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

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Objective To investigate the management of Graves' disease in Jiangsu province. Methods According to the 2011 management of GD survey from American Thyroid Association and the 2013 survey from European Thyroid Association, a questionnaire was designed for this survey to acquire the diagnosis, treatment, and follow-up of Graves' disease among endocrinologists from 35 tertiary hospitals in Jiangsu province. Results A total of 476 valid questionnaires were collected. For patients with symptoms of hyperthyroidism, a large majority of respondents monitored serum FT3 , FT4 , TSH, thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody, and finding of thyroid ultrasound, accounted for 95. 6％, 95. 0％, 95. 4％, 95. 8％, 90. 3％, 90. 5％, and 93. 9％physicians, respectively. 91.2％ of physicians preferred anti-thyroid drugs as the first-line treatment, and 92. 6％ of them gave priority to the use of methimazole. For the duration of anti-thyroid drugs therapy, 41.2％of endocrinologists chose 24 months, while 20％ chose 18 months. When patients have moderate and active ophthalmopathy, most respondents with medium or senior professional titles preferred anti-thyroid drugs, while most resident physicians chose radioactive iodine plus corticosteroids. When pregnancy was confirmed in the patients of Graves' disease, 88％ of respondents preferred propylthiouracil during the first trimester of pregnancy, and 58. 4％ of them would continue propylthiouracil into the second trimester. Conclusions The mastering of basic perception of Graves' disease knowledge is satisfactory among the endocrinologists. But by comparing to the American and European survey results and related guidelines, there are still some differences in diagnosis and treatment. Therefore, physicians should notice those differences and make improvement on standardized treatment for patients to raise the response ratio while reducing the recurrent events.

Objective To investigate the influence factors of serum Angptl 2 levels is to explore the relationship between serum Angptl 2 and carotid atherosclerosis (CAS) in patients with type 2 diabetes mellitus (T2DM). Methods 114 cases of T2DM in clinic were selected.According to the results of color doppler ultrasonography,the patients were divided into T2DM with CAS group(T2DM + CAS,n=58)and simple T2DM group(n= 56).56 healthy subjects were selected as normal control (NC)group during the same period.ELISA method was used to detect the level of serum Angptl 2. Results Serum Angptl 2 levels were significantly higher in T2DM + CAS group and T2DM group than in NC group [(69.83 ± 12.07) vs (42.93 ± 10.44)vs (24.26 ± 8.78)ng/ml,P< 0.01].Correlation analysis showed that serum Angptl 2 was positively correlated with age,BMI,SBP,DBP,TC,TG,LDL-C,FPG and HbA1c in T2DM patients (r=0.574,0.325,0.528,0.308,0.396,0.387,0.295,0.536 and 0.601,respectively,P<0.01),and negatively correlated with HDL-C and FIns in T2DM patients (r= -0.248,-0.352,P<0.01).Similarly,multiple regression analysis showed that FIns,and HbA1c were the independent factors of serum Angptl 2 (β= -2.186,2.680,P<0.01). Conclusion Serum Angptl 2 level is closely related to obesity,blood pressure,blood glucose,blood lipid and insulin.Serum Angptl 2 may play an important role in the development of T2DM and carotid atherosclerosis.

Objective To analyze the effects of bone morphogenetic protein 7 (BMP 7) on insulin signaling pathway in mice and its involved molecular mechanisms. Methods To increase BMP7 expression in liver, adenovirus bearing BMP7 was injected into mice via tail vein. The impact of BMP7 overexpression on glucose metabolism was assayed by glucose tolerance test and insulin tolerance test. The levels of proteins involved in insulin signaling pathway and c-Jun N-terminal kinase ( JNK) signaling pathway were analyzed by Western blot. Results The blood glucose level was increased by BMP7 overexpression (P>0. 05), while the glucose tolerance and insulin tolerance were decreased by BMP7. The p-Akt and p-GSK3βin liver and epididymal white adipose tissue (WAT) were reduced in the BMP7-overexpressed mice (P>0. 01), indicating insulin signal transduction was inhibited. In gastrocnemius muscle, the insulin signal transduction was not altered by BMP7. Mechanistically, the JNK pathway was activated by BMP7 in liver and epididymal WAT (P>0. 01), while the JNK pathway in skeletal muscle was not changed. Conclusions In mice, BMP7 elevated blood sugar and decreased glucose and insulin tolerance. BMP7 inhibited the insulin signaling pathway in liver and WAT. These inhibitory effects on insulin signaling pathway was likely to be achieved by an activating JNK signaling pathway.

Objective To investigate the relationships between plasma secreted frizzled-related protein (SFRP) 5 level with type 2 diabetes (T2DM ) and carotid atherosclerosis (CAS). Methods According to the results of carotid color Doppler ultrasound ,56 T2DM patients were divided into 28 with carotid atherosclerosis (CAS group) and 28 without carotid atherosclerosis (NAS group). 28 healthy volunteers served as normal control (NC group). Serum SFRP5 was measured by ELISA. Results The level of serum SFRP5 in T2DM patients was lower than NC group (114.36 ± 25.48) vs (48.19 ± 11.82) , (43.88 ± 8.19)pg/ml ,(P<0.01). The difference of serum SFRP5 between CAS and NAS group shared no statistical significance [CAS (43.88 ± 8.19 ) vs NAS (48.19 ± 11.82 )pg/ml ,P> 0.05 ]. Pearson correlation analysis showed that serum SFRP5 was negatively correlated with age ,TG ,hsC-RP ,FPG ,FIns , HOMA-IR ,HbA1c ,TC ,LDL-C and BMI (P<0.01) ,and positively correlated with HDL-C (P<0.01). There were no significant correlations between SFRP5 and gender ,TC ,systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P>0.05). Multiple linear regression results showed that age ,FIns and HbA1 c were independent influencing factors of serum SFRP5. Conclusion SFRP5 may be a protective factor for T2DM by ameliorating insulin resistance which may provide a new clue for the prevention and treatment of T 2DM.

Objective To investigate the effects of bone morphogenetic protein-7 ( BMP7 ) on insulin signaling transduction in C2C12 myotubes and HepG2 hepatocytes, and the underlying mechanisms were studied preliminarily.Methods The C2C12 myotubes and HepG2 cells were treated with BMP7 at different concentrations.The insulin signal transduction was analyzed by Western blot.Meanwhile, total RNA was extracted and quantitative PCR was employed for detecting the effects of BMP7 on gene expressions of effectors involved in insulin signal pathway.Furthermore, JNK signal pathway was also measured.Results The protein levels of p-IR, p-Akt and p-GSK3β, as well as glucose uptake, were significantly stimulated by insulin in the C2C12 myotubes and HepG2 cells.However, these stimulations induced by insulin were largely attenuated by BMP7.The mRNA levels of Akt1, Igf1r, Insr, and Irs1 were not altered by the treatment of BMP7.The JNK signal pathway was activated by a 5-min exposure of BMP7 in the HepG2 cells, and this activation was gradually reduced along with the treating time.Conclusion BMP7 attenuates the insulin signal transduction in the HepG2 cells and C2C12 myotubes, and this attenuation effect may be through JNK activation.

Objective To evaluate the efficacy and safety of epalrestat, an aldose reductase inhibitor, and epalrestat plus methylcobalamine on diabetic peripheral neuropathy, as compared with methylcobalamine. Methods A total of 444 subjects with diabetic neuropathy were enrolled in the study, and divided into methylcobalamine group ( n= 145 ) , epalrestat group ( n = 143 ) , and methylcobalamine combined with epalrestat group ( n = 156 ) . Therapeutic efficacay was assessed in terms of clinical symptoms and physical examinations by using Michigan Neuropathy Screening Instrument ( MNSI ) , and electrophysiological assessments. Results After 4 to 12-weeks′treatment, symptoms and signs of neuropathy ( using MNSI ) are significantly improved in the three groups ( P<0. 01). The mean changes of MNSI ( questionnaire) score from baseline were higher in epalrestat group and methylcobalamine combined with epalrestat group as compared with that of methylcobalamine group(P<0. 05), but no difference was detected in the change of MNSI ( physical examination ) score from baseline among three groups. After treatment for 12 weeks, motor nerve conduction velocity ( MNCV ) was significantly improved in epalrestat group and methylcobalamine combined with epalrestat group(P<0. 05), but no difference was detected in MNCV at 12 week among three groups(P>0. 05). Conclusion Epalrestat is effective and safe in the treatment of diabetic neuropathy. Furthermore, epalrestat is more efficacious in ameliorating symptoms and MNCV of neuropathy than methylcobalamine. However, while no improved efficacy is shown with the combined treatment.

Objective To analyze the efficacy and safety of glimepiride treatment as initial monotherapy in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods This was a subgroup analysis of the GREAT study,which investigated the efficacy and safety of glimepiride as initial monotherapy in Chinese patients with T2DM.This analysis was performed in 209 patients with disease duration less than 6 months and never received any anti-diabetic drugs.The change of HbA1C,fasting plasm glucose (FPG),2 h postprandial blood glucose (2hPPG),homeostasis model assessment for β-cell function index (HOMA-β),homeostasis model assessment for insulin-resistance index(HOMA-IR),the percentage of patients with HbA1C ＜ 7.0％ at endpoint and the incidence of hypoglycemia were evaluated after 16-weeks treatment.Results After 16-weeks glimepiride treatment,HbA1C value reduced significantly from baseline to endpoint,the reduction was statistically significant (9.21％ ± 1.65％ to 6.69％±0.83％,P＜0.001),69.7％ of the patients achieved HbA1C ＜7.0％ at study endpoint.Glimepiride-treated patients also achieved a significant improvement in FPG [from (10.15 ± 2.13) mmol/L to (7.23 ± 1.50) mmol/L,P＜0.001] and 2hPPG [from (17.21 ±4.14) mmol/L to (11.62 ± 3.34) mmol/L].HOMA-β was improved from 17.21± 15.19 [11.62 (2.90,115.8)] to 41.13 ± 44.12 [28.00 (5.1,360.00)],and HOMA-IR was reduced from 2.32± 1.90 [1.76 (0.60,12.80)] to 2.07 ± 1.74 [1.63 (0.4,12.3)].The incidence of all reported symptomatic hypoglycemia was 18.2％,and the incidence of confirmed hypoglycemia was 3.8％.Conclusion This analysis showed that glimepiride treatment as an initial mono-therapy could effectively improve blood glucose control in newly diagnosed patients with T2DM,and the treatment may improve islet β cell function,and the safety profile is reasonably good.

Objective To explore the clinical effect of high intensity focused ultrasound(HIFU)combined with transcatheter arterial chemoembolization(TACE)in the treatment of primary liver cancer.Methods A total of 106 patients with primary liver cancer were divided into two groups:50 cases were treated with TACE,and the other 56 were treated with combination of HIFU and TACE.The changes of AFP levels and the size of tumors after three months treatment were analyzed and compared with each other.The survival rates for one,two and three years were calculated with Kaplan-Meier method and compared between the two groups.Results In the two groups,AFP decreased significantly after treatment,but the combined group was superior to the other in AFP decrease.In the combined group,the 1-,2-and 3-year survival rates were higher than those in the TACE group with 82.3%,60.8%and 39.2% vs 68.0%,42.6%and 21.0%respectively(P＜0.01).No serious complications were seen,such as burn of skin,bleeding,gastrointestinal perforation. Conclusion The use of HIFU combined with TACE in the treatment of patients with primary liver cancers is feasible and safe.The combined group is superior to simple TACE for the management of primary liver cancers,and the former is more effective in decreasing AFP level and improving survival rates.