Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

Aspects of the Molecular Markers of Hemostatic Mechanism in Qinical Medicine

Thrombosis is the pathological process resulting from the inappropriate and propagation of the hemostatic response. The principle determinants of thrombosis can be categorized in contemporary terms according to Virchow' s paradigm: abnormalities in endothelial function ( vessel function ), rheotogy ( blood flow ), or blood component,either alone or in combination, can promote thrombus formation.

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

Monte Carlo method for evaluation of surface emission rate measurement uncertainty

The aim of this study is to evaluate the uncertainty of 2πα and 2πβ surface emission rates using the windowless multiwire proportional counter method.This study used the Monte Carlo method (MCM) to validate the conventional Guide to the Expression of Uncertainty in Measurement (GUM) method.A dead time measurement model for the two-source method was established based on the characteristics of a single-channel measurement system,and the voltage threshold correction factor measurement function was indirectly obtained by fitting the threshold correction curve.The uncertainty in the surface emission rate was calculated using the GUM method and the law of propagation of uncertainty.The MCM provided clear definitions for each input quantity and its uncertainty distribution,and the simulation training was realized with a complete and complex mathematical model.The results of the surface emission rate uncertainty evaluation for four radioactive plane sources using both methods showed the uncertainty’s consistency E_(n)<0.070 for the comparison of each source,and the uncertainty results of the GUM were all lower than those of the MCM.However,the MCM has a more objective evaluation process and can serve as a validation tool for GUM results.

Pharmacological effects of bioactive agents in earthworm extract:A comprehensive review

This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Left lower lobe sleeve resection for the clear cell variant of pulmonary mucoepidermoid carcinoma:A case report

BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.

Clinical effect of laparoscopic radical resection of colorectal cancer based on propensity score matching

BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery;and(5)Physical status:One month after surgery,the Karnofsky performance score in the observation group was higher than that in the control group.CONCLUSION Laparoscopic radical resection of CRC has significant benefits,such as reducing postoperative pain and postoperative inflammatory response,avoiding excessive immune inhibition,and contributing to postoperative recovery.

Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury

AIM:To investigate the protective effects,antioxidant potential,and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-Daspartate(NMDA)-induced retinal ganglion cell(RGC)injury in a mouse model of glaucoma.METHODS:The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining.Intracellular reactive oxygen species(ROS)production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry.The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina.The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatographymass spectroscopy(LC-MS)and untargeted metabolomics analyses.RESULTS:Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro.Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model.Untargeted metabolomics analyses showed that eicosane increased multiple metabolites,including L-arginine and L-carnitine,in the retina.CONCLUSION:Eicosane has protective effects,antioxidant potential,and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

Correlation of preoperative inflammatory factors and emotional disorders with postoperative delirium in patients with craniocerebral trauma

BACKGROUND Traumatic brain injury(TBI)imposes a substantial societal and familial burden due to its high disability and fatality rates,rendering it a serious public health problem.Some patients with TBI have poor treatment outcomes and are prone to postoperative delirium(POD),which affects their quality of life.Anxiety has been linked to increased POD incidence in some studies,while others have found no correlation.AIM To investigate the correlation of POD risk factors,preoperative inflammatory factors,and mood disorders in patients with TBI.METHODS We retrospectively collected data on the treatment of 80 patients with TBI from November 2021 to September 2023.Patients were grouped as POD and non-POD,according to their POD status,and the general data of the two groups were compared.Inflammatory factor levels were detected preoperatively,and the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)were used to investigate the risk factors associated with POD in these patients.Logistic regression was used to identify the independent risk factors.RESULTS Twenty-one patients(26.25%)developed POD,including 7,10,and 4 cases of the excitatory,inhibitory,and mixed types,respectively.There were 59 cases(73.75%)in the non-POD group.Compared with the non-POD group,the POD group had a significantly higher proportion of patients with low Glasgow Coma Scale(GCS)scores before admission,unilateral mydriasis,preoperative hemorrhagic shock,intraventricular hemorrhage(IVH),and postoperative hyperglycemic hyperosmolar disease(P<0.05).In the POD group,interleukin-6(IL-6),human tumor necrosis factor-α(TNF-α),myeloperoxidase levels,HAMA,and HAMD scores were higher than those in the non-POD group(all P<0.05).Logistic multivariate analysis showed that GCS score at admission,IVH,IL-6,TNF-α,HAMA,and HAMD were independent risk factors for POD in patients with TBI(P<0.05).CONCLUSION Low GCS score at admission,IVH,elevated IL-6 and TNF-α,other inflammatory indicators,anxiety,and depression,can increase the risk of POD in patients with TBI after surgery.

Prolonged course of Paxlovid administration in a centenarian with COVID-19:A case report

BACKGROUND According to the population statistics in 2023,there were 110000 people aged over 100 years in China,and the experience of using Paxlovid(nirmatrelvir/ritonavir)for centenarians is particularly valuable.This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019(COVID-19)infection.CASE SUMMARY A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days.During treatment,the patient was complicated with lung infection and heart failure,and nucleic acid remained positive.After expert consultation,a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days.Meanwhile,anti-heart failure and antibiotics were administered;the heart failure and pulmonary infection were improved.Finally,on the 33^(th) day of admission,nucleic acid turned negative,body temperature returned to normal,cough and sputum,fatigue,poor appetite and other symptoms basically improved.The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function,diarrhea,nausea and vomiting,myalgia,chest tightness and other side effects,and was discharged from hospital with good recovery.CONCLUSION This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.

Changes in visual performance after implantation of different intraocular lenses

AIM:To evaluate the trending visual performance of different intraocular lenses(IOLs)over time after implantation.METHODS:Ninety-one patients received cataract surgery with implantations of monofocal(Mon)IOLs,segmental refractive(SegRef)IOLs,diffractive(Dif)IOLs,and extendeddepth-of-focus(EDoF)IOLs were included.The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared.RESULTS:Most of the visual parameters improved over the postoperative 6mo.The postoperative visual acuity(POVA)of the Mon IOL,SegRef IOL,and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group.Nevertheless,the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo.The optical quality initially improved in the EDoF IOL group,then in the Mon IOL,SegRef IOL,and Dif IOL groups.POVA and objective visual performance of the Mon IOL and EDoF IOL groups,as well as POVA and visual quality of the Dif IOL group,improved in the postoperative 1mo and stabilized.Within the postoperative 6mo,gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group,as well as in the postoperative optical quality of the Dif IOL group.CONCLUSION:The visual performance is different among eyes implanted with different IOLs.The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).

Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.

Enhanced proliferation,invasion,and epithelial-mesenchymal transition of nicotine-promoted gastric cancer by periostin

AIM:To investigate the contribution of periostin in nicotine-promoted gastric cancer cell proliferation,survival,invasion,drug resistance,and epithelial-mesenchymal transition(EMT).METHODS:Gastric cancer cells were treated with nicotine and periostin protein expression was determined by immunoblotting.Periostin mRNA in gastric cancer cells was silenced using small interfering RNA(siRNA) techniques and periostin gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Gastric cancer cells transfected with control or periostin siRNA plasmid were compared in terms of cell proliferation using the methylthiazolyldiphenyl-tetrazolium bromide assay.Cell apoptosis was compared using annexin V-fluoresceine isothiocyanate and propidium iodine double staining.Tumor invasion was determined using the Boyden chamber invasion assay,and the EMT marker Snail expression was evaluated by immunoblotting.RESULTS:Nicotine upregulated periostin in gastric cancer cells through a COX-2 dependent pathway,which was blocked by the COX-2-specific inhibitor NS398.Periostin mRNA expression was decreased by ～87.2% by siRNA in gastric cancer cells,and stable periostinsilenced cells were obtained by G418 screening.Periostin-silenced gastric cancer cells exhibited reduced cell proliferation,elevated sensitivity to chemotherapy with 5-fluorouracil,and decreased cell invasion and Snail expression(P < 0.05).CONCLUSION:Periostin is a nicotine target gene in gastric cancer and plays a role in gastric cancer cell growth,invasion,drug resistance,and EMT facilitated by nicotine.

Effect of ulinastatin combined rivaroxaban on deep vein thrombosis in major orthopedic surgery

Objective:To explore the effect of ulinastatin(UTI) continuous infusion combined Rivaroxaban on the deep vein thrombosis in patients undergoing major orthopedic surgery.Methods:Forty-five patients undergoing major orthopedic surgery were randomly divided into three groups:ulinastatin continuous infusion(Uc) group,ulinastatin single injection(Us) group and control(C) group.All patients received patient-controlled intravenous analgesia(PCIA) after operation,and took Rivaroxaban 10 mg orally 12 hours after operation.Ulinastatin(5 000 U/kg)was given intravenously to both Uc and Us groups preoperatively.Group C was given isometric normal saline,group Uc was pumped UTI continuous intravenously at the end of surgery(10 000U/kg) to 48 hours through PCIA pump.The values of hematocrit(HCT),thrombomodulin(TM),Interleukin(IL-6),thrombin-antithrombin complex(TAT),D-Dimer(D-D) were normally tested before surgery(T1),at the end of the surgery(T2),12 hours(T3).24 hours(T4) and 48 hours(T5)after surgery.Results:Compared with T1,there was an upward tendency in TM,IL-6,TAT,and D-D after operation in group C group(P <0.05).The values of them were significandy increased from nearly 24-hour after surgery in Us group(P<0.05).In group Uc.there were no significant changes in these indices after operation(P>0.05).Conclusions:During the perioperative period,ulinastatin continuous infusion combined Rivaroxaban can correct blood hypercoagulability through different approaches in patients undergoing major orthopedic surgery.

Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema Correlation with variation in apparent diffusion coefficient

To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 pL shRNA- aquaporin-4 （control group） or siRNA- aquaporin-4 solution （1：800） （RNA interference group） into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25- 6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5 4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson＇s correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient （r = -0.806, P 〈 0.01）. These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracelfular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

Clinicopathological Characteristics and Prognosis of Hepatoid Adenocarcinoma of the Stomach:Evaluation of a Pooled Case Series

Hepatoid adenocarcinoma of the stomach (HAS)is an extremely rare and unique gastric malignancy.The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis.We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016,as well as 294 cases reported prior to 2017 in research databases.Among these patients,45.6%(115/252)had lesions in the gastric antrum and 77.0%(235/305)were male.Elevated levels of serum alpha-fetoprotein (AFP)were detected in most patients(75/93,80.6%).Vascular invasion(199/286,69.6%),lymph node metastasis (222/283,78.4%),and preoperative distant metastasis (121/328,36.9%)were commonly observed.The 5-year disease-free survival (DFS)and disease-specific survival (DSS) were 20.7%and 29.2%,respectively.DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS:P<0.001, hazard ratio (HR)=-1.831,95%confidence interval (CI):0.060-0.429;DSS:P<0.001,HR=-2.185, 95%CI:0.032-0.401].In conclusion,HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer.Complete surgery,early pTNM stage,and adjuvant therapy may predict a more favorable prognosis.Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.

Discrimination of Metastatic from Non-metastatic Mesorectal Lymph Nodes in Rectal Cancer Using Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Preoperative detection of lymph nodes（LNs） metastasis is always highly challenging for radiologists nowadays. The utility of quantitative dynamic contrast-enhanced magnetic resonance imaging（QDCE-MRI） in identifying LNs metastasis is not well understood. In the present study, 59 patients with histologically proven rectal carcinoma underwent preoperative QDCE-MRI. The short axis diameter ratio, long axis diameter ratio, short-to-long axis diameter ratio and QDEC-MRI parameters（Ktrans, Kep, fPV and Ve） values were compared between the non-metastatic（n=44） and metastatic（n=35） LNs groups based on pathological examination. Compared with the non-metastatic group, the metastatic group exhibited significantly higher short axis diameter（7.558±0.668 mm vs. 5.427±0.285 mm）, Ktrans（0.483±0.198 min-1 vs. 0.218±0.116 min^-1） and Ve（0.399±0.118 vs. 0.203±0.096） values（all P〈0.05）. The short-to-long axis diameter ratio, long axis diameter ratio, Kep and fPV values did not show significant differences between the two groups. In conclusion, our results showed that for LNs larger than 5 mm in rectal cancer, there are distinctive differences in the Ktrans and Ve values between the metastatic and non-metastatic LNs, suggesting that QDCE-MRI may be potentially helpful in identifying LNs status.