The efficacy and safety of venetoclax combined with demethylating agents in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.

Correlation of lipocalin 2 and glycolipid metabolism and body composition in a large cohort of children with osteogenesis imperfecta.

PURPOSE: Lipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI). METHODS: A total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function. RESULTS: Serum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P < 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P < 0.01). Grip strength was significantly lower (P < 0.05), and the TUG was significantly longer in OI patients than healthy control (P < 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-ß, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P < 0.05). CONCLUSIONS: Insulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.

Retraction Note: MicroRNA-132 stimulates the growth and invasiveness of trophoblasts by targeting DAPK-1.

The article "MicroRNA-132 stimulates the growth and invasiveness of trophoblasts by targeting DAPK-1, by Y.-P. Wang, P. Zhao, J.-Y. Liu, S.-M. Liu, Y.-X. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (19): 9837-9843-DOI: 10.26355/eurrev_202010_23193-PMID: 33090386" has been retracted by the authors due to some inaccuracies in the miRNA-132 primer sequence. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/23193.

Molecular, biochemical and enzymatic characterization of photorespiratory 2-phosphoglycolate phosphatase (PGLP1) in rice.

Phosphoglycolate phosphatase (PGLP, EC3.1.3.18) is a key enzyme in photorespiration. However, genes encoding the rice photorespiratory PGLP have not yet been identified or characterized. Here, PGLP for photorespiration in rice was identified and its enzymatic properties were investigated. In order to define the function of PGLP homologs, rice PGLP mutants were constructed using CRISPR/Cas9, the transcriptional expressions were analyzed by RT-qPCR, and subcellular localizations were detected via rice protoplast transient expression analysis. Based on sequence alignment, proteins encoded by genes OsPGLP1, OsPGLP2, and OsPGLP3 in the rice genome were predicted to have PGLP activity. Subsequent experimentation showed that OsPGLP1 and OsPGLP3 are chloroplast proteins, while OsPGLP2 is localized in the cytoplasm. In rice leaves, levels of PGLP1 transcript were substantially higher than those of PGLP2 and PGLP3, whereas in roots, levels of PGLP2 transcript were higher than those of PGLP1 and PGLP3. There was no detectable PGLP activity in leaves of the OsPGLP1 mutant, which was non-viable in ambient air condition (400 ppm CO2 ) and high CO2 (4000 ppm) was unable to restore normal growth. In contrast, mutations of PGLP2 or PGLP3 did not result in visible phenotypes and the leaf PGLP activities were also unaffected It is suggested that PGLP1, encoded by Os04g0490800, is responsible for photorespiration. Furthermore, PGLP1 is a dimer with an apparent molecular mass of ca.65 kDa, and its Km is 272 µM, with a higher broad optimum pH (7.5 to 10.0) for PGLP activity than that in other higher plants.

Secular trends of incidence and hospitalization cost of hip fracture in Tangshan, China.

We investigated the secular trends of the incidence and hospitalization cost of hip fracture in Tangshan, China. The incidence of hip fracture and the hospitalization cost were both increasing during the observation period. INTRODUCTION: The present study aimed to determine sex-, age-, and fracture type-specific incidence and annual changes in hip fractures in Tangshan, China, between 2007 and 2018. METHODS: We analyzed annual hip fracture incidence using urban hospital data during 2007-2018 and calculated incidence rate/100,000 person years in each age group and sex. We assessed annual changes in incidence among people aged >60 years using linear-by-linear association tests and evaluated hospitalization costs with the Kruskal-Wallis test. RESULTS: During the study period, we observed an increasing proportion of hip fractures in people >60 years old from 14.2 to 22.79%. Crude hip fracture incidence increased markedly from 140.87 to 306.56/100,000 in women (p < 0.01) and from 124.83 to 167.19/100,000 in men (p < 0.01) in the age group >60 years. Type-specific analysis indicated significantly increased trends in incidence of cervical and trochanteric fractures among women and cervical fracture among men (p < 0.01). In people aged 36-60 years, the trend of hip fracture increased significantly in both sexes. The total and cervical-to-trochanteric ratio in men increased, with significant upward trends (p < 0.01). The proportion of cervical fracture was higher than that for trochanteric fracture in women, with stable levels from 2007 to 2018. Hospitalization costs for cervical and trochanteric fractures increased by 51.91% and 53.20%, respectively, during 2011-2018. CONCLUSION: Tangshan will have an increasing burden on health care resources attributable to a considerable rise in hip fracture incidence and the older population. Further investigation of risk factors and subsequent implementation of effective measures to prevent hip fracture are needed.

