Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.
Biomarkers, Tumor ; Carcinoembryonic Antigen ; Humans ; Inflammation/classification* ; Lymphocytes ; Neutrophils ; Nomograms ; Preoperative Period ; Prognosis ; Rectal Neoplasms/surgery* ; Retrospective Studies

Objective To forecast the future burden and its attributable risk factors of infective endocarditis (IE). Method We analyzed the disease burden of IE and its risk factors from 1990 to 2019 using the Global Burden of Disease 2019 database and projected the disease burden from 2020 to 2030 using a Bayesian age-period-cohort model. Results By 2030, the incidence of IE will increase uncontrollably on a global scale, with developed countries having the largest number of cases and developing countries experiencing the fastest growth. The affected population will be predominantly males, but the gender gap will narrow. The elderly in high-income countries will bear the greatest burden, with a gradual shift to middle-income countries. The incidence of IE in countries with middle/high-middle social-demographic indicators (SDI) will surpass that of high SDI countries. In China, the incidence rate and the number of IE will reach 18.07 per 100,000 and 451,596 in 2030, respectively. IE-associated deaths and heart failure will continue to impose a significant burden on society, the burden on women will increase and surpass that on men, and the elderly in high-SDI countries will bear the heaviest burden. High systolic blood pressure has become the primary risk factor for IE-related death. Conclusions This study provides comprehensive analyses of the disease burden and risk factors of IE worldwide over the next decade. The IE-associated incidence will increase in the future and the death and heart failure burden will not be appropriately controlled. Gender, age, regional, and country heterogeneity should be taken seriously to facilitate in making effective strategies for lowering the IE disease burden.
Male ; Humans ; Female ; Aged ; Global Burden of Disease ; Bayes Theorem ; Global Health ; Risk Factors ; Cost of Illness ; Endocarditis ; Heart Failure

