Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be answered.By merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+cells within M1.These PRX1+cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation.Deeper into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1+cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway.The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1.Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs.These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

Objective:To evaluate the safety and efficacy of enteromorpha prolifera enzymatic hydrolysate in alleviating scalp sensitive symptoms.Methods:The inhibitory effects of different concentrations of enteromorpha prolifera hydrolysate on tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-6, and other inflammatory factors were observed through in vitro experiments. Subsequently, the abilities to scavenge [2, 2＇-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS) and to promote proliferation of mouse fibroblasts were evaluated. A prospective study was conducted on 20 patients with scalp sensitivity at Qingdao Hiser Hospital Affiliated to Qingdao University from April 2023 to October 2023. The patients included 2 males and 18 females with an average age of (34.9±10.3) years. They were treated with a scalp essence containing 10% enteromorpha enzymatic hydrolysate for consecutive 28 days. Changes in scalp cuticle water content, transepidermal water loss (TEWL), and oil content were measured before and after 14 and 28 days of treatment. Expert interviewers assessed the skin irritation test to elucidate any undesirable side effects.Results:The results of in vitro experiments demonstrated that enteromorpha protophora enzymatic hydrolysate at different concentrations exhibited inhibitory effects on the expression of IL-1α, IL-6, and TNF-α, while it also displayed a dose-dependent ability to scavenge ABTS free radicals. Furthermore, it effectively promoted the proliferation of mouse fibroblasts, resulting in a significant increase of 43.22% in fibroblast viability when the concentration of enteromorpha protophora enzymatic hydrolysate was 0.10%. The outcomes from clinical trials revealed that after using a scalp essence containing enteromorpha protophora enzymatic hydrolysate for 14 and 28 days, there were significant improvements observed in terms of increased water content in the scalp epidermis, along with decreased oil content and TEWL value (all P< 0.001). Moreover, remarkable effective rates were achieved for treating various scalp conditions including redness (80.0%, 16/20), dandruff (80.0%, 16/20), itching (85.0%, 17/20), stinging sensation (90.0%, 18/20), and tightness (80.0%, 16/20) after using the scalp essence for 28 days. Adverse effects on the skin were not observed in any subject during the test period. Conclusions:The enzymatic hydrolysate of enteromorpha demonstrates both safety and efficacy in alleviating symptoms associated with scalp sensitivity.

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Gene Expression Regulation, Developmental ; Odontogenesis ; Signal Transduction ; Tooth/metabolism* ; Humans

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1⁺ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1⁺ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1⁺ cells in PDL cells. The behavior of PRX1⁺ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1⁺ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1⁺ cells; during transplanted teeth PDL reconstruction, PRX1⁺ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1⁺ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.
Animals ; Cell Differentiation ; Mesenchymal Stem Cells ; Mice ; Molar ; Osteogenesis/physiology* ; Periodontal Ligament

BACKGROUND: Regenerative medicine by using stem cells from dental pulp is promising for treating patients with critical limb ischemic (CLI). Here, we investigated the difference in the angiogenetic ability of stem cells from human exfoliated deciduous teeth (SHED) and human dental pulp stem cells (DPSC). METHODS: SHED and DPSC were harvested from dental pulp and analyzed in flow- cytometry for detecting the expression of surface markers. Levels of angiogenetic marker were examined by RT-PCR and Western-blot. Eighteen immunodeficient mice of critical limb ischemic model were divided into three groups: SHED, DPSC and saline, which was administered with SHED, DPSC or saline intramuscularly. Histological examination was performed to detect the regenerative results. RESULTS: A highly expression of CD146 was detected in SHED. Moreover, cells with negative expression of both CD146 and CD31 in SHED were more in comparison with those in DPSC. Expression of angiogenesis factors including CXCL12, CXCR4, Hif-1a, CD31, VEGF and bFGF were significant higher in SHED than DPSC by the RT-PCR and Western-Blot results. SHED induced more CD31 expression and less fibrous tissue formation in the critical limb ischemic model as compare with DPSC and saline. CONCLUSION Both SHED and DPSC possessed the ability of repairing CLI. With expressing more proangiogenesis factors, SHED may have the advantage of repairing CLI.

