This study is to screen the Chinese herbal compounds which could inhibit the production of Abeta and investigate the underlying mechanism. Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial. The cell models which used could overexpress Abeta and beta-secretases or Abeta and gamma-secretases. Extracellular Abeta was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 micromol x L(-1)), separately. Then the compounds were selected which could inhibit extracellular Abeta and their best concentration ranges were decided, too. Furthermore, the cell viability and apoptosis rate, the level of intracellular Abeta, beta and gamma-secretases were determined after the cell models treated with different concentrations of selected compounds. The results showed that 4 of the 10 compounds could reduce the level of extracellular Abeta; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 micromol x L(-1), respectively. Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Abeta were more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of beta and gamma-secretases, with the maximum inhibiting rates of 78.2% and 80.3%, respectively. In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit the expression and secretion of Abeta, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the beta and gamma-secretase activities, respectively.

Objective To explore the application value of lung volumes from 64 multi-slice CT (MSCT) images in patients with chronic obstructive pulmonary disease (COPD) and study the correlation between lung volumes measured by MSCT and pulmonary function test (PFT) results. Methods 24 patients clinically diagnosed with COPD (COPD group) and 22 healthy people (control group) were selected and underwent both chest MSCT scans and PFT within one week. The total lung was scanned at full inspiration and full expiration with MSCT,respectively. The total lung volumes were measured by CT Pulmo software (Siemens,Forchheim,Germany). The quantitative total lung volumes from MSCT images were compared with PFT and SPSS13.0 was applied to assess the correlation. Results Compared with control group,the full inspiration volume (Vin) (P

Objective To compare the efficacy of the radical resection by laparoscopy versus open approach in perioperative period on the patients with rectal carcinoma,and investigate the feasibility,safety and oncological clearance of the laparoscopy.Methods The clinical data of 44 patients who underwent radical resection of rectal carcinoma by laparoscopy in our hospital were reviewed and compared with another 53patients who underwent an open approach in the same period.The surgery-related data,postoperative recovery status,tumor radical resection index,and postoperative complications by laparoscopy were analyzed by statistics,and compared with those by open approach,and evaluated the deference of too kinds of operation.Results This study showed a longer surgical time (260.45 ± 67.46) min vs ( 179.25 ± 40.92) min,P ＜0.05,a less intra-operative blood loss( 125.20 ±61.80) mL vs ( 198.02 ± 131.24) mL,P ＜0.05,in laparoscopic group compared with open approach.Meanwhile,it also showed an earlier recovery of bowel functions for discharge gas from anus,taking in food,and out-of-bed activity (4.34 ± 1.55) d vs(5.45 ± 1.55) d,P ＜0.05,in the laparoscopic group compared with open approach.There was no statistical difference of incidence of post-operative complications (5 cases vs 11 cases,P ＞0.05) between the two groups and the laparoscopic approach was also equal to the open approach as regard to post-operative stay (15.34 ±6.62) d vs (16.82±5.73) d,P ＞0.05,and demand of intra-operative blood transfusion (4 case vs 8 cases,P＞0.05 ).Conclusions Compared with open surgery,the radical resection of rectal carcinoma by laparoscopy has shown obvious advantages in smaller incision,less blood loss,less pain,earlier recovery of bowel and bladder functions,and earlier out-of-bed activity.And it is also possible by laparoscopy approach to decrease the post-operative complications and post-operative stay.Meanwhile,there is no significant deference on oncological clearance for laparoscopy compared with open approach during perioperative period,while the long term follow-up data is still needed to support the results.

Objective:To analyze the reflux parameters of patients with gastroesophageal reflux disease (GERD) in upright position, supine position and at 2 h after meals, and to explore the cut-off value, sensitivity and specificity of the reflux parameters in different positions and at 2 h after meals in GERD diagnosis.Methods:From January 2016 to July 2020, 200 GERD patients (GERD group) and 61 non-GERD patients (control group) who visited Huazhong University of Science and Technology Union Shenzhen Hospital (Former Nanshan District People′s Hospital), were selected. All the patients of the two groups received gastroesophageal reflux disease questionnaire (GERDQ), upper gastrointestinal endoscopy, esophageal high resolution manometry and 24 h esophageal pH combined impedance monitoring. T test, non-parametric test and chi-square test were used to compare the related parameters in upright position, supine position and at 2 h after meals between two groups and within each group. Receiver oparative characteristic (ROC) curves of reflux parameters in upright position, supine position and 2 h after meals were drawn to determine the cut-off value, sensitivity and specificity in GERD diagnosis. Results:The proportion of patients with acid reflux in supine position of the control group was higher than that of the GERD group (41.0%, 25/61 vs. 8.50%, 17/200), and the difference was statistically significant ( χ2=36.53, P<0.01). In the control group, the acid reflux time in upright position, number of acid reflux, acid exposure time (AET), longest reflux time and number of weak acid reflux were more than those of in supine position in the same group (6.00 min(2.00 min, 13.50 min) vs. 0.00 min(0.00 min, 1.50 min), 16.00(8.00, 27.00) vs. 1.00(0.00, 3.00), 0.90%(0.33%, 1.88%) vs. 0.00%(0.00%, 0.30%), 2.00 min(1.00 min, 4.00 min) vs. 0.00 min(0.00 min, 1.00 min), 7.00(3.00, 11.00) vs. 1.00(0.00, 2.00), respectively) and the differences were statistically significant ( Z=5.43, 6.61, 5.06, 3.58 and 6.24, all P<0.01). In the GERD group, the acid reflux time, number of acid reflux, AET, longest reflux time and number of weak acid reflux in upright position were higher than those in supine position (51.00 min, (31.00 min, 86.75 min) vs. 8.00 min(1.00 min, 42.00 min), 60.00(48.00, 83.75) vs.6.00(2.00, 19.50), 7.30%(3.90%, 12.10%) vs. 1.50%(0.20%, 6.50%), 7.00 min(4.00, 12.00 min) vs. 4.00 min(1.00 min, 17.00 min), 1.00(0.00, 3.00) vs. 0.00(0.00, 2.00), 7.00(3.00, 12.00) vs. 0.00(0.00, 1.00), respectively) and the differences were statistically significant ( Z=7.92, 11.22, 6.90, 2.56, 5.11 and 11.76, all P<0.05). The acid reflux time, number of acid reflux, AET, longest reflux time and number of weak acid reflux at 2 h postprandial were 3.00 min(2.00 min, 9.00 min), 10.00(5.00, 18.00), 0.90%(0.40%, 1.98%), 1.00 min(0.00 min, 3.00 min), 4.00(1.50, 8.50)and 28.50 min(15.00 min, 54.75 min), 35.00(24.00, 52.00), 8.30%(4.32%, 15.83%), 6.00 min(3.00 min, 11.00 min), 4.00(2.00, 7.25), in the control and GERD groups, respectively, which were significantly higher than those in supine position in the same group ( Z=4.30, 6.33, 5.50, 3.40, 5.71 and 3.76, 9.21, 5.76, 1.97, 10.46, all P<0.05). Among 200 GERD patients, 125 patients had symptoms recorded during the 24 h esophageal pH combined impedance monitoring, the incidence of reflux symptoms in upright position was higher than that in supine position (89.6%, 112/125 vs. 65.6%, 82/125), and the difference was statistically significant ( χ2=20.71, P<0.01). The results of ROC curve analysis showed that the accuracy of acid reflux time in upright position in GERD prediction was the highest, with AUC value of 0.94 and cut-off value of 24.5 min, and the sensitivity and specificity in GERD diagnosis were 81.50% and 95.08%, respectively. The prediction accuracy of acid reflux times in upright position and AET in upright position for GERD was secondary, AUC value both were 0.93 and the cut-off value of the acid reflux number in upright position was 39.5, and the sensitivity and specificity in GERD diagnosis were 84.00% and 95.08%, respectively. The cut-off value of AET in upright position was 2.75%, the sensitivity and specificity in GERD diagnosis were 85.00% and 93.33%, respectively. The AUC value, cut-off value, sensitivity and specificity of AET at 2 h postprandial were 0.91, 4.60%, and 73.49% and 95.00%, respectively. Conclusions:Both GERD patients and non-GERD patients have more reflux in upright position, especially within 2 h after meals. The diagnostic values of acid reflux time in upright position, number of acid reflux, AET and AET 2 h after meals for GERD is high, and the AUC values are all >0.90, which can be used as a more comprehensive basis for the analysis and diagnosis of GERD.

