Vaccination is the preferred strategy for preventing infections such as influenza in elderly individuals;however,its efficacy is often suboptimal due in part to age-related declines in immune function.In this study,we...Vaccination is the preferred strategy for preventing infections such as influenza in elderly individuals;however,its efficacy is often suboptimal due in part to age-related declines in immune function.In this study,we discovered that the infusion of mesenchymal stromal cells(MSCs)restored defects in the splenic stromal cell network and lymphocyte architecture in aged mice while also increasing specific antibody levels following vaccine immunization.This significantly protected aging mice from influenza infection.Mechanistically,the delivered MSCs localized in the splenic marginal zones,where they positioned themselves near marginal reticular cells(MRCs)and stimulated MRC proliferation,partially through the action of vascular endothelial growth factor A(VEGFA).This MSC‒MRC interaction orchestrated the reconstruction of the stromal network,thereby restoring lymphocyte homeostasis and germinal center reactions.Importantly,the MSC-mediated enhancement of the vaccine response was further validated in aged cynomolgus monkeys.Collectively,our findings provide new insights into the application of MSCs in addressing age-related immune decline and highlight splenic MRCs as critical therapeutic targets.展开更多
A novel aperiodically intermittent impulse control(AIIC)method is proposed to investigate the exponential synchronization in mean square(ESMS)of a class of impulsive stochastic infinite-dimensional systems with Poisso...A novel aperiodically intermittent impulse control(AIIC)method is proposed to investigate the exponential synchronization in mean square(ESMS)of a class of impulsive stochastic infinite-dimensional systems with Poisson jumps(ISIDSP).The AIIC control strategy inherits the flexibility of aperiodically intermittent control,including the variable control period,adjustable control interval length,and the discretization of impulsive control.In addition,this article introduces a novel mild Itô's formula.By leveraging semigroup theory,the contraction mapping principle,and graph theory,along with constructing the Lyapunov function,the criterion for the existence and uniqueness of a mild solution of ISIDSP is thereby established.Furthermore,the mean-square exponential synchronization problem of the above systems is resolved,and the constraints within the mild solution domain are alleviated.These criteria clarify the impact of control parameters,control intervals and network topology on ESMS.The theoretical results are subsequently applied to a class of neural networks with reaction-diffusion processes,and the validity of the results is verified using numerical simulations.展开更多
Background:Large language models(LLMs)have shown considerable promise in supporting clinical decision-making.However,their adoption and evaluation in dermatology remains limited.This study aimed to explore the prefere...Background:Large language models(LLMs)have shown considerable promise in supporting clinical decision-making.However,their adoption and evaluation in dermatology remains limited.This study aimed to explore the preferences of Chinese dermatologists regarding LLM-generated responses in clinical psoriasis scenarios and to assess how they prioritize key quality dimensions,including accuracy,traceability,and logicality.Methods:A cross-sectional,web-based survey was conducted between December 25,2024,and January 22,2025,following the Checklist for Reporting Results of Internet E-Surveys guidelines.A total of 1247 valid responses were collected from practicing dermatologists across 33 of China's provincial-level administrative divisions.Participants evaluated responses to five categories of clinical questions(etiology,clinical presentation,differential diagnosis,treatment,and case study)generated by five LLMs:ChatGPT-4o,Kimi.ai,Doubao,ZuoYiGPT,and Lingyi-agent.Statistical associations between participant characteristics and model preferences were examined using chi-square tests.Results:ChatGPT-4o(Model 1)emerged as the most preferred model across all clinical tasks,consistently receiving the highest number of votes in case study(n=740),clinical presentation(n=666),differential diagnosis(n=707),etiology(n=602),and treatment(n=656).Significant variation in model preference by professional title was observed only for the differential diagnosis task(χ^(2)=21.13,df=12,p=0.0485),while no significant differences were found across hospital tiers(p>0.05).In terms of evaluation dimensions,accuracy was most frequently rated as“very important”(n=635).A significant association existed between hospital tier and the most valued dimension(χ^(2)=27.667,df=9,p=0.0011),with dermatologists in primary hospitals prioritizing traceability more than their peers in higher-tier hospitals.No significant associations were found across professional titles(p=0.127).Conclusions:Chinese dermatologists suggest a strong preference for ChatGPT-4o over domestic LLMs in psoriasis-related clinical tasks.While accuracy remains the primary criterion,traceability and logicality are also critical,particularly for clinicians in lower-tier hospitals.These findings suggest that future clinical LLMs should prioritize not only content accuracy but also source transparency and structural clarity to meet the diverse needs of different clinical settings.展开更多
Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination...Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion.This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence,aiming to provide general guidance on appropriate imaging examination selection,comprehensive and accurate imaging assessment for early orthodontic treatment patients.展开更多
Enamel demineralization,the formation of white spot lesions,is a common issue in clinical orthodontic treatment.The appearance of white spot lesions not only affects the texture and health of dental hard tissues but a...Enamel demineralization,the formation of white spot lesions,is a common issue in clinical orthodontic treatment.The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment.The prevention,diagnosis,and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties.This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment,advocating for proactive prevention,early detection,timely treatment,scientific follow-up,and multidisciplinary management of white spot lesions throughout the orthodontic process,thereby maintaining the dental health of patients during orthodontic treatment.展开更多
Protrusive facial deformities,characterized by the forward displacement of the teeth and/or jaws beyond the normal range,affect a considerable portion of the population.The manifestations and morphological mechanisms ...Protrusive facial deformities,characterized by the forward displacement of the teeth and/or jaws beyond the normal range,affect a considerable portion of the population.The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse,requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field.To further optimize the correction of protrusive facial deformities,this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans.It emphasizes the use of orthodontic strategies,including jaw growth modification,tooth extraction or non-extraction for anterior teeth retraction,and maxillofacial vertical control.These strategies aim to reduce anterior teeth and lip protrusion,increase chin prominence,harmonize nasolabial and chin-lip relationships,and improve the facial profile of patients with protrusive facial deformities.For severe skeletal protrusive facial deformities,orthodonticorthognathic combined treatment may be suggested.This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide,offering reference strategies for the correction of protrusive facial deformities.展开更多
The prevalence of Class Ⅲ malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can serio...The prevalence of Class Ⅲ malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore,early orthodontic treatment for Class Ⅲ malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class Ⅲ malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class Ⅲ malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class Ⅲ malocclusion through early orthodontic treatment.展开更多
Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health,function,and aesthetics,ensuring both patient satisfaction and long-term stability.Managing ...Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health,function,and aesthetics,ensuring both patient satisfaction and long-term stability.Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues,especially in severe cases.Therefore,close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment,along with diligent patient compliance throughout the entire process,is crucial for achieving favorable treatment outcomes.Moreover,long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success.This expert consensus,informed by the latest clinical research and practical experience,addresses clinical considerations for orthodontic treatment of periodontal patients,delineating indications,objectives,procedures,and principles with the aim of providing clear and practical guidance for clinical practitioners.展开更多
Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian cloc...Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.展开更多