Objective:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban.Methods:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment.Results:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg·kg -1·min -1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg·kg -1·min -1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg·kg -1·min -1], but without significant difference ( P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg·kg -1·min -1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg·kg -1·min -1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Conclusion:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.

Objective:To investigate the effectiveness and safety of soothing moisturizing repair cream on acne depressed scar exfoliative fractional laser wound repair.Methods:From October 2018 to June 2020, the Department of Dermatology, Qingdao Haici Hospital Affiliated to Qingdao University took 33 patients with acne depressed scars as the research object, including 8 males and 25 females, aged from 20 to 36 years (29.6±8.6) years. The left and right face comparison method was adopted. After laser operation, the trial side was given a soothing moisturizing repair cream, and the control side was given a placebo. By collecting the patient's facial pictures and objective skin data before and after the laser operation, 1 h, 1 d, 3 d, 7 d, 21 d, and combined with the researcher's semi-subjective evaluation and patient's subjective evaluation the wound skin reaction and wound healing were observed.Results:At 1, 3, 7, 21 days after laser operation, the skin water content of the test side was higher than that of the control side ( P<0.05), and the skin water loss was lower than the control side ( P<0.05); at 3, 7, 21 days, the skin pigment of the test side was lower than the control side ( P<0.05); at 3, 7 d, the test side skin erythema index was lower than the control side ( P<0.05); at 1, 3, 7 d, the test side wound skin erythema, edema, dryness and tightness, etc. were better than the control side ( P<0.05). The duration of pain, crusting time, scab removal time, and complete healing time of the wound on the test side were shorter than those on the control side ( P<0.05). The patient's satisfaction with the moisturization and comfort of the nursing products on the trial side was better than that on the control side ( P<0.05). Conclusions:There is no adverse reaction to the soothing moisturizing repair cream after laser surgery, which can better inhibit skin inflammation, reduce post-inflammatory pigmentation, promote skin healing, and help repair the wound after laser surgery.

Objective:To discuss how to avoid the occurrence of adverse events and provides basis for improving the extracorporeal membrane oxygenation (ECMO) transport safety management to formulate the corresponding preventive measures through analyzing the causes and characteristics of adverse events in transport of ECMO.Methods:By using a self-designed ECMO transport observation table to collect data, with a retrospective study of adverse events in patients with ECMO transport in ECMO center of Beijing Chaoyang Hospital from January 2013 to June 2017, carrying out classification and analysis according to the causes of adverse events and the potential risks of the patients, thus put forward the feasible preventive measures.Results:There were 53 cases of ECMO transport in study period, with 18 cases (33.96%) of adverse events, among which the incidence of adverse events in inner-hospital transport was 34.21% (13/38) and that in inter-hospital transport was 33.33% (5/15). There was no patient died in ECMO transport. In the adverse events of ECMO transport, the main causes were related to transport staff, transport equipment and patient, which accounting for 1/3 of each. Among them, the most prominent was 4 cases (22.22%) of equipment lacking and 3 cases of battery and power supply (16.67%). In classification according to the risk degree of patients, 6 cases (33.33%) of third grade risk were found.Conclusions:It is safe and feasible to carry out ECMO transport in inner-hospital transport and inter-hospital transport based on ECMO transport team and transport process of this hospital. However the unexpected events of high risk or crisis of life is inevitable in ECMO transport. Through standardized training for ECMO team, with full assessment before transport, by the use of ECMO checklist and strict implementation of various transport processes and specifications, the incidence of adverse events in ECMO transport may be reduced.

Objective:To analyze the relationship and clinical value between serum matrix metalloproteinases-3 (MMP-3) and rheumatoid arthritis (RA).Methods:By using retrospective study to collect 123 patients with RA diagnosed in our hospital from January 2019 to January 2020 as the RA group. Among the patients, there are 25 males and 98 females, the median age is 60 years old. During the same term, 53 healthy people were selected as the control group, with 12 males and 41 females, the median age is 55 years old. MMP-3, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hs-CRP), rheumatoid facotrs (RF), anti-cyclocitrulline factor (ACCP) in peripheral blood of all subjects were detected. Disease activity score of 28 joints (DAS28) were collected. This research used T test, Spearman correlation analysis and receiver operating characteristic curve (ROC curve) to analyze the relationship between MMP-3 and other clinical biochemical indices, and the efficacy of MMP-3 in the diagnosis of RA.Results:Compared with the control group (26.30±14.83)ng/ml, the levels of serum MMP-3 in the RA group (79.71±123.54) ng/ml had significantly increased ( t=-4.95, P<0.001). The serum concentration of MMP-3 in RA patients was significantly correlated with ESR, hs-CRP and DAS28 ( r value were 0.521, 0.372, 0.405 respectively, P<0.001). The area under the curve (AUC) of MMP-3 to diagnose RA was 0.765, and the sensitivity was 64.44%, and the specificity was 75.76%, cut-off of MMP-3 were 32.50 ng/ml. Conclusions:The levels of serum MMP-3 in the RA group had significantly increased. MMP-3 and the disease activity were highly correlated. MMP-3 can be used as an indicator of RA disease activity, also can significantly improve the diagnostic efficacy, treatment and warning of early RA.

Objective To analyze the clinical profile of primary Sj(o)gren's syndrome (pSS) patientswith central nervous system (CNS) involvement.Methods Thirty-eight pSS-CNS patients at Nanjing Drum Tower Hospital between 2012 and 2016 were enrolled.These patients were divided into high activity group and moderate activity group,according to European League against Rheumatism Sj(o)gren's syndrome Disease Activity Index (ESSDAI).The imaging characteristics,clinical features,laboratory examinations and treatment of 38 cases were retrospectively analyzed.Quantitative differences were analyzed by the student's t-test and qualitative data were analyzed with chi-square or Fisher's exact test.Results The prevalence of central nervous system involvement in pSS patients was 2.93％(38/1 296),while 32％(12/38) as the initial symptom of pSS.Recurrence rate was 39％(15/38).Limb weakness,speech difficulty,sensory disorders,blurred visionwere the most frequent symptoms in pSS-CNS.Multiple lesions in Magnetic resonance imaging (MRI) examination and cerebrospinal fluid abnormality were seen in 94％ (15/16) pSS-CNS patients,among which intra-thecal IgG level increased in 50％ (8/16).In addition,the frequencies of lung involvement,immune associated thrombocytopenia,high-titer antinuclear antibody (ANA) were significantly higher in high activity group of pSS-CNS than those of moderate activity group.The value of above items was 4.7,5.0 and 5.3,respectively,and all the differences were significant (P＜0.05).After high-dose corticosteroids and immunosuppressive therapy,61％ (23/38) patient improved,37％(14/38) were unresponsive to treatment,and 3％(1/38) died because of acute massive cerebral infarction.For those unresponsive patients,mesenchymal stem cell transplantation or immune adsorption treatment might be effective.Conclusion The clinical manifestations of central nervous system are diverse,may be the initial presentations in some pSS patients,with low morbidity and high recurrence rate.Image and lumbar puncture are important for diagnosis.Pulmonary involvement,immune thrombocyto-penia,and high-titer ANA are frequently associated with the activity of pSS-CNS.Most patients have good response to the treatment regimens of high-dose corticosteroids and immunosuppressive therapy,mesenchymal stem cell transplantation or immuno-sorption therapy may be considered in those unresponsive cases.