Objective:To explore the expression of microRNA-3162-3p in different clinical stages of childhood primary immune thrombocytopenia(ITP)and its significance.Methods:Ninety-six children with ITP were enrolled and divided into new diagnosis group(n=40),persistent group(n=30)and chronic group(n=26)according to the course of disease.80 healthy children were selected as the control group.Peripheral blood mononuclear cells(PBMNC)of ITP children and healthy children were isolated and cultured,and the expression of microRNA-3162-3p in PBMNC of subjects was detected by real-time fluorescence quantitative PCR.The contents of IL-17,IL-23,IL-10 and TGF-β in PBMNC of subjects were determined by ELISA.The correlation between microRNA-3162-3p and platelet count,IL-17,IL-23,IL-10 and TGF-β was analyzed.Results:Compared with the control group,the expression of microRNA-3162-3p and IL-10 in PBMNC and platelet count of ITP children were significantly decreased(P＜0.05),while IL-17,IL-23 and TGF-β were significantly increased(P＜0.05).With the prolongation of the disease course,the expressions of microRNA-3162-3p and IL-10 in PBMNC and platelet count were significantly decreased(P＜0.05),while the expressions of IL-17,IL-23 and TGF-β were significantly increased(P＜0.05).The expression of microRNA-3162-3p in PBMNC was positively correlated with platelet count and IL-10(r=0.716,0.667),and negatively correlated with IL-17,IL-23,and TGF-β(r=-0.540,-0.641,-0.560).Conclusion:MicroRNA-3162-3p expression is significantly reduced in PBMNC of children with ITP,and is involved in the regulation of Th17/Treg imbalance,which can be used as a potential therapeutic target of ITP.

Objective:To explore the value of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) of MRI in evaluating the response of osteosarcoma to neoadjuvant chemotherapy (NAC) in different cycles, and to analyze the diagnostic efficacy of each ADC and its difference.Methods:A total of 31 patients with pathologically confirmed osteosarcoma in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2019 to December 2022 were retrospectively analyzed. All patients received NAC before surgery, and routine MRI and DWI were performed before and during chemotherapy. The ADC values were measured before, during and after chemotherapy (ADCpre, ADCmid, ADCpost), and the difference were calculated. According to whether the tumor necrosis rate was more than 90%, the patients were divided into good response group and poor response group. The differences of ADC values in each stage within the two groups were compared, and the differences of related parameters between the two groups were compared, and the diagnostic efficacy of each parameter in predicting tumor necrosis rate was analyzed by receiver operating characteristic(ROC) curve.Results:The ADC values of the two groups at different stages of NAC were compared. Except for the intermediate ADCmid and ADCpost in the poor response group ( P = 0.226), all the ADC values were statistical differences ( P<0.05). There were significant differences in ADCmid and ADCpost between the good response group and the poor response group (1.52 ± 0.39 vs. 1.39 ± 0.25, 1.65 ± 0.16 vs. 1.46 ± 0.44, P<0.05), but there was no significant difference in ADCpre between the two groups ( P>0.05). ROC curve showed that the area under the curve of ADCmid, ADCpost and △ADC3 (ADCpost -ADCpre) were 0.897, 0.810 and 0.714, respectively, and ADCmid had the best diagnostic efficiency. Conclusions:ADCmid, ADCpost and △ADC3 can be used to evaluate the efficacy of NAC in osteosarcoma. The ADCmid can provide some reference for the adjustment and improvement of clinical treatment.

Objective:To prepare a recombinant hemagglutinin trimer (HA-Tri) vaccine against influenza viruses and to study its immunogenicity in a mouse model.Methods:A stable CHO cell line that could express HA-Tri was constructed. Western blot, single radial immunodiffusion, protein particle size detection and N-glycosylation site analysis were performed for qualitative and quantitative analysis of the recombinant protein. According to the different treatment conditions such as dosage and adjuvant, BALB/c mice were divided into 11 groups and subjected to consistent immunization procedures. Serum neutralizing antibody titers were measured on 56 d after the first immunization to evaluate the immunogenicity of HA-Tri.Results:The constructed CHO cells could secret and express HA-Tri proteins. The HA-Tri proteins were biologically active and capable of forming precipitation rings in the single radial immunodiffusion. The particle size of HA-Tri was approximately 18.79 nm and 10 N-glycosylation sites were detected, including high mannose, complex glycoforms and heterozygous glycoforms. After prime-boost immunization, there was no statistically significant difference in the titers of neutralizing antibodies induced in mice by 3.75 μg of HA-Tri in combination with RFH01 adjuvant and 15 μg of monovalent vaccine stock solution ( P=0.431 2, U=36). Serum antibody titers in the HA-Tri+ RFH01 groups were higher than those in the corresponding HA-Tri groups without RFH01 adjuvant, and the highest titer was induced in the 15 μg HA-Tri+ RFH01 group, which was 1 280. Conclusions:The recombinant HA-Tri protein was successfully prepared. HA-Tri in combination with RFH01 adjuvant could induce humoral immune responses against influenza viruses in BALB/c mice, which would provide reference for the development of influenza virus recombinant subunit vaccines.

