Neutrophil gelatinase-associated lipocalin regulates intracellular accumulation of Rh123 in cancer cells.

Multidrug resistance (MDR) is a major problem facing patients with cancer. Although Neutrophil gelatinase-associated lipocalin (NGAL) is highly expressed in various cancers, the possible role of NGAL in MDR is still obscure. In this article, we evaluated the effect of NGAL on Rh123 accumulation in cancer cells. NGAL was first down-regulated by short hairpin RNA-mediated interference. In correlation with the reduced NGAL expression, intracellular Rh123 accumulation was significantly decreased. We finally observed that inhibiting both of the ERK1/2 and p38 MAPK could seriously down-regulate NGAL expression and also decrease the intracellular accumulation of Rh123, indicating that NGAL-mediated Rh123 accumulation is regulated by the phosphorylation of ERK1/2 and p38 MAPK. Pretreatment of MDA-MB-231 with NGAL recombinant protein and antibody had significant effects on the intracellular accumulation of Rh123, whereas little effect was observed in K562 cells treated with the same method, suggesting that NGAL was involved in the regulation of Rh123 accumulation in these two types of cancers, although different pathways. Here we provide new evidence that directly shows the possibility of small chemical substances Rh123 intracellular accumulation that is regulated by NGAL. These results suggest the possibility of NGAL involvement in drug transportation and cancer MDR formation, and indicate the potential of NGAL in cancer therapy.

Comparative Study on Topological Properties of the Whole-Brain Functional Connectome in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease Without RBD.

Purpose: Idiopathic rapid eye movement Sleep Behavior Disorder (iRBD) is considered as a prodromal and most valuable warning symptom for Parkinson's disease (PD). Although iRBD and PD without RBD (nRBD-PD) are both α-synucleinopathies, whether they share the same neurodegeneration process is not clear enough. In this study, the pattern and extent of neurodegeneration were investigated and compared between early-stage nRBD-PD and iRBD from the perspective of whole-brain functional network changes. Methods: Twenty-one patients with iRBD, 23 patients with early-stage nRBD-PD, and 22 matched healthy controls (HCs) were enrolled. Functional networks were constructed using resting-state functional MRI (fMRI) data. Network topological properties were analyzed and compared among groups by graph theory approaches. Correlation analyses were performed between network topological properties and cognition in the iRBD and nRBD-PD groups. Results: Both patients with iRBD and patients with early-stage nRBD-PD had attention, executive function, and some memory deficits. On global topological organization, iRBD and nRBD-PD groups still presented small-worldness, but both groups exhibited decreased global/local efficiency and increased characteristic path length. On regional topological organization, compared with HC, nRBD-PD presented decreased nodal efficiency, decreased degree centrality, and increased nodal shortest path length, while iRBD presented decreased nodal efficiency and nodal shortest path. For iRBD, brain regions with decreased nodal efficiency were included in the corresponding regions of nRBD-PD. Nodal shortest path changes were significantly different in terms of brain regions and directions between nRBD-PD and iRBD. Attention deficits were correlated with local topological properties of the occipital lobe in both iRBD and nRBD-PD groups. Conclusion: Both global and local efficiency of functional networks declined in nRBD-PD and iRBD groups. The overlaps and differences in local topological properties between nRBD-PD and iRBD indicate that iRBD not only shares functional changes of PD but also presents distinct features.

Novel Mutation of Hydroxymethylbilane Synthase in a Case of Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome.

