BACKGROUND:Neurotrophins represent a novel therapeutic approach for spinal cord injury,showing promising clinical applicability.Autophagy modulation is one of the mechanisms by which neurotrophins exert their effects,yet the specific signaling pathways involved remain unclear. OBJECTIVE:To explore how neurotrophin-3(NT-3)modulates autophagy in oligodendrocytes via switching between P75NTR and TrkC receptors and promotes neurological function recovery after spinal cord injury,aiming to further clarify the specific molecular mechanisms involved. METHODS:Twenty-four Sprague-Dawley rats were randomly divided into three groups:sham operation,spinal cord injury,and NT-3 groups.The therapeutic effect of NT-3 on spinal cord injury in rats was evaluated using the Basso,Beattie,and Bresnahan locomotor rating scale.The expression levels of NT-3,Olig1,myelin basic protein,and the autophagy marker LC3B in rat spinal cord tissue were detected by western blot.In a cellular experiment,oligodendrocytes were cultured in vitro and divided into six groups:oxygen-glucose deprivation(OGD),OGD+NT-3,OGD+NT-3+P75NTR plasmid,OGD+NT-3+TrkC plasmid,OGD+3-methyladenine(an autophagy inhibitor),and OGD+rapamycin(an autophagy activator).Oligodendrocyte morphology was observed under a light microscope,cell apoptosis was assessed by TUNEL staining,and the expression of TrkC receptor,P75NTR,LC3B,and the phosphorylation status of the PI3K/AKT/mTOR and AMPK/mTOR signaling pathways were evaluated by western blot. RESULTS AND CONCLUSION:Animal experiments demonstrated that compared with the sham operation group,NT-3 expression significantly increased after spinal cord injury(P<0.05);exogenous NT-3 treatment accelerated neurological function recovery in rats post spinal cord injury(P<0.05)and increased the expression of Olig1 and myelin basic proteins(P<0.05).Cellular experiments revealed that 3 hours marked the early to middle/late phase transition.Compared with the OGD group,oligodendrocytes in the OGD+NT-3 group could maintain their morphology for a longer period of time,TrkC receptor expression was lower in the early phase and significantly upregulated in the middle/late phase(P<0.05),whereas P75NTR protein expression was upregulated in the early phase and downregulated in the middle/late phase(P<0.05),and autophagy levels showed an initial increase followed by a decrease(P<0.05).By comparing the morphology and TUNEL staining results of cells in the OGD+NT-3,OGD+rapamycin,and OGD+3-methyladenine groups,we found that either promoting or inhibiting autophagy alone had adverse effects on oligodendrocyte survival,whereas modulating autophagy in a manner similar to NT-3 could maximally maintain cell survival.NT-3 could promote autophagy in the early phase via the P75NTR/AMPK/mTOR signaling pathway and inhibit autophagy in the later phase through the TrkC/PI3K/AKT/mTOR signaling pathway.Based on these findings,it is concluded that NT-3 can bidirectionally regulate autophagy in oligodendrocytes through the switching of P75NTR/TrkC receptors,thereby maintaining cell survival and facilitating the recovery of neurological functions in rats after spinal cord injury.

Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals ; OX40 Ligand/physiology* ; Purpura, Thrombocytopenic, Idiopathic/immunology* ; Cell Differentiation ; Mice ; T-Lymphocytes, Helper-Inducer/cytology* ; T Follicular Helper Cells/cytology* ; Signal Transduction ; Receptors, OX40 ; Mice, Inbred C57BL ; Humans ; Female

