Objective To study the efficacy and safety of combined therapy of compound azintamide and domperidone in functional dyspepsia. Methods A randomised, double-blind, placebo-controlled trial.Two hundred and eight patients with functional dyspepsia were randomly grouped into group A (experimental group, 102 cases) and group B (control group, 106 cases). The patients in the group A were given 2 tablets of compound azintamide 3 times a day in addition to domperidone 10 mg 3 times per day for four weeks. The patients in the group B were only given domperidone 10 mg 3 times per day for 4 weeks. The therapeutic efficacy was evaluated by modified Severity of Dyspepsia Assessment (mSODA) and Global Patient Assessment (GPA). Results Subscore in mSODA:the change of bloating/pain intensity score in group A is -12.35±5.48 while group B is -10.52±4.65(P=0.009), the change of non-bloating/pain symptoms score in group A is -5.75±3.31 while group B is - 4. 86 ± 2.65 (P=0.033), and the change of satisfaction score in group A is 7. 09 ± 3. 78 while group B is 5.62 ± 3. 54 (P = 0. 004). The response rate in group A is 89. 2% which is significantly higher than 76.4% in group B (P=0. 015). Other symptoms for response assessment included loss of appetite, early satiety, fullness after meal, diarrhea. No severe side-effect was found in both groups. Conclusions Combined therapy of compound azintamide and domperidone may lead to bigger improvement in overall efficacy and health related quality of life in patients with functional dyspepsia than use of motility medicine alone. Potential mechanisms that may account for the efficacy of compound azintamide in functional dyspepsia include modulation of visceral sensitivity and/or gastrointestinal motility.

ObjectiveTo study the scope of excison in breast-conserving surgery for breast carcinoma.MethodsClinical data of 275 breast cancer patients undergoing breast-conserving surgery in t he First Affiliated Hospital of Nanjing Medical University,the Affiliated Zhenjiang Hospital of Jiangsu University and Changzhou Traditional ChineseMedicine Hospital were retrospectively analyzed.The operation procedure and postoperative adjuvant therapy were carried out with the same protocol.Local and general conditions of patients were followed up regularly.Results271 out of 275 patients got follow-up.The follow-up rate was 98.5％.The follow-up time ranged from 1 month to 117 months,median follow-up time was 34 months.Six patients died of distant metastasis,2 with local recurrence.The 1-year,3-year,and 5-year overall survival rates were 99.5％,98.1％,and 95.7％,respectively.ConclusionsIt is safe to excise 1 cm normal breast tissue with clear margin confirmed by frozen section,followed by postoperative adjuvant therapy,endocrine therapy,and radiotherapy,this improves the life quality of patients with breast cancer.It is safe and effective to determine whether the disease is multicentric or multifocal by mammogram plus clinical breast examination.

Objective To preliminarily investigate the levels of interleukin (IL)-1 family and IL-34 in serum of patients with ankylosing spondylitis (AS) and their roles.Methods Serum IL-1 family levels were detected from 6 AS patients and 4 healthy controls by using protein-chip technique.Enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of serum IL-34 from 65 AS patients and 85 healthy controls and the relationships of serum IL-34 levels and clinical or laboratory features were analyzed.T test and Spearman correlation were used for statistical analysis.Results IL-1Ra [(3302±1352) pg/ml vs (10778±2764) pg/ml]and IL-36Ra [(1363±194) pg/ml vs (3875±996) pg/ml] levels were significantly down-regulated in AS patients compared with that of healthy controls (t=5.363 and 4.289 respectively,both P＜0.05).The levels of IL-1α,IL-18,IL-36α and IL-37 were increased more remarkable in AS patients than in healthy controls (t=-2.532,-5.400,-5.023 and-5.783 respectively,both P＜0.05).Moreover,serum IL-34 levels were elevated more significantly in AS patients than in healthy controls [(169±153) pg/ml vs (54±31) pg/ml,t=6.722,P＜0.01] and were positively correlated with the levels of CRP and ESR.Serum IL-34 levels were markedly up-regulated in human leukocyte antigen (HLA)-B27 positive patients than in HLA-B27 negative patients(P＜0.05).Conclusion Part of IL-1 family and IL-34 may be involved in inflammatory or immunological process of AS.

