Piezo1 is a Ca²⁺-permeable mechanosensitive ion channel that plays a central role in mechanosensing and signal transduction in dental and periodontal tissues. In tooth tissue, Piezo1 is a key factor mediating dentin sensitive pain. The flow of dentinal tubule fluid induced by external stimulation can activate the Piezo1 channel on odontoblasts, triggering neuronal signals through the pannexin-1-purinergic 2X3 receptor (PANX-1-P2X3) receptor axis, resulting in pain perception. In addition, Piezo1 has a dual regulatory role in the process of pulp inflammation and repair : on the one hand, its expression is up-regulated in an inflammatory environment, which may aggravate pain sensitivity ; on the other hand, it activates the migration, proliferation and odontogenic differentiation of dental pulp stem cells by mediating Ca²⁺influx, ATP release and downstream purinergic 2X7 receptor (P2X7R), MEK / ERK signaling pathways, thereby promoting reparative dentin formation. In periodontal tissue, Piezo1 plays a central role in maintaining periodontal tissue homeostasis and regulating alveolar bone remodeling by sensing mechanical stimuli such as bite force. During orthodontic tooth movement, Piezo1 promotes osteogenic differentiation by activating Wnt / Ca²⁺, Notch and other pathways on the tension side. It affects osteoclast activity by regulating receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) balance on the pressure side. At the same time, Piezo1 is also a key regulator of periodontal immune microenvironment. It is expressed in immune cells such as macrophages, neutrophils and dendritic cells. Its activation can promote the polarization of macrophages to pro-inflammatory M1 type, enhance the release of pro-inflammatory factors and matrix metalloproteinases, and thus aggravate the inflammatory destruction of periodontal tissue.In view of its multiple functions, Piezo1 has become a potential therapeutic target, including local or systemic application of its inhibitors, mechanical intervention, physical therapy, gene therapy and stem cell therapy, showing a broad clinical transformation prospect in the treatment of oral diseases. In this paper, the structural characteristics, signal transduction mechanism of Piezo1 and its expression distribution, function and regulatory network in tooth tissue and periodontal tissue are reviewed, so as to provide ideas for the development of oral disease treatment strategies targeting Piezo1.

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

Objective:To explore the factors influencing adherence to voice therapy among patients with voice disorders in China. Methods:Patients with voice disorders who visited the Voice Therapy Center at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from February to May 2022 were enrolled in the study. Adherence was assessed using the URICA-Voice scale, while influencing factors were assessed through the Voice Handicap Index（VHI） scale and a general information questionnaire. Correlation analysis was conducted using univariate and multivariate logistic regression analysis. Results:A total of 247 patients were included in the study, comprising 57 males（23.08%） and 190 females（76.92%）. The results revealed that: ①Female patients demonstrated higher likelihood of being in the contemplation stage（OR=0.22） compared to males. ②Patients with a monthly family income per capita>6 000 yuan were more likely to be in the contemplation stage than those with<3 000 yuan with an OR = 13.94. ③High vocal-demand occupations increased contemplation stage probability（OR=7.70） compared to moderate-demand occupations. ④Residence within 30-minute commute predicted action/maintenance stages（OR=7.14） versus≥60-minute commute. ⑤Patients whose occupations had high voice demands were more likely to be in the action and maintenance stages than those with average voice demands, with an OR of 16.20. Conclusion:Gender, monthly family income per capita, occupational voice demands, and distance to the hospital significantly impact the URICA-Voice compliance stages of patients. Patients who are female, have higher family income, have occupations with high voice demands, and live closer to the hospital exhibit higher compliance with voice training.
Humans ; Male ; Female ; Voice Disorders/therapy* ; Patient Compliance ; Voice Training ; Surveys and Questionnaires ; China ; Middle Aged ; Adult ; Voice Quality ; Logistic Models ; Aged

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

Objective To investigate the therapeutic efficacy of combination of dapagliflozin and sacubitril valsartan on patients with heart failure(HF)complicated with type 2 diabetes mellitus(T2DM).Methods A retrospective study was conducted on 160 patients with HF and T2DM admitted to our hospital from November 2020 to November 2022.According to drug treatment,they were classified into sacubitril valsartan group(80 cases)and combined group(dapagliflozin combined with sacubitril valsartan,80 cases).After 3 months of treatment,the differences were compared between the two groups in following aspects:blood glucose fluctuations,left ventricular diastolic function,and vascular endothelial function,and the incidence of adverse events after 1 year of follow-up.Results After 3 months of treatment,serum FPG,2 h-PG and HbAlc levels,and MAGE,LAGE,MODD and SDBG values were significantly lower in the combined group than the sacubitril valsartan group(P＜0.05,P＜0.01).The combined group had obviously higher e'and LVEF values while lower LVMI and BNP levels than the other group(P＜0.05,P＜0.01).After 3 months of treatment,NO and FMD were notably higher[96.18±6.70 ng/L vs 92.34±6.85 ng/L,P=0.000;(8.25±1.16)％vs(7.72±1.28)％,P=0.007],while ET-1(59.72±4.95 ng/L vs 63.90±4.63 ng/L,P=0.000)was remarkably lower in the combined group than the sacubitril valsartan group.There was no statistical significance in the total incidence of adverse events between both groups after 1 year of follow-up(P＞0.05).Conclusion The combination of dapagliflozin and sacubitril valsartan has a significant improvement effect on blood glucose,left ventricular diastolic function and vascular endothelial function in T2DM patients with HF,with good drug safety.

Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16％.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P＜0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P＜0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.

Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1 930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NF-κB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NF-κB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.

Objective:To compare the efficiency and characteristics of different carrier proteins and signal sequences in delivering antigens into Escherichia coli outer membrane vesicles (OMVs). Methods:The fusion protein F1V, which consisted of the main protective antigen of Yersinia pestis F1 and LcrV, was expressed using the carrier proteins such as cytolysin A (ClyA), outer membrane protein A (OmpA), or β-lactamases (Bla) signal sequence as a carrier protein. The expression, localization, and content of F1V protein in OMVs were compared and analyzed. Results:All three delivery methods successfully incorporated F1V protein into OMVs and localized it on the surface of OMVs. Notably, when OmpA was used as the carrier protein, the F1V fusion protein constituted up to 30% of the total protein in OMVs. The highest yield of OMVs, reaching 4.2 mg/L, was achieved when Bla signal sequence was used as the carrier.Conclusions:There is a significant difference in the efficiency of different carrier proteins in delivering the F1V antigen into OMVs of Escherichia coli. Considering both the yield of OMVs and the proportion of antigen in the total protein of OMVs, the carrier Bla signal sequence demonstrated the highest efficiency in delivering F1V into OMVs, showing a potential for the future development of OMVs-based plague vaccines.

Objective To systematically review and quantify the content and structure of the non-accompanied wards policy texts at the provincial level in China from the perspective of policy tools,providing references and insights for optimizing and implementing future policies.Methods Using the policy analysis tools as framework,it applies content ana lysis to construct a two-dimensional analytical framework with the X-dimension and Y-dimension.A total of 19 policy texts related to non-accompanied ward issued by provincial governments in China from January 2000 to August 2024 were coded and analyzed.Results A total of 141 entries were coded.In the X-dimension,supply-oriented,demand-oriented,and environment-oriented policy tools accounted for 21.28%,19.86%,and 58.86%,respectively,indicating a greater reliance on environmental-oriented policy tools;In the Y-dimension,policies from the"12th Five-Year Plan"(16.31%),"13th Five-Year Plan"(14.89%),and"14th Five-Year Plan"(68.80%)phases were analyzed.The number of policies in the"14th Five-Year Plan"phase was the highest among the three periods.Conclusion The policy framework for non-accompanied wards in China is still in its initial exploration phase and has room for improvement.It is recommended that future policies optimize the use of policy tools,strengthen coordination among them,and support the development of non-accompanied wards.