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.

Resveratrol(Res) is a kind of polyphenolic compound, possessing multiple biological activities such as antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. In recent years, the cardiovascular protective mechanism of Res has become a research hotspot. Studies have shown that Res has a protective effect on the cardiovascular system through various pathways, such as inhibiting oxidative stress, regulating ferroptosis of cells, improving ischemia-reperfusion(I/R) injury, regulating lipid metabolism, suppressing inflammatory responses, and enhancing endothelial function. It can also alleviate cardiotoxicity caused by drugs and chemicals. In terms of oxidative stress, Res reduces the level of intracellular reactive oxygen species(ROS) by enhancing the expression of proteins such as silent information regulator 1(SIRT1) and regulating mitochondrial function, thereby alleviating myocardial cell damage. Regarding ferroptosis, Res inhibits the occurrence of ferroptosis by regulating the expression of proteins related to iron metabolism. Res can also improve I/R injury through mechanisms such as activating autophagy and the mitochondrial quality control network. In regard to improving endothelial function, Res protects the function of endothelial cells by regulating multiple signaling pathways, such as downregulating the PREP1-mediated pathway. Res can also regulate lipid metabolism and inhibit the progression of atherosclerosis. In terms of inflammatory responses, Res exerts anti-inflammatory effects through mechanisms such as inhibiting the nuclear factor-kappa B(NF-κB) signaling pathway. In addition, Res has an improving effect on cardiotoxicity caused by different drugs or environmental factors. However, the clinical application of Res still faces limitations such as poor pharmacokinetic properties. In the future, in-depth exploration is needed at multiple levels from basic research to clinical application to clarify the dose-response relationship and standardize the standards of medication regimens with the expectation of providing more effective strategies for the prevention and treatment of cardiovascular diseases.
Humans ; Resveratrol/pharmacology* ; Animals ; Cardiotonic Agents/pharmacology* ; Oxidative Stress/drug effects* ; Cardiovascular Diseases/genetics* ; Cardiovascular System/metabolism* ; Signal Transduction/drug effects*

OBJECTIVE: To explore clinical efficacy of percutaneous endoscopic discectomy with a lateral approach and dual-channel method in treating highly free lumbar disc herniation(LDH). METHODS: A retrospective analysis was conducted on 54 patients with highly free LDH who were treated with spinal endoscopic techniques from January 2021 to December 2022. Twenty-seven patients were treated with lateral approach dual-channel(lateral approach dual-channel group), including 16 males and 11 females, with an average age of (54.6±10.5) years old. Twenty-seven patients were treated with unilateral biportal endoscopic (UBE group), including 17 males and 10 females, with an average age of (52.9±12.3) years old. The number of intraoperative fluoroscopy, operation time and hospital stay, as well as visual analogue scale (VAS) and Oswestry diability index (ODI) of low back and leg pain between two patients before operation, 1 day, 1, 3, and 12 months after operation, and the efficacy was evaluated by the modified MacNab criteria at 12 mohths after operation. RESULTS: All patients were successfully completed surgical and were followed up, the time raged from 12 to 22 months with an average of (13.57±4.12) months. There was no statistically significant difference in operation time between two groups (P>0.05). The hospital stay of lateral approach dual-channel group was (3.9±1.1) days, which was shorter than that of UBE group (6.5±1.4) days, the number of intraoperative fluoroscopy in lateral approach dual-channel group was (12.7±2.1) times, which was more than that in UBE group (6.6±1.3) times, the differences were statistically significant (t=5.197, -7.532;P<0.05). VAS and ODI for low back pain at 1 day and 1 month after operation, and VAS for leg pain at 1 day after operation of lateral approach dual-channel group were superior to those of UBE group, and the differences were statistically significant (P<0.05). However, there were no statistically significant differences in VAS and ODI for low back and leg pain between two groups before operation and 3 and 12 months after operation (P>0.05). VAS and ODI of low back and leg pain were significantly improved at each time point before and after operation in both groups, and the difference were statistically significant (P<0.05). At 12 months after operation, according to the modified MacNab criteria, the excellent and good rates of therapeutic effects between lateral approach dual-channel group and UBE group were 92.6% (25/27) and 88.9% (24/27), respectively, and the difference was not statistically significant (χ²=0.22, P>0.05). CONCLUSION For patients with highly free lumbar intervertebral disc protrusion, both of lateral approach dual-channel method and UBE endoscopic surgery are safe and effective. Endoscopic surgery with lateral approach and dual-channel method could be performed under local anesthesia, allowing for the removal of the nucleus pulposus under direct vision. It is simpler, more efficient.
Humans ; Male ; Female ; Intervertebral Disc Displacement/surgery* ; Middle Aged ; Diskectomy, Percutaneous/methods* ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Adult ; Retrospective Studies ; Aged

OBJECTIVE: To investigate platelet count trajectories after induction therapy with venetoclax combined with azacitidine (VA regimen) in newly diagnosed AML patients and further analyze its clinical significance. METHODS: Clinical date of 50 newly diagnosed AML patients who received VA treatment from March 2020 to July 2023 in Department of Hematology of the First Hospital of Lanzhou University were retrospectively collected. The platelet trajectories after induction chemotherapy were constructed by using group-based trajectory modeling. To study the association between diverse trajectories of platelet counts and compound complete remission (cCR) rate, overall response rate (ORR), minimal residual disease (MRD) negative rate and overall survival (OS) rate. The Cox proportional hazard model was used to evaluate the relationship between platelet trajectory and OS. The logistic regression was used to analyze the influence of individual characteristics on platelet trajectory. RESULTS: Two platelet trajectories were identified based on the model, including platelet slowly increased group (n=31, 62.0%) and platelet rapidly increased group (n=19, 38.0%). There were statistically significant differences in cCR rate, ORR and OS rate between platelet slowly increased group and platelet rapidly increased group (all P < 0.05). The Cox regression analysis showed that platelet rapidly increased group was associated with a decreased risk of mortality compared with platelet slowly increased group (HR=0.153, 95%CI : 0.045-0.527, P =0.003). Logistic regression analysis showed that IDH1/2 mutation (OR =3.908, 95%CI : 1.023-14.923, P =0.046) and platelet transfusion (OR =0.771, 95%CI : 0.620-0.959, P =0.020) were independent influencing factors of platelet trajectory. CONCLUSION The dynamic trajectory of platelet counts in newly diagnosed AML patients who received VA treatment can serve as a significant indicator to observe the efficacy and prognosis. The platelet rapidly increased is an independent protective factor for good prognosis. TheIDH1 /2 mutation and platelet transfusion are independent influencing factors of platelet trajectory.
Humans ; Leukemia, Myeloid, Acute/blood* ; Sulfonamides/administration & dosage* ; Azacitidine/therapeutic use* ; Platelet Count ; Retrospective Studies ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Induction Chemotherapy ; Survival Rate

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans ; Female ; Breast Neoplasms/diagnostic imaging* ; Middle Aged ; Lymphatic Metastasis/diagnostic imaging* ; Axilla ; Retrospective Studies ; Nomograms ; Ultrasonography ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging* ; Risk Factors ; Ki-67 Antigen

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.