OBJECTIVETo study the therapeutic effect of intranasal administration of temozolomide (TMZ) for brain-targeting delivery in a rat model bearing orthotopic C6 glioma xenografts.

METHODSForty Wistar rat bearing brain C6 glioma xenograft were randomly divided into 4 groups and treated with physiological saline solution or with TMZ by intravenous injection, gavage or intranasal administration. The tumor size, rat survival time and pathological changes were observed in each group.

RESULTSMagnetic resonance imaging showed a significantly reduced volume of glioma in intranasal TMZ group compared with that in the control, intraveneous TMZ injection group and TMZ gavage groups (12.45∓2.49 mm(3) vs 60.16∓4.12, 33.17∓3.56, and 35.16∓4.36 mm(3), respectively, P<0.05). The median survival time of the C6 glioma-bearing rats was also significantly longer in intranasal TMZ group than in the other 3 groups (31.0 days vs 20, 19, and 21.5 days, respectively, P<0.05). In the glioma xenografts, PCNA expression was the lowest and tumor cell apoptosis rate the highest in intranasal TMZ group.

CONCLUSIONIntranasal TMZ administration can suppress the growth of C6 glioma in rats and may serve as an effective strategy for glioma treatment.

Administration, Intranasal ; Animals ; Antineoplastic Agents, Alkylating ; administration & dosage ; Apoptosis ; Brain Neoplasms ; drug therapy ; Cell Line, Tumor ; Dacarbazine ; administration & dosage ; analogs & derivatives ; Drug Delivery Systems ; Glioma ; drug therapy ; Magnetic Resonance Imaging ; Neoplasm Transplantation ; Rats ; Rats, Wistar

Objective To study the therapeutic effect of intranasal administration of temozolomide (TMZ) for brain-targeting delivery in a rat model bearing orthotopic C6 glioma xenografts. Methods Forty Wistar rat bearing brain C6 glioma xenograft were randomly divided into 4 groups and treated with physiological saline solution or with TMZ by intravenous injection, gavage or intranasal administration. The tumor size, rat survival time and pathological changes were observed in each group. Results Magnetic resonance imaging showed a significantly reduced volume of glioma in intranasal TMZ group compared with that in the control, intraveneous TMZ injection group and TMZ gavage groups (12.45±2.49 mm3 vs 60.16±4.12, 33.17±3.56, and 35.16±4.36 mm3, respectively, P<0.05). The median survival time of the C6 glioma-bearing rats was also significantly longer in intranasal TMZ group than in the other 3 groups (31.0 days vs 20, 19, and 21.5 days, respectively, P<0.05). In the glioma xenografts, PCNA expression was the lowest and tumor cell apoptosis rate the highest in intranasal TMZ group. Conclusion Intranasal TMZ administration can suppress the growth of C6 glioma in rats and may serve as an effective strategy for glioma treatment.

Objective To study the therapeutic effect of intranasal administration of temozolomide (TMZ) for brain-targeting delivery in a rat model bearing orthotopic C6 glioma xenografts. Methods Forty Wistar rat bearing brain C6 glioma xenograft were randomly divided into 4 groups and treated with physiological saline solution or with TMZ by intravenous injection, gavage or intranasal administration. The tumor size, rat survival time and pathological changes were observed in each group. Results Magnetic resonance imaging showed a significantly reduced volume of glioma in intranasal TMZ group compared with that in the control, intraveneous TMZ injection group and TMZ gavage groups (12.45±2.49 mm3 vs 60.16±4.12, 33.17±3.56, and 35.16±4.36 mm3, respectively, P<0.05). The median survival time of the C6 glioma-bearing rats was also significantly longer in intranasal TMZ group than in the other 3 groups (31.0 days vs 20, 19, and 21.5 days, respectively, P<0.05). In the glioma xenografts, PCNA expression was the lowest and tumor cell apoptosis rate the highest in intranasal TMZ group. Conclusion Intranasal TMZ administration can suppress the growth of C6 glioma in rats and may serve as an effective strategy for glioma treatment.

OBJECTIVETo establish the model of microdialysis, and study the ocular pharmacokinetics of puerarin in anesthetic rabbits.

METHODImplanted the probe into anterior chamber of anesthetic rabbit by surgery. After balanced for 2 h, 1% puerarin eye drop (100 microL) was applied into the cul-de-sac with micropipette. Immediately the dialysate was collected at different time and detected by HPLC with the detection wavelength of 249 nm. The mobile phase was methanol and 0.1% citric acid solution (30:70); the flow rate was 1.0 mL x min(-1).

RESULTAfter the administration, puerarin can be absorbed into aqueous humor quickly. The peak concentration of puerarin appeared at about 1 h and then reduced gradually. The peak concentration(C(max)) is (2.52 +/- 0.31) mg x L(-1). The other lower peak was shown at 3.5 h during the eliminate phase. This might be attributed to the inhibition of aqueous humor production by the puerarin and resulted in a high drug concentration. The area under concentration-time curve (AUC(0-t)) is (5.04 +/- 0.21) mg x h x L(-1) and the eliminate half life (t1/2) is (0.38 +/- 0.13) h.

CONCLUSIONThe microdialysis technique can be used to detect the ocular pharmacokinetics of puerarin, and support the valuable pharmacokinetics parameter for the clinical applications of puerarin eye drop.

Anesthesia ; Animals ; Eye ; metabolism ; Female ; Isoflavones ; pharmacokinetics ; Male ; Microdialysis ; methods ; Ophthalmic Solutions ; Rabbits

Objective:To compare the effect for establishing rat model of chronic obstructive pulmonary disease(COPD)be-tween two methods,inhalation of PM2.5 and intratracheal instillation of PM2.5 suspension.Methods:A total of 30 adult rats were randomly divided into control group(group A),group fumigated with PM2.5(group B),and group instilled intratracheal-ly with PM2.5 suspension(group C).Then the lung function of rats,the counts of inflammatory cells in bronchoalveolar lavage fluid(BALF),and the pathological sections of lung tissues,were observed on different phases.Results:Compared with that in group A,the body mass in group B or group C decreased.And the tidal volume(VT)and the peak expiratory flow(PEF)de-creased.Furthermore,total cell count,lymphocyte count(L),neutrophil count(N),lymphocyte proportion(L%),and neutro-phil proportion(N%)in BALF increased.All the differences showed statistical significance(all P <0.05).Morphological de-tection showed enlarged alveolar space,disruption of alveolar septa,fusion of alveoli,and formation of emphysema in group B. And it also showed disordered arrangement of airways epithelial cells,partial airway epithelial hyperplasia,inflammatory cell infiltration and proliferation of smooth muscle in group B.Furthermore,mean linear intercept (MLI)and mean alveolar num-ber (MAN)in group B increased,while compared with that in group A.The pathological changes in group C were similar to those in group B.However,the degrees of pathological changes in group C were more severe,and most of them were acute in-juries.Conclusions:Rat model of COPD established by inhalation of PM2.5 was more reasonable than that established by intra-tracheal instillation of PM2.5 suspension.

Objective:To investigate the clinical characteristics of dermatomyositis (DM) patients with positive anti-melanoma differentiation-associated protein 5 (MDA5) antibody-complicated with pneumomediastinum.Methods:Clinical data of patients with anti-MDA5 antibody-positive DM with or without pneumomediastinum from March 2017 to December 2019 in Ningbo First Hospital were collected and analyzed. The international literature were reviewed and compared. T-test or Mann-Whitney U test was used for measurement data, chi-square test or Fisher exact probability was used for count data. Logistic regression analysis was used to analyze the risk factors for anti-MDA5 antibody-positive DM with pneumomediastinum. Results:Twelve DM patients with -positive anti-MDA5 antibody without pneumomediastinum, and 1 DM patient with positive anti-MDA5 antibody-complicated with pneumomediastinum. Pooling with literature review, 16 DM patients with positive anti-MDA5 antibody-complicated with pneumomediastinum were compared. It was found that the serum ferritin (SF) level [991.6(548.5, 2875.1) ng/ml vs 355 (143.5, 395) ng/ml, Z=-2.506, P=0.012] and the rate of rapid progressive pulmonary interstitial disease (RPILD) in the pneumo-mediastinum group [76.5% vs 16.7%, χ2=10.076, P=0.002] were significantly higher than those in the non-pneumome-diastinum group. Further Logi-stic regression analysis did not show male gender [ OR=0.192, 95% CI(0.009, 4.125), P=0.291]; SF [ OR=1.002, 95% CI(0.998, 1.006), P=0.279]; RPILD[ OR=0.084, 95% CI(0.003, 2.178), P=0.136]; CADM[ OR=0.258, 95% CI(0.009, 7.419), P=0.429] was risk factor for pneumomediastinum. Conclusion:DM patients with positive anti-MDA5 antibody and high seral SF level and rapid progression of pulmonary interstitial disease are more likely to complicate with pneumomediastinum.

Objective:To explore the value of the Wilcoxon-Mann-Whitney generalized dominance ratio (T max-weighted ratio) based on residual tissue time to peak (T max) delayed severity weighting in predicting the moderate to severe edema after acute anterior circulation ischemic stroke. Methods:The clinical and imaging features of patients with acute anterior circulation ischemic stroke from January 2019 to April 2022 in Yidu Central Hospital of Weifang were retrospectively analyzed. A total of 85 patients were enrolled, including 60 males and 25 females, with the age from 34 to 93 (67±11) years old. Patients underwent non-contrast CT, CT angiography of the head and neck, and CT perfusion imaging of the head, and ischemic core volume and the ratio of T max 4-6 s volume, T max 6-8 s volume, T max 8-10 s volume, and T max >10 s volume relative to the entire hypo-perfused area (T max>4 s volume) was measured, and the T max-weighted ratio was calculated, the collateral circulation were assessed. Patients were divided into mild edema group and moderate to severe edema group according to whether local swelling exceeded 1/3 of the unilateral cerebral hemisphere on non-contrast CT at 24-48 h. The indicators were compared between the two groups by independant t test, Mann-Whitney U and χ 2 test. The performance to predict moderate to severe edema was assessed using the receiver operating characteristic (ROC) curve. The univariate and multivariate logistic regression was used to analyze the risk factors for the moderate to severe edema. Differences in baseline National Institutes of Health Stroke Scale (NIHSS) score and infarct core volume were equalized by 1∶1 propensity score matching (PSM) and the differences of T max-weighted ratio between the two groups were further compared. Results:There were 52 cases in the mild edema group and 33 cases in the moderate to severe edema group. Baseline NIHSS score, T max>10 s volume, ischemic core volume, T max-weighted ratio and proportion of poor collateral circulation were higher in the moderate-severe edema group than those in the mild edema group ( P<0.001), T max 4-6 s volume was lower than in the mild edema group ( P<0.001). ROC analysis showed that the area under the curve (AUC) of T max-weighted ratio for predicting the incidence of moderate to severe edema was 0.885 (95%CI 0.798-0.944), with an optimal cut-off value of 1.17, sensitivity of 84.85% and specificity of 82.69% before PSM. The predictive ability based on T max-weighted ratio was similar to ischemic core volume( Z=0.64, P=0.520), T max 4-6 s volume ( Z=1.48, P=0.140) and superior to T max 6-8 s volume( Z=5.65, P<0.001), T max 8-10 s volume( Z=4.46, P<0.001), T max >10 s volume ( Z=2.91, P=0.004). Multivariate logistic regression analysis showed that T max-weighted ratio>1.17 was an independent predictor of the development of moderate to severe edema (OR=10.40,95%CI 2.65-40.83, P=0.001) through adjusted for baseline NIHSS score and ischemic core volume. After PSM, 14 patients in each group were included; the T max-weighted ratio was higher in the moderate-to-severe edema group than that in the mild edema group ( P<0.001), and the differences in other factors were not statistically significant (all P>0.05); ROC analysis showed that the AUC of T max-weighted ratio to predict the occurrence of moderate-to-severe edema was 0.852 (95%CI 0.667-0.957). Conclusion:The T max-weighted ratio can predict the occurrence of moderate-to-severe edema in brain tissue after acute anterior circulation ischemic stroke.