Royal jelly(RJ)is rich in various nutrients with multiple health-promoting properties.This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice.Male C57BL/6J mice drank RJ soluti...Royal jelly(RJ)is rich in various nutrients with multiple health-promoting properties.This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice.Male C57BL/6J mice drank RJ solution daily for 9 months.Determination of serum lipids and pathological analysis exhibited that triglycerides,serum cholesterol,and low-density lipoprotein cholesterol were decreased by 31.15%,9.96%,and 22.58%,respectively,the morphology of brain nerve cells was also effectively recovered after RJ intervention.Lipidomic analysis showed that RJ could improve the levels of different kinds of lipids in aging mice brain,especially by increasing the content of antioxidant ether ester,and that the ratio of monounsaturated fatty acid to polyunsaturated fatty acid was up by 23.46%,which could alleviate oxidative stress.Moreover,the metabolism of glycerol phospholipids,glycerols,and fatty acids in aging mice could be regulated by RJ.RJ intervention can effectively improve lipid metabolism disorders caused by aging.展开更多
Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims...Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.展开更多
Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)sig...Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.展开更多
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 den...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.展开更多
Objective Establishing a highly sensitive real-time fluorescence quantitative PCR (qPCR) method for universal testing of epidemic African swine fever virus (ASFV) strains. Methods The ASFV p72 gene was targeted to des...Objective Establishing a highly sensitive real-time fluorescence quantitative PCR (qPCR) method for universal testing of epidemic African swine fever virus (ASFV) strains. Methods The ASFV p72 gene was targeted to design primer probes covering 24 p72 genotypes. The optimal amount of dimethylsulphoxide (DMSO) for qPCR amplification was determined, Various sensitivity and limit of detection (LOD) tests were performed, and clinical samples from China and imported goods were tested. Results The optimal primer-probe combination could specifically detect ASFV, 1.5% DMSO was optimal for qPCR, and LOD reached 3.2 copies/μL with good reproducibility (n = 20, p = 0.369). The method was employed to test 142 clinically suspected samples, of which 30 pig blood and 37 pig tissue samples were ASFV-positive. Moreover, the positive testing rate for ASFV was higher than for the standard qPCR method recommended by the Office International Des Epizooties (OIE), and for the commercially available kit. Thus, our method is superior for testing weakly positive samples with low virus titre, and epidemic strains present in imported goods. Conclusion Our method could be employed for universal testing of epidemic ASFV strains worldwide, ensuring wider coverage of hosts and ASFV strains/endemic strains, reducing false<span style="font-family:;" "=""> </span><span style="font-family:Verdana;">negatives, and benefitting early diagnosis.</span>展开更多
Cardiovascular disease is still the leading cause of mortality worldwide.Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases.Many studies have indicated that periodontal path...Cardiovascular disease is still the leading cause of mortality worldwide.Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases.Many studies have indicated that periodontal pathogens,especially Porphyromonas gingivalis,are closely correlated with vascular endothelial homeostasis,but the function of P.gingivalis and the underlying mechanisms are still elusive.To illuminate the effects and elucidate the mechanisms of P.gingivalis on endothelial structural integrity,we developed P.gingivalis infection models in vivo and in vitro.Endothelial cell proliferation,differentiation and apoptosis were detected.Here,we showed that P.gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells,which reduce the cell levels and cause the endothelium to lose its ability to repair itself.A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P.gingivalis,suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P.gingivalis.These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease.展开更多
基金supported by grants from the National Key Research and Development Program of China,Stem Cell and Translational Research(2022YFA1104100,2022YFA1105000,2018YFA0801404)the National Natural Science Foundation of China(82570270,82270230,32130046,82171617,82471689,82170540,82471462,82270566)+8 种基金the Guangdong Basic and Applied Basic Research Foundation(2023B1515020119)the Key Research and Development Program of Guangdong Province(2023B1111050006)the Key Scientific and Technological Program of Guangzhou City(2023B01J1002,202206080002)the Pioneering Talents Project of the Guangzhou Development Zone(2021-L029)the Guangdong Special Support Program(2019BT02Y276)the Shenzhen Science and Technology Program(KJZD20230923114504008)the Sanming Project of Medicine in Shenzhen Nanshan(SZSM2021034008)the Science and Technology Planning Project of Gaozhou(20240619111622)the Special Funds for the Cultivation of Guangdong College Students'Scientific and Technological Innovation(pdjh2025ak003).
