BACKGROUND:Defective outgrowth of chondrocyte mitophagy causes degenerative chondrocyte pathological changes such as apoptosis and matrix loss.OBJECTIVE:To investigate the effects and possible mechanism of Juanbi Decoction-containing serum on interleukin-1β-induced inflammatory response and apoptosis of rat knee joint chondrocytes.METHODS:Fifty male Sprague-Dawley rats were randomly given saline,Juanbi Decoction in low,medium and high doses(1.24,2.48 and 4.96 g/kg),and celecoxib(positive drug)group.Drug-containing serum was obtained by continuous gavage for 2 weeks.(1)Chondrocytes were isolated and randomly divided into control group,interleukin-1β group,Juanbi Decoction low,medium and high dose containing serum groups and positive drug serum group.Cell counting kit-8 assay was used to detect cell viability;immunofluorescence double staining was used to detect mitophagy level;immunofluorescence was used to detect the phosphorylated AMP-activated protein kinase level;western blot was used to detect the expression of PTEN induced putative kinase 1/Parkin pathway-related protein and cleaved caspase-3;and ELISA was used to detect inflammatory factor level.(2)PTEN induced putative kinase 1 siRNA and Compound C were used for intervention to explore the role of AMP-activated protein kinase/PTEN induced putative kinase 1/Parkin pathway in the regulation of mitophagy by Juanbi Decoction-containing serum.RESULTS AND CONCLUSION:(1)Compared with the control group,chondrocyte survival,type II collagen,phosphorylated AMP-activated protein kinase,PTEN induced putative kinase 1,Parkin,and microtubule-associated proteins 1 light chain 3 protein levels,and mitophagy levels were significantly lower in the interleukin-1β group(P<0.05),while cleaved caspase-3 protein levels,interleukin-6,interleukin-8 and tumor necrosis factor-α levels were significantly higher(P<0.05).Compared with the interleukin-1β group,opposite changes in all the above indexes were observed in Juanbi Decoction low,medium and high dose containing serum groups and positive drug serum group(P<0.05).(2)PTEN induced putative kinase 1 siRNA significantly inhibited the effect of Juanbi Decoction-containing serum on mitophagy in interleukin-1β-treated chondrocytes and reduced the protective effect of Juanbi Decoction-containing serum on interleukin-1β-induced inflammation and apoptosis in chondrocytes;Compound C reversed the effect of Juanbi Decoction-containing serum on the PTEN induced putative kinase 1/Parkin signaling pathway in interleukin-1β-treated chondrocytes.To conclude,Juanbi Decoction-containing serum inhibits chondrocyte inflammation and apoptosis by affecting the level of mitochondrial autophagy,thereby attenuating interleukin-1β-induced chondrocyte degradation by a mechanism that may be related to the regulation of the AMP-activated protein kinase/PTEN induced putative kinase 1/Parkin pathway.

Objective:To explore the relationship between stress perception and problematic short video use among college students, as well as the chain mediating role of mind wandering and self-control.Methods:From October to November 2023, a cross-sectional survey of 434 college students was conducted by the stress perception scale, the problematic short video media use scale, the mind wandering scale and the self-control scale. Common method bias test, descriptive statistics and Pearson correlation analysis were performed using SPSS 27.0 statistical software, and Bootstrap method of PROCESS 4.0 macro program was used for chain mediation effect test.Results:The scores of stress perception, mind wandering, self-control and problematic short video use were (38.03±7.28), (16.08±4.71), (64.27±10.34), and (36.80±8.70).Pearson correlation analysis showed that stress perception, mind wandering and problematic short video use were significantly positively correlated ( r=0.35, 0.43, 0.57, all P<0.01). Stress perception, mind wandering and problematic short video use were significantly negatively correlated with self-control ( r=-0.55, -0.59, -0.54, all P<0.01). The mediating effect results showed that direct effect was not significant ( P>0.05), and mind wandering and self-control played complete mediating effects.Stress perception affected the problematic short video use through the following three pathways: the mediating effect size of mind wandering was 0.202 (95% CI=0.134-0.276). The effect size of self-control was 0.133 (95% CI=0.078-0.198). The chain mediating effect size of mind wandering and self-control was 0.069 (95% CI=0.040-0.104). Conclusion:Stress perception can indirectly affect the problematic short video use through the complete chain mediation of mind wandering and self-control.