Acute intermittent porphyria (AIP) is an autosomal, dominant, hereditary metabolic disease caused by an inherited deficiency of hydroxymethylbilane synthase (HMBS), a crucial enzyme in the heme biosynthetic pathway. It can affect the central, peripheral, and autonomic nervous systems. We report a 23-year Chinese woman who presented with severe abdominal pain, convulsions, constipation, tachycardia, quadriparesis, and hyponatremia, accompanied by posterior reversible encephalopathy syndrome (PRES). The clinical diagnosis of AIP was made after positive urine Watson-Schwartz test for porphobilinogen (PBG). Genetic testing is important for AIP patients in confirming the diagnosis. We identified a new insertion mutation in intron 14 [c.1005dupC (p.I336Hfs*23)] of the HMBS in her genomic DNA. Timely and accurate treatment of AIP may improve disease prognosis. Key Words: Acute intermittent porphyria, Mutation, Posterior reversible encephalopathy syndrome.

COVID-19 and preventive strategy.

In December 2019, an unprecedented outbreak of the novel coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread internationally, now impacting more than 293,750,692 patients with 5,454,131 deaths globally as of January 5, 2022. COVID-19 is highly pathogenic and contagious which has caused a large-scale epidemic impacting more deaths than the severe acute respiratory syndrome (SARS) epidemic in 2002-2003 or the Middle East respiratory syndrome (MERS) epidemic in 2012-2013. Although COVID-19 symptoms are mild in most people, in those with pre-existing comorbidities there is an increased risk of progression to severe disease and death. In an attempt to mitigate this pandemic, urgent public health measures including quarantining exposed individuals and social distancing have been implemented in most states, while some states have even started the process of re-opening after considering both the economic and public health consequences of social distancing measures. While prevention is crucial, both novel agents and medications already in use with other indications are being investigated in clinical trials for patients with COVID-19. The collaboration between healthcare providers, health systems, patients, private sectors, and local and national governments is needed to protect both healthcare providers and patients to ultimately overcome this pandemic. The purpose of this review is to summarize the peer-reviewed and preprint literature on the epidemiology, transmission, clinical presentation, and available therapies as well as to propose a preventive strategy to overcome the present global pandemic.

Abnormal Striatal-Cortical Networks Contribute to the Attention/Executive Function Deficits in Idiopathic REM Sleep Behavior Disorder: A Resting State Functional MRI Study.

INTRODUCTION: The structural and functional damages of the striatum were evident in idiopathic REM sleep behavior disorder (iRBD). With the research on iRBD deepens, cognitive impairment in iRBD is getting increasing attention. However, the mechanism of cognitive impairment in iRBD was poorly understood. METHODS: Neuropsychological assessment was carried out in 21 polysomnographies (PSGs) confirmed iRBD patients and 22 normal controls. Both regional homogeneity (ReHo) and seed-based functional connectivity (FC) rs-fMRI analyses were applied to explore the FC abnormalities and its association with cognition in iRBD patients. Positive ReHo clusters were set as seeds for further FC analysis. RESULTS: Idiopathic REM sleep behavior disorder patients presented cognitive deficits in attention/working memory, executive function, immediate memory, and visuo-spatial ability. ReHo analysis revealed abnormal spontaneous brain activities in the striatum (right caudate, left pallidum and bilateral putamen) in iRBD. FC analysis showed decreased striatum-related FCs in the frontal, temporal, occipital lobes, thalamus, anterior cingulate gyrus, as well as decreased intrinsic FCs between bilateral putamen and between caudate and pallidum. Deficits in attention/working memory, executive function, and immediate memory were associated with abnormal striatal-cortical FCs including frontal, temporal, and anterior cingulate cortices. CONCLUSION: Functional changes of striatum and cognitive impairment in iRBD were reconfirmed in the present study. Abnormal striatal-cortical networks, especially the striatal-frontal network, contribute to the working memory/executive function deficits in iRBDs. These findings supported the role of striatum not only in motor but also in cognition impairment in iRBD.

Blood lead level in Chinese adults with and without coronary artery disease.

