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.

Objective:To investigate the effects of the novel oral edaravone(EDA)on rats with diabetic encepha-lopathy(DE).Methods:The network pharmacology research methodology was employed to elucidate the mechanism of action of oral EDA in the treatment of diabetes mellitus,identify intersecting targets,and conduct initial validation of these findings in vivo.Thirty male SD rats were randomly assigned to three groups:A normal control(control)group,a diabetic encephalopathy DE(DE)group,and an oral edaravone treatment(DE+EDA)group.Diabetic encephalop-athy was induced in both the DE and DE+EDA groups using the streptozotocin(STZ)method.After successful model-ing,the DE+EDA group received oral administration of EDA,while the other two groups were administered equal doses of saline as controls.Serum samples were examined for lipid release rate,and the protein expression levels of oxidative stress factor 3-nitrotyrosine(3-NT)and apoptotic factor cysteinyl aspartate specific proteinase-3(caspase-3)in brain tissues were detected by Western blot.Brain samples were stained with HE staining to observe the pathological changes.Histopathological changes were observed through hematoxylin-eosin(HE)staining.Results:Network pharmacological analysis yielded 27 core targets,and functional annotation of gene bioprocesses showed that the intersecting targets were mainly enriched in response to oxidative stress and neuronal apoptosis.Serum-related lipid assay showed that the DE+EDA group had significantly improved lipid metabolism disorders compared with the DE group.Additionally,expression levels of 3-NT and caspase-3 were significantly higher in the DE group when compared with controls(P＜0.05);How-ever,both markers exhibited a significant decrease within the DE+EDA treatment cohort as opposed to their counter-parts in the DE group(P＜0.05).HE staining showed that in DE group the cellular arrangement was disordered,the cells were shrunk with intact plasma membrane,and the nuclei were condensed showing karyopyknosis,fragmented and dissolved.Compared with the DE group,the brain tissue in the DE+EDA group was relatively dense and neatly ar-ranged,and the cell karyopyknosis,fragmentation and lysis were significantly improved.Conclusion:Both network pharmacology and in vivo experiments provide preliminary evidence that oral EDA reduces damage in diabetic encepha-lopathy rats.

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.

Objective:To investigate the effect of Omaha system interventional management on therapeutic effect and incidence of major adverse cardiovascular events(MACE)during follow-up in patients with heart failure(HF).Methods:This randomized controlled study enrolled 110 HF patients treated in Second Affiliated Hospital of Chi-nese PLA Air Force Military Medical University between January 2021 and January 2023.They were divided into control group(n=55,routine nursing)and intervention group(n=55,interventional management based on Omaha system).Both groups received intervention for 1 month and were followed up for 6 months.The heart function,negative emotion,self-care capacity,quality of life,and cumulative incidence of MACE during the 6-month fol-low-up were compared between two groups.Results:Compared with patients in the control group,those in the in-tervention group had significant higher left ventricular ejection fraction(LVEF)[(60.32±4.79)％vs.(50.11±4.58)％],scores of exercise of self-care agency(ESCA)[(142.33±6.58)points vs.(89.26±7.19)points]and General Quality of Life Inventory 74(GQOLI-74)[(88.61±4.15)points vs.(70.59±7.85)points](P＜0.001 all),and significant lower left atrial diameter(LAD)[(36.18±2.98)mm vs.(40.25±3.05)mm],left ventricu-lar end-systolic diameter(LVESd)[(42.11±3.46)mm vs.(48.49±3.78)mm],scores of hospital anxiety and depression scale[HADS(A)][(10.05±2.11)points vs.(14.33±2.05)points]and HADS(D)[(9.15±1.31)points vs.(13.37±2.18)points](P＜0.001 all).The incidence rate of MACE in intervention group(9.09％vs.29.09％)was significantly lower than that of control group(P=0.004).Conclusion:Omaha system interventional management could significantly improve cardiac function and negative emotions,improve self-care capacity and quality of life,and reduce the incidence of MACE during follow-up in patients with heart failure.

Objective:To investigate the relationship between collateral circulation and viable myocardium (VM) in patients with coronary chronic total occlusion (CTO).Methods:A total of 88 patients (76 males, 12 females, age (61.0±9.8) years) with coronary CTO were retrospectively analyzed. All patients underwent both 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT myocardial perfusion imaging and 18F-FDG PET myocardial metabolism imaging for evaluation of VM at the First People′s Hospital of Changzhou between September 2012 and June 2023, and they were scheduled to receive coronary revascularization. The perfusion/metabolism mismatch myocardium was regarded as VM. The VM index within the CTO region was calculated, reflected the quantities of VM: VM index=(summed rest score within the CTO region-summed 18F-FDG uptake score within the CTO region)/reduced perfusion myocardial segments×4×100%. Rentrop grading of collateral circulation was performed based on coronary angiography. The differences of VM index within the CTO region between poor-developed (PD, Rentrop grade 0-1) and well-developed (WD, Rentrop grade 2-3) collateral circulation, and among different Rentrop grades were analyzed by the independent-sample t test or Kruskal-Wallis rank sum test. The linear regression analysis was used to evaluate the relationship between Rentrop grading and VM index within the CTO region. The ROC curve was constructed to analyze the predictive value of Rentrop grading for VM within the CTO region. Results:The VM index within the CTO region was significantly higher in WD patients ( n=54) compared to those in PD patients ( n=34): (45.8±16.3)% vs (21.3±16.7)% ( t=-6.79, P<0.001). Moreover, the VM index within the CTO region increased with increased Rentrop grade, and there was a significant difference among 4 groups ( H=30.22, P<0.001). Multiple linear regression analysis showed that only the Rentrop grading was an independent influencing factor for the VM index within the CTO region ( β=9.29, 95% CI: 5.91-12.67, P<0.001). ROC curve showed that the sensitivity and specificity of Rentrop grading score≥2 for predicting the presence or absence of VM within the CTO region were 65.8%(52/79) and 7/9, with the AUC of 0.724(95% CI: 0.619-0.814). Conclusions:In CTO patients who are scheduled for revascularization and evaluation of VM, as the Rentrop grading increases, the VM index within the CTO region also increases. The presence of VM within the CTO region can be predicted with Rentrop grading score ≥2.

Objective:To investigate the relationship between collateral circulation and viable myocardium (VM) in patients with coronary chronic total occlusion (CTO).Methods:A total of 88 patients (76 males, 12 females, age (61.0±9.8) years) with coronary CTO were retrospectively analyzed. All patients underwent both 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT myocardial perfusion imaging and 18F-FDG PET myocardial metabolism imaging for evaluation of VM at the First People′s Hospital of Changzhou between September 2012 and June 2023, and they were scheduled to receive coronary revascularization. The perfusion/metabolism mismatch myocardium was regarded as VM. The VM index within the CTO region was calculated, reflected the quantities of VM: VM index=(summed rest score within the CTO region-summed 18F-FDG uptake score within the CTO region)/reduced perfusion myocardial segments×4×100%. Rentrop grading of collateral circulation was performed based on coronary angiography. The differences of VM index within the CTO region between poor-developed (PD, Rentrop grade 0-1) and well-developed (WD, Rentrop grade 2-3) collateral circulation, and among different Rentrop grades were analyzed by the independent-sample t test or Kruskal-Wallis rank sum test. The linear regression analysis was used to evaluate the relationship between Rentrop grading and VM index within the CTO region. The ROC curve was constructed to analyze the predictive value of Rentrop grading for VM within the CTO region. Results:The VM index within the CTO region was significantly higher in WD patients ( n=54) compared to those in PD patients ( n=34): (45.8±16.3)% vs (21.3±16.7)% ( t=-6.79, P<0.001). Moreover, the VM index within the CTO region increased with increased Rentrop grade, and there was a significant difference among 4 groups ( H=30.22, P<0.001). Multiple linear regression analysis showed that only the Rentrop grading was an independent influencing factor for the VM index within the CTO region ( β=9.29, 95% CI: 5.91-12.67, P<0.001). ROC curve showed that the sensitivity and specificity of Rentrop grading score≥2 for predicting the presence or absence of VM within the CTO region were 65.8%(52/79) and 7/9, with the AUC of 0.724(95% CI: 0.619-0.814). Conclusions:In CTO patients who are scheduled for revascularization and evaluation of VM, as the Rentrop grading increases, the VM index within the CTO region also increases. The presence of VM within the CTO region can be predicted with Rentrop grading score ≥2.

