BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

Objective To establish and validate a multimodal MRI radiomics model based on intratumoral and peritumoral heterogeneity for prediction of spatial pattern of locally recurrent high-grade gliomas(HGGs).Methods A retrospective analysis was conducted on the clinical and imaging data of all HGGs patients who underwent maximum safe resection followed by postoperative radiotherapy combined with temozolomide treatment and experienced in local recurrence in Army Medical Center of PLA from 2012 to 2021.Two radiologists independently assessed the spatial patterns of locally recurrence HGGs through continuous follow-up MRI data,and primarily categorized the pattern into intra-resection cavity recurrence and extra-resection cavity recurrence.The subjected patients were randomly divided into a training set and a validation set in a 7∶3 ratio.In the training set,Pearson or Spearman correlation analysis and least absolute shrinkage and selection operator(LASSO)analysis were employed to screen radiomic features within the intratumoral and peritumoral regions,as well as to calculate radiomic scores.A radiomics model was established using logistic regression analysis.The performance of the model was assessed using calibration curves,Hosmer-Lemeshow goodness-of-fit test,and the area under the receiver operating characteristic curve(AUC).Validation of the model was performed in the validation set.Results A total of 121 patients with locally recurrent HGGs were enrolled in this study,including 54 in intra-resection cavity recurrence group and 67 in extra-resection cavity recurrence group.Among them,84 were assigned into the training set and 37 into the validation set.In the training set,the radiomics score for the extra-resection cavity recurrence group was 0.424(0.278,0.573),which was higher than that for the intra-resection cavity recurrence group[-0.030(-0.226,0.248),P<0.001].In the validation set,the radiomics score for the extra-resection cavity recurrence group was 0.369(0.258,0.487),which was higher than that for the intra-resection cavity recurrence group[0.277(0.103,0.322),P=0.033].The established radiomics model exhibited good calibration and performed well in predicting spatial recurrence patterns,with an AUC value of 0.844(95%CI:0.749～0.914)in the training set and 0.706(95%CI:0.534～0.844)in the validation set.Conclusion Our multimodal radiomics model combined with intratumoral and peritumoral heterogeneity can predict the spatial pattern of locally recurrent HGGs,providing a basis for individualized treatment of HGGs.

Objective To analyze the expression levels of miR-27a-3p mRNA and Yes-associated protein 1(YAP1)mRNA in breast cancer,and to explore their relationships with clinicopathological features and the survival prognosis of patients.Methods A total of 130 breast cancer patients who underwent mastectomy in our hospital between January 2019 and January 2021 were enrolled.The expression levels of miR-27a-3p and YAP1 mRNA in breast tumor tissues and adjacent normal breast tissues were assessed by qRT-PCR.Furthermore,the relationships between their expression and clinicopathological features,as well as the survival prognosis of patients,were investigated.Results Compared with adjacent normal breast tissues,the expression of miR-27a-3p mRNA in breast tumor tissues was lower(P＜0.05),while that of YAP1 mRNA was higher(P＜0.05).A negative correlation was observed between the expression of miR-27a-3p mRNA and YAP1 mRNA in breast tumor tissues(r=-0.456,P＜0.05).The expression of miR-27a-3p mRNA was correlated with tumor diameter,histological grade,tumor staging by the TNM system,lymph node metastasis,and vascular invasion in patients with breast cancer(P＜0.05).The YAP1 mRNA expression was correlated with histological grade,tumor staging by the TNM system,lymph node metastasis,and vascular invasion(P＜0.05).Kaplan-Meier survival analysis revealed that the 3-year overall survival rate of the miR-27a-3p low-expression group was 71.60％(48/67),which was lower than the 91.50％(54/59)of the miR-27a-3p high-expression group(log-rank x2=8.211,P=0.004).The 3-year overall survival rate of the YAP1 high-expression group was 73.80％(45/61),lower than that of the YAP1 low-expression group(87.70％,57/65)(log-rank x2=4.429,P=0.035).Multivariate regression analysis indicated that lymph node metastasis(hazard ratio[HR]=1.409;95％CI,1.057-1.644;P=0.046),vascular invasion(HR=1.541;95％CI,1.076-1.869;P=0.045),low miR-27a-3p mRNA expression(HR=0.593;95％CI,0.388-0.925;P=0.018),and high YAP1 mRNA expression(HR=0.628;95％CI,0.405-0.912;P=0.022)were relevant factors affecting the 3-year overall survival of patients with breast cancer.Conclusion A significant downregulation of miR-27a-3p mRNA and upregulation of YAP1 mRNA are observed in breast tumor tissues.The low expression of miR-27a-3p mRNA and the high expression of YAP1 mRNA are associated with adverse clinicopathological features and poor survival prognosis,and are risk factors affecting the 3-year overall survival of patients with breast cancer.They show promise as new potential therapeutic targets for breast cancer.

