Background: The paired-box gene 6 (PAX6) is an important transcription factor in the central nervous system, mainly regulating the development and differentiation of embryonic eyes and the nervous system. PAX6 expression is significantly decreased in glioma, and the expression levels are closely related to glioma development and prognosis. Therefore, it is important to study and elucidate the biological function of PAX6 in glioma to further our understanding of the occurrence and development of glioma. Methods: This study focused on the expression and regulation of PAX6 and hypoxia-inducing factor (HIF-1α) and investigated the molecular mechanism of ferroptosis regulated by PAX6 and HIF-1α. Firstly, immunohistochemistry, qPCR, Western blot, and other methods were used to detect PAX6 and HIF-1α expression in glioma tissues and cells, as well as the specific way in which PAX6 regulates HIF-1α. Then, some relative indicators of ferroptosis regulated by PAX6 in glioma were studied. Results: The results showed that PAX6 inhibited HIF-1α expression by regulating the levels of reactive oxygen species (ROS); overexpression of PAX6 promoted the expression of ROS and lipid peroxides (LPOs) in glioma cells and decreased the expression of intracellular antioxidant systems glutathione peroxidase 4 (GPX4) and glutathione (GSH). Conclusions: Downregulation of PAX6 plays an important role in regulating ferroptosis in glioma cells. Our research provides a reference basis for a deeper understanding of the role of PAX6 in ferroptosis of glioma.

Triclosan (TCS), a typical endocrine disruptor, is widely used as an antibacterial agent in consumer goods. However, there are few studies on the effects of long-term low-dose TCS exposure on ovarian function in F1 female mice. In this paper, F1 female mice were exposed to TCS (0-3000 μg/kg/day) from intrauterine to postnatal day (PND) 91 to investigate its effects on the ovary. The results revealed that the number of total follicles was decreased, while atretic follicles was increased after TCS exposure. At the hormonal level, the secretion of estradiol was reduced, while follicle-stimulating hormone and luteinizing hormone were increased after TCS exposure. Observation of vaginal smear showed that TCS disrupted the estrous cycle of F1 female mice, especially at the dose of 3000 μg/kg/day. Moreover, TCS promoted cell apoptosis by activating the p38-MAPK signaling pathway and oxidative stress in vitro. In addition, analysis of the fecal microbiome and serum metabolomics revealed that exposure to TCS may cause gut microbiota disruption and metabolic abnormalities in F1 female mice. In conclusion, long-term low-dose TCS exposure may induce primary ovarian insufficiency phenotype in F1 female mice via inducing cell apoptosis and disrupting gut microbiota and metabolism.

