Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P＜0.001,P＜0.001,P＜0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P＜0.001,P＜0.001)and invasion(all P＜0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P＜0.001,P＜0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P＜0.001,P＜0.001)and reactive oxygen species accumula-tion(all P＜0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P＜0.001,P＜0.001),heme oxygenase 1(P=0.015,P＜0.001,P＜0.001),and Bc12(P=0.039,P＜0.001,P＜0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P＜0.001)and up-regulated Bax expression(both P＜0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P＜0.001),apoptosis(P＜0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Cirrhotic portal hypertension (CPH) is a manifestation of decompensated liver cirrhosis, with ascites, portal collateral circulation formation, hypersplenism and splenomegaly as the typical clinical symptoms. In recent years, the incidence of CPH has been increasing year by year, and the treatment of CPH has gradually become a hot issue in medical research. In order to further explore the diagnosis and treatment scheme of CPH. We briefly describe the pathophysiological mechanism and diagnosis of CPH, and the current situation of CPH treatment and the new progress of internal and external treatment were reviewed.

Objective:To master the changes of Kashin-Beck disease and the examination and acceptance in Zhalantun City, and to provide scientific basis for formulating prevention and control strategies of Kashin-Beck disease.Methods:From 2016 to 2017, in each county under the jurisdiction of Zhalantun City, 5 townships affected by the disease were selected, 3 villages were selected from each township, and the prevalence of Kashin-Beck disease of all residential children aged 7 to 12 years who lived in the villages for more than 6 months were investigated. The clinical and X-ray diagnosis were performed according to the "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010) standard, and the prevalence of Kashin-Beck disease in children aged 7 to 12 years in Zhalantun City in 2016 and 2017 were compared. In accordance with the "Key Endemic Disease Control and Elimination Evaluation Measures" ([2014]79), the condition of Kashin-Beck disease and the implementation of its prevention and control measures was assessed.Results:From 2016 to 2017, 1 697 children aged 7 to 12 years were examined, there were no clinical cases of Kashin-Beck disease and 11 cases of X-ray positive changes. Among them, 844 children were examined in 2016, the positive rate of X-ray was 0.24% (2/844), the positive rate of metaphyseal was 0.24% (2/844), and no positive changes of extremities and triad were detected. A total of 853 children were examined in 2017, the positive rate of X-ray was 1.06% (9/853), the positive rate of metaphyseal was 1.06% (9/853), and no positive changes of extremities and triad were detected. The positive rate of X-ray and metaphyseal of Kashin-Beck disease in children aged 7 - 12 years in 2017 were higher than those in 2016 (χ 2 = 4.409, 4.409, P < 0.05). All surveyed villages had reached the national elimination standard (no clinical cases for children aged 7 - 12 years, X-ray positive rate ≤3% and no cases of hand bone end changes); the organization management scores of Kashin-Beck disease prevention and treatment in Zhalantun City in 2016 and 2017 were 88 points, reaching the qualified standard ( > 85 points). Conclusion:The condition of Kashin-Beck disease in Zhalantun City has reached the standard of elimination, which lays a foundation for further comprehensive elimination of Kaschin-Beck disease in Hulunbuir City.

Objective To explore the value of CT quantitative analysis in differentiating lepidicGpredominant adenocarcinoma (LPA)from invasive nonGlepidicGpredominant adenocarcinoma (INV)manifested as subsolid nodules (SSN).Methods A total of patients with lung adenocarcinoma manifested as SSNs on CT images were divided into LPA group and INV group according to their pathological results.Total volume,solid volume,solid volume percentage,total mass,solid mass,solid mass percentage and threeGdimensional mean CT value of the nodules were calculated after segmenting pulmonary nodules by a 3DGCT segmentation software,meanwhile the oneGdimensional mean CT value and maximal diameter were manually measured.SPSS 22.0 software was used for statistical analysis. Results Solid volume (0.1 6 ±0.3 6 cm3 vs 1.2 6 ±2.1 7 cm3 ,P＜0.00 1),solid volume percentage (4.7 9 ±5.40% vs 2 6.3 3 ± 1 5.6 3%, P＜0.001),total mass (1 180.64±1 751.46 mg vs 2 386.59±3 224.54 mg,P＝0.010),solid mass (151.64±337.53 mg vs 1 257.34± 2 220.9 2 mg,P＜0.00 1 ),solid mass percentage (7.9 8 ± 8.5 8% vs 3 7.2 3 ± 1 8.83%,P＜0.00 1 ),threeGdimensional mean CT value (－492.26±71.21 HU vs －350.73±94.52 HU,P＜0.001 )and oneGdimensional mean CT value (－472.29 ± 1 12.46 HU vs －282.02 ± 1 5 9.13 HU,P＜0.001)in LPA group were found significantly lower than those in INV group.There were no significant differences in the maximal diameter and total volume between LPA group and INV group.Solid volume percentage and solid mass percentage were selected according to stepwise discriminant analysis.The accuracy of Bayes modes by using substitution method and cross validation method were 84.2% and 83.3%,respectively.Conclusion Solid volume percentage and solid mass percentage were important parameters for differentiating LPA from INV.Quantitative analysis of SSN was very helpful to preoperatively evaluate the subtypes and prognosis of lung adenocarcinoma by using 3DGCT segmentation technique.

Objective To investigate the clinical, radiological and pathological characteristics, treatment and prognosis of pulmonary benign metastasizing leiomyoma (PBML). Methods The clinical and image data of 6 patients with PBML confirmed by pathology from October 2012 to December 2016 were retrospectively analyzed, and the related literature was reviewed. Results Six cases were female, age was from 32 to 55 (43.80 ± 7.17) years. Two cases were found by physical examination, 2 cases had chest distress and asthma, 1 case had chest pain, and 1 case had hemoptysis. Pulmonary abnormalities were detected between 1 month and 15 years after uterine myomectomy. Chest CT showed that multiple lung nodules or masses were observed in 5 patients, among which random distribution was in 3 cases, diffuse military nodule pattern was in 2 cases, and single mass combined with primary lung adenocarcinoma was in 1 case. Fluorine-18-fluorodeoxyglucose positron emission tomography/CT (18F- FDG PET/CT) of one patient showed no obvious uptake of the maximum standardized uptake value. All patients were confirmed histologically with CT guided lung biopsy (2 cases), thoracoscopic lung biopsy (2 cases), and thoracoscopic lobectomy with wedge resection (2 cases). Tumor cells revealed the characteristics of smooth muscle cell differentiation. Immunohistochemistry showed strong positive express of Desmin, SMA smooth muscle specific markers, estrogen receptor and progesterone receptor. Three patients were treated with oral tamoxifen anti estrogen therapy with follow-up from 5 months to 5 years. Four cases had a good prognosis, and 2 cases were lost in follow-up. Conclusions PBML is a rare disease that is prone to occur in women of childbearing age. The clinical symptoms are atypical. Imaging examination and pathology are necessary for diagnosis. Surgery combined with endocrine therapy is effective.

OBJECTIVE:To reduce drug repercussion of outpatient pharmacy,and to promote safe drug use.METHODS:By quality control circle (QCC),the data of drug repercussion were selected from outpatient pharmacy of our hospital in Sept.2016.The drug repercussion reason check list was designed to master the situation of drug repercussion in outpatient department,formulate improvement measures and confirm effect through field inspection.The case number of drug repercussion and the improvement of circle members' ability were compared one month before and after QCC (Mar.2017).Finally,the effects of QCC were evaluated.RESULTS:Referring to the reasons for the repercussion of adjunct drugs for inspection and the repercussion of unsuitable drug use in our hospital,those problems were improved by formulating manual for drug use examination project,optimizing and examining drug delivery process in the department,etc.The case number of drug repercussion in outpatient pharmacy decreased from 31 cases per month to 12 cases per month;the rate of goal achievement was 119％;the rate of improvement was 61％.The ability of QCC members to solve problems and the ability to use QCC skills were increased positively.CONCLUSIONS:The development of QCC activity in our hospital reduces case number of drug repercussion and optimizes drug delivery process in outpatient pharmacy,and promotes safe drug use.

OBJECTIVETo observe the clinical effects of acupuncture combined with auricular point sticking based on the western medication for post stroke depression (PSD).

METHODSSixty patients with PSD were randomly assigned into an acupuncture plus auricular application group (a combination group) and a medication group, 30 cases in each one. 20 mg paroxetine hydrochloride was prescribed orally in the medication group, once a day for continuous 8 weeks. Based on the above treatment, 30-minute acupuncture was used in the combination group for 8 weeks at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7), Neiguan (PC 6), Taichong (LR 3), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Fenglong (ST 40), once the other day and three times a week. Auricular point sticking therapy for 8 weeks was applied at shenmen (TF), pizhixia (AT), xin (CO), and gan (CO), with pressing 3 times a day and once 3-5 days. The total score and each factor scores of Hamilton's depression scale (HAMD) were observed in the two groups before and after treatment, and Asberg's antidepressant side-effect rating scale (SERS) and clinical effect were evaluated.

RESULTSAfter treatment, the total HAMD scores of the two groups decreased compared with those before treatment (both<0.05), with better effect in the combination group (<0.05). The scores of the combination group after treatment were lower than those in the medication group, including the anxiety/somatization factor, sleep disturbance factor, hopelessness factor (all<0.05). The total effective rate of the combination group was 86.7% (26/30), which was better than 66.7% (20/30) of the medication group (<0.05). The SERS score of the combination group was lower than that of the medication group (<0.05).

CONCLUSIONSAcupuncture combined with auricular point sticking can improve the clinical symptoms and are effective and safe for PSD.