The clinical internship is an important transitional period for humanistic spirit cultivation of the medical students.But in this period there are some problems exposed.For example,there is the lack of transitional link in management; the clinical instruction doctors lack educational consciousness or guidance ability,the medical students pay little attention to enhancing the individual humanistic spirit level and there is a gap between theory and practice of humanistic spirit for them.Strengthening training for students,attaching importance to training,selection and incentive of clinical instruction doctors and revising handbook of clinical internship will help to solve the problems.

Objective:To explore an ideal method for establishing a mouse model of chronic atrophic gastritis (CAG).Methods:CAG mouse models were established with five different modeling methods ( N-methyl- N′-nitro- N-nitrosoguanide (MNNG), sodium salicylate, sodium deoxycholate, Helicobacter pylori infection, and combinations of them) in BALB/c and C57 mice. The effect of each modeling method was evaluated by histological observation of gastric mucosa, plasma biochemical parameters, inflammatory response score, and the expression of anti-inflammatory factors. Results:The results of histological observation of gastric mucosa showed that all of the 5 methods could successfully establish CAG mouse models. In BALB/c mice, compared with the healthy control group, significant features of CAG accompanied with intestinal metaplasia was found in the model group established by combination of MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate. From the results of serological detection, compared with the normal control group, the mRNA expression levels of related anti-inflammatory factors interleukin-2, interleukin-10, interleukin-13 and growth differentiation factor-15 of each model group decreased, which indicated that the mice of each CAG model group had different degrees of inflammation. The results of plasma biochemical parameters indicated that plasma gastrin of each group decreased and the ratio of pepsinogen Ⅰ and pepsinogen Ⅱ significantly dropped. The above results demonstrated that in BLAB/c mice, MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate was better than other four modeling methods. For C57 mice, it was also found that simple chemical drug mutagenesis and Helicobacter pylori replication method both could successfully establish CAG models. No matter from pathological observation, relative expression of anti-inflammatory factors and analysis of plasma biochemical parameters, the effects of combination of the two methods was better. Conclusion:The CAG mouse model established by MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate can provide a certain reference for the establishment and application of mouse model in CAG experiments in the future for pharmacological research.

Objective: To investigate the prognostic effect of neonatal morbidities on poor outcomes at 12 months corrected age in very low birth weight (VLBW) premature infants . Method: From November 2013 to October 2014, a multi-center retrospective study was conducted in 8 tertiary Maternal and Children′s hospitals in Guangdong, Hunan and Fujian. The premature infants survived to a postmenstrual age (PMA) of 36 weeks with birth weight less than 1 500 g and without congenital diseases were included, and divided into two groups according to poor outcomes. The birth weight, gestational age, morbidities and poor outcomes (death, cerebral palsy, cognitive delay, et al) were recorded. Data were analyzed with Chi-square test to investigate the relationship between morbidities and poor outcomes. And the predictive effect of the top three morbidities were analyzed by Logistic regression analysis. Result: Total of 834 VLBW premature infants (473 boys and 361 girls) finished the follow-up, whose average gestational age and birth weight were (30.6±1.8) weeks and (1 189±159)g. The incidences of BPD, severe ROP, NEC, brain injury and sepsis were 207 (24.8%), 119 (14.3%), 58 (7.0%), 281 (33.7%) and 124 (14.9%), respectively. There were significant differences between the two groups in the incidences of BPD, severe ROP, NEC, brain injury and sepsis(χ²=42.10, 47.20, 4.81, 44.28, 18.63, all P<0.01), which had significant correlation with poor outcomes at 12 months corrected age. The three top morbidities were severe ROP, BPD and brain injury(OR=3.82, 2.90, 2.80). Combined morbidities with BPD, severe ROP and brain injury correlated with higher risk of poor outcomes (one morbidity, OR=3.14, β=1.15; two morbidities, OR=7.31, β=1.99; three morbidities, OR=22.41, β=3.11; all P<0.01). Conclusion BPD, severe ROP, NEC, brain injury and sepsis were the risk factors of poor outcomes at 12 months corrected age in VLBW infants. And the more combined morbidities with severe ROP, BPD and brain injury, the higher risk of poor outcomes in this population. Trial registration Clinical Trails, NCT03104946.

Objective To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule(XFC)on interleukin(IL)-1β-induced impairment of chondrocytes.Methods XFC-medicated serum was collected from SD rats with XFC gavage,and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry.Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2.In cultured human chondrocytes induced with IL-1β,the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum,alone or in combination,on expression levels of IL-1β,tumor necrosis factor-α(TNF-α),IL-4,and IL-10 were examined with ELISA,and the changes in the expressions of collagen type Ⅱ alpha 1(COL2A1),matrix metalloproteinase 13(MMP13),adisintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR,Western blotting,and immunofluorescence assay.Results In cultured human chondrocytes,treatment with IL-1β significantly decreased the cell viability,increased cell apoptosis rate,lowered miR-502-5p,IL-4,IL-10,and COL2A1 expressions,and enhanced IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 expressions(P<0.05),and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20％(P<0.05).Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 and lowered expressions of miR-502-5p,IL-4,IL-10,and COL2A1,and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor.Conclusion XFC can inhibit IL-1β-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.

Objective To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule(XFC)on interleukin(IL)-1β-induced impairment of chondrocytes.Methods XFC-medicated serum was collected from SD rats with XFC gavage,and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry.Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2.In cultured human chondrocytes induced with IL-1β,the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum,alone or in combination,on expression levels of IL-1β,tumor necrosis factor-α(TNF-α),IL-4,and IL-10 were examined with ELISA,and the changes in the expressions of collagen type Ⅱ alpha 1(COL2A1),matrix metalloproteinase 13(MMP13),adisintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR,Western blotting,and immunofluorescence assay.Results In cultured human chondrocytes,treatment with IL-1β significantly decreased the cell viability,increased cell apoptosis rate,lowered miR-502-5p,IL-4,IL-10,and COL2A1 expressions,and enhanced IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 expressions(P<0.05),and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20％(P<0.05).Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 and lowered expressions of miR-502-5p,IL-4,IL-10,and COL2A1,and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor.Conclusion XFC can inhibit IL-1β-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.

“Deficiency cause， cold accumulation， and qi stagnation” originates from Essentials from the Golden Cabinet （《金匮要略》）， which is a guiding principle for the pathogenesis of women's diseases， pioneering the differentiation and treatment of women's diseases based on patterns， and having a profound influence on future generations. Following the classical principles and simplifying the complexities， this paper explored the pathogenesis and mechanism of polycystic ovary syndrome （PCOS） from the perspective of “deficiency cause， cold accumulation， and qi stagnation”， and believed that depletion of essence and blood， long-term accumulation of internal cold， and qi constraint and blood stasis are the causes of PCOS， with depletion of essence and blood， and lack of nourishment of zang-fu （脏腑） organs as the root， and cold pathogen invasion， qi constraint and blood stasis as the branch. The main treatment principle is “treating deficiency with supplementation”， and dispelling pathogen while reinforcing healthy qi， along with “treatment of cold by warming” and “treatment of stagnation by dispersing”. This is of great significance for the treatment of polycystic ovary syndrome. Clinically， these methods can be used flexibly to guide treatment and formula selection for PCOS， with the goal of harmonizing qi and blood and regulating menstruation.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.