Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Objective To establish a fast,stable,and sensitive zebrafish model of osteoporosis(OP)using different method.Methods OP models were induced by iron overload or prednisolone(Pred),and bone formation and mortality were observed.The groups were divided into:Control group,model group(include FAC group and Pred group),and positive control group(AC group).Ammonium ferric citrate was used as the model drug in the iron-overload induction method.For the Pred induction models,the modeling time for the Pred-3 days post-fertilization(dpf)method was 3～9 dpf,the modeling time for the Pred-5 dpf method was 5～10 dpf,and Pred was administered from 3 dpf and removed from 7～9 dpf for the Pred withdrawal method.To compare the anti-osteoporosis(OP)effects of commonly used drugs such as Alfacalcidol(AC),Calcitriol(CA),and Alendronate(AL),it's important to select a stable and sensitive positive control drug and to further optimize different staining methods and conditions.Results There was no significant effect of ammonium ferric citrate 500 μg/mL on bone formation.Bone formation and the length of the first vertebra were significantly decreased in the Pred group induced by Pred-3 dpf compared with those in the control group(P＜0.01,P＜0.05),but zebrafish mortality was higher.There was no significant difference between the Pred-5 dpf method,but bone formation was significantly reduced in the Pred withdrawal group(P＜0.01),with no mortality.Alfacalcidol,calcitriol,and alendronate all had anti-OP effects,with CA having the most sensitive and stable anti-OP effect.Alizarin red staining showed that the optimal dye parameters were 0.02%concentration for dyeing 2 h,with washing in 0.5%KOH and glycerol under the conditions of a 3∶1 ratio for 3 h followed by a 1∶1 ratio for 14 h.The result of staining showed that calcein was more sensitive for staining bone nodes and ARS staining was more sensitive for staining the first vertebra.Conclusions The Pred withdrawal method can be used to establish a rapid,stable,and sensitive OP model in zebrafish as a reliable model for studying OP.

Objective:Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal disease in the emergency department. Identifying low-risk patients suitable for outpatient treatment is the focus of clinical and research. A simple predictive model was developed to identify patients with UGIB who could safely avoid hospitalization, thus providing a feasible basis for triage by emergency physicians.Methods:A retrospective cohort study was conducted on patients with UGIB treated at Zhongda Hospital Southeast University from January 2015 to December 2020. Baseline demographic data and clinical parameters at the initial presentation were recorded. Multivariate logistic regression model was performed to identify predictors of safe discharge.Results:Six hundred and twelve patients (45.9%) were not safely discharged. There were significant differences in age, Charlson comorbidity index, systolic blood pressure, pulse rate, hemoglobin, albumin, blood urea nitrogen, creatinine and international normalized ratio between the safe discharge group and the non-safe discharge group ( P<0.05). Using multivariate logistic regression analysis, a total of 7 variables were included in the clinical prediction model of UGIB risk stratification: Charlson comorbidity index > 2, systolic blood pressure < 90 mmHg, hemoglobin < 10 g/dL, blood urea nitrogen ≥6.5 mmol/L, albumin <30 g/L, pulse ≥100 beats/min and international normalized ratio ≥1.5. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting unsafe discharge were 98.37%, 24.10%, 52.3%, and 94.6%, respectively, with the best cutoff value ≥1. The area under the receiver operating characteristic (AUROC) curve was 0.822, which was significantly higher than Glasgow Blatchford score (GBS) 0.786 (95% CI: 0.752-0.820, P< 0.01) and AIMS65 0.676 (95% CI: 0.638-0.714, P< 0.01). Conclusions:The predictive model has a reliable predictive value, which can provide references for emergency medical staff to triage patients with UGIB, thereby reducing medical expenses and having certain social and economic benefits.

