Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model

AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.

The cost of obsessive- compulsive disorder (OCD) in China: a multi- center cross- sectional survey based on hospitals

Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in China.Methods The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China.The direct method was used to get the direct cost of OCD.Indirect costs associated with OCD were estimated using the human capital approach.Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost.Sensitivity analysis was used to analyse the uncertainty of total cost.Results The mean quality of life score for OCD was 52.78(20.46).The annual total cost of OCD per capita was 24503.78(95%CI:22621.53 to 26386.03)renminbi(RMB)(US$3465.88(95%CI:US$3199.65 to US$3732.11)).The annual cost of OCD in China was estimated to be 37.74 billion(95%CI:34.95 billion to 40.53 billion)RMB(equal to US$5.34 billion(95%CI:US$4.94 billion to US$5.73 billion)).Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB(US$3.27 billion)and 370.00 billion RMB(US$52.33 billion).Worse social function status,more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale(Y-BOCS)score were associated with worse quality of life.The numbers of clinic visits and hospitalisations,socioeconomic status,education,Y-BOCS scores and age were found to be significantly associated with total cost.Conclusions OCD is associated with low quality of life and high costs in China.The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis,the provision of evidence-based treatments and relapse prevention strategies.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer:Results from 24 hospitals in China

BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.

Chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease:Correlations with blood eosinophil level

Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LD grade 4,middle lobe of right lung WT grade 5,upper lobe of right lung WA grade 4,middle lobe of right lung WA grade 5 and lower lobe of left lung WA grade 3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LD grade 4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.

Diagnostic value of digital continuous bowel sounds in critically ill patients with acute gastrointestinal injury: A prospective observational study

BACKGROUND Acute gastrointestinal injury(AGI)is common in intensive care unit(ICU)and worsens the prognosis of critically ill patients.The four-point grading system proposed by the European Society of Intensive Care Medicine is subjective and lacks specificity.Therefore,a more objective method is required to evaluate and determine the grade of gastrointestinal dysfunction in this patient population.Digital continuous monitoring of bowel sounds and some biomarkers can change in gastrointestinal injuries.We aimed to develop a model of AGI using continuous monitoring of bowel sounds and biomarkers.AIM To develop a model to discriminate AGI by monitoring bowel sounds and biomarker indicators.METHODS We conducted a prospective observational study with 75 patients in an ICU of a tertiary-care hospital to create a diagnostic model for AGI.We recorded their bowel sounds,assessed AGI grading,collected clinical data,and measured biomarkers.We evaluated the model using misjudgment probability and leave-one-out cross-validation.RESULTS Mean bowel sound rate and citrulline level are independent risk factors for AGI.Gastrin was identified as a risk factor for the severity of AGI.Other factors that correlated with AGI include mean bowel sound rate,amplitude,interval time,Sequential Organ Failure Assessment score,Acute Physiology and Chronic Health Evaluation II score,platelet count,total protein level,blood gas potential of hydrogen(pH),and bicarbonate(HCO3-)level.Two discriminant models were constructed with a misclassification probability of<0.1.Leave-one-out cross-validation correctly classified 69.8%of the cases.CONCLUSION Our AGI diagnostic model represents a potentially effective approach for clinical AGI grading and holds promise as an objective diagnostic standard for AGI.

Novel magnetic compression technique for the treatment of postoperative anastomotic stenosis in rectal cancer:A case report

BACKGROUND The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging.Endoscopic balloon dilation and radial incision are not effective in all patients.We present a new endoscopy-assisted magnetic compression technique(MCT)for the treatment of rectal anastomotic stenosis.We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer.A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago.A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed.The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT.We performed endoscopy-assisted magnetic compression surgery for rectal stenosis.The magnets were removed 16 d later.A follow-up colonoscopy performed after 4 months showed good anastomotic patency,following which,ileostomy closure surgery was performed.CONCLUSION MCT is a simple,non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer.The technique can be widely used in clinical settings.

Influence of different magnetic forces on the effect of colonic anastomosis in rats

BACKGROUND Despite much work having been conducted on magnetic compression anastomo-sis(MCA)in the digestive tract,there are no reports on the influence of magnetic force on the anastomosis.AIM To investigate the effect of different magnetic force magnets on the MCA of the digestive tract.METHODS Two groups of magnets of the same sizes but different magnetic forces were designed and produced.A total of 24 Sprague-Dawley rats were randomly assigned into two groups(powerful magnet group and common magnet group),with 12 rats in each group.Two types of magnets were used to complete the colonic side-to-side anastomosis of the rats.The operation time and magnet discharge time were recorded.The anastomotic specimens were obtained 4 wk after the operation and then the burst pressure and diameter of the anastomosis were measured,and the anastomosis was observed via the naked eye and subjected to histological examination.RESULTS The magnetic forces of the powerful and common magnet groups at zero distance were 8.26 N and 4.10 N,respectively.The colonic side-to-side anastomosis was completed in all 24 rats,and the operation success rate and postoperative survival rate were 100%.No significant difference was noted in the operation time between the two groups.The magnet discharge time of the powerful magnet group was slightly longer than that of the common magnet group,but the difference was not statistically significant(P=0.513).Furthermore,there was no statistical difference in the burst pressure(P=0.266)or diameter of magnetic anastomosis(P=0.095)between the two groups.The gross specimens of the two groups showed good anastomotic healing,and histological observation indicated good mucosal continuity without differences on healing.CONCLUSION In the rat colonic side-to-side MCA model,both the powerful magnet with 8.26 N and the common magnet with 4.10 N showed no significant impact on the anastomosis establishment process or its effect.

Dynamic expression of nerve growth factor and its receptor Trk A after subarachnoid hemorrhage in rat brain

Delayed ischemic neurologic deficit after subarachnoid hemorrhage results from loss of neural cells.Nerve growth factor and its receptor Trk A may promote regeneration of neural cells,but their expression after subarachnoid hemorrhage remains unclear.In the present study,a rat model of subarachnoid hemorrhage was established using two injections of autologous blood into the cistern magna.Immunohistochemical staining suggested that the expression of nerve growth factor and Trk A in the cerebral cortex and brainstem increased at 6 hours,peaked at 12 hours and decreased 1 day after induction of subarachnoid hemorrhage,whereas the expression in the hippocampus increased at 6 hours,peaked on day 1,and decreased 3 days later.Compared with those for the rats in the sham and saline groups,neurobehavioral scores decreased significantly 12 hours and 3 days after subarachnoid hemorrhage（P 〈 0.05）.These results suggest that the expression of nerve growth factor and its receptor Trk A is dynamically changed in the rat brain and may thus participate in neuronal survival and nerve regeneration after subarachnoid hemorrhage.

Prognostic factors of refractory NSCLC patients receiving anlotinib hydrochloride as the third-or further-line treatment

Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.

Impact of cigarette smoking on recurrence of hyperlipidemic acute pancreatitis

AIM To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis(HLAP).METHODS A total of 863 patients were admitted to our hospital for acute pancreatitis(AP) from January 2013 to March2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During followup, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival(RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test.RESULTS No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP(50.0% and 77.8%, respectively) than non-smokers(9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23(26.1%) patients. Multivariate analysis identified current smoking(HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers(23 mo vs 42 mo), but no significant difference was documented between ex-smokers(34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers.CONCLUSION Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.

A radiomic nomogram based on an apparent diffusion coefficient map for differential diagnosis of suspicious breast findings