One gut microbiota, Fusobacterium nucleatum aggravates Neonatal necrotizing enterocolitis by induction of IRF5 expression through lncRNA ENO1-IT1/miR-22-3p axis.

OBJECTIVE: We explored the effects of Fusobacterium nucleatum (F. nucleatum) in Neonatal necrotizing enterocolitis (NEC) and its possible mechanism. MATERIALS AND METHODS: Patients with Neonatal NEC and normal healthy volunteers were collected for this study. Neonatal mice were administered with LPS and then exposed to hypoxia as a mice model of NEC. THP-1 cells were stimulated with LPS as an in vitro model of NEC. RESULTS: We have demonstrated F. nucleatum abundance correlated with patients with Neonatal NEC or mice with Neonatal NEC. Furthermore, F. nucleatum stimulated colitis and increased inflammation in mice and in vitro models. LncRNA ENO1-IT1 was an important target for F. nucleatum in NEC-inflammation. MiR-22-3p was a target gene of F. nucleatum in NEC via LncRNA ENO1-IT1. Next, IRF5 was a target gene of miR-22-3p in the function of F. nucleatum in NEC via LncRNA ENO1-IT1. Silencing IRF5 or over-expressing miR-22-3p relieved the role of lncRNA ENO1-IT1 on inflammation in NEC via CD206 and CD86 expression. CONCLUSIONS: Taken together, these results demonstrate that F. nucleatum is mechanically, biologically and clinically connected to NEC. LncRNA ENO1-IT1 may be important targets for F. nucleatum in NEC-inflammation, and a meaningful in treating patients with Neonatal NEC with elevated F. nucleatum.

Author Correction: The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

Correction to: European Review for Medical and Pharmacological Sciences 2020; 24 (22): 11939-11944-DOI: 10.26355/eurrev_202011_23854-PMID: 33275267, published online 30 November, 2020. The authors state that "Figures 3 and 4 were used twice due to a careless mistake during the preparation of Figures". There are amendments to this paper.  The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/23854.

The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency; unfortunately, there is currently no treatment for improving outcomes or reducing viral-clearance times in infected patients. The aim of the present study was to evaluate the efficacy of interferon (IFN) with or without lopinavir and ritonavir as antiviral therapeutic option for treating COVID-19 infection. PATIENTS AND METHODS: The present study enrolled 148 patients that received either standard care, treatment with IFN alfa-2b, or IFN alfa-2b combined with lopinavir plus ritonavir. Viral testing was performed using Reverse-Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: There was no significant difference in the viral-clearance time at 28 days after treatment between patients receiving standard care and those receiving anti-viral treatments. However, the average viral-clearance time of patients receiving standard care (14 days) was shorter than that for patients receiving IFN alfa-2b or IFN alfa-2b combined with lopinavir plus ritonavir (15.5 or 17.5 days) (p<0.05). Patients treated with IFN alfa-2b within five days or IFN alfa-2b combined with lopinavir plus ritonavir after three days of symptoms exhibited shorter viral-clearance times than the other groups (p<0.05). Moreover, viral-clearance times were significantly longer in patients receiving standard care or anti-viral treatment 5 days after symptoms appeared than those of patients who received these treatments within five days of symptom onset (p<0.05). CONCLUSIONS: Early symptomatic treatment is most critical for maximizing amelioration of COVID-19 infection. Anti-viral treatment might have complicated effect on viral-clearance.

