The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

Objective To screen the prevalence and related risk factors of minor hallucinations(MH)in newly diagnosed Parkinson's disease(PD).Methods From November 2018 to December 2022,274 newly diagnosed patients with untreated PD were enrolled in the PD Clinic of Brain Hospital Affiliated to Nanjing Medical University.According to the score of item 2 of the unified PD rating scale Ⅰ(UPDRSⅠ),the PD patients with MH were selected(MH group,score≥2).The patients matched in age,sex,education and course of disease level were screened in non-MH PD patients(NMH group,score = 0).Cognitive function,depressive symptoms,anxiety symptoms,sleep quality,non-motor symptoms,rapid eye movement sleep disorder(RBD)symptoms,activities of daily life,motor function and disease severity were evaluated with appropriate scales.The differences between two groups were compared,and the risk factors of MH in PD patients were analyzed by univariate and multivariate progressive Logistic regression.Results Among the 274 newly diagnosed PD patients,11 cases(4.01%)had MH.Compared with those in NMH group(22 cases),MH group had higher Hamilton depression scale(HAMD)scores,higher Hamilton anxiety scale(HAMA)scores,higher PD non motor symptoms(PDNMS)scores and higher RBD scores(all P＜0.05).Univariate Logistic regression analysis showed that high HAMD scores,high HAMA scores,high PDNMS scores and high RBD scores were risk factors for MH in PD patients(all P＜0.05).Multivariate Logistic regression analysis showed that high HAMD score(OR =1.182,95%CI:1.004-1.392,P =0.045)and high RBD score(OR =4.448,95%CI:1.066-18.557,P =0.041)were independent risk factors for MH in PD patients.Conclusions MH may occur in newly diagnosed PD patients with probability.Depression and RBD are independent risk factors for MH in PD patients.Attention should be paid to screening patients like this and early intervention measures should be taken.

Hospital fire safety management is not only a key aspect of hospital safety management,but also bears the im-portant mission of ensuring the safety of the lives and property of patients within the hospital.With the continuous development of intelligent technology,the fire safety industry is gradually moving towards intelligence,digitization,and networking.This article will combine the practical situation of smart fire protection at Guangdong Second People's Hospital,actively explore new models of smart fire protection construction and application under the new situation,in order to provide reference for major hospitals to build strong fire safety barriers.

Objective To investigate the value of plain and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI for differentiating clear cell hepatocellular carcinoma(CCHCC)and non-otherwise specified hepatocellular carcinoma(NOS-HCC).Methods Totally 36 CCHCC(CCHCC group)patients and 72 age-matched NOS-HCC(NOS-HCC group)patients were enrolled.Univariate analysis and multivariate logistic regression were used to retrospectively analyze the clinical,pathological and plain upper abdominal MRI as well as Gd-EOB-DTPA enhanced MRI data,so as to screen the independent predictors for distinguishing CCHCC and NOS-HCC.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of MRI-related independent predictors for distinguishing CCHCC and NOS-HCC individually and in combination.Results Pathologic Edmondson-Steiner grade of HCC,lesions with fat components showed on MRI,the ratio of lesion-to-liver signal intensity on plain T1WI(LLRT1WI)and the ratio of lesion-to-muscle signal intensity on plain T1WI(LMRT1WI)were all independent predictors for distinguishing CCHCC from NOS-HCC(all P＜0.05).The AUC of lesions with fat components,LLRT1WI and LMRT1WI for distinguishing CCHCC and NOS-HCC alone was 0.652,0.689 and 0.687,respectively,and of the combination was 0.762,higher than that of lesions with fat components(Z=-2.401,P=0.016)but not different with AUC of LLRT1WI(Z=-1.841,P=0.066)and LMRT1WI(Z=-1.440,P=0.150)alone.Conclusion Plain and Gd-EOB-DTPA enhanced MRI could be used to distinguish CCHCC and NOS-HCC.

Objective To observe the effects of electroacupuncture on the motor function and mitochondrial dynamics of skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in improving the motor dysfunction of Alzheimer disease(AD)from the perspective of mitochondrial dynamics.Methods Totally 18 SAMP8 mice were divided into model group and electroacupuncture group,with 9 mice in each group,and the SAMR1 mice with the same age were set as control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,and electroacupuncture was performed daily for 20 min,8 d as a course of treatment.Each course of treatment was separated by 2 d,for a total of 3 courses of treatment.The model group and the control group were not intervened.The motor function of mice was tested by grip strength test,suspension test,hind limb extension test and Morris water maze experiment.The morphology and structure of gastrocnemius were observed by HE staining,ATP content in gastrocnemius was determined by colorimetry,the mRNA expression of optic atrophy 1(OPA1),mitofusin 2(MFN2)and dynamin-related protein 1(DRP1)in gastrocnemius were detected by real-time quantitative PCR,the expressions of OPA1,MFN2 and DRP1 in gastrocnemius were detected by Western blot.Results Compared with the control group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment of mice in model group significantly decreased(P<0.01);the arrangement of fibers in the gastrocnemius muscle tissue was disordered,the gaps become wider,and the distribution of nuclei was uneven;the ATP content in the gastrocnemius muscle tissue was significantly decreased(P<0.01),the mRNA and protein expressions of OPA1 and MFN2 were significantly decreased(P<0.01),and the expression of DRP1 mRNA and protein significantly increased(P<0.01).Compared with the model group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment in electroacupuncture group significantly increased(P<0.01);the arrangement of gastrocnemius muscle tissue was relatively neat,the gaps become narrower,and the distribution of nuclei was more uniform;the ATP content in gastrocnemius muscle tissue significantly increased(P<0.01),while the mRNA and protein expressions of OPA1 and MFN2 significantly increased(P<0.05,P<0.01),the expression of DRP1 mRNA and protein significantly decreased(P<0.01).Conclusion Electroacupuncture can improve the skeletal muscle morphological structure and motor dysfunction of SAMP8 mice,and the mechanism may be related to the correction of skeletal muscle mitochondrial dynamic imbalance and the increase of skeletal muscle ATP content.

Objective To observe the effects of electroacupuncture on the motor function and expressions of Irisin,Decorin and Myostatin in skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in the treatment of the motor dysfunction of Alzheimer disease(AD).Methods Totally 247-month-old male SAMP8 mice were randomly divided into model group and electroacupuncture group,with 12 mice in each group,and the 12 male SAMR1 mice with the same age were set as the control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,once a day,8 days as one course of treatment,with an interval of 2 days,for a total of 3 courses.The control group and the model group were not intervened.The motor function of mice was tested by grip strength test,pole climbing test and open field test,the mRNA expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by RT-qPCR,and the protein expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by immunohistochemistry and Western blot.Results Compared with the control group,the grip peak and duration of the mice in the model group decreased,head turning time and pole climbing time were prolonged(P<0.01),the mRNA and protein expressions of Irisin and Decorin decreased(P<0.05,P<0.01),and the expressions of Myostatin mRNA and protein increased(P<0.05).Compared with the model group,the grip peak and duration of the mice in the electroacupuncture group increased,head turning time and pole climbing time were decreased(P<0.05),the mRNA and protein expressions of Irisin and Decorin increased(P<0.05),and the expressions of Myostatin mRNA and protein decreased(P<0.05).Conclusion Electroacupuncture can improve the motor dysfunction of SAMP8 mice,and its mechanism may be related to regulating the expressions of Irisin,Decorin and Myostatin in skeletal muscle.

Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.

Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

Carotid atherosclerotic plaque is the main cause of ischemic stroke. In recent years, with the continuous innovation of novel imaging technologies, numerous classification standards for carotid plaques provide more powerful evidence for the features of carotid plaques and perioperative vascular assessment, as well as the reference for surgeons in choosing therapeutic decisions. Ultrasound is the preferred non-invasive and convenient screening tool for carotid stenosis. Invasive examinations such as CT angiography and magnetic resonance angiography are suitable for carotid stenosis patients to determine the plaque composition and stability, which can guide surgical decision-making and help to prevent serious cardiovascular and cerebrovascular adverse events. Advances in the treatment of carotid artery stenosis have focused on the improvement and innovation of vascular interventional devices and surgical procedures, including double-layer stents, coated stents and transcarotid artery revascularization. As technology continues to evolve, molecular imaging and more minimally invasive screening as well as therapies will be the way forward.