OBJECTIVES:Paired box gene 6 (PAX6) plays a major role in the regulation of embryonic development. Abnormal expression of PAX6 is associated with the development of various tumors. PAX6 can play a role in promoting or suppressing cancer in different tumors. This study aim to observe the effect of overexpression of PAX6 on the growth of hepatocellular carcinoma cells, and the killing of hepatocellular carcinoma cells via natural killer (NK) cell and the possible mechanism.METHODS:The protein levels of PAX6, soluble major histocompatibility complex class I-like protein A (sMICA) and soluble UL16 binding protein 2 (sULBP2) in peripheral blood from 68 cases of hepatocellular carcinoma (HCC) patients and 10 healthy volunteers were detected by ELISA. Hepatocellular carcinoma cell line (HepG2, LM3) and human normal liver cells (LO2) were cultured at 37 ℃ and 5% CO2 condition in vitro. The PAX6 overexpressed plasmid (PAX6-OE) and empty vector (NC) were transferred into HepG2 and LM3 cells to construct stable cell lines. The mRNA and protein expression levels of PAX6 in HepG2 and LM3 cells were detected by real-time PCR, Western blotting and immunofluorescence, respectively. PAX6 was overexpressed in HepG2 and LM3 cells, the cell growth and migration ability were detected by CCK-8 method and cell scratch assay, and the levels of sMICA and sULBP2 in the supernatant were detected by ELISA. Matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9) and disintegrin and metalloproteinase 10 (ADAM10) in HepG2 and LM3 cells were detected by Western blotting. The killing ability of NK cells against these 2 HCC cells was detected by flow cytometry.RESULTS:Compared with the healthy volunteers, the expressions of PAX6 in the HCC patients were significantly decreased (P=0.002), while the expression of sMICA and sULBP2 were significantly increased (P=0.004 and P<0.001, respectively). Real-time PCR and Western blotting results showed that compared with LO2 cells, mRNA and protein expressions of PAX6 in HepG2 and LM3 cells were significantly decreased (all P<0.05). Immunofluorescence results also showed that the expressions of PAX6 in HepG2 and LM3 were lower than those of LO2 cells. Compared with the NC group, the ability of proliferation and migration of HepG2 and LM3 cells were decreased (both P<0.05). The protein expressions of MMP2, MMP9 and ADAM10 in HepG2 and LM3 cells in the PAX6-OE group were significantly decreased, and the levels of sMICA and sULBP2 in superneant of HepG2 and LM3 cells in the PAX6-OE group were significantly lower than those in the NC group (all P<0.05). Flow cytometry results showed that compared with the NC group, the proportion of NK cells killing HepG2 and LM3 cells in PAX6-OE group was significantly increased (both P<0.05).CONCLUSIONS:The expression of PAX6 is decreased in serum of HCC patients and hepatocellular carcinoma cell lines. Overexpression of PAX6 can inhibit the growth of hepatocellular carcinoma cells, enhance the killing efficiency of NK cells against hepatoma cells. The mechanism is related to the inhibition of the expression of metalloproteinase via PAX6 and the decrease of the secretion levels of sMICA and sULBP2.

AbstractCervical cancer is a major health concern for women worldwide, and cervical cytology screening is a widely used and effective technique for early detection. In this study, we built a large-scale database of digital WSIs from 49 hospitals in China, comprising of 76,614 WSIs with 3,435,463 cell-level annotations by 26 cytopathologists using manual and semi-automatic approaches. A novel AI diagnostic system called CCA-DIAG was developed for cervical cancer screening based on a hybrid machine learning framework, which is capable of efficient WSI-level classification for various sedimentations. Our results of multi-center validation show that the system can make classifications at the WSI-level with high sensitivity (ASCUS+:0.89, LSIL+:0.99) for diverse sedimentations and significantly improve the time efficiency of cytopathologists by approximately 4 times. These findings suggest that CCA-DIAG is a promising tool for cervical cancer screening and could potentially improve diagnosis accuracy and efficiency in clinical practice.

BackgroundAs a new type of regulatory cell death, ferroptosis has been proven to be involved in cancer pathogenesis and therapeutic response. However, the detailed roles of ferroptosis or ferroptosis-associated genes in glioma remain to be clarified. MethodsHere, we performed the TMT/iTRAQ-Based Quantitative Proteomic Approach to identify the differentially expressed proteins between glioma specimens and adjacent tissues. Kaplan-Meier survival was used to estimate the survival values. We also explored the regulatory roles of abnormally expressed formin homology 2 domain-containing protein 1 (FHOD1) in glioma ferroptosis sensitivity. ResultsIn our study, FHOD1 was identified to be the most significantly upregulated protein in glioma tissues. Multiple glioma datasets revealed that the glioma patients with low FHOD1 expression displayed favorable survival time. Functional analysis proved that the knockdown of FHOD1 inhibited cell growth and improved the cellular sensitivity to ferroptosis in glioma cells T98G and U251. Mechanically, we found the up-regulation and hypomethylation of HSPB1, a negative regulator of ferroptosis, in glioma tissues. FHOD1 knockdown could enhance the ferroptosis sensitivity of glioma cells via up-regulating the methylated heat-shock protein B (HSPB1). Overexpression of HSPB1 significantly reversed FHOD1 knockdown-mediated ferroptosis. ConclusionsIn summary, this study demonstrated that the FHOD1-HSPB1 axis exerts marked regulatory effects on ferroptosis, and might affect the prognosis and therapeutic response in glioma.

