±1.14)mmol·L-1;p-AKT protein expression level were 1.27±0.21 and 0.51±0.19;Glut2 protein expression level were 1.17±0.17 and 0.79±0.09,respectively.The above indexes in M-BMSC-CS-m group were significantly different from those in normal mouse group(P＜0.05).Conclusion BMSC culture supernatant from diabetic mice induced insulin resistance of normal HepG2 hepatocytes in vitro and normal mice in vivo.