Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease characterized by excess fat accumulation within liver cells.The main causes include obesity,diabetes,and hyperlipidemia.In recent years,NAFLD and other metabolic diseases have become global public health issues.Although some progress has been made in the drug treatment of NAFLD,the efficacy is limited and there are many adverse effects.As a treatment method with high safety and few adverse effects,exercise therapy has good application prospects in the treatment of NAFLD and other metabolic diseases.However,challenges remain in overcoming patients'low exercise compliance and in finding safe and effective exercise therapy drug targets.This article explores the mechanisms and application prospects of exercise therapy in the treatment of NAFLD and other metabolic diseases,summarizes the energy consumption,metabolic pathways,and inter-organ communication induced by exercise,aiming to provide useful references for clinical practitioners.

Objective To analyze the accuracy of the new generation intraocular lens(IOL)formula and the Wang-Koch(WK)adjustment in individuals with severe myopia undergoing combined anterior-posterior surgery.Methods A total of 100 patients(100 eyes)with axial length(AL)＞26 mm undergoing combined anterior and posterior segment surgery in our department from June 2015 to June 2021 were enrolled in this study.Totally 13 IOL calculation formulas,such as Barrett Universal Ⅱ(BU Ⅱ),Emmetropia Verifying Optical(EVO),Kane,Haigis,Hoffer Q,Holladay,and SRK/T as well as the first generation linear WK eye axis optimization formula(Haigis-WK1,SRK/T-WK1,Hoffer Q-WK1,Holladay 1-WK1)and the second generation linear WK eye axis optimization formula(SRK/T-WK2,Holladay 1-WK2),were utilized to determine IOL diopter.The mean prediction error(ME),mean absolute error(MAE),median absolute error(MedAE),and percentage of prediction error within different refractive thresholds were calculated to assess the accuracy of each formula.In order to investigate the impact of AL on accuracy of IOL calculation,the patients were categorized into group A(38 eyes,26.00 mm＜AL≤28.00 mm),group B(28 eyes,28.00 mm＜AL≤30.00 mm),and group C(34 eyes,AL＞30.00 mm).Additionally,the patients were also divided into silicone oil(63 eyes)and non-silicone oil(37 eyes)groups based on preoperative intraocular filling to determine the effect of intraocular filling on IOL calculation.Results The MedAE values of the new-generation IOL formulas(BU Ⅱ,EVO,and Kane)were significantly lower(0.34D,0.31D,0.35D)than those of traditional formulas(P＜0.05).Additionally,the percentage of prediction errors within±0.25 D,±0.50 D,±0.75 D,and±1.00 D were significantly higher with the new formulas when compared to traditional ones(P＜0.05).Traditional formulas exhibited a hyperopic deviation(0.35D～0.65 D),which could be corrected using the WK eye axis adjustment.WK2 was effective in improving the accuracy of calculation in SRK/T and Holladay 1 formulas,and there was no statistical difference in the MedAE values of SRK/T-WK2 and Holladay 1-WK2 formulas with the new-generation IOL formulas.When comparing the formulas across different axial eye length groups in terms of MedAE,the new IOL formulas(BU Ⅱ,kane and EVO)and WK-corrected formulas(Haigis-WK1,SRK/T-WK 1,SRK/T-WK2,Hoffer Q-WK1,Holladay 1-WK1,Holladay 1-WK2)showed no significant differences among the different AL groups.However,there were significant differences in the MedAE values of traditional formulas among the different AL groups(P＜0.01),with group C displaying the largest MedAE values(Haigis:0.84D,SRK/T:1.10D,Hoffer Q:1.23D,Holladay 1:1.20D).Comparing the MedAE values of different formulas in various preoperative intraocular filling groups,it was observed that the MedAE values of the new-generation IOL formulas(BU Ⅱ,kane and EVO),Haigis,and SRK/T formulas were significantly higher in the silicone oil-filled eye group than the non-silicone oil-filled eye group(P＜0.05).Conclusion In patients with high myopia undergoing combined anterior and posterior segment surgery,the precision and consistency of the new-generation IOL formulas and the second-generation linear WK axis correction formula exhibit significant improvements when compared to traditional formulas.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.
Humans ; Asthma/prevention & control*

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.
Humans ; Asthma/prevention & control*

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

AIM: To investigate the changes in retinal nerve fiber layer(RNFL)and macular retinal thickness(MRT)in children with refractive abnormalities and amblyopia, and their predictive value of outcome.METHODS: A total of 168 children with myopic refractive abnormalities and monocular amblyopia admitted to our hospital from January 2020 to October 2022 were selected as the observation group, with 118 cases of mild to moderate amblyopia and 50 cases of severe amblyopia, and 168 children with normal vision were included as the control group in a 1:1 ratio during the same period. The changes of RNFL and MRT in two groups of children were statistically counted, and the correlation between the severity of refractive abnormalities and RNFL and MRT in children with amblyopia was analyzed. Additionally, the observation group was divided into effective subgroup and ineffective subgroup based on the therapeutic effect. The general information, as well as RNFL and MRT of the effective subgroup and the ineffective subgroups before and after treatment were compared. Logistic was used to analyze the factors influencing efficacy, and ROC curves was plotted to analyze the predictive value of RNFL and MRT alone or in combination for efficacy.RESULTS: RNFL and MRT of cases of severe amblyopia were higher than those of the mild to moderate amblyopia and the control groups(all P<0.05); the severity of amblyopia in children with refractive abnormalities is positively correlated with RNFL and MRT(rs=0.745 and0.724, both P<0.001); among patients of mild to moderate and severe, there were statistically significant differences between the effective and ineffective subgroups in terms of initial treatment age, fixation form, treatment compliance, as well as RNFL, MRT, and their differences before and 1mo postoperatively(all P<0.05). Logistic analysis showed that initial treatment age, fixation nature, treatment compliance, RNFL and MRT before and 1mo postoperatively were all factors influencing the therapeutic effect of amblyopia with refractive abnormalities in children(all P<0.05); after 1mo of treatment, the combined prediction of RNFL and MRT was significantly better than that of single prediction in children with mild to severe amblyopia.CONCLUSION:There are differences in RNFL and MRT in children with abnormal refractive amblyopia, and they are closely related to the different degrees and curative effects of children. The combination of RNFL and MRT after 1mo of treatment has certain value in predicting children with different degrees of abnormal refractive amblyopia.