OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

Network Meta-analysis was conducted to evaluate the efficacy and safety of different traditional Chinese medicine injections combined with conventional western medicine in treatment of cerebral small vessel disease(CSVD). Computerized searches were conducted in PubMed, Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, VIP, and SinoMed for randomized controlled trial(RCT) published in Chinese or English using traditional Chinese medicine injections to treat CSVD. The search time is from the inception to July 15, 2024. Literature screening and statistical analysis were conducted with NoteExpress 3.0.3, RevMan 5.3.5, and Stata 15.1.6. A total of 45 articles were included, involving 3 717 patients, with 1 944 patients in the treatment group and 1 773 patients in the control group. A total of 15 kinds of traditional Chinese medicine injections were involved. Network Meta-analysis indicated that,(1) in terms of improving clinical total effective rate, the best intervention in SUCRA was Ciwujia Injection + conventional western medicine.(2) In terms of reducing NIHSS scores, the best intervention in SUCRA was Xueshuantong Injection + conventional western medicine.(3) In terms of improving ADL scores, the best intervention in SUCRA was Danshen Injection + conventional western medicine.(4) In terms of improving MMSE scores, the best intervention in SUCRA was Xueshauntong Injection + conventional western medicine.(5) In terms of improving MoCA scores, the best intervention in SUCRA was Salvianolate Injection + conventional western medicine.(6) In terms of reducing plasma viscosity(PV), the best intervention in SUCRA was Danhong Injection + conventional western medicine.(7) In terms of reducing the hematocrit, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(8) In terms of reducing fibrinogen, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(9) In terms of reducing erythrocyte sedimentation rate(ESR), the best intervention in SUCRA was Danshen Injection + conventional western medicine.(10) In terms of reducing total cholesterol(TC), triglycerides(TG), and low-density lipoprotein(LDL), the best intervention in SUCRA was Danshen Injection + conventional western medicine. The radar chart results indicated that the advantage of Salvianolate Injection lies in improving cognitive function, while the advantage of Xueshuantong Injection lies in improving neurological function. The advantage of Xuesaitong Injection lies in improving hemodynamic parameters, and the advantage of Danshen Injection lies in improving behavioral ability, hemodynamics, and blood lipid levels. In terms of safety, there was no significant difference in the incidence of adverse reactions between the traditional Chinese medicine injection treatment group and the conventional western medicine group, and no serious adverse reactions occurred. The results showed that the combination of traditional Chinese medicine injections and conventional western medicine can effectively improve the clinical total effective rate, the neurological and cognitive functions, hemodynamic parameters, and blood lipid levels of patients suffering from CSVD. In addition, more double-blind, multi-center, large-sample RCT is needed to verify these findings and to provide more high-quality evidence on the efficacy and safety of traditional Chinese medicine injections for CSVD.
Humans ; Cerebral Small Vessel Diseases/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Injections ; Randomized Controlled Trials as Topic

Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.

Objective:Analysis of the composition of pathogen spectrum and prevalence characteristics in throat swabs of patients with acute respiratory infections (ARI) in Yucheng city, Henan province, from March to June 2023.Methods:After 1 153 throat swabs were collected from ARI patients in Yucheng, 18 respiratory pathogens were tested using a real-time fluorescence quantitative polymerase chain reaction (qPCR) method. The characterization of pathogens spectrum was analyzed.Results:A total of 1 153 throat swabs from ARI patients were collected from March to June 2023 in Yucheng, including 171 outpatients and 982 hospitalized patients. A total of 244 positive samples for common respiratory pathogens were detected (at least one pathogen per sample was detected). The total detection rate of respiratory pathogens was 21.16%, and the top three detection rates were, in descending order, human bocavirus (HBoV), enterovirus (EV), and human parainfluenza virus (HPIV). The main detection month for pathogens was May, with a detection rate of 42.3% (60/142). The main respiratory pathogens detected are HBoV, EV, and HPIV. The detection rate of the age group under 1 year old was the highest, at 25.1% (49/195), mainly consisting of HBoV, respiratory syncytial virus (RSV), and HPIV. The main clinical manifestations of respiratory pathogen-positive patients were fever and cough, and the clinical diagnosis was mainly lower respiratory tract infection, all of which were hospitalized patients.Conclusions:The respiratory pathogens in ARI patients were mainly HBoV, EV, and HPIV from March to June, 2023 in Yucheng. The peak of the epidemic was in May, mainly infecting children under 5 years of age.

Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.

Objective:To analyze the differentially expressed genes and related functional pathways of mouse sciatic nerves of Schwann cells(SCs)in early in vitro Wallerian degeneration(WD).Methods:The sciatic nerves of adult male C57BL/6J mice were Wallerian degeneration in vitro,and total RNA was extracted and transcriptome sequencing was performed at 3 h and 6 h after degeneration,respectively.The differentially expressed genes(DEGs),gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment were analyzed by bioinformatics.Results:Compared with the Control group,3961 and 5538 DEGs were screened in the WD 3 h group(WD3h)and the 6 h group(WD6h)of in vitro,respectively.The most significantly up-regulated genes mainly included molecules related to inflammation and immunity and neurotrophic factors.GO analysis showed that DEGs in both groups were enriched in positive transcriptional regulation and metabolic processes.KEGG pathway enrichment analysis revealed that DEGs were mainly concentrated in TNF signaling pathway,MAPK signaling pathway and ribosome production.Conclusion:At the early stage of WD,SCs up-regulates the genes related to inflammation and immunity to promote the progression of WD and secrete neurotrophic factors to support the survival of neurons,accompanied by the activation of TNF signaling path-way and MAPK signaling pathway.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.