BACKGROUND: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD. METHODS: In this prospective, observational study, 450 consecutive patients admitted to Beijing Anzhen Hospital with suspected CAD from November 1, 2018, to January 30, 2019, were enrolled. All patients underwent coronary angiography, and an experienced heart team calculated the SYNTAX scores (SXscore) for all available coronary angiograms. BLLs were determined with atomic absorption spectrophotometry and compared between patients with angiographically diagnosed CAD and those without CAD. RESULTS: In total, 343 (76%) patients had CAD, of whom 42% had low (0-22), 22% had intermediate (23-32), and 36% had high (≥ 33) SXscore. BLLs were 36.8 ± 16.95 µg/L in patients with CAD and 31.2 ± 15.75 µg/L in those without CAD (P = 0.003). When BLLs were categorized into three groups (low, middle, high), CAD prevalence increased with increasing BLLs (P < 0.05). In the multivariate regression model, BLLs were associated with CAD (odds ratio (OR): 1.023, 95% confidence interval (CI): 1.008-1.039; P = 0.0017). OR in the high versus low BLL group was 2.36 (95% CI: 1.29-4.42,P = 0.003). Furthermore, BLLs were independently associated with intermediate and high SXscore (adjusted OR: 1.050, 95% CI: 1.036-1.066; P < 0.0001). CONCLUSION: BLLs were significantly associated with angiographically diagnosed CAD. Furthermore, BLLs showed excellent predictive value for SXscore, especially for complex coronary artery lesions.

Cardiovascular risk and complications associated with COVID-19.

In December 2019, an unprecedented outbreak of pneumonia cases associated with acute respiratory distress syndrome (ARDS) first occurred in Wuhan, Hubei Province, China. The disease, later named Coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), was caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and on January 30, 2020, the WHO declared the outbreak of COVID-19 to be a public health emergency. COVID-19 is now a global pandemic impacting more than 43,438,043 patients with 1,158,596 deaths globally as of August 26th, 2020. COVID-19 is highly contagious and has caused more deaths than SARS in 2002-2003 or the Middle East Respiratory Syndrome (MERS) in 2012-2013 combined and represents an unprecedented human affliction not seen since the influenza pandemic of 1918. COVID-19 has been associated with several cardiac complications, including hypercoagulability, acute myocardial injury and myocarditis, arrhythmias, and acute coronary syndromes. Patients with pre-existing cardiovascular disease (CVD) are at the highest risk for myocardial injury and mortality among infected patients. The mechanism by which COVID-infected patients develop cardiac complications remains unclear, though it may be mediated by increased ACE-2 gene expression. Despite initial concerns, there is no evidence that angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy increases risk for myocardial injury among those infected with COVID-19. In the current report, we summarize the peer-reviewed and preprint literature on cardiovascular risks and complications associated with COVID-19, as well as provide insights into its pathogenesis and management.

[Establishment of internet-based online database of orthopedic failure surgery and summary of 102 cases].

OBJECTIVE: To summarize the experience of internet-based online database of orthopedic failure surgery. METHODS: Based on the OrthoChina project, a sub-database for orthopedic failure surgery was established, open to the orthopedic surgeons for viewing, uploading, and sharing the experience. All cases were uploaded by the orthopedic surgeon users registering in the OrthoChina project from 25 August 2006 to 31 December 2007 were summarized. RESULTS: 102 failure surgery cases had been uploaded in the database, in which 87 were caused by internal instrumentation, 5 by external fixation, 7 by conservative treatment, and 3 by hip arthroplasty. Sixty-seven cases involved the poor performance of the orthopedic surgeons, 4 involved the patients related, and the causes of the other 31 cases remained unknown. Six failure cases occurred in class 1 hospitals, 76 cases in class 2 hospitals, and 20 in class 3 hospitals. CONCLUSION: Internet based online database for orthopedic failure surgery helps collect the failed orthopedic treatment from different surgeons and different hospitals. Sharing such experience helps the orthopedic surgeons avoid such therapeutic errors and improve their work. Qualified training and certification are necessary for the application of new techniques and implants.

Musculoskeletal trauma services in China.

