ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

OBJECTIVES: To investigate the therapeutic mechanism of Sangma Zhike Formula (SMZKF) for relieving cough sensitivity and airway inflammation in rats with postinfectious cough (PIC). METHODS: Male SD rat models were established by cigarette smoke exposure with intranasal LPS instillation and capsaicin aerosol inhalation. From day 19 following the start of PIC modeling, the rats received daily treatment with saline (model group), low-, medium-, and high-dose SMZKF, and compound methoxyphenamine (ASM) via gavage for 10 consecutive days (n=8). The assessments included behavioral changes, cough sensitivity (latency and frequency), lung histopathology, inflammatory cell counts and cytokine/mediator levels in the bronchoalveolar lavage fluid (BALF), oxidative stress markers in the lung tissue, and expressions of proteins related with cough hypersensitivity and pyroptosis. RESULTS: The rat models of PIC exhibited reduced mental alertness, accelerated respiration, and pronounced symptoms such as coughing, sneezing, and facial scratching with significantly shortened cough latency and increased 5-min cough frequency. Histopathological analysis revealed collapsed alveolar structures, thickened alveolar septa, and extensive inflammatory cell infiltration in the bronchi and peribronchial regions, accompanied by elevated bronchial and alveolar inflammation scores of the rat models. In the BALF, inflammatory cell counts and the levels of IL-1β, TNF-α, IL-6, COX-2, PGE-2, and TXA-2 were all markedly elevated, and the pulmonary oxidative stress markers (ROS and MDA) and myeloperoxidase (MPO) activity were also significantly increased. The pulmonary expressions of cough hypersensitivity-related proteins (TRPV1, SP, CGRP, and NK1R) and pyroptosis-associated markers (P-NF-κB, NLRP3, ACS, cleaved caspase-1, cleaved IL-1β, and GSDMD-N) were significantly upregulated in the model group. SMZKF interventions significantly ameliorated these pathological changes in the rat models, and high-dose SMZKF produced a similar therapeutic efficacy to that of ASM. CONCLUSIONS SMZKF alleviates cough sensitivity and airway inflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/caspase-1/GSDMD pyroptosis pathway.
Animals ; Cough/metabolism* ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Male ; TRPV Cation Channels/metabolism* ; Rats ; Drugs, Chinese Herbal/pharmacology* ; Inflammation ; Signal Transduction

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

ObjectiveTo investigate the prevalence and its influencing factors of hyperuricemia (HUA) among the employed individuals who undergo occupational health screening in Shanghai, so as to provide a scientific basis for the prevention and control of HUA and for the health promotion in this population. MethodsCluster sampling methods were performed to recruit all the employed individuals who underwent routine health check-ups at the Shanghai Health and Medical Center from January to December 2023. Relevant data, including physical examination results, laboratory tests, and questionnaire surveys, were collected for analyses. Based on the diagnostic criteria for HUA, participants were categorized into HUA group and non-HUA group. Logistic regression analysis was used to identify the influencing factors of HUA. ResultsThe detection rate of HUA in the employed population of Shanghai was 23.26%, with a significantly higher rate in males (31.12%) than that in females (10.43%) (χ²=381.853,P<0.001). The detection rate of HUA increased with age (χ²_trend=5.728, P_trend=0.017). Logistic regression analysis revealed that males had a higher risk for HUA the females, with overweight, obesity, meat-predominant diet, hypertension, and dyslipidemia being positively correlated with HUA risk. While, individuals aged 40‒ and 50‒ years had a lower risk for HUA compared with those aged 20‒ years. ConclusionThe prevalence of HUA among the employed individuals who undergo health check-ups in Shanghai is relatively high. Attention should be paid to maintaining a healthy lifestyle and keeping a balanced diet. Targeted health management should prioritize for males, individuals with hypertension and BMI overweight and obesity, and those with dyslipidemia to reduce the risk of HUA.

Objective To enhance the cyclic peptide compound's membrane permeability,structural stability,and neuroprotective activity,based on the amino acid sequence of peptides of Tat-GluA2-3Y,by designing and synthesizing a serial of cyclic peptides through strategies including polypeptide cyclization,replacement of the cell-penetrating peptide,substitution with D-amino acids,and incorporation of mini polyethylene glycol fragments.Methods The target peptides were synthesized based on standard Fmoc solid-phase method,followed by analysis and purification via reverse phase high-performance liguid chromatography(RP-HPLC).The cytoprotective activity of the peptides was evaluated by using the HT-22 cell model.The transmembrane transport efficiency of the peptides was determined based on the Caco-2 monolayer intestinal epithelial cell model.Plasmatic plasma and metabolic stability of the peptides were measured by in vitro co-incubation experiments with rat plasma and human liver microsomes.Finally,the in vivo neuroprotective activity of the peptides was validated by using a mouse middle cerebral artery occlusion model.Results Seven cyclic peptides were successfully designed and synthesized by using the standard Fmoc solid-phase method,with purities exceeding 90%as confirmed by RP-HPLC.Cytoprotective activity assay demonstrated that both Tat-GluA2-3Y and CMT-C3Y exhibited activity at concentrations above 125 nmol/L,with CMT-C3Y showing superior activity as compared to Tat-GluA2-3Y.The results of the transmembrane assay demonstrated that,compared to Tat-GluA2-3Y,CMT-C3Y exhibited significant transmembrane capabilities at all tested concentrations(P<0.001).CMT-C3Y was classified as a highly permeable compound,whereas Tat-GluA2-3Y was categorized as a moderately permeable compound.Plasma stability studies indicated that over 50%of Tat-GluA2-3Y was metabolized after 4 h of co-incubation with rat plasma.After 8 h of coincubation with CMT-C3Y,the remaining amount was 88.1%,and no obvious degradation phenomenon occurred.In human liver microsomal stability tests,the half-life of Tat-GluA2-3Y was 26.1 min,as compared to 103.8 min for CMT-C3Y,highlighting the enhanced stability of CMT-C3Y.Tat-GluA2-3Y and CMT-C3Y were classified as a fast-metabolizing drug and a moderate-metabolizing drug,respectively.Animal experiments further demonstrated that at a dose of 8 mg/kg the neuroprotective activity of CMT-C3Y was significantly superior to that of Tat-GluA2-3Y(P<0.001).Conclusion The designed bicyclic peptide CMT-C3Y demonstrates significantly higher cell-penetrating efficiency and superior plasma stability as compared to Tat-GluA2-3Y,along with enhanced neuroprotective activity at both cellular and animal levels.