Objective： To develop and validate a radiomic nomogram based on an apparent diffusion coefficient （ADC） mapfor differentiating benign and malignant lesions in suspicious breast findings classified as Breast Imaging Reportingand Data System （BI-RADS） category 4 on breast magnetic resonance imaging （MR2）.Methods： Eighty-eight patients diagnosed with BI-RADS 4 findings on breast MRI in the First AffiliatedHospital of China Medical University from December 2014 to December 2015 were retrospectively analyzed inthis study. Sixty-three were randomized electronically to establish forecasting models, and the other 25 were usedfor validation. Radiomic features based on the ADC map were generated automatically by Artificial Intelligence Kitsoftware （A.K. software; GE Healthcare, China）. Feature reduction was conducted using the Mann-Whitney testand Spearman correlation after pre-treatment. A prediction model of ADC radiomics was established by logisticlinear regression and cross-validation. A nomogram was established based on ADC radiomic features,pharmacokinetics and clinical features, including the morphology and ADC value for breast BI-RADS 4 lesionson MRI.Results： A total of 396 radiomic features were extracted automatically by the A.K. software. Five features wereselected after pre-processing, Mann-Whitney tests and Spearman correlation analysis. The area under the ROCcurve of the prediction model comprising ADC radiomie features was 0.79 when the cutoffvalue was 0.45, and theaccuracy, sensitivity and specificity were 80.0%, 0.813 and 0.778, respectively. A visualized differential nomogrambased on the radiomic score, pharmacokinetics and clinical features was established. The decision curve showedgood consistency.Conclusions： ADC radiomie features could provide an important reference for differential diagnosis betweenbenign and malignant lesions in suspicious BI-RADS 4 lesions. The visualized nomogram based on ADC radiomicfeatures, pharmaeokinetics and clinical features may have good prospects for clinical application.

Value of pretransplant albumin-bilirubin score in predicting outcomes after liver transplantation

BACKGROUND Due to the significant shortage of organs and the increasing number of candidates on the transplant waiting list, there is an urgent need to identify patients who are most likely to benefit from liver transplantation. The albuminbilirubin(ALBI) grading system was recently developed to identify patients at risk for adverse outcomes after hepatectomy. However, the value of the pretransplant ALBI score in predicting outcomes after liver transplantation has not been assessed.AIM To retrospectively investigate the value of the pretransplant ALBI score in predicting outcomes after liver transplantation.METHODS The clinical data of 272 consecutive adult patients who received donation after cardiac death and underwent liver transplantation at our centre from March 2012 to March 2017 were analysed in the cohort study. After the exclusion of patients who met any of the exclusion criteria, 258 patients remained. The performance of the ALBI score in predicting overall survival and postoperative complications after liver transplantation was evaluated. The optimal cut-off value of preoperative ALBI was calculated according to long-term survival status. The outcomes after liver transplantation, including postoperative complications and survival analysis, were measured.RESULTS The remaining 258 consecutive patients were included in the analysis. The median follow-up time was 17.30(interquartile range: 8.90-28.98) mo. Death occurred in 35 patients during follow-up. The overall survival rate was 81.0%.The preoperative ALBI score had a significant positive correlation with the overall survival rate after liver transplantation. The calculated cut-off for ALBI scores to predict postoperative survival was-1.48. Patients with an ALBI score >-1.48 had a significantly lower survival rate than those with an ALBI score ≤-1.48(73.7% vs 87.6%, P < 0.05), and there were no statistically significant differences in survival rates between patients with a model for end stage liver disease score ≥ 10 and < 10 and different Child-Pugh grades. In terms of the specific complications,a high ALBI score was associated with an increased incidence of biliary complications, intraabdominal bleeding, septicaemia, and acute kidney injury after liver transplantation(P < 0.05 for all).CONCLUSION The ALBI score predicts overall survival and postoperative complications after liver transplantation. The ALBI grading system may be useful in risk-stratifying patients on the liver transplant waiting list.

Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

AIM： To study the effects of lysophosphatidic acid （LPA） on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action. METHODS： Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transweU migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol. RESULTS： LPA significantly stimulated SW480 cell proliferation in a dose-dependent and timeependent manner compared with the control group （P 〈 0.05） while the mitogen-activated protein kinase （MAPK） inhibitor, PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner （P 〈 0.05）. Rho kinase inhibitor, Y-27632, significantly inhibited the upegulatory effect of LPA on adhesion and migration （P 〈 0.05）. LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU （P 〈 0.05）, but the phosphoinositide 3-kinase （PI3K） inhibitor, LY294002, significantly blocked the protective effect of LPA on apoptosis. CONCLUSION： LPA stimulated proliferation, adhesion,migration of 5W480 cells, and protected from apoptosis. The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3K- AKT/PKB signal pathways may be involved.

