Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (P<0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.
Humans ; Adult ; Male ; Female ; Middle Aged ; Aged ; Histones/genetics* ; Brain Neoplasms/pathology* ; Proto-Oncogene Proteins B-raf/metabolism* ; Glioma/pathology* ; Astrocytoma/pathology* ; Mutation

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

OBJECTIVE: To compare the clinical effect on intestinal dysfunction of spinal cord injury (SCI) between the comprehensive therapy of moxibustion (moxibustion for opening the governor vessel and regulating the spirit) and rehabilitation training and the simple treatment with rehabilitation training. METHODS: A total of 60 patients with intestinal dysfunction of SCI were randomized into a comprehensive therapy group and a rehabilitation group, 30 cases in each one (3 cases were dropped out in each group). On the base of the routine western medicine treatment and rehabilitation training, the bowel training and rectal function training were provided, once a day in the rehabilitation group. In the comprehensive therapy group, on the base of the treatment as the rehabilitation group, the moxibustion was exerted at Yaoyangguan (GV 3), Mingmen (GV 4), Zhiyang (GV 9), Dazhui (GV 14) and Baihui (GV 20), etc, once a day, 30 min each time. In both groups, the treatment for 4 weeks was as one course and 3 courses of treatment were required. Separately, before treatment, after 4, 8 and 12 weeks of treatment, the scores of neurogenic bowel dysfunction (NBD) and World Health Organization quality of life scale (WHOQOL-BREF) were observed and the clinical effect was evaluated after 12 weeks of treatment. RESULTS: After treatment, the total effective rate was 88.9% (24/27) in the comprehensive therapy group, which was higher than 74.1% (20/27) in the rehabilitation group (<0.05). After 4, 8 and 12 weeks of treatment, NBD scores were all reduced obviously as compared with those before treatment in the two groups (all <0.01). After 8 and 12 weeks of treatment, NBD scores in the comprehensive therapy group were lower than the rehabilitation group (both <0.05). After 4, 8 and 12 weeks of treatment, the scores of all of the domains (psychology, physiology, social relations and environment) in WHOQOL-BREF were higher than those before treatment in the two groups (all <0.01). After 4 weeks of treatment, the scores in the psychology and physiology domains in the comprehensive therapy group were higher than the rehabilitation group (all <0.05). After 8 and 12 weeks of treatment, the scores of all of the domains in the comprehensive therapy group were higher than the rehabilitation group (all <0.05). CONCLUSION The comprehensive treatment of moxibustion and rehabilitation training achieves the better effect on intestinal dysfunction of SCI than the simple rehabilitation training and greatly improves the quality of life in SCI patients.
Acupuncture Points ; Humans ; Moxibustion ; Quality of Life ; Spinal Cord Injuries ; therapy

Aim: To study the induction of apoptotic effect of sodium selenite on human lung cancer A549 cells and its mechanisms. Methods: A549 cells were exposed to different concentrations of sodium selenite for 24 h. MTT assay was applied to determine A549 cell proliferation. Inverted fluorescence microscope was used to investigate the morphological changes in A549 cells. Flow cytometry analysis was applied to assess the apoptotic rates of A549 cells. Laser confocal microscope was employed to measure the reactive oxygen species (ROS) fluorescence intensity. A multi-detection reader was used to determine the antioxidant parameter. Western blot was utilized to detect the expression of Keapl, Nrf2, HO-1 and Nrf2 in cytoplasm and nucleus. Results: MTT results showed that sodium selenite inhibited the proliferation of A549 cells in a concentration-dependent manner. After treatment with sodium selenite for 24 h, the apoptotic rate of A549 cells was markedly increased through Hoechst 33342 staining and flow cytometry measurement. Sodium selenite significantly up-regulated ROS and malondialdehyde (MDA) content and down-regulated the levels of superoxide dismutase (SOD) and glutathione (GSH). Meanwhile, sodium selenite treatment also reduced the expressions of Keapl, Nrf2 and HO-1 at protein levels and inhibited Nrf2 protein nuclear translocation in A549 cells. Conclusions: Treatment with sodium selenite induces A549 cells apoptosis, which may contribute to the anti-proliferation activity, induction of apoptosis and regulation of oxidative stress reaction and Keapl/Nrf2/ARE antioxidative signaling pathway expression.

The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1β, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1β, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1β, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, and the regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.
Animals ; Ankle Joint ; physiopathology ; Arthritis, Gouty ; drug therapy ; CARD Signaling Adaptor Proteins ; metabolism ; Caspase 1 ; metabolism ; Fallopia japonica ; chemistry ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Plant Extracts ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism ; Uric Acid

OBJECTIVEWe aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China.

METHODSA prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels.

RESULTSWe adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05).

CONCLUSIONParticipants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.

Asian Continental Ancestry Group ; C-Reactive Protein ; metabolism ; Cardiovascular Diseases ; epidemiology ; genetics ; China ; Genetic Predisposition to Disease ; Humans ; Prospective Studies ; Risk Factors ; Stroke ; epidemiology

OBJECTIVEWe aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1 (ApoB/ApoA-1) ratio on the incidence of ischemic stroke (IS) or coronary heart disease (CHD) in a Mongolian population in China.

METHODSFrom June 2003 to July 2012, 2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation. All the participants were divided into four subgroups according to C-reactive protein (CRP) level and ApoB/ApoA-1 ratio. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the IS and CHD events in all the subgroups.

