Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction

BACKGROUND Nocturnal hypertension is reported as a risk factor for cardiovascular disease.This study aimed to explore the potential association between nocturnal hypertension and heart failure(HF)rehospitalization in patients with HF with preserved ejection fraction(HFpEF).METHODS A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study.Cox regression analysis was used to reveal the potential association between nighttime blood pressure(BP)levels,nocturnal hypertension and nocturnal BP patterns and HF rehospitalization.Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups.RESULTS There were 537 patients with HFpEF were included in the final analysis.The mean age of the study population was 77.14±8.68 years,and 41.2% of patients were men.After a median follow-up duration of 10.93(4.19–21.13)months,176 patients(32.7%)with HFpEF were readmitted for HF.Cox regression analysis had revealed that nighttime systolic BP level[hazards ratio(HR)=1.018,95%CI:1.008–1.028,P=0.001],nighttime diastolic BP level(HR=1.024,95%CI:1.007–1.042,P=0.007),nocturnal hypertension(HR=1.688,95%CI:1.229–2.317,P=0.001)were associated with HF rehospitalization.Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate(log-rank P<0.001).Furthermore,patients with a riser pattern had a higher risk of HF rehospitalization(HR=1.828,95%CI:1.055–3.166,P=0.031)and lower eventfree survival rate(log-rank P=0.003)than those with a dipper pattern.These findings were also confirmed in patients with HFpEF and hyperuricemia.CONCLUSIONS Nighttime BP levels,nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF,and prominently in patients with HFpEF and hyperuricemia.Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

The KEu(WO_(4))_(2)Red Phosphor Co-doped with Li^(+)and SO_(4)^(2-)for Synergistic Enhancement of High Efficiency and Thermal Stability

A series of tungstate red phosphors K_(1-x)Li_(x)Eu(WO_(4))_(2-y)(SO_(4))_(y)were successfully prepared by sol-gel method,and the effects of the introduction of Li~+and SO_(4)^(2-)on the fluorescence intensity and thermal quenching properties of the prepared K_(1-x)Li_(x)Eu(WO_(4))_(2-y)(SO_(4))_(y)phosphors were investigated.The X-ray diffraction data show that the prepared(Li^(+)and SO_(4)^(2-))-doped KEu(WO_(4))_(2)phosphors have a monoclinic tetragonal structure.In addition,the emission intensities of all the observed emission peaks change significantly with the increase of Li~+doping concentration,especially the intensity of the emission peaks at 615 nm fluctuated significantly and reached the maximum at x=0.3 and y=0.2.The K_(1-x)Li_(x)Eu(WO_(4))_(2-y)(SO_(4))_(y)phosphors are found to have the highest fluorescence intensity at x=0.3 and y=0.2.Moreover,the K_(0.7)Li_(0.3)Eu(WO_(4))_(1.8)(SO_(4))_(0.2)phosphor has better thermal quenching properties and luminescence efficiency,and the experimental results indicates that the fluorescence intensity and thermal burst performance of KEu(WO_(4))_(2)red phosphor could be effectively improved by using low-cost bionic doping of Li^(+)and SO_(4)^(2-).

Comment on“Comparison of different versions of the quick sequential organ failure assessment for predicting in-hospital mortality of sepsis patients”

Dear editor,We have read with great interest the recent article“Comparison of different versions of the quick sequential organ failure assessment for predicting in-hospital mortality of sepsis patients:A retrospective observational study”.[1]They showed that the performance of the procalcitonin-enhanced qSOFA(PqSOFA)was similar to that of the qSOFA,and the lactate-enhanced qSOFA(LqSOFA)and the modified qSOFA(MqSOFA)were superior to the qSOFA for predicting in-hospital mortality.Further,they suggested that the MqSOFA should be a candidate for the qSOFA in the emergency department(ED).We congratulate the authors for their contributions.However,we has several concerns about this research.

Prognosis after splenectomy plus pericardial devascularization vs transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding

BACKGROUND Portal hypertension combined with esophagogastric variceal bleeding(EGVB)is a serious complication in patients with hepatitis B virus(HBV)-related cirrhosis in China.Splenectomy plus pericardial devascularization(SPD)and transjugular intrahepatic portosystemic shunt(TIPS)are effective treatments for EGVB.However,a comparison of the effectiveness and safety of those methods is lacking.AIM To compare the prognosis after SPD vs TIPS for acute EGVB after failure of endoscopic therapy or secondary prophylaxis of variceal rebleeding(VRB)in patients with HBV-related cirrhosis combined with portal hypertension.METHODS This retrospective cohort study included 318 patients with HBV-related cirrhosis and EGVB who underwent SPD or TIPS at West China Hospital of Sichuan University during 2009-2013.Propensity score-matched analysis(PSM),the Kaplan-Meier method,and multivariate Cox regression analysis were used to compare overall survival,VRB rate,liver function abnormality rate,and hepatocellular carcinoma(HCC)incidence between the two patient groups.RESULTS The median age was 45.0 years(n=318;226(71.1%)males).During a median follow-up duration of 43.0 mo,18(11.1%)and 33(21.2%)patients died in the SPD and TIPS groups,respectively.After PSM,SPD was significantly associated with better overall survival(OS)(P=0.01),lower rates of abnormal liver function(P<0.001),and a lower incidence of HCC(P=0.02)than TIPS.The VRB rate did not differ significantly between the two groups(P=0.09).CONCLUSION Compared with TIPS,SPD is associated with higher postoperative OS rates,lower rates of abnormal liver function and HCC,and better quality of survival as acute EGVB treatment after failed endoscopic therapy or as secondary prophylaxis of VRB in patients with HBV-related cirrhosis combined with portal hypertension.There is no significant between-group difference in VRB rates.

Surface Characterization and Tribology Behavior of PMMA Processed by Excimer Laser

Polyoxymethylene methacrylate (PMMA) is widely used in ophthalmic biomaterials. Misuse of PMMA in extreme environments is likely to damage the ocular surface and intraocular structures. The surface characterization and tribological behavior of PMMA processed using an excimer laser were investigated in this study by contrasting diferent lubrication conditions and friction cycles. The results show that the roughness of the material surface increases with laser processing, which changes its physical structure. Under lubrication, the laser-treated PMMA exhibits better hydrophilicity, especially during the use of eye drops. No obvious relationship exists between the laser-processing time and friction behavior. However, the laser treatment may contribute to the formation of friction and wear mechanisms of PMMA materials. Laser-treated PMMA in saline solution exhibits better abrasive resistance by showing a lower wear rate than that in eye drops, although it has a higher friction coefcient. In this study, the diferent friction stages in laser-treated PMMA were clarifed under two lubrication conditions. The wear rates of the laser-treated PMMA were found to decrease with the number of cycles, and the friction coefcient has a similar variation tendency. The wear behavior of the laser-treated PMMA is dominated by the main abrasive wear and secondary transferred flm formation. This study provides a theoretical basis for the development and application of ophthalmic biomaterials in complex environments by examining the material surface interface behavior and wear mechanism after laser processing using PMMA as the research matrix.

护士心理负荷的影响因素:一项潜在剖面分析

目的采用潜在剖面分析的方法探讨临床护理人员心理负荷现状及其影响因素。方法于2023年3月-7月,以便利抽样法采用人口学资料调查表、领悟社会支持量表、简易应对方式问卷和NASA-任务负荷指数量表对我国5所三级医院的526名临床护士进行问卷调查。分别使用Mplus 7.3和SPSS 24.0软件进行潜在剖面分析和多元logistic回归分析,探讨心理负荷不同潜在剖面的影响因素。结果护理人员心理负荷总分为(69.57±16.93)分,可分为“低心理负荷-高自评”组(n=70,13.3%)、“中心理负荷”组(n=273,51.9%)和“高心理负荷-低自评”组(n=183,34.8%)3个潜在类型。在“高心理负荷-低自评”亚组中,工作年限≥5年、无子女、月收入≥6000元、健康状况差、近1年未接受过心理培训和遭受过工作场所暴力的护士比例高于其他亚组,组间差异具有统计学意义(P<0.05)。此外,logistic回归分析显示,与较高的心理负荷伴随的是消极的应对方式和较低的领悟社会支持。结论护士工作心理负荷可分为3个潜在类型。月收入、健康状况、心理培训、工作场所暴力、消极应对方式和领悟社会支持是心理负荷的影响因素。

