Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

OBJECTIVE: To explore the effectiveness of additional anti-rotation steel plate assisted intramedullary nail technology in treatment of aseptic femoral non-union patients. METHODS: A retrospective analysis was conducted on 21 patients with aseptic femoral non-union who admitted between September 2020 and October 2024 and treated with additional anti-rotation steel plate assisted intramedullary nail technology. There were 17 males and 4 females, aged 25-67 years (mean, 44 years). There were 19 cases of femoral anterograde intramedullary nail fixation, 1 case of femoral retrograde intramedullary nail fixation, and 1 case of steel plate fixation with fatigue fracture. There were 9 cases of hypertrophic non-union and 12 cases of atrophic non-union. All patients had varying degrees of fracture end atrophy/sclerosis. Among them, 20 patients who were fixed with intramedullary nails underwent removal of soft tissue and hardened bone at the fracture end, and cortical treatment resulted in the appearance of "chili sign" at the fracture end. Iliac bone grafting and anti-rotation steel plate fixation were performed. One patient with steel plate fixation was removed the steel palte and fixed with a retrograde intramedullary nail, while the hardened bone at the fracture end was removed, iliac bone grafting and anti-rotation steel plate fixation were performed. Postoperative follow-up observation included the incision healing, maximum knee flexion range of motion, bone healing, length of lower limbs, and subjective satisfaction. The lower extremity functional scale (LEFS) score was used to evaluate the lower limb function. RESULTS: All incisions healed by first intention. All patients were followed up 7-26 months (mean, 15.5 months). At last follow-up, the femoral fracture healed with the obvious callus formation at the fracture end; the maximum knee flexion range of motion was 95°-127° (mean, 112.67°). The LEFS score increased from 29.9±6.7 before operation to 75.9±3.0 at last follow-up, and the difference was significant (t=-29.622, P<0.001). Except for 1 patient who underwent intramedullary nail dynamic treatment before operation and had a lower limb shortening of about 0.9 cm, the other patients had bilateral lower limbs of equal length. All patients had no postoperative infections, mal-union of fractures, deep vein thrombosis, joint stiffness, or other complications. CONCLUSION The use of additional anti-rotation steel plate assisted intramedullary nail technology in the treatment of aseptic femoral non-union not only overcomes the drawbacks of insufficient stability at the fracture end of intramedullary nails, but also overcomes the shortcomings of biased fixation with steel plates. It has the advantages of minimal trauma, effective maintenance of fracture stability, and ideal postoperative functional recovery, making it an effective treatment for aseptic femoral non-union.
Humans ; Male ; Fracture Fixation, Intramedullary/instrumentation* ; Female ; Bone Plates ; Middle Aged ; Adult ; Femoral Fractures/surgery* ; Retrospective Studies ; Bone Nails ; Aged ; Fractures, Ununited/surgery* ; Treatment Outcome ; Bone Transplantation/methods* ; Steel ; Fracture Healing

OBJECTIVE: To identify protein markers that may be associated with ulcerative colitis (UC) by analyzing differential proteins in the salivary exosomes from newly diagnosed patients with active UC and healthy controls (HC), and to investigate the function of salivary exosome-specific high-expression proteins in UC patients and their potential role in the pathogenesis of UC. METHODS: All patients and healthy controls were recruited from Peking University People' s Hospital. Whole saliva was obtained from 37 patients with newly diagnosed active ulcerative colitis (n=37) and apparently healthy controls (n=10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The differentially expressed protein genes underwent gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis using the DAVID tool. In vitro, macrophages were co-cultured with salivary exosomes from UC group and those from HC group, respectively, and real-time quantitative polymerase chain reaction (qPCR) was used to detect levels of CD80⁺ and CD86⁺. Additionally, ELISA was performed to measure secretion levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in the cell supernatant. RESULTS: A total of 259 proteins were co-expressed in saliva exosomes from UC group and HC group, among which 11 proteins were highly expressed in the UC group, including PDIA4, A2M, EEF2, C3, PSMA2, PSMB6, PSMA1, IGHG1, IGHG3, IGHG4 and SERPING1, while 4 proteins were lowly expressed in UC group, including TCN1, SLPI and SERPING. Functional analysis of these 15 proteins, along with 129 specific proteins found only in the UC patients and 69 specific proteins found only in HC patients, respectively, was conducted using GO/KEGG. The results revealed that in the UC group, proteasome-related proteins such as PSMA1, PSMA2 and PSMB6 expressions were increased in salivary exosomes while many key molecules involved in complement cascade pathways, such as C3 were up-regu-lated. In vitro co-culture experiments demonstrated that compared with healthy controls, the salivary exosomes of the UC patients in active stage could play a pro-inflammatory role by promoting the transformation of macrophages into M1 type cells that secrete inflammatory factors IL-1β, IL-6 and TNF-α. CONCLUSION Salivary exosomes in the UC patients may have the function of promoting inflammation. Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups. Among them, C3, PSMA2, PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group. These findings suggest that proteins with high specific expression in salivary exosomes of the UC patients have the potential to be used as a disease marker for UC diagnosis and may contribute to the pathogenesis of UC.
Humans ; Colitis, Ulcerative/metabolism* ; Exosomes/metabolism* ; Saliva/metabolism* ; Biomarkers/analysis* ; Male ; Female ; Adult ; Case-Control Studies ; Interleukin-6/metabolism* ; Middle Aged

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective:To analyze the effects of paroxetine combined with aniracetam on the treatment of senile depression and the levels of 5-hydroxytryptamine (5-HT), cortisol and cystatin C(CysC).Methods:A total of 80 patients admitted to the psychiatric Department of Psychiatry, Suzhou City Guangji Hospital from January 2020 to January 2023 were selected and divided into two groups by random number table method: control group (40 cases) and observation group (40 cases). The control group was treated with oral paroxetine hydrochloride tablets, and the observation group was treated with oral paroxetine hydrochloride combined with aniracetam tablets. Negative emotions were assessed by Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) before and after treatment, and sleep quality was assessed by Pittsburgh Sleep Quality Scale (PSQI). Serum levels of central neurotransmitters [norepinephrine (NE) and 5-HT], neurotrophic factor (BDNF), oxidative stress [cortisol and malondialdehyde (MDA)] and amino acid metabolism [cysteine (Hcy) and CysC] were measured before and after treatment.Results:After treatment, SAS and SDS scores in both groups were significantly decreased (all P<0.05), and SAS and SDS scores in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, the sleep quality, sleep time, sleep time, sleep efficiency, sleep disorders, hypnotic drugs, daytime function scores and PSQI total scores of the two groups were significantly decreased (all P<0.05), and the above scores of the observation group were significantly lower than those of the control group ( P<0.05). After treatment, the serum levels of NE, 5-HT and BDNF in 2 groups were significantly increased, and the serum levels of NE, 5-HT and BDNF in the observation group were significantly higher than those in control group (all P<0.05). After treatment, the levels of serum cortisol and MDA in both groups were significantly decreased, and the levels of serum cortisol and MDA in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, the serum Hcy and CysC levels in 2 groups were significantly decreased, and the serum Hcy and CysC levels in the observation group were significantly lower than those in the control group (all P<0.05). Conclusions:Paroxetine combined with aniracetam is more effective than paroxetine alone in the treatment of senile depression, which can effectively relieve anxiety and depression symptoms, improve sleep quality, and have positive effects on serum neurotransmitters, neurotrophic factors, oxidative stress and amino acid metabolism levels of patients.

