Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Objective:To investigate the adverse reactions and postoperative inflammatory reactions of Bill-Roth Ⅱ (BⅡ) gastroenterostomy with jejunal anastomosis and jejunal nutrient tube placement using linear cutting and closing device in gastric cancer surgery.Methods:A retrospective case-control study was conducted on 93 patients undergoing gastric cancer surgery in The Affiliated Hospital of North China University of Science and Technology from February 2017 to April 2020. According to 2016 (American Joint Committee on Cancer/Universal Integrated Circuit Card) AJCC/UICC, (Tumor, Node, stage; Tumor lymph node metastasis; Distant metastasis) TNM, there were 11 cases in stage ⅠA, 14 cases in stage ⅠB, 13 cases in stage ⅡA, 15 cases in stage ⅡB, 11 cases in stage ⅢA, 13 cases in stage ⅢB, and 16 cases in stage ⅢC. There were 51 cases of gastric antrum carcinoma, 26 cases of gastric body carcinoma and 16 cases of gastric pylorus carcinoma. There were 27 cases of papillary adenocarcinoma, 26 cases of tubular adenocarcinoma, 22 cases of mucinous adenocarcinoma, 9 cases of signet-ring cell carcinoma, 7 cases of adenosquamous carcinoma, and 2 cases of squamous carcinoma. The patients were divided into experimental group (48 cases) and control group (45 cases) according to whether or not the linear cutting and closing device was added and jejunal anastomosis was performed and jejunal nutrition tube was placed. The gender composition, age, lesion site, pathological type, pathological stage, postoperative hospital stay and postoperative complications were compared between the two groups, and the white blood cell count WBC, C-reactive protein CRP on the 7th day after surgery, erythrocyte Sedimentation rate (ESR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) inflammation indicators were compared between the two groups.Results:There was no significant difference in gender composition, age, lesion location, pathological type and pathological stage between the two groups (all P>0.05). The incidence of abdominal pain, abdominal distension, nausea, vomiting and pleural effusion in 93 patients were 18.3%(17/93), 21.5%(20/93), 23.7%(22/93), 17.2%(16/93) and 18.3%(17/93), respectively. The complication rates of the above indexes in the two groups were 10.4% (5/48) Compared with 26.7% (12/45), 12.5% (6/48) and 31.1% (14/45), 15.6%(7/48) and 33.3% (15/45), 8.3%(4/48) and 26.7% (12/45), 8.3% (4/48) and 28.9% (13/45) (χ 2 values were 4.11, 4.77, 4.52, 4.27 and 5.27, respectively; P values were 0.043, 0.029, 0.033, 0.039 and 0.022, respectively). There was no significant difference in lower extremity venous thrombosis, anastomotic bleeding, accumulated pneumonia and incision dehiscence between the two groups ( P>0.05). WBC on the 7th day after operation in the experimental group and the control group (7.02±1.83)×10 9/L and (8.39±2.27)×10 9/L ( t=3.22, P=0.002), TNF-α (2.44±0.70) μg/L and (3.56±1.14) μg/L ( t=5.71, P<0.001), IL-6 (235.31±41.72) μg/L and (365.91±73.16) μg/L ( t=10.66, P<0.001) there was significant difference between the two groups. There was no significant difference in CRP and ESR between the two groups on the 7th day after operation ( P>0.05). The postoperative hospital stay between the experimental group and the control group was (13.88±2.81) d and (22.78±2.51) d, the difference was statistically significant ( t=16.07, P<0.001). Conclusion:The application of side-to-side jejunostomy combined with jejunal nutrition tube for enteral nutrition in gastric cancer surgery can reduce the occurrence of adverse reactions such as postoperative abdominal pain, abdominal distension, accumulated pneumonia, nausea, vomiting and pleural effusion, reduce the postoperative hospital stay and reduce the postoperative inflammatory reaction to a certain extent.

Objective To compare the effect of enteral nutrition by jejunum colostomy nutrition infusion pump of patients after Whipple surgery as well as reduce adverse reactions in patients.Methods Sixty-five cases with the implementation of Whipple and jejunum of colostomy were selected as our subjects,who were hospitalized in the Affiliated hospital of Hebei United University from Feb.2009 to Nov.2013.All patients were divided into observation group (33 cases) and control group (32 cases) according to the methods of nutrient input.Patients in observation group were given nutrition infusion pump pumping (15 to 50 ml/h) ;and patients in control group were adopted disposable infusion connection infusion with the speed of 30 drops/min with the thermostat heating temperature and the water pipe.The blood glucose,serum albumin,blood electrolyte concentration of postoperative,and the adverse reactions during input nutrient solution including vomiting,abdominal distention,diarrhea and other adverse circumstance were recorded.Results At 1st,3rd,5th day,there was no statistically significant difference in terms of the levels of glucose,blood albumin,blood C1,Na +,K + between two groups(blood glucose:F inner grouP =3.01,P ＞ 0.05 ; F between group =2.90,P ＞ 0.05 ; F cross group =2.87,P ＞ 0.05 ; serum albumin:F inner group =2.94,P ＞ 0.05 ; F between group =2.89,P ＞ 0.05 ; F cross group =2.76,P ＞ 0.05 ; blood Cl:F inner group =1.78,P ＞ 0.05 ; F between group =1.96,P ＞ 0.05 ; F cross group =1.88,P ＞ 0.05 ; blood Na +:F inner group =1.06,P ＞ 0.05 ; F between group =1.35,P ＞ 0.05 ; F cross group =1.27,P ＞ 0.05 ; blood K +:F inner group =3.12,P ＞ 0.05 ; F between group =3.04,P ＞ 0.05 ; F cross group =2.93,P ＞ 0.05).There were significant differences regarding of the rate of vomiting,abdominal distention,diarrhea and other adverse conditions compared with the infusion enteral nutrition has good clinical effect,postoperative blood (x2 =4.029,4.381,4.905 respectively; P ＜ 0.05).Conclusion The methods of colostomy enteral nutrition with infusion pump after Whipple surgery is proved to be with the better clinical effect in reducing postoperative vomiting,abdominal distention,diarrhea and other adverse conditions compared with the infusion enteral nutrition,and there are no significant difference in the terms of the levels of glucose,blood albumin,blood Cl,Na +,K +.