文摘Vaccination is the preferred strategy for preventing infections such as influenza in elderly individuals;however,its efficacy is often suboptimal due in part to age-related declines in immune function.In this study,we discovered that the infusion of mesenchymal stromal cells(MSCs)restored defects in the splenic stromal cell network and lymphocyte architecture in aged mice while also increasing specific antibody levels following vaccine immunization.This significantly protected aging mice from influenza infection.Mechanistically,the delivered MSCs localized in the splenic marginal zones,where they positioned themselves near marginal reticular cells(MRCs)and stimulated MRC proliferation,partially through the action of vascular endothelial growth factor A(VEGFA).This MSC‒MRC interaction orchestrated the reconstruction of the stromal network,thereby restoring lymphocyte homeostasis and germinal center reactions.Importantly,the MSC-mediated enhancement of the vaccine response was further validated in aged cynomolgus monkeys.Collectively,our findings provide new insights into the application of MSCs in addressing age-related immune decline and highlight splenic MRCs as critical therapeutic targets.
基金supported in part by the National Natural Science Foundation of China(12471422,62573274,12371173)the Natural Science Foundation of Shandong Province of China(ZR2022LLZ003,ZR2024MF001)the Funding for Visiting Studies and Research by Teachers in Ordinary Undergraduate Colleges and Universities in Shandong Province。
文摘A novel aperiodically intermittent impulse control(AIIC)method is proposed to investigate the exponential synchronization in mean square(ESMS)of a class of impulsive stochastic infinite-dimensional systems with Poisson jumps(ISIDSP).The AIIC control strategy inherits the flexibility of aperiodically intermittent control,including the variable control period,adjustable control interval length,and the discretization of impulsive control.In addition,this article introduces a novel mild Itô's formula.By leveraging semigroup theory,the contraction mapping principle,and graph theory,along with constructing the Lyapunov function,the criterion for the existence and uniqueness of a mild solution of ISIDSP is thereby established.Furthermore,the mean-square exponential synchronization problem of the above systems is resolved,and the constraints within the mild solution domain are alleviated.These criteria clarify the impact of control parameters,control intervals and network topology on ESMS.The theoretical results are subsequently applied to a class of neural networks with reaction-diffusion processes,and the validity of the results is verified using numerical simulations.
基金National Key Research and Development Program of China,Grant/Award Number:2024YFF0507404Special Clinical Business Fund for High-Level Hospitals of China-Japan Friendship Hospital,Grant/Award Number:2024-NHLHCRF-TS-01。
文摘Background:Large language models(LLMs)have shown considerable promise in supporting clinical decision-making.However,their adoption and evaluation in dermatology remains limited.This study aimed to explore the preferences of Chinese dermatologists regarding LLM-generated responses in clinical psoriasis scenarios and to assess how they prioritize key quality dimensions,including accuracy,traceability,and logicality.Methods:A cross-sectional,web-based survey was conducted between December 25,2024,and January 22,2025,following the Checklist for Reporting Results of Internet E-Surveys guidelines.A total of 1247 valid responses were collected from practicing dermatologists across 33 of China's provincial-level administrative divisions.Participants evaluated responses to five categories of clinical questions(etiology,clinical presentation,differential diagnosis,treatment,and case study)generated by five LLMs:ChatGPT-4o,Kimi.ai,Doubao,ZuoYiGPT,and Lingyi-agent.Statistical associations between participant characteristics and model preferences were examined using chi-square tests.Results:ChatGPT-4o(Model 1)emerged as the most preferred model across all clinical tasks,consistently receiving the highest number of votes in case study(n=740),clinical presentation(n=666),differential diagnosis(n=707),etiology(n=602),and treatment(n=656).Significant variation in model preference by professional title was observed only for the differential diagnosis task(χ^(2)=21.13,df=12,p=0.0485),while no significant differences were found across hospital tiers(p>0.05).In terms of evaluation dimensions,accuracy was most frequently rated as“very important”(n=635).A significant association existed between hospital tier and the most valued dimension(χ^(2)=27.667,df=9,p=0.0011),with dermatologists in primary hospitals prioritizing traceability more than their peers in higher-tier hospitals.No significant associations were found across professional titles(p=0.127).Conclusions:Chinese dermatologists suggest a strong preference for ChatGPT-4o over domestic LLMs in psoriasis-related clinical tasks.While accuracy remains the primary criterion,traceability and logicality are also critical,particularly for clinicians in lower-tier hospitals.These findings suggest that future clinical LLMs should prioritize not only content accuracy but also source transparency and structural clarity to meet the diverse needs of different clinical settings.