RESULTSThe HRs (95% CI) for IS and CHD were 1.33 (0.84-2.12), 1.14 (0.69-1.88), and 1.91 (1.17-3.11) in the 'low CRP level with high ApoB/ApoA-1', 'high CRP level with low ApoB/ApoA-1', and 'high CRP level with high ApoB/ApoA-1' subgroups, respectively, in comparison with the 'low CRP level with low ApoB/ApoA-1' subgroup. The risks of IS and CHD events was highest in the 'high CRP level with high ApoB/ApoA-1' subgroup, with statistical significance.

CONCLUSIONHigh CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population. This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Adult ; Apolipoproteins A ; classification ; genetics ; metabolism ; Apolipoproteins B ; genetics ; metabolism ; C-Reactive Protein ; genetics ; metabolism ; Cohort Studies ; Coronary Disease ; epidemiology ; etiology ; Gene Expression Regulation ; Humans ; Mongolia ; epidemiology ; Prospective Studies ; Risk Factors ; Stroke ; epidemiology ; etiology ; Young Adult

Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.
Acetamides ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; pathology ; Cell Line, Tumor ; Drug Design ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo explore the exposure level and risk factors of heavy metal among Shanghai infants in their prenatal period.

METHODSA total of 1652 pregnant or puerperal women were recruited from 10 midwifery-qualified hospitals in Shanghai since October 2008 to October 2009, by the stratified cluster sampling method. They answered the questionnaire and their umbilical cord blood and serum were collected to detect the content of Pb, Hg, Mn, Cd, As and Tl. The risk factors were analyzed by single and multiple regression methods respectively.

RESULTSThe median value of the content of Pb, Hg, Mn, Cd, As and Tl were 41.00, 1.88, 4.10, 0.03, 0.86 and 0.02 µg/L respectively. The Hg concentration of pregnant women who ate fish for 4 - 7 times per week (9.7% (160/1652)) was 2.76 µg/L, which was higher than that of pregnant women who only ate fish for 1-3 times per week (49.3% (814/1652)) and those who seldom ate fish (40.0% (661/1652)); the Hg concentration in the two groups above were 2.41 and 2.03 µg/L separately. The difference had statistical significance (χ(2) = 36.40, P < 0.001). Meanwhile, the concentrations of Pb and Tl in the group of pregnant women whose houses were remodeled by PVC pipe (85.0% (1404/1652)) was higher than the concentrations in group of pregnant women whose houses were remodeled by galvanized pipe (15.0% (248/1652)); the Pb concentration in the two groups above were 45.54 and 40.00 µg/L (Z = 2.54, P < 0.05) and the Tl concentration in the two groups above were 0.021 and 0.018 µg/L (Z = 2.97, P < 0.05). However, the As concentration in the group of PVC pipe remodeled was 4.33 µg/L, which was lower than that in the group of galvanized pipe (9.37 µg/L). The difference had statistical significance (Z = 3.99, P < 0.01). The concentrations of Mn, Cd and Tl in the groups of pregnant women whose house had been remodeled in the last 3 years (38.0% (628/1652)) were 14.78, 0.51 and 0.022 µg/L separately, which were all significantly higher than those in the groups of women whose houses' were not remodeled (62.0% (1024/1652)), whose concentrations were 11.01, 0.29 and 0.02 µg/L respectively. The differences had statistical significance (Mn: Z = 2.46, P < 0.05; Cd: Z = 2.38, P < 0.05; Tl: Z = 2.81, P < 0.01).

CONCLUSIONThe infants in Shanghai were exposed to heavy metals in their prenatal period. The main sources of the exposure were daily diet and remodeled pollution.

Adult ; China ; Environmental Pollution ; Female ; Fetal Blood ; chemistry ; Humans ; Infant, Newborn ; Male ; Maternal Exposure ; adverse effects ; Metals, Heavy ; adverse effects ; Pregnancy ; Risk Factors ; Surveys and Questionnaires

OBJECTIVETo study the effect of glutamate on the expression of vascular endothelial growth factor (VEGF) mRNA and protein in cultured rat astrocytes under hypoxia.

METHODSCultured rat astrocytes were randomly divided control group, glutamate group, hypoxia group and hypoxia+glutamate group. The cells in the control and glutamate groups were cultured under nomoxic condition (95% air and 5% CO(2)), and those in the other two groups under hypoxic condition (94% N(2), 5% CO(2) and 1% O(2)). The total RNA was extracted from the cells at different time points of hypoxic exposure for real-time FQ-PCR and ELISA to detect the expression of VEGF mRNA and protein in cultured astrocytes, respectively.

RESULTSThe expressions of VEGF mRNA and protein underwent no significant changes in the control glutamate groups, but increased obviously in both hypoxia and hypoxia+glutamate groups at 2, 4, 6, 8 and 12 h of hypoxic exposure. At these time points, VEGF expressions at both the mRNA and protein levels were significantly higher in hypoxia+glutamate group than in hypoxia group.

CONCLUSIONGlutamate at 1 micromol/L can further increase the expression of VEGF mRNA and protein in astrocytes exposed to hypoxia, which may result from the adaptive changes of glutamate receptors in hypoxic astrocytes.

Animals ; Animals, Newborn ; Astrocytes ; cytology ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Female ; Glutamic Acid ; pharmacology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; genetics ; metabolism