Objective: This study analyzed the correlation between genetic mutation and prognostic significance in childhood acute lymphoblastic leukemia (ALL) . Methods: Targeted exome by next-generation sequencing (NGS) technology was used to carry out molecular profiling of untreated 141 children with ALL in Fujian Medical University Union Hospital from November 2016 to December 2019. Correlation of genetic features and clinical features and outcomes was analyzed. Results: Among the 141 pediatric patients with ALL, 160 somatic mutations were detected in 83 patients (58.9% ) , including 37 grade Ⅰ mutations and 123 grade Ⅱ mutations. Single nucleotide variation was the most common type of mutation. KRAS was the most common mutant gene (12.5% ) , followed by NOTCH1 (11.9% ) , and NRAS (10.6% ) . RAS pathway (KRAS, FLT3, PTPN11) , PAX5 and TP53 mutations were only detected, and NRAS mutations was mainly found in B-ALL while FBXW7 and PTEN mutations were only found, and NOTCH1 mutation was mainly detected in T-ALL. The average number of mutations detected in each child with T-ALL was significantly higher than in children with B-ALL (4.16±1.33 vs 2.04±0.92, P=0.004) . The children were divided into mutation and non-mutation groups according to the presence or absence of genetic variation. There were no statistically significant differences in sex, age, newly diagnosed white blood cell count, minimal or measurable residual disease monitoring results, expected 3-year event-free survival (EFS) and overall survival (OS) between the two groups (P>0.05) . On the other hand, the proportion of T-ALL and fusion gene negative children in the mutant group was significantly higher than the non-mutation group (P=0.021 and 0.000, respectively) . Among the patients without fusion gene, the EFS of children with grade I mutation was significantly lower than children without grade I mutation (85.5% vs 100.0% , P=0.039) . Among children with B-ALL, the EFS of those with TP53 mutation was significantly lower than those without TP53 mutation (37.5% vs 91.2% , P<0.001) . Conclusion: Genetic variation is more common in childhood ALL and has a certain correlation with clinical phenotype and prognosis. Therefore, targeted exome by NGS can be used as an important supplement to the traditional morphology, immunology, cytogenetics, and molecular biology classification.
Child ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Technology

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Objective To compare the differences in pathogenicity and gene expression profiles between adult Schistosoma japonicum isolated from hilly and marshland and lake regions of Anhui Province, so as to provide the scientific evidence for formulating the precise schistosomiasis control strategy in different endemic foci. Methods C57BL/6 mice were infected with cercariae of S. japonicum isolates from Shitai County (hilly regions) and Susong County (marshland and lake regions) of Anhui Province in 2021, and all mice were sacrificed 44 days post-infection and dissected. The worm burdens, number of S. japonicum eggs deposited in the liver, and the area of egg granulomas in the liver were measured to compare the difference in the pathogenicity between the two isolates. In addition, female and male adult S. japonicum worms were collected and subjected to transcriptome sequencing, and the gene expression profiles were compared between Shitai and Susong isolates of S. japonicum. The differentially expressed genes (DEGs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results The total worm burdens [(14.50 ± 3.96) worms/mouse vs. (16.10 ± 3.78) worms/mouse; t = 0.877, P = 0.392], number of female and male paired worms [(4.50 ± 0.67) worms/mouse vs. (5.10 ± 1.45) worms/mouse; t = 1.129, P = 0.280], number of unpaired male worms [(5.50 ± 4.01) worms/mouse vs. (5.60 ± 1.69) worms/mouse; t = 0.069, P = 0.946], number of eggs deposited in per gram liver [(12 116.70 ± 6 508.83) eggs vs. (16 696.70 ± 4 571.56) eggs; t = 1.821, P = 0.085], and area of a single egg granuloma in the liver [(74 359.40 ± 11 766.34) µm² vs. (74 836.90 ± 13 086.12) µm²; t = 0.081, P = 0.936] were comparable between Shitai and Susong isolates of S. japonicum. Transcriptome sequencing identified 584 DEGs between adult female worms and 1 598 DEGs between adult male worms of Shitai and Susong isolates of S. japonicum. GO enrichment analysis showed that the DEGs between female adults were predominantly enriched in biological processes of stimulus response, cytotoxicity, multiple cell biological processes, metabolic processes, cellular processes and signaling pathways, cellular components of cell, organelles and cell membranes and molecular functions of binding and catalytic ability, and KEGG enrichment analysis showed that these DEGs were significantly enriched in pathways of vascular endothelial growth factor signaling, glutathione metabolism, arginine and proline metabolism. In addition, the DEGs between male adults were predominantly enriched in biological processes of signaling transduction, multiple cell biological processes, regulation of biological processes, metabolic processes, development processes and stimulus responses, cellular components of extracellular matrix and cell junction and molecular functions of binding and catalytic ability, and these DEGs were significantly enriched in pathways of Wnt signaling, Ras signaling, natural killer cells-mediated cytotoxicity, extracellular matrix-receptor interactions and arginine biosynthesis. Conclusions There is no significant difference in the pathogenicity between S. japonicum isolates from hilly and marshland and lake regions of Anhui Province; however, the gene expression profiles vary significantly between S. japonicum isolates.

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

OBJECTIVE: To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL). METHODS: The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy. RESULTS: One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033). CONCLUSION The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.
Child ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Phenotype ; Prognosis ; Remission Induction ; Retrospective Studies