Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To analyze the safety of idarubicin or daunorubicin combined with cytarabine in the treatment of patients with acute myeloid leukemia.Methods The Chinese Biomedical Database,Chinese Journal Full-text Database,Chinese Science and Technology Journal Full-text Database,Wanfang Database,Embase,PubMed,Cochrane Library were searched.The randomized controlled trials(RCTs)of idarubicin combined with cytarabine(treatment group)and daunorubicin combined with cytarabine(control group)were collected.The search time was from 2014-01-01 to 2024-02-23.RevMan 5.4 software was used to perform meta-analysis,sensitivity analysis and publication bias analysis on adverse drug reactions of the included studies.Results A total of 11 RCTs involving 1 818 patients were included in the Meta-analysis.The treatment and control groups were enrolled 912 and 906 cases,respectively.The results of meta-analysis showed that the total incidence of adverse drug reactions in the treatment group and the control group was 22.9％(56 cases/245 cases)and 42.9％(105 cases/245 cases),respectively,and the difference was statistically significant[relative risk(RR)=0.53,95％confidence interval(CI)=0.41-0.69,P＜0.001)].In the specific adverse drug reactions,there were no statistically significant differences in the incidence of hematological toxicity,digestive system toxicity,cardiac toxicity,liver and kidney toxicity,infection,bleeding between the two groups(all P＞0.05).Sensitivity analysis showed that the results were stable and reliable.The results of publication bias analysis showed that this study was less likely to have publication bias.Conclusion The incidence of adverse drug reactions of idarubicin combined with cytarabine in the treatment of patients with acute myeloid leukemia is significantly lower than that of daunorubicin combined with cytarabine,so the former has better safety.

Objective To compare the efficacy and safety of Saccharomyces boulardii and other probiotics in the treatment of pediatric diarrhea.Methods Retrieved from PubMed,Embase,CBM,Wanfang data,CNKI and VIP,randomized controlled trial(RCTs)about Saccharomyces boulardii(treatment group)vs other probiotics(control group)were collected.After screening the literature,extracting data and evaluating the quality,Meta-analysis was performed by using RevMan 5.3 and Stata 17.0 software.Results A total of 30 RCTs were included,involving 3 082 children.Results of Meta-analysis showed there was no statistical significance in the duration of diarrhea[mean difference(MD)=-0.65,95％confidence interval(CI)=-1.44-0.14,P＞0.05]or the total incidence of adverse reactions[odds ratio(OR)=0.85,95％CI=0.44-1.62,P＞0.05].The total effective rate(OR=1.60,95％CI=1.08-2.36,P＜0.05)and the number of stools(MD=-0.66,95％CI=-1.00--0.32,P＜0.01)in the treatment group were significantly better than control group.There was statistically significant difference in the duration of diarrhea between the two groups treated with diarrhea with fever(MD=1.81,95％CI=1.12-2.49,P＜0.01)and rotavirus gastroenteritis(MD=-0.92,95％CI=-1.20--0.64,P＜0.01).In the treatment of diarrhea with fever,the duration of diarrhea in the control group was significantly shorter than that in the treatment group.The duration of diarrhea in the treatment group was significantly shorter than that control group.At the same time,the duration of diarrhea in children with diarrhea treated with treatment group was significantly shorter than that of control group Bifidobacterium tetragenous viable(MD=-0.84,95％CI=-1.09--0.58,P＜0.01)and control group combined Bacillus subtilis and Enterococcus faecium enteric-coated(MD=-1.35,95％CI=-2.30-0.39,P＜0.01).Conclusion The safety of Saccharomyces boulardii are similar to other probiotics.The efficacy and the number of stools with Saccharomyces boulardii are significantly better than other probiotics in the treatment of diarrhea.The duration of diarrhea in Saccharomyces boulardii group was significantly shorter than other probiotics,while in the treatment of antibiotic-associated diarrhea,the duration of diarrhea of Saccharomyces boulardii was the same as that of other probiotics.However,the duration of diarrhea in children with diarrhea treated with Saccharomyces boulardii was significantly longer than other probiotics.