High-grade myofibroblastic sarcoma in the liver: A case report

Only two cases of myofibroblastic sarcoma in the liver have been reported in the literature. Here, we report the case of a male patient with high-grade myofibroblastic sarcoma mimicking echinococcosis in the liver. The 25-year-old male patient complained of right upper quadrant swelling pain for one week and was initially diagnosed with echinococcosis. He was then scheduled for an exploratory laparotomy. During the operation, a huge mass exceeding 16 cm in diameter was found to occupy nearly the entire right trisegment of the liver, with a clear boundary and a round shape, and the mass was resected by right hepatic trisegmentectomy. Immunohistochemical staining revealed that the tumor tissue was positive for desmin, alpha-smooth muscle actin, CD56, and vimentin and negative for ALK-1, myogenin, calponin, beta-catenin, S100, and glypican-3, with a Ki-67 (MIB-1) index of approximately 20%. Based on the histological manifestations and immunohistochemical staining, a diagnosis of myofibroblastic sarcoma was established. The postoperative recovery was uneventful. There was no evidence of recurrence or metastasis through the last follow-up, 6 mo after surgery, despite a lack of postoperative chemotherapy or radiotherapy. To the best of our knowledge, the present case is the first reported case of high-grade myofibroblastic sarcoma in the liver, and it is also the first reported case in a male patient.

Cisplatin-induced vestibular hair cell lesion-less damage at high doses

Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50-100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM. The U-shaped doseresponse function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctrl, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin.

Collagenous nodule mixed simple cyst and hemangioma coexistence in the liver

A 20-year-old female patient presented with two masses located in the left liver.In this patient, a computed tomography(CT) scan revealed a hypodense mass and a second well-defined mass with a calcified nodule in the left hepatic lobe.No enhancements were apparent in or around the masses.A laparotomy was performed due to the patient's symptoms, namely, the atypical CT findings and a risk of rupture of the subcapsular lesion.The operation revealed two masses in the left hepatic lobe and a left liver resection was subsequently performed.One of the masses involved segment Ⅲ and the other mass was located in segment Ⅳ.The histopathologic findings supported a diagnosis of collagenous nodule mixed simple cyst and hemangioma.A diagnosis of collagenous nodule mixed simple hepatic cyst is extremely rare and radiologically mimics a teratoma, hepatolithiasis, parasitic cyst, or hemangioma.Although hepatic hemangiomas are the most common benign tumors found in the liver, the present case showed atypical radiographic features.

Transepithelial transport of nanoparticles in oral drug delivery:From the perspective of surface and holistic property modulation

Despite the promising prospects of nanoparticles in oral drug delivery,the process of oral administration involves a complex transportation pathway that includes cellular uptake,intracellular trafficking,and exocytosis by intestinal epithelial cells,which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic effects.Current researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells,including surface properties such as ligand modification,surface charge,hydrophilicity/hydrophobicity,intestinal protein corona formation,as well as holistic properties like particle size,shape,and rigidity.Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery systems.Therefore,this review provides a comprehensive overview of the surface and holistic properties that influence the transepithelial transport of nanoparticles,elucidating the underlying principles governing their impact on transepithelial transport.The review also outlines the chosen of parameters to be considered for the subsequent design of oral drug delivery systems.

Zwitterionic polymers-armored amyloid-like protein surface combats thrombosis and biofouling

Proteins,cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection,resulting in significant clinical mortality.Here,we report a zwitterionic polymers-armored amyloid-like protein surface engineering strategy we called as“armored-tank”strategy for dual functionalization of medical devices.The“armored-tank”strategy is realized by decoration of partially conformational transformed LZM(PCTL)assembly through oxidant-mediated process,followed by armoring with super-hydrophilic poly-2-methacryloyloxyethyl phosphorylcholine(pMPC).The outer armor of the“armored-tank”shows potent and durable zone defense against fibrinogen,platelet and bacteria adhesion,leading to long-term antithrombogenic properties over 14 days in vivo without anticoagulation.Additionally,the“fired”PCTL from“armored-tank”actively and effectively kills both Gram-positive and Gram-negative bacterial over 30 days as a supplement to the lacking bactericidal functions of passive outer armor.Overall,this“armored-tank”surface engineering strategy serves as a promising solution for preventing biofouling and thrombotic occlusion of medical devices.

