[摘 要] 目的：探究甘氨胆酸（GCA）对肺腺癌A549细胞移植瘤小鼠放射治疗敏感性的影响及其机制。方法：建立A549人肺腺癌细胞裸鼠移植瘤模型，随机分为移植瘤对照组（对照组）、GCA组、放疗组（RT组）和GCA + 放疗组（GCA + RT组）。RT组和GCA + RT组接受单次10  Gy照射，GCA组及GCA + RT组连续7 d每日灌胃GCA 280  mg/kg。间隔2 d测量1次移植瘤体积，末次给药后处死小鼠并取移植瘤组织，检测移植瘤组织中超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GSH-Px）活性，qPCR法和WB法分别检测放疗关键基因（MCM6、ITGA6、CASP3等）mRNA和蛋白表达水平，H-E染色观察移植瘤组织的形态变化。通过GEO（GSE276500、GSE294906、GSE218171）及TCGA数据库数据验证放疗关键基因。结果：GCA单用对瘤体生长有一定抑制作用，但联合放疗的GCA + RT组相比单纯放疗组表现出放疗抵抗的效应（P < 0.05）。GCA处理显著提高移植瘤组织SOD活性（P < 0.01）、降低GSH-Px活性（P < 0.01），提示GCA可改变移植瘤抗氧化酶平衡，减弱放疗诱导的氧化应激。GCA干预上调移植瘤组织中MCM6与ITGA6 mRNA表达、下调CASP3 mRNA表达（均P < 0.05）。GCA + RT组移植瘤组织中的MCM6蛋白表达显著高于对照组（P < 0.05）。H-E染色显示，GCA组部分瘤组织坏死，而GCA + RT组坏死组织面积较RT组有所缩小。GEO和TCGA数据库验证支持MCM6、ITGA6高表达与放疗抵抗和预后不良相关。结论：GCA通过增强SOD活性、降低GSH-Px活性并上调ITGA6、MCM6的表达改变氧化应激与关键信号网络，从而削弱A549移植瘤对放疗的敏感性。

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

Objective:To evaluate the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in treating pediatric Diamond-Blackfan anemia (DBA).Method:Clinical data of five pediatric DBA recipients who underwent haplo-HSCT at the Children's Hospital of Soochow University between June 2018 and June 2023 were retrospectively analyzed. The conditioning regimen comprised a backbone protocol of fludarabine, busulfan, and rabbit anti-human thymocyte immunoglobulin (Bu+Flu+ATG), with optional cyclophosphamide, rituximab, or thiotepa. Post-transplant prophylaxis for graft-versus-host disease (GVHD) included cyclosporine A/tacrolimus combined with mycophenolate mofetil and methotrexate. Outcome measures included neutrophil and platelet engraftment times, hematopoietic reconstitution, incidence and severity of post-transplant complications, hemoglobin maintenance, and survival status. Literature was searched in CNKI, Wanfang, and PubMed using the keywords "Diamond-Blackfan anemia" "DBA" and "haplo-HSCT" in both English and Chinese.Result:The median age at transplantation was 61 months. Human leukocyte antigen (HLA) matching ranged from 5-8/10 loci. Stem cell sources included bone marrow alone (1 case), bone marrow plus peripheral blood stem cells (PBSCT, 2 cases), umbilical cord blood (CB-HSCT, 1 case), and PBSCT combined with CB-HSCT (1 case). All five recipients achieved successful engraftment with complete hematopoietic and immune reconstitution. Median neutrophil and platelet engraftment times were 11 days and 9 days, respectively, with erythroid reconstitution at 25 days post-transplant. Complications included grade IV acute GVHD (aGVHD) in one recipient, grade I aGVHD in two recipients, and chronic GVHD (cGVHD) in one recipient. Cytomegalovirus (CMV) infection occurred in three cases, and Epstein-Barr virus (EBV) infection in one case, all of which resolved with ganciclovir. No other transplant-related complications were reported. At a median follow-up of 44.8(4.8-59.2) months, all recipients were alive with sustained erythroid reconstitution and disease-free survival. Literature review (six studies) confirmed HSCT as an effective treatment for DBA, with prognosis closely related to age at transplantation, conditioning regimens, and donor selection.Conclusion:Haplo-HSCT can be considered as a viable treatment option for pediatric DBA recipients.

