Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis(OSF),a premalignant disease that is largely induced by betel quid chewing.However,the lack of available models has challenged studies of angiogenesis in OSF.Here,we found that the expression of thrombospondin 1(THBS1),an endogenous angiostatic protein,was elevated in the stroma of tissues with OSF.Using a fibroblast-attached organoid(FAO)model,the overexpression of THBS1 in OSF was stably recapitulated in vitro.In the FAO model,treatment with arecoline,a major pathogenic component in areca nuts,enhanced the secretion of transforming growth factor(TGF)-β1 by epithelial cells,which then promoted the expression of THBS1 in fibroblasts.Furthermore,human umbilical vein endothelial cells(HUVECs)were incorporated into the FAO to mimic the vascularized component.Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs(vFAOs).Consistently,treatment with arecoline reduced the expression of CD31 in vFAOs,and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36,a receptor of THBS1.Finally,in an arecoline-induced rat OSF model,THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo.Overall,we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

With the improvement of China's socioeconomic status,the issue of aging has become increasingly prominent,making cerebral infarction a common disease among the elderly.In recent years,research on cerebral infarction has gradually deepened,shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit,covering various aspects such as the blood-brain barrier,astrocytes,microglia,and autophagy.This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction,offering strong support for innovative future treatment strategies.In this review,we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction,emphasized the intricate interactions among these biological components,which might lay the groundwork for more effective managements and treatments of cerebral infarction.By comprehensively reviewing existing literatures,we proposed future research directions,aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction.

Objective To explore the effect of 4-week repetitive downhill treadmill running on the mi-tochondrial structure,function,and autophagy in skeletal muscle of rats,so as to analyze the role of FKBP8-mediated mitophagy in exercise-induced mitochondrial damage in their skeletal muscles.Meth-ods Thirty-two male adult Sprague-Dawley rats were randomly divided into a 2-week quiet control group(2C group,n=8),a 4-week quiet control group(4C group,n=8),a 2-week exercise group(2E group,n=8)and a 4-week exercise group(4E group,n=8).Rats in 2E and 4E groups performed dai-ly 90-minute downhill treadmill running(-16°,16 m/min)5 days a week for two and four weeks,re-spectively.Then,they rested for 24 hours and received an exhaustive exercise test.Running distance and blood lactate were measured prior to and at the time of exercise cessation.Moreover,mitochondri-al ultrastructural changes in soleus muscles were observed by using a transmission electron microscope.The protein expression of mitochondrial succinate dehydrogenase subunit B(SDHB),cytochrome C oxi-dase subunit 1(MTCO1),FK506 binding protein 8(FKBP8)and microtubule associated protein 1 light chain 3(LC3)in the soleus muscle were measured using Western blotting.Meanwhile,the co-localiza-tion of FKBP8 with LC3 and cytochrome C oxidase subunit Ⅳ(COXⅣ)with LC3,lysosomal associat-ed membrane protein 2(LAMP2)were detected by the immunofluorescence double labeling technique.Results(1)The running distance of one exhaustive exercise and the blood lactate before and after the test in 2E group were significantly higher than 2C and 4E groups(P<0.05 or P<0.01),and the run-ning distance of 4E group was significantly higher than 4C group(P<0.01).However,there was no sig-nificant difference between 4E and 4C groups in the blood lactate before and after the exhaustive exer-cise test(P>0.05).(2)In both 2E and 4E groups,significant mitochondrial swelling and accumulation under cell membrane,as well as a number of mitophagosomes and mitophagolysosomes were observed,together with a significant reduce in the number of mitochondria(P<0.05),which was more severe in 2E group than 4E group.(3)The protein expression of mitochondrial SDHB and MTCO1 in 2E and 4E groups were lower than 2C and 4C groups,respectively,with significantly greater changes of these proteins in 4E group than 2E group(P<0.05 or P<0.01).(4)The protein expression of mitochondrial FKBP8 and LC3,as well as the co-localization of FKBP8 with LC3 and COXⅣ with LC3,LAMP2 in 2E and 4E groups were higher than 2C and 4C groups,respectively,with significantly greater changes in 4E group than 2E group(P<0.05 or P<0.01).Conclusion After 4-week downhill treadmill running,the structure,quantity and function of mitochondria in skeletal muscle are impaired.FKBP8-mediated mitophagy is activated,but is insufficient to degrade the damaged mitochondria,leading to muscular damage,as well as the increasing and falling down of running capacity.

Guangdong-Hong Kong-Macao Greater Bay Area (GBA) has three public health systems under different systems, which plays an important role in the construction of the public health system in China. Further strengthening the construction of the public health system in the GBA will play an important reference role in the optimization and upgrade of China's public health system in the future. Based on the key consulting project of "research on the strategy of the modern public health system and capacity building in China" by Chinese Academy of Engineering, this paper deeply analyzes the current status and existing problems of public health system construction in GBA and suggests to improve and innovate the mechanisms of collaborative prevention and control of public health risks, resource coordination and joint research and result sharing, information sharing and exchange, personnel training and team building in order to comprehensively improve the capacity of public health system in GBA, and promote the construction of Healthy China.
Humans ; China ; Hong Kong ; Macau ; Public Health

Infant ; Infant, Newborn ; Humans ; Infant, Premature ; Extracorporeal Membrane Oxygenation

Objective To observe the effect of cervical degenerative change on the expression of vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor-2(VEGFR-2).Methods The C3 to C7 segments of bilateral healthy cervical vertebrae of adult cadavers were taken as the control group,and the C3 to C7 segments of bilateral degenerative cervical vertebrae of adult cadavers were taken as the experimental group.The expression changes of VEGF and VEGFR-2 of the two groups were observed and analyzed by immunohistochemistry,immunofluorescence staining and real-time quantitative PCR.Results The protein and mRNA expressions of VEGF and VEGFR-2 in the experimental group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Cervical Luschka joint degenerative change significantly up-regulates the expression of VEGF and VEGFR-2,which is closely related to the microenvironmental changes around the Luschka joint caused by degeneration of joint-like structure.

Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.
Acute Kidney Injury ; Aged ; Aged, 80 and over ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Female ; Heart Valve Prosthesis ; Humans ; Male ; Middle Aged ; Myocardial Infarction/surgery* ; Retrospective Studies ; Risk Factors ; Stroke ; Stroke Volume ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome ; Ventricular Function, Left

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors