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 investigate the effect of splenectomy on the repair of full-thickness skin tissue defects,as well as the impact of different recovery times after splenectomy on the healing of skin tissue defects.Methods According to a random number table,39 8-week-old female C57 mice were randomly divided into three groups:sham surgery group(sham group,n=13),splenectomy group with 3 days of recovery(Spx3d group,n=13),and splenectomy group with 3 weeks of recovery(Spx3w group,n=13).Full-thickness skin defects were created on the backs of the mice in each group.The wound healing conditions at different times after skin defects were observed,and the wound healing rates after the injury were calculated.Peripheral blood cell analysis was performed on day 14 after the defect,and tissue samples from the wound area were taken for hematoxylin and eosin(HE)staining to observe the granulation tissue thickness at the defect site and the re-epithelialization rate.Masson's trichrome staining was used to observe the proportion of collagen fibers.Results After splenectomy and sham surgery,the mice recovered well without significant discomfort.From 1 to 14 days after the skin defect modeling,the wound areas of the mice in all three groups gradually decreased.Compared with sham group,the wound areas were smaller in Spx3d and Spx3w groups at 3,5 and 7 days after the injury,and the differences were statistically significant(P<0.05).The wound healing rates were also significantly higher(P<0.05).Moreover,at 3 days and 5 days after the injury,the wound healing rates of Spx3d group were significantly higher than those of Spx3w group(P<0.05 or P<0.01).The peripheral blood white blood cell(WBC)count in Spx3w group was significantly higher than that in sham group and Spx3d group(P<0.01).The platelet counts in both sham group and Spx3w group were significantly higher than that in Spx3d group(P<0.05).Additionally,the lymphocyte and neutrophil counts in Spx3w group were markedly higher than those in sham group(P<0.05).No statistically significant differences in red blood cell(RBC)counts were observed among the three groups(P>0.05).HE staining results showed that compared with sham group,the wound healing of the mice in Spx3d and Spx3w groups were better,and the thickness of the granulation tissue in Spx3d group were better than that in Spx3w group.At 7 days,the thickness of the granulation tissue in Spx3d and Spx3w groups was significantly higher than that in sham group(P<0.01,P<0.05)and the re-epithelialization rate in Spx3d group was significantly higher than that in sham group and Spx3w group(P<0.05).At 14 days,the re-epithelialization rates of Spx3d and Spx3w groups were significantly higher than those of sham group(P<0.05).The results of Masson's staining showed that the collagen fiber proportion in the wounds of Spx3d group at 7 and 14 days and that of Spx3w group at 14 days were significantly higher than that in sham group(P<0.05).Conclusion The healing of skin defects in mice is accelerated after splenectomy,and the recovery time after splenectomy has a certain effect on the healing of skin defects.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective:To review the clinical status based on the best evidence of drug administration in patients with dysphagia, systematically analyze the obstacle factors and promoting factors in the process of evidence transformation, and formulate reform strategies.Methods:Based on the evidence-based nursing research method and the guidance of the Ottawa Model of Research Use (OMRU), the review indicators were developed based on the best evidence. The current status of clinical practice behaviors of 223 patients and 75 nurses in the Neurology, Neurosurgery and Geriatric departments of the Affiliated Hospital of Jiangsu University were reviewed from July to December 2021.Based on the results of the review, qualitative interviews were conducted with 32 potential adopters, and content analysis was used to assess the barriers and contributing factors to the clinical translation of evidence in three aspects: evidence-based change, potential adopters and practice environment, so as to develop effective strategies.Results:Based on the 22 best evidence selected, the evidence-based team developed 25 review indicators to carry out clinical review, showing that the compliance rate of 16 indicators were less than 60%. By analyzing and summarizing the interview results of potential adopters, the main obstacles leading to the low compliance rate of nurses were analyzed as follows: evidence-based reform changed the traditional work mode, and the application of evidence was not convenient; at the level of potential adopters, nurses had poor knowledge and practice, heavy work burden, and low awareness of patients and caregivers; at the level of practice environment, there was lack of nursing norms and procedures for clinical transformation of evidence, and the channels of multi-disciplinary collaboration and communication were not smooth. The main promoting factors were the perfect supervision mechanism of evidence-based nursing projects, the evidence-based group had rich experience in evidence transformation, the management was willing to change, and the practitioners were good at innovation.Conclusions:There is still a large gap between the clinical practice and the best evidence of drug administration in patients with dysphagia. The promoting factors should be fully utilized to overcome the obstacles and implement improvements to promote the effective transformation of evidence into clinical practice.

Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.

Objective:To assess the real-world patient satisfaction with the outcomes in Chinese patients who received HYC-24/HYC-24+ for the treatment of moderate to severe nasolabial folds (NLF).Methods:This study was a prospective, observational, multicenter, real-world cohort study in which patients accepted treatment with HYC-24/HYC-24+ in China during a period from August 2018 to August 2020 at Beijing Lidu Medical Beauty Hospital, Hangzhou Yanshu Yuerong Medical Aesthetic Clinic, and Guangzhou Yuexiu Plastic Surgery Hospital and were followed up for up to 1 year. Patients were adults aged 18 to 65 years with moderate to severe NLF who had not received cosmetic treatment for NLF within 6 months prior to study enrollment. Post-treatment study visits were conducted at Months 1, 6, 9, and 12, but only Months 6 and 9 were required visits. The primary patient-reported outcomes endpoints included the FACE-Q satisfaction with outcome total score (a score from 0 to 100: a higher score indicates better outcomes and higher patient satisfaction), FACE-Q appraisal of lines - NLFs total questionnaire score mean change from baseline (a score from 0 to 100: a higher score indicates the patient was less troubled by NLF in the past week), and proportion of patients who reported that they looked younger than the actual age on the FACE-Q patient perceived age visual analog scale (VAS). Investigator-assessed endpoints included the proportion of patients with a global aesthetic improvement scale (GAIS) score of ≥ 1 point and the proportion of patients with an improvement in NLF severity of ≥ 1 point using the nasolabial fold severity scale (NLFSS). Statistical analyses were performed with SAS software, version 9.4. Measurement data were expressed as Mean±SD, and count data were expressed using cases(%). For both measurement and count data, P values were calculated on the difference between score values at different time points versus baseline using the Wilcoxon signed rank test. Results:A total of 52 subjects were enrolled and treated. Among these subjects, 7 were not included in the 6-month effectiveness analysis data set because the visit time exceeded the visit assessment window, and only 9 patients completed the 12-month visit. All patients were Chinese women, aged 26 to 62 years old, with a mean age of 40.7 years. The FACE-Q satisfaction with outcome total score was (68.76 ± 21.03) points (38-100) at Month 6, and (65.44±18.24) points (24-100) at Month 9, indicating high patient satisfaction with the treatment. The FACE-Q appraisal of lines-NLFs total score was (42.4±15.1) points (10-69) at baseline, (76.9±20.6) points (36-100) at Month 6, and (74.2±16.7) points (36-100) at Month 9, both significantly higher than the baseline scores (both P<0.01). The mean change from baseline in the FACE-Q appraisal of lines-NLFs total scores at Month 6 and Month 9 were 34.9 and 31.8 points, respectively, indicating the disturbance caused by NLF was relatively mild after treatment. The proportion of patients who believed they looked younger than their actual age on the FACE-Q patient perceived age VAS increased from 28.9% (15/52) at baseline to 77.8% (35/45) at Month 6, and 73.1% (38/52 ) at Month 9. The differences were all statistically significant compared to baseline ( P <0.01). At each post-baseline visit, all patients had ≥ 1-point improvement on the GAIS scale, indicating an improvement in patient NLF appearance in the investigators’ opinion. In terms of the NLFSS assessment, 97.8% (44/45) and 82.7% (43/52) of patients achieved a ≥ 1-point improvement on the NLFSS at Months 6 and 9, respectively. No adverse events were reported during the study. Conclusion:In a real-world setting, after the administration of HYC-24/HYC-24+ to Chinese patients, the patients were satisfied with the outcomes based on validated questionnaires. The patients also reported looking younger than their actual age and being less disturbed by NLF. Clinician-reported outcomes were consistent with patient-reported outcomes, indicating improvement in NLF.

Objective:To assess the real-world patient satisfaction with the outcomes in Chinese patients who received HYC-24/HYC-24+ for the treatment of moderate to severe nasolabial folds (NLF).Methods:This study was a prospective, observational, multicenter, real-world cohort study in which patients accepted treatment with HYC-24/HYC-24+ in China during a period from August 2018 to August 2020 at Beijing Lidu Medical Beauty Hospital, Hangzhou Yanshu Yuerong Medical Aesthetic Clinic, and Guangzhou Yuexiu Plastic Surgery Hospital and were followed up for up to 1 year. Patients were adults aged 18 to 65 years with moderate to severe NLF who had not received cosmetic treatment for NLF within 6 months prior to study enrollment. Post-treatment study visits were conducted at Months 1, 6, 9, and 12, but only Months 6 and 9 were required visits. The primary patient-reported outcomes endpoints included the FACE-Q satisfaction with outcome total score (a score from 0 to 100: a higher score indicates better outcomes and higher patient satisfaction), FACE-Q appraisal of lines - NLFs total questionnaire score mean change from baseline (a score from 0 to 100: a higher score indicates the patient was less troubled by NLF in the past week), and proportion of patients who reported that they looked younger than the actual age on the FACE-Q patient perceived age visual analog scale (VAS). Investigator-assessed endpoints included the proportion of patients with a global aesthetic improvement scale (GAIS) score of ≥ 1 point and the proportion of patients with an improvement in NLF severity of ≥ 1 point using the nasolabial fold severity scale (NLFSS). Statistical analyses were performed with SAS software, version 9.4. Measurement data were expressed as Mean±SD, and count data were expressed using cases(%). For both measurement and count data, P values were calculated on the difference between score values at different time points versus baseline using the Wilcoxon signed rank test. Results:A total of 52 subjects were enrolled and treated. Among these subjects, 7 were not included in the 6-month effectiveness analysis data set because the visit time exceeded the visit assessment window, and only 9 patients completed the 12-month visit. All patients were Chinese women, aged 26 to 62 years old, with a mean age of 40.7 years. The FACE-Q satisfaction with outcome total score was (68.76 ± 21.03) points (38-100) at Month 6, and (65.44±18.24) points (24-100) at Month 9, indicating high patient satisfaction with the treatment. The FACE-Q appraisal of lines-NLFs total score was (42.4±15.1) points (10-69) at baseline, (76.9±20.6) points (36-100) at Month 6, and (74.2±16.7) points (36-100) at Month 9, both significantly higher than the baseline scores (both P<0.01). The mean change from baseline in the FACE-Q appraisal of lines-NLFs total scores at Month 6 and Month 9 were 34.9 and 31.8 points, respectively, indicating the disturbance caused by NLF was relatively mild after treatment. The proportion of patients who believed they looked younger than their actual age on the FACE-Q patient perceived age VAS increased from 28.9% (15/52) at baseline to 77.8% (35/45) at Month 6, and 73.1% (38/52 ) at Month 9. The differences were all statistically significant compared to baseline ( P <0.01). At each post-baseline visit, all patients had ≥ 1-point improvement on the GAIS scale, indicating an improvement in patient NLF appearance in the investigators’ opinion. In terms of the NLFSS assessment, 97.8% (44/45) and 82.7% (43/52) of patients achieved a ≥ 1-point improvement on the NLFSS at Months 6 and 9, respectively. No adverse events were reported during the study. Conclusion:In a real-world setting, after the administration of HYC-24/HYC-24+ to Chinese patients, the patients were satisfied with the outcomes based on validated questionnaires. The patients also reported looking younger than their actual age and being less disturbed by NLF. Clinician-reported outcomes were consistent with patient-reported outcomes, indicating improvement in NLF.

Objective To study the use of phospholipase A2(PLA2)to open blood brain barrier(BBB)by affecting the physiological barrier function and promote the antidote drug asoxime(HI-6)to take effect in brain,providing a new research idea for the treatment of central nervous system organophosphorus poisoning.Methods The stability of the complex of PLA2-HI-6 was characterized through methods such as release and stability experiments.The cerebral delivery ability of the complex was evaluated through brain tissue FLU fluorescence pathology.The effect of PLA2 on cell membrane permeability was evaluated by observation with propidium iodide(PI)staining.The mouse model of soman poisoning was established to evaluate cerebral effects of the complex against soman central poisoning:(1)measuring the reactivation rate of mouse brain acetylcholinesterase(AChE);(2)observing pathological sections of mouse brain tissues;(3)calculating the survival time of mice in different groups.The safety of PLA2 was evaluated at both cellular and animal levels.Results Releasing and stability test results showed that the addition of PLA2 didn't affect the release and degradation of HI-6.PLA2 helped FLU transport into brain tissues,demonstrating excellent central delivery capability.The complex of PLA2-H1-6 significantly increased the reactivation rate of AChE in the brain of poisoned mice to 50％,about 12 times higher than that treated by HI-6 alone.Pathological results of mouse brain tissue showed that the complex effectively counteracted the cerebral nervous system damage caused by organophosphorus poisoning,significantly prolonged the survival time of mice at three times the lethal dose,and significantly alleviated symptoms of central toxicity.Research on delivery mechanisms found that complex achieved central delivery by increasing the permeability of the cell membrane to crossing the cell.Safety tests at the cellular and animal levels showed that the dosage of PLA2 used in this study was safe and reliable,and did not cause any adverse reactions.Conclusion By using PLA2 as an open material,combined with the therapeutic drug of HI-6,a complexcapable of effectively penetrating the BBB was successfully constructed.This complex has a certain central targeting ability and significantly improves the reactivation rate of AChE in the brain after organophosphorus poisoning,whichprovides a referencefor solving the difficult problem of enzyme reactivation incentral nervous system organophosphorus poisoning.

Objective To explore the safety and management mode of hysteroscopy in three different modes:outpatient,daily and inpatient.Methods The quality control data of patients who underwent hysteroscopic surgery in Hysterscopy Centre,Obstetrics and Gynecology Hospital,Fudan University from Jan 2019 to Dec 2021 were collected through the electronic information system of the hospital and the monthly quality control report of hysteroscopy center.The amount of surgery,the proportion of grade Ⅳsurgery,the analysis of operation types,the indicator including complications,and unanticipated secondary surgery were retrospectively analyzed.Results From 2019 to 2021,5 162 outpatient hysteroscopic patients,15 331 daily hysteroscopic patients and 5 942 inpatient hysteroscopic patients were admitted in our hospital.The age of inpatient hysteroscopic patients was significantly older than those of outpatient and daily patients(P<0.001).In the past three years,the proportion of daily hysteroscopy gradually increased,and the proportion of inpatient hysteroscopy gradually decreased(P<0.001).The total percentage of grade Ⅳ hysteroscopic surgery was 12.9%,in which inpatient was higher than daily,and daily was higher than outpatient(P<0.001).The incidence of complications and accidents during hysteroscopy was 0.117%(31/26 435),including 17 cases of uterine perforation,7 cases of hysteroscopy failure,3 cases of excessive intraoperative bleeding,2 cases of fluid overload,1 case of intestinal injury,and 1 case of anesthesia accident.The incidence of hysteroscopy in outpatient,daily and inpatient were 0.020%(1/5 162),0.137%(21/15 331)and 0.151%(9/5 942)respectively.Conclusion Hysteroscopy in outpatient,daily and inpatient are all safe and reliable.Outpatient and daily hysteroscopy can improve the efficiency of medical services,which has gradually become a trend.

Objective:To analyze the immune microenvironment characteristics of human dental follicle tissues from the third molars and to explore the mutual communication and the effects of innate immune cells and adaptive immune cells within the dental follicle.Methods:Sequencing data(GSA-Human:HRA008022)in the GSA database were analyzed.Bioinformatics tools were employed for gene identification and GO enrichment analysis was performed to define the biological function of innate and adaptive immune cells.CellChat analysis was used for explaining intercellular communication among immune cell populations.Results:Using t-SNE dimen-sionality reduction analysis for immune cell populations,innate immune cell populations were obtained,including innate lymphoid cells,dendritic cells,mast cells and macrophages,and adaptive immune cell populations including T cells and B cells.Pearson corre-lation analysis showed that innate immune cells,specifically innate lymphoid cells and macrophages,had a strong correlation with adap-tive immune cell populations.GO enrichment analysis revealed mutual coordination among innate immune cell populations and regulato-ry effects on adaptive immune cell populations.Further CellChat analysis indicated biological signal transmission between innate and a-daptive immune cell populations,with CLEC,MIF,ADGRE5,COLLAGEN and MIF signaling pathways is the most significant.Con-clusion:Dental follicle tissues are rich in immune cells and innate immune cell populations interact with adaptive immune cells to regulate immune responses and participate in maintaining the homeostasis of dental follicle.