Cancer is a common cause of death worldwide. Despite significant advances in cancer treatments, the morbidity and mortality are still enormous. Tumor heterogeneity, especially intratumoral heterogeneity, is a significant reason under-lying difculties in tumor treatment and failure of a number of current therapeutic modalities, even of molecularly targeted therapies. The development of a virtually noninvasive“liquid biopsy”from the blood has been attempted to characterize tumor heterogeneity. This review focuses on cell-free circulating tumor DNA (ctDNA) in the bloodstream as a versatile biomarker. ctDNA analysis is an evolving field with many new methods being developed and optimized to be able to successfully extract and analyze ctDNA, which has vast clinical applications. ctDNA has the potential to accurately genotype the tumor and identify personalized genetic and epigenetic alterations of the entire tumor. In addition, ctDNA has the potential to accurately monitor tumor burden and treatment response, while also being able to monitor minimal residual disease, reducing the need for harmful adjuvant chemotherapy and allowing more rapid detection of relapse. There are still many challenges that need to be overcome prior to this biomarker getting wide adoption in the clinical world, including optimization, standardization, and large multicenter trials.

ObjectiveTo test the susceptibility of Penicilliosis marneffei (PM) isolates from Guangxi bamboo rats and patients to voriconazole and several commonly used antifungal agents.MethodsAccording to the Clinical and Laboratory Standards Institute(CLSI) M27-A2 and M38-A document,a microdilution method was used to determine the minimum inhibitory concentration(MIC) of voriconazole,itraconazole,terbinafine,amphotericin B,and fluconazole against mycelial phase (25 ℃) and yeast phase (37 ℃) of 14 PM isolates from Guangxi Bamboo rats and 25 PM isolates from patients.The difference in MIC of the antifungals was assessed by two-sample t test between Bamboo rat PM isolates and clinical PM isolates,and by paired t test between the mycelial and yeast phase of PM isolates.Results The MIC ranges of voriconazole,itraconazole,terbinafine,amphoteriein B and fluconazole were 0.0313-0.1250,0.1250-1.0000,0.0313-0.5000,0.2500-4.0000,2.0000-8.0000 mg/L,respectively for mycelial phase of Bamboo rat PM isolates,0.0078-0.2500,0.0313-0.5000,0.0313-1.0000,0.2500-2.0000,1.0000-8.0000 mg/L,respectively for yeast phase of Bamboo rat PM isolates,0.0313-0.2500,0.0625-1.0000,0.0313-1.0000,0.2500-4.0000,2.0000-32.0000 mg/L,respectively for mycelial phase of clinical PM isolates,0.0039-0.2500,0.0313-0.5000,0.0313-2.0000,0.1250-2.0000,2.0000-16.0000 mg/L,respectively for yeast phase of clinical PM isolates.None of the PM isolates was resistant to any of the antifungals.The MIC of voriconazole was found to be the lowest for PM isolates from both Bamboo rats and patients at the same temperature (37 ℃ or 25 ℃),followed by itraconazole,terbinafine,amphotericin B and fluconazole.Statistical difference was found in the MIC values of itraconazole,terbinafine,amphotericin B between the yeast and mycelial phase of the same PM isolate,but not found in antifungal MIC values between Bamboo rat isolates and clinical isolates at the same phase.ConclusionsOf the tested drugs,voriconazole shows the strongest antifungal potency. The PM isolates from Guangxi Bamboo rats are similar to clinical PM isolates in the sensitivity to voriconazole,itraconazole,terbinafine,amphotericin B and fluconazole.The phase of PM isolates may affect their susceptibility to itraconazole,amphotericin B and terbinafine.

OBJECTIVETo develop a novel vaccine by immobilizing interleukin-21 (IL-21) on the surface of MB49 cells and evaluate its effect in inducing specific cytotoxic T lymphocytes (CTLs) and antitumor immunity in a mouse model of subcutaneous metastatic bladder cancer.

METHODSSA-IL-21 was immobilized on the surface of 30% ethanol-fixed MB49 cells to prepare the cell vaccine. C57BL/6 mice with subcutaneous implantation of MB49 bladder cancer cells were randomized into 5 groups to receive treatments with IL-21/MB49 vaccine, soluble IL-21, GFP surface-modified MB49 cells, ethanol-fixed MB49 cells, or PBS. The tumor growth and CTL were examined to assess the antitumor efficacy of the vaccine.

RESULTSIL-21 surface-modified MB49 cell vaccine significantly inhibited the tumor growth and generated a long-lasting memory response (P<0.05). At the same effector-target (E:T) ratio, the specific CTLs induced by IL-21/MB49 vaccine showed the most potent cytotoxicity against MB49 cells (P<0.05).

CONCLUSIONWith the protein-anchor technique, IL-21 can be efficiently immobilized on the surface of MB49 cells to prepare IL-21/MB49 cells vaccine. The novel vaccine can maintain its biological activity and significantly enhance the cytotoxicity of CTLs against bladder cancer cells.

Amino Acid Motifs ; Animals ; Cancer Vaccines ; therapeutic use ; Cell Line, Tumor ; Female ; Immunotherapy ; Interleukins ; immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasms, Experimental ; therapy ; T-Lymphocytes, Cytotoxic ; immunology ; Urinary Bladder Neoplasms ; therapy

OBJECTIVETo investigate the efficacy and safety of laparoscopic fundoplication for gastroesophageal reflux disease (GERD)-related cough.

METHODSRetrospective review of 70 patients with GERD-related cough who received laparoscopic fundoplication in GERD Department of The Second Artillery General Hospital during June 2008 to June 2013 was carried out. GERD-related symptoms (reflux, heartburn, cough, expectoration, globus sensation and hoarseness) before and after surgery were compared through questionnaire, and the symptom remission rate (preoperative symptom score - postoperative symptom score)/preoperative symptom score×100%) was calculated. Complication morbidity and satisfaction degree of patients were investigated.

RESULTSThe GERD-related symptom scores of regurgitation, heartburn, cough, expectoration, globus sensation and hoarseness all significantly decreased (all P<0.01) after the anti-reflux laparoscopic fundoplication, with the corresponding symptom remission rates as (79.4±23.2)%, (82.0±21.5)%, (72.2±28.5)%, (62.6±28.9)%, (76.1±31.5)% and (70.8±39.3)% respectively. No major complication and death occurred. Five cases (7.1%) had pneumoperitoneum-related chest or neck subcutaneous emphysema, 17 cases (24.3% ) had various degree of early and late dysphagia, 6 cases (8.6%) had increased flatus and 2 cases had bloating after surgery. All the complications could be cured by appropriate treatment. Among all the patients, 16 cases (15.7%) felt very satisfied, 37 cases (52.9%) felt satisfied, 11 cases (15.7%) felt acceptable, 4 cases (5.7%) felt unsatisfied and 2 cases felt very unsatisfied with the surgery.

CONCLUSIONLaparoscopic fundoplication is safe and effective for GERD-related cough, with quite high satisfaction degree form patients.

Cough ; Deglutition Disorders ; Fundoplication ; Gastroesophageal Reflux ; Humans ; Laparoscopy ; Retrospective Studies ; Surveys and Questionnaires