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95％CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95％CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95％CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95％CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95％CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95％CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95％CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Objective To investigate the learning curve of Da Vinci robot-assisted laparoscopic radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 42 patients who underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer in the First Affiliated Hospital of Xi'an Jiaotong University from October 2017 to August 2018 were collected.There were 30 males and 12 females,aged from 36 to 84 years,with an average age of 59 years.The learning curve was evaluated using the cumulative sum (CUSUM) analysis and the best fitting curve method.According to the minimum number of surgeries required to cross the learning curve,the patients were divided into learning stage group and mastery stage group.Then general data and surgical efficacy of the two groups were compared.Observation indicators:(1) surgical situations;(2) results of CUSUM analysis;(3) comparison of general data between the two groups;(4) comparison of surgical efficacy between the two groups;(5) follow-up.Patients were followed up by outpatient examination or telephone interview to detect the postoperative complications,tumor recurrence and metastasis up to February 2019.Measurement data with normal distribution were presented as Mean±SD,and comparison between groups was done using the independent sample t test.Count data were represented as absolute number,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test.Results (1) Surgical situations:all the 42 patients underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer successfully,without conversion to open surgery or perioperative death.Fourteen out of 42 patients underwent Da Vinci robot-assisted total radical gastrectomy and 28 underwent Da Vinci robot-assisted distal radical gastrectomy.The operation time and docking time were (213±31)minutes and (26± 11)minutes.The operation time and docking time had a tendency to decreasing as the surgical cases increasing.(2) Results of CUSUM analysis.The CUSUM learning curve were best modeled as a polynomial with equation:CUSUM (operation time)=0.016 9X3-1.913 3X2+ 50.985X-16.595,CUSUM (docking time) =0.012 8X3-1.070 7X2 + 22.189X-23.097 respectively (X means the surgical case).The P value of fitting test of models was ＜ 0.05,with goodness-of-fit (R2) as 0.960 and 0.985.The CUSUM learning curve of operation time reached its peak when the number of surgical cases accumulated to the 19th case.Nineteen cases were the minimum number of surgeries required to cross the learning curve.Similarly,The CUSUM learning curve of docking time reached its peak when the number of surgical cases accumulated to the 14th case,and 14 cases were the minimum number of surgeries required to skillfully master robot installation across the learning curve.(3) Comparison of general data between the two groups:patients were divided into learning stage group and mastery stage group with 19 cases as the cut-off point.Males,females,age,body mass index (BMI),cases in grade 1,2,3 of American society of anesthesiologists (ASA),cases with previous abdominal surgery history,cases with basic diseases,cases in T1,T2,T3,T4 stages of preoperative ultrasonic gastroscopic tumor T staging,maximum tumor diameter,cases in Ⅰ,Ⅱ,Ⅲ stages of postoperative clinical staging,cases with total gastrectomy and distal gastrectomy (surgical method) were 14,5,(60± 13)years,(23.7±2.9)kg/m2,1,16,2,3,8,5,3,3,8,(4.1±3.5)cm,6,7,6,10,9 in the learning stage group,and 16,7,(58±10)years,(23.7±1.3)kg/m2,1,17,5,2,14,3,6,9,5,(4.7±2.7)cm,8,9,6,18,5 in the mastery stage group,respectively.There was no significant difference in the sex,age,BMI,ASA score,basic diseases,preoperative ultrasonic gastroscopic tumor T staging,maximum tumor diameter,postoperative clinical staging,and surgical method between the two groups (x2 =0.086,t =0.475,-0.007,Z =-0.884,x2 =1.469,Z =-0.301,t =-0.651,Z =-0.079,-0.236,x2 =3.076,P ＞ 0.05).There was no significant difference in the previous abdominal surgery history between the two groups (P ＞ 0.05).(4) Comparison of surgical efficacy between the two groups:operation time,volume of intraoperative blood loss,number of lymph nodes harvested,time to first liquid food intake,cases with postoperative complications and duration of postoperative hospital stay were (230±25) minutes,(176± 103) mL,21±7,(5.1 ± 2.0) days,2,(9.3± 2.5)days in the learning stage group,and (191±18) minutes,(95±41)mL,21±6,(4.7±1.7)days,3,(8.4± 2.1)days in the mastery stage group,respectively.There were statistically significant differences in the operation time and volume of intraoperative blood loss between the two groups (t =5.951,-3.359,P＜0.05).There was no statistically significant difference in number of lymph nodes harvested,time to first liquid food intake,and duration of postoperative hospital stay between the two groups (t =-0.120,0.538,1.303,P＞0.05).There was no significant difference in the cases with postoperative complications between the two groups (P＞0.05).(5) Follow-up:all the 42 patients were followed up for 6-16 months,with a median time of 11 months.No serious long-term complications,tumor recurrence and metastasis or death occurred during the follow-up.Conclusions The CUSUM learning curve of Da Vinci robot-assisted radical gastrectomy for gastric cancer can be divided into the learning stage and the mastery stage.It is suggested that the surgeons need to finish 19 cases or more to master Da Vinci robot-assisted radical gastrectomy for gastric cancer.

OBJECTIVETo study the inhibitory effect of paeoniflorin (PAE) on TNF-α-induced TNF receptor type I (TNFR1)-mediated signaling pathway in mouse renal arterial endothelial cells (AECs) and to explore its underlying molecular mechanisms.

METHODSMouse AECs were cultured in vitro and then they were treated by different concentrations PAE or TNF-α for various time periods. Expression levels of intercellular cell adhesion molecule-1 (ICAM-1) were detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 6-h TNF-α 30 ng/mL), the low dose PAE group (cultured by 2-h PAE 0.8 μmo/L plus 6-h TNF-α 30 ng/mL), the middle dose PAE group (cultured by 2-h PAE 8 μmol/L plus 6-h TNF-α 30 ng/mL), the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 6-h TNF-α 30 ng/mL) with Western blot analysis. Nuclear translocation of transcription factor NF-κB (NE-κB) was detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 45-mm TNF-α 30 ng/mL), and the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 45-min TNF-α 30 ng/mL) by immunofluorescent staining. Expression levels of the phosphorylation of extracellular signal-regulated (protein) kinase (ph-ERK) and p38 (ph- p38) were detected in the normal group (cultured by serum-free culture media) and the high dose PAE group (2-h PAE 80 μmol/L culture) by Western blot. NF-κB inhibitor-α (IκBα) protein expressions were detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 30-min TNF-α 30 ng/mL), the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 30-min TNF-α 30 ng/mL), the p38 inhibitor group (SB group, pretreatment with SB238025 25 μmol/L for 30 min, then treated by PAE 80 μmol/L for 2 h, and finally treated by TNF-α 30 ng/mL for 30 min), the ERK inhibitor group (PD group, treated by PD98059 50 μmol/L for 30 min, then treated by PAE 80 μmol/L for 2 h, and finally treated by TNF-α 30 ng/mL for 30 min) by Western blot.