Objective:To explore the relationship between stress perception and problematic short video use among college students, as well as the chain mediating role of mind wandering and self-control.Methods:From October to November 2023, a cross-sectional survey of 434 college students was conducted by the stress perception scale, the problematic short video media use scale, the mind wandering scale and the self-control scale. Common method bias test, descriptive statistics and Pearson correlation analysis were performed using SPSS 27.0 statistical software, and Bootstrap method of PROCESS 4.0 macro program was used for chain mediation effect test.Results:The scores of stress perception, mind wandering, self-control and problematic short video use were (38.03±7.28), (16.08±4.71), (64.27±10.34), and (36.80±8.70).Pearson correlation analysis showed that stress perception, mind wandering and problematic short video use were significantly positively correlated ( r=0.35, 0.43, 0.57, all P<0.01). Stress perception, mind wandering and problematic short video use were significantly negatively correlated with self-control ( r=-0.55, -0.59, -0.54, all P<0.01). The mediating effect results showed that direct effect was not significant ( P>0.05), and mind wandering and self-control played complete mediating effects.Stress perception affected the problematic short video use through the following three pathways: the mediating effect size of mind wandering was 0.202 (95% CI=0.134-0.276). The effect size of self-control was 0.133 (95% CI=0.078-0.198). The chain mediating effect size of mind wandering and self-control was 0.069 (95% CI=0.040-0.104). Conclusion:Stress perception can indirectly affect the problematic short video use through the complete chain mediation of mind wandering and self-control.

BACKGROUND:Defective outgrowth of chondrocyte mitophagy causes degenerative chondrocyte pathological changes such as apoptosis and matrix loss.OBJECTIVE:To investigate the effects and possible mechanism of Juanbi Decoction-containing serum on interleukin-1β-induced inflammatory response and apoptosis of rat knee joint chondrocytes.METHODS:Fifty male Sprague-Dawley rats were randomly given saline,Juanbi Decoction in low,medium and high doses(1.24,2.48 and 4.96 g/kg),and celecoxib(positive drug)group.Drug-containing serum was obtained by continuous gavage for 2 weeks.(1)Chondrocytes were isolated and randomly divided into control group,interleukin-1β group,Juanbi Decoction low,medium and high dose containing serum groups and positive drug serum group.Cell counting kit-8 assay was used to detect cell viability;immunofluorescence double staining was used to detect mitophagy level;immunofluorescence was used to detect the phosphorylated AMP-activated protein kinase level;western blot was used to detect the expression of PTEN induced putative kinase 1/Parkin pathway-related protein and cleaved caspase-3;and ELISA was used to detect inflammatory factor level.(2)PTEN induced putative kinase 1 siRNA and Compound C were used for intervention to explore the role of AMP-activated protein kinase/PTEN induced putative kinase 1/Parkin pathway in the regulation of mitophagy by Juanbi Decoction-containing serum.RESULTS AND CONCLUSION:(1)Compared with the control group,chondrocyte survival,type II collagen,phosphorylated AMP-activated protein kinase,PTEN induced putative kinase 1,Parkin,and microtubule-associated proteins 1 light chain 3 protein levels,and mitophagy levels were significantly lower in the interleukin-1β group(P<0.05),while cleaved caspase-3 protein levels,interleukin-6,interleukin-8 and tumor necrosis factor-α levels were significantly higher(P<0.05).Compared with the interleukin-1β group,opposite changes in all the above indexes were observed in Juanbi Decoction low,medium and high dose containing serum groups and positive drug serum group(P<0.05).(2)PTEN induced putative kinase 1 siRNA significantly inhibited the effect of Juanbi Decoction-containing serum on mitophagy in interleukin-1β-treated chondrocytes and reduced the protective effect of Juanbi Decoction-containing serum on interleukin-1β-induced inflammation and apoptosis in chondrocytes;Compound C reversed the effect of Juanbi Decoction-containing serum on the PTEN induced putative kinase 1/Parkin signaling pathway in interleukin-1β-treated chondrocytes.To conclude,Juanbi Decoction-containing serum inhibits chondrocyte inflammation and apoptosis by affecting the level of mitochondrial autophagy,thereby attenuating interleukin-1β-induced chondrocyte degradation by a mechanism that may be related to the regulation of the AMP-activated protein kinase/PTEN induced putative kinase 1/Parkin pathway.