Objective To investigate effect of the venom peptide liquor on adjunctive arthritis (AA) in mice .Methods The male Kunming mice were randomly divided into 6 groups ,named as the control group ,model group ,positive control group(1 mg/kg dex-amethason) ,wine group(10 mL/kg) ,low dosage of venom peptide liquor group(8 .3 mL/kg) and high dosage of venom peptide liq-uor group(33 .2 mL/kg);the right toes ,ankle diameter and whole body weight were measured at 7-day intervals ;the spleen index , serum level of circulating immune complexes(CIC) were determined after the thirty-fourth day when the mice was put to death .Re-sults The level of CIC in AA mice decreased significantly (P<0 .05) ,the decrease of spleen index and the reduction of toe and an-kle swelling in the low dose group were significant(P<0 .01) .Conclusion The venom peptide liquor exhibited apparent inhibitory effect on AA in mice .

Objective To evaluate the efficacy of parecoxib sodium combined with epidural morphine for multi-mode analgesia after gynecologic operation in a randomized,double-blind,placebo-controlled,multicenter,prospective study.Methods Two hundred and forty ASA Ⅰ or Ⅱ female patients,aged 18-64 yr,scheduled for elective gynecologic operation under combined spinal-epidural anesthesia,were randomly divided into 2 groups:control group (group C) and parecoxib sodium group (group P).Normal saline 2 ml or parecoxib sodium 40 mg was injected intravenously 30 min before the start of operation and was injected again 12,24 and 36 h later.Patient-controlled epidural analgesia with morphine was used for postoperative analgesia in both groups.VAS score was maintained ≤ 3 after operation.When VAS score ＞ 4,tramadol was injected as rescue analgesic.The number of attempts,the number of successfully delivered doses,the amount of morphine used,requirement for the rescue analgesic within 48 h after operation and patient' s satisfaction at 48 h after operation were recorded.Blood samples were taken at 48 h after operation for determination of serum creatinine (Cr),blood urea nitrogen (BUN),alanine aminotransferase (ALT),aspartate transaminase (AST),total bilirubin levels and coagulation function.The abnormality in the parameters was recorded.The adverse effects (nausea,vomiting,pruritus) and recovery of gastrointestinal function were recorded within 48 h after operation.Results Of the 225 patients who completed the study,there was 112 cases in group P and 113 cases in group C.Compared with group C,the number of attempts,the number of successfully delivered doses,amount of morphine used and requirement for the rescue analgesic were significantly decreased,the satisfaction score was increased and the incidence of postoperative vomiting was decreased in group P (P ＜ 0.05 or 0.01).There was no significant difference in the incidence of nausea and pruritus,recovery of gastrointestinal function,and abnormality in the parameters of liver and kidney functions and coagulation function between the two groups (P ＞ 0.05).Conclusion Parecoxib sodium combined with epidural morphine can be safely and effectively used for multi-mode analgesia after gynecologic operation and reduce the requirement for morphine and side effects of morphine.

AIM: To investigate the effect of Sini decoction (SND)on the ultrastructure of small intestinal epithelial cells in rats with intestinal ischemia-reperfusion. METHODS: Thirty-two Sprague-Dawley rats of both sexes were randomly divided into 4 groups: (1) Control group in which sham operation was performed; (2) Model group in which intestinal I/R was produced by clamping super mesenteric artery(SMA) for 1 hour and declamping SMA for 3 hours; (3) SND1 group in which SD (0.6 g/200 g rat) was given via stomach tube 3 d before intestinal I/R; (4) SND2 group in which SD (1.2 g/200 g rat)was given via stomach tube 3 d before intestinal I/R. A strip of small intestine was taken from distal end of ileum for electron microscopic examination. The two-dimensional structural parameters and three-dimensional structural parameters of mitochondria were calculated. RESULTS: (1)Morphological changes of small intestine: In control group, epithelial cells were orderly arranged, with normal mitochondria and intestinal villi. In model group, the gaps between epithelial cells widened. There were a lot of apoptotic cells. Microvilli were short and swelled. Mitochondria were swelled obviously with broken ridges. Endoplasmatic reticulum was severely dilated. In SND1 and SND2 groups, microvilli and epithelial cells were orderly arranged relatively, mitochondria was slightly swelled. (2) Structural parameters of mitochondria: In model group, there were the least mitochondria and the swelling of mitochondria was severe. In SND1 and SND2 groups, the mitochondria was more than that of model group and the swelling were slight. CONCLUSION: Sini decoction can protect small intestine from ischemia-reperfusion injury without dose-dependent effect.