Objective To investigate the effects of Larotrectinib(Lar)on autophagy,proliferation and migration of colon cancer cells and its molecular mechanism.Methods Human colon cancer cell lines COLO 205,HCT 116 and human colonic epithelial cell line CP-H040 were treated with different concentrations of Lar(0,100,200,400,800,1600 and 3 200 nmol/L).CCK-8 assay was used to detect the cell viability of COLO 205,HCT 116 and CP-H040 cells.COLO 205 and HCT 116 cells were randomly divided into control group(Con group),Lar group,Chloroquine group(CQ group)and Lar+CQ group.Cell invasion was detected by Transwell assay.Scratch test was used to detect cell migration ability.Ki67 immunofluorescence staining was used to detect cell proliferation.Real-time quantitative polymerase chain reaction was used to detect the mRNA expression of epithelial-mesenchymal transition related markers in colon cancer cells.Autophagy was detected by adenovirus transfection experiment and transmission electron microscopy.Western blot was used to detect the expression of adenosine monophosphate-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR)pathway related proteins.Results Lar significantly inhibited the viability of COLO 205 and HCT 116 cells in a concentration-dependent manner(F=355.181,403.758,all P<0.001).Compared with the Con group,the number of invasive cells,Ki67 fluorescence intensity and scratch healing rate of colon cancer cells in the Lar group were decreased,the expression of E-cadherin mRNA was increased,the expressions of Vimentin and MMP2 mRNA were decreased,the formation of autophagosomes and autophagic flow,the ratio of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ and p-AMPK/AMPK were increased,and the expression of p62 protein and p-mtor/mTOR ratio were decreased,with significant differences(t=4.399～54.214,all P<0.05).Compared with the Lar group,the formation of autophagosome was decreased and the expression of p62 protein was increased in the Lar+CQ group,and the difference was statistically significant(t=2.755～24.784,all P<0.05).Conclusion Lar can inhibit the proliferation and migration of colon cancer cells,and the underlying mechanism is related to activation of the AMPK/mTOR signaling pathway and thus inducts autophagy.

Obesity contributes to reduced fertility, infertility and adverse maternal and infant outcomes through multiple mechanisms. Individuals with obesity encounter numerous impediments during fertility treatments and subsequent pregnancy, leading to intensified physical, psychological, and socio-economic burdens. Given the recent progress in research and the expansion of treatment modalities, there is an imperative need to refine the diagnostic and therapeutic frameworks for obese patients with infertility through a multidisciplinary approach. The Reproductive Medicine Specialized Committee of the Chinese Medical Doctor Association (CMDA) has established a multidisciplinary team of experts to develop an evidence-based guideline. This guideline's development will adhere to both national and international standards for guideline development and reporting. This proposal mainly describes the significance and purpose of guideline development, the method of evidence retrieval and quality assessment, the process of guideline development, and the plan for publication, implementation and dissemination of the guideline.

Obesity contributes to reduced fertility, infertility and adverse maternal and infant outcomes through multiple mechanisms. Individuals with obesity encounter numerous impediments during fertility treatments and subsequent pregnancy, leading to intensified physical, psychological, and socio-economic burdens. Given the recent progress in research and the expansion of treatment modalities, there is an imperative need to refine the diagnostic and therapeutic frameworks for obese patients with infertility through a multidisciplinary approach. The Reproductive Medicine Specialized Committee of the Chinese Medical Doctor Association (CMDA) has established a multidisciplinary team of experts to develop an evidence-based guideline. This guideline's development will adhere to both national and international standards for guideline development and reporting. This proposal mainly describes the significance and purpose of guideline development, the method of evidence retrieval and quality assessment, the process of guideline development, and the plan for publication, implementation and dissemination of the guideline.

Objective:To explore the application and potential optimization of the collaborative and competitive learning model in the Health Education course. Methods:Undergraduate medical students participating in Health Education course practice tasks were selected to conduct discussions and reach consensus according to research objectives based on the e fast anonymous consensus-forming tool (eFAST). The meeting records were analyzed for theme identification using the keyword classification method. Results:Nine medical students participated in eFAST discussions. The students considered the following five aspects as the most important for undertaking Health Education course practice tasks using the collaborative and competitive learning model: timely communication, problem evaluation, report content enrichment, reasonable task allocation within groups, and task topic selection by group members together. They also proposed suggestions on improvement of the assessment method, including teacher involvement in scoring, intra-group scoring based on inter-group scoring, all students participating in inter-group scoring, and using mobile applications for scoring and summarization. Conclusions:The collaborative and competitive learning model can be used in the teaching of Health Education, but further optimization is needed in course task design, implementation, reporting, and assessment.

