Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

Detrusor-sphincter dyssynergia (DSD) is a lower urinary tract dysfunction syndrome caused by disorders of the neural regulatory pathways for micturition. Its core feature is that the urethral sphincter fails to relax coordinately during detrusor contraction; instead, the persistent abnormal contraction leads to a series of severe complications such as dysuria, elevated intravesical pressure, and upper urinary tract damage.DSD is common in patients with central nervous system lesions, such as spinal cord injury and multiple sclerosis. This paper systematically reviews the latest research progress on the neural mechanisms of DSD, including ① loss of central regulation and excessive excitation of the spinal cord center, i.e., the loss of supraspinal inhibition leading to sacral spinal reflex hyperactivity; ② imbalance of key neurotransmitters and receptors, involving excessive glutamatergic excitation, weakened gamma-aminobutyric acid ergic/glycinergic inhibition, and the involvement of purinergic and endocannabinoid systems; ③ neuroimmunity and inflammatory response, where the activation of microglia and astrocytes after spinal cord injury releases pro-inflammatory factors, exacerbating neuronal excitability and circuit remodeling; ④ peripheral nerve and gut-bladder axis mechanisms, where sphincter structural remodeling and the gut microbiota-neuroimmunity crosstalk form a vicious cycle. The paper focuses on the sacral Onuf's nucleus as the“core hub”and key therapeutic target of DSD, discussing the central role of its dysfunction in the occurrence of synergistic disorders. In terms of therapeutic strategies, the paper summarizes existing traditional methods, such as drugs, botulinum toxin injection and neuromodulation, and envisions the cutting-edge directions of targeted intervention, such as precise strategies including gene therapy and neurotrophic support, as well as the challenges faced in clinical translation. Finally, the paper discusses the application prospects of precision medicine and artificial intelligence in the diagnosis and treatment of DSD, including precise classification based on multi-omics data, artificial intelligence-assisted recommendation of individualized treatment plans, and the development of dynamic closed-loop regulation systems. This paper aims to provide a theoretical basis and research direction for in-depth understanding of the neural mechanisms of DSD, and to promote the precise diagnosis, treatment and neural function remodeling.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Objective:To analyze the clinical efficacy and safety of endoluminal treatment of complex renal artery aneurysm (RAA).Methods:The clinical data and follow-up results of 19 patients with complex RAA admitted to Renji Hospital, Shanghai Jiaotong University School of Medicine from November 2014 to September 2021 were retrospectively analyzed. Two patients were treated with simple spring coil embolization into the aneurysmal artery, 14 patients were treated with simple spring coil embolization of the aneurysmal cavity, and 3 patients were treated with stent-assisted + spring coil embolization technique. Based on the location of the aneurysm, RAA were classified into type Ⅰ, Ⅱ, and Ⅲ. 7 patients with type Ⅰ, 10 patients with type Ⅱ, and 2 patients with type Ⅲ were studied. Variance analysis was used to compare the differences in glomerular filtration rate(GFR) of the affected side when the tumor was located at different locations, and Pearson was used to analyze the correlation between the number of coils implanted and the size of the tumor and GFR.Results:Ten of the 19 patients who were underwent successful endoluminal intervention. The average size of the patients′ aneurysms was (20.89±6.65) mm, and the average number of spring coils implanted was 8.22±3.08. The preoperative and postoperative serum creatinine were in the normal range, and no RAA tumor enlargement or recurrence was found during the follow-up period. The postoperative GFR was abnormal in patients with type Ⅰ, type Ⅱ, and type Ⅲ renal aneurysms, and the mean GFR value differed among the three types of patients( P=0.003). There was a negative correlation between the postoperative GFR values of the affected kidney and the number of spring coils implanted ( P=0.047), and no significant relationship between GFR and aneurysm size. Conclusion:The endovascular technique is an effective and safe means of treating complex RAA.

Objective:To evaluate the efficacy and safety of drug-coated balloon (DCB) with paclitaxel in the treatment of femoropopliteal arteriosclerosis obliterans (ASO).Methods:From Dec 2016 to Dec 2018, clinical data of femoropopliteal artery disease patients treated with paclitaxel DCB in Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively analyzed.Results:A total of 83 patients (95 lower limbs) underwent DCB therapy. Including 50 chronic total occlusion (CTO) lesions (52.6%) with mean lesion length of (18.35±10.61) cm. Twenty-four lesions (25.3%) were moderately or severely calcified. Bail-out stent implantation was performed in 29.5% cases. The mean follow-up time was 17.5 months. Twelve months after intervention, the all-cause mortality rate was 6.0%, the major amputation rate was 4.3%, the primary patency rate was 60.6%, the primary assisted patency rate was 72.4%, the secondary patency rate was 83.4%, and the freedom rate from clinically-driven target lesion revascularization(F-TLR) was 77.0%. Moderate to severe calcification was an independent risk factor for the primary patency of DCB therapy.Conclusion:DCB is a safe and effective endovascular therapy for femoropopliteal artery disease.

Objective To investigate the clinical value of fetal echocardiography in prenatal diagnosis , classification and outcome of abnormal origin of pulmonary artery from ascending aorta ( AOPA) . Methods From January 2014 to June 2018 ,18 cases of AOPA diagnosed by echocardiography in 43966 fetuses from Shaanxi Fetal Congenital Heart Disease Diagnostic Center were retrospectively analyzed . The echocardiographic features ,pathological and anatomical classification ,genetic characteristics and outcome of postnatal echocardiography were summarized . Results Abnormal origin of pulmonary artery branches could be demonstrated by color Doppler imaging system in 18 cases . Ten cases ( 55 .6％ ) of right pulmonary artery abnormalities originated from ascending aorta ( AORPA ) ,in which 6 cases ( 60％ ) were distal pulmonary artery abnormalities ,4 cases ( 40％ ) were proximal pulmonary artery abnormalities . Eight cases( 44 .4％ ) of left pulmonary artery abnormalities originated from ascending aorta ( AOLPA ) ,including 7 cases ( 87 .5％ ) of distal pulmonary artery abnormalities and 1 case ( 12 .5％ ) of proximal pulmonary artery abnormalities . Twelve AOPAs were associated with other intracardiac malformations with 6 right ventricular double outlet (DORV) accompanying with pulmonary stenosis ,3 tetralogy of fallots( TOF) ,2 atrioventricular septal defects( AVSD) ,1 single ventricle with single atrium ,and 1 Berry syndrome ,and no casese were associated with extracardiac malformations .Amniocentesis karyotype analysis and gene chip detection in 5 cases showed normal results . Four of 18 cases were born ,in which 3 cases died and 1 case was progressively suffered with right pulmonary artery atresia ,10 cases were inducted of labor ( 4 autopsy) and following-up was lost in 4 cases . Conclusions Incidence of AOLPA and distal type in fetal AOPA is higher than that in child and adult from references ,DORV is abnormal type mostly associated with intracardiac malformation . AOPA has no obvious genetic result for less cases . The main risk after AOPA birth is pulmonary infection . Echocardiography is of great value for AOPA in prenatal diagnosis , outcome observation and surgical planning after birth .

With the gradual increase of China's total expenditure on research and development (R&D),the national megaprojects implementation of state-dominated megaprojects should solve major national problems and meet the national great strategic demand according joint research of multiunit and multi-discipline.The importance of management for research cooperation agreement and business contracts are increasingly prominent.Based on the author's own experience,a scientific research institute's perspective,contractual agreements on the management audit and review the content of the key points are summarized.It gives the reference for the staff of scientific management.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder. Here, we report a rare case of multi-system LCH in a 20-month-old children presenting nasal congestion, fever, abnormal liver function, anemia, and skin damage. The radiograph computed tomography showed an osteolytic lesion in the lateral skull base with tumor extension. Pathological biopsy was performed, and the histopathologic diagnosis was LCH. A general review of LCH, including clinical manifestations, diagnosis, treatment, and prgognosis, is presented.
Histiocytosis, Langerhans-Cell ; diagnosis ; Humans ; Infant ; Rare Diseases