In recent years, mesenchymal stem cell-derived exosomes (MSC-EXO) have garnered increasing attention in the field of stomatology and have become an established research area in biomedical research. This article reviews the engineering of exosomes derived from mesenchymal stem cells and their application in the field of stomatology, in order to provide new ideas for the development of stomatology. Exosomes are nanoscale membrane vesicles secreted by cells and contain a variety of proteins, RNAs, lipids, and other biomolecules. They are transported through the circulatory system and can interact with other cells to regulate their biological behavior and participate in a variety of physiological and pathological processes. In the treatment of oral diseases, exosomes have shown great potential due to their natural biological activity and versatility. However, studies have found that relying solely on the function of natural exosomes may not fully meet the complex clinical requirements. Therefore, the concept of engineered exosomes has emerged. Engineered exosomes can be modified by bioengineering technology to enhance their targeting, allowing them to reach the lesion site more accurately. At the same time, engineered exosomes can also be surface modified or loaded internally to carry specific therapeutic molecules, such as drugs, gene editing tools or signaling molecules to improve the therapeutic effect. In addition, this engineered treatment can also confer greater stability to exosomes, making them better able to resist clearance by the immune system when circulating in the body, extending their half-life, and improving the effectiveness of treatment. Although engineered exosomes have attracted extensive attention in the fields of stomatology and other fields, their application is still mainly in the stage of basic research. To promote the clinical application of engineered exosomes, it is necessary to provide more sufficient evidence of biocompatibility and clarify their therapeutic effect and mechanism.

Objective:To investigate the biocompatibility of coral-like barium titanate nano-piezoelectric coatings and the influence of ultrasound-excited piezoelectric effect on the early osteogenic differentiation.Methods:The barium titanate nano-piezoelectric coating (the coating group) was prepared on the surface of titanium metal by anodic oxidation, hydrothermal reaction and high-temperature annealing, and polished titanium specimens were used as control group. The surface morphology, composition, and crystal phase and hydrophilicity of the two groups of titanium specimens were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy and contact angle meter. The piezoelectric properties of the materials were characterized by piezoresponse force microscopy. Rat bone marrow mesenchymal stem cells (BMSC) were cultured and identified and seeded the surface of titanium specimens in two groups. The cells seeded on blank culture plates were used as blank group. After low intensity pulsed ultrasound intervention, cell proliferation and live/dead staining were detected to evaluate cytocompatibility of the coatings. Alkaline phosphatase (ALP) activity of each group was detected by ALP staining kit, and the expression of osteogenesis-related genes [integrin, bone morphogenetic protein 2 (BMP-2), Runt-related transcription factor 2 (RUNX2)] was detected by real-time fluorescent quantitative PCR (RT-qPCR) to evaluate the effect of the coating on promoting the early osteogenic differentiation of BMSC.Results:The surface of titanium specimens in the coating group showed a uniform coral-like morphology, and the diameter of the coral tentacles was 70-100 nm. The main component was tetragonal barium titanate. The surface hydrophilicity of the coating group (water contact angle 10.12°± 0.93°) was significantly better than that of the control group (water contact angle 78.32°±0.71°) ( F= 10 165.91, P<0.001). The coating has a stable piezoelectric property with a piezoelectric constant of about 5 pC/N. Cell experiments showed that, with or without ultrasound, the cell proliferation activity of the coating group was significantly lower than that of the blank group and the control group on the third day ( P<0.05). On the fifth day, with or without ultrasound, there was no significant difference in cell proliferation activity between the three groups ( P>0.05). After 7 days of culture, the ALP activity of the coating group was significantly higher than that of the blank group and the control group ( P<0.05). The results of RT-qPCR showed that the mRNA expression of integrin and BMP-2 in the coating group with ultrasound was significantly higher than that in the other groups with ultrasound, and was higher than that of the coating group without ultrasound ( P<0.05). The expression of integrin mRNA in the control group with ultrasound was significantly higher than that in the control group without ultrasound ( P<0.05). The expression of RUNX2 mRNA in the coating group with ultrasound was significantly higher than that in the coating group without ultrasound ( P<0.05). Conclusions:The coral-like barium titanate nano-piezoelectric coating exhibits favorable biocompatibility and stable piezoelectric property, and facilitates the early osteogenic differentiation of BMSC under the excitation of low-intensity pulsed ultrasound.

Objective To analyze the value of serum C1q tumor necrosis factor related protein 12(CTRP12)in early pregnancy in predicting gestational diabetes(GDM).Methods 182 pregnant women who underwent prenatal examinations in our department from March 2020 to October 2022 were selected,serum CTRP12 levels were measured at 6～14 weeks of pregnancy.At 24～28 weeks of pregnancy,they were divided into normal glucose tolerance(n=152,NGT)group and GDM group(n=30,GDM)based on OGTT results.The serum CTRP12 levels of the two groups were compared and its predictive value for GDM was analyzed.Results The incidence rate of GDM was 16.48%.Compared with NGT group,the age,pre pregnancy BMI,FPG and family history of diabetes in GDM group were significantly higher,and the serum level of CTRP12 was significantly lower(P<0.05).BMI before pregnancy,family history of diabetes,FPG and serum CTRP12 were the influencing factors of GDM.Receiver operating characteristic analysis showed that the AUC of serum CTRP12 for predicting GDM was 0.822(95%CI 0.759～0.885),the optimal cut-off value was 5.66 ng/ml,with the sensitivity 68.2%and the specificity 90.3%,respectively.Compared with the high level group of CTRP12,the incidence rate of GDM in the low level group of CTRP12 was significantly higher(P<0.05).Conclusions The serum CTRP12 level in GDM patients decreases in the early pregnancy.CTRP12 as an influencing factor may have certain predictive value for GDM.

Since 2016, Binzhou Medical University began to carry out the blended learning reform in the organ-systems based curriculum (OSBC) of the experimental class of clinical medicine. Based on the traditional face-to-face teaching method, the blended learning mode of the integrated course of endocrine system under OSBC has been carried out by using the small private online course (SPOC) of MOOC platform of China universities. Many teaching methods have been adopted and formed, including case-based learning (CBL), problem-based learning (PBL), professional bilingual teaching, scientific research teaching and virtual simulation experiment teaching. The evaluation system for the combination of formative and summary assessment has been also adopted in the whole process to assess the students' academic achievement, and the teaching effect as well. The blended learning mode of the integrated course of the endocrine system under OSBC is still in the exploratory stage. There are some limitations, such as too high requirements for teachers' quality, long preparation time for teaching, and great difficulty in supervising online learning. However, the practice of teaching reform that has been carried out shows that it is effective, feasible, and worth popularizing.

Objective:To explore the clinical and pathological features of Dubin-Johnson syndrome.Methods:The clinical and pathological characteristics of 18 cases of Dubin-Johnson syndrome diagnosed in the Department of Pathology of the Third Affiliated Hospital of Sun Yat-sen University from 2008 to 2018 were analyzed. Related literature was reviewed.Results:There were 15 male and three female patients. The male-to-female ratio was 5∶1. The age of the patients ranged from 17 to 73 years (median 24 years). Common clinical manifestations were jaundice, anorexia, and abnormal liver function tests. The pathological feature was the deposition of dark brown particles in the hepatocytes, especially those around the central veins.Conclusions:Dubin-Johnson syndrome mainly occurs in young people. The characteristic pathological changes are the deposition of dark brown particles in the hepatocytes around the central veins of the liver. The diagnosis of Dubin-Johnson syndrome mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing. The understanding of Dubin-Johnson syndrome can help reduce the rates of missed diagnosis and misdiagnosis of the disease.

Objective To compare diagnostic values of the 2015 American Thyroid Association (ATA) Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer with the thyroid imaging reporting and data system (TI-RADS) for sonographic malignancy risk stratification of thyroid nodules.Methods From November 2011 to December 2015,485 thyroid nodules in 331 patients (mean age,42.9 years± 10.4)were included in this study.Characteristics includingsize,composition,shape(nonparallel or parallel),margin,echogenicity,calcifications and extrathyroidal extension of thyroid nodules were evaluated.Every nodule was stratificated by criteria set by TI-RADS and ATA guidelines,and malignant rate of each risk stratification were calculated and analysed.With pathology as the gold standard,different cutoff were taken to diagnose malignant nodules,and the sensitivity,specifity,positive predictive value,negativepredictive value and accuracy of the two methodologies were calculated at each cutoff.And the two methodologies were evaluated and measured by ROC curve.Finally their Kappa value were calculated at the best cutoff.Results Of the 485 thyroid nodules,96 were benign and 389 were malignant.The malignancy rates under TI-RADS category 2,3,4a,4b,4c,and 5 nodules were 0,12.0％ (3/25),22.2％ (10/45),29.8％ (14/47),99.2％ (261/363) and 100％ (101/101).Malignancy rates under ATA guidelines of benign,very low,low,intermediate,and high suspicion for malignancy were 0,12.5％ (1/8),16.1％ (10/62),27.7％ (13/47),and 99.2％ (365/368).There were significant differences inside each patterns (P ＜ 0.01) respectively and high correlation between risk stratification with TI-RADS (r=0.70) and ATA guidelines (r=0.83).Areas under the ROC curve of the TI-RADS and ATA guidelines classifications were 0.966 and 0.959.Best cut-off point for diagnosing malignant by TI-RADS and ATA guideline classifications were ≥ 4c and ≥ high suspicion,and at that point,diagnostic value of TI-RADS and ATA guidelines were nearly the same(sensitivity,93.1％vs 93.8％;specificity,97.9％ vs 96.9％;PPV,99.5％ vs 99.2％;NPV,75.7％vs 79.5％;and accuracy,94.0％vs94.4％),and there was no significant differences (P=0.50,P=0.50,P=0.50,P=0.53,P=0.55),Kappa=0.97.Conclusions Both TI-RADS and the ATA guidelinesprovide effective malignancy risk stratification for thyroid nodules.The diagnosticvalue of TI-RADS when considering ≥ 4c and ATA guidelines when considering ≥ high-suspicion nodules as malignant were nearly the same and both high.

Objective: To investigate the predictive value of an early inflammatory response factor, Rho kinase activity for left ventricle remodeling (LVR) in patients with acute ST-segment elevation myocardial infarction (STEMI).
Methods: A total of 120 acute STEMI patients treated in our hospital from 2010-10 to 2013-06 were studied, all patients were ifrst time received primary percutaneous coronary intervention (PCI) with stent implantation. Rho kinase activity and B-type natriuretic peptide (BNP) were measured before PCI, echocardiography was conducted at 24 hours and 12 months after STEMI respectively to clarify LVR diagnosis. The patients were divided into 2 groups as LVR group, n=97 and Non-LVR group, n=23, the above indexes were compared between 2 groups.
Results: The level of Rho kinase was higher in LVR group than that in Non-LVR group, P<0.001, after adjustment, Rho kinase was the independent predictor for LVR (OR 3.36, 95%CI 2.01–5.78, P<0.001). The ROC of Rho kinase was 0.88 (95%CI 0.82–0.94) and the ROC of BNP was 0.54 (95%CI 0.41–0.70).
Conclusion: High Rho kinase activity could predict LVR in acute STEMI patients with primary PCI and stent implantation.

Binzhou Medical University began to launch an experimental class of the clinical medical science in 2012 aimed at the undergraduates only.In this class,the ‘centered on the subject’ teaching mode was transformed into the ‘ organ-systems based curriculum’ or ‘ OSBC’ for short.Under the OSBC,the morphology combined the following three subjects:anatomy,hyphology and pathematology into an organic unity.This new subject pays more attention to the relationship among the morphology' s characters,the functional situation and the change of the pathogenesis.A variety of forms such as combining theories with experiments,the case-oriented teaching,translocation type teaching and bilingual teaching are used.To evaluate the students' performance more comprehensively,and to judge the teaching quality more objectively,the formative and summative assessments are used together.The morphology under this new mode is still on its exploration stage.Though with the shortage of corresponding teaching materials and the qualified teachers,it bears fruit and is feasible.

Objective To investigate the status quo of the assurance and subsidy for severe diseases acquired by juvenile in rural areas in Qinghai, and provide evidences for building a subsidy system for such population. Methods Quantitative surveys were made to collect data on medical expenses and the compensation practice for such expenses for severe diseases of juvenile in the area, for a knowledge of the present medication and disease load in question; specialists in two hospitals were interviewed to learn the present treatnents for such a population, and their expenditures in case of such diseases. Results Juveniles in rural Qinghai rely on the new rural cooperative medical scheme, under which however the reimbursement rate was only 26% ～35%. Families with juvenile patients of severe diseases were found to suffer heavy burdens. As a result, a high percentage of the patients give up treatment. To make things worse, as only two hospitals in the provincial capital city can provide professional treatment for children with severe diseases, rural children have to pay heavy indirect costs other than medication such as heavy travel expenses. Conclusion It is critical to build a medical assurance system for juvenile with severe diseases. It is also imperative to build and strengthen the capacity of medical centers for such a population in Qinghai, and upgrade the diagnosis and treatment competence of local health providers, ensuring adequate medical resources for juvenile with severe diseases upon joint development of both healthcare providers and the medical insurance system.

Objective To isolate enterovirus 71 from a death children,and analyze whether the neurovirulence was related to the variation of nucleotide and amino acid. Methods Enterovirus 71 was isolated from throat swabs which were colleted from Shandong Linyi People's Hospital. The full length genome was sequenced by amplification with RT-PCR and sequencing of 9 overlapped gene fragments covering full length of the genomes. The nucleotide and amino acid sequenced was aligned by BLAST, Bioedit and MEGA 4. Results A strain of enterovirus 71 was isolated and named as SDLY107. The full length was 7405 bp. The results of homology analysis of overall nucleotide sequence showed that strain Fuyang. Anhui. P. R. C/17.08/2 had highest homology (98.6%)with strain SDLY107, and the homology was 80.0% between strain SDLY107 with prototype strain BrCr/70,and 86. 5% between strain SDLY107 with nerve strain MS/87. Phylogenetic analysis showed that the phylogeny was close between SDLY107 with some isolated strains from Chinese Mainland, such as Beijing, Henan, Guangxi, Sbenzhen, Lanzhou, Fuyang, Chongqing and Zhejiang strains, which was clustered for C4 subtype. The results of amino acid sequence analysis showed that there were 2 mutations, E947D and K1873R, for strain SDLY107. Conclusion SDLY107 belonged to C4 subtype, amino acid mutations E947D and K1873R of which may be relevant to the pathogenicity of EV71.