[Analysis of risk factors for venous thromboembolism in patients with polycythemia vera and establishment of a prediction model].

Objective: To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. Methods: PV patients with JAK2V617F gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age M (Q1, Q3) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [M (Q1, Q3)] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Results: Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all P<0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all P<0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (P=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (P<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (HR=2.031, 95%CI: 1.297-3.179, P=0.002), V617F%≥50% (HR=2.141, 95%CI: 1.370-3.347, P=0.001), ASXL1 mutation (HR=4.632, 95%CI: 1.497-14.336, P=0.008), spleen subcostal≥5 cm (HR=1.771, 95%CI: 1.047-2.996, P=0.033) are the risk factors of venous thrombosis in PV patients. According to HR values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95%CI: 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Conclusions: Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.

[Anti-HMGCR immune-mediated necrotizing myopathy: A case report].

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

[Analysis of risk factors for thromboembolism in patients with JAK2V617F gene mutation positive myeloproliferative neoplasms].

Objective: To analyze the risk factors of thrombosis in patients with JAK2V617F mutation positive myeloproliferative neoplasms (MPN). Methods: A total of 223 MPN patients with JAK2V617F mutation in the Second Hospital of Tianjin Medical University from September 2017 to May 2023 were retrospectively enrolled, including 111 males and 112 females, aged [M(Q1,Q3)] 57(21,66) years. According to the presence or absence of thromboembolism during follow-up, the patients were divided into thrombosis group (n=102) and non-thrombosis group (n=121). The clinical characteristics, laboratory characteristics, cytogenetics and other disease progression and survival of the two groups of patients were analyzed. As of March 31, 2023, the follow-up period [M (Q1, Q3)] was 6 (3, 10) years. The influencing factors of thrombosis in JAK2V617F positive MPN patients were analyzed by using the Cox risk model. Results: Among 223 JAK2V617F positive MPN patients, 144 were polycythemia vera (PV), 51 were essential thrombocythemia (ET) and 28 were primary myelofibrosis (PMF). The mutation rates of ASXL1 and BCORL1 genes in the thrombosis group were 19.6% (20/102) and 6.9% (7/102), respectively, which were higher than those in the non-thrombosis group [9.1% (11/121) and 0.8% (1/121)] (both P<0.05). The proportion of monocytes, C-reactive protein (CRP), interleukin-1ß (IL)-1ß, IL-8 and tumor necrosis factor-ß (TNF-ß) increased in the thrombosis group were higher than those in the non-thrombosis group (all P<0.05). Multivariate analysis showed that age≥60 years (HR=2.132, 95%CI: 1.376-3.303, P=0.001), history of thrombosis (HR=3.636, 95%CI: 2.121-6.202, P<0.001), ASXL1 mutation positive (HR=2.245, 95%CI: 1.093-3.231, P=0.022) and elevated TNF-ß (HR=2.009, 95%CI: 1.113-3.624, P=0.021) were risk factors for thrombosis in JAK2V617F positive MPN patients. Conclusions: In addition to age, history of thrombosis and positive ASXL1 mutation, elevated TNF-ß is also an influencing factor of thrombosis in JAK2V617F positive MPN patients. Intervention of inflammation may have a certain effect on the prevention and treatment of thrombosis.

[Advances in diagnosis and treatment of Wolfram syndrome and related molecular mechanism].

Wolfram syndrome is a rare genetic spectrum disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, accompanied by other variable clinical manifestations. At present, the prognosis of this syndrome is very poor, the specific molecular mechanism is not clear, effective treatments are lacking to delay, prevent or reverse the development of Wolfram syndrome, and many patients die prematurely due to severe neurological dysfunction. This increases the urgency of the research on the pathogenic molecular mechanism related to Wolfram syndrome and the development of new therapies. This article summarizes the research progress on the pathogenic molecular mechanism and treatment status of Wolfram syndrome, in order to provide reference for the further mechanism research, prevention and treatment of Wolfram syndrome.

[Attention should be paid to the establishment and management of glaucoma records].

Glaucoma is the world's leading cause of irreversible blindness. As a chronic disease, it requires lifelong follow-up and management. In the long-term follow-up of glaucoma patients, a diagnosis and treatment management system is helpful. Despite the availability of various means of informationalized record management, there remain problems and challenges, like a lack of unified file management standards, data incompatibility, and barriers to inter-hospital data sharing, which lead to the failure to establish a comprehensive and standardized glaucoma record for patients. It is necessary to form a standardized management system so as to improve the efficiency and accuracy of the diagnosis and treatment of glaucoma, better maintain the visual function of patients and reduce the burden on society and family.