Objective To observe MRI features of H3K27M mutant type and wild type astrocyte differentiated diffuse midline glioma(DMG)in spinal cord.Methods Totally 91 patients with astrocyte differentiation diffuse midline glioma(DMG)in spinal cord confirmed by pathology were retrospectively enrolled and divided into mutant group(n=44)and wild group(n=47)according to H3K27M status.Clinical and MRI manifestations were compared between groups,and logistic regression analysis was used to screen the impact factors of H3K27M mutation.Results The incidence of peritumoral edema and spinal cord cavity in mutant group were lower than those in wild group(both P＜0.05),while no significant difference of other parameters was found between groups(all P＞0.05).All clinical and MRI parameters were included in logistic regression analysis,and the result showed that they were not influencing factors of H3K27M mutation(all P＞0.05).Conclusion The incidence of peritumoral edema and spinal cord cavity in spinal cord H3K27M mutant type astrocyte differentiated DMG were lower than those of wild type,yet not sufficient to be regarded as impact factors for predicting H3K27M mutation of DMG.

The transgender children and adolescents(TCAs)face serious social dilemmas in the process of gender identity and expression,which hinders this group from seeking reasonable and equal rights to survival and development.From the perspective of equal rights and the theoretical framework of social dilemma,by interviewing TCAs who seek help from medical social workers in a hospital's multi-disciplinary transgender clinic,this paper revealed that under the traditional system of"binary gender",TCAs lacked social inclusiveness and infrastructure,which led to the two major social dilemmas of"social traps"and"social barriers"encountered by this group in the process of gender expression and gender identity.Specifically,the social gender selection of TCAs often leads to collective irrational reactions and gender punishment,preventing their legal and effective medical services.To this end,the research team used critical methodology to construct a joint disciplinary diagnosis and treatment path for TCAs with the participation of medical social workers,as well as verified that the path has significant intervention effects in rationalizing the needs of TCAs and their families,alleviating their psychological pressure and social adaptation problems in the process of gender identity,fostering a diverse dialogue environment in their families,as well as enhancing their self-efficacy and social participation,to provide assistahce to the TCAs groups in social difficulties,assisting their rights and interests be included in the child-friendly indicator system,and improving the whole society's tolerance and understanding for TCAs group.

Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.