BACKGROUND:Glioblastoma is one of the most common fatal intracranial malignancies. Lysine-specific demethylase 1 (LSD1) reportedly has therapeutic effects on a variety of tumors. This study explored the therapeutic effect of LSD1 inhibition on glioblastoma cell lines and the possible underlying mechanisms. METHODS:The MTT assay was utilized to screen for the sensitivity of U87, U251 and T98G cells to 4, 5-dimethoxycarrageenin-6-one. qRT-PCR and western blot were used to measure the proliferation, apoptosis, and pyroptosis signaling pathway expression to observe the effect of LSD1 inhibition on U251 and T98G cells. Flow cytometry, immunofluorescence, immunohistochemistry, wound scratch, clone formation, and TUNEL assay were used to analyze the effects of 4, 5-dimethoxycanthin-6-one on glioblastoma cells. The effect of 4, 5-dimethoxycanthin-6-one was examined in vivo in BALB/c nude mice injected with U251 cells. HE staining was used to detect the histopathology of the tumor. RESULTS:LSD1 specifically catalyzes the demethylation of monomethylated and demethylated histone H3 lysine at position 4 (h3k4me1, h3k4me2, h3k4me3) and lysine at position 9 (h3k9me1). This regulated the transcriptional activity of proliferation, apoptosis, and pyroptosis signaling pathway genes. In vitro, the proliferation of glioblastoma cells was decreased in the 4, 5-dimethoxycanthin-6-one group. The expression of Caspase1 in glioblastoma cells treated with 4, 5-dimethoxycanthin-6-one increased, and the number of apoptotic cells increased. The tumor volume of mice injected with 4, 5-dimethoxycanthin-6-one decreased significantly. CONCLUSION:4, 5-Dimethoxycanthin-6-one could act as a novel inhibitor of LSD1 to regulate glioblastoma, which could inhibit the proliferation of U251 and T98G cells and induce their apoptosis and pyroptosis. It is a potential drug for the treatment of glioblastoma.

In recent years, the incidence rate of hypertensive intracerebral haemorrhage (HICH) has been increasing, accompanied by high mortality and morbidity, which has brought a heavy burden to the social economy. However, the pathogenesis of HICH is still unclear. This study intends to explore the mechanism of gut microbiota metabolism and inflammation in the process of HICH to provide a theoretical basis for the diagnosis and treatment of HICH.

Triage procedure remains at a developing stage in mainland China, and few studies have reported the current status. This study aimed to explore the triage practices presently implemented in emergency departments in mainland China. A descriptive online national survey was administered to nurses with experience in emergency department triage who worked in 64 hospitals in 2019. A total of 361 participants completed the survey. Only 210 nurses (58.2%) used triage systems. Approximately 5% of the participants reported that no nurse was allocated to triage during the evening and night shifts in their emergency departments. Most participants had fewer than 5 years of nursing experience (47%) and emergency nursing experience (58.2%) before fulfilling the triage role. This study shows the variability in triage guidelines as well as the inconsistency between different hospitals in nurses' entry qualifications to triage, in hospital workforce arrangements, and in triage training. These problems underscore the need to unify triage guidelines and to establish reasonable entry qualifications and appropriate workforce arrangements for triage nurses that ensure high triage quality and high levels of patient safety.