Engineering anti-thrombogenic and anti-infective catheters through a stepwise metal-catechol-(amine)surface engineering strategy

Thrombosis and infection are pivotal clinical complications associated with interventional blood-contacting devices,leading to significant morbidity and mortality.To address these issues,we present a stepwise metal-catechol-(amine)(MCA)surface engineering strategy that efficiently integrates therapeutic nitric oxide(NO)gas and antibacterial peptide(ABP)onto catheters,ensuring balanced anti-thrombotic and anti-infective properties.First,copper ions were controllably incorporated with norepinephrine and hexanediamine through a one-step molecular/ion co-assembly process,creating a NO-generating and amine-rich MCA surface coating.Subsequently,azide-polyethylene glycol 4-N-hydroxysuccinimidyl and dibenzylcyclooctyne modified ABP were sequentially immobilized on the surface via amide coupling and bioorthogonal click chemistry,ensuring the dense grafting of ABP while maintaining the catalytic efficacy for NO.This efficient integration of ABP and NO-generating ability on the catheter surface provides potent antibacterial properties and ability to resist adhesion and activation of platelets,thus synergistically preventing infection and thrombosis.We anticipate that this synergistic modification strategy will offer an effective solution for advancing surface engineering and enhancing the clinical performance of biomedical devices.

Monascus pigment-protected bone marrow-derived stem cells for heart failure treatment

Mesenchymal stem cells(MSCs)have demonstrated significant therapeutic potential in heart failure(HF)treatment.However,their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species(ROS)microenvironment.In this study,monascus pigment(MP)nanoparticle(PPM)was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs(BMSCs).Meanwhile,in order to load PPM and reduce the mechanical damage of BMSCs,injectable hydrogels based on Schiff base cross-linking were prepared.The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities,significantly enhancing BMSCs survival and activity in HF microenvironment.This hydrogel demonstrates superior biocompatibility,injectability,and tissue adhesion.With the synergistic effects of injectable,adhesive hydrogel and the microenvironment-modulating properties of MP,cardiac function was effectively improved in the pericardial sac of rats.Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.

Influence of biological treatments on intestinal microbiota of psoriasis patients

To the Editor:Psoriasis is a common,chronic inflammatory skin disease occurring worldwide and presenting at any age.[1]Biologics are the most important therapeutic advances in psoriasis treatment.[2]With the development of 16S rRNA sequencing technology,the association between psoriasis and intestinal flora has been gradually revealed.Some bacteria secrete short-chain fatty acids(SCFAs)with anti-inflammatory properties,serving as active microbial metabolites that regulate the function of immune cells in the intestine and other tissues.[3]However,the impact of biological treatment on gut microbiota and related functional changes in psoriasis patients remains unclear.Our study aimed to explore the effects of biological treatments on the intestinal microbiota of psoriasis patients.

An insect sclerotization-inspired antifouling armor on biomedical devices combats thrombosis and embedding

Thrombus formation and tissue embedding significantly impair the clinical efficacy and retrievability of temporary interventional medical devices.Herein,we report an insect sclerotization-inspired antifouling armor for tailoring temporary interventional devices with durable resistance to protein adsorption and the following protein-mediated complications.By mimicking the phenol-polyamine chemistry assisted by phenol oxidases during sclerotization,we develop a facile one-step method to crosslink bovine serum albumin(BSA)with oxidized hydrocaffeic acid(HCA),resulting in a stable and universal BSA@HCA armor.Furthermore,the surface of the BSA@HCA armor,enriched with carboxyl groups,supports the secondary grafting of polyethylene glycol(PEG),further enhancing both its antifouling performance and durability.The synergy of robustly immobilized BSA and covalently grafted PEG provide potent resistance to the adhesion of proteins,platelets,and vascular cells in vitro.In ex vivo blood circulation experiment,the armored surface reduces thrombus formation by 95%.Moreover,the antifouling armor retained over 60%of its fouling resistance after 28 days of immersion in PBS.Overall,our armor engineering strategy presents a promising solution for enhancing the antifouling properties and clinical performance of temporary interventional medical devices.

Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-κB Signaling

Background and Aims:Hepatic fibrosis(HF)is a critical step in the progression of hepatocellular carcinoma(HCC).Gene associated with retinoid-IFN-induced mortality 19(GRIM19),an essential component of mitochondrial respiratory chain complex I,is frequently attenuated in various human cancers,including HCC.Here,we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis.Methods:GRIM19 expression was evaluated in normal liver tissues,hepatitis,hepatic cirrhosis,and HCC using human liver disease spectrum tissue microarrays.We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein-9(Cas9)lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo.We performed flow cytometry,immunofluorescence,immunohistochemistry,western blotting,and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF.Results:Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues,including hepatitis,cirrhosis,and HCC tissues.Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice.In addition,GRIM19 loss caused chronic liver injury through reactive oxygen species(ROS)-mediated oxidative stress,resulting in aberrant NF-κB activation via an IKK/IKB partner in hepatocytes.Further-more,GRIM19 loss activated NLRP3-mediated IL33 signaling administration of the NLRP3 inhibitor MCC950 dramatically via the ROS/NF-κB pathway in hepatocytes.Intraperitoneal alleviated GRIM19 loss-driven HF in vivo.Conclusions:The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-κB signaling,providing potential therapeutic approaches for earlier HF prevention.