China is a developing country with a population over 1.3 billion with the second largest group of people in poverty next to India. There are about 159 million motor vehicles, with 163,887,372 drivers. From 2001 to 2004 over 100,000 people died each year in traffic accidents. With law enforcement and public education, traffic accidents have decreased, and the death rate is now less than 100,000 each year.

Musculoskeletal training for orthopaedists and nonorthopaedists in China.

No diploma for orthopaedic surgery is available in the current medical education and licensing system in China. The orthopaedist generally receives on-the-job training in a clinical practice after getting a license to practice surgery. There are multiple training pathways to and opportunities in orthopaedic surgery, and these vary from hospital to hospital and from region to region. These include on-the-job training, academic visits, rotation through different departments based on local medical needs, fellowship training in large general or teaching hospitals (locally, regionally, nationally, or internationally), English language training, postgraduate diploma training, and Internet CME. Due to the current training system, orthopaedic techniques and skill levels vary greatly from hospital to hospital.

Orthochina.org: case-based orthopaedic Wiki project in China.

Traditional continuing medical education (CME) depended primarily on periodic courses and conferences. The cost-effectiveness of these courses has not been established, and often the content is not tailored to best meet the needs of the students. Internet training has the potential to accomplish these goals. Over the last 10 years, we have developed a Web site entitled "Orthochina.org," based upon the wiki concept, which uses an interactive, case-based format. We describe the development of online case discussions, and various technical and administrative requirements. As of December 31, 2007, there were 33,984 registered users, 9,759 of which passed the confirmation procedures. In 2007, an average of 211 registrants visited daily. The average number of first page clicks was 4,248 per day, and the average number of posts was 70 per day. All cases submitted for discussion include the patient's complaint, physical examination findings, and relevant images based on specific criteria for case discussion. The case discussions develop well professionally. No spam posting or unauthorized personal advertisement is permitted. In conclusion, online academic discussions proceed well when the orthopaedic surgeons who participate have established their identities.

[Spatial Variation of Heavy Metals in Soils and Its Ecological Risk Evaluation in a Typical Carya cathayensis Production Area].

In recent years, the problem of soil pollution has become more and more serious. The problem of soil heavy metal pollution and its related human health risks has become a hot spot at home and abroad. Carya cathayensis is a unique high-grade woody nut and oil tree from China, and there are few reports on heavy metal pollution in Carya cathayensis plantation soils. Therefore, in order to study the spatial variability of heavy metals and the risk of pollution in Carya cathayensis soil and to promote the sustainable development of the Carya cathayensis industry, Lin'an, a typical Carya cathayensis plantation area, was selected for this study. A total of 188 soil samples were collected from the study area. We systematically studied the spatial heterogeneity of soil heavy metal content in the study area based on GIS technology, geostatistics, Moran's I, and other spatial analysis methods. The single factor pollution index method, the Nemerow comprehensive pollution index method, and the potential ecological risk assessment method were used to evaluate the heavy metal pollution in the study area. The results indicated that the mean content of soil cadmium (Cd), copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and chromium (Cr) were 0.37, 40.76, 87.61, 30.10, 28.33, 56.57 mg·kg-1, respectively. The average values of Cd and Cu were 1.33 and 2.87 times of the background values, respectively, and the average content of other heavy metals did not exceed the background values. The results of the single factor Nemerow pollution index and potential ecological risk assessment methods showed that heavy metals in the study area exceeded the soil background values in some samples, and the second grade standard of soil environmental quality was exceed for Cd, Cu, Zn, Pb, and Ni in 31.38%, 31.38%, 2.65%, 0.53%, and 17.02% of the samples, respectively. This indicated that the soils in the study area had different accumulation characteristics for Cd, Cu, Zn, Pb, Ni, and Cr, and the local soil had reached pollution levels for Cd, Cu, Zn, Pb, and Ni. Among them, Cd was the most serious, reaching the degree of strong ecological damