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 study the effect of anti-melanoma differentiation-related gene 5(MDA5) antibody positive dermatomyositis on the heart of patients.Methods:A total of 71 patients with dermatomyositis diagnosed in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 1, 2014 to December 31, 2019 were enrolled as the sample group, including anti-MDA5 (+) group( n=28); anti-MDA5(-) groups( n=43). Electrocardiogram and echocardiography were performed in the sample group and the control group. The electrocardiogram, echocardiography and other relevant clinical data of the anti-MDA5 (+) group, anti-MDA5 (-) group and the healthy control group were retrospectively analyzed. The logistic regression analysis model was used to analyze the related factors influencing cardiac involvement in anti-MDA5 (+) patients. Results:In the anti-MDA5 (+) group, more than half of the patients showed elevated levels of lactate dehydrogenase (21/28, 75%) and α-hydroxybutyrate dehydrogenase (16/28, 57%), and 11%(3/28) showed elevated levels of creatine kinase isoenzyme and myoglobin. Compared with the anti-MDA5 (-) group, the white blood cell count in the blood routine of the anti-MDA5 (+) group [5.2 (4.0, 6.5) ×10 9/L vs. 7.8 (5.6, 10.6)×10 9/L, Z=-3.447, P=0.001], creatine kinase [62.5 (29.3, 108.3) U/L vs. 481.0 (179.0, 2 738.0) U/L, Z=-5.895, P<0.001], lactate dehydrogenase [313.0 (239.0, 362.0) U/L vs. 448.0 (291.0, 542.0) U/L, Z=-3.236, P<0.001], creatine kinase isoenzyme [1.9 (1.1, 3.9)ng/ml vs. 17.7 (4.0, 67.2) ng/ml, Z=-4.724, P<0.001], myoglobin [28.2 (20.0, 43.0) ng/ml vs. 307.4 (48.1, 612.2) ng/ml, Z=-4.800, P<0.001]. Electrocardiogram analysis showed that QRS axis [33.5±265.9 vs. 46.9±22.4, t=-2.900, P=0.004], SV1 amplitude [0.7 (0.4, 0.9) vs. 0.9 (0.7, 1.0), Z=-2.148, P=0.023] in anti-MDA5 antibody (+) group in anti-MDA5 antibody (+) group were lower than anti-MDA5 antibody (-) group. QRS duration [84.0 (78.0, 96.5) vs.92.0 (87.8, 100.5), Z=-2.900, P=0.004], QRS axis [33.5±265.9 vs. 46.9±20.4, Z=-2.32, P=0.023] in the anti-MDA5 antibody (+) group were lower than those in healthy control group. Echocardiographic analysis showed that the E peak of anti-MDA5 (+) group [63.0 (52.5, 69.5)] was significantly lower than that of anti-MDA5 (-) group [85.0 (68.0, 108.0), Z=-4.926, P<0.001)]and healthy control group [67.0 (62.8, 80.3), Z=-2.897, P=0.004]. The peak A of anti-MDA5 (+) group [65.5 (56.5, 80.0)] was significantly lower than that of anti-MDA5 (-) group [76.0 (65.0, 90.0), Z=-2.631, P=0.011], but higher than that of healthy control group [55.0(51.0, 66.5), Z=-4.550, P<0.001]. There was no significant difference in echocardiographic findi-ngs among the other groups. All patients with anti-MDA5 (+) dermatomyositis had interstitial lung disease (28/28, 100%). Patients with MDA5 antibody (+++) are more likely to have cardiac involvement than patients with MDA5 antibody (++). Conclusion:The results of relevant examinations in anti-MDA5-DM patients suggest that there is damage to myocardial cells and cardiac function.

Objective To reveal the development characteristics of fat percentage and muscle mass in three nomadic populations in the Hexi Corridor of Gansu.Methods Bioelectrical impedance analysis was used to determine the values of 13 indexes of fat percentage and muscle mass in 263 cases of Gansu Kazakhs,400 cases of Gansu Mongols,and 362 cases of Yugu adults.Results In the three nomadic populations of the Hexi Corridor,visceral fat level of males was significantly positively correlated with age,while total body muscle mass and estimated bone mass were significantly negatively correlated with age.In females,percent body fat,visceral fat grade,percent left and right upper limb fat,percent right lower limb fat and percent trunk fat were all significantly positively correlated with age,while trunk muscle mass was significantly negatively correlated with age.The result of principal component analysis showed that the three nomadic populations in the Hexi Corridor were close to each other in terms of fat percentage and muscle mass characteristics,with high visceral fat grades in males and normal visceral fat grade in females.Among the 13 populations,three nomadic groups in the Hexi Corridor had high fat percentage and muscle mass.Overall,the nomadic population had greater fat percentage and muscle mass than the semi-agricultural and semi-pastoral population,and even more significantly greater than the agrarian population.The long-term integration of the historical Hexi Corridor populations result ed in the relative proximity of the genetic structure of three nomadic populations,which was a genetic factor for the proximity of their fat percentage and muscle mass.Higher per capita disposable income was a socio-economic factor for high fat percentage and muscle mass among Gansu Kazakhs and Gansu Mongolians.Low average annual temperature was an environmental factor for high muscle mass among Gansu Kazakhs and Yugus.Conclusion Gansu Kazakhs,Gansu Mongols,and Yugus have the fat percentage and muscle mass characteristic of northern Chinese populations.

Objective:To study the effect of anti-melanoma differentiation-related gene 5(MDA5) antibody positive dermatomyositis on the heart of patients.Methods:A total of 71 patients with dermatomyositis diagnosed in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 1, 2014 to December 31, 2019 were enrolled as the sample group, including anti-MDA5 (+) group( n=28); anti-MDA5(-) groups( n=43). Electrocardiogram and echocardiography were performed in the sample group and the control group. The electrocardiogram, echocardiography and other relevant clinical data of the anti-MDA5 (+) group, anti-MDA5 (-) group and the healthy control group were retrospectively analyzed. The logistic regression analysis model was used to analyze the related factors influencing cardiac involvement in anti-MDA5 (+) patients. Results:In the anti-MDA5 (+) group, more than half of the patients showed elevated levels of lactate dehydrogenase (21/28, 75%) and α-hydroxybutyrate dehydrogenase (16/28, 57%), and 11%(3/28) showed elevated levels of creatine kinase isoenzyme and myoglobin. Compared with the anti-MDA5 (-) group, the white blood cell count in the blood routine of the anti-MDA5 (+) group [5.2 (4.0, 6.5) ×10 9/L vs. 7.8 (5.6, 10.6)×10 9/L, Z=-3.447, P=0.001], creatine kinase [62.5 (29.3, 108.3) U/L vs. 481.0 (179.0, 2 738.0) U/L, Z=-5.895, P<0.001], lactate dehydrogenase [313.0 (239.0, 362.0) U/L vs. 448.0 (291.0, 542.0) U/L, Z=-3.236, P<0.001], creatine kinase isoenzyme [1.9 (1.1, 3.9)ng/ml vs. 17.7 (4.0, 67.2) ng/ml, Z=-4.724, P<0.001], myoglobin [28.2 (20.0, 43.0) ng/ml vs. 307.4 (48.1, 612.2) ng/ml, Z=-4.800, P<0.001]. Electrocardiogram analysis showed that QRS axis [33.5±265.9 vs. 46.9±22.4, t=-2.900, P=0.004], SV1 amplitude [0.7 (0.4, 0.9) vs. 0.9 (0.7, 1.0), Z=-2.148, P=0.023] in anti-MDA5 antibody (+) group in anti-MDA5 antibody (+) group were lower than anti-MDA5 antibody (-) group. QRS duration [84.0 (78.0, 96.5) vs.92.0 (87.8, 100.5), Z=-2.900, P=0.004], QRS axis [33.5±265.9 vs. 46.9±20.4, Z=-2.32, P=0.023] in the anti-MDA5 antibody (+) group were lower than those in healthy control group. Echocardiographic analysis showed that the E peak of anti-MDA5 (+) group [63.0 (52.5, 69.5)] was significantly lower than that of anti-MDA5 (-) group [85.0 (68.0, 108.0), Z=-4.926, P<0.001)]and healthy control group [67.0 (62.8, 80.3), Z=-2.897, P=0.004]. The peak A of anti-MDA5 (+) group [65.5 (56.5, 80.0)] was significantly lower than that of anti-MDA5 (-) group [76.0 (65.0, 90.0), Z=-2.631, P=0.011], but higher than that of healthy control group [55.0(51.0, 66.5), Z=-4.550, P<0.001]. There was no significant difference in echocardiographic findi-ngs among the other groups. All patients with anti-MDA5 (+) dermatomyositis had interstitial lung disease (28/28, 100%). Patients with MDA5 antibody (+++) are more likely to have cardiac involvement than patients with MDA5 antibody (++). Conclusion:The results of relevant examinations in anti-MDA5-DM patients suggest that there is damage to myocardial cells and cardiac function.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

In order to study the analgesic effect of Shaoyao Gancao Decoction, this paper discussed material basis and mechanism from the perspective of macromolecules in traditional Chinese medicine. Inspired by the phenomenon of turbidity after boiling Chinese medicine, this experiment took Shaoyao Gancao Decoction as the research object to study the formation process of precipitation during boiling. The results showed that aggregates with a certain shape were formed in the solvent during the boiling process, and the precipitate was obtained by standing and centrifuging. Analysis found that the precipitation was mainly composed of small molecules such as paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid, isoliquiritin and gallic acid, and macromolecules such as protein and polysaccharide. The composition of precipitate was consistent with that of Shaoyao Gancao Decoction, but the analgesic effect of Shaoyao Gancao Decoction after removing the precipitate was significantly reduced. Based on these results, we isolated small molecular compounds, polysaccharides and protein from Shaoyao Gancao Decoction and their contents are 60.4, 700.7 and 207.2 mg·g^-1 respectively. We get the ratio, polysaccharide: small molecule = 11.6∶1, protein: small molecule = 3.4∶1, the precipitate is prepared in the state of boiling. The characterization results showed that the particle size of the precipitate will change significantly after co-heating, and the content determination results showed that the content of the six small molecular compounds which was free in solvent was significantly reduced after the formation of the precipitate. The acetic acid writhing experiment proved that the precipitate has a good analgesic effect, and effectively reduced the levels of inflammatory factors prostaglandin E2 and nitric oxide, and increased the level of anti-inflammatory factor interleukin-10. These results proved that the precipitate in Shaoyao Gancao Decoction is an important material basis for analgesic effect, and macromolecules such as protein and polysaccharide are the main components of the precipitate. The study of macromolecules in the precipitate of Shaoyao Gancao Decoction not only provides new ideas and methods for elucidating the pharmacodynamic material basis of Shaoyao Gancao Decoction, but also provides a reference for analyzing the scientificity of traditional decoction.