Objective To investigate the clinical significance of setting nasojejunal nutrition tube in Whipple operation,which can promote patient recovery and prevent complications.Methods Fourty-one patients were undergone Whipple operation and they were randomly divided into eternal nutrition (EN) and parenteral nutrition group (PN).Patients in EN group were set nasojejunal nutrition tube during Whipple operation in order to supply eternal nutrition at earlier period,while in PN group were supplied parenteral nutrition in earlier period.The operative procedure time,the complication in post-operation,the cost of hospitalization and the periods of hospitalization of two groups were recorded.The scores of nutritional status were measured.Results The operative time in EN group and PN group were (200.71 ±51.33)min and (160.48 ± 47.62) min,and no significant difference was found between two groups (t =-1.524,P ＞ 0.05).The hospitalization expenses in EN group was (38835.65 ± 537.69)yuan,lower than that in PN group ((47833.18 ±659.24) yuan,t =2.073,P ＜ 0.05).The hospital periods of EN group and PN group were 10 (3) d and 18(3) d,and the difference was significant (Z =-5.374,P ＜0.001).There were 2 cases who occurred complications after operation in EN group,including 1 cases with incision infection,and 1 cases of pancreatic fistula.Nine cases occurred complications in PN group,including 3 cases with incision infection,2 cases with pancreatic fistula,2 cases with pulmonary infection,2 cases with gastric paralysis,and all were cured by conservative treatment.There was statistically significant difference in the incidence of postoperative complications (P =0.027).All cases with complication were recovery after corresponding treatment.At 7th day after operation,hemoglobin in EN group and PN group were (113.09 ± 12.35) g/L and (107.04 ± 11.81) g/L,and the difference was significant (t =2.035,P ＜ 0.05).The levels of retinol binding protein,serumalbumin,serum prealbumin,serum transferrin in EN group were (42.62 ± 5.64) mg/L,(40.24 ± 6.79) g/L,(321.43±31.28) mg/L,(32.86±4.67) mg/L,(32.86 ±4.67) mg/L,significant different from those in PN group ((15.50 ± 4.26) mg/L,(31.52 ± 5.92) g/L; (197.86 ± 37.71) mg/L,(23.59 ± 4.32) mg/L; t=2.398,2.606,2.119,2.569; P ＜0.01 or P ＜ 0.05).Conclusion Nutritional status and prognosis are improved obviously by setting nasojejunal nutrition tube in Whipple operation.And the cost of hospitalization,the periods of hospitalization are decrease.

Objective To study the effects of toys for laboratory animals on reproductive performance and growing development of experimental mice.Methods ICR mice were fed with toys, the informations of reproductive performance and growing development were recorded.Results All the data of reproductive performance of the test group were higher than the control group except the number of newborn mice, and showed significant difference ( P <0.05 ) .The data of growing development of the test group were higher than the control group too, but showed no significant difference ( P >0.05).Conclusion Toys for laboratory animals have good effects on reproductive performance and growing development of mice, and suggested to be used into the process of experimental mice raising.

Professor XUE Bo-shou skills in treating internal stubborn disease by ancient prescriptions.This article lists XUE Bo-shou treating reactive arthritis,seborrheic alopecia,chloasma,lung cancer by Huangqi Chifeng decoction.His clinic experience can be used as references by clinic practice.

Objective To characterize the localization and expression of cyclooxygenase (COX) in thoracic spinal cord before and after acute contusion. Methods 48 Sprague Dawley rats, 250 to 300 g in weight, were used for the study. The injuries of spinal cord were induced at the T8,9 level by dropping a weight of 10.24 g form a height of 50 mm (Allen’ s model). All the animals with spinal cord injury were sacrificed at time points ranging from 2 to 48 hours (2, 4, 8, 16, 24, and 48 hours) after management. Expressions of COX- 1 and COX- 2 in the thoracic spinal cords, normal and injured, were studied with immunohistochemistry. Results COX- 1 immunoreactivity was found to constitutively express in cytoplasmof glial cells and neuropils in white matter. Tiny COX- 1 immunoreactivity was found in glial cells, neuropils and neurons in the gray substance. It was found that COX- 2 immuno- labeling expressed constitutively in cytoplasm and closely surrounding the nucleus of neurons in both ventral and dorsal horns. Contusion to the spinal cord did not result in changes of COX- 1 protein localization and expression according to evaluation of immunohistochemistry. COX- 2 immunoreactivity improved only in neurons 4 hours following contusion. The positive COX- 2 protein reactivity reached the peak 24 hours after contusion. Conclusions In contrast to their expression in the majority of peripheral tissues, both COX isoforms express constitutively in the normal rat thoracic spinal cord. The major isoform of COX involved in the secondary spinal cord injury is COX- 2 after the spinal cord is mechanically injured.