Objective:To investigate the effects of oral probiotics on intestinal microbiota and cognitive dysfunction in breast cancer chemotherapy patients. Methods:Thirty breast cancer patients who received anthracycline chemotherapy between December 2021 and June 2022 in the Department of Oncology, the First Affiliated Hospital of Bengbu Medical University were included in this study. The patients were randomly divided into the observation and control groups (15 cases per group). During chemotherapy, the observation group was additionally given oral probiotics. The fecal microbiota compositions before and after chemotherapy were detected using 16S rDNA sequencing. The changes in patients' subjective and objective cognitive function levels were evaluated by Montreal Cognitive Assessment (MoCA) and Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog), respectively. Results:The microbiota diversity, as indicated by the Chao, Ace, Shannon and Simpson indices, showed no significant difference between two groups (P>0.05). As compared with the control group, the relative abundance of the genus Actinomyces in the feces was significantly higher than in the observation group (P<0.05). By contrast, the relative abundance of the genera Acetoanaerobium, Lachnospiracea_incertae_sedis, and unclassified_Frankineae bacteria was significantly lower in the observation group (P<0.05). The total scores of the objective and subjective cognitive function as well as the scores of each dimension in both groups were markedly decreased after chemotherapy (P<0.05). The scores in the observation group were higher than those in the control group after chemotherapy (P<0.05). During chemotherapy, the presence of the gastrointestinal adverse reactions (constipation, nausea and vomiting, diarrhea and abdominal distension) in the observation group were significantly lower than in control group (P<0.05). Conclusion:Oral probiotics could improve the cognitive impairment and reduce the presence of the gastrointestinal side effects in the breast cancer patients receiving chemotherapy, which may be caused by modulating the intestinal microbiota.

Objective:To summarize the best evidence on case management of patients with home enteral nutrition.Methods:Relevant evidence on the case management of home enteral nutrition patients was retrieved by literature search,and the evidence was extracted and summarized for the literature that met the quality requirements.Result:A total of 10 literatures were included,including 1 guideline,3 expert consensus,2 industry standards,1 systematic review and 3 randomized controlled trials.By establishment of archives,policy management,establishment of multidisciplinary teams,overall evaluation of home enteral nutrition,as well as implementation management,a total of 33 home enteral nutrition case management was summarized from 6 aspects including health education and follow-up,etc.Conclusion:All the summarized relevant evidence about case filing and management of home enteral nutrition patients can be applied in clinical practice to promote the standardized management of home enteral nutrition.

Objective To elucidate the clinical significance of high expression levels of endonuclease meiosis 1(EME1)in the prognosis of hepatocellular carcinoma(HCC).Methods The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues.A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed.Immunohistochemistry analysis was employed to detect the EME1 expression levels.Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients.Additionally,gene enrichment analysis was applied to predict the function of EME1 in HCC.Results A total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed,revealing significantly higher EME1 expression in HCC tissues.Microarray analysis of 107 samples within the GEO database(70 HCC tissues and 37 non-tumor tissues)confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues(P<0.05).The 5-year overall survival(OS)rate was notably lower in high EME1 expression group than that in low expression group(44.1%vs.53.0%,P<0.05).Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression(32.8%vs.45.0%,P<0.05).Multivariate COX regression analysis identified that high EME1 expression(HR=2.234,95%CI 1.073-4.649,P=0.032)and advanced China liver caner(CNLC)staging(HR=4.317,95%CI 1.799-10.359,P=0.001)were independent risk factors for the 5-year OS of post-operation patients with HCC.Conclusion Elevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.

Objective To investigate the effects of astragaloside Ⅳ(AS-Ⅳ)on axon growth inhibitory factor A(Nogo-A)and its downstream pathway protein RHO-associated coiled spiral kinase 2(ROCK2)in experimental autoimmune encephalomyelitis(EAE)mice,and to explore the mechanism by which it promotes axon repair and regeneration.Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55(MOG35-55).Mice were randomly divided into EAE group and AS-Ⅳ group(n=8 per group).EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization,while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d)once daily,0.2 ml per injection,for 25 consecutive days.On the 28th day post-immunization,the expression levels of growth-associated protein 43(GAP-43),neuronal core antigen(NeuN),microtubule associated protein 2(MAP-2),glial fibroacidic protein(GFAP),and Iba1 in the spinal cord were detected using immunofluorescence assay.Real-time fluorescence quantitative PCR(qRT-PCR)was conducted to detect mRNA expression levels of GAP-43,Nogo-A,and Nogo receptor(NgR)genes.Western blotting was utilized to determine the expression levels of GAP-43,Nogo-A,ROCK2,phosphorylated myosin phosphatase(p-MYPT1),B-lymphoblastoma-2(Bcl-2),and Bcl-2 associated X protein(Bax).Results Compared with EAE group,AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord(P<0.01 and P<0.001,respectively),while it also increased the positive expression rates of NeuN and MAP-2(P<0.001 and P<0.05,respectively).The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2(P<0.001)and downregulated the expression level of pro-apoptotic factor Bax(P<0.05),leading to an increase in Bcl-2/Bax ratio(P<0.05).Furthermore,AS-Ⅳ enhanced the expression of GAP-43 protein(P<0.05)and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor(NgR)and ROCK2 gene(P<0.001,P<0.05,respectively);as well as decreased the expression levels of Nogo-A,ROCK2 and p-MYPT1 proteins(P<0.05,P<0.001).Conclusion AS-Ⅳ may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK 2,thereby promoting the expression of GAP-43,NeuN and MAP-2,alleviating neuronal damage,and facilitating axon repair and regeneration.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]