Sepsis one-hour bundle management combined with psychological intervention on negative emotion and sleep quality in patients with sepsis

BACKGROUND Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening.Patients usually experience depression and anxiety,which affect their sleep quality and post-traumatic growth levels.AIM To investigate the effects of sepsis,a one-hour bundle(H1B)management was combined with psychological intervention in patients with sepsis.METHODS This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People’s Hospital between June 2022 and June 2023.According to different intervention methods,the participants were divided into a simple group(SG,n=150)and combined group(CG,n=150).H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG.The changes of negative emotion,sleep quality and post-traumatic growth and prognosis were compared between the two groups before(T0)and after(T1)intervention.RESULTS After intervention(T1),the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG(P<0.001).Sleep time,sleep quality,sleep efficiency,daytime dysfunction,sleep disturbance dimension score,and the total score in the CG were significantly lower than those in the SG(P<0.001).The appreciation of life,mental changes,relationship with others,personal strength dimension score,and total score of the CG were significantly higher than those of the SG(P<0.001).The scores for mental health,general health status,physiological function,emotional function,physical pain,social function,energy,and physiological function in the CG were significantly higher than those in the SG(P<0.001).The mechanical ventilation time,intensive care unit stay time,and 28-d mortality of the CG were significantly lower than those of the SG(P<0.05).CONCLUSION H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.

NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer

BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

The application of the strip-shaped cymba conchae orthosis in the nonsurgical correction of complex auricular deformity

Objective: This study aims to evaluate the efficacy and safety of using a strip-shaped cymba conchae orthosis for the nonsurgical correction of complex auricular deformities. Methods: Clinical data were collected from 2020 to 2021 for 6 patients who underwent correction using a stripshaped cymba conchae orthosis. The indications, corrective effects, and complications associated with use of the orthosis were analyzed. Results: There were four indications for treatment: cryptotia with helix adhesion;cryptotia with grade I microtia;cryptotia with excessive helix thickness;and auricular deformity beyond the treatment time window(≥6 months). Excellent corrective effects were observed in all 6 patients. Complications occurred in one patient, who recovered after symptomatic treatment. Conclusion: The use of a strip-shaped cymba conchae orthosis alone or combined with a U-shaped helix orthosis presents a feasible approach for correcting complex auricular deformities or deformities beyond the treatment time window in pediatric patients.

Treatment and surveillance for non-muscle-invasive bladder cancer:a clinical practice guideline(2021 edition)

Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.

Stromal cell-derived factor-1α regulates chondrogenic differentiation via activation of the Wnt/β-catenin pathway in mesenchymal stem cells

BACKGROUND Mesenchymal stem cells(MSCs)have been applied to treat degenerative articular diseases,and stromal cell-derived factor-1α(SDF-1α)may enhance their therapeutic efficacy.However,the regulatory effects of SDF-1αon cartilage differentiation remain largely unknown.Identifying the specific regulatory effects of SDF-1αon MSCs will provide a useful target for the treatment of degenerative articular diseases.AIM To explore the role and mechanism of SDF-1αin cartilage differentiation of MSCs and primary chondrocytes.METHODS The expression level of C-X-C chemokine receptor 4(CXCR4)in MSCs was assessed by immunofluorescence.MSCs treated with SDF-1αwere stained for alkaline phosphatase(ALP)and with Alcian blue to observe differentiation.Western blot analysis was used to examine the expression of SRY-box transcription factor 9,aggrecan,collagen II,runt-related transcription factor 2,collagen X,and matrix metalloproteinase(MMP)13 in untreated MSCs,of aggrecan,collagen II,collagen X,and MMP13 in SDF-1α-treated primary chondrocytes,of glycogen synthase kinase 3β(GSK3β)p-GSK3βandβ-catenin expression in SDF-1α-treated MSCs,and of aggrecan,collagen X,and MMP13 in SDF-1α-treated MSCs in the presence or absence of ICG-001(SDF-1αinhibitor).RESULTS Immunofluorescence showed CXCR4 expression in the membranes of MSCs.ALP stain was intensified in MSCs treated with SDF-1αfor 14 d.The SDF-1αtreatment promoted expression of collagen X and MMP13 during cartilage differentiation,whereas it had no effect on the expression of collagen II or aggrecan nor on the formation of cartilage matrix in MSCs.Further,those SDF-1α-mediated effects on MSCs were validated in primary chondrocytes.SDF-1αpromoted the expression of p-GSK3βandβ-catenin in MSCs.And,finally,inhibition of this pathway by ICG-001(5μmol/L)neutralized the SDF-1α-mediated up-regulation of collagen X and MMP13 expression in MSCs.CONCLUSION SDF-1αmay promote hypertrophic cartilage differentiation in MSCs by activating the Wnt/β-catenin pathway.These findings provide further evidence for the use of MSCs and SDF-1αin the treatment of cartilage degeneration and osteoarthritis.