Diffuse pediatric-type high-grade glioma (pHGG), H3- and isocitrate dehydrogenase (IDH)-wild-type, is a World Health Organization (WHO) grade 4 diffuse glioma with malignant histological features, which typically affects in children and adolescents. This multidisciplinary treatment case involves a 24-year-old young female patient initially diagnosed via biopsy. After concurrent chemoradiotherapy reduced the tumor size, complete resection was achieved, followed by adjuvant therapy with temozolomide and regorafenib. After recurrence, the tumor was resected again, and a second course of radiotherapy was administered, but the disease ultimately progressed rapidly, with an overall survival exceeding 32 months. pHGGs are highly malignant, aggressive, and associated with poor prognosis. Accurate diagnosis and targeted intervention require close collaboration among a multidisciplinary team, which highlights the critical value of multidisciplinary manage-ment in clinical practice.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To evaluate clinical efficacy of adjuvant radiotherapy (RT) for central neurocytoma (CN) after surgical resection.Methods:Clinical data of 136 CN patients admitted to Beijing Tiantan Hospital and Xuanwu Hospital from January 2001 to December 2020 were retrospectively analyzed. Preliminary interventions consisted of craniotomy (gross total resection, subtotal resection and partial resection, the latter two belonging to incomplete resection) and postoperative radiotherapy. Three-dimensional conformal or intensity-modulated radiotherapy was adopted, with a median radiotherapy dose of 54 Gy. Post-recurrence treatment included salvage surgery and radiotherapy. The overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate analysis was performed by log-rank test to evaluate the effect of each prognostic factor on OS and PFS. The effects of multiple prognostic factors on PFS and OS were assessed by Cox regression model.Results:The median age was 28 years (range: 6-66 years). The median follow-up was 94.5 months (12-237 months). Among all patients, 79 cases underwent total resection, and 68 of them received adjuvant radiotherapy. Thirty-eight patients underwent subtotal resection, and 37 of them were treated with adjuvant radiotherapy. Sixteen patients received partial resection and adjuvant radiotherapy. Three cases received biopsy and postoperative radiotherapy. Among all patients, 3 cases died, including 2 from tumor recurrence and 1 from postoperative complication. Eight patients had recurrences during follow-up. Among them, 7 patients had recurrences at the primary site,1 had tumor dissemination to the spinal cord. The 5- and 10-year OS rates were 98.5% and 96.8%, and the 5- and 10-year PFS rates were 95.3% and 91.6% for the in the entire cohort. In the gross total resection without radiotherapy group, the 5- and 10-year PFS rates were 90.9% and 90.9%, and 96.6% and 96.6% in the gross total resection + radiotherapy group ( P=0.338). The 5- and 10-year OS rates were 100% and 100% in the gross total resection without radiotherapy group, and 98.5% and 98.5% in the gross total resection + radiotherapy group ( P=0.693). The 10-year PFS rates between the gross total resection±radiotherapy group and the incomplete resection+radiotherapy group was 95.8% vs. 90.3% ( P=0.368), and the 10-year OS rate was 98.6% vs. 94.7% ( P=0.436). Multivariate analysis showed that tumor site, degree of surgical resection, adjuvant radiotherapy and age exerted no significant effects on PFS and OS. A total of 81 patients had late neurotoxicities, including 69 cases at grade 1, 9 cases at grade 2, and 3 cases at grade 3. And 64.2% (52/81 cases) of patients suffered from short-term memory impairment. Conclusions:Gross total resection alone yields high efficacy for CN. Postoperative radiotherapy is not required. Incomplete resection combined with postoperative adjuvant radiotherapy can achieve equivalent clinical efficacy to gross total resection.

Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

Objective To explore the prognostic value of early relevant clinical indicators in hemoperfusion patients with severe acute organophosphorus poisoning(AOPP).Methods The clinical data of 91 patients with severe AOPP admitted to Baoding NO.2 Central Hospital from March 2018 to October 2022 were retrospectively analyzed,including gender,age,comorbidities,body mass index(BMI),amount of drug taken,time from drug taking to gastric lavage,number of hemoperfusion,white blood cell count(WBC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),blood urea nitrogen(BUN),serum cholinesterase(ChE)activity,lymphocyte count,pH value,arterial partial pressure of carbon dioxide(PaCO2),arterial partial pressure of oxygen(PaO2),blood K+,Na+,Cl-and inflammatory cytokine levels,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ),Glasgow coma scale(GCS),the occurrence of complications.The patients were divided into the death group and the survival group according to the prognosis within 72 hours.Differences in early clinical indicators between the two groups were compared,independent risk factors affecting the short-term prognosis of AOPP patients were analyzed by multivariate Logistic regression,and the predictive efficacy of each risk factor on the prognosis of patients was analyzed by plotting the receiver operator characteristic curve(ROC curve).Results The age of the death group was significantly higher than that of the survival group,the proportion of complicated with coronary heart disease,patients with dose of poison,time from poison to gastric perfusion,WBC,ALT,TNF-α,IL-1β and IL-6 levels at admission were significantly higher than those in survival group,and the number of hemoperfusion,TBil,ChE activity,PaCO2 were significantly lower than those in survival group(all P<0.05).Multivariate Logistic regression analysis showed that dose of poison,number of hemoperfusion,ALT,ChE activity and TNF-α were independent risk factors for poor prognosis in AOPP patients[odds ratio(OR)and 95％confidence interval(95％CI)were 1.865(1.032-3.370),2.282(1.406-3.703),2.522(1.258-5.057),2.843(1.036-7.802),2.077(1.107-3.897),respectively,all P<0.05];ROC curve analysis showed that dose of poison,number of hemoperfusion,ALT,ChE activity,TNF-α and the above combined indicators had certain predictive value for the prognosis of AOPP patients,and the combined detection had the highest predictive value,area under the ROC curve(AUC)=0.976,95％CI was 0.919-0.996.AOPP exhibited a sensitivity of 100.0％and a specificity of 85.7％,all P<0.05.With the increase of hemoperfusion times,compared with admission,the levels of WBC,ALT,AST,TBil,serum creatinine(SCr),ChE activity,TNF-α,IL-1β and IL-6 showed a significant decrease trend,while the levels of PaCO2 and PaO2 showed a significant increase trend(all P<0.05).Conclusion The early dose of poison,number of hemoperfusion,ALT,ChE activity,and TNF-α in severe AOPP patients can help predict short-term prognosis.

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged