AIM:To investigate the effect of activation of retinoid X receptor (RXR) on transforming growth factor β1 (TGF-β1) induced collagen synthesis under hypoxic environment in rat cardiac fibroblasts (CFs) and underlying molecular mechanisms .METHODS: CFs were cultured using myocardial tissue with dry method .Hypoxic environment was established for CFs by continuous nitrogen supplement .Type I and type III collagens in supernatants were detected by ELISA.Nuclear and cytoplasmic extractions were prepared using NE-PER nuclear and cytoplasmic extraction reagents .The protein levels of Smad2 and p-Smad2 were determined by Western blot and immunocytochemical staining .RESULTS:Un-der hypoxic condition , TGF-β1 (0.01~10 μg/L) increased the synthesis of type I and type III collagens in a dose-de-pendent manner in the CFs .At the concentration of 5μg/L, the synthesis of collagen I and III was significantly increased as compared with control group (P<0.01).RXR agonist 9-cis-retinoic acid (9-cis-RA;10 -9 ~10 -6 mol/L) decreased TGF-β1 (5μg/L)-induced synthesis of type I and III collagens in a dose-dependent manner in the CFs under hypoxic con-dition.The synthesis of type I and type III collagens was significantly inhibited by 9-cis-RA (P<0.01).Smad2 inhibitor ( 20 nmol/L) showed similar inhibitory effect on the synthesis of type I and III collagens induced by TGF -β1 under hypoxic condition.Compared with TGF-β1 intervention group, the cytoplasmic level of p-Smad2 in the CFs was significantly in-creased in TGF-β1+9-cis-RA group, but the nuclear p-Smad2 level was significantly decreased (P<0.05).CONCLU-SION:Retinoid X receptor agonist 9-cis-RA inhibits TGF-β1-induced synthesis of type I and type III collagens in the CFs by repressing p-Smad2 nuclear translocation under hypoxic condition .

[ABSTRACT]AIM:ToexploretheeffectofretinoidXreceptor(RXR)agonistbexarotene(Bex)andvitaminD receptor (VDR) agonist calcitriol (Cal) on the expression of nuclear factor-kappa B (NF-κB) and the development of atherosclerosis in streptozotocin-induced diabetic apolipoprotein E knockout ( STZ-ApoE-/-) mice.METHODS: Male mice were treated for 12 weeks as follows:(1) C57+vehicle;(2) ApoE-/-+vehicle;(3) STZ-ApoE-/-+vehicle;(4) STZ-ApoE-/-+Bex (10 mg· kg-1· d-1);(5) STZ-ApoE-/-+Cal (10 μg/kg, twice a week);(6) STZ-ApoE-/-+Bex (10 mg· kg-1· d-1) +Cal (10 μg/kg, twice a week).Intraperitoneal injection of STZ was performed to establish the diabetic animal model .Western blotting and immunohistochemical method was used to detect NF-κB level in the thorac-ic aorta.Plaque area in the thoracic aorta was measured using HE staining .RESULTS:Compared with the C57 mice, the fasting blood glucose in the ApoE-/-mice was not remarkably changed .The levels of total cholesterol ( TC) and low-densi-ty lipoprotein ( LDL) were greatly increased .The fasting blood glucose and lipid levels in STZ-ApoE-/-group were much higher than those in ApoE-/-group.Compared with STZ-ApoE-/-group, the fasting blood glucose and lipid levels in Bex group and Cal group were not significantly changed .Compared with the C57 mice, the protein expression of NF-κB in the ApoE-/-mice and the STZ-ApoE-/-mice was remarkably increased .Compared with STZ-ApoE-/-group, the levels of NF-κB in Bex group, Cal group and combination group were greatly decreased .Compared with STZ-ApoE-/-group, the thoracic artery plaque areas in Bex group and Cal group were inhibited (both P<0.05).Compared with Bex group, the plaque area of the thoracic artery in combination group was significantly decreased (P<0.05).CONCLUSION:Bexaro-tene or calcitriol decreases the development of atherosclerosis in streptozotocin -induced diabetic ApoE-/-mice.Bexarotene combined with calcitriol affords greater protection than monotherapy .The mechanism may be involved in down-regulating the expression of NF-κB.

OBJECTIVE:To observe the clinical effect and safety of Xuebijing injection in the treatment of moderate and se-vere infection of stage Ⅲ-Ⅳ pressure ulcer. METHODS:A total of 130 cases of moderate and severe infection of stage Ⅲ-Ⅳ pres-sure ulcer admitted to our hospital from Jul. 2011 and Jun. 2016 were randomly divided into observation group and control group, with 65 cases in each group. Control group was treated with 0.5%Iodophor disinfectant to disinfect the sore surface,given wet ster-ile gauze soaked with 0.5% Iodophor disinfectant to compress sore surface for 30 min,and then given Aikangfu absorptive silver ion antibacterial healing dressing to fill wound,changed dressing after 2/3 was soaked. Observation group was additionally given Xuebijing injection 50 mL added into normal saline 100 mL intravenously for 30-40 min,2-3 times a day,for consecutive 7 days,on the basis of control group. Treatment course of both groups lasted for 4 weeks. The clinical efficacy,the score of pres-sure ulcer scale for healing(PUSH),debridement time,the time of local symptom and SIRS disappearance as well as the occur-rence of ADR were compared between 2 groups. RESULTS:The total response rate of observation group(93.85%)was signifi-cantly higher than that of control group (80.00%),and debridement time,the time of local symptom and SIRS disappearance were all significantly shorter than control group,with statistical significance(P<0.05). Before treatment,there was no statisti-cal significance in PUSH score between 2 groups (P>0.05). After 1-4 weeks of treatment,PUSH score of 2 groups was de-creased significantly compared to before treatment,and the score of observation group was significantly lower than that of con-trol group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:For moderate and severe infection of stage Ⅲ-Ⅳ pressure ulcer,Xuebijing injection effectively reduces inflammatory exudation,improves the ab-sorption of necrotic tissue,relieves local symptom and systematic inflammatory reaction,promotes the healing of pressure ulcers and has good clinical effect and safety.

Objective To evaluate the stability and compressive mechanical functions of the lumbar spine following insertion of a new self-made allograft interbody fusion cage.Methods Anti-bending intensity with three points test,anti-rotation intensity and compressive stiffness were measured at L4-L5 lumbar spine on five adult human fresh cadaveric specimens following insertion of a new self-made allograft interbody fusion cage and compared with that of before and after nucleus pulposus removal.Results The anti-bending intensity of flexion and extension of lumbar spine after inserting a new allograft interbody fusion cage was increased significantly(P

Objective To evaluate CT characteristics of pulmonary sclerosing hemangioma(PSH) so that to improve the knowledgeof this disease.Methods CT characteristics of PSH pathologically verified were retrospectively analysed.Conventional scan andcontrast-enhanced scan were performed in all the patients.Results 14 lesions were in right lung,while 10 were in left,Diameters of these lesions ranged from 0.8 to 10 cm,and the average diameter was 3.08 cm.3 lesions were located in hilum of lung,while the rest(87.5%)were located in peripheral lung tissue.20 lesions were oval,and 4 were lobulated in morphology.21 lesions were smooth in edge.45.8% of the cases had calcification.All the lesions enhanced obviously on contrast-enhanced scan,and average CT value of(46.62?9.47) HU was increased.The dilated and distorted blood vessels could be detected in 2 large lesions.Conclusion On the basis of general benign tumor features, obvious enhancement and calcification are the characteristics of PSH on CT.

