Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavior.Methods Sixty 6～8-week-old SPF-grade ICR male mice were divided into two groups.5-Aza-CdR was administered to one group of mice via lateral ventricular injection,while the control group was injected with bovine serum albumin.Notch1 and HES1 mRNA and protein expression levels were detected by Real-time PCR and Western blot 24 hours after injection;5-bromo-2'-deoxyuridine-positive cells were observed by laser confocal microscopy,and Notch1 expression in hippocampal dentate gyrus was viewed with laser confocal microscopy.Notch1 methylation changes were detected by ethylation-specific PCR,and learning and memory behaviors of mice were assessed by passive avoidance tests and shuttle avoidance assays.Results Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity,promoted neuronal regeneration in the DG region,decreased methylation levels in the Notch1 promoter region,and enhanced the ability of mice to perform active avoidance behavior.Conclusions The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch 1 pathway.

Objective:To observe the effects of Sanjia Powder on myocardial fibrosis in diabetic cardiomyopathy (DCM) model rats; To elaborate its mechanism.Methods:A DCM rat model was constructed using STZ single intraperitoneal injection combined with high-sugar and high-fat feeding. The model rats were divided into model group, TCM group, Western medicine group, miR-21 inhibition group, and miR-21 inhibition control group using a random number table method, with 10 rats in each group; another 10 SD rats were set as normal group. TCM group was orally administered with Sanjia Powder water decoction at a dose of 6.2 g/kg, and the Western medicine group was administered metformin 250 mg/kg + enalapril 45 mg/kg by gavage. miR-21 inhibition group, miR-21 inhibition control group, normal group, and model group were given the same volume of distilled water by gavage, once a day, for 4 weeks; at the same time, the normal group, the model group, TCM group, and the Western medicine group were injected with the same amount of normal saline in the tail vein. The miR-21 inhibition group received tail vein injection of miR-21 inhibitor at a dose of 20 mg/kg, and the miR-21 inhibition control group received tail vein injection of miR-21 inhibitor NC at a dose of 20 mg/kg, twice a week, for 4 weeks. The morphological changes of myocardial tissue were observed using HE; the expression of Collagen-Ⅰ in myocardial tissue was detected using Western Blot; the expressions of endothelial cell marker CD31 and stromal cell marker FSP1 in myocardial tissue were detected using immunofluorescence method.Results:Compared with the model group, the pathological morphology of myocardial tissue improved in the TCM group, Western medicine group, and miR-21 inhibition group, while the expressions of Collagen-Ⅰ and FSP1 decreased ( P<0.01) and the expression of CD31 increased ( P<0.01); there was no statistically significant difference in the expressions of Collagen-Ⅰ, CD31, and FSP1 between the TCM group and the miR-21 inhibition group ( P>0.05). Conclusion:Sanjia Powder can improve myocardial fibrosis in rats with diabetic cardiomyopathy, and its mechanism may be related to the up-regulation of CD31 expression and down-regulation of FSP1 expression, thereby inhibiting endothelial mesenchymal transition, and may also be related to the inhibition of miR-21 expression.

Objective·To explore the influencing factors of oral nutritional supplement compliance in postoperative patients with digestive tract cancer based on COM-B model,and to analyze the mediating role of medication belief and self-efficacy in oral nutritional supplement.Methods·A total of 300 postoperative gastrointestinal cancer patients were selected by convenience sampling method.The General Information Questionnaire,Morisky Medication Adherence Scale,Digestive Cancer Patients Nutrition Knowledge,Attitude and Practice Questionnaire,Multidimensional Scale of Perceived Social Support,Beliefs about Medicines Questionnaire and General Self-Efficacy Scale were used.A mediating effect model was used to analyze the influencing factors of compliance with oral nutritional supplements.Results·The score of Morisky Medication Adherence scale was 1.61±1.38,which was at a low level.Oral nutritional supplement compliance was significantly positively correlated with nutrition knowledge,social support,medication belief and self-efficacy(r=0.391,0.401,0.438,0.410,all P＜0.01).Medication belief had a partial mediating effect between nutrition knowledge and adherence to oral nutritional supplements(effect size=0.097,accounting for 18.00%of the total effect).Self-efficacy had a partial mediating effect between nutrition knowledge and oral nutritional supplement compliance(effect size=0.044,accounting for 8.16%of the total effect).Self-efficacy had a partial mediating effect between social support and oral nutritional supplement compliance(effect size=0.044,accounting for 16.67%of the total effect).Conclusion·The compliance of oral nutritional supplements in postoperative patients with gastrointestinal cancer is at a low level.The individualized nursing intervention can increase the nutritional knowledge of patients,improve the social support,reduce the concerns of patients about oral nutrition,and improve the self-efficacy of patients,so as to promote the compliance of patients with oral nutritional supplements.

Objective:To investigate the prognostic relationship between serum KL-6 level and rheumatoid arthritis(RA)combined with interstitial lung disease(RA-ILD).Methods:In Affiliated Hospital of Inner Mongolia Medical University from January 2018 to January 2021,seventy patients with RA were selected and divided into RA-ILD group(34 cases)and RA(36 cases)accord-ing to whether they were complicated with ILD,clinicopathological characteristics of the two groups of patients were analyzed by uni-variate analysis,focusing on the comparison of the expression level of KL-6 in the serum of the two groups and the correlation analysis with laboratory indexes,lung function and imaging,multivariate Logistic regression analysis risk factors affecting RA-ILD.Results:There were significant differences in gender,smoking history,age,age of onset,course of disease,DAS28,KL-6,WBC,UA,RF,anti-CCP antibody,TLC%Pred and DLCO%Pred between the two groups(P<0.05).In RA-ILD group,the proportion of clinical symp-toms was more prominent,joint pain was more prominent,and the thickening of pleural adhesion was more prominent on HRCT;Spearson correlation analysis showed that the level of serum KL-6 in RA-ILD group was significantly negatively correlated with TLC%Pred,VC%Pred and DLCO%Pred(P<0.05);there was a significant positive correlation with RF and anti-CCP antibody levels(P<0.05);there was no significant correlation with FEV1%Pred and FEV1/FVC(P>0.05);expression level of KL-6 in RA-ILD group was significantly higher than that in RA group before treatment,and there was no significant difference after treatment(P>0.05);Fol-lowed up for one year,six patients died in RA-ILD group.The expression level of KL-6 in death group was significantly higher than that in non death group(P<0.05);multivariate Logistic regression analysis showed that old age,male,smoking,increased anti CCP antibody and KL-6 were independent risk factors for RA-ILD(P<0.05);the maximum area under the ROC curve predicted by serum KL-6 was 0.802,the 95%CI was 0.743～0.866,the sensitivity was 0.853,the specificity was 0.827,and the maximum area under the ROC curve detected jointly was 0.854,indicating that the prediction ability of the model was strong.Conclusion:Serum KL-6 levels in RA-ILD patients are significantly increased.KL-6 can be used as a serological index for early detection of ILD,and combined with lung function detection can detect ILD earlier.Early diagnosis is of great significance for treatment and prognosis.

Objective:To investigate the clinical value of early gastroscopy for patients with hypopharyngeal cancer.Methods:A total of 231 cases of hypopharyngeal cancer diagnosed and treated in the First Affiliated Hospital of Xiamen University from January 2010 to December 2014 were included in the retrospective analysis. The 5-year survival rate of hypopharyngeal cancer and patients accompanied with synchronous esophageal cancer (including early and advanced esophageal cancer), as well as the detection rate of synchronous esophageal cancer by gastroscopy and systemic PET-CT examination were statistically analyzed.Results:The 5-year survival rate of hypopharyngeal cancer was 38.96% (90/231). The 5-year survival rates of 62 patients accompanied with synchronous esophageal cancer and 169 patients without were 27.42% (17/62) and 43.20% (73/169), respectively, with statistic difference ( χ2=4.747, P=0.029). The 5-year survival rate of 49 patients accompanied with synchronous early esophageal cancer was 30.69% (17/49). Among the 13 patients with synchronous progressive esophageal cancer, none had a survival period of 5 years, which was significantly different compared with the patients with synchronous early esophageal cancer ( P=0.013). The detection rates of synchronous esophageal carcinoma by gastroscopy and by systemic PET-CT were 26.84% (62/231) and 14.29% (33/231), respectively, with statistic difference ( χ2=11.14, P<0.01). The detection rates of synchronous early esophageal carcinoma by gastroscopy and by systemic PET-CT were 21.21% (49/231) and 8.66% (20/231), respectively, and the difference was also statistically significant ( χ2=14.328, P<0.01). Conclusion:Hypopharyngeal cancer accompanied with synchronous esophageal cancer is of high risk, which affects the survival rate of patients. Early gastroscopy in hypopharyngeal cancer patients can significantly improve the detection rate of synchronous esophageal cancer, which helps to design individualized regimen to improve the survival rate of patients.

Objective:To analyze the correlation of the short diameter of residual lymph nodes with the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy (CRT), and establish a Nomogram prediction model to predict the prognosis of ESCC patients.Methods:Clinical data of 143 ESCC patients who underwent CRT in Second People′s Hospital of Huai′an from August 2018 to September 2020 were collected. The survival analysis was conducted with Kaplan- Meier method, log-rank test and univariate prognostic analysis. Multivariate prognostic analysis was performed with Cox models. Finally, a Nomogram prediction model was established to predict the 1-year and 2-year progression-free survival (PFS) of patients, and the C-index, AUC, and calibration curve were used to evaluate the performance of the model. Results:Logistic regression analysis results showed that differentiation, TNM staging, PG-SGA scores before and after radiotherapy (RT) and short diameter of residual lymph nodes were the independent predictors of clinical efficacy of ESCC patients treated with CRT. Cox regression analysis demonstrated that differentiation, TNM staging, PG-SGA scores before and after RT and short diameter of residual lymph nodes were the independent prognostic predictors of ESCC patients undergoing CRT. Conclusions:The short diameter of residual lymph nodes is significantly correlated with the efficacy and prognosis of ESCC patients undergoing CRT. The Nomogram prediction model established after comprehensive clinical baseline characteristics is a practical and reliable tool for predicting clinical prognosis of ESCC patients.

Objective:To study the efficacy of dental floss traction-assisted endoscopic submucosal dissection (ESD) for gastric angle mucosal lesions.Methods:Data of 127 patients with gastric angle mucosal lesions admitted to the endoscopic center of the First Affiliated Hospital of Xiamen University from January 2015 to December 2018 were retrospectively analyzed. According to the surgical methods, patients were divided into the dental floss traction-assisted ESD group (the traction group, n=51) and the traditional ESD group (the traditional group, n=76). The 41 fibrosis cases were further divided into the traction group (n=23) and the traditional group (n=18). The operation time, en block resection rate, curative resection rate and the incidence of adverse events such as bleeding, muscle layer injury and perforation were compared between the two groups.Results:There was no significant difference in age, sex, lesion size or morphology between the traction group and the traditional group ( P > 0.05). The operation time of the traction group was significantly shorter than that of the traditional group (65.4±36.5 min VS 103.5±43.2 min, P=0.012). The en block resection rate was higher in the traction group [100.00% (51/51) VS 90.79% (69/76), P=0.026], and the curative resection rate was higher too [94.12% (48/51) VS 81.58% (62/76), P=0.042]. The incidences of muscular layer damage [5.88% (3/51) VS 25.00% (19/76), P=0.010] and intraoperative bleeding [47.06% (24/51)VS 82.89% (63/76), P=0.010] were lower in the traction group. Perforation occurred in two patients (2.63%) of fibrosis in the traditional group; no perforation occurred in the traction group. There was no significant difference in the perforation incidence ( P=0.243). In the cases of fibrosis, the operation time of the traction group was significantly shorter compared with that of the traditional group (81.4±29.3 min VS 119.3±37.6 min, P=0.010). The en block resection rate and curative resection rate were also higher in the traction group [100.00% (23/23) VS 72.22% (13/18), P=0.007; 95.65% (22/23) VS 72.22% (13/18), P=0.035]. The incidences of muscular layer damage [8.70% (2/23) VS 72.22% (13/18), P=0.001] and intraoperative bleeding [78.26% (18/23) VS 100.00% (18/18), P=0.035] were lower in the traction group. Conclusion:The dental floss traction-assisted ESD is safe and effective for gastric angle mucosal lesions and fibrotic lesions, with shorter operation time, higher curative resection rate and lower incidence of adverse events.

OBJECTIVE： To study the anti-inflammatory effect and its mechanism of the extract of Dcsmodium microphyllum， so as to provide experiment reference for further study of D. microphyllum. METHODS： Acute inflammatory model was established by xylene，glacial acetic acid and carrageenan. Using dexamethasone as positive control （0.005 g/kg）， inhibitory effects of intragastric different doses of the extract of D. microphyllum （50， 30， 15 g/kg） on xylene-induced ear swelling in normal mice and adrenalectomized mice， glacial acetic acid-induced permeability increasing of abdominal capillaries in normal mice， carrageenan-   induced paw swelling in normal mice and adrenalectomized mice were investigated. The levels of MDA， SOD and NO in the inflammatory tissue of toes of adrenalectomized mice were detected in carrageenan-induced inflammation model. Blank group was set for control （ig. equal volumn of water）. RESULTS： Compared with blank group， ear swelling degree of normal mice and adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups while inhibitory rate of ear swelling was increased significantly； the permeability of abdominal capillaries of normal mice was significantly decreased in D. microphyllum extract groups； the swelling degree of toes in normal mice of D. microphyllum extract high-dose and middle-dose groups and adrenalectomized mice were significantly decreased while inhibitory rate of toe swelling was increased significantly （P＜0.05 or P＜0.01）. The levels of MDA and NO in the toe inflammatory site of adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups， while the level of SOD was increased significantly （P＜0.05）. CONCLUSIONS： D. microphyllum extract can inhibit acute inflammation in mice significantly. Its anti-inflammatory mechanism is associated with decreasing MDA and NO while increasing SOD levels， and the anti-inflammatory effect does not depend on the hypothalamus-pituitary-adrenal axis system.

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10⁷/kg on day 0) and (4.0-6.8) ×10⁷/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

Objective To investigate the serum levels of 25-hydroxyvitamin D3 (25 (OH)D3) and urine vitamin D binding protein(uVDBP) in patients with diabetic nephropathy (DN),and to determine the relationship between 25 (OH) D3,uVDBP and DN,in order to provide a new method for early diagnosis and treatment of DN.Methods From January 2015 to December 2015,85 DN patients admitted into Weihai Municipal Hospital were selected.According to the ratio of UALB to UCR(UACR),the patients were divided into three groups.Type 2 diabetes had 28 cases of normal albuminuria group,31 cases of microalbuminuria group,and 26 cases of clinical albuminuria group.We also enrolled 25 healthy people who received outpatient service as control group.Serum 25 (OH) D3 levels were measured by chemiluminescence method.Urine VDBP levels were assayed by ELISA.FPG,HbA1 c,UREA,SCr,TC,TG were measured by electrochemiluminescence.Results The results showed that serum 25 (OH)D3 was significantly lower in the normal albuminuria group,microalbuminuria group and clinical proteinuria group than that in the control group (P ＜ 0.05),and there was statistically significant difference among the four groups [(20.04 ± 7.52) ng/mL,(16.54 ± 6.51) ng/mL,(10.77 ± 4.63) ng/mL,(29.65 ± 5.47) ng/mL,F =86.294,P ＜ 0.001].The results showed that uVDBP was significantly higher in the DN group than that in the control group(all P ＜ 0.05),and there was statistically significant difference among the four groups [(8.44 ± 3.20) mg/L,(14.22 ± 3.26) mg/L,(2 1.77 ± 5.87) mg/L,(4.95 ± 1.34) mg/L,F =125.583,P ＜ 0.001].Correlation analysis showed that serum 25 (OH) D3 decreased gradually with the increase of DN and negatively correlated with UACR (r =-0.575,P ＜ 0.01),while uVDBP level was positively correlated with UACR (r =0.436,P =0.015).Conclusion With the progress of DN,serum 25 (OH) D3 levels gradually decreased,indicating that 25 (OH) D3 may play an important role in the pathogenesis of DN;uVDBP may be an early diagnostic method for DN.