OBJECTIVE To investigate the effects of overexpression of long noncoding RNA (lncRNA) MEG3 on the proliferation and invasion of glioblastoma U251 cells by suppressing the expression of hypoxia inducible factor 1α(HIF1α). METHODS The expression of lncRNA MEG3 and HIF1α mRNA were examined in human fetal glial cells (HFGCs) and U251 cells using realtime quantitative PCR (qRT-PCR), and the expression of HIF1α protein was detected with Western blotting.U251 cells in normal culture or transfected with pcDNA3.1 vector (NC group) or pcDNA3.1-MEG3 vector via lipofectamine2000 were exposed to hypoxia for 12h, and the expressions of HIF1α mRNA and protein were detected with qRT-PCR and Western blotting, respectively.MTT assay and Transwell assay were employed to examine the influence of MEG3 overexpression on the proliferation and invasion of U251 cells. RESULTS The expression of MEG3 was significantly lower and HIF1α mRNA and protein expressions were significantly higher in U251 cells than in HFGCs (P < 0.05).In U251 cells, overexpression of MEG3 significantly decreased the mRNA and protein expressions of HIF1α(P < 0.05).Hypoxic exposure for 12h also resulted in significantly lowered expression of HIF1α protein in U251 cells (P < 0.05).Overexpression of MEG3 obviously suppressed the proliferation and invasiveness of U251 cells (P < 0.05). CONCLUSIONS MEG3 overexpression inhibits the proliferation and invasion of U251 cells through suppressing the expression of HIF1α mRNA and protein, suggesting that MEG3 may serve as a potential therapeutic target for glioblastomas.

Background: There have been few studies to evaluate early warning score (EWS) systems, or track and trigger systems (TTS), to identify early clinical deterioration in patients following brain tumor surgery who are admitted to the Intensive Care Unit (ICU). The National Early Warning Score (NEWS2) is an established method used in the U.K. National Health Service to improve care for in-hospital patients. This retrospective study from a single center aimed to compare the performance of NEWS2 with 24 other types of EWS to evaluate unplanned ICU admissions within 72 h after brain tumor surgery. Material/Methods: A total of 326 patients with brain tumors were included in the study. Patients who experienced unplanned ICU transfer after surgery (69 cases) were diagnostically matched with patients who did not require intensive care (257 controls). We collected the physiological variables to calculate the area under the receiver operator characteristic curve (AUROC), sensitivity, specificity, Youden index values, cutoff values, positive predictive values, and negative predictive values. Results: The NEWS2 identified postoperative brain tumor patients with AUROC (860, p=0.000). The Patient-At-Risk (PAR) score was higher than NEWS2 in terms of AUROC value (0.870, P=0.000), Youden index (0.589 vs 0.542). Conclusions: The findings showed that although the NEWS 2 performed well when used to evaluate unplanned ICU admissions within 72 h of postoperative brain tumor patients, the PAR score was also an accurate EWS.

目的 探讨外源性硫化氢(H2S)对氧糖剥夺/复氧(OGD瓜)诱导的神经元细胞自噬和损伤的影响,明确H2S减轻大鼠脑缺血再灌注损伤的分子机制.方法 以大鼠神经元PC12细胞为研究对象,采用经典的OGD/R诱导细胞损伤,硫氢化钠(NaHS)作为H2S的供体预处理后观察H2S对OGD/R诱导的细胞自噬抑制蛋白mTOR、AMPK及其磷酸化AMPK的影响.为明确AMPK在H2S调节PC12细胞自噬中的作用,采用AMPK过表达质粒进行干预,并观察其对H2S减轻PC12细胞损伤的影响.结果 OGD/R处理的PC12细胞mTOR磷酸化水平降低、AMPK活性增强,NaHS预处理可部分逆转上述改变.而AMPK过表达后,可消除NaHS对OGD/R诱导的自噬和细胞凋亡的抑制作用.结论 H2S可通过抑制AMPK活化,进而抑制缺血再灌注时大脑神经元过度的自噬和凋亡,最终减轻神经元损伤.

目的:探讨甲基转移酶样蛋白9(Mettl9)基因过表达对氧糖剥夺(OGD)大鼠离体星形胶质细胞损伤的影响及机制.方法:体外原代培养SD大鼠大脑皮层星形胶质细胞,建立OGD诱导的星形胶质细胞损伤模型.实验分为正常对照(Con)组、慢病毒空载体转染(NC)组、慢病毒重组载体pLenti6.3-Mettl9转染组(Mettl9组)、正常对照+OGD处理(Con+OGD)组、慢病毒空载体转染+OGD处理(NC+OGD)组及慢病毒重组载体pLenti6.3-Mettl9+OGD处理(Mettl9+OGD)组.慢病毒载体pLenti6.3-Mettl9转染后48 h,收集细胞,采用RT-qPCR及Western blot法检测Mettl9的表达以验证转染效率.采用MTT法检测各组细胞活力;以乳酸脱氢酶(LDH)漏出率作为细胞损伤指标;RT-qPCR法检测Bcl-2和Bax的mRNA表达;Western blot法检测Bcl-2和Bax的蛋白表达.结果:慢病毒载体pLenti6.3-Mettl9转染星形胶质细胞后,RT-qPCR及Western blot检测结果显示Mettl9的mRNA和蛋白表达水平均升高(P<0.05),获得了Mettl9基因过表达的星形胶质细胞.与Con组比较,Mettl9组星形胶质细胞的LDH漏出率升高,细胞活力下降(P<0.05),促凋亡蛋白Bax的mRNA及蛋白表达升高,而抗凋亡蛋白Bcl-2的mRNA及蛋白表达降低(P<0.05).与Con+OGD组比较,Mettl9+OGD组星形胶质细胞的LDH漏出率显著升高,细胞活力显著下降(P<0.05),Bax的mRNA及蛋白表达显著升高,而Bcl-2的mRNA和蛋白表达显著降低(P<0.05).结论:Mettl9基因过表达促进OGD大鼠离体星形胶质细胞损伤,其机制可能与调控Bcl-2/Bax信号通路有关.

近年来,医联体模式作为一种新型的医疗卫生体制改革方案,受到了国家及各大医院的大力推崇.以湖南省长沙市2018年实施脑卒中医联体为例,运用双重差分(DID)的方法对脑卒中医联体模式下重大疾病患者的医疗费用降低效应进行分析,得出在重大疾病脑卒中单病种,实施医联体模式能有效降低患者医疗费用的结论,并提出相应对策建议,以期为医联体的后续管理及发展提供一定参考与启示.

为进一步深化医疗体质改革的成果、优化医疗资源配置,自2013年,我国建立了以政府为主导、医疗保险政策为向导、医疗机构为资源整合对象的“医联体”新格局.本文旨在梳理各类“医联体”现有问题的基础上,通过规范单病种纳入条件、制定分级诊疗规范、确立患者纳入原则、建立单病种临床路径和实施统一的质量控制标准,探索出一条能缓解当地医疗资源结构性矛盾、适宜当地医疗资源整合的重大疾病单病种“医联体”协作路径,以充分优化当地医疗配置、降低医疗运行成本,构建优势互补、协作诊疗、互利共赢的医疗新格局.