Objective To investigate the therapeutic mechanism of Sangma Zhike Formula(SMZKF)for relieving cough sensitivity and airway inflammation in rats with postinfectious cough(PIC).Methods Male SD rat models were established by cigarette smoke exposure with intranasal LPS instillation and capsaicin aerosol inhalation.From day 19 following the start of PIC modeling,the rats received daily treatment with saline(model group),low-,medium-,and high-dose SMZKF,and compound methoxyphenamine(ASM)via gavage for 10 consecutive days(n=8).The assessments included behavioral changes,cough sensitivity(latency and frequency),lung histopathology,inflammatory cell counts and cytokine/mediator levels in the bronchoalveolar lavage fluid(BALF),oxidative stress markers in the lung tissue,and expressions of proteins related with cough hypersensitivity and pyroptosis.Results The rat models of PIC exhibited reduced mental alertness,accelerated respiration,and pronounced symptoms such as coughing,sneezing,and facial scratching with significantly shortened cough latency and increased 5-min cough frequency.Histopathological analysis revealed collapsed alveolar structures,thickened alveolar septa,and extensive inflammatory cell infiltration in the bronchi and peribronchial regions,accompanied by elevated bronchial and alveolar inflammation scores of the rat models.In the BALF,inflammatory cell counts and the levels of IL-1β,TNF-α,IL-6,COX-2,PGE-2,and TXA-2 were all markedly elevated,and the pulmonary oxidative stress markers(ROS and MDA)and myeloperoxidase(MPO)activity were also significantly increased.The pulmonary expressions of cough hypersensitivity-related proteins(TRPV1,SP,CGRP,and NK1R)and pyroptosis-associated markers(P-NF-κB,NLRP3,ACS,cleaved caspase-1,cleaved IL-1β,and GSDMD-N)were significantly upregulated in the model group.SMZKF interventions significantly ameliorated these pathological changes in the rat models,and high-dose SMZKF produced a similar therapeutic efficacy to that of ASM.Conclusion SMZKF alleviates cough sensitivity and airway inflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/caspase-1/GSDMD pyroptosis pathway.

ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.

Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Pro-teomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the associa-tion between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed.Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients.In addition,SND1 was predominantly present in the cytoplasm of LUAD cells.Enrichment analysis showed that SND1 was closely associated with the cell cycle,as well as DNA replication,and chro-mosome segregation.Immune infiltration analysis showed that SND1 was closely associated with various immune cell popula-tions,including T cells,B cells,cytotoxic cells and dendritic cells.In vitro studies demonstrated that silencing of SND1 inhib-ited cell proliferation,invasion and migration of LUAD cells.Besides,cell cycle was blocked at G,phase by down-regulating SND1.Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

Objective To analyze the characteristics and related influencing factors of transfusion reactions in pediatric patients,so as to provide evidence for clinical treatment and prevention of transfusion reactions.Methods A retrospective study was conducted on children who received blood transfusions at our hospital from 2019 to 2023 in terms of the incidence,types,time of occurrence,and related influencing factors of transfusion reactions.Results A total of 69 926 transfusions were performed from 2019 to 2023,with 711 cases of transfusion reactions,resulting in an incidence of 1.02%.The inci-dence of transfusion reactions decreased annually from 2019(1.89%)to 2022(0.50%).The incidence of transfusion reac-tions to apheresis platelets,frozen plasma,suspended leukocyte-depleted red blood cells and cryoprecipitate coagulation fac-tor were 2.16%(551/25 565),0.50%(92/18 277),0.25%(65/25 679)and 0.74%(3/405),respectively,with a-pheresis platelet transfusion of a significantly higher incidence compared to other blood components(P<0.05).As of trans-fusion reaction types,allergic reactions accounted for 86.22%(613/711),febrile non-hemolytic transfusion reactions(FNHTR)accounted for 13.08%(93/711),and acute hemolytic transfusion reactions accounted for 0.70%(5/711).Multivariate logistic regression analysis showed that apheresis platelet transfusion was an independent risk factor for allergic reactions(P<0.05),while suspended leukocyte-depleted red blood cells transfusion was an independent risk factor for FNHTR(P<0.05).In terms of the occurrence time of transfusion reactions,compared to apheresis platelets and frozen plas-ma,transfusion reactions caused by suspended leukocyte-depleted red blood cells transfusion occurred later(apheresis platelets P<0.05,frozen plasma P<0.05).Conclusion The results suggest that blood components transfused are significant influencing factors for the characteristics of transfusion reactions in pediatric patients,affecting the incidence,types,and oc-currence time of transfusion reactions,which provides reference for clinical treatment and prevention of transfusion reactions.