RESULTSCompared with the normal group, ICAM-1 protein expression levels obviously increased (P < 0.01). Compared with the TNFα group, ICAM-1 protein expression levels were obviously inhibited in the high dose PAE group (P < 0.05). Protein expression levels of ph-p38 and ph-ERK were obviously higher in the hIgh dose PAE group (P < 0.05). Compared with the normal group, IκBα protein expression levels obviously decreased in the TNF-α group (P < 0.01). Compared with the TNFα group, TNF-α-induced IκBα degradation could be significantly inhibited in the high dose PAE group (P < 0.01); the inhibition of PAE on IκBα degradation could be significantly inhibited in the SB group (P < 0.05). NF-κB/p65 signal was mainly located in cytoplasm in the normal group. NF-κB/p65 was translocated from cytoplasm to nucleus after stimulated by 45 min TNF-α in the TNF-α group, while it could be significantly inhibited in the high dose PAE group.

CONCLUSIONSPAE inhibited TNF-α-induced expression of lCAM-1. Its action might be associated with inhibiting TNFR1/NF-κB signaling pathway. p38 participated and mediated these actions.

Animals ; Cells, Cultured ; Endothelial Cells ; cytology ; drug effects ; Glucosides ; pharmacology ; Intercellular Adhesion Molecule-1 ; metabolism ; Mice ; Monoterpenes ; pharmacology ; NF-kappa B ; metabolism ; Receptors, Tumor Necrosis Factor ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology

Ebola virus (EBOV) is an aggressive pathogen that causes a highly hemorrhagic fever syndrome in humans and other mammalian species.Early detection and proper treatment is the best defense against EBOV because of high mortality rate (70％-90％).Currently,there are eleven FDA approved Ebola tests,kits,or assays for emergency use,which can be divided into two main categories:rRT-PCR and viral antigen methods.In BSL 4 lab,rRT-PCR is the most sensitive technique to detect nucleic acid of Ebola virus,including Ebola Zaire (EZ1) rRT-PCR (TaqMan) Assay,Ebola Virus NP and VP40 Real-time RTPCR Assay,FilmArray NGDS BT-E and Biothreat-E test,RealStar Ebolavirus RT-PCR kit,LightMix Ebola Zaire rRT-PCR test,and Xpert Ebola Assay.Antigen-based technology (ReEBOV Antigen Rapid Test,and OraQuick Ebola Rapid Antigen Test) provides rapid Ebola antigen test without relying on special PCR equipment.How to develop,manufacture,and market point-of-care and field testing will be the next major challenge for EBOV on various samples.

OBJECTIVETo investigate the pharmacokinetic effect of Sappan Lignum on hydroxysafflor yellow A (HSYA) in Carthami Flos.

METHODConcentration of HSYA in rat plasma was detected by RP-HPLC after rats were orally administered with extracts of Carthami Flos or Carthami Flos combined with Sappan Lignum. Pharmacokinetic parameters were calculated by DAS 2.0 pharmacokinetic software.

RESULTIn vivo pharmacokinetic models of HSYA were two-compartment open models in both of the Carthami Flos group and the Carthami Flos combined with Sappan Lignum group. After compatibility, HSYA showed a significant lower in apparent volumes of distribution of t(1/2Ka), t(1/2alpha) and V1/F, with slight advance in T(max).

CONCLUSIONSappan Lignum can accelerate absorption, distribution and metabolic process of HSYA in vivo and reduce its accumulation in vivo.

Administration, Oral ; Animals ; Caesalpinia ; chemistry ; Carthamus tinctorius ; chemistry ; Chalcone ; administration & dosage ; analogs & derivatives ; isolation & purification ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Drug Synergism ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Female ; Flowers ; chemistry ; Male ; Quinones ; administration & dosage ; isolation & purification ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Wood ; chemistry

Adult ; Female ; Foot Deformities, Congenital ; diagnosis ; genetics ; Hand Deformities, Congenital ; diagnosis ; genetics ; Humans ; Male ; Pedigree ; Young Adult