Tributyrin supplementation in pasteurized waste milk: Effects on growth performance, health, and blood parameters of dairy calves.

This study evaluated the effects of incremental tributyrin supplementation in pasteurized waste milk on growth performance, health, and blood metabolism of dairy calves before and after weaning. Forty-eight newborn female Holstein dairy calves (39.6 ± 2.75 kg; mean ± standard deviation) were blocked by age and randomly assigned to 3 treatments: pasteurized waste milk (1) without supplementation, (2) with 1 g/L of tributyrin products (unprotected solid powder; containing 35% tributyrin), or (3) with 2 g/L of tributyrin products. The calves were weaned on d 56 and were raised until d 77. Data were analyzed for the preweaning, postweaning, and overall periods. The results showed that starter intake and hay intake were not different among treatments in any period of the trial, but the crude protein intake tended to increase linearly with tributyrin supplementation during the overall period. Although tributyrin supplementation had no effects on body weight during preweaning and overall periods, body weight increased linearly with tributyrin supplementation postweaning. The average daily gain tended to increase linearly during postweaning and overall periods. No effects were observed on feed efficiency in any period. A positive linear relationship between body length and tributyrin supplementation was observed during the postweaning period, but no differences were found for the other body structural measurements in any period. The results of diarrhea showed that tributyrin concentration had a negative linear relationship with diarrhea frequency during preweaning and overall periods. The rectal temperature did not differ among treatments in any period, but a treatment × week effect for rectal body temperature was observed. For blood metabolism, tributyrin supplementation had no effects on insulin, growth hormone, total protein, albumin, or globulin. No differences were found in serum amyloid A concentration in any of the periods, yet haptoglobin concentration decreased linearly with increasing tributyrin concentration during postweaning and overall periods. Endothelin concentration showed a tendency to decrease linearly during preweaning and postweaning periods and decreased linearly with tributyrin supplementation during the overall period. An increasing tributyrin concentration was associated with a negative linear relationship with IL-1ß concentration during the preweaning period, and no differences were found in the other periods. The concentration of IL-6 and tumor necrosis factor α were not different among treatments in any of the periods. These data suggest that increasing the concentration of tributyrin in pasteurized waste milk could increase growth performance and health of dairy calves, and incremental tributyrin supplementation could linearly reduce haptoglobin, endothelin, and IL-1ß concentrations, indicating a positive effect of tributyrin on alleviating oxidative stress and inflammatory status of dairy calves. Calves fed pasteurized waste milk supplemented with tributyrin products (containing 35% tributyrin) at 2 g/L compared with 1 g/L of milk had more improved growth and health.

[Incidence and mortality of corpus uteri cancer in China, 2015].

Objective: To estimate the incidence and mortality of corpus uteri cancer in China, 2015. Methods: Quality audit and evaluation of the data from 2015 cancer registration reported by 501 cancer registries were conducted, and 368 cancer registries were included in the analysis. The incidence rate and mortality rate of corpus uteri cancer were calculated according to the factors of the region (urban, rural, east, central, western), sex and age groups. The incidence and mortality of corpus uteri cancer with the 2015 population were estimated. Chinese standard population in 2000 and world Segi's population were used for the calculation of age-standardized rates (ASR) of incidence and mortality. Results: In 2015, 368 cancer registries included in the analysis covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were about 68 900 new cases of corpus uteri cancer in 2015, the incidence rate was 10.28/10(5), age-standardized incidence rates by Chinese standard population (ASR China) and world standard population (ASR world) were 6.86/10(5) and 6.66/10(5), respectively. The incidence rate of urban area (11.35/10(5)) was higher than that of rural area (8.90/10(5)), and the incidence of eastern region (12.12/10(5)) was higher than the central region (9.94/10(5)) and the western region (8.25/10(5)). It is estimated that in 2015, there were about 16 000 deaths of corpus uteri cancer, the mortality rate was 2.39/10(5), ASR China was 1.49/10(5), ASR world was 1.47/10(5). The mortality in urban areas (2.40/10(5)) is close to rural areas (2.39/10(5)); the mortality in central areas (2.55/10(5)) was higher than the eastern areas (2.32/10(5)) and the western areas (2.31/10(5)). Conclusions: In China, the incidence of corpus uteri cancer is on the rise and has a trend of youth, the burden of disease is gradually increasing, which threatens the health of women. Targeted prevention and control measures should be carried out in the different regions.

[Endovascular treatment strategies for distal entry tear of Stanford type B aortic dissection].

Currently, thoracic endovascular aortic repair (TEVAR) is the first-line treatment for patients with complicated Stanford type B aortic dissections. However, TEVAR does not occlude the distal entry tear of dissections, and blood flow persists in the false lumen. Dissections might progress in some patients. Studies showed that distal entry tear increased the possibility of late aortic events during follow-up. Thus, treatment of distal entry tear is necessary in some high-risk patients after TEVAR. In this article, the current treatment strategies of distal entry tear are summarized, which include PETTICOAT, STABILISE, covered stent, fenestrated and branched stent-grafts, false lumen embolization, vascular occluder, and Knickerbocker. However, the number of the cases of most approaches is so limited that the indications and effectiveness need to be further studied. Selecting the right treatment for the right patient is of great importance.

[Platelet derived growth factor-BB regulates phenotype transformation of pulmonary artery smooth muscle cells via SIRT3 affecting glycolytic pathway].

Objective: To investigate whether platelet-derived growth factor-BB (PDGF-BB) can regulate phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) via SIRT3 affecting glycolytic pathway. Methods: The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into 3 groups by using 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway: normal control group, PDGF-BB group(30 ng/ml) and PDGF-BB (30 ng/ml)+2-DG (10 mmol/L) group. In lentivirus-mediated overexpression assay, cells were divided into control group, PDGF-BB group(30 ng/ml), PDGF-BB+deacetylase sirtuin-3 (SIRT3) overexpression group and PDGF-BB+empty vector group. The expression levels of phenotype related index such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), calponin, vimentin were detected by qRT-PCR and Western blot. Meanwhile, the expression of α-SMA was detected by cellular immunofluorescence staining. EDU staining was used to detect the proliferation of PASMCs. The expression of SIRT3 was detected by Western blot. The expressions of glucose transporter 1 and aerobic glycolytic enzymes were detected by qRT-PCR and Western blot in lentivirus-mediated overexpression assay. Results: (1) PDGF-BB affects PASMCs phenotypic transformation through glycolytic pathway: compared with normal control group, PDGF-BB significantly decreased the expressions of contractile phenotype markers such as α-SMA, SM-MHC, calponin mRNA and protein (all P<0.05), but it increased the expressions of the synthetic phenotype marker vimentin mRNA and protein (both P<0.05). Cellular immunofluorescence assay showed that PDGF-BB significantly decreased the number of α-SMA positive cells, while 2-DG reversed the process. (2) PDGF-BB promoted cell proliferation through glycolytic pathway: the proliferation of PASMCs was significantly higher in PDGF-BB group than in control group (P<0.05), and which could be significantly reduced by 2-DG (P<0.05). (3) PDGF-BB inhibited the expression of SIRT3 protein in PASMCs: the expression of SIRT3 protein in PDGF-BB group was lower than that in control group (P<0.05). (4) PDGF-BB affected glycolytic pathway through SIRT3:compared with the control group, PDGF-BB significantly increased the expression levels of glucose transporter 1 (Glut1), hexokinase 2 (HK2) and 6-phosphfructo-2-kinase 3 (PFKFB3) mRNA (all P<0.05), which was reserved by over-expression of SIRT3. There were no significant difference in mRNA expression levels between PDGF-BB group and PDGF-BB+empty vector group (P>0.05).Compared with the control group, PDGF-BB significantly increased the expression levels of Glut1, HK2 and PFKFB3 protein(all P<0.05), which was reserved by over-expression of SIRT3. There were no significant differences in protein expression levels between PDGF-BB group and PDGF-BB+empty vector group (all P>0.05). Conclusion: PDGF-BB regulates phenotypic transformation of PASMCs via SIRT3 affecting glycolytic pathway.

Medicolegal Identification of Medical Malpractices in Orthopaedic Surgery.

OBJECTIVES: To analyze the characteristics of medical malpractices in orthopaedic surgeries, to explore principles and methods in medical legal identification, and to provide basic data for uniform medicolegal standard for the future medical identification. METHODS: A retrospective analysis was conducted on 100 cases of medical malpractices in orthopaedic surgery, among the 364 cases archived in Medicolegal Expertise Center of Xi'an Jiaotong University during 2002-2015. RESULTS: In the 100 cases of orthopedic medical malpractices, with 104 hospitals involved in, 95 cases were judged with medical errors and the other 9 cases with no error. The top 3 reasons for errors were （1） inadequate observation or estimation of diseases （27.9%）, （2） intraoperative improper operation （17.3%）, and （3） delayed or missed diagnosis and treatment （12.5%）. The consequences of medical malpractices were mostly disability （61%）, followed by prolonged diseases （31%） and death （8%）. With regard to the causal relationship between medical errors and consequences, 95 cases （91.4%） were with causality and the other 9 cases （8.6%） with no causality. Specifically, 56 cases （53.9%） were with medical errors as the secondary causes accounting for 25% causative potency, and 20 cases （19.2%） were with medical errors as the major causes accounting for 75% causative potency. CONCLUSIONS: It is pivotally important for determining the causative potency of medical errors to analyse the causes of damages in orthopaedic surgery and to distinguish subjective factors from objective ones of medical errors.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

[Safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions].

Objective: To investigate the safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions. Methods: In this retrospective study,a total of 31 consecutive patients with coronary chronic total occlusion(CTO) lesions underwent rotational atherectomy in our hospital from February 2004 to December 2016 were enrolled,and the clinical features were analyzed. Coronary atherectomy was performed if balloon failed to cross the CTO lesions or balloon could not be fully dilated in the CTO lesions after wire crossing. The definition of procedure success was defined as residual stenosis less than 20% after implantation of drug eluting stent and rotational atherectomy. After the procedure, the patients were followed up to observe major adverse cardiac and cerebral vascular events which including cardiogenic death, myocardial infarction, cerebrovascular accident, and target lesion revascularization. Results: The 1.25 mm diameter burr was firstly selected in 80.6% (25/31) patients,and 96.8%(30/31) patients used only 1 burr to complete the rotational atherectomy procedure. The complication rate was 9.8% (3/31) including 1 patient with coronary dissection and 3 patients with slow flow or no flow. There was 1 patent with both coronary dissection and slow flow. The procedure success rate was 96.8%(30/31). Interventional treatment related myocardial infarction occurred in 3 patients during hospitalization.The 30 patients with procedure success were followed up 36(11, 96) months. The incidence rate of major adverse cardiac and cerebral vascular events was 13.3% (4/30), of which the cardiogenic death rate was 3.3% (1/30), the myocardial infarction rate was 6.7% (2/30), cerebrovascular accident rate was 3.3%(1/30),and the target lesion revascularization rate was 6.7% (2/30). Conclusion: Rotational atherectomy is safe and effective in the interventional treatment of coronary CTO lesions.

Rab3A, Rab27A, and Rab35 regulate different events during mouse oocyte meiotic maturation and activation.

Rab family members play important roles in membrane trafficking, cell growth, and differentiation. Almost all components of the cell endomembrane system, the nucleus, and the plasma membrane are closely related to RAB proteins. In this study, we investigated the distribution and functions of three members of the Rab family, Rab3A, Rab27A, and Rab35, in mouse oocyte meiotic maturation and activation. The three Rab family members showed different localization patterns in oocytes. Microinjection of siRNA, antibody injection, or inhibitor treatment showed that (1) Rab3A regulates peripheral spindle and cortical granule (CG) migration, polarity establishment, and asymmetric division; (2) Rab27A regulates CG exocytosis following MII-stage oocyte activation; and (3) Rab35 plays an important role in spindle organization and morphology maintenance, and thus meiotic nuclear maturation. These results show that Rab proteins play important roles in mouse oocyte meiotic maturation and activation and that different members exert different distinct functions.

Fabrication of Ag-Decorated CaTiO3 Nanoparticles and Their Enhanced Photocatalytic Activity for Dye Degradation.

CaTiO3nanoparticles of 30-40 nm in size were synthesized via a polyacrylamide gel route. Ag nanoparticles with size of 8-16 nm were deposited onto CaTiO3particles by a photochemical reduction method to yield CaTiO3@Ag composites. The photocatalytic activity of prepared samples was evaluated by degrading methyl orange under ultraviolet irradiation. It is demonstrated that Ag-decorated CaTiO3 particles exhibit an enhanced photocatalytic activity compared to bare CaTiO3 particles. After 60 min of photocatalysis, the degradation percentage of MO increases from 54% for bare CaTiO3particles to 72% for CaTiO3@Ag composites. This can be explained by the fact that photogenerated electrons are captured by Ag nanoparticles and photogenerated holes are therefore increasingly available to react with OH⁻/H2O to generate hydroxyl (·OH) radicals. ·OH radicals were detected by fluorimetry using terephthalic acid as a probe molecule, revealing an enhanced yield on the irradiated CaTiO3@Ag composites. In addition, it is found that the addition of ethanol, which acts as an ·OH scavenger, leads to a quenching of ·OH radicals and simultaneous decrease in the photocatalytic efficiency. This suggests that ·OH radicals are the dominant active species responsible for the dye degradation.

Analysing codon usage bias of cyprinid herpesvirus 3 and adaptation of this virus to the hosts.

The codon usage patterns of open reading frames (ORFs) in cyprinid herpesvirus 3 (CyHV-3) have been investigated in this study. The high correlation between GC12 % and GC3 % suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage and base component in the CyHV-3, while mutational pressure effect results from the high correlation between GC3 % and the first principal axis of principle component analysis (Axis 1) on the relative synonymous codon usage (RSCU) value of the viral functional genes. However, the interaction between the absolute codon usage bias and GC3 % suggests that other selections take part in the formation of codon usage, except for the mutational pressure. It is noted that the similarity degree of codon usage between the CyHV-3 and goldfish, Carassius auratus (L.), is higher than that between the virus and common carp, Cyprinus carpio L., suggesting that the goldfish plays a more important role than the common carp in codon usage pattern of the CyHV-3. The study of codon usage in CyHV-3 can provide some evidence about the molecular evolution of the virus. It can also enrich our understanding about the relationship between the CyHV-3 and its hosts by analysing their codon usage patterns.

Sevoflurane induces neurotoxicity in young mice through FAS/FASL signaling.

Sevoflurane, the most widely used anesthetic in clinical practice, has been shown to induce apoptosis, inhibit neurogenesis, and cause learning and memory impairment in young mice. However, the underlying mechanism is still unknown. In this study, wild-type and the FAS- or FAS ligand (FASL)-knockout mice (age 7 days) were exposed to sevoflurane or pure oxygen. Western blotting was used to examine the expression of FAS protein. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and bromodeoxyuridine (BrdU) staining were employed to quantify the apoptotic cells and newborn cells in the hippocampus and Morris water maze (MWM) in order to evaluate learning and memory status. Sevoflurane significantly increased the expression of FAS protein in wild-type mice. Compared to FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane-treated wild-type mice exhibited more TUNEL-positive hippocampal cells and less BrdU-positive hippocampal cells. The MWM showed that compared with FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane treatment of wild-type mice significantly prolonged the escape latency and reduced platform crossing times. These data suggest that sevoflurane induces neurotoxicity in young mice through FAS-FASL signaling.

Effects of food intake on pharmacokinetics of mosapride in beagle dogs.

This study was performed to determine the pharmacokinetic profile of mosapride in fasting and fed states. A single 5-mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs, and the plasma concentrations of mosapride were measured by liquid chromatography-tandem mass spectrometry. The resultant data were analyzed by noncompartmental analysis (NCA). Mosapride was absorbed in fasted and fed dogs with similar Tmax . Both Cmax and AUC were significantly higher in the fasting group than in fed dogs, being four times (10.51 µg/mL vs. 2.76 µg/mL) and 3.5 times higher (38.53 h · µg/mL vs. 10.22 h · µg/mL), respectively. These findings suggest that food intake affects the pharmacokinetics of mosapride and that the dosage regimen for this drug need to be reconsidered.

Effects of DNA damage and short-term spindle disruption on oocyte meiotic maturation.

DNA damage has recently been shown to inhibit or delay germinal vesicle breakdown (GVBD) in mouse oocytes, but once meiosis resumes, DNA-damaged oocytes are able to extrude the first polar body. In this study, using porcine oocytes, we showed that DNA damage did not affect GVBD, but inhibited the final stages of maturation, as indicated by failure of polar body emission. Unlike mitotic cells in which chromosome mis-segregation causes DNA double-strand breaks, meiotic mouse oocytes did not show increased DNA damage after disruption of chromosome attachment to spindle microtubules. Nocodazole-treated oocytes did not display increased DNA damage signals that were marked by γH2A.X signal strength, but reformed spindles and underwent maturation, although aneuploidy increased after extended nocodazole treatment. By using the mouse for parthenogenetic activation studies, we showed that early cleavage stage embryos derived from parthenogenetic activation of nocodazole-treated oocytes displayed normal activation rate and normal γH2A.X signal strength, indicating that no additional DNA damage occured. Our results suggest that DNA damage inhibits porcine oocyte maturation, while nocodazole-induced dissociation between chromosomes and microtubules does not lead to increased DNA damage either in mouse meiotic oocytes or in porcine oocytes.