Brain injury in combination with tacrolimus promotes the regeneration of injured peripheral nerves

Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was（or was not） induced. After sciatic nerve injury, tacrolimus, an immunosuppressant, was（or was not） intraperitoneally administered. At 4, 8 and 12 weeks after surgery, Masson＇s trichrome, hematoxylin-eosin, and toluidine blue staining results revealed that brain injury or tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and sciatic nerve fiber impairment on the experimental side, simultaneously improved sciatic nerve function, and increased gastrocnemius muscle wet weight on the experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or tacrolimus treatment increased action potential amplitude in the sciatic nerve trunk. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive neurons in the anterior horn of the spinal cord was greatly increased. Brain injury in combination with tacrolimus exhibited better effects on repair of injured peripheral nerves than brain injury or tacrolimus alone. This result suggests that brain injury in combination with tacrolimus promotes repair of peripheral nerve injury.

Incremental value of three-dimensional and contrast echocardiography in the evaluation of endocardial fibroelastosis and multiple cardiovascular thrombi: A case report

BACKGROUND Endocardial fibroelastosis(EFE)is a rare heart disease characterized by thickening of the endocardium caused by massive proliferation of collagenous and elastic tissue,usually leading to impaired cardiac function.Multimodality cardiovascular imaging for the evaluation of EFE with thrombi is even rarer.CASE SUMMARY We report a rare case of EFE associated with multiple cardiovascular thrombi.Three-dimensional(3D)and contrast echocardiography(CE)were used to assess ventricular thrombi.Anticoagulant therapy was administered to eliminate the thrombi.The peripheral contrast-enhanced thrombi with the highest risk were dissolved with anticoagulant therapy at the time of reexamination,which was consistent with the presumption of fresh loose thrombi.CONCLUSION This new echocardiography technique has a great advantage in the diagnosis and treatment of EFE.On the basis of conventional echocardiography,3D echocardiography is used to display the position,shape,and narrow base of the thrombus.CE does not only help to confirm the diagnosis of thrombus,but also determines its risk.

Review and prospect of immune checkpoint blockade therapy represented by PD-1/PD-L1 in the treatment of clear cell renal cell carcinoma

As a common tumor of the urinary system,the morbidity and mortality related to renal carcinoma,are increasing annually.Clear cell renal cell carcinoma(CCRCC)is the most common subtype of renal cell carcinoma,accounting for approximately 75%of the total number of patients with renal cell carcinoma.Currently,the clinical treatment of ccRCC involves targeted therapy,immunotherapy,and a combination of the two.In immunotherapy,PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment.However,as treatment progresses,some patients gradually develop resistance to immunotherapy.Meanwhile,other patients experience great side effects after immunotherapy,resulting in a survival status far lower than the expected survival rate.Based on these clinical problems,many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results.We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.

Light/pH dual controlled drug release"nanocontainer"alleviates tumor hypoxia for synergistic enhanced chemotherapy,photodynamic therapy and chemodynamic therapy

Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer treatment.Herein,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA coating.These nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic properties.The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-lapachone.Notably,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic effect.In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and biocompatibility.Together,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

Effects of psychological nursing in Parkinson's related depression patients undergoing functional magnetic resonance imaging:A randomized controlled trial

BACKGROUND Patients with Parkinson’s disease(PD)often experience depression,and some may require magnetic resonance imaging(MRI)for diagnosis,which can lead to MRI failure due to claustrophobia.AIM To explore the value of psychological interventions in successfully completing functional MRI scans of the brain for PD-related depression.METHODS Ninety-six patients with PD were randomly divided into two groups.The control group(47 patients)received general care,and the experimental group(49 patients)received general care combined with psychological care.The Unified Parkinson's Disease Assessment Scale(UPDRS),Hamilton Depression Scale(HAMD),and Geriatric Depression Scale(GDS)-15 scores,heart rate,systolic blood pressure,and MRI-Anxiety Questionnaire(MRI-AQ)scores before and after the scan were recorded.The completion rate of magnetic resonance(MR)scanning,scanning duration,and image quality scores were recorded.RESULTS Before scanning,no statistically significant difference was observed between the two groups in terms of heart rate,systolic blood pressure,and UPDRS,HAMD,GDS-15,and MRI-AQ scores.After scanning,systolic blood pressure,MRI-AQ score,and scan time in the experimental group were significantly lower than those in the control group,whereas the scan completion rate and image quality score were significantly higher than those in the control group.CONCLUSION Psychological nursing interventions are helpful in alleviating PD-related depression and assessing MR depression scores and may be helpful in the successful completion of functional MRI scans of the patient's brain.

Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer

BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered CAFs-associated gene signature,which can be employed to estimate BC patient outcomes conveniently and accurately.

Angiofibrolipoma of the spermatic cord

Dear Sir, I am Dr Qing-Li Liu, from the Department of Urology of the First Hospital of Qinhuangdao in Qinhuangdao, Hebei Province, China. I write to present a case report of spermatic cord angiofibrolipoma.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy

AIM:To analyze the distribution of fibrovascular proliferative membranes(FVPMs)in proliferative diabetic retinopathy(PDR)patients that treated with pars plana vitrectomy(PPV),and to evaluate the outcomes separately.METHODS:This was a retrospective and cross-sectional study.Consecutive 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April 2020.According to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type group.All patients were followed up for over one year.General characteristics,operation-related variables,postoperative parameters and complications were recorded.RESULTS:Among 103 eyes recruited,the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different(both P<0.01),with 95(92.23%)FVPMs located in the nasal quadrants,and 74(71.84%)in the inferior.The eyes with a central FVPM required the longest operation time,with silicon oil used in most patients,generally combined with tractional retinal detachment(RD)and rhegmatogenous RD,the worst postoperative bestcorrected visual acuity(BCVA)and the highest rates of recurrent RD(all P<0.05).FVPM type,age of onset diabetes mellitus,preoperative BCVA,and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement(all P<0.05).Compared with the central type group,the arcade type group had higher rates of BCVA improvement.CONCLUSION:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels.Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

Automatic segmentation of foveal avascular zone based on adaptive watershed algorithm in retinal optical coherence tomography angiography images

The size and shape of the foveal avascular zone(FAZ)have a strong positive correlation with several vision-threatening ret inovascular diseases.The identification,segmentation and analysis of FAZ are of great significance to clinical diagnosis and treatment.We presented an adaptive watershed algorithm to automatically extract F AZ from retinal optical coherence tomography angiography(OCTA)images.For the traditional watershed algorithm,"over-segmentation"is the most common problem.FAZ is often incorrectly divided into multiple regions by redundant"dams".This paper analyzed the relationship between the"dams"length and the maximum inscribed circle radius of FAZ,and proposed an adaptive watershed algorithm to solve the problem of"over-segmentation".Here,132 healthy retinal images and 50 diabetic retinopathy(DR)images were used to verify the accuracy and stability of the algorithm.Three ophthal-mologists were invited to make quan titative and qualitative evaluations on the segmentation results of this algorithm.The quantitative evaluation results show that the correlation coffi-cients between the automatic and manual segmentation results are 0.945(in healthy subjects)and 0.927(in DR patients),respectively.For qualitative evaluation,the percentages of"perfect segmentation"(score of 3)and"good segmentation"(score of 2)are 99.4%(in healthy subjects)and 98.7%(in DR patients),respectively.This work promotes the application of watershed algorithm in FAZ segmentation,making it a useful tool for analyzing and diagnosing eye diseases.

Permeable Resin Applied to Surface of Sealed Demineralized Enamel

The self-made demineralized teeth samples treated with preamble resin to seal or not were observed under electron microscopy and tested microhardness value to show surface structure and hardness of demineralized enamel.The experimental results showed that the permeable resin formed longer resin tags on the surface of the enamel and a lot of cracks in the deep part which has a higher microhardness value than ordinary enamel.

Epidemiological Investigation of Brucellosis Spondylitis and Optimal Selection of Clinical Drug Compatibility, Treatment Course and Treatment Plan

Background: Brucellosis is a zoonotic endemic disease, the main source of infection is infected cattle, sheep, pigs and their products. In recent years, the global incidence of brucellosis spondylitis has increased year by year, and it has spread from pastoral areas to semi-agricultural and semi-pastoral areas, agricultural areas and cities. It has changed from a mainly occupational disease to a mainly food-borne disease, and it is also a zoonotic specific spinal infectious disease that WHO and governments around the world pay great attention to. Due to the low cure rate and high recurrence rate of traditional drug therapy regimen. Therefore, to carry out epidemiological investigation and Related research on clinical drug therapy of brucellosis spondylitis has practical significance for improving diagnosis rate, cure rate and reducing recurrence rate. Objective: To analyze the epidemiological characteristics of Brucellosis spondylitis and explore the choice of drugs and the best drug treatment plan, so as to provide scientific basis for improving the prevention and control of the disease and treatment effect. Methods: Clinical epidemiodogical materials were collected from 113 patients with brucellar spondylitis. All these patients were divided into 5 different groups according to 5 kinds of drugs adopted respectively, and then the patients were given different course of treatment. Results: In the 113 patients, brucellar spondylitis morbility of female patients were higher than that of male ones, and the morbility of Bashang were higher than that of Baxia. These patients were infected mainly through browsing and breeding beasts. Lumbars were the major focus of infection. It was very comnlon that two adjacent lumbars were involved in concurrently. L4 was the most common infection location and its demolishment was most serious. The curative effect of group treated with doxycycline was better than that of group treated without doxycycline. If the course of treatment Was increased, the curative effect Was not increased obviously. Conclusions: There are characteristic features in clinical epidemiology of brucell spondylitis. Doxycycline + Rifampicin + Sulfamethoxazole was used as the preferred antibiotic. Using antibiotics adequately and jointly by two courses of treatment for a long time is the most reasonable way to treat the disease and prevent the disease from recurrence.

Clinical Study on Treatment of Type II/III Lumbar Brucellar Spondylitis by Unilateral Biportal Endoscopy

Objective: Explore the feasibility and clinical efficacy of using unilateral biportal endoscopy for the treatment of Type II/III lumbar brucellar spondylitis. Methods: A retrospective study of the clinical data of 20 patients with Type II/III lumbar brucellar spondylitis admitted to the First Affiliated Hospital of Hebei North University from January 2020 to May 2022, including 15 males and 5 females, aged 41 - 60 years old, average age (48.11 ± 7.28) years old. After admission, the patient can isolate brucella through metagenomic Next-Generation Sequencing (mNGS), meeting the tertiary diagnostic criteria. Preoperative conventional drug treatment, unilateral biportal endoscopic minimally invasive surgery was performed when nutrition was improved, perioperative control of various indexes was stable, and erythrocyte sedimentation was declining. It was completed under an endoscope. The lesion was cleared, spinal nerve compression was relieved, interbody fusion was performed, and the spine was fixed by a percutaneous pedicle screw. Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Visual Analogue Scale (VAS), Japanese Orthopedic Association (JOA) score and Oswestry Disability Index (ODI) were analyzed at 1 month, 3 months, 6 months and the last follow-up. At the final follow-up of all patients, the clinical efficacy criteria and the Bridwell grading criteria were used to evaluate the recovery and intervertebral bone graft fusion, respectively. Results: All patients’ lower back and leg pain was relieved the next day after surgery. At a follow-up of one month after surgery, both systemic and local symptoms significantly improved. At the last follow-up, clinical symptoms disappeared and there was no tenderness or percussion pain in the local area. With the passage of time, 1 month, 3 months, 6 months after the operation, and the last follow-up are all evaluation indicators compared with those before the operation. No matter VAS, JOA, ODI score, or ESR, CRP is significantly improved compared with preoperative (P All 20 cases in this group reached the BS clinical cure standard, and the excellent rate of intervertebral bone graft fusion was 95%. Conclusion: On the basis of .

