OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Objective: To investigate the influencing factors of depressive symptoms and to construct and verify the prediction model of depressive symptoms in middle school students, so as to provide risk assessment tools for effectively screening depressive symptom. Methods: Physical examination and questionnaire survey were conducted among middle school students in one city in Guangdong Province from September to October in 2021 ( n =2 376) and from September to October in 2022 ( n =4 344) by a multistage cluster sampling method, and a nomographic prediction model of depressive symptoms in middle school student was constructed. The questionnaire survey was conducted using the student health status and influencing factors questionnaire (secondary school version) and the Center for Epidemiological Studies Depression Scale (CES-D) to measure the lifestyle and depressive symptom of middle school students. Results: The detection rate of depressive symptoms in 2021 was 23.3%. Multivariate Logistic regression analysis showed that irregular breakfast ( OR =2.64), school bullying ( OR =4.28), being beaten by parents ( OR =2.86), using mobile devices for a long time ( OR =1.08) and sitting for a long time ( OR =1.05) were positively related to depressive symptoms in middle school students ( P <0.05). Long sleep duration ( OR =0.78) and outdoor activity durations of 1-<2, 2-<3 and ≥3 h/d (compared with <1 h/d, OR =0.63, 0.61, 0.49) were negatively related to depressive symptoms in middle school students ( P < 0.05 ). Multivariate Logistic regression analysis showed that 7 statistically signifucant predictive factors constructed a nomogram, and the AUC of the nomogram was 0.77, which had been verified internally and externally with good differentiation and reliability. Conclusions The nomogram prediction model of depressive symptoms provides a convenient and effective risk assessment tool for depressive symptoms among middle school students. The life behavior, diet behavior and injury behavior of middle school students play an important role in the formation of depressive symptoms. It should pay attention to the impact of the behavioral factors on the mental health of middle school students.

Objective To observe the effects of electroacupuncture at"Ciliao","Zhongji","Sanyinjiao"and"Dazhui"on urodynamics and expression of ERK/CREB/Bcl-2 pathway in spinal cord tissue of neurogenic bladder rats after suprasacral spinal cord injury.Methods Sixty female SD rats randomly selected 24 and divided into blank group and sham-operation group(12 rats in each group),the remaining 36 rats were subjected to surgical modeling.After modeling,rats were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.The electroacupuncture group received unilateral electroacupuncture stimulation at acupoints"Ciliao","Zhongji","Sanyinjiao",and"Dazhui"for 30 minutes each time,once a day,for 7 consecutive days.After administration,urodynamic testing was performed,HE staining was used to observe the morphology of bladder detrusor tissue,TUNEL method was used to detected apoptosis in spinal cord tissue,Western blot was used to detected expressions of p-ERK1/2,p-CREB,p-p90Rsk,CRE,Bcl-2,and Bax proteins in spinal cord tissue.Results Compared with the sham-operation group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the model group increased significantly(P<0.01),while the maximum capacity and compliance of the bladder decreased significantly(P<0.01);the structure of bladder smooth muscle cells was severely damaged and disorderly arranged,accompanied by a large amount of inflammatory cell infiltration;the apoptosis rate of spinal cord tissue cells significantly increased(P<0.01),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue were significantly decreased,while the expression of Bax protein significantly increased(P<0.01).Compared with the model group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the electroacupuncture group decreased significantly(P<0.05),while the maximum capacity and compliance of the bladder increased significantly(P<0.05,P<0.01);the integrity of bladder smooth muscle cells was enhanced,the degree of cell edema was reduced,and inflammatory cell infiltration was reduced;the apoptosis rate of spinal cord tissue cells was significantly reduced(P<0.05),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue significantly increased,while the expression of Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion Electroacupuncture can promote the repair of bladder detrusor tissue in rats with neurogenic bladder model after suprasacral spinal cord injury,increase the maximum capacity and compliance of the bladder,alleviate the high pressure state in the bladder,and its mechanism is related to activating the ERK/CREB/Bcl-2 pathway,reducing secondary apoptosis of damaged neurons,effectively improving bladder innervation,and protecting bladder function.

Background Comorbid attention-deficit/hyperactivity disorder(ADHD)and emotional dysregulation may represent a distinct subtype of ADHD,which is characterized by an increased risk of anxiety or depressive disorder and a poor clinical prognosis,so research is urgently required to explore its unique executive functioning profile and clinical characteristics.However,there is limited research comparing the clinical symptoms and executive function in children with ADHD in terms of the presence or absence of emotional dysregulation.Objective To explore the executive function and clinical characteristics of ADHD children with emotional dysregulation.Methods From June 2020 to December 2023,118 children aged 7 to 12 with ADHD attending the Mental Health Center of West China Hospital,Sichuan University and fulfilling the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)diagnostic criteria were enrolled.Children were classified into emotional dysregulation group(n=68)and non-emotional dysregulation group(n=50)based on the standard T-scores of Achenbach's Child Behavior Checklist(CBCL)-anxious/depressed,aggressive behavior and attention problems subscales.All children were then subjected to complete the Chinese version of Swanson Nolan and Pelham,Version IV Scale-parent form(SNAP-IV),Chinese Wechsler Intelligence Scale for Children(C-WISC),Weiss Functional Impairment Scale-Parent form(WFIRS-P)and 4 tests of the Cambridge Neuropsychological Test Automated Battery(CANTAB):①Stockings of Cambridge(SOC)testing spatial planning.②Intradimensional-extradimensional Set Shifting(IED)testing cognitive/attentional flexibility,adjusting the total errors across the task.③Spatial Working Memory(SWM)testing spatial working memory.④Rapid Visual Information Processing(RVP)testing sustained attention.Results The SNAP-IV Inattention,Hyperactivity/Impulsivity and Oppositional Defiant Disorder domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=3.206,5.088,6.316,6.553,P<0.01).The WFIRS-P family,school learning,life skills,self-concept,social activities and risky activities domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=6.074,4.406,4.143,3.984,6.575,6.662,8.254,P<0.01).In CANTAB,emotional dysregulation group made more total adjusted errors across the IED task compared with non-emotional dysregulation group(t=2.168,P<0.05).Conclusion Children with ADHD who exhibit emotional dysregulation have been observed to experience more severe core symptoms,impaired social functioning and poorer performance on tests assessing executive function,particularly in the area of cognitive flexibility.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

This study was performed to explore the effect of flagellin+rapamycin on the growth and metastasis of 4T1 breast cancer in tumor-bearing mice,and their regulatory effect on several immunocytes.4T1 cell line was applied to establish an breast cancer model in Balb/c mice,which then injected with flagellin+rapamycin,and the volume and inhibition rate of tumor were recorded.MTT assay was used to detect the inhibitory effect of flagellin+rapamycin against 4T1 cells.Data showed that the combination of flagellin and rapamycin had the best inhibition effect on 4T1 cells,and the same results were found in animal model experiments.Flow cytometry result indicated that flagellin+rapamycin significantly down-regulated the levels of CD11b+Gr-1+myeloid-derived suppressor cells(MDSCs)and CD11b+F4/80+tumor-associated macrophages(TAMs)of tumor-bearing mice.Furthermore,flagellin+rapamycin alleviates the metastasis of 4T1 cancer cells into liver and lung.Taken together,flagellin+rapamycin can inhibit proliferation and metastasis of 4T1 cells,thus exert antitumor effects in mice,which may related with its regulatory effects on immunocytes in tumor microenvironment.