ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L^-1）， baicalin（1 078.37-1 411.52 mg·L^-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L^-1）， timosaponin BⅡ（245.10-604.89 mg·L^-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L^-1）， rutin（46.91-1 553.61 mg·L^-1）， glycyrrhizic acid（55.97-391.47 mg·L^-1）， neomangiferin（37.45-127.03 mg·L^-1）， nuciferine（0.89-63.48 mg·L^-1）， hyperoside（6.96-136.78 mg·L^-1）， liquiritin（30.89-122.78 mg·L^-1）， liquiritigenin（26.64-110.67 mg·L^-1）， protodioscin（58.57-284.26 mg·L^-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L^-1）， pseudoprotodioscin（5.49-22.96 mg·L^-1）， ginsenoside Rb₁（7.31-23.87 mg·L^-1）， ginsenoside Rg₁（10.78-28.33 mg·L^-1）， ginsenoside Re（7.78-24.76 mg·L^-1）， ophiopogonin D（2.08-4.29 mg·L^-1）， methylophiopogonanone A（0.74-1.67 mg·L^-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Objective:To investigate the satisfaction of clinical interns to the department and teachers under the merging mode of standardized residency training and clinical practice, and to explore the feasibility to further implement the mode in clinical practice.Methods:Cluster sampling was used to design the scale, which included the importance attached by department to the teaching work, the rationality of the arrangement of practice content, the implementation of teaching activities, the quality of teaching activities, the status of out-department examination, the demonstration of medical ethics of teachers, the teaching attitude and knowledge lecturing of teachers, the revision of medical records and the guidance of skills operation, etc. The questionnaire survey was conducted among clinical interns in a hospital from July 2018 to June 2019. SPSS 22.0 was used to conduct t test or rank sum test of two independent samples, and the analysis of multiple groups of data was performed by means of variance analysis. Results:A total of 1 230 questionnaires were sent out, and 1 195 were returned, with an effective recovery rate of 97.15%. The overall satisfaction of interns was (9.62±0.39). The interns gave the highest evaluation on the medical ethics and medical style of the teacher (9.75±0.78), and the lowest evaluation on the teaching quality of all departments (9.52±1.15). There were significant differences among the evaluations ( F=7.30, P<0.001). Conclusion:Under the merging mode of standardized residency training and clinical practice management, all teaching and research sections and departments have fulfilled various teaching tasks according to the requirements, but the teaching quality and connotation construction need to be further strengthened.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1^G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).
Humans ; NF-kappa B/metabolism* ; Ginsenosides/pharmacology* ; Amyotrophic Lateral Sclerosis/genetics* ; Culture Media, Conditioned/pharmacology* ; Superoxide Dismutase-1 ; Neurodegenerative Diseases ; Neurons/metabolism* ; Apoptosis

Guided bone regeneration technology applied in alveolar bone defect regeneration is based on the barrier function and space maintenance of the barrier membrane. Therefore, traditional development strategies for barrier membranes focus on their physical barrier function, degradation characteristics and biocompatibility to avoid immunogenicity. However, not only does the barrier membrane passively block connective tissue, it is recognized as a “foreign body”that triggers a persistent host immune response, known as a foreign body reaction. The theories of osteoimmunology reveal a close relationship between the immune system and bone system and emphasize the role of immune cells in bone tissue-related pathophysiological processes. Based on these findings, we propose a novel development strategy for barrier membranes based on immune microenvironment regulation: by manipulating mechanical properties, surface properties and physiochemical properties, barrier membranes are endowed with an improved immunomodulation ability, which helps to regulate immune cell reactions to induce a favorable local immune microenvironment, thus coordinating osteogenesis and osteoclastogenesis as well as barrier membrane degradation to increase the efficiency of barrier membranes in GBR applications. In this paper, we review the development of barrier membranes and their close relationship to the immune microenvironment concerning bone regeneration and membrane degradation. Additionally, the outcomes of research on barrier membranes based on the regulation of the immune microenvironment have been summarized to improve the osteogenesis efficiency of barrier membranes and solve the problem of the regeneration and repair of bone defects, especially alveolar bone defects.

Objective:To investigate the systemic expression profile of S100A8 and S100A9 in healthy and inflamed periodontal tissues.Methods:Experimental periodontitis models were established by ligations around the mandibular second molars of six beagle dogs for 12 weeks (ligation group). The mandibular second molars on the opposite side were kept clean (healthy control group). The expressions of S100A8 and S100A9 in healthy and inflamed periodontal tissues of six beagle dogs were examined by immunohistochemistry. The expressions of S100A8 and S100A9 in primary human gingival fibroblasts (hGF) from 3 subjects and human periodontal ligament cells (hPDLC) from 3 other subjects were detected by immunocytochemistry.Results:After the ligation for 12 weeks, the mean probing depth of ligation group [(3.86±0.14) mm] was significantly higher than that of healthy control group [(2.11±0.28) mm] ( P<0.01). Results of immunohistochemistry analysis indicated that S100A8 and S100A9 could be expressed in gingival epithelial cells and might infiltrated neutrophils in the healthy periodontium. Except for the gingival epithelial cells and neutrophils, both proteins were induced and expressed in gingival fibroblasts, periodontal ligament cells, microvascular endothelial cells and bone marrow fibroblasts under inflammatory conditions. The distribution of S100A8 and S100A9 differed in the healthy oral gingival epithelium (OGE), which becomes consistent in inflamed OGE. Additionally, the expressions of S100A8 and S100A9 were confirmed in primary hGF and hPDLC. Conclusions:Periodontal inflammation might enlarge the expression scope of S100A8 and S100A9 and enrich multiple cells with expressions of S100A8 and S100A9.

Objective:To evalute the accuracy and clinical outcome of a real-time navigation system for the placement of quad zygomatic implants.Methods:Twenty-four patients [9 males and 15 females, mean age was (50.8±14.7) years old], from January 2015 to December 2019, with 96 zygomatic implants placed under a real-time navigation system in Department of Second Dental Center and Department of Oral Implantology of Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine were included in the study. The preoperative and the postoperative multislice CT or cone-beam CT were fused to measure and record the entry, exit and angle deviation between the planned and placed implants. The implants were divided into groups according to implant insertion approach (real-time navigation and free-hand), implant length (<47.5 mm and ≥47.5 mm) and implant position (proximal and distal implant). And the differences of implant accuracy were analyzed. The intraoperative and postoperative complications were also recorded. The implant survival rate was evaluated after 6 months follow-up. A P value<0.05 indicates statistical significance. Results:The mean entry, exit and angle deviation of zygomatic implants were (1.49±0.64) mm, [2.03(1.58, 2.40)] mm and (2.49°±1.12°), respectively. The average entry, exit and angle deviation of the navigation guided implant insertion group were (1.45±0.60) mm, (1.96±0.44) mm and (2.66±1.13°) respectively, while those of the free-hand group were (1.50±0.64) mm, (2.04±0.79) mm and (2.50°±1.13°) respectively. There was no significant difference between the two groups ( P>0.05). The average entry, exit and angle deviation of the group with length<47.5 mm were (1.42±0.60) mm, (2.13±0.60) mm and (2.61°±1.08°) respectively and those of the group with length ≥ 47.5 mm were (1.52±0.65) mm, (1.98±0.82) mm and (2.43°±1.14°) respectively. No significant difference was found between the two groups ( P>0.05). In proximal implant group, the average entry, exit and angle deviation were (1.55±0.69) mm, (2.05±0.92) mm and (2.48°±1.16 °) respectively while those of distal implant group were (1.43±0.57) mm, (2.01±0.57) mm and (2.49°±1.10°), respectively. No significant difference was detected between the two groups ( P>0.05). All zygomatic implants were placed uneventfully. There were no intra-operative complications, and post-operative reversible complications developed in 3 patients. Two zygomatic implants were lost and the overall zygomatic implant survival rate was 97.9% (94/96) within a follow-up of 6 months. Conclusions:Quad zygomatic implant placement can be achieved with high accuracy and predictable clinical outcome under guidance of a real-time navigation system.

Objective:To evaluate the effects of fluorinated porcine hydroxyapatite (FPHA) on guided bone regeneration of peri-implant buccal bone defects in canine mandible.Methods:Six male beagle dogs were randomly divided into two groups with different time points (4 weeks and 12 weeks after implants placement), with 3 dogs in each group. Bilateral mandibular second premolars, first molars, and second molars in each dog were extracted. The wounds were allowed to heal for 12 weeks. For each dog, four implant beds were prepared in each side and standardized peri-implant buccal bone defect was created at each implant site. After implants placement, the defect sites were randomly allocated in a split-mouth design to blank control group, deproteinized bovine bone mineral (DBBM), the porcine hydroxyapatite (PHA), FPHA and covered with collagen membranes. The animals were sacrificed 4 or 12 weeks after the surgery. Biopsies of the implant sites were obtained for micro-CT evaluation [bone volume fraction (BV/TV) and bone trabecular separation degree (Tb.Sp)] and histological analysis.Results:Micro-CT results showed that 4 weeks after implants placement, PHA, FPHA and DBBM successfully maintained the contour of alveolar ridge at the buccal aspect of the implants, while the contour of alveolar ridge collapsed in the blank control group. BV/TV in the FPHA group [(24.77±2.20) %] was significantly higher than that in the PHA group [(16.89±1.70)%] and DBBM group [(15.68±3.15)%] ( P<0.05). Tb.Sp in the FPHA group (0.70±0.07) was significantly lower than that in the DBBM group (1.03±0.19) ( P<0.05). Twelve weeks after implants placement, the alveolar ridge contour of the grafted sites in PHA, FPHA and DBBM group remained stable. The alveolar ridge of the blank control group was still collapsed. There was no significant difference in BV/TV and Tb.Sp between PHA group, FPHA group and DBBM group. The histomorphological analysis showed that 4 weeks after implants placement, in the central area of the defect, the amount and maturity of new bone (NB) around the material particles in FPHA group was higher than that in PHA group and DBBM group. Osseointegration could be observed between the NB and implant surface in all the four groups. Twelve weeks after implants placement, the material particles were surrounded by a large number of mature NB in PHA, FPHA and DBBM group. Conclusions:The incorporation of fluoride ion into PHA could effectively promote the repair of peri-implant bone defects in the early stage of guided bone regeneration.

Objective To investigate medication adherence and its influencing factors in community-based hypertensive patients in the Pearl River Delta of Guangdong Province, and lay the foundation for the development of targeted compliance interventions. Methods Between July 2015 and October 2016, a multi-stage cluster sampling method was used to conduct a community-based diagnostic survey in the Pearl River Delta region.A total of 1 829 community-based hypertension patients in this survey population were used to investigate medication adherence, the factors of which were derived through a multi-factor logistics regression analysis.Results The average medication-adherence score of hypertensive patients surveyed in this study was (4.6 ± 1.8), and patients with good medication adherence accounted for 62.82%(1 149/1 829).There were significant differences in medication adherence among patients according to their age, household registration types, marital status, level of education, employment status, medical payment methods,per capita monthly household income,drinking status,and family history of hypertension (P<0.05).Multivariate logistic regression analysis found that medication adherence was affected substantially by the type of household registration:local household types (OR= 0.537, 95% CI: 0.415-0.695); education level: college,bachelor and above (OR=2.139,95% CI:1.100-4.160); employment status: self-paying (OR=0.591, 95% CI: 0.376-0.930); and a family history of hypertension (OR= 1.279, 95% CI: 1.012-1.617).Conclusions It is necessary to pay more attention to medication adherence in patients with hypertension in communities.Given the influencing factors and characteristics illuminated by this study,it is suggested that various measures be taken to prevent and intervene in poor medication adherence, to improve the curative effect of hypertensive patients in communities.

The aim of this study was to investigate the effect of Paris saponin I (PS I) on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms. The proliferation of SGC7901 cells was monitored by the MTT cell viability assay, while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining. Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained cells. Western blotting was used to examine the expression of several cell cycle proteins, including cyclin B1 and Cdk1, and the apoptosis-regulated proteins Bcl-2, Bax, cytochrome c, procaspase-9, and procaspase-3. The MTT assay demonstrated that PS I could induce significant dose- and time-dependent inhibition of SGC7901 cell proliferation. Marked morphological changes, including condensation of chromatin, nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining. PSI treatment also resulted in the disruption of the cell cycle at G(2)/M and the induction of apoptosis. Following PSI treatment, the cell cycle-related proteins cyclin B1 and Cdk1 were down-regulated. Expression of the pro-apoptotic protein Bax was increased, while anti-apoptotic protein Bcl-2 decreased. PSI treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3. These data indicate that PS acts as an inhibitor of proli I feration in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis. PSI is a potential therapeutic agent against human gastric carcinoma.

The aim of this study was to investigate the effect of Paris saponin Ⅰ (PS Ⅰ ) on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms.The proliferation of SGC7901 cells was monitored by the MTT cell viability assay,while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining.Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained cells.Western blotting was used to examine the expression of several cell cycle proteins,including cyclin B1 and Cdkl,and the apoptosis-regulated proteins Bcl-2,Bax,cytochrome c,procaspase-9,and procaspase-3.The MTT assay demonstrated that PSⅠ could induce significant doseand time-dependent inhibition of SGC7901 cell proliferation.Marked morphological changes,including condensation of chromatin,nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining.PSⅠ treatment also resulted in the disruption of the cell cycle at G2/M and the induction of apoptosis.Following PSⅠ treatment,the cell cycle-related proteins cyclin B 1 and Cdk1 were downregulated.Expression of the pro-apoptotic protein Bax was increased,while anti-apoptotic protein Bcl-2decreased.PSⅠ treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3.These data indicate that PSⅠ acts as an inhibitor of proliferation in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.PSⅠ is a potential therapeutic agent against human gastric carcinoma.