Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Spinal cord injury is a serious disabling disease and its pathological and physiological processes mainly consist of primary and secondary injury. Primary injury is mainly caused by instantaneous mechanical injury while secondary injury is chiefly triggered by long-term inflammatory cascade reactions. With myelin sheath damaged in primary mechanical injury and secondary inflammatory injury, there was a large amount of cholesterol-rich myelin debris in the damaged area, which is mainly swallowed by bone marrow-derived macrophages (BMDMs). Owing to the limited capacity for processing cholesterol and insufficient efflux pump function of BMDMs, a large number of intracellular lipid droplets composed of neutral fat will be formed, as a result of which BMDMs show a"foamlike"shape and develop into foam cells. Foam cells further aggravate the local inflammation of the injury, prolong the inflammation and promote the formation of local scars, thus hindering nerve regeneration and recovery of sensory and motor functions. Currently, there has been no comparatively complete summary concerning the formation, mechanism of action, intervention of foam cells in spinal cord injury. To this end, the authors reviewed the research progress on the influence and regulation of foam cells on the pathological process of spinal cord injury, hoping to provide new ideas for the related basic research and clinical treatment of spinal cord injury.

OBJECTIVE To analyze influential factors for dabigatran exposure in elderly patients with non-valvular atrial fibrillation. METHODS The clinical information of 75 elderly patients diagnosed with non-valvular atrial fibrillation was collected from our hospital in Jan. 2019-Jun. 2020. One or two steady-state blood drug concentration samples were collected from each patient. NONMEM 7.2.0 software was used to establish a population pharmacokinetics model of dabigatran； the effects of different covariates on the apparent clearance of dabigatran were investigated， and the final model was verified by goodness of fit and Bootstrap method； NONMEM 7.2.0 software was used to analyze the drug exposure of ordinary elderly patients and elderly patients after taking dabigatran ester in different disease states. RESULTS Totally 122 blood concentration samples of dabigatran were collected. Advanced age， creatinine clearance and history of chronic heart failure were screened out as three significant covariates that influenced the clearance of dabigatran in elderly patients. The exposure of population with advanced age increased by about 50% compared with the general elderly， the exposure of population with history of chronic heart failure increased by nearly 30% compared with population without， and the exposure of population with moderate and severe renal injury increased by about 30% and 80% compared with mild. CONCLUSIONS Advanced age， renal injury and history of chronic heart failure are influential factors for elevated systemic exposure of dabigatran.

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

High-dose intravenous immunoglobulin (IVIG) has emerged as an effective treatment option for some refractory and severe dermatoses with few adverse reactions. The Fab and Fc fragments of IgG can exert anti-inflammatory effect by mediating specific downstream reactions via binding to a variety of autoantigens, autoantibodies and complements. This review summarizes action mechanisms of IVIG, focuses on the progress towards its application in severe dermatoses (such as severe drug eruption, refractory dermatomyositis and autoimmune bullous diseases) and special populations, as well as its adverse reactions.

Objective:To investigate the effect of IKKε on autophagy during abdominal aortic aneurysm formation in mice.Methods:We stimulated ApoE -/- mice and ApoE -/-IKKε -/- mice with AngⅡ and saline for 28 days. Metaboilic levels and aortic diameter of ApoE -/- mice and ApoE -/-IKKε -/- mice were measured. The arterial fibrosis of mice was detected by Masson staining and HE staining, mitochondrial reactive oxides were detected by fluorescence assay, the expression levels of autophagy factors LC3B and Beclin-1 were detected by immunohistochemistry, and the protein level of LC3B was detected by Western blot. Results:There was no significant difference in metaboilic levels between ApoE -/- mice and ApoE -/- IKKε -/- mice. However, the aortic diameterf ApoE -/-IKKε -/- mice was significantly less than that of ApoE -/- mice. The fibrosis level of ApoE -/-IKKε -/- mice was significantly lower than that of ApoE -/- mice. Furthermore, ROS in ApoE -/-IKKε -/- mice was lower than that in ApoE -/- mice. In addition, immunohistochemical and western blot showed that the expression levels of LC3B and Beclin-1 in ApoE -/-IKKε -/- mice were significantly lower than in ApoE -/- mice. Conclusion:IKKε -/- deficiency can significantly inhibit autophagy, thus reducing the development of abdominal aortic aneurysm in mice.

Objective:To investigate the ultrasonographic features and evolution of thyroid shrinking nodules in order to improve the differential diagnosis and management strategy and avoid unnecessary biopsy.Methods:A total of 245 patients with old bleeding of benign thyroid nodules diagnosed via fine needle aspiration cytology (FNAC) from May 2015 to July 2020 in the southern part of the Shanghai General Hospital Affiliated to the Medical College of Shanghai Jiaotong University, including 263 nodules. The sonographic parameters such as size, shape, aspect ratio, echo, edge, boundary, periphery, halo, calcification, posterior echo enhancement and posterior acoustic attenuation of nodules were analyzed retrospectively, and the ultrasonic appearances of nodules were classified; 41 nodules from 40 patients, who did ultrasound examinations more than twice and had both complete ultrasonographic data, were compared and then classified in order to explore the evolution rules of the nodules.Results:Two hundred and sixty-three thyroid shrinking nodules in 245 cases were classified into 4 types: "cystic wall shrinkage sign" type(71.48%, 188/263), "carcinoma-like" type (22.05%, 58/263), "inflammation-like" type(3.04%, 8/263) and "undefined atypical solid nodules" type(3.42%, 9/263). Of the 41 consecutive follow-up nodules, 37 cases showed obvious cystic wall shrinkage sign, and 7 of them developed into "carcinoma-like" type and 6 cases into "inflammation-like" type.Conclusions:The ultrasonographic appearance of thyroid shrinking nodules is a dynamic process, which can be divided into 4 types: "cystic wall shrinkage sign" , "carcinoma-like" , "inflammation-like" and "undefined atypical solid nodules" types. The "cystic wall shrinkage sign" type is typical and common. The "cystic wall shrinkage sign" type can develope into the "carcinoma-like" type or the "inflammation-like" type.

Objective:To discuss how to make the surgical strategy for tibial tubercle fracture associated with bicondylar tibial plateau fracture.Methods:Data of thirty-five patients of tibial tubercle fractures associated with bicondylar tibial plateau fractures who were treated from October 2014 to May 2018 were retrospectively analyzed. There were 26 males and 9 females with an average age of 37.6 years (range, 21-68 years). According to Schatzker classification in tibial plateau fracture, 16 cases were type V and 19 cases were type VI. According to the integrity of tibial tubercle fracture and cortical bone of the proximal tibia in bicondylar tibial plateau fracture, they were divided into four types: type A, tibial tubercle fracture fragment and cortical bone of the proximal tibia are both complete; type B, tibial tubercle fracture fragment is complete but cortical bone of the proximal tibia is comminuted; type C, tibial tubercle fracture fragment is comminuted but cortical bone of the proximal tibia is complete; type D, both of them are comminuted. The surgical approaches and fixation methods of all the tibial tubercle fractures were according to the four different types. There were 22 cases with type A and B that were treated via an anterolateral and a medial incision, 13 cases with type C and D were treated via an anterior midline and a medial incision. There were 4 cases belonging to type A fixed with lag screws singly, 18 cases with type B fixed with 1/4 tubular plates, 7 cases with type C and 6 cases with type D fixed by 1/4 tubular plates combined with lag screws.Results:Thirty-five patients were followed up for 16.8 months (range, 12-24 months). All fractures healed with an average time of 4.7 months (range, 3-6 months). Loss of reduction didn’t occur in 34 cases except one. According to Rasmussen radiographic evaluation, the average score was 14.1 (range, 10-18) and clinical outcomes were rated with excellent in 11 cases, good in 19, fair in 5. The excellent and good rate was 85.7% (30/35) . The mean Hospital for Special Surgery (HSS) scores of all cases were 86.8 (range, 64-98) and the functional scores were excellent in 22 cases, good in 10 cases and fair in 3 cases with the excellent and good rate of 91.4% (32/35) . Surgical complications included fat liquefaction in 2 cases, superficial wound infection in 1, loosening of implant in 1and traumatic arthritis in 1.Conclusion:This kind of tibial tubercle fracture associated with bicondylar tibial plateau fracture is rare and special. Therefore, the preoperative plan should be made by considering the morphological features of the tibial tubercle fragments and the cortical bone of the proximal tibia. The middle longitude approach is the best way to expose tibial tubercle fragments which should be fixed with 1/4 tubularplate and/or lag screws.