Objective : To investigate the diagnostic value of linear array endoscopic ultrasonography ( EUS) for common bile duct microlithiasis． Methods : Data of patients who attended in the hospital and diagnosed as common bile duct microlithiasis and biliary sludge by EUS were selected．A total of 85 patients with magnetic resonance cholangiopancreatography ( MRCP) examination and ERCP treatment during hospitalization were enrolled．The results of endoscopic retrograde cholangiopancreatography / endoscopic sphincterotomy ( ERCP / EST) were the gold standard for diagnosis．The results of EUS，MRCP，and diagnostic ERCP were compared with the gold standard， and the sensitivity，specificity，positive predictive value，negative predictive value，and diagnostic accuracy of the three methods were calculated，respectively．The chi-square test was used for comparison of the above indices． Results : Of all 85 patients，63 had positive EUS results，among whom 5 had false positive results; 22 had negative EUS results，among whom 1 had false negative results．Of all 85 patients，49 had positive MRCP results，among whom 4 had false positive results; 36 had negative MRCP results，among whom 14 had false negative results．Of all 85 patients，59 had positive diagnostic ERCP results，among whom 10 had false positive results; 26 had negative diagnostic ERCP results，among whom 10 had false negative results．The sensitivity，specificity，positive predictive value( PPV) ，negative predictive value ( NPV) ，and accuracy of EUS in diagnosing common bile duct microlithia- sis were 98. 3% ，80. 8% ，92. 1% ，95. 4% and 92. 9% ，respectively． For MRCP，these values were 76. 3% ， 84. 6% ，91. 8% ，61. 1% and 78. 8% ，respectively．For diagnostic ERCP，these values were 83. 1% ，61. 5% ， 83. 1% ，61. 5% and 76. 5% ，respectively．The EUS group had a significantly higher accuracy than the MRCP group ( χ2 = 6. 986，P ＜0. 05) and diagnostic ERCP group ( χ2 = 8. 900，P ＜0. 05) ．The areas under the ROC curves ( AUC) and 95% CI of EUS group，MRCP group and diagnostic ERCP were 0. 895 ( 95% CI: 0. 802 - 0. 988，P＜0. 001) ，0. 804 ( 95% CI: 0. 702 －0. 907，P ＜0. 001) and 0. 723 ( 95% CI: 0. 598 －0. 848，P = 0. 001) ，respectively． Conclusion EUS has a high diagnostic value in the diagnosis of common bile duct microli- thiasis and thus can be used as the preferred examination before therapeutic ERCP．

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

Objective:To investigate the effects of the novel oral edaravone(EDA)on rats with diabetic encepha-lopathy(DE).Methods:The network pharmacology research methodology was employed to elucidate the mechanism of action of oral EDA in the treatment of diabetes mellitus,identify intersecting targets,and conduct initial validation of these findings in vivo.Thirty male SD rats were randomly assigned to three groups:A normal control(control)group,a diabetic encephalopathy DE(DE)group,and an oral edaravone treatment(DE+EDA)group.Diabetic encephalop-athy was induced in both the DE and DE+EDA groups using the streptozotocin(STZ)method.After successful model-ing,the DE+EDA group received oral administration of EDA,while the other two groups were administered equal doses of saline as controls.Serum samples were examined for lipid release rate,and the protein expression levels of oxidative stress factor 3-nitrotyrosine(3-NT)and apoptotic factor cysteinyl aspartate specific proteinase-3(caspase-3)in brain tissues were detected by Western blot.Brain samples were stained with HE staining to observe the pathological changes.Histopathological changes were observed through hematoxylin-eosin(HE)staining.Results:Network pharmacological analysis yielded 27 core targets,and functional annotation of gene bioprocesses showed that the intersecting targets were mainly enriched in response to oxidative stress and neuronal apoptosis.Serum-related lipid assay showed that the DE+EDA group had significantly improved lipid metabolism disorders compared with the DE group.Additionally,expression levels of 3-NT and caspase-3 were significantly higher in the DE group when compared with controls(P＜0.05);How-ever,both markers exhibited a significant decrease within the DE+EDA treatment cohort as opposed to their counter-parts in the DE group(P＜0.05).HE staining showed that in DE group the cellular arrangement was disordered,the cells were shrunk with intact plasma membrane,and the nuclei were condensed showing karyopyknosis,fragmented and dissolved.Compared with the DE group,the brain tissue in the DE+EDA group was relatively dense and neatly ar-ranged,and the cell karyopyknosis,fragmentation and lysis were significantly improved.Conclusion:Both network pharmacology and in vivo experiments provide preliminary evidence that oral EDA reduces damage in diabetic encepha-lopathy rats.