ObjectiveTo evaluate the function of the salivary glands with gustatory stimulation by using MR DWI.MethodsA prospective study was conducted in 30 patients with nasopharyngeal carcinoma who had normal salivary function.A DWI sequence was performed on the salivary glands at resting state,and continually repeated on the parotid immediately after oral ascorbic acid stimulation over a period of 21 minutes (once every 18 seconds).The multiple b-values (0,400,600,800,1000 s/mm2) were used.ADC maps were evaluated with a manually placed region of interest including the entire salivary gland.The ADC of each gland was obtained by taking the mean of values on three contiguous sections containing the largest areas of the gland.The paired two-tailed Student t test was used to compare the ADC values of the parotid and the submandibular glands at rest,and of the parotid before and after stimulation.ResultsThe mean ADC value at rest was significantly lower in the parotid [ (1.23 ±0.12) × 10-3 mm2/s] than in the submandibular glands [(1.34 ± 0.07 ) × 10 -3 mm2/s,t =4.545,P ＜ 0.01 ].After acid stimulation,the ADC value increased from the baseline to (1.41 ±0.19) × 10-3 mm2/s firstly and then fluctuated at the following time,with a peak value of ( 1.49 ± 0.20 )× 10 -3 mm2/s and the average value of ( 1.36 ±0.17) × 10-3 mm2/s.The average value was significantly different from the baseline value (t =15.127,t =11.905,P ＜ 0.01 ).The minimum value [ ( 1.24 ± 0.14) × 10-3 mm2/s] was not significantly different compared to the baseline value (t =1.329,P ＞ 0.05 ).ConclusionMR DW1 can noninvasively evaluate the physiologic changes of salivary glands before and after acid stimulation.

Objective:To investigate the correlation between certain unhealthy lifestyles and the incidence of gastroesophageal reflux disease (GERD),thus to provide the lifestyle guidelines for GERD patients.Methods:Retrospective study were conducted for 402 GERD and 276 non-GERD out-patients in Department of Gastroenterology,Third Xiangya Hospital,Central South University from August,2014 to August,2015 based on questionnaire survey,then the correlation of unhealthy lifestyles with GERD were analyzed.Results:The top 10 common symptoms for GERD were as follows:reflux,acid regurgitation,postprandial fullness,heartburn,swallow obstruction or pain,epigastric burning sensation,paraesthesia pharynges,poststernal pain,chronic laryngopharyngitis,and chronic cough.The top 8 unhealthy habits closely related to GERD were as follows:fast-eating,over-eating,spicy preferred diet,sweets preferred diet,anxious,soup preferred diet,high-fat diet,and hot eating.Single-factor analysis showed that GERD was markedly correlated to gender (male),age (≥ 60 years),BMI,smoking,alcohol fast-eating,over-eating,hot-eating,spicy preferred diet,high-fat diet,acid preferred diet,sweets preferred diet,hard food preference,strong tea preference,coffee preference,immediately on bed after meal,difficult defecation,dyscoimesis,anxious,and too tight belt,respectively (P＜0.05).Logistic multiple regression analysis indicated that the largest risk factor for GERD was the fast-eating (OR=3.214,95％ CI 2.171 to 4.759,P＜0.001) followed by the overeating (OR=2.936,95％ CI 1.981 to 4.350,P＜0.001),elderly population (OR=2.047,95％ CI 1.291 to 3.244,P=0.002),too tight belt (OR=2.003,95％ CI 1.013 to 3.961,P=0.046),and hot-eating (OR=1.570,95％ CI 1.044 to 2.362,P=0.030).Conclusion:The elderly people are at high risk for GERD,and unhealthy habits like fast-eating,over-eating,too tight belt,and hot-eating is closely related to GERD.The lifestyles such as chewing food thoroughly,splitting the meals up,warm and cool diet,keeping patients out of the too tight belt are necessary for GERD patients.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

To study the pharmacokinetics characteristic of loganin, ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique, the concentrations were determined by HPLC-UV. Johnson spherigel C18 column (4.6 mm x 250 mm, 5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0.01% glacial acetic acid in a gradient mode, with the flow rate at 1.0 mL x min(-1), column temperature at 30 degrees C and injection volume of 10 μL. According to the findings, loganin was determined at 235 nm, ferulic acid and stilbene glucoside were determined at 320 nm, with the sample size of 10 μL. The pharmacokinetic parameters of loganin, ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: C(max) was (0.369 ± 0.042), (0.387 ± 0.071), (0.233 ± 0.044) mg x L(-1); t(max) was (0.226 ± 0.022), (0.282 ± 0.031), (0.233 ± 0.044) h; t(½β) was (6.89 ± 0.20), (10.73 ± 0.11), (6.93 ± 0.09) h; AUC(0-∞) was (1.91 ± 0.36), (3.22 ± 0.52), (1.52 ± 0.33) mg x h x L(-1); AUCO(0-t) was (1.62 ± 0.33), (2.58 ± 0.43), (1.30 ± 0.30) mg x h x L(-1); CL was (20.2 ± 4.0), (1.39 ± 0.23), (31.7 ± 6.9) L x h(-1) x kg(-1), respectively. The results showed that after the oral administration with Bushen Tongluo formula, loganin, ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model, with a rapid absorption, loganin and stilbene glucoside was excreted at a moderate speed, and ferulic acid was excreted slowly (but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.
Administration, Oral ; Animals ; Biological Availability ; Coumaric Acids ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Iridoids ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; administration & dosage ; blood ; pharmacokinetics

Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of pLKB1, were measured in CD34(+)CD38(-) KG1a cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34(+)CD38(-) KG1a cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34(+)CD38(-) KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in the senescence of AML stem cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; genetics ; pathology ; Neoplastic Stem Cells ; drug effects ; Phosphorylation ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Sirtuin 1 ; genetics ; metabolism ; Stilbenes ; pharmacology

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CCl₄ (a mixture of pure CCl₄ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)₂D₃(0.5 µg/100 g) and the vehicle were administered simultaneously with CCl₄ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CCl₄-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.
Animals ; Apoptosis ; Bacterial Translocation ; Cholestasis ; Enterocytes ; Fibrosis ; Heme Oxygenase-1 ; Heme ; Humans ; Liver ; Liver Diseases ; Olive Oil ; Oxidative Stress ; Rats ; Tight Junctions ; Vitamin D ; Vitamins

BACKGROUNDMost indices for evaluating a diagnostic test can be expressed as functions of sensitivity (SEN) and specificity (SPE). Practically, all existing methods suffer from the inability to weight sensitivity and specificity relative to their importance. In this paper, we developed a novel index, the weighted Youden index, that allows Youden index to be a combination of sensitivity and specificity with user-defined weights.

METHODSThe weighted Youden index Jw is defined as Jw = 2(w×SEN + (1-w)SPE)-1 (0 ≤ w ≤ 1). It has three properties: (1) the sum of the weights which are attached to sensitivity and specificity should be equal to 1; (2) the range of Jw should be within [-1, 1], which is the range of the Youden index J; (3) Jw should be equal to J when sensitivity and specificity have equal weights. According to the central limit theorem, we obtain the standard error of Jw, and propose a statistical inference method to compare two weighted Youden indices. The monotonicity of the test statistic was discussed.

RESULTSAn example of comparing two diagnostic tests for pheochromocytoma was used to demonstrate the weighted Youden index method. Weighted Youden index, the confidence interval for each test and the hypothesis test of comparing two independent diagnostic tests were presented. Assigning the weights is essential to the weighted Youden index approach.

CONCLUSIONThe weighted Youden index can broaden its applications in diagnostic test development and motivate further research in weighting sensitivity and specificity explicitly.