Epidemiological analysis of 18 patients with COVID-19.

OBJECTIVE: The present study aimed to explore the transmission pattern and the incubation period of coronavirus disease 2019 (COVID-19) as well as the clinical characteristics of infants with COVID-19 to provide a scientific basis for introducing further measures to reduce the infection rate and control the pandemic. PATIENTS AND METHODS: A descriptive epidemiological study of 18 patients with COVID-19 in People's Hospital of Deyuan was carried out. Among these patients, 16 cases were connected with clusters (11 family-cluster cases and 5 public-cluster cases). The basic characteristics, clinical symptoms, and epidemiological characteristics of the patients were considered in the investigation. RESULTS: The median age of the 18 patients was 44.5 years (37.5-52.0 years), and there were 10 males and 8 females in the sample. The main clinical symptoms were fever and cough. The epidemiological characteristics were as follows: (1) the median incubation period was 8 days (with an interquartile range of 4-12 days); (2) the incubation period in one case was ≥18 days; (3) one infant patient was asymptomatic prior to their diagnosis; and (4) two asymptomatic patients had a positive nucleic acid test after their family members were diagnosed with COVID-19. CONCLUSIONS: COVID-19 can be transmitted in many ways, including via respiratory droplets and indirect contact, and it spreads easily among close contacts. People with a history of contact with areas affected by the disease should be isolated at home for 14 days. Moreover, attention should be focused on the issues of asymptomatic infectors, asymptomatic infants, and infants with mild symptoms.

MicroRNA-132 stimulates the growth and invasiveness of trophoblasts by targeting DAPK-1.

OBJECTIVE: The purpose of this study was to elucidate the regulatory effects of microRNA-132 on the growth and invasiveness of trophoblasts, thus influencing the development of preeclampsia (PE). PATIENTS AND METHODS: Placenta tissues from 24 PE pregnancies and 24 healthy pregnancies were collected. Expression levels of microRNA-132 and DAPK-1 in collected placenta tissues were detected. Then, the regulatory effects of microRNA-132 and DAPK-1 on expression levels of apoptosis-associated genes, viability, and invasiveness in trophoblasts were assessed. Finally, through Dual-Luciferase reporter assay, the binding relationship between microRNA-132 and DAPK-1 was determined. RESULTS: The results showed that microRNA-132 was downregulated in placenta of PE pregnancies, while DAPK-1 was upregulated. Overexpression of microRNA-132 stimulated viability and invasiveness, but inhibited apoptosis in trophoblasts. Besides, it was found that DAPK-1 was the target gene binding microRNA-132, and a negative correlation was identified between their expression levels. Notably, the overexpression of DAPK-1 inhibited viability and invasiveness, but stimulated apoptosis in trophoblasts. CONCLUSIONS: MicroRNA-132 stimulates proliferative and invasive capacities and inhibits apoptosis in trophoblasts by targeting DAPK-1.

Cerebral Microbleeds Are Associated with Loss of White Matter Integrity.