AIM:To explore the effects of atorvastatin (Atorv) on atherosclerosis in streptozotocin (STZ)-in-duced diabetic apolipoprotein E knockout ( ApoE-/-) mice with fat-rich diet and the possible mechanism .METHODS:C57 mice served as control.ApoE-/-mice (n=34) fed with high-fat diet were randomly divided into ApoE-/-group, STZ-ApoE-/-group and STZ-ApoE-/-+Atorv group.Intraperitoneal injection of streptozotocin was performed to create di-abetic animal model .Blood glucose was determined by glucose oxidase method .Blood lipid levels were detected by enzymic method or selective homogeneous method .The plaque area in the thoracic aorta was measured by HE staining .The protein level of nicotinamide-adenine dinucleotide phosphate ( NADPH) oxidase subunit gp91phox in the thoracic aorta was deter-mined by Western blotting .The levels of reactive oxygen species ( ROS) in blood and thoracic aorta homogenates were de-tected by Fenton reaction and Griess reagent .Human umbilical vein endothelial cells ( HUVECs ) were isolated from healthy umbilical cords by collagenase I and cultured .ROS production was detected by flow cytometry .NADPH oxidase ac-tivity was measured using lucigenin assay .Effects of retinoid X receptor α( RXRα) on inhibition of oxidative stress by ator-vastatin were evaluated by RNA interference and plasmid transfection .RESULTS: (1) Compared with C57 group, the plaque areas of the thoracic aorta in ApoE-/-group were increased .No difference of the fasting glucose between the 2 groups was observed.The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in ApoE-/-group than those in C57 group.(2) Compared with ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-group were further enlarged [(314.13 ±35.72) μm2 vs (215.88 ±34.19) μm2, P<0.05].The levels of blood glucose, TG, TC and LDL-C, thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in STZ-ApoE-/-group than those in ApoE-/-group (P<0.05).(3) Compared with STZ-ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-+Atorv group were reduced [(217.47 ±24.56) μm2 vs (314.13 ±35.72) μm2, P<0.05].The levels of blood glucose , LDL-C, TC, HDL-C and TG showed no significant difference between the 2 groups.Thoracic aorta gp91phox protein level and ROS production in blood and thoracic aorta homogenates were lower in STZ -ApoE-/-+Atorv group than those in STZ-ApoE-/-group (P<0.05).(4) High glucose-induced increases in NADPH oxidase activity and gp91phox expression were significantly inhibited by atorvastatin (10-6 mol/L) in HUVECs.The inhibitory effects of atorvasta-tin on high glucose-induced ROS production and NADPH oxidase activation were largely impaired when the cells were trans -fected with RXRαsiRNA.However , the effect of atorvastatin was significantly strengthened when RXRαwas over-expressed in the HUVECs transfected with RXRαplasmid.CONCLUSION: Atorvastatin inhibits atherogenesis by depressing high glucose-induced oxidative stress in diabetic ApoE-/-mice with fat-rich diet.The anti-oxidative stress effect of atorvastatin is mediated by RXRα.

Objective To investigate the feasibility and clinical value of medical history and clinical manifestation-based protocol(MHCMP) for the diagnosis of spontaneous coronary artery dissection(SCAD)using intravascular ultrasound (IVUS).Methods Based on the MHCMP designed in our centre,intraoperative sequential analysis was performed in patients with acute coronary syndrom and clinical tip of SCAD,SCAD and its classification were defined according to the result of IVUS.Results Of the 37 patients admitted with ACS at the Cardiology Service,29 patients had SCAD as the cause(78.4 ％).All the patients underwent coronary angiography and IVUS,of which 9 patiens were type I (24.3 ％),15 patients were type Ⅱ (40.5％) and 5 patients were type Ⅲ (13.5％).The left anterior descending artery was the most frequently affected (16 patients),followed by the the right coronary artery (7 patients),while 5 patients had dissection of the circumflex artery and 1 patient had dissection of the left main coronary artery.Type I (evident arterial wall stain):this was the pathognomonic angiographic appearance of SCAD with contrast dye staining of the arterial wall with multiple radiolucent lumens.Type Ⅱ (diffuse stenosis of varying severity):this angiographic appearance was not well appreciated and was often missed or misdiagnosed.SCAD commonly involved the mid to distal segments of coronary arteries,and could be so extensive that it reached the distal tip.There was an appreciable (often subtle) abrupt change in arterial caliber,with demarcation from normal diameter to diffuse narrowing.This diffuse and usually smooth narrowing could vary in severity from inconspicuous mild stenosis to complete occlusion.Type Ⅲ (mimic atherosclerosis):this appearance was the most challenging to differentiate from atherosclerosis and most likely to be misdiagnosed,while IVUS was helpful for the differential diagnosis.Conclusions MHCMP is able to screen out all kinds of SCAD and guide the treatment decisions making.

OBJECTIVETo explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE(-/-)) mice.

METHODSEight C57BL/6 mice served as control, 46 apoE(-/-) mice were randomized into 4 groups: apoE(-/-) group (n = 10), STZ+apoE(-/-) group (n = 12), STZ+apoE(-/-)+Bex 10 (10 mg×kg⁻¹×d⁻¹)group (n = 12), STZ+ apoE(-/-)+Bex 30 (30 mg×kg⁻¹×d⁻¹) group (n = 12). Diabetic apoE(-/-) animal model was established by intraperitoneal injection of STZ. Blood glucose was determined by glucose oxidase method. Patch area in thoracic aorta was measured by HE staining. Western blotting was used to determine the RXR and gp91(phox) protein level in thoracic aorta. Reactive oxygen species (ROS) level in blood and thoracic aorta homogenates was detected by Fenton and Griess method.