Objective: To observe the intervention effect of auricular point sticking on dry eye in myopia patients after small-incision lenticule extraction (SMILE) surgery.Methods: This was a prospective randomized controlled study conducted among the myopia patients who received SMILE surgery at Eye and ENT Hospital of Fudan University. The post-SMILE operation patients who screened by the inclusion and exclusion criteria were randomized into a control group and a treatment group. Patients in the control group were given 0.1％ fluorometholone and 0.5％ carboxymethylcellulose sodium eye drops, while the treatment group was given additional unilateral auricular point sticking for 1 month. The patients were estimated using ocular surface disease index (OSDI), Schirmer tear test-1 (STT-1), tear film break-up time (TF-BUT), corneal fluorescein staining (CFS) score, corneal sensitivity (CS) and visual quality (VQ) at 1 d, 1 week and 1 month after surgery; the changes in anxiety and depression were also observed in the patients. Results: Compared with the first day after operation, CS in the nasal region was improved in the treatment group, and the VQ score increased in the control group patients at 1 week after operation (both P<0.05); at 1 month after operation, the TF-BUT increased, CFS score decreased, CS in the central and nasal regions increased (all P<0.05), and VQ score increased (P<0.01) in the treatment group, and the CS in the central, upper, lower and nasal regions were improved (all P<0.05), and VQ score increased (P<0.01) in the control group. The between-group comparison showed that the differences in the change of TF-BUT were statistically significant at 1 week and 1 month after surgery, respectively (both P<0.05). Conclusion: Auricular point sticking therapy can increase the TF-BUT and accelerate the repair of ocular surface function in post-SMILE patients.

Objective:To investigate the safety and surgical treatment effect of da Vinci robot in male thyroid surgery.Methods:Clinical data of 276 male patients undergoing robotic thyroid surgery with bilateral axillo-breast approach (BABA) admitted to our hospital from Feb. 2014 to Jan. 2020 were retrospectively analyzed. They were compared with 372 male patients (open group) who had open surgery by the same team during the same time. Surgical time, the amount of fluid selitransteise after surgery, the length of hospitalization after surgery, the number of metastatic lymph node (for malignant tumor) , cosmetic effect satisfaction, injury of recurrent laryngeal nerve and decrease of parathyroid function and other related surgical complications were analyzed. SPSS 20.0 software was employed to carry out statistical analysis, the measurement data were compared with t-test, and the counting data were analyzed by χ2 test. Results:All operations were successfully completed and on one in the robot group was converted into open surgery. Compared with the open group, surgical time of the robot group (benign: 96.78±9.67min, malignant: 143.93±15.73min) was significantly longer than that of the open group (benign: 70.40±12.49min, malignant: 112.26±15.72min) ( P<0.05) , but the postoperative beauty effect of the robot group (benign: 9.62±0.33 points, malignant: 9.59±0.31 min) was better than that of the open group (benign: 5.33±0.37 points, malignant: 5.87±1.65 points) ( P<0.05) . In patients with pathological malignancy, the average age of the robot group (40.89±11.45 years) was lower than that of the open group (44.84±11.88 years) (P<0.05) . There was no significant difference in the amount of fluid induced after surgery, the length of hospital stay after surgery or the number of cases with lymph node metastasis in the two groups ( P>0.05) . There were 2 cases in the robot group and 5 cases in the open surgery group had recurrent metastasis in the side of the neck after surgery. None of the patients had permanent larynx reflux nerve damage or permanent parathyroid dysfunction. The average follow-up time was (25.36±16.13) months, ranging from 1 to 72 months. Conclusion:Compared with traditional open surgery, da Vinci robot surgery system is safe and feasible in male thyroid surgery, with better beauty effect, and provides new options for male thyroid surgery patients with neck beauty needs.

Objective To construct the LV3-human EGF-like domain 7-targeted small hairpin RNA (LV3-hEGFL7-shRNA)-expressing plasmid system.Methods Sequence of hEGFL7-targeted shRNA was designed by Oligo Designer 3.0 based on the mRNA sequence of hEGFL7 which was obtained from the Genbank.They were recombined with the plasmid pGLV3/H1/GFP + Puro,and then those plasmids were identified by gene sequencing to make sure they were correctly connec-ted.Then those plasmids were transfected into 293T cells and fluorescence expression was observed.Results The sequence of EGFL7-shRNA was demonstrated that the inserted sequences were correct,and the titer of virus was 2 × 10s TU · mL-1.Conclusion The hEGFL7-targeted shRNA expressing plasmids were successfully constructed,identification can meet test requirements.