Objective To explore the regulatory effect of oral probiotics as adjuvant therapy on the imbalance of helper T cell 1(Th1)/helper T cell 2(Th2),intestinal flora and lung function in children with allergic asthma and its clinical efficacy.Methods A retrospective analysis was con-ducted in the clinical data of 122 children with allergic asthma.According to different treatment regi-mens,the children were divided into control group(n=60)and observation group(n=62).The control group received conventional treatment combined with budesonide,while the observation group received oral probiotics as adjunctive therapy in addition to the treatment in the control group.The asthma control effects[Childhood Asthma Control Test(C-ACT)score],intestinal flora(Escherichia co-li,Bifidobacterium,Lactobacillus),relevant lung function indicators[peak expiratory flow as a percentage of predicted value(PEF％pred),fractional exhaled nitric oxide(FeNO),forced expiratory volume in one second as a percentage of predicted value(FEV1％pred)],respiratory mechanics parameters[work of breathing(WOB),airway resistance(Raw),peak inspiratory pressure(PIP),dynamic lung compliance(Cdyn)],levels of sputum adhesion molecules[integrin α4β1,vascular cell ad-hesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1)],levels of Th1/Th2 cytokine-related indicators[interleukin-4(IL-4),interferon--y(IFN-γ),the ratio of IFN-γ to IL-4(IFN-γ/IL-4),the ratio of Th1 to Th2(Th1/Th2)],symptom disappearance time,clinical effica-cy,and the incidence of adverse reactions were compared between the two groups.Results After treatment,the observation group demonstrated significantly higher C-ACT scores,overall clinical re-sponse rates,IFN-γ/IL-4 and Th1/Th2 ratios,along with elevated levels of Lactobacillus,Bifidobacterium,PEF％pred,FEV1％pred,Cdyn and IFN-γ compared to the control group(P＜0.05).Conversely,adverse reaction rates,and levels of Escherichia coli,FeNO,Raw,WOB,PIP,integrin α4β1,VCAM-1,ICAM-1 and IL-4 were significantly lower in the observation group(P＜0.05).Symptom resolution time was also shorter in the observation group(P＜0.05).The total Naranjo scale score was 3,indicating a"possible"causal relationship between adverse drug re-actions and probiotic use.Conclusion Oral probiotics as adjunctive therapy can effectively regulate Th1/Th2 imbalance induced by allergic asthma in children,improve clinical outcomes,pulmonary function,respiratory mechanics,intestinal microbiota composition,and sputum adhesion molecule levels.

Limosilactobacillus reuteri is a microbe intricately linked to humans and animal health.A thor-ough assessment of its safety and potential benefits is imperative prior to its application in human and ani-mals.In this investigation,we performed a comprehensive analysis encompassing genome sequencing,genomic analysis,and phenotypic characterization of L.reuteri Q35,an exceptionally proficient producer of reuterin.The whole genome sequencing results showed that the complete genome sequence spans 2145158 bp with a GC content of 38.9％ and encompasses 2121 genes.Initial identification of antibiotic-re-sistant genes,virulence factors,and toxin-coding genes in the genome substantiated the strain' s low-risk status.Subsequent tests for antibiotic resistance,acute oral toxicology,and hemolysis further confirmed its elevated safety level.The genome of L.reuteri Q35 was found to contain genes associated with adhe-sion and stress tolerance.Following exposure to artificial gastric juice and bile salt,the strain exhibited a higher survival rate and demonstrated a strong scavenging ability for hydroxyl free radicals in antioxidant capacity tests.These findings suggested that L.reuteri Q35 possesses unique probiotic properties.Addi-tionally,the genome of strain Q35 harbors three truncated oxaloyl-CoA decarboxylase genes (oxc1,oxc2 and oxc3),overexpression of which resulted in a significant increase in ammonium oxalate degradation from 29.5％ to 48.8％.These findings highlight that L.reuteri Q35 exhibits both favorable safety charac-teristics alongside beneficial properties,making it a promising candidate for treating metabolic disorders such as hyperoxaluria.

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.
Female ; Humans ; Uterine Cervical Neoplasms/pathology* ; HeLa Cells ; Fibronectins/metabolism* ; Culture Media, Conditioned ; Carcinoma, Squamous Cell/metabolism* ; Adenocarcinoma ; Cadherins/metabolism* ; RNA, Messenger/metabolism* ; Cell Movement ; Epithelial-Mesenchymal Transition/genetics* ; Cell Line, Tumor ; Cell Proliferation ; S100 Calcium Binding Protein A7/metabolism*

Humans ; Pyriform Sinus/surgery* ; Thyroid Neoplasms/diagnosis* ; Fistula/surgery* ; Diagnostic Errors ; Pharyngeal Diseases/surgery*

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Nucleophosmin ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Leukemia, Myeloid, Acute/genetics* ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Heart Neoplasms/genetics* ; Hemangiosarcoma/genetics* ; Humans ; Mediastinal Neoplasms ; Thymus Neoplasms

ObjectiveTo investigate effect of conducting training of autism spectrum disorder （ASD） early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021， the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training， the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals， confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training， the number of children with suspected ASD referred by primary care hospitals was more than that before training ［（16.65±11.60） vs. （3.40±2.23）， t=5.431， P<0.01］， the number of children diagnosed with ASD was more than that before training［（6.85±4.93） vs. （2.45±1.67）， t=4.171， P<0.01］， and the differences were statistically significant. As for the diagnosed age of ASD children， after training， the average age was lower than that before training ［（34.95±11.67） vs. （42.2±14.64）， t=-2.553， P=0.019］. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.

Aim To investigate the reeovery of I FN-7- tion and the protective effect of Prepared Radix Reh- secreting T and NK cells after low dose X-ray irradia- manniae ( PRR ).Methods X-ray 2.5Gy was used to establish a mouse irradiated model,and some irradiated mice were used to establish a melanoma lung cancer metastasis model or to be treated by PRR.The propor¬tion and number of Tel , Thl and NK1 cells with the phenotypes of IL-12R and IL-15R were detected by flow cytometry.The transcription levels of IL-12,1L- 15 ,STAT4 and T-bet were detected by RT-qPCR.Re¬sults Within four days after irradiation,Thl ,Tcl and NK1 cells were significantly reduced ( P < 0.05 , P < 0.01).The expression of IL-12R and IL-15R de¬creased in Thl and Tel cells , and increased in NK1 cells ( P < 0.05 ).On day 8 of irradiation , NK1 and Tc 1 cells recovered or exceeded basic level, but Th 1 was still lower than normal level ( P < 0.05 ) , and tumor load of irradiated mice increased significantly (P <0.01).Compared with radiation group, the propor¬tion and absolute numbers of NK1 ,Tel and Thl were up-regulated by PRR (P <0.05 <0.01) ,and tumor load was down-regulated ( P < 0.05 ).Conclusions The impaired reconstitution of Thl cells after irradia¬tion affects the anti-tumor ability.PRR promotes the recover}' of IFN-∗y-secreting T and NK cells after radia¬tion and reduces the risk of tumor metastasis in mice.

OBJECTIVE: To investigate the antileukemia activity of phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 on human leukemia cell line U937. METHODS: MTT, soft agar assay, flow cytometric analysis and western blot were used to detect the effect of ZSTK474 on U937 cell proliferation, tumorigenicity, cell cycle, cell apoptosis and phosphorylation levels of the key factor of PI3K/AKT pathway. Chou-Talalay method was used to evaluate the combination of ZSTK474 with Cytarabine or Homoharringtonine. RESULTS: PI3K inhibitor ZSTK474 could inhibit the proliferation and tumorigenicity of U937 cell, induce G CONCLUSION ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Glycogen Synthase Kinase 3 beta ; Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Triazines ; U937 Cells

Objective:To investigate the biological essence of the content variation of differential primary and secondary metabolites in fresh roots of Scutellaria baicalensis under drought stress. Method:The changes of metabolites were analyzed by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass/mass （UHPLC-ESI-Q-TOF-MS/MS）. Result:A total of 11 differential compounds were identified from the roots of S. baicalensis （VIP≥2）. Under drought stress， citric acid content increased and shikimic acid content decreased， indicating that the drought stress weakened the primary metabolism but strengthened secondary metabolism. Drought stress raised the content and regulated the proportion of various secondary metabolites by modulating the biosynthesis and biotransformation of them. To be specific， the content of free flavonoids with many phenolic hydroxyl groups and high biological activity and pharmacological activity， such as baicalin， wogonoside， baicalein， wogonin， chrysin， eriodictyol， 5，2'，6'-trihydroxy-7，8-dimethoxyflavone， 5，8-dihydroxy-6，7-dimethoxyflavone， and 3，5，7，2'，6'-pentahydroxyflavanone， was significantly increased. The massive compounds， like an intricate buffer， maintain metabolism stable as quickly and accurately as possible through biosynthesis and biotransformation， thus responding to the changing environment， which reveals how the quality of genuine regional drugs is influenced and why compounds in herbal medicine are complex. Conclusion:Secondary metabolites with low content but high activity are important influencing factors of medicinal material quality and metabolites with high content and high activity are evaluation indicators of genuine regional drug quality.