RESULTS(1) Patch areas of thoracic aorta were larger in apoE(-/-) group than in C57BL/6 group [(38.40 ± 8.95)µm² vs. (0.10 ± 0.01) µm², P < 0.01], further increased in STZ+apoE(-/-) group [(94.06 ± 8.04)µm², P < 0.05 vs. apoE(-/-) group] and significantly reduced in STZ+apoE(-/-)+Bex 10 group [(78.72 ± 4.62)µm², P < 0.05 vs. STZ+apoE(-/-) group] and further educed in STZ+apoE(-/-)+Bex 30 group [(46.13 ± 7.56)µm², P < 0.05 vs. STZ+apoE(-/-)+Bex 10 group]. (2) Blood glucose level, TG, TC, LDL-C, thoracic aorta gp91(phox) protein level and ROS level in blood and thoracic aorta homogenates were significantly higher in STZ+apoE(-/-) group than in apoE(-/-) group (all P < 0.05). Blood glucose level and TG, TC, LDL-C levels were similar between STZ+apoE(-/-)+Bex10 and STZ+apoE(-/-) group. Thoracic aorta gp91(phox) protein level and ROS level in blood and thoracic aorta homogenates were lower in STZ+apoE(-/-)+Bex 10 group than in STZ+apoE(-/-) group (P < 0.05). Blood glucose level, TG, TC, LDL-C levels, gp91(phox) expression in thoracic aorta, ROS level in blood and thoracic in STZ+apoE(-/-)+Bex 30 group were lower than in STZ+apoE(-/-) group (all P < 0.05).

CONCLUSIONBexarotene treatment could attenuate arteriosclerosis progression in STZ induced diabetic apoE(-/-) mice, the underlying mechanism might be related to suppressing oxidative stress and decreasing blood glucose level and improving lipids metabolism.

Animals ; Apolipoproteins E ; genetics ; Atherosclerosis ; etiology ; metabolism ; prevention & control ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; metabolism ; Retinoid X Receptors ; agonists ; metabolism ; Tetrahydronaphthalenes ; pharmacology

Background: Decompensated liver cirrhosis is a common disease in department of gastroenterology, and the prognosis is poor. There are many liver cirrhosis-related scoring models, but all have certain limitations. Aims: To explore the clinical value of serum calcium level combined choline esterase, MELD-Na score for predicting prognosis in patients with decompensated cirrhosis. Methods: A total of 169 patients with decompensated cirrhosis from Jan. 2017 to Dec. 2020 at the Quzhou Affiliated Hospital of Wenzhou Medical University were enrolled. Serum calcium level, choline esterase, creatinine, international normalized ratio (INR), prothrombin time, total bilirubin (TBIL) and serum sodium level were detected, and MELD score and MELD-Na score were calculated. ROC curve was used to analyze the value of parameters in evaluating prognosis of patients with decompensated cirrhosis. Results: After 6 months' follow-up, 125 patients survived and 44 died. TBIL, creatinine, INR, prothrombin time, MELD score, MELD-Na score were significantly lower in survival group than in death group (P<0.05), while serum albumin, sodium, calcium, choline esterase levels were significantly higher (P<0.05). ROC curve showed that AUC of serum calcium level, choline esterase, MELD score and MELD-Na score for predicting prognosis of patients with decompensated cirrhosis were 0.824, 0.783, 0.781 and 0.839, respectively. AUC of serum calcium level combined with choline esterase and MELD-Na score was 0.897. Conclusions: The combination of serum calcium level, choline esterase and MELD-Na score has a higher predictive value for the 6-months prognosis of decompensated cirrhosis patients.

Driven by multiple factors such as policy incentives,enhanced economic capacity of residents,aging popula-tion,and medical system reform,China's rehabilitation industry has been in a rapid development stage where opportunities and challenges coexist.Various rehabilitation hospitals urgently need new development thinking on how to seize the new opportunities for the development of rehabilitation medicine,give full play to the benefits of high-quality rehabilitation medical resources,and deal with the development of rehabilitation institutions under the new situation.Taking the tertiary rehabilitation hospital where the authors work as an example,this paper deeply analyzes the practical difficulties and challenges faced by the development of reha-bilitation hospital under the new circumstance,further explores the construction of a new working mode based on people-oriented and medical-rehabilitation integration.It also briefly summarizes the beneficial experiences and practices in the reform of rehabili-tation service models,and elaborates on the periodic achievement,so as to provide a meaningful reference for the majority of re-habilitation hospitals to plan and practice high-quality development and reform.