Objective:To explore the diagnostic reference level(DRL)of computed tomography(CT)based on size-specific dose estimate(SSDE)for child's head,and estimate the SSDE by using tube current time production.Methods:The CT data of head of 1259 pediatric patients who underwent CT examination in Children's Hospital of Nanjing Medical University from January 2023 to December 2023 were retrospectively collected.They were divided into six groups according to different ages:<6 months group,6 months to<1 year group,1 to<3 years group,3 to<6 years group,6 to<12 years group,and≥12 years group.Additionally,they were divided into five groups based on body size:<12.5 cm group,12.5 to<14 cm group,14 to<15 cm group,15 to<16 cm group,and≥16 cm group.The volume CT dose index(CTDIVOL),tube current time production(mAs),left and right diameter(LRD),area(AROI)and CT value(CTROI)of region of interest of different age groups were respectively measured and recorded.The water equivalent diameter(DW),conversion factor(f H16)and SSDE based on DW(SSDEDW)were calculated.The DRLs distribution based on age and body size was analyzed by statistic method,and the correlation between DW and mAs was analyzed by regression analysis,and a regression model between SSDEDW and mAs was further established.The intra-group correlation coefficient(ICC)was used to analyze the consistency.Results:In DRLs of various age groups,the CTDIVOL range and SSDEDW range were respectively(12.32 mGy-21.66 mGy)and(13.47 mGy to 17.83 mGy).In the DRL of various body size groups,the CTDIVOL range and SSDEDW range were(13.52 mGy-21.86 mGy)and(13.91 mGy-17.92 mGy).In different ages group of pediatric patients,the range of deviation rates of local DRL(LDRLs)value of radiation dose on head of CTDIVOL value to SSDEDW was-8.54%-21.48%.There were strong positive correlations between DW and mAs at 100 and 120 kVp(r=0.96,0.89,P<0.001),respectively.There was stronger consistency between the calculated value by using SSDEDW and actual measurement value by using sAs(ICC=0.98).Conclusion:SSDEDW can more accurately reflect radiation dose,and SSDEDW can be more quickly calculated to control the radiation dose by using the regression models between SSDEDW and mAs.

Objective:To explore the prevalence and associated factors of anxiety symptoms among the work-ing population in Shandong Province.Methods:Multi-stage stratified cluster sampling method was used to recruit 172 396 working individuals aged 18 years or older from various cities of Shandong Province.Participants complete-da demographic questionnaire covering gender,age,education,lifestyle factors,etc.Anxiety symptoms and occupa-tional burnout were assessed with the Self-Rating Scale for Anxiety(SAS)and Burnout Scale(MBI-GS).Corre-lates were analyzed using multifactor logistic regression.Results:The prevalence of anxiety symptoms was 17.0％(25 991/152 759).Multivariate logistic regression analysis indicated that female(OR=1.17),primary education or below(OR=1.58),divorced(OR=1.24),previous drinking habit(OR=1.23),smoking habit(OR=1.20),poor physical health(OR=24.85),and experiencing burnout(OR=5.48)were risk factors for anxiety symptoms(P＜0.05).Conclusion:The prevalence rate of anxiety is relatively high in working population in Shandong Prov-ince,and anxiety is mainly associated with gender,education level,marital status,smoking,alcohol consumption,physical health status and burnout.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Ensuring food security requires new green pesticides. Double-stranded RNA (dsRNA) pesticides trigger RNA interference by exogenous dsRNA specifically targeting pests and diseases. They can inhibit the expression of key genes in pathogens or pests, thereby achieving effective control of specific pests and diseases. DsRNA pesticides are environmentally friendly, with strong specificity and efficient gene silencing ability, while they have problems such as high production costs. Using engineering strains to produce dsRNA is a feasible strategy, whereas currently there is no cost-effective engineering strain for producing dsRNA. This article reviews the research progress and production strategies of using microorganisms to produce dsRNA, hoping to provide reference for dsRNA production.
RNA, Double-Stranded/genetics* ; Genetic Engineering/methods* ; RNA Interference ; Pesticides ; Animals

OBJECTIVE To analyze the blood components of Suanzaoren Decoction after oral administration using UHPLC-Q Exactive Orbitrap-MS technology.METHODS Female Sprague-Dawley(SD)rats were used as experimental subjects,and Suanza-oren Decoction was administered orally.Serum samples were collected,and the aqueous extract of Suanzaoren Decoction and the serum were analyzed using UHPLC-Q Exactive Orbitrap-MS technology to identify the prototype components and metabolites absorbed into the blood by comparing and analyzing with the LuMet-TCM database.RESULTS It showed that a total of 458 components were iden-tified in the aqueous extract of Suanzaoren Decoction,and 26 chemical components were identified in the blood,including 23 prototype components and 3 metabolites.CONCLUSION The prototype components absorbed into the blood discovered in this study may be the active ingredients of Suanzaoren Decoction,providing a reference for the research on the pharmacodynamic material basis of Suanza-oren Decoction.