A modified HEART risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome

ObjectiveTo validate a modified HEART [History, Electrocardiograph （ECG）, Age, Risk factors and Troponin] risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome （NSTE-ACS） in the emergency department （ED）.Methods This retrospective cohort study used a prospectively acquired database and chest pain patients admitted to the emergency department with suspected NSTE-ACS were enrolled. Data recorded on arrival at the ED were used. The serum sample of high-sensitivity cardiac Troponin I other than conventional cardiac Troponin I used in the HEART risk score was tested. The modified HEART risk score was calculated. The end point was the occurrence of major adverse cardiac events （MACE） defined as a composite of acute myocardial infarction （AMI）, percu-taneous intervention （PCI）, coronary artery bypass graft （CABG）, or all-cause death, within three months after initial presentation.Results A total of 1,300 patients were enrolled. A total of 606 patients （46.6%） had a MACE within three months： 205 patients （15.8%） were diag-nosed with AMI, 465 patients （35.8%） underwent PCI, and 119 patients （9.2%） underwent CABG. There were 10 （0.8%） deaths. A progres-sive, significant pattern of increasing event rate was observed as the score increased （P ＆lt; 0.001 byχ2 for trend）. The area under the receiver operating characteristic curve was 0.84. All patients were classified into three groups： low risk （score 0-2）, intermediate risk （score 3-4）, and high risk （score 5-10）. Event rates were 1.1%, 18.5%, and 67.0%, respectively （P ＆lt; 0.001）.ConclusionsThe modified HEART risk score was validated in chest pain patients with suspected NSTE-ACS and may complement MACE risk assessment and patients triage in the ED. A prospective study of the score is warranted.

Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota

BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.

Detection of infectious pathogens located in the peripheral lung field by metagenomic next-generation sequencing combined with virtual bronchoscopic navigation

.To the Editor:Lower respiratory tract infections(LRTIs)are among the deadliest diseases and remain one of the leading causes of death over the last 15 years,especially in low-income countries,and are of great concern to immunosuppressed individuals.Infections located in the peripheral lung field(PLF)are located within the outerthird elliptical regions around the hilum on computedtomography(CT)scans.[1]They are surrounded by normal lung parenchyma and are unlikely to be visualized and accurately diagnosed by bronchoscopy.

Emancipatory reflection on a nursing practice-based ethical issue about nurses' paternalistic decision-making for patients

Objective: This study aimed to demonstrate and promote the skill of critical emancipatory reflection through reflecting on a nursing practice-based ethical issue about nurses' paternalistic decision-making for patients. Meanwhile, critical awareness will be developed and the underlying issues of paternalism in nursing decision-making will be analyzed. Then, by applying the procedure, improvement in nursing decision-making practice will be expected.Methods: Taylor's model of emancipatory reflection with four steps, including construction, deconstruction, confrontation, and reconstruction, is utilized to guide the author's reflection.Results: Guided by the socialization theory, the author's personal and professional socialization is seen to be associated with the formation of the value of paternalism. The theory of reflexivity is applied to unearth the related issues, including deeper personal value,work environment, as well as historical and cultural contexts. Moreover, the power derived from policy, work relationship, and nursing administration, which could induce paternalism in the author's nursing decision-making practice, was critically debated using the hegemony theory. Finally, new insights into paternalism will be achieved, which enable change in terms of how to facilitate patients' autonomous decision-making.Conclusions: The process of refection makes it clear that respecting patients' right and performing patient-centered caring are the bases to change the paternalism existing in the nursing decision-making practice currently. The reconstruction step assists the author in terms of how to value the patients' autonomy and balance patients' safety and choice, rather than being overprotective; carry out risk assessment, and search for strong evidence to counterbalance the positive and negative aspects of risk-taking; communicate with patients appropriately in a manner that they can comprehend; spend more time to explore patients' preference and choice; make every effort to elevate the patients' decision-making capacity; implement patient-centered care and shared decision-making in nursing practice; consult with other colleagues and obtain the required support when limitations or challenges exist; try to justify and avoid hidden paternalism behind policy or guidelines; deal with the power in hand well and fairly; and also positively face the powers that constrain the author.

ICU Delirium： A concept analysis

Objective： To explore and analyze the concept of intensive care unit （ICU） delirium. Method： Walker and Avant’sstrategy of analysis was adopted to this research. Results： ICU delirium is defined as the presence of an acute cognitiveimpairment, accompanied by a disturbance of consciousness with fluctuating inattention, and the array of dysfunctionsonly developed for a short period of time in ICU. The antecedents of ICU delirium include （1） the high severity of illness,（2） pain, （3） sedative use, （4） immobilization, （5） sleep deprivation and （6） unpleasant awareness. The consequencesinvolve （1） promoting the risks of self-extubation and unplanned removal of catheters, （2） prolonging the length of ICUstay, （3） increasing the mortality of critical patients and （4） Some different ICU delirium assessment instruments aregathered. Confusion Assessment Method for Intensive Care Unit assessment tool （CAM-ICU） was the most populardiagnostic tool used by nurses. Conclusion： Concept analysis as an extension and development of nursing theory cancreate a linkage between practice and theory. It will create a knowledge foundation of ICU delirium and provide atheoretical basis to construct nursing theory. This study can help ICU nurses to understand and recognize ICU delirium.ICU nurses will be enlightened to develop effective interventions of ICU delirium to improve critical patients’ clinicaloutcomes.

Application of erector spinae plane block guided by ultrasound for postoperative analgesia in breast cancer surgery:A randomized controlled trial

Dear Editor,Breast cancer is the most common malignant tumor in women and surgical management remains a key component of treatment and cure[1].However,the surgical procedure is often associated with varying degrees of postoperative pain.Approximately 60%of women after breast cancer surgery complain of severe acute pain[2].In addition,failure to manage acute postoperative pain may lead to the development of chronic pain which may be persistent for years[3,4].As chronic persistent pain arises in approximately 50%of patients after breast cancer surgery[5],it is therefore necessary to explore efficacious techniques that can reduce postoperative pain for such patients.

Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease

Background:Right ventricular(RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction(HFpEF).Coronary artery disease(CAD)can contribute to the pathophysiological characteristics of HFpEF.This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD.Methods:This prospective study included 250 consecutive acute HFpEF patients with CAD.Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value,based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure(TAPSE/PASP).The primary endpoint was a composite of all-cause death,recurrent ischemic events,and HF hospitalizations.Results:TAPSE/PASP≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling(area under the curve,0.731;sensitivity,61.4%;and specificity,76.6%).Of the 250 patients,150 and 100 patients could be grouped into the RV-arterial coupling(TAPSE/PASP>0.43)and uncoupling(TAPSE/PASP≤0.43)groups,respectively.Revascularization strategies were slightly different between groups;the RV-arterial uncoupling group had a lower rate of complete revascularization(37.0%[37/100]vs.52.7%[79/150],P<0.001)and a higher rate of no revascularization(18.0%[18/100]vs.4.7%[7/150],P<0.001)compared to the RV-arterial coupling group.The cohort with TAPSE/PASP≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP>0.43.Multivariate Cox analysis showed TAPSE/PASP≤0.43 as an independent associated factor for the primary endpoint,all-cause death,and recurrent HF hospitalization(hazard ratios[HR]:2.21,95%confidence interval[CI]:1.44-3.39,P<0.001;HR:3.32,95%CI:1.30-8.47,P=0.012;and HR:1.93,95%CI:1.10-3.37,P=0.021,respectively),but not for recurrent ischemic events(HR:1.48,95%CI:0.75-2.90,P=0.257).Conclusion:RV-arterial uncoupling,based on TAPSE/PASP,is independently associated with adverse outcomes in acute HFpEF patients with CAD.

Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin

Background Gefitinib, an inhibitor of epidermal growth factor receptor （EGFR） tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer （NSCLC）, and is generally well tolerated.However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction.This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib.C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline.Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells.In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR （p-EGFR）.Furthermore, quantitative real-time PCR （qRT-PCR） demonstrated that gefitinib inhibited the accumulation of collagens Ⅰ and Ⅲ.Conclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.