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis

AIM:To determine the long-term efficacy of autologous bone marrow mononuclear cells(BM-MNCs)transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.METHODS:A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial,including32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment,and 15 patients receiving medical treatment only as controls.Fortythree of 47 patients were infected with hepatitis B virus.Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery.The efficacy of BM-MNCs transplantation was monitored during a24-mo follow-up period.RESULTS:Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion.Prealbumin level was 118.3±25.3 mg/L vs 101.4±28.7 mg/L(P=0.047);albumin level was 33.5±3.6g/L vs 30.3±2.2 g/L(P=0.002);total bilirubin 36.9±9.7 mmol/L vs 45.6±19.9 mmol/L(P=0.048);prothrombin time 14.4±2.3 s vs 15.9±2.8 s(P=0.046);prothrombin activity 84.3%±14.3%vs 74.4%±17.8%(P=0.046);fibrinogen 2.28±0.53 g/L vs1.89±0.44 g/L(P=0.017);and platelet count 74.5±15.7×109/L vs 63.3±15.7×109/L(P=0.027)in the treatment group and control group,respectively.Differences were statistically significant.The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group.Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls.However,these improvements disappeared 24 mo after transplantation.CONCLUSION:BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis.It also decreases the incidence of serious complications.

Effect of TRPV1 Channel on Proliferation and Apoptosis of Airway Smooth Muscle Cells of Rats

Airway remodeling is an important pathological feature of asthma and the basis of severe asthma. Proliferation of airway smooth muscle cells （ASMCs） is a major contributor to airway remod- eling. As an important Ca2＋ channel, transient receptor potential vanilloid 1 （TRPV1） plays the key role in the cell pathological and physiological processes. This study investigated the expression and activity of TRPV1 channel, and further clarified the effect of TRPV1 channel on the ASMCs proliferation and apoptosis in order to provide the scientific basis to treat asthmatic airway remodeling in clinical practice Immunofluorescence staining and reverse transcription polymerase chain reaction （RT-PCR） were used to detect the expression of TRPVI in rat ASMCs. Intracellular Ca2＋ was detected using the single cell confocal fluorescence microscopy measurement loaded with Fluo-4/AM. The cell cycles were observed by flow cytometry. MTT assay and Hoechst 33258 staining were used to detect the proliferation and apoptosis of ASMCs in rats respectively. The data showed that： （1） TRPV1 channel was present in rat ASMCs. （2） TRPV1 channel agonist, capsaicin, increased the Ca2~ influx in a concentration-dependent manner （EC50=284.3＋58 nmol/L）. TRPV1 channel antagonist, capsazepine, inhibited Ca2＋ influx in rat ASMCs. （3） Capsaicin significantly increased the percentage of S＋G2M ASMCs and the absorbance of MTT assay. Capsazepine had the opposite effect. （4） Capsaicin significantly inhibited the apoptosis, whereas capsazepine had the opposite effect. These results suggest that TRPV1 is present and mediates Ca2＋ influx in rat ASMCs. TRPV1 activity stimulates proliferation of ASMCs in rats.

Nursing care of 22 patients with complex intracranial aneurysms treated with flow-diverting stents:A retrospective study

Objective:To summarize the nursing treatment of patients who underwent implantation of a blood flow diverter to treat complex intracranial aneurysms.Methods:Data from 22 patients with complex aneurysms,diagnosed at an interventional center for blood flow diverter implantation between February 2015 and February 2016,treated in the Henan Provincial People’s Hospital(Zhengzhou,China),were retrospectively analyzed.Nursing methods,including preoperative,intraoperative,and postoperative care,were analyzed.Results:All 22 patients underwent successful surgery,with no related complications or hospital mortality,and were cured in hospital.Conclusion:Interventional flow diverter therapy for patients with complex intracranial aneurysms is a new technology,and involves intensive care by nursing staff and appears to be a promising new treatment method.

Safety and efficacy of the Separ GateTM balloon-guiding catheter in neurointerventional surgery: Study protocol of a prospective multicenter single-arm clinical trial

Background: The balloon-guiding catheter(BGC) reportedly reduces the number of retrievals and occurrence of distal emboli, achieving superior revascularization results and improved clinical outcomes in acute stroke. This study will aim to examine the efficacy and safety of the new Separ GateTM BGC.Design: This prospective multicenter single-arm clinical trial will aim to include 128 patients who fulfill its inclusion and exclusion criteria. All patients will receive endovascular interventional therapy with BGC assistance.The primary endpoint will be the immediate surgical success rate, while the secondary endpoint will be product performance. The safety evaluation will include serious adverse events such as puncture site hematoma and bleeding, cerebral vasospasm, vessel dissection, vessel perforation, air embolism, thrombus(acute or subacute),vessel occlusion, distal embolization, infection, adverse reaction to antiplatelet and anticoagulant drugs, intracranial hemorrhage, stroke, death, and device defect.Discussion: The prospective multicenter trial will provide safety and efficacy information for the Separ GateTM BGC.Its findings will provide a clinical reference for endovascular adjuvant therapy of cerebrovascular disease.Trial registration: Chi CTR1800014459.

