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Background Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). Results In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. Conclusion This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs. Graphical Abstract

To study the pathologic feature of sudden cardiac death in Yunnan province and to investigate the role of myocarditis.During the period from 1991 to 2006, there were 29 cases of sudden cardiac death with autopsy performed. Fourteen of these cases were diagnosed to have myocarditis based on Dallas criteria and World Heart Federation's consensus. The clinical and pathologic findings were reviewed. The cardiac conduction system was examined in details by serial sectioning in 3 cases.Fourteen cases suffered with myocarditis, which accounted for 48% of all cases of sudden cardiac death studied. The age of the deceased ranged from 8 to 68 years (mean = 30 years), with male-to-female ratio equaled to 9:5. Lymphocytic myocarditis and neutrophil myocarditis were the two major types, affecting 11 and 3 cases, respectively. The inflammatory infiltrates were often patchy rather than diffuse. The inflammatory foci were detected only in 8% to 42% (average = 20%) of the paraffin sections of the heart tissue. These lesions were usually located in the lateral wall of left ventricle and occasionally in interventricular septum and right ventricular wall. Myocardial injury was mild in most cases while patchy myocytolysis or coagulation necrosis was observed only in a few cases. Most of the lesions were relatively new and histologic evidence of myocardial repairing sometimes coexisted. Pericarditis and subacute endocarditis were also identified in 4 and 1 cases, respectively. Atrioventricular node was involved by myocarditis in 1 of the 3 cases examined for cardiac conduction system. Two cases showed gross evidence of cardiac dilatation (either left ventricle or biventricular). Respiratory tract and pulmonary infection was present in 5 cases.Myocarditis represents one of the major pathologic changes of sudden cardiac death occurring in Yunnan province. The inflammation is usually focal. Further studies are required for delineation of possible etiologies which may include virus, bacteria or exogenous toxin.

To understand the epidemiologic and clinical characteristics of the "Yunnan unknown-cause sudden cardiac death (YUSCD)".Cases of YUSCD occurred in 2002-2004 were investigated with cross-sectional study. Clinical manifestation was observed and analyzed.The YUSCD areas were mountainous and most of the YUSCD cases appeared between June and August. Most of the YUSCD cases were young farmers and showed family/village clustering nature. Most of the patients died quickly with only few recovered. The overall incidence of YUSCD was 1.83% with mortality as 1.51%. The fatality rate of YUSCD appeared to be 78.1%.The YUSCD cases had a clustering feature along with time and area. The clinical manifestation of YUSCD could not be specifically identified, making the clinical diagnosis and treatment difficult when practicing in the fields that called for further studies on epidemiology, clinical work and etiology.

To identify the epidemiological and clinical features of unexpected sudden cardiac deaths (SUD) in Yunnan.Choosing the old SUD cases from Xiangyun, Heqing, Nanjian and Dayao counties and using the standardized verbal autopsy Form, we interviewed the family members of the cases, witnesses and doctors as well as reviewing their medical files to get relative information.We identified 116 SUDs in 21 villages from 1984 to 2004. The village-specific annually standardized incidence rates were ranged from 0.2/1000 to 8.9/1000 (median = 0.8/1000). 66% and 29% of the SUDs occurred in July and August respectively. The incidence rates of SUD were higher (1.6/1000, chi(2) = 16, P0.01) in 10 - 39 year-olds, and higher in females than in males (RR = 1.6, 95% CI: 1.1 - 2.3). Seventy percent of SUD occurred in families having clustering nature and 60% of the additional cases in the family were occurred within 24 hours (median = 20 hours) after the first SUD identified in the family. SUD occurred in 23 families followed the first affected family in a village during the same season. In these 23 families, 61% of the first SUD occurred within 8 days after the first SUD in the first affected family. 68% and 66% of the SUDs did not have any complaints or signs during the last 3 weeks or from 3 weeks to 2 days prior to the onset of the disease. 63% of the SUDs had cardiac symptoms within the last 2 days prior to the onset with major symptoms as dizziness, nausea, faintness, unconsciousness, weakness and palpitation. The median duration from acute onset to death was 2 hours.The extreme time-space clustering of SUD in families and in villages suggested that the risk factors occurred in specific time and location. Familial clustered SUD cases had common exposure pattern. Sudden onset of acute cardiac symptoms often followed by sudden death. Epidemiological study on new cases was necessary to identify risk factors and to develop hypothesis for causation. In July 2005, we instituted a special SUD surveillance system for all the affected counties together with 10 counties which had no reported cases.

INTRODUCTION: Since the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006-2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms. METHODS: We established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in

To investigate the clinical features of unexpected sudden death (SUD) clustered in families in Yunnan province.This retrospective study analyzed the clinical features of SUD occurred between July to September 2005 in 7 families in Yunnan province.All 16 SUD patients shared common clinical features such as fatigue and repeated syncope and one group of SUD patients (n = 8 from 4 families) presented with the gastric intestinal tract manifestations including nausea, vomiting, abdominal pain and diarrhea with suspected dietary history and abnormal laboratory enzyme findings (GOT/GPT, CK/CKMB, LDH/LDH1 etc.). In SUD patients without gastric intestinal tract manifestations (n = 8 from 3 families), there were no clear symptoms before death and repeated ventricular tachycardia and ventricular fibrillation were recorded in one survivor. There was no clear evidence for the involvements of hereditary and infectious factors for observed SUD.The reason for the unexpected sudden death clustered in 7 families in Yunnan remains unclear. Repeated syncope and fatigue served as the common clinical features in the presence or absence of gastric intestinal tract manifestations in all SUD cases. Further studies are needed to clarify the pathology and detailed clinical manifestations of SUD occurred in this area.