Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Immature permanent teeth refer to those that have erupted but have not yet formed and matured in terms of shape and structure. The characteristics of their disease onset and treatment methods are different from those of ordinary permanent teeth. Children with special healthcare needs often lack the capacity to cooperate during routine dental procedures, making treatment under general anesthesia (GA) the preferred option. With social advancements, the demand for pediatric dental GA has considerably increased. This study discuss the treatment strategies for immature permanent teeth under GA, including diagnosis, therapeutic principles, key considerations, and clinical approaches for dental caries, pulpitis periapical periodontitis, etc.
Child ; Humans ; Anesthesia, General ; Dental Caries/diagnosis* ; Dentition, Permanent ; Periapical Periodontitis/therapy* ; Pulpitis/therapy*

BACKGROUND:Biomimetic design of bioactive materials to restore,maintain or improve the function of tissue based on the understanding of anatomy on the function and structure of biological tissue is a research hotspot in the field of regenerative medicine at present. OBJECTIVE:To discuss the effect of mechanical properties,three-dimensional spatial structure,and biochemical activity of biomedical scaffolds on cell behavior and review the application of biomedical scaffolds in the field of tissue engineering. METHODS:The articles published in CNKI,Wanfang,Web of Science,and PubMed databases from January 2003 to April 2023 were searched by computer.The Chinese search terms were"extracellular matrix,tissue engineering,scaffolds,biomaterials,biomimetic structures,mechanical properties,three-dimensional structures,tendon-bone interface,osteochondral,neural conduits,artificial blood vessels".English search terms were"extracellular matrix,tissue engineering,scaffolds,biomimetic structures,biomaterials,tendon bone interfaces,osteochondral,neural conduits,artificial blood vessels". RESULTS AND CONCLUSION:Cells are in a complex and dynamic three-dimensional environment,so the extracellular matrix is the ultimate target of biomaterial simulation.The bionic structure of biomedical scaffolders needs to be similar to the real microenvironment,so that cells can stick to the wall,grow and migrate normally,and maintain their diverse physiological functions.Biomimetic design of extracellular matrix in terms of mechanical properties,three-dimensional spatial structure,and biochemical properties of biomedical scaffolds can play a decisive role in tissue repair,thus affecting the final result of tissue repair.Biomimetic biomedical scaffolds have been widely used in tendon-bone interface,bone cartilage interface,nerve,vascular regeneration,and other fields,providing a promising new idea in clinical practice.

In recent years,the generation,maintenance and regulation of the intestinal mucosal barrier have become a re-search focus in the occurrence,development,treatment,and prognosis of inflammatory bowel disease(IBD)and colitis associated color-ectal cancer(CAC).Tight junction(TJ)proteins are an important component of the intestinal mucosal barrier,which the Claudin fami-ly proteins have become a research hotspot.This review mainly introduces the changes of Claudin protein in IBD and CAC,as well as the latest research progress on its role in the occurrence,development and clinical treatment of IBD and CAC.