基金supports by the National Natural Science Foundation of China(Nos.82201135)"2015"Cultivation Program for Reserve Talents for Academic Leaders of Nanjing Stomatological School,Medical School of Nanjing University(No.0223A204).
文摘Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion.This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence,aiming to provide general guidance on appropriate imaging examination selection,comprehensive and accurate imaging assessment for early orthodontic treatment patients.
基金funded with National Key R&D Program of China(2022YFC2405904)National Natural Science Foundation of China(11932012,and 32171348).
文摘Enamel demineralization,the formation of white spot lesions,is a common issue in clinical orthodontic treatment.The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment.The prevention,diagnosis,and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties.This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment,advocating for proactive prevention,early detection,timely treatment,scientific follow-up,and multidisciplinary management of white spot lesions throughout the orthodontic process,thereby maintaining the dental health of patients during orthodontic treatment.
基金supported by the National Clinical Key Specialty Project of China nos.GJLCZDZK-2023-01Shanghai Top Priority Research Center Project nos.2023ZZ02009+2 种基金National Natural Science Foundations of China Nos.82230030Clinical Innovation Project of Shanghai Shenkang Hospital Development Center nos.SHDC12021108Angelalign Scientific Research Fund no.EARD20220725046。
文摘Protrusive facial deformities,characterized by the forward displacement of the teeth and/or jaws beyond the normal range,affect a considerable portion of the population.The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse,requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field.To further optimize the correction of protrusive facial deformities,this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans.It emphasizes the use of orthodontic strategies,including jaw growth modification,tooth extraction or non-extraction for anterior teeth retraction,and maxillofacial vertical control.These strategies aim to reduce anterior teeth and lip protrusion,increase chin prominence,harmonize nasolabial and chin-lip relationships,and improve the facial profile of patients with protrusive facial deformities.For severe skeletal protrusive facial deformities,orthodonticorthognathic combined treatment may be suggested.This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide,offering reference strategies for the correction of protrusive facial deformities.
文摘The prevalence of Class Ⅲ malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore,early orthodontic treatment for Class Ⅲ malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class Ⅲ malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class Ⅲ malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class Ⅲ malocclusion through early orthodontic treatment.
基金supported by the National Key R&D Program of China(2022YFC2504200)Chongqing Young and Middle-aged Medical Excellence Team ProjectJiangsu Province Key Research and Development Program(BE2022670)。
文摘Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health,function,and aesthetics,ensuring both patient satisfaction and long-term stability.Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues,especially in severe cases.Therefore,close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment,along with diligent patient compliance throughout the entire process,is crucial for achieving favorable treatment outcomes.Moreover,long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success.This expert consensus,informed by the latest clinical research and practical experience,addresses clinical considerations for orthodontic treatment of periodontal patients,delineating indications,objectives,procedures,and principles with the aim of providing clear and practical guidance for clinical practitioners.
基金supported in part by grants from the National Key R&D Program of China(2021YFC2400400/04 to L.L.C.)the National Natural Science Foundation of China for Key Program Projects(82030070 to L.L.C.)+2 种基金the National Natural Science Foundation of China for Distinguished Young Scholars(22025102 to Q.W.)the National Natural Science Foundation of China(82271036 to Y.F.W.,22277033 to J.Z.,22177034 to L.K.M.)the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001 to Y.F.W.)。
文摘Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.
基金supported by the Science and Technology Department of Jiangxi Province(20212AEI91010)National Natural Science Foundation of China(31772067)+1 种基金Jiangxi Agriculture Research System(JXARS-14)Research Project of State Key Laboratory of Food Science and Technology(SKFL-ZZB-2)。
文摘Royal jelly(RJ)is rich in various nutrients with multiple health-promoting properties.This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice.Male C57BL/6J mice drank RJ solution daily for 9 months.Determination of serum lipids and pathological analysis exhibited that triglycerides,serum cholesterol,and low-density lipoprotein cholesterol were decreased by 31.15%,9.96%,and 22.58%,respectively,the morphology of brain nerve cells was also effectively recovered after RJ intervention.Lipidomic analysis showed that RJ could improve the levels of different kinds of lipids in aging mice brain,especially by increasing the content of antioxidant ether ester,and that the ratio of monounsaturated fatty acid to polyunsaturated fatty acid was up by 23.46%,which could alleviate oxidative stress.Moreover,the metabolism of glycerol phospholipids,glycerols,and fatty acids in aging mice could be regulated by RJ.RJ intervention can effectively improve lipid metabolism disorders caused by aging.
文摘Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.
基金National Natural Science Foundation of China(U21A20411)Innovative Research Group Program of Hunan Provincial Natural Science Foundation (2024JJ1007)Hunan Provincial Natural Science Foundation(2023JJ30473)。
文摘Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
基金supported by the National Natural Science Foundation of China(no. 82320108004)the Construction Engineering Special Fund of “Taishan Scholars” of Shandong Province (ts20190975)the National Clinical Key Specialty(Periodontology) Construction Project。
文摘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.
文摘Objective Establishing a highly sensitive real-time fluorescence quantitative PCR (qPCR) method for universal testing of epidemic African swine fever virus (ASFV) strains. Methods The ASFV p72 gene was targeted to design primer probes covering 24 p72 genotypes. The optimal amount of dimethylsulphoxide (DMSO) for qPCR amplification was determined, Various sensitivity and limit of detection (LOD) tests were performed, and clinical samples from China and imported goods were tested. Results The optimal primer-probe combination could specifically detect ASFV, 1.5% DMSO was optimal for qPCR, and LOD reached 3.2 copies/μL with good reproducibility (n = 20, p = 0.369). The method was employed to test 142 clinically suspected samples, of which 30 pig blood and 37 pig tissue samples were ASFV-positive. Moreover, the positive testing rate for ASFV was higher than for the standard qPCR method recommended by the Office International Des Epizooties (OIE), and for the commercially available kit. Thus, our method is superior for testing weakly positive samples with low virus titre, and epidemic strains present in imported goods. Conclusion Our method could be employed for universal testing of epidemic ASFV strains worldwide, ensuring wider coverage of hosts and ASFV strains/endemic strains, reducing false<span style="font-family:;" "=""> </span><span style="font-family:Verdana;">negatives, and benefitting early diagnosis.</span>
基金This work was supported by the National Science Foundation for Distinguished Young Scholars of China(31725011 to Lili Chen)Young Scientists of China(81800986 to Qingming Tang)the Chinese Stomatological Association(CSAZ2015-01 to Lili Chen).
文摘Cardiovascular disease is still the leading cause of mortality worldwide.Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases.Many studies have indicated that periodontal pathogens,especially Porphyromonas gingivalis,are closely correlated with vascular endothelial homeostasis,but the function of P.gingivalis and the underlying mechanisms are still elusive.To illuminate the effects and elucidate the mechanisms of P.gingivalis on endothelial structural integrity,we developed P.gingivalis infection models in vivo and in vitro.Endothelial cell proliferation,differentiation and apoptosis were detected.Here,we showed that P.gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells,which reduce the cell levels and cause the endothelium to lose its ability to repair itself.A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P.gingivalis,suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P.gingivalis.These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease.