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China:A nationwide,multi-center,population-based cross-sectional study

Background:Cardiovascular disease(CVD)has emerged as the leading cause of death from prostate cancer(PCa)in recent decades,bringing a great disease burden worldwide.Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy(ADT).The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling.CVD was defined as myocardial infarction,arrhythmia,heart failure,stroke,ischemic heart disease,and others.CVD risk was estimated by calculating Framingham risk scores(FRS).Patients were accordingly divided into low-,medium-,and high-risk groups.χ2 or Fisher’s exact test was used for comparison of categorical variables.Results:A total of 4253 patients were enrolled in the present study.A total of 27.0%(1147/4253)of patients had comorbid PCa and CVD,and 7.2%(307/4253)had two or more CVDs.The enrolled population was distributed in six regions of China,and approximately 71.0%(3019/4253)of patients lived in urban areas.With imaging and pathological evaluation,most PCa patients were diagnosed at an advanced stage,with 20.5%(871/4253)locally progressing and 20.5%(871/4253)showing metastasis.Most of them initiated prostatectomy(46.6%,1983/4253)or regimens involving ADT therapy(45.7%,1944/4253)for prostate cancer.In the present PCa cohort,43.1%(1832/4253)of patients had hypertension,and half of them had poorly controlled blood pressure.With FRS stratification,as expected,a higher risk of CVD was related to aging and metabolic disturbance.However,we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT.This was in accordance with clinical practice,i.e.,aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery.Among patients who underwent medical castration,only 4.0%(45/1118)received gonadotropin releasing hormone antagonists,in stark contrast to the grim situation of CVD prevalence and risk.Conclusions:PCa patients in China are diagnosed at an advanced stage.A heavy CVD burden was present at the initiation of treatment.Patients who accepted ADT-related therapy showed an original higher risk of CVD,but the awareness of cardiovascular protection was far from sufficient.

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients betweenNovember 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classifiedinto 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymphnode (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and livermetastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane(below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostatecancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showedthat patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, andpatients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those inG5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015;medianOS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC,and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicatethat the farther the NRLNs are located, the more aggressive the disease is.

Current strategies for improving limitations of proteolysis targeting chimeras

Proteolysis targeting chimeras(PROTACs)are bifunctional degrader molecules via hijacking the ubiquitinproteasome system(UPS)to specifically eliminate targeted proteins.PROTACs have gained momentum as a new modality of attractive technologies in the drug discovery landscape,since it allows to degrade disease-related proteins effectively.Although some PROTACs drugs reached the clinical research,they are still facing some bottlenecks and challenges that should not be neglected,such as poor oral bioavailability and potential toxic side effects.To overcome these limitations,herein,we provide an overview of recent strategies for improving the durability of PROTACs by enhancing cell permeability and reducing toxic side effects.Meanwhile,the impact of these strategies on improving oral bioavailability as well as their advantages and drawbacks will also be discussed.This review will give a useful reference toolbox for PROTACs design and further promote its clinical application.

A“built-up”composite film with synergistic functionalities on Mg-2Zn-1Mn bioresorbable stents improves corrosion control effects and biocompatibility

Control of premature corrosion of magnesium(Mg)alloy bioresorbable stents(BRS)is frequently achieved by the addition of rare earth elements.However,limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after.Herein,we report a“built-up”composite film consisting of a bottom layer of MgF2 conversion coating,a sandwich layer of a poly(1,3-trimethylene carbonate)(PTMC)and 3-aminopropyl triethoxysilane(APTES)co-spray coating(PA)and on top a layer of poly(lactic-co-glycolic acid)(PLGA)ultrasonic spray coating to decorate the rare earth element-free Mg-2Zn-1Mn(ZM21)BRS for tailoring both corrosion resistance and biological functions.The developed“built-up”composite film shows synergistic functionalities,allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling.Of special importance is that the synergistic corrosion control effects of the“built-up”composite film allow for maintaining the mechanical integrity of stents for up to 3 months,where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries.Moreover,the functionalized ZM21 BRS accomplished re-endothelialization within one month.