Background and purpose:Abnormal DNA methylation is closely associated with the onset and progression of tumors.This study aimed to investigate the expression of intermediate filament family orphan 1(IFFO1),a methylation-driven gene(MDG)in pancreatic adenocarcinoma(PAAD),along with its effects on the invasion and metastasis of PAAD cells,as well as its potential as a diagnostic and prognostic biomarker.Methods:mRNA expression data(TCGA-PAAD-mRNA),DNA methylation data(TCGA-PAAD-meth,GSE53051,PACA-AU)of PAAD and adjacent normal tissues,as well as DNA methylation data of healthy individuals'blood(GSE69270),were obtained from the The Cancer Genome Atlas(TCGA),International Cancer Genome Consortium(ICGC)and Gene Expression Omnibus(GEO)databases.By performing differential expression analysis combined with differential methylation analysis,we screened for MDG in PAAD.In the TCGA database,Pearson correlation tests were employed to verify the relationship between IFFO1 promoter methylation level and its expression level.Additionally,Kaplan-Meier survival analysis was conducted to evaluate the relationship among IFFO1 promoter methylation level,expression level,and the prognosis of PAAD.Pathological sections of cancer tissues and corresponding adjacent tissues from 27 PAAD patients were obtained from Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine.All samples involved in this study were approved by the human ethics committee of Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine(ethics number:hospital ethics review[2017]No.53).Immunohistochemistry staining(IHC)was utilized to detect the expression of IFFO1 in cancer tissues and corresponding adjacent tissues from 27 PAAD patients.Based on the median expression level of IFFO1,patients in the TCGA database were classified into high-expression and low-expression groups.Subsequently,differential analysis,gene ontology(GO)enrichment analysis and gene set enrichment analysis(GSEA)were performed.Western blot and real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)were employed to assess the expression variations of IFFO1 between the normal pancreatic ductal epithelial cell line H6C7 and the PAAD cell lines MIA PaCa2,BxPC-3,AsPC-1 and Capan-2.The impact of IFFO1 overexpression on the migration and invasion capacities of PAAD cell lines AsPC-1 and Capan-2 was evaluated using scratch and invasion assays.Additionally,receiver operating characteristic(ROC)curves and Kaplan-Meier survival analysis were utilized to assess the diagnostic and prognostic significance of IFFO1 methylation levels in the TCGA pan-cancer cohort.Results:Through the cross-screening of five datasets,41 MDG in PAAD were identified.Among these,IFFO1 was found to be the gene most closely associated with the prognosis of PAAD[hazard ratio(HR)=0.28,P＜0.001].IFFO1 exhibited high methylation and low expression levels in PAAD.Moreover,a significant negative correlation was observed between the methylation level of its promoter and its expression level(r=-0.55,P＜0.001).IHC results indicated that IFFO1 expression was significantly lower in PAAD tissues than in adjacent non-tumor tissues(P＜0.05).TCGA survival analysis demonstrated that patients with high methylation or low expression of IFFO1 had poorer overall survival(P＜0.05).Both GO and GSEA analyses indicated that the pathway"Negative regulation of cell migration"was enriched in patients with high IFFO1 expression.Western blot and RTFQ-PCR results demonstrated that IFFO1 expression in normal pancreatic ductal epithelial cells H6C7 was significantly higher compared with PAAD cell lines MIA PaCa2,BxPC-3,AsPC-1,and Capan-2.Overexpression of IFFO1 significantly inhibited the migration and invasion of the PAAD cell lines AsPC-1 and Capan-2.Additionally,pan-cancer analysis revealed that IFFO1 exhibited abnormal promoter methylation and low expression across various cancer types,with its methylation levels demonstrating significant diagnostic and prognostic prediction value among different tumors.Conclusion:Promoter hypermethylation results in decreased expression of IFFO1 in PAAD.IFFO1 may suppress the invasion and migration abilities of PAAD cells.Furthermore,IFFO1 methylation holds great promise as a novel biomarker for the diagnosis and prognosis of PAAD.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective To investigate the role of LncRNA-gm33782 in tubular injury in acute kidney injury(AKI)and the mechanism by which isorhamnetin ameliorates inflammatory cell apoptosis of tubular cells in AKI.Methods Forty-eight male C57BL/6J mice were randomly assigned to four groups:control group,AKI model group,electroporation+AKI group,and treatment group(oral administration of 30 mg/kg isorhamnetin).AKI was induced by a one-time intraperitoneal injection of 20 mg/kg cisplatin.Chromatin isolation by RNA purification was used to capture the LncRNA-gm33782 binding protein in AKI-affected kidneys for mass spectrometry,revealing the direct target protein of LncRNA-gm33782.The role of LncRNA-gm33782 in AKI was evaluated by observing the renal function,pathological structure,and expression of renal inflammatory factors(interleukin-1β,interleukin-6,and tumor necrosis factor-α)in mice after electrotransfection and isorhamnetin treatment.Nuclear factor-κB was detected as a critical mediator of inflammation.The expression levels of Bax and Bcl-2 protein were detected and flow cytometry was performed to evaluate the therapeutic effect of isorhamnetin on tubular cell apoptosis in AKI.Results Kidneys with cisplatin-induced AKI showed severe renal tubule injury,macrophage infiltration,and inflammation.Isorhamnetin treatment and LncRNA-gm33782 electrotransfection knockdown alleviated these signs of AKI.LncRNA-gm33782 was mainly expressed in renal tubular cells with AKI.LncRNA-gm33782 binding protein was detected by mass spectrometry,and complement factor H was found to have a direct binding relationship with LncRNA-gm33782.After LncRNA-gm33782 was overexpressed in vitro,the expression of complement factor-H immediately increased,and the therapeutic effect of isorhamnetin on apoptosis of AKI-affected inflammatory cells was inhibited.Conclusions Isorhamnetin alleviates apoptosis of tubular inflammatory cells in AKI by inhibiting the regulatory effect of LncRNA-gm33782 on complement factor H.

Levothyroxine anaphylaxis is a rare yet severe adverse reaction to exogenous levothyroxine. While levothyroxine desensitization is commonly employed, its direct application in patients with severe shock poses considerable risks. Omalizumab may offer a potential adjunctive approach to induce tolerance to levothyroxine. We reported a case of a 30-year-old female with a history of thyroid papillary carcinoma who developed anaphylactic shock following oral administration of 50 μg levothyroxine daily after surgery. High serum level of immunoglobulin E (IgE 99.2 kU/L) and positive intradermal tests to all brands of levothyroxine available in China confirm a type Ⅰ hypersensitivity reaction. Several reports have proven the role of omalizumab in desensitization protocol in IgE-mediated diseases; therefore, she was pretreated with three courses of omalizumab (150 mg intradermal injection every four weeks). She then successfully completed oral levothyroxine desensitization and tolerated treatment dose of levothyroxine without experiencing allergic symptoms along with normalization of thyroid function. Further research is warranted to assess its potential as a standard treatment in difficult-to-treat levothyroxine hypersensitivity.

Objective To explore the clinical characteristics and influencing factors of acute colonic pseudo-obstruction(ACPO)after emergency cesarean section.Methods A total of 22 parturients with ACPO after emergency cesarean section who were admitted to Hebei Children's Hospital from January 2019 to June 2023 were retrospectively selected and assigned to the ACPO group,and 110 parturients without ACPO after emergency cesarean section during the same period were selected as the non-ACPO group,according the ratio of 5∶1.The clinical characteristics of the ACPO group were observed.The clinical data of the two groups were collected and compared.Multivariate logistic regression methods were used to analyze the risk factors of ACPO after emergency cesarean section.Results All the patients with ACPO after emergency cesarean section presented with progressive abdominal dull pain,nausea and vomiting,abdominal distension,cessation of defecation and exhaust or a small amount of defecation and exhaust.Physical examination showed abdominal bulge,especially in the upper and right abdomen,with mild tenderness and with no rebounding pain.Univariate analysis showed that there were no significant differences in the maternal age,gestational weeks,embryo number,gravidity,parity,prenatal body mass index(BMI),cause of emergency cesarean section,pregnant complications,general anesthesia,preoperative albumin level or postoperative analgesia between the two groups(all P>0.05);the proportions of operation time≥60 min,blood loss≥800 ml,history of abdominal surgery,cocurrent chronic pelvic inflammatory disease,and intraoperative removal of uterine fibroids in the ACPO group were significantly higher than those in the non-ACPO group(all P<0.05).Multivariate logistic regression analysis showed that operation time≥60 min(OR=5.761),concurrent chronic pelvic inflammatory disease(OR=3.241),and intraoperative removal of uterine fibroids(OR=4.319)were the risk factors of ACPO after emergency cesarean section(all P<0.05).Conclusion Operation time≥60 min,concurrent chronic pelvic inflammatory disease,and intraoperative removal of uterine fibroids are the risk factors of ACPO after emergency cesarean section.More attention should be paid to the parturients with the above-mentioned risk factors after emergency cesarean section,and preventive measures should be taken in advance to effectively reduce the risk of postoperative ACPO.