Quantitative computed tomography analysis for stratifying the severity of Coronavirus Disease 2019

To examine the feasibility of using a computer tool for stratifying the severity of Coronavirus Disease 2019(COVID-19)based on computed tomography(CT)images.We retrospectively examined 44 confirmed COVID-19 cases.All cases were evaluated separately by radiologists(visually)and through an in-house computer software.The degree of lesions was visually scored by the radiologist,as follows,for each of the 5 lung lobes:0,no lesion present;1,<1/3 involvement;2,>1/3 and<2/3 involvement;and 3,>2/3 involvement.Lesion density was assessed based on the proportion of ground-glass opacity(GGO),consolidation and fibrosis of the lesions.The parameters obtained using the computer tool included lung volume(mL),lesion volume(mL),lesion percentage(%),and mean lesion density(HU)of the whole lung,right lung,left lung,and each lobe.The scores obtained by the radiologists and quantitative results generated by the computer software were tested for correlation.A Chi-square test was used to test the consistency of radiologist-and computer-derived lesion percentage in the right/left lung,upper/lower lobe,and each of the 5 lobes.The results showed a strong to moderate correlation between lesion percentage scores obtained by radiologists and the computer software(r ranged from 0.7679 to 0.8373,P<0.05),and a moderate correlation between the proportion of GGO and mean lesion density(r=-0.5894,P<0.05),and proportion of consolidation and mean lesion density(r=0.6282,P<0.05).Computer-aided quantification showed a statistical significant higher lesion percentage for lower lobes than that assessed by the radiologists(x^2=8.160,P=0.004).Our experiments demonstrated that the computer tool could reliably and accurately assess the severity and distribution of pneumonia on CT scans.

Comparison of visual outcomes with implantation of trifocal versus bifocal intraocular lens after phacoemulsification: a Meta-analysis

AIM： To compare a trifocal intraocular lens （IOL） and a bifocal IOL implantation in improving visual function after cataract surgery. METHODS： Eligible literatures were systematically searched through EMBASE and PubMed databases. The inclusion criteria were prospective comparative clinical trials on cataract surgery comparing trifocal IOL with bifocal IOL implantation that assessed visual acuity, contrast sensitivity and subjective vision quality. The effects were computed as standardized mean differences and pooled using fixed-effect or random-effect models. RESULTS： Four prospective randomized controlled trials （RCTs） and five cohorts provided data were included by a systematic review, comprising 265 eyes implanted with trifocal IOLs and 264 eyes implanted with bifocal IOLs. Monocular distance visual acuity （VA） showed a statistically significant but small difference that favored trifocal IOLs （MD=.0.06; 95%CI, -0.10 to -0.02; Z=2.90, P=0.004 for uncorrected distance VA, and MD- -0.02; 95%CI, -0.03 to .0.00; Z=2.02, P=0.04 for corrected distance VA）, but the data did not suggest that the effect of trifocal IOL implantation would clinically outperform bifocal IOL implantation. There was no significant difference in monocular near VA （MD=.0.01; 95%CI, -0.07 to 0.04; Z=0.42, P=-0.68 for distance-corrected near VA, and MD=-0.01; 95%CI, -0.06 to 0.03; Z=0.55, P=0.58 for corrected near VA） or refraction between two groups. Contrast sensitivity and subjective visual quality had no conclusive results. CONCLUSION： All results indicate that trifocal IOL and bifocal IOL had similar levels of monocular distance and near VA.

Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

AIM: To explore the synergistic effect of docosahexaenoic acid(DHA)/5-fluorouracil(5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes(METCs)?Ⅰ, Ⅱ and Ⅴ in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU(G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase(G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells.CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.

Serial lumbar puncture reduces cerebrospinal fluid (CSF) infection during removal of hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling

The present study aimed to compare the complications and clinical outcomes of serial lumbar puncture（LP） and lumbar cerebrospinal fluid（CSF） drainage（LD） of patients with aneurysmal subarachnoid hemorrhage and provide more evidence to guide clinical management.In this retrospective study,41 and 39 aneurysmal subarachnoid hemorrhage patients were enrolled in the LP and LD group,respectively.Clinical outcomes,including CSF infection,intracerebral hemorrhage,vasospasm,hydrocephalus,death,length of stay,duration of drainage and the Glasgow Outcome Scale score were compared between the two groups.By comparing with the LP group,the LD group showed a significantly higher rate of CSF infection（P= 0.029） and shorter duration of drainage（P〈 0.001）.Both groups displayed similar rates of vasospasm,hydrocephalus,intracerebral hemorrhage,the Glasgow Outcome Scale score one month after endovascular coiling and length of stay（P〉 0.05,respectively）.In conclusion,both LD and serial LP are effective methods in the treatment of aneurysmal subarachnoid hemorrhage; besides,serial LP can reduce the incidence of CSF infection in draining hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling.

Parafoveal retinal massage combined with autologous blood cover in the management of giant,persistent or recurrent macular holes

AIM:To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes(MHs)and present the surgical procedure.METHODS:Patients with giant(minimum diameter>800 pm),recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study.After surgery,all patients were informed to maintain a prone position for at least 7d.Preoperative and postoperative best-corrected visual acuities(BCVAs)were compared and MH closure rate was measured as the main outcome.RESULTS:A total of 13 MH patients consisted of 6 giant MHs,4 persistent holes and 3 recurrent holes(5 men and 8 women;average age was 56.40±11.72y)were enrolled in this study.MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed.Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed.No intraoperative complications were observed.BCVA improved from 1.73 IogMAR to 0.74 IogMAR at 6mo postoperation.There was significant difference in BCVA before versus after the surgery(P<0.05).There were no adverse events occurred during the follow-up period.CONCLUSION:With easier surgical procedure,parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.

Clinical characteristics and current management of hepatitis B and C in China

AIM: To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status. METHODS: A multicenter, cross-sectional study of HBV- and/or HCV-infected patients was conducted from August to November, 2011 in western China. Patients >= 18 years of age with HBV and/or HCV infections who visited outpatient departments at 10 hospitals were evaluated, whether treated or not. Data were collected on the day of visit from medical records and patient interviews. RESULTS: A total 4010 outpatients were analyzed, including 2562 HBV- infected and 1406 HCV-infected and 42 HBV/HCV co-infected patients. The median duration of documented infection was 7.5 years in HBV- infected and 1.8 years in HCV-infected patients. Cirrhosis was the most frequent hepatic complication (12.2%), appearing in one-third of patients within 3 years prior to or at diagnosis. The HCV genotype was determined in only 10% of HCV-infected patients. Biopsy data were only available for 54 patients (1.3%). Antiviral medications had been received by 58.2% of patients with HBV infection and 66.6% with HCV infection. Nucleos(t) ide analogs were the major antiviral medications prescribed for HBV- infected patients (most commonly adefovir dipivoxil and lamivudine). Ribavirin + pegylated interferon was prescribed for two-thirds of HCV-infected patients. In the previous 12 mo, around one-fifth patients had been hospitalized due to HBV or HCV infection. CONCLUSION: This observational, real-life study has identified some gaps between clinical practice and guideline recommendations in China. To achieve better health outcomes, several improvements, such as disease monitoring and optimizing antiviral regimens, should be made to improve disease management. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

The aim of this study was to evaluate the effects of low-dose tibolone therapy on ovarian area, uterine volume and endometrial thickness, and define the cut-off value of endometrial thickness for curettage during uterine bleeding. We followed 619 postmenopausal women, aged 40-60 years, for two years. There were 301 subjects in the low-dose tibolone treatment group and 318 subjects in the control group. The ovarian area, uterine volume and endometrial thickness in all participants were measured by transvaginal ultrasound prior to, one and two years post enrollment, respectively. Endometrial specimens were collected from all subjects with abnormal uterine bleeding during the follow-up period. We found that the uterine volume in the treatment group was greater than that in the control group, and the difference was significant （P〈0.05）, but there were no significant differences in ovarian area and endometrial thickness between the two groups （P〉0.05）. When the cut-off value for endometrial thickness was 7.35 ram, the sensitivity and specificity were 100% and 79.07%, respectively, and 85.71% and 93.02% when 7.55 mm was set as the cut-offduring tibolone therapy. The results indicate that low-dose tibolone therapy may postpone uterine atrophy and the cut-off value of endometrial thickness may be appropriately adjusted for curettage.