Bone cancer pain (BCP) is common in patients with advanced cancers when the tumors are metastasized to bone. The limited understanding of the complex pathogenesis of BCP leads to the poor effectiveness of clinical treatment. Previous studies have shown that astrocyte-specific connexin (Cx) 43, a forming protein of gap junction (GJ) and hemichannel, and N-methyl-D-aspartate receptors (NMDARs), especially the phosphorylated NMDAR 2B subunit (NR2B) phosphorylated NR2B (p-NR2B) subunit are involved in BCP. However, the relationship between Cx43 and p-NR2B in BCP remains unclear. In the present study, we investigated the expressions of Cx43, glial fibrillary acidic protein (GFAP, a marker of astrocytes), and p-NR2B in the spinal dorsal horn (SDH) in a mouse model of BCP established by intra-femural inoculation of Lewis lung carcinoma (LLC) cells via intrathecal (ith) injection of the GJ/hemichannel blocker carbenoxolone (CARB) and the NMDAR antagonist MK801, respectively. We found that the characters of BCP were mimicked by intra-femural inoculation of LLC cells in mice, and the expressions of Cx43, GFAP and p-NR2B in BCP mice were remarkably increased in a time-dependent manner from day 7 to day 21 after cell inoculation with a gradual aggravate in spontaneous pain and mechanical allodynia. Furthermore, Cx43 was predominantly expressed in the spinal astrocytes. Both CARB and MK801 inhibited the expressions of Cx43, GFAP and p-NR2B with attenuated pain hypersensitivity in BCP mice. In addition, Cx43 was co-localized with p-NR2B in the SDH, which further evidenced the presence of functional NR2B in the spinal astrocytes in BCP mice. Our findings demonstrate that inhibition of Cx43 and p-NR2B in spinal astrocytes could attenuate BCP in mice and Cx43 and p-NR2B in the astrocytes of the SDH may play an important role via their combination action in the development and maintenance of BCP in mice. These results may provide a potential therapeutic target in the prevention and/or treatment of BCP.

Cerebral ischemia caused severe disability, and associated with a series of neurological events. Long non-coding RNA SNHG12 was found to be upregulated in mouse brain microvascular endothelial cells by cerebral ischemia. Moreover, it was reported that SNHG12 could directly interact with miR-199a and sirtuin 1 (SIRT1) as a direct target of miR-199a in other diseases. However, the function and mechanism of SNHG12 in cerebral ischemia and reperfusion (I/R) injury of neuronal cells remains unclear. The present study was thus designed to explore the potential effect of SNHG12 and to investigate the underlying mechanism in I/R neuronal cells. we found that SNHG12 was upregulated in primary neuronal cells and N2a cells and peaked at 12 h and 24 h after OGD/R treatment, respectively. Meanwhile, MTT assay showed that knockdown SNHG12 inhibited cell proliferation under OGD/R condition. And flow cytometry analyses revealed more apoptosis rate was caused by SNHG12 knockdown. Mechanistically, SNHG12 interacted with miR-199a and decreased the expression of miR-199a. Overexpression miR-199a largely inhibited the cell proliferation and induced the cell apoptosis. Meanwhile, SNHG12 was proven to target miR-199a and then activated SIRT1 expression, which finally led to activation of AMPK signaling pathway. In summary, we demonstrate SNHG12 targets miR-199a to upregulate SIRT1 expression, which attenuates cerebral ischemia/reperfusion injury through AMPK pathway activation. Our findings provide molecular mechanism by which SNHG12 attenuates cerebral I/R injury and facilitate development of therapeautical strategies for treating ischemia-induced stroke.

目的 构建shRNA-PAX6慢病毒载体并观察其对胶质瘤U251细胞增殖的影响。方法 根据文献报道的PAX6靶点序列， 设计两条PAX6基因的siRNA靶点干扰序列，引物退火形成带粘性末端的双链，与经BamH I、EcoR I双酶切后线性化的慢病毒 载体进行连接、转化，构建shRNA-PAX6慢病毒重组载体，再经菌落PCR及测序鉴定重组载体； 在293T细胞中包装病毒，将包装 后的shRNA-PAX6慢病毒重组载体感染U251细胞。Real-time PCR检测PAX6 mRNA的表达水平，Western blot检测PAX6蛋 白的表达，MTT法检测U251细胞增殖。结果 慢病毒载体pLKD-CMV-G&NR-U6-shRNA经双酶切后可见线性化的8208 bp大 片段，菌落PCR及测序鉴定证实shRNA-PAX6慢病毒重组载体构建成功，构建的shRNA-PAX6慢病毒载体在293T细胞完成包 装，测得慢病毒滴度为6.73×108 TU/mL；Real-time PCR结果显示，沉默PAX6的表达可见U251细胞PAX6 mRNA表达水平明显 低于正常对照组及慢病毒空载体组（P<0.05）；Western blot结果显示，PAX6蛋白表达亦明显低于正常对照组及慢病毒空载体组 （P<0.05）；MTT结果显示，与正常对照组及慢病毒空载体组细胞比较，感染shRNA-PAX6慢病毒重组载体组的细胞，细胞增殖 能力明显增强（P<0.05）。结论 成功构建人PAX6基因的shRNA-PAX6慢病毒重组载体，沉默PAX6基因的表达， U251细胞的 增殖能力增强。

Ischemic stroke is a leading cause of death and disability worldwide, and autophagy may be involved in the pathological process of cerebral ischemia/reperfusion injury. Hydrogen sulfide (H2S) is an endogenous gasotransmitter with protective effects against multiple diseases. Here, we tested the effect of H2S on cerebral ischemia/reperfusion injury in rats. Sodium hydrosulfide (NaHS), an H2S donor, improved neurological function and reduced the size of the infarcts induced by transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats. NaHS treatment reduced the lactate dehydrogenase (LDH) activity in the serum (a marker of cellular membrane integrity) and the expression of cleaved caspase-3 (a marker for apoptosis) in the brains of MCAO rats. We also found that autophagy was overactivated in the brains of MCAO rats, as indicated by an increased ratio of LC3 II to I, decreased expression of p62, and transmission electron microscope detection. NaHS treatment significantly inhibited the autophagic activity in the brains of MCAO rats. Furthermore, PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic MCAO in vitro. We found that NaHS treatment reduced cellular injury and suppressed overactivated autophagy induced by OGD/R in PC12 cells. An autophagy stimulator (rapamycin) eliminated the protective effect of NaHS against LDH release and caspase-3 activity induced by OGD/R in PC12 cells. An autophagy inhibitor (3-methyladenine, 3-MA) also reduced the cellular injury induced by OGD/R in PC12 cells. In conclusion, the results indicate that overactivated autophagy accelerates cellular injury after MCAO in rats and that exogenous H2S attenuates cerebral ischemia/reperfusion injury via suppressing overactivated autophagy in rats.

统计数据显示我国精神卫生资源空间配置的均衡性和公平程度较差,尤以西藏地区的精神卫生资源配置需求最为迫切.经济因素、制度因素、地理因素是精神卫生资源空间配置均衡性的主要影响因素.精神卫生事业的特殊性决定了政府对其资源空间配置必须承担职责,提供全国一致的制度保障,执行政策必须落实到位,对精神卫生资源匮乏地区承担损益补偿责任,以促进精神卫生资源空间均衡配置.

目的:探讨二烯丙基二硫(DADS)对胃癌细胞NADPH氧化酶活性的影响及其机制.方法:用DADS作用于胃癌AGS细胞后,检测细胞NADPH氧化酶活性与miR-34a的表达,以及Src-Gab1-Shp2通路的活性,期间采用不同的干预,分析NADPH氧化酶、miR-34a、Src-Gab1-Shp2通路之间的关系.结果:DADS作用后,AGS细胞NADPH氧化酶活性以及miR-34a表达均明显升高(均P＜0.05),而DADS升高NADPH氧化酶活性的作用被添加Src激酶抑制剂PP2所取消;DADS或miR-34a作用后,AGS细胞Src、Gab1、Shp2 mRNA的表达均明显降低(均P＜0.05),且DADS作用后,AGS细胞中磷酸化Src、Gab1、Shp2蛋白水平明显降低(均P＜0.05).结论:DADS能升高NADPH氧化酶活性,该作用可能与其上调miR-34a表达,从而抑制Src-Gab1-Shp2通路活性有关.