Evaluation of using a double helical, closed-cell stent-retriever(Skyflow) for thrombectomy procedures in acute arterial occlusion: A preclinical study and a clinical trial

Background and purpose:Stent retriever thrombectomy is the standard therapeutic approach for ischemic stroke with acute large-vessel occlusion.This study evaluated the safety and efficacy of a new thrombectomy device(Skyflow)in the treatment of acute ischemic stroke.Methods:After an arterial occlusion model was established,stent-retriever thrombectomy was performed.Digital subtraction angiography(DSA)and autopsy were carried out immediately after thrombectomy in six animals in the acute experimental group.Simulated stent-retriever thrombectomy was performed for three animals in the subacute experimental group,and follow-up angiography and vascular pathological examination were assessed 90 days after the operation.In the clinical trial,192 patients with intracranial anterior circulation large vessel occlusion,within 8 h of symptom onset,were included to undergo thrombectomy with either Skyflow or Solitaire FR stent retriever.Efficacy and safety endpoints were recorded(including successful reperfusion,favorable clinical outcomes,time from puncture to reperfusion,instrument operation success rates and National Institutes of Health Stroke Scale(NIHSS)scores at 7 days for efficacy endpoints,and symptomatic intracranial hemorrhage(sICH),subarachnoid hemorrhage(SAH)and all-cause mortality rates for safety endpoints).Results:All blood vessels achieved successful recanalization in the animal models.In the clinical trial,successful recanalization was attained in 88.4%of patients of the Skyflow group,which was comparable to that of the Solitaire FR group(82.5%)in the full analysis set of the clinical trial.There were no severe complications on DSA,an animal autopsy,or vessel pathological examination in animal experiments.Additionally,no statistically significant difference was observed between the Skyflow and Solitaire FR groups in the clinical trial regarding the safety endpoints.Conclusion:This study showed that the new Skyflow stent retriever is safe and effective for the treatment of acute large vessel occlusion,as demonstrated in our animal study and human trial.

Edaravone Enhances the Viability of Ischemia/reperfusion Flaps

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion（IR） and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups： control group（n=16）, IR group（n=16）, and edaravone-treated IR group（n=16）. An island flap at left lower abdomen（6.0 cm×3.0 cm in size）, fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone（10 mg/kg）, once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde（MDA） and activity of superoxide dismutase（SOD） were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin（HE） staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling（TUNEL） assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy（TEM）. Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia(2021 Edition)

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Ventricular tachycardia originating from the His bundle: A case report

BACKGROUND Ventricular tachycardia(VT)commonly occurs among patients with heart failure and can even cause sudden cardiac death.VT originating from the His bundle branch has been rarely reported.We present the case of a patient with VT from the His bundle branch.CASE SUMMARY A 58-year-old female complained of paroxysmal palpitations and dizziness for approximately 6 mo.She had a history of fatty liver and cholecystitis,and carotid atherosclerosis could not be excluded from the ultrasound results.An evaluation of the electrocardiogram obtained after admission showed spontaneous conversion between two different morphologies.The possible electrophysiologic mechanism suggested that the dual-source VT originated from the same source,the His bundle branch.Finally,the His bundle branch was ablated,and a dualchamber pacemaker was inserted into the patient’s heart.No further VT occurred during the 3-year follow-up after hospital discharge.CONCLUSION The diagnosis of VT originating from the His bundle is rare and difficult to establish.The results of this study showed VT originating from the His bundle based on a careful evaluation of the electrocardiogram,and the diagnosis was confirmed by an intracardiac electrophysiologic examination.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review

BACKGROUND Primary malignant melanoma of the esophagus(PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.AIM To investigate the clinical features and survival factors in Chinese patients with PMME.METHODS The clinicopathological findings of ten cases with PMME treated at Henan Provincial People’s Hospital were summarized. Moreover, the English-and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.RESULTS A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients(55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients(36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis(LNM) was 51.2%(107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the p T stage [P < 0.001, odds ratio(OR): 2.47, 95% confidence interval(CI): 1.72-3.56] and larger tumor size(P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival(OS) was 11.0 mo(range: 1-204 mo). The multivariate Cox analysis showed both the p T stage [P = 0.005, hazard ratio(HR): 1.70, 95%CI: 1.17-2.47] and LNM(P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival(DFS) was 5.3 mo(range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced p T stage(P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME.CONCLUSION The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and p T stage are independent prognosis factors for OS, and the p T stage is the prognosis factor for DFS in patients with PMME.

Use of Impella cardiac axial flow pump for cardiogenic shock(A newer alternative)-How good is the evidence?

The adverse outcomes of a ventricular heart failure(left,right or biventricular)caused by cardiogenic shock are aggravated by lung oedema and organ mal perfusion.Despite advances in medical sciences,revascularisation and mechanical hemodynamic support have proved ineffective in reducing the mortality rate in such patients.A thorough study of the data available about cardio-vascular diseases reveals that the application of conventional methods of treatment are least helpful to practically restore normal functions of heart when it experiences end-stage systolic ventricular failure.Thus,to overcome the challenges and find alternatives to address this issue,percutaneous ventricular support devices/machines were designed and successfully introduced.These devices have revolutionized the treatment of ventricular heart failures and are now in use all over the world.In this review paper a newer mechanical circulatory support(MCS)device,Impella,has been discussed and compared with a few other devices like(Intra-aortic Balloon Pump(IABP),Extracorporeal Circulation(ECLS)and Veno-arterial Extracorporeal Membrane Oxygenation(VA-ECMO).This article studies the challenges being faced during the treatment of cardiogenic shock,and thoroughly discusses the use and effectiveness of Impella Cardiac Axial Pump in each emergency.It can be said that mechanical circulatory support(MCS)device use during percutaneous coronary intervention(PCI)should be individualized based on multiple factors with a recommended use in patients with the greatest potential benefit and a relatively low risk of device-related complications.The current literature suggests that the outcomes of use of Impella and other mechanical circulatory support devices like IABP and VA-ECMO are comparable.Though there seem to be a few advantages of Impella over the others,sufficiently powered,multi-centric,randomised control trials are needed to establish its superiority.

Endovascular transvenous treatment for superficial intracranial arteriovenous malformations

Objective:The objective of this study was to evaluate the feasibility and outcomes of transvenous endovascular embolization(TVE) for superficial intracranial arteriovenous malformations(AVMs).Methods:After collecting clinical and imaging data,a prospective series of 11 patients presenting with superficial AVMs were treated by endovascular embolization using a transvenous approach between November 2016 and October 2018.Results:Ten patients(90.9%) had ruptured AVMs before TVE.The mean nidus size was 3.27 ± 1.47 cm,and the median Spetzler-Martin grade was II.The rate of immediate angiographic occlusion of the AVMs was 90.9%(10/11).One patient was treated with transarterial embolization since TVE was not achieved due to an unsuccessful positioning of the microcatheter.Two patients(cases 8 and 11) suffered a intracranial hemorrhage and a cerebral infarction with encephaledema,respectively,but no procedure-related mortalities were observed.Eight patients(72.7%) were independent with a modified Rankin Score(mRS) 2 at discharge and the m RSs of all patients,which were collected 30 days postintervention,were not more than 2.The mean follow-up period was 17 months.There were no nidus recurrences during the follow-up period.Conclusions:The curative transvenous embolization of superficial AVMs seems feasible and effective while carefully monitoring for embolization-related complications.

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

Reporting quality evaluation of clinical practice guidelines for pulmonary nodules with the RIGHT checklist

To the Editor:Pulmonary nodules are defined as localized opacities of up to 30 mm in diameter,surrounded by pulmonary parenchyma or located adjacent to the pleura.^([1])The ideal management for pulmonary nodules is to diagnose and treat malignant nodules as early as possible and minimize radiation exposures,based on the general guidance.Clinical practice guidelines(CPGs)always provide efficient recommendations based on systematic reviews of high-quality evidence and reporting to optimize patient care.^([2])Accumulating evidence shows that adherence to the guidelines improves patient outcomes.^([3])However,the reporting quality of CPGs seems poor.^([4])Several instruments have been generated to evaluate the quality of CPGs.

Integrative analysis of tumor stemness and immune microenvironment deciphers novel molecular subtypes in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a highly heterogeneous tumor,with dynamic equilibrium and complex interplay between its intricate tumor nature and ambient tumor immune microenvironment(TIME).1 Elegant research has indicated that cancer stem cells,a small subset of neoplastic cells confined within dedicated niches,display stem cell-like properties and interact with cells in TIME,thereby imparting an indelible impact on stemness regulation,tumor heterogeneity,and cancer cell plasticity.2 Previous taxonomies solely from the perspective of stemness or TIME may introduce some degree of bias in the comprehension of HCC carcinogenesis,3,4 and thus it is of paramount importance to systematically consider tumor stemness and TIME as a whole to truly portray the biological landscape of HCC.