Cardiovascular and cerebrovascular diseases have be-come a great health threat.Increasing evidence has shown that both asymmetric dimethylarginine (ADMA)and symmetric dim-ethylarginine (SDMA)play important and independent roles in the development of cardiovascular and cerebrovascular diseases as well as in the prediction of cardiovascular and cerebrovascular events.Alanine-glyoxylate aminotransferase 2 (AGXT2 )is re-cently observed to be involved in ADMA metabolism.Deficiency in the expression and activity of AGXT2 may thus play a role in the development of cardiovascular and cerebrovascular diseases by affecting ADMA levels in vivo.Several single-nucleotide poly-morphisms at AGXT2 locus are observed to be associated with plasma SDMA level.This review summarizes recent advances in AGXT2 and its role in ADMA metabolism and the clinical rele-vance.

PURPOSE: Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. This study evaluated the therapeutic role of ferroptosis in classic chemotherapy drugs, including the underlying mechanism. MATERIALS AND METHODS: Cell viabilitywas detected by using the methylthiazoltetrazlium dye uptake method. RNAiwas used to knockout iron-responsive element binding protein 2, and polymerase chain reaction, western blot was used to evaluate the efficiency. Intracellular reduced glutathione level and glutathione peroxidases activitywere determined by related assay kit. Intracellularreactive oxygen species levelswere determined by flowcytometry. Electron microscopywas used to observe ultrastructure changes in cell. RESULTS: Among five chemotherapeutic drugs screened in this study, cisplatin was found to be an inducer for both ferroptosis and apoptosis in A549 and HCT116 cells. The depletion of reduced glutathione caused by cisplatin and the inactivation of glutathione peroxidase played the vital role in the underlying mechanism. Besides, combination therapy of cisplatin and erastin showed significant synergistic effect on their anti-tumor activity. CONCLUSION: Ferroptosis had great potential to become a new approach in anti-tumor therapies and make up for some classic drugs, which open up a new way for their utility in clinic.
Apoptosis ; Blotting, Western ; Carrier Proteins ; Cell Death ; Cisplatin* ; Drug Therapy ; Glutathione ; Glutathione Peroxidase ; HCT116 Cells ; Methods ; Oxygen ; Peroxidases ; Polymerase Chain Reaction

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

OBJECTIVEMucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome is an autosomal recessive lysosomal storage disease caused by a deficiency of arylsulfatase B(ARSB), which is required in the degradation of dermatan sulfate and chondroitin sulfate. The deficiency of ARSB leads to an accumulation of dermatan sulfate and chondroitin sulfate in lysosomes and gross excretion in the urine.Few articles about clinical study and ARSB gene mutation analysis of Chinese MPS VI patients were published. This study aimed to explore the clinical features and characteristics of ARSB gene in Chinese children with MPS VI.

METHODThirteen children were diagnosed as MPS VI by ARSB enzyme activity determination during the period from 2009 to 2013. Their clinical features, radiological findings and urine glycosaminoglycan (GAG) levels were retrospectively reviewed. Direct sequencing was used to identify any mutation in the ARSB gene.

RESULTThirteen children were diagnosed at the average age of (3.9 ± 2.2) years with 6 male and 7 female. All of these children presented with severe form and onset at an early age of (1.5 ± 0.8) years.Other clinical features included coarse facies, short stature, skeleton deformity, corneal clouding, hepatosplenomegaly with normal intelligence. The radiological findings in all children were characteristic of dysostosis multiplex, like abnormal development of vertebral bodies of the spine, campylorrhachia and paddle-shaped widened ribs. The MRI in case 2 showed cervical cord compression and multiple cysts degeneration in the corona radiate, cella lateralis and callosum.High urine GAG levels were detected, (307.10 ± 112.14) mg/L (Normally below 70 mg/L) and (722.28 ± 245.68) µg/mg creatinine. The ARSB enzyme activity in leukocytes was low, (13.29 ± 6.22) nmol/(mg×h) [Normal range (47-169) nmol/(mg×h)] by fluorogenic assay and (0.24 ± 0.18) U/g [Normal range (1.01-11.47) U/g] by colorimetric assay. A total of 11 mutations were identified by molecular analysis, including seven previously reported mutations (p.L72R, p.G167R, p.G303E, p.F399L, p. T442M, p.Y255X and p.R327X) and four novel mutations (p.Y175D, p.S403X, p.S464X and large deletion including ex. 2, 3). The c.1197C>G (p.F399L) mutation was the most common mutation in this study (31%).

CONCLUSIONThe severe form of MPS VI is characterized by early onset and rapid illness progression. Both the radiological findings and increased urine GAG are important clues to diagnose MPS VI.Large decrease or absence of ARSB activity is diagnostic for MPS VI.Four novel mutations of ARSB gene were identified. The reported mutation c.1197C>G (p.F399L) was the hot-spot mutation in this study.

Bone and Bones ; diagnostic imaging ; pathology ; Brain ; pathology ; Child ; Child, Preschool ; Exons ; genetics ; Female ; Glycosaminoglycans ; urine ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Mucopolysaccharidosis VI ; diagnosis ; enzymology ; genetics ; Mutation ; N-Acetylgalactosamine-4-Sulfatase ; genetics ; metabolism ; Polymerase Chain Reaction ; Radiography ; Retrospective Studies ; Sequence Analysis, DNA

Objective    To investigate the safety and feasibility of laryngeal mask general anesthesia as a replacement of tracheal intubation general anesthesia in the "three-port" thoracoscopic thymectomy via subxiphoid and subcostal arch for thymoma patients without myasthenia. Methods    From January 2018 to June 2019, clinical data of patients with thymoma who underwent the novel "three-port" operation in our institution were analyzed retrospectively. The patients were divided into two groups according to the anesthesia methods, including a tracheal intubation general anesthesia group and a laryngeal mask general anesthesia group. There were 70 patients in the tracheal intubation general anesthesia group, including 42 males and 28 females, with an average age of 45.83±15.89 years. There were 39 patients in the laryngeal mask general anesthesia group, including 26 males and 13 females, with an average age of 43.31±15.64 years. The clinical data of the two groups were compared. Results    The baseline characteristics of the patients in the two groups were well balanced (P>0.05). No massive bleeding, conversion to thoracotomy, postoperative myasthenia or death occurred in those patients. No patient with laryngeal mask anesthesia had a conversion to tracheal intubation anesthesia during the operation. There was no significant difference in the operation time, intraoperative bleeding, intraoperative maximum partial pressure of CO2, lowest partial pressure of oxygen and anesthesia effect score between the two groups (P>0.05). There was also no statistical difference in postoperative aspiration, gastrointestinal discomfort, length of hospital stay, pain score and patient satisfaction degree between the two groups (P>0.05). However, the anesthesia time before operation and the time of awake after anesthesia in the laryngeal mask anesthesia group were significantly shorter than those in the tracheal intubation general anesthesia group (P<0.05), and the incidence of transient arrhythmia, laryngeal discomfort and hoarseness in the laryngeal mask general anesthesia group was significantly lower than that in the tracheal intubation general anesthesia group (P<0.05). Conclusion    The "three-port" thoracoscopic thymectomy via subxiphoid and subcostal arch under laryngeal mask general anesthesia is safe and feasible in the treatment of thymoma without myasthenia, and can be recommended routinely.