Objective:To explore application value of observed tumor enhancement characteristics by dynamic enhancement magnetic resonance imaging(MRI)in assessing blood supply of small hepatocellular cancer.Methods:The cases data of 80 patients with suspected small hepatocellular cancer who admitted to Yichang Central People's Hospital from January 2019 to January 2023 were retrospectively analyzed.The enhancement characteristics of tumors of all patients were real-timely observed by MRI scanner,which included the relative enhancement degree(RSI),enhancement mode,time-signal intensity curve,etc.The enhanced characteristics of the tumors were recorded,which were combined with a series of variables included disease history,tumor type,tumor size,the number of tumor,liver function status of patients to conduct analysis.The receiver operating characteristics(ROC)curve was adopted to analyze the application value of the observed tumor enhancement characteristics by dynamic enhancement MRI in assessing the status of blood supply of small hepatocellular cancer.Results:There were statistically significant differences in the RSI(F=40.151,P＜0.05),enhancement degree(x2=27.374,P＜0.05),and time-signal intensity curve(x2=20.950,P＜0.05)of dynamic enhanced MRI among different stages of small hepatocellular cancer.The differences in medical history(F=17.844,P＜0.05),tumor type(x2=11.219,P＜0.05),tumor size(x2=14.081,P＜0.05),and the number of tumor(x2=74.310,P＜0.05)among different enhancement degrees of arterial phase were also statistically significant.With the enhancement degree increased,the asymptomatic period increased,and the number of malignant tumors increased,and tumor size increased.The differences in liver function status among different time-signal intensity curves were statistically significant(F=330.182,325.872,216.689,P＜0.05).The area under curve(AUC)value of the ROC of the RSI of observed tumor enhancement characteristics by dynamic enhancement MRI was 0.582(95％CI:0.493-0.670)in assessing blood supply of small hepatocellular cancer.Conclusion:Dynamic enhancement MRI can observe the vascular generation and hemodynamic changes of small hepatocellular cancer,which has a certain application value in assessing blood supply of small hepatocellular cancer,and it can help doctors to choose appropriate treatment plan and assess treatment effect.

Objective Motortherapy and neck muscle resistance training are used to study the effects of resistance training on neck pain level and surface myoelectric activity of student pilots of carrier aircraft.Methods We conducted an intervention experiment on the neck pain of the carrier-based aircraft student pilots.The experiment period was 3 months.The experimental subjects were male carrier-based aircraft student pilots aged from 23 to 35.Questionnaires,including the Cervical Dysfunction Index and the Chinese Physical Activity Questionnaire,were issued,followed by cervical muscle function tests,including cervical maximum muscle strength,cervical range of motion,and surface electromyography tests.The experimental subjects were randomly divided into the control group and the resistance training group,with 8 in each.The subjects in the control group recieved usual military training.Those in the resistance training group recieved targeted training programs developed by using the self-developed cervical spondylosis prevention training device in addition to usual military training.The programs were carried out for resistance training three times a week for 20 minutes in each.Cervical maximum muscle strength,cervical range of motion,and surface electromyography were tested again before the end of the intervention experiment.The data were analyzed by SPSS 22.0.The results were expressed by mean±standard deviation((-x)±s).P<0.05 was considered statistically significant.Results(1)After 12-week intervention,resistance training had a significant effect on visual pain analog scale(VAS).(2)After the intervention,the comparison results of the subjects'cervical spine dysfunction index(NDI)before and after their own tests showed that the level of cervical spine dysfunction was significantly improved.(3)After the intervention,the results of inter-group comparison of the subjects'own joint motion showed that the self-variation difference of the subjects in the resistance training group was significantly different in forward flexion,backward extension,left flexion,right flexion,right rotation and left rotation.(4)After the intervention,the comparison results between the two groups of subjects'own neck muscle strength showed that there was no significant difference in the self-change of the six movements of subjects in the resistance training group.(5)The root mean square(RMS)values in the four movement tests of flexion,extension,flexion and flexion before and after the intervention in the resistance training group showed no significant difference between the left and right sternocleidomastoid muscle and the right and right trapezius muscle.(6)The integrated electromyography(iEMG)in the four movement tests of flexion,extension,flexion and flexion before and after the intervention in the resistance training group showed no significant difference between the left and right sternocleidomastoid muscle and the right and right trapezius muscle superior bundle.Conclusion After 12 weeks of resistance training,VAS scores and NDI scores of resistance training subjects are significantly reduced,indicating that resistance training can alleviate neck pain and improve cervical spine dysfunction.12-week resistance training can enhance the strength of neck muscles of carrier-based aircraft student pilots and improve the anti-fatigue ability of neck muscles.Meanwhile,it can enhance the range of motion of neck joints,improve the load of the deep and shallow muscle fibers of the four tested muscles in the neck and optimize the activation mode of the deep and shallow muscles in the neck.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.