BACKGROUND AND PURPOSE: Previous studies have shown that diffusion tensor imaging suggests a diffuse loss of white matter integrity in people with white matter hyperintensities or lacunes. The purpose of this study was to investigate whether the presence of cerebral microbleeds and their distribution are related to the integrity of white matter microstructures. MATERIALS AND METHODS: The study comprised 982 participants who underwent brain MR imaging to determine microbleed status. The cross-sectional relation between microbleeds and the microstructural integrity of the white matter was assessed by 2 statistical methods: a multilinear regression model based on the average DTI parameters of normal-appearing white matter and Tract-Based Spatial Statistics analysis, a tract-based voxelwise analysis. Fiber tractography was used to spatially describe the microstructural abnormalities along WM tracts containing a cerebral microbleed. RESULTS: The presence of cerebral microbleeds was associated with lower mean fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity, and the association remained when cardiovascular risk factors and cerebral small-vessel disease markers were further adjusted. Tract-Based Spatial Statistics analysis indicated strictly lobar cerebral microbleeds associated with lower fractional anisotropy, higher mean diffusivity, and higher radial diffusivity in the internal capsule and corpus callosum after adjusting other cerebral small-vessel disease markers, while only a few voxels remained associated with deep cerebral microbleeds. Diffusion abnormalities gradients along WM tracts containing a cerebral microbleed were not found in fiber tractography analysis. CONCLUSIONS: Cerebral microbleeds are associated with widely distributed changes in white matter, despite their focal appearance on SWI.

Effect of atorvastatin on pulmonary hypertension rats through regulating notch signaling pathway.

OBJECTIVE: To study the effect of atorvastatin on pulmonary hypertension (PAH) rats through regulating the Notch signaling pathway. MATERIALS AND METHODS: The rat model of PAH was established via hypoxic feeding and the Control group (n=10), PAH model group (Model group, n=10) and atorvastatin treatment group (ATO group, n=10) were set up. The right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined, the wet/dry weight (W/D) ratio of lung tissues was determined, and the tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining and the apoptosis level was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Finally, the Notch signaling pathway and apoptosis level in tissues were detected via quantitative Polymerase Chain Reaction (qPCR), and the protein expression level of Notch pathway in lung tissues was determined through Western blotting. RESULTS: Both RVSP and RVHI in Model group were significantly higher than those in Control group and ATO group (p<0.05). In Model group, the levels of inflammatory factors MPO, IL-6, and TNF-α were significantly increased, and the W/D ratio was also significantly increased compared with those in Control group (p<0.05). The results of HE staining showed that the lung tissue injury in Model group was severe (p<0.05). According to the TUNEL staining results, the number of apoptotic cells in lung tissues was markedly larger in Model group than that in ATO group (p<0.05), and the expression levels of Caspase-3 and IL-6 in Model group were remarkably higher than those in ATO group (p<0.05), while the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was remarkably lower than that in ATO group (p<0.05). Besides, the gene and protein expression levels of Notch1 in ATO group were evidently lower than those in Model group (p<0.05), indicating that atorvastatin can effectively suppress the expression of Notch. CONCLUSIONS: Atorvastatin can inhibit PAH in rats by suppressing the Notch pathway.

Identification and characterization of differentially expressed lncRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental pollutant and also a strong teratogen for cleft palate (CP). But up to now, the underlying molecular mechanisms of TCDD-induced CP are largely unknown. More recently, accumulating evidences are revealing important roles of long noncoding RNAs (lncRNAs) in all kinds of diseases including CP. However, the role and molecular mechanism of lncRNAs in TCDD-induced CP are still largely unexplored. Thus, identification of differentially expressed lncRNA (DEL) might help figuring out the mechanism of CP induced by TCDD. In this study, a CP offspring model of C57BL/6 female mice was generated by TCDD (64 µg/kg body weight) induce on embryo day 10 (E10). The incidence rate of CP was 100% in the TCDD group (105) after cervical dislocation on E16. Then, the high-throughput RNA sequencing (RNA-seq) was established to search a comprehensive profile of the lncRNAs. In addition, a coexpression network of lncRNA and messenger RNA (mRNA) was performed to discern potential mechanism. The result showed that 26,246 novel lncRNAs and 9635 known lncRNAs were screened out, and 413 lncRNA transcripts and 65 mRNA transcripts were identified as being significantly different between the CP group and control group. Notably, we found that there are seven lncRNAs that can target Smad1 and Smad5, which are key molecules of bone morphogenetic protein (BMP) signaling pathway, which suggested that they may be concerned with BMP signaling in TCDD-induced CP. In addition, some lncRNAs targeted the important molecules of Hippo and Wnt signaling pathways. These results suggested that characteristic lncRNA alterations may play a critical role in TCDD-induced CP, which provided a theoretical basis for further research.

Effects of MiR-26a on respiratory distress syndrome in neonatal rats via the wnt/ß-catenin signaling pathway.

OBJECTIVE:   Micro ribonucleic acids (miRNAs) are crucial to post-transcriptional regulation of the gene expression. Whether miR-26a affects respiratory distress syndrome (RDS) in neonatal rats through the Wnt/ß-catenin signaling pathway was investigated in this study. PATIENTS AND METHODS: The neonatal rat model of RDS was established, and the expressions of miR-26a and glycogen synthase kinase-3ß (GSK-3ß) in RDS in neonatal rats and their correlation were analyzed. The cascade relationship between miR-26a and the Wnt/ß-catenin signaling pathway and the influence of miR-26a on the expression of inflammatory cytokines were subsequently verified. Finally, the influences of miR-26a on the expressions of important markers, receptor for advanced glycation endproducts (RAGE), high mobility group box 1 (HMGB1), and plasminogen activator inhibitor-1 (PAI-1), through the Wnt/ß-catenin signaling pathway were analyzed. RESULTS: Compared with those in normal tissues, the expression of miR-26a in lung tissues of neonatal rats with RDS was significantly decreased (p<0.05), while the expression of GSK-3ß messenger RNAs (mRNAs) was notably increased (p<0.01), and the GSK-3ß expression was negatively correlated with the miR-26a expression (r=-0.6693, p=0.0064). In addition, miR-26a mimics significantly inhibited the GSK-3ß protein expression and activated the Wnt/ß-catenin signaling pathway. Moreover, miR-26a could reduce the expressions of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6, as well as RAGE, HMGB1, and PAI-1. CONCLUSIONS: MiR-26a can affect inflammatory responses and markers through the Wnt/ß-catenin signaling pathway in neonatal rats with RDS.

ZEB1 causes the production of hsa-microRNA-99b/let-7e/microRNA-125a cluster and promotes invasion of liver cancer cells.

OBJECTIVE: To explore the role of hsa-microRNA-99b/let-7e/microRNA-125a cluster in the progression of liver cancer and its possible regulatory mechanisms. PATIENTS AND METHODS: Ten liver cancer tissues were randomly selected and matched with normal liver tissue samples. The mRNA expression levels of miR-99b, let-7e and miR-125a were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The three miRNA mimics were transfected alone or together into hepatoma cells SMMC-7721; at the same time, the knockdown of the three miRNAs was also performed. Then the cell invasive and migratory abilities were examined through transwell assay. Bioinformatics analysis was used to detect the potential transcription factors that bind to the hsa-microRNA-99b/let-7e/microRNA-125a promoter sequence, and the binding of the two was verified by the Luciferase reporting assay. The level of hsa-microRNA-99b/let-7e/microRNA-125a mature mRNA was detected after ZEB1 was inhibited by ZEB1 siRNA. Meanwhile, after interfering with Drosha and ZEB1, the expression level of hsa-microRNA-99b/let-7e/microRNA-125a of the primary transcript was examined. Rescue experiments were carried out to assess the role of hsa-microRNA-99b/let-7e/microRNA-125a in the ZEB1 regulation of invasive cell capacity. RESULTS: The mRNA levels of microRNA-99b, let-7e, and microRNA-125a in 10 selected hepatocarcinoma tissues were significantly higher than those in the matched paracancerous tissues. After overexpressing the three miRNA mimics either alone or together, cell invasive and migratory abilities were extensively enhanced, and vice versa. It was found that there is a binding site in the upstream sequence of the promoter region of the hsa-microRNA-99b/let-7e/microRNA-125a cluster for ZEB1. The Luciferase reporter gene results showed an increase in the Luciferase activity of the cells transfected with E-box element wild-type sequence, while mutant E-box element group did not change. After knocking out ZEB1, the levels of mature microRNA-99b, let-7e and microRNA-125a were reduced. However, when DROSHA was knocked out, the levels of immature microRNA-99b, let-7e and microRNA-125a were increased, while simultaneous knocking out ZEB1 reversed this effect. Besides, the invasive ability of SMMC-7721 cells decreased after KEB1 was knocked down, while the opposite result was observed after transfection of hsa-microRNA-99b/let-7e/microRNA-125a alone or together. CONCLUSIONS: Hsa-microRNA-99b/let-7e/microRNA-125a cluster is highly-expressed in hepatocarcinoma, and its expression can be regulated by ZEB1. In addition, the overexpression of this cluster can promote the invasion of liver cancer cells and advance liver cancer progression.

Retigabine attenuates focal cerebral ischemic injury through inhibiting mitochondria-dependent apoptotic pathway.

OBJECTIVE: We explored the protective effect of retigabine (RTG) on focal cerebral ischemic injury and the potential molecular mechanism. MATERIALS AND METHODS: A mouse model of middle cerebral artery occlusion (MCAO) was established to induce cerebral ischemic injury. Blood samples were collected for the measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH). The brain infarct volume was stained by triphenyltetrazolium chloride. The cell apoptosis was observed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. The expression of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), cleaved caspase 3, p-p38 and p-JNK, were determined by Western blot. RESULTS: RTG treatment reduced the MCAO-induced increase in brain infarct volume and neurological deficit scores. RTG treatment reduced the level of MDA and increased the activity of SOD and GSH. RTG treatment also decreased the Bax/Bcl-2 ratio and cleaved caspase 3 expression in the ischemic tissues. Further, RTG treatment decreased the phosphorylation levels of p38 and JNK in the ischemic tissues. CONCLUSIONS: RTG attenuated cerebral ischemic injury through reducing oxidative stress and mitochondria-mediated apoptosis via inhibiting p38 and JNK phosphorylation.

I125 brachytherapy guided by individual three-dimensional printed plates for recurrent ameloblastoma of the skull base.

Ameloblastoma is one of the most common benign odontogenic tumours of the mandible and the maxilla. Wide excision of the tumour is the first choice for treatment (except for unicystic ones). Patients with invaded margins or unresectable lesions may require radiotherapy. Today, permanent implantation of I125 seeds is widely used in the treatment of cancer of the head and neck. We report a case of recurrent ameloblastoma of the base of the skull that was treated with I125 brachytherapy. The outcome has been encouraging, with total disappearance of the tumour on positron emission tomography 18 months later.

Toxic effects of ketamine on reproductive system via disrupting hypothalamic-pituitary-testicular axis.

OBJECTIVE: In this paper, we focused on the toxic effect of ketamine on the reproductive system in male rats and its underlying mechanisms. MATERIALS AND METHODS: Rats were randomly allocated into four groups (n=10), i.e. a control group and 3 ketamine groups (high-dose, mid-dose, low-dose). Animals in the ketamine groups received an intraperitoneal injection of ketamine (20, 40 or 60 mg/kg) every 3 days for 7 times. Control rats were injected with normal saline instead. To investigate the disruption potential on the hypothalamic-pituitary-testicular (HPG) axis, the relative hormone levels in serum and mRNA expressions for some reproduction-related genes in reproductive organs were evaluated. RESULTS: Ketamine significantly decreased the serum concentrations of testosterone (T), inhibin B, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Meanwhile, the mRNA expressions of GnRH in the hypothalamus, GnRH receptor, LH-ß and FSH-ß in the pituitary, and LH receptor and FSH receptor in testes were also significantly inhibited by ketamine compared with the control (p<0.01). CONCLUSIONS: These results demonstrated that the ketamine had a toxic effect on the reproductive system via breaking the HPG equilibrium.