Objective: To explore the clinical features and treatment strategies of tibial plateau fractures sustained with hyperextension varus. Methods: Data of 11 patients of tibial plateau fractures with hyperextension varus treated from January 2008 to November 2017 were retrospectively analyzed. There were 7 males and 4 females with an average age of 41.2 years old (range, 25-67 years). Injuries were caused by falling down in 7 cases, traffic accident in 3 cases, and falling from height in 1 case, respectively. On the basis of Luo's three columns classification in tibial plateau, there were 9 cases of medial column fracture and 2 cases of medial combined with posterior column fracture. Six cases were concomitant with fibular head fracture and 2 cases with the injury of common peroneal nerve. Preoperative magnetic resonance imaging showed that there were anterior cruciate ligament injury in 3 cases, posterior cruciate ligament injury in 4 cases, medial meniscus injury in 5 cases, lateral meniscus injury in 3 cases, medial collateral ligament injury in 6 cases, iliotibial band injury in 2 cases and posterolateral complex injury of the knee joint in 9 cases, respectively. All tibial plateau fractures were treated firstly by open reduction and internal fixation via medial approach of the knee. The medial meniscuses and collateral ligaments were explored, in which of them there were 2 medial meniscuses with the marginal tear been sutured simultaneously. Then the knee joints which were still unstable after the examination of stable tests in 6 cases with posterolateral complex injuries were repaired surgically via lateral approach. Fibular head fractures were fixed with anchor nails or cannulated screws in 6 cases. The ruptured posterior cruciate ligaments in 2 cases were reconstructed with autologous tendon transplantation under endoscopy. Results: All the patients were followed up for an average period of 16.2 months (range, 12-22 months). All fractures were healed in 10-20 weeks with an average time of 16.5 weeks. The range of extension of the affected knee joint in all patients was 0° and the average flexion was 135° (range, 120°-145°) one year after surgery. The average flexion of affected knee in 4 cases which were only treated with the tibial plateau fracture without the mild ligament injuries was 137° (range, 132°-145°) and the average flexion of affected knee in 7 cases who were treated with tibial plateau fracture and severe posterolateral complex included posterior cruciate ligaments completely broken with reconstruction was 132° (range, 120°-140°). According to Rasmussen radiographic evaluation, the average score of all patients was 16.3 (range, 14 to 18) and clinical outcomes were rated with excellent in 10 cases and good in 1. The excellent and good rate was 100% (11/11). The mean of the hospital for special surgery (HSS) score was 86.7 (range, 79-96) and the functional scores were excellent in 9 cases, good in 2 cases thus the excellent and good rate was 100% (11/11). Both varus stress test 30° and dial test were positive in one case considered for the ligament laxity postoperatively who didn’t accept further treatment and the stabilization tests were negative in the other 10 cases. There were no intraoperative complications in all patients such as neurovascular injury. No incision infection, failure of the implants and fracture nonunion occurred postoperatively. Traumatic arthritis of the affected knee occurred one year after surgery in 1 case who had no obvious pain after treated with oral medicine. Conclusion The hyperextension varus injuries of the knee are rare clinically. The posterolateral complex should be evaluated thoroughly for this injury pattern. If it's necessary, the posterolateral structures must be repaired surgically after the tibial plateau fractures are fixed.