Objective:To investigate the clinical characteristics and efficacy of children with acute lymphoblastic leukemia (ALL) and TP53 mutation, and to explore the relationship between TP53 mutation and the prognosis of children with ALL.Methods:The clinical data of 141 children with newly diagnosed ALL from November 2016 to December 2019 in Fujian Medical University Union Hospital were collected, and the whole-exome gene assay was performed in bone marrow samples of the children by using next-generation sequencing technology. The clinical characteristics of children with TP53 mutation were retrospectively analyzed, and the Kaplan-Meier method was used to compare the overall survival (OS) and event-free survival (EFS) of children with or without TP53 mutation.Results:Among the 141 children with newly diagnosed ALL, TP53 mutations were detected in 5 children (3.5%), all of which were B-precursor acute lymphoblastic leukemia (B-ALL). No TP53 mutation was detected in T-cell acute lymphoblastic leukemia (T-ALL) children, and TP53 mutation accounted for 4.0% (5/126) of B-ALL children. The types of TP53 mutation were all single nucleotide variants. Five ALL children with TP53 mutation were male, with a median age of 60 months (16- 156 months). At the time of onset, all children had anemia and elevated lactate dehydrogenase, and 4 children had subcutaneous hemorrhage and hyperuricemia. The immunophenotypes of all children were precursor B-cell type, and 4 children had myeloid antigen expression. Among 4 ALL children with TP53 mutation who received standard treatment, 2 cases relapsed, and the recurrence time was 8.9 months and 12.1 months, respectively. The expected 15-month EFS rate and OS rate of ALL children with TP53 mutation were lower than those of ALL children without TP53 mutation (37.5% vs. 97.7%, χ2 = 29.90, P < 0.001; 37.5% vs.98.3%, χ2 = 24.90, P < 0.001). Conclusions:ALL children with TP53 mutation are more commonly found in male and B-cell type, with high early recurrence rate and poor efficacy. TP53 mutation may become a necessary supplement for prognostic assessment.

Iron, an indispensable element for life, is involved in all kinds of vital physiological activities. Due to its potential toxicity, the body has a strict regulation mechanism of iron metabolism to maintain the "iron homeostasis". Dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the development and progression of leukemia. Specifically, due to the pro-oxidative nature of iron and its damaging effects on DNA, excess iron promotes the progression of leukemia; on the other hand, leukemia cells need to obtain more iron than normal cells to maintain rapid growth and proliferation, which is known as "iron addiction". Iron chelators can remove iron in leukemia cells and induce differentiation and apoptosis of leukemia cells. However, "iron addiction" makes leukemia cells more susceptible to iron overload, and is more sensitive to a new form of iron-catalyzed cell death which was named ferroptosis. According to the different needs of leukemia cells and normal cells for iron, the method of selectively killing leukemia cells through iron overload may become a new strategy for leukemia treatment. This paper reviews the strategy of targeting iron homeostasis for leukemia therapy.

Objective:To investigate the clinical characteristics and prognosis of IL3-IGH fusion gene-positive pediatric acute lymphoblastic leukemia (ALL) with hypereosinophilia as the first presentation.Methods:The clinical data of 1 pediatric IL3-IGH fusion gene-positive ALL patient with hypereosinophilia as the first presentation in January 2021 in Fujian Medical University Union Hospital was retrospectively analyzed and relevant literature was reviewed.Results:This 11-year-old male patient underwent bone marrow examination, and results showed that the proportion of eosinophils was increased; immunophenotyping disclosed that there were about 49.4% abnormal naive B lymphocytes in bone marrow; 43 leukemia fusion genes showed all negative; the whole transcriptome sequencing showed IL3-IGH fusion gene-positive. The patient was finally diagnosed as B-ALL with IL3-IGH fusion gene. According to the Chinese Children Cancer Group (CCCG)-ALL 2020 regimen, eosinophils returned to normal after induction therapy. Bone marrow examination on day 19 of induction showed that the proportion of promyelocytes was 0.005, the proportion of eosinophils was 0.05, and the minimal residual disease (MRD) was 23.02%. Bone marrow examination on day 46 of induction showed remission, and MRD was 0.18%. Consolidation chemotherapy used CAT (cyclophosphamide 1 g/m 2 once; cytarabine 50 mg/m 2, 12 h once, 7 days in total; mercaptopurine 40 mg/m 2, once per night, 7 days in total) regimen. Then the patient was added with lusotinib (75 mg 12 h once) orally and continued to receive high-dose methotrexate (5 g/m 2) regimen chemotherapy for 2 courses, the MRD was 0.20%. Chimeric antigen receptor T-cell (CAR-T) regimen was administered, followed by negative MRD. Conclusions:IL3-IGH fusion gene ALL is more frequently found in males, and more common in older children and young adults. It is prone to organ infiltration damage, and it has a high rate of induction failure and recurrence as well as poor prognosis.