Objective:To explore the efficacy and safety of treating advanced esophageal cancer by implanting the common stent and the radioactive 125I particle stent with endoscope. Methods:The clinical data of patients with advanced esophageal cancer admitted to Jingbian County People's Hospital of Shaanxi Province, the First Affiliated Hospital of Xi'an Medical University, Xijing Hospital of Digestive Diseases of Air Force Medical University and the First Hospital of Yulin of Shaanxi Province from December 2014 to December 2020 were retrospectively analyzed. Patients were divided into common stent group ( n=66) and radioactive particle stent group ( n=34) according to different stent types. The postoperative complications, Karnofsky performance status (KPS) score, dysphagia score, restenosis rate and quality of life were compared between the two groups. Results:The incidences of postoperative retrosternal pain in the common stent group and the radioactive particle stent group were 65.2% (43/66) and 47.1% (16/34) respectively. The incidences of pharyngeal pain and hoarseness were 12.1% (8/66) and 5.9% (2/34) . The incidences of abdominal pain were 9.1% (6/66) and 2.9% (1/34) . The incidences of errhysis were 3.0% (2/66) and 2.9% (1/34) . The incidences of vomiting and nausea were 7.6% (5/66) and 5.9% (2/34) respectively. There were no statistically significant differences between the two groups ( χ2=3.04, P=0.081; χ2=0.40, P=0.527; χ2=0.53, P=0.467; χ2<0.01, P>0.999; χ2<0.01, P>0.999) . In the two groups, KPS scores in the first, second, third and sixth month after operation were higher than those before operation (all P<0.05) . KPS scores of the radioactive particle stent group in the second, third and sixth month were significantly higher than those of the common stent group [ (89.73±7.84) points vs. (82.37±7.42) points, t=4.62, P<0.001; (93.63±8.13) points vs. (88.33±7.28) points, t=3.74, P<0.001; (92.78±6.26) points vs. (87.28±8.73) points, t=3.77, P<0.001]. The dysphagia scores of patients in the two groups in the first, second, third and sixth month were lower than those before operation (all P<0.05) . The dysphagia scores of the radioactive particle stent group in the third and sixth month after operation were significantly lower than those of the common stent group [ (0.68±0.12) points vs. (2.33±0.32) points, t=26.20, P<0.001; (0.82±0.22) points vs. (2.67±0.24) points, t=36.92, P<0.001]. In the third month after operation, the restenosis rate of the radioactive particle stent group was significantly lower than that of the common stent group [5.88% (2/34) vs. 42.4% (28/66) , χ2 =14.27, P<0.001]. The scores of QLQ-C30 and OES-18 scales in the first, second, third and sixth month after operation were lower than those before operation (all P<0.05) . The scores of QLQ-30 scale in the radioactive particle stent group in the second, third and sixth month were significantly lower than those in the common stent group [ (19.12±3.02) points vs. (21.22±2.87) points, t=3.39, P=0.001; (15.04±1.68) points vs. (20.43±2.23) points, t=12.39, P<0.001; (14.38±2.18) points vs. (19.77±3.67) points, t=9.20, P<0.001]. The scores of OES-18 scale in the radioactive particle stent group were also significantly lower than those in the common stent group [ (17.13±2.07) points vs. (20.64±2.11) points, t=7.95, P<0.001; (15.22±1.88) points vs. (19.24±1.76) points, t=10.62, P<0.001; (14.74±2.36) points vs. (18.53±3.27) points, t=6.01, P<0.001]. Conclusion:The radioactive particle stent can improve the quality of life of patients with advanced esophageal cancer with esophageal stenosis, so as to improve dysphagia and reduce the restenosis rate after operation. However, whether it is obviously superior to common stent in prolonging survival time and reducing complications needs to be further confirmed by a multicenter, prospective, large-sample randomized controlled study.

By searching for the Canadian Licensed Natural Health Products Database, (LNHPD), this paper analyzed the characteristics and current status of 92 Chinese patent medicines successfully registered and listed in Canada, and found that the enterprises of successfully registered enterprises are mainly located in areas with better development condition of Traditional Chinese Medicine (TCM) such as Beijing, Guangdong and Tianjin; The successfully registered Chinese patent medicines include 64 kinds of single medicine or medicine with single active ingredient (69.6%) and 28 kinds of compound medicine (30.4%), the forms of the dosage are mainly tablets and capsules, which have the characteristics of accuracy in dosage and stable physicochemical properties. There are also granules, solutions, powders and other dosage forms, which can be preserved for a long time and have low requirements on technic and environment. These Chinese patent medicines are mainly used to treat respiratory and circulatory system diseases, some are used to treat urogenital and digestive system diseases, and few are used to treat difficuilt diseases like tumors, diabetes. There are some other health care products. It is suggested to strengthen the connection between domestic standards of TCM registration and international standards, and promote the scientific and technological capacity of relevant enterprises, and encourage enterprises to strengthen international registration of advantageous products, so as to accelerate the speed of international development of TCM in China.

The innovative healthcare plus elderly care model is a major move for China to combat population aging. Given its initial success, there still exist challenges in the systems and economic conditions, for which family doctors can play a key role as population health " gatekeepers" . From the perspective of supply-side reform, this paper analyzed the current progress and challenges in this regard, and proposed a win-win mode. This mode combined the advantages of the family doctor system to optimize the community-based healthcare and elderly care as well as aging care resources.Family doctors are centered to build a community elderly care supply mode, to promote mutual development of primary medical institutions and the elderly-healthcare sector in China.