Objective To investigate the predictive value of combined radiomic features derived from chest CT scans with clinical characteristics for epidermal growth factor receptor(EGFR)gene mutations in non-small cell lung cancer(NSCLC).Methods A multi-center case-control study was conducted on the clinical data and CT images of 1 070 NSCLC patients from the radiology departments of the 3 medical institutions between January 2013 and October 2023.The 719 NSCLC patients from the First Affiliated Hospital of Army Medical University were randomly divided into a training set and an internal validation set in a ratio of 7∶3;The 173 patients in the Eastern Theatre General Hospital and the 178 patients in Army Medical Centre of PLA were assigned into the external validation set 1 and 2,respectively.Least absolute shrinkage and selection operator(LASSO)regression was employed to identify the optimal radiomic features,which were subsequently used to construct a radiomics model.Univariate and multivariate logistic regression analyses were applied to identify clinical features associated with EGFR mutation,thereby developing a clinical model.The radiomic and clinical features were subsequently combined to develop a comprehensive model.All the 3 classification models were built using random forest(RF)machine learning.The area under curve(AUC),accuracy,sensitivity and specificity were utilized to evaluate the predictive performance of the models.Calibration curve was plotted to assess the goodness of fit of the comprehensive model,while decision curve analysis was performed to assess the clinical utility of the model.Results The AUC value of the radiomics model was 0.762 4(95%CI:0.692 4～0.825 1),0.745 4(95%CI:0.671 1～0.814 3),and 0.724 7(95%CI:0.639 7～0.801 6),respectively,in the internal validation set,external validation set 1,and external validation set 2;The AUC value of the clinical prediction model was 0.691 7(95%CI:0.627 9～0.757 6),0.652 5(95%CI:0.576 7～0.729 1),and 0.779 2(95%CI:0.712 5～0.847 3),respectively in the above sets in turn;The comprehensive model constructed based on clinical features and radiomic features showed the best predictive efficacy,with an AUC value of 0.818 0(95%CI:0.757 7～0.874 3),0.782 4(95%CI:0.703 1～0.848 2),and 0.796 6(95%CI:0.718 1～0.868 6),respectively in the above sets.Calibration curve analysis indicated that the comprehensive model had a good fit,while decision curve analysis revealed that the model provided a favorable net benefit.Conclusion Our comprehensive model constructed based on chest CT radiomic features and clinical characteristics shows superior predictive performance for EGFR gene mutations in NSCLC across multiple center datasets,which may be helpful for clinical decision-making for treatment strategies.

Objective To evaluate the predictive value of deep learning features from chest CT images combined with clinical and radiomics features for epidermal growth factor receptor(EGFR)mutations in non-small cell lung cancer(NSCLC).Methods This case-control study retrospectively analyzed clinical and imaging data of 1 070 NSCLC patients from radiology departments at three hospitals(January 2013 to October 2023).Patients were divided into:a training set(n=502)and internal validation set(n=217)via 7∶3 randomization of 719 cases from the First Affiliated Hospital of Army Medical University;external validation set 1(n=173)from General Hospital of Eastern Theater Command;external validation set 2(n=178)from Daping Hospital of Army Medical University.Deep learning features were extracted using a 2.5D convolutional neural network(CNN)with ResNet101 backbone,radiomics features were derived from CT images,and clinical risk factors were identified to construct models.An integrated model combined deep learning,clinical,and radiomics features.All four models were developed using random forest(RF)classifiers.Calibration curves assessed goodness-of-fit,and decision curve analysis(DCA)evaluated clinical utility.Results The deep learning model achieved AUCs of 0.833 7(95%CI:0.770 6～0.884 7),0.815 1(0.741 6～0.882 8),and 0.810 1(0.745 2～0.873 6)in the internal and two external validation sets,respectively.Clinical models yielded AUCs of 0.731 0(0.660 2～0.802 1),0.746 0(0.666 4～0.824 9),and 0.813 4(0.743 1～0.883 6);radiomics models showed AUCs of 0.762 4(0.692 4～0.825 1),0.745 4(0.671 1～0.814 3),and 0.724 7(0.639 7～0.801 6).The integrated model demonstrated optimal performance with AUCs of 0.905 5(0.857 0～0.945 4),0.832 7(0.763 3～0.896 4),and 0.889 0(0.834 4～0.934 3).DCA indicated significant net benefit for EGFR prediction at threshold probabilities of 0.15～0.85 using the integrated model.Conclusion Deep learning features from CT images effectively predict EGFR mutation status in NSCLC.The integrated model combining deep learning,clinical,and radiomics features further enhances predictive performance.

BackgroundSuicide ideation in adolescent inpatients with depression is a multi-factorial problem， and perceived stress is considered to be closely related to suicide ideation， while its mediating role in suicide ideation among adolescent inpatients with depression remains unclear. ObjectiveTo explore the mediating effect of psychological capital on the relationship between perceived stress and suicide ideation among adolescent inpatients with depression， so as to provide references for preventing the onset of suicide ideation in adolescent inpatients with depression. MethodsA sample of 585 adolescent patients who were hospitalized in Beijing Huilongguan Hospital from June 2021 to March 2023 and fulfilling the International Classification of Diseases， 10th edition （ICD-10） diagnostic criteria for depression were enrolled. All patients were evaluated using self-designed questionnaire， Chinese Perceived Stress Scale （CPSS）， Positive Psychological Capital Questionnaire （PPQ） and Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）. Pearson correlation was used to assess the correlation among the scores of the above scales. Bootstrap method was employed to verify the mediating effect of psychological capital on the relationship between perceived stress and suicide ideation. ResultsCPSS score in adolescent inpatients with depression was positively correlated with BSI-CV score （r=0.375， P<0.01）， and CPSS score and BSI-CV score were negatively correlated with PPQ score （r=-0.481， -0.436， P<0.01）. Psychological capital played a significant yet a partial role in mediating the link between perceived stress and suicide ideation， with an indirect mediating effect value of 0.160 （95% CI： 0.178~0.373）， accounting for 30.42% of the total effect. ConclusionThe perceived stress of adolescent inpatients with depression can affect the onset of suicide ideation both directly and indirectly through psychological capital.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; SARS-CoV-2 ; Critical Illness ; Treatment Outcome

Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.

The quality management system of occupational diseases diagnosis is belonged to one part of the hospital quality management system. It must be adhered to the quality management concept of comprehensive, full staff and whole process. To establish and improve the quality management system should be included: (1) Formulated a quality management manual for occupational disease diagnosis, including organization construction, rules and regulations, responsibilities, work flow, operating procedures and clinical pathways, standard instrument, etc. (2) Managed the document of occupational diseases diagnosis. (3) The continuous improvement of quality management. The quality management of occupational diseases diagnosis focuses on the mastery and implementation of the manual by employees, which is reflected in the continuous improvement of daily work, internal assessment and external assessment.

Objective To investigate the effect of growth hormone(GH)pretreatment on the improvement of eu-ploid and pregnancy outcome.Methods A prospective analysis was conducted on 134 patients undergoing preim-plantation genetic testing for aneuploidy(PGT-A),among whom 30 patients were self-controlled and 104 patients were inter-group controlled.According to whether GH was added,the patients were divided into GH pretreatment group and GH non-pretreatment group.GH pretreatment included subcutaneous injection of GH 2U/day for 4-6 weeks before the start of gonadotropin(Gn),and the dose was doubled on the day of Gn until the trigger day.GH non-pretreatment meant no GH treatment,GH pretreatment was given when the previous PGT-A cycle failed within one year when the PGT-A was performed again,forming the self-control group.The basic situation,blastocyst situa-tion and pregnancy outcome were compared between the groups by inter-group and self-control.Results No matter in the group control or self-controlled group,the endometrial thickness on the day of HCG,ovarian sensitivity index(OSI),number of oocytes obtained,MII oocytes,2PN number,2PN fertilization rate,available oocyte rate,num-ber of biopsy blastocysts,number of euploid blastocysts,euploid blastocyst rate,and at least one euploid rate sig-nificantly increased after GH pretreatment,with statistically significant differences(P＜0.05).The total amount of Gn,Gn days,number of mosaic blastocysts,and mosaic blastocyst rate were not significantly changed after GH pretreatment,with no statistically significant differences.The implantation rate and clinical pregnancy rate in-creased after GH pretreatment,but with no statistically significant differences.Conclusion GH pretreatment can significantly improve the number and rate of euploid embryos in patients undergoing PGT-A,and has a tendency to improve pregnancy outcome.

The quality management system of occupational diseases diagnosis is belonged to one part of the hospital quality management system. It must be adhered to the quality management concept of comprehensive, full staff and whole process. To establish and improve the quality management system should be included: (1) Formulated a quality management manual for occupational disease diagnosis, including organization construction, rules and regulations, responsibilities, work flow, operating procedures and clinical pathways, standard instrument, etc. (2) Managed the document of occupational diseases diagnosis. (3) The continuous improvement of quality management. The quality management of occupational diseases diagnosis focuses on the mastery and implementation of the manual by employees, which is reflected in the continuous improvement of daily work, internal assessment and external assessment.