Autophagy-lysosomal pathway (ALP) is the degradation system that remove unfolded proteins and damaged organelles in cells, and plays an important role in maintaining intracellular homeostasis.The process of autophagy mainly includes autophagosome formation, autophagosome-lysosome fusion, and degradation of cargoes in mature lysosomes by lysosomal enzymes.Dry eye disease, meibomian gland dysfunction and keratopathy are common ocular surface diseases associated with diabetes mellitus, and clinical manifestations include dry eyes, reduced tear secretion, persistent corneal epithelial defects, neuropathy (decreased corneal sensitivity) and endothelial cell dysfunction.Aberrant expression of gene, oxidative stress and inflammation related advanced glycosylation end products and reactive oxygen species are significant pathogenesis of ocular surface diseases related to diabetes.Moreover, the above pathogenesis involves defects of autophagy regulatory gene, abnormal expression of autophagy related protein and activation of autophagy signaling pathway which lead to the defects of ALP such as autophagosome lysosome fusion disorder, accumulation of cargoes and abnormal lysosomal function, and the deficiency of autophagy further promoting the oxidative stress and release of inflammatory factors.The occurrence and development of ocular surface diseases associated with diabetes are closely related to the defects of ALP.This article reviews the basic research status between the defects of ALP and diabetic ocular surface diseases to provide new ideas for the mechanism and treatment research.

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Objective To investigate the predictive value of serum forkhead box protein O3(FOXO3)and thioredoxin interacting protein(TXNIP)for major adverse cardiovascular event(MACE)in elderly patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI).Methods In total,120 elderly patients with CHD who underwent successful PCI at our hospital between June 2021 and May 2023 were enrolled.After 12 months of follow-up(6 patients lost to follow-up),the patients were divided into the MACE group(n=40)and non-MACE group(n=74)based on whether they experienced MACE,such as recurrent angina pectoris,acute myocardial infarction,and severe arrhythmia.Enzyme-linked immunosorbent assay was used to detect FOXO3 and TXNIP levels in serum.The Pearson analysis was used to analyze the correlation between serum FOXO3 and TXNIP levels in patients with CHD.A receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum FOXO3 and TXNIP levels for MACE in patients with CHD after PCI.Logistic regression was used to analyze the factors affecting the occurrence of MACE in patients with CHD after PCI.Results The serum FOXO3 level in the MACE group was significantly lower than that in the non-MACE group,while TXNIP levels were significantly higher(P＜0.05).Pearson analysis revealed that serum FOXO3 and TXNIP levels in patients with CHD were negatively cor-related(r=-0.586,P＜0.001).Logistic regression analysis revealed that FOXO3 and TXNIP were factors influencing MACE in patients with CHD after PCI(P＜0.05).The combined prediction of serum FOXO3 and TXNIP for MACE in patients with CHD after PCI had higher area under the curve than using FOXO3 and TXNIP alone(Z=7.583,P＜0.001;Z=8.640,P＜0.001).Conclusion The elderly CHD patients with MACE after PCI showed low FOXO3 expression and high TXNIP expression,which have a clinical predictive value for MACE occurrence in patients with CHD after PCI.

OBJECTIVE To quantify pulmonary vascular endothelial subpopulations during bleomycin-induced pulmonary fibrosis in mice.METHODS Sixty male C57BL/6 mice were randomly divided into five groups(n=12 per group)corresponding to distinct observation timepoints:0,1,2,3,and 4 weeks.A model was established via intratracheal instillation of bleomycin(3 mg·kg-1).Lung tissues were harvested at 0,1,2,3 and 4 weeks post-bleomycin induction.Pathological staining was performed to assess lung histoarchitecture and collagen fiber deposition.Single-cell suspensions were analyzed by flow cytometry to quantify temporal changes in pulmonary vascular endothelial subpopulations,including pulmonary macrovascular endothelial cells,general capillaries,and aerocyte capillaries.Immunofluo-rescence staining was performed to validate the expressions of endothelial markers(CD31,APLN,APLNR,CD93).Single-cell transcriptomic data from the Tabula Muris database was analyzed to evalu-ate gene expression profiles of vascular endothelial subpopulations.RESULTS Pathological staining revealed progressive destruction of lung histoarchitecture and collagen deposition during bleomycin-induced pulmonary fibrosis.Flow cytometry demonstrated three-phase dynamics in vascular endothelial cells(CD45-CD31+CD90.2-):a significant decrease during the acute inflammatory phase,stabilization in the fibrotic phase,and partial recovery during the resolution phase.The proportion of von Willebrand factor-positive(VWF+)vascular endothelial cells significantly decreased during the resolution phase,whereas VWF-vascular endothelial cells increased.Single-cell transcriptomics identified Cd93 asa specific gene for general capillary endothelial cells,with a negative correlation with"aerocyte"genes enriched in gas-exchange alveolar capillary endothelial cells.Immunofluorescence confirmed CD93 localization to general capillary endothelial cells.A flow sorting strategy based on CD45-CD31+CD90.2-VWF-CD93-effectively enriched alveolar capillary endothelial cells.This subpopulation trended upward in pulmonary vascular endothelial composition during bleomycin induction.CONCLUSION During bleo-mycin-induced pulmonary fibrosis in mice,pulmonary vascular endothelial subpopulations exhibit dynamic compositional heterogeneity across fibrotic injury and repair phases.

Autophagy-lysosomal pathway (ALP) is the degradation system that remove unfolded proteins and damaged organelles in cells, and plays an important role in maintaining intracellular homeostasis.The process of autophagy mainly includes autophagosome formation, autophagosome-lysosome fusion, and degradation of cargoes in mature lysosomes by lysosomal enzymes.Dry eye disease, meibomian gland dysfunction and keratopathy are common ocular surface diseases associated with diabetes mellitus, and clinical manifestations include dry eyes, reduced tear secretion, persistent corneal epithelial defects, neuropathy (decreased corneal sensitivity) and endothelial cell dysfunction.Aberrant expression of gene, oxidative stress and inflammation related advanced glycosylation end products and reactive oxygen species are significant pathogenesis of ocular surface diseases related to diabetes.Moreover, the above pathogenesis involves defects of autophagy regulatory gene, abnormal expression of autophagy related protein and activation of autophagy signaling pathway which lead to the defects of ALP such as autophagosome lysosome fusion disorder, accumulation of cargoes and abnormal lysosomal function, and the deficiency of autophagy further promoting the oxidative stress and release of inflammatory factors.The occurrence and development of ocular surface diseases associated with diabetes are closely related to the defects of ALP.This article reviews the basic research status between the defects of ALP and diabetic ocular surface diseases to provide new ideas for the mechanism and treatment research.

ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.