Objective:To compare the fracture resistance of roots of mandibular premolar with different apical preparation diameters.Methods:Sixty single-rooted single canal permanent mandibular premolar teeth extracted newly for orthodontic reason without immatureness,fracture or cracks were selected,with a curvature less than 10°,and internal length:short diameter of less than 2 at a level 5 mm from the apex.All the teeth were decoronated,leaving roots 13 mm in length.The initial apical file size for the teeth was ≤ 15#.The roots were assigned to 6 groups based on weights with random block design.Group A:blank control group,no instrumentation was performed.Groups B-F:the master apical file (MAF) was 40#,45#,50#,55# and 60#,respectively.In the five experimental groups the roots were instrumented using hand files with step-back technique at 1 mm increments,resulting in a taper of 0.05.The irrigant used was distilled water.After mounted in acrylic resin,all the teeth were subject to vertical loading using an Instron testing machine until fractured.The occurrence of fractures was detected when the applied load suddenly decreased.The fracture load values and fracture modes were recorded.Oneway ANOVA and post-hoc Tukey test were used to determine the difference of fracture load values between the groups (P ＜ 0.05).Chi-square tests were used to compare the modes of root fracture.Results:Five experimental groups exhibited lower fracture load values than that of control group [(1 444 ± 155) N].The mean fracture load values for roots instrumented to an apical diameter of 50# [(1 027 ± 128) N],55# [(994 ± 150) N] and 60# [(983 ± 166) N] were significantly lower than that of control group and 40# group [(1 339 ± 131) N] and 45# [(1 287 ± 144) N] (P ＜0.05).Buccal-lingual fracture,mesio-distal fracture and compound fracture occurred 55％,13％ and 32％,respectively.No difference of fracture mode was detected in the six groups.Conclusion:The fracture resistance reduced significantly when the roots were instrumented to an apical diameter of 50# or larger.

Objective To study absorption characteristic of dioscin from Dioscorea nipponica Makino extract in rat intestine.Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC was used to determine the concentrations of dioscin.The effects of different intestinal segments,drug concentration and P-glycoprotein (P-gp) inhibitor on intestinal absorption were investigated.Results Dioscin could be absorbed in the whole intestine,the absorption rate constant (Ka) and the apparent coefficient (Papp) of dioscin decreased following the sequence of ileum > duodenum =jejunum > colon.Absorption parameters of dioscin had no significant difference at different concentrations (40,80,120 mg·L-1).There were significant differences in Ka and Papp values between P-gp inhibitor group and no P-gp inhibitor group(P<0.05).Conclusion The saturate phenomena was not observed under the test range of drug concentration,and the absorption mechanism may be passive diffusion transport.Dioscin in Dioscorea nipponica Makino extract may be the substrate of P-gp.

Objective To investigate changes and the significance of Th17/Treg immune imbalance in secondary systemic infection in patients with severeacute pancreatitis.Methods We selected 21 patients with severe acute pancreatitis and secondary systemic infection (infection group),25 patients with severe alone (non-infection group),20 healthy cases undergoing annual health checkup (control group) in this study.The expression levels of Th17/Treg cells and related cytokines were compared between groups.Results There were significant differences in mortality rate and duration of ICU stay between infection group and non-infection group [23.8％ vs.4.0％,(11.3±3.4) d vs.(7.5±2.8) d,x2=3.949,t=2.890,P=0.047 and0.045].The percentages of Th17 cell andTreg cell,Th17/Treg ratio,mRNA expressions of IL-6,IL-17,IL-23,TGF-β and orphan receptor γt were higher in infection and non infection groups than in control group [(26.4 ± 1.2) ％,(12.8 ± 0.9)％ vs.(3.1±0.8) ％;(6.7±1.6)％,(4.2±1.3)％ vs.(1.3±0.4)％;(4.3±1.0)％,(3.2±1.1)％ vs.(2.4±0.9)％;(7.1±0.8)ng/L,(5.3±0.7)ng/L vs.(0.2±0.1)ng/L;(22.9±2.4)ng/L,(15.6±2.8)ng/L vs.(10.3± 1.5)ng/L;(15.7±2.1)ng/L,(10.2± 1.5)ng/L vs.(8.3± 1.4)ng/L;(23.6±2.2)ng/L,(16.3±1.7)ng/L vs.(11.6±1.1)ng/L;(0.052±0.014),(0.035± 0.010) vs.(0.004±0.001);F=15.761,55.745,9.437,102.788,21.038,16.239,36.957,23.924,respectively,P=0.555,0.000,0.014,0.000,0.002,0.004,0.000,0.000].The mRNA expressions of IL-10 and Foxp3-T were lower in infection and non-infection groups than in control group [(6.4±1.1)ng/L,(10.5 ± 2.1) ng/L vs.(15.4±2.0)ng/L;(0.005±0.001),(0.020±0.007) vs.(0.032±0.009),F=18.995 and 20.608,P=0.003 and 0.002].Conclusions The secondary infection can aggravate the Th17 / Treg immune imbalance in patients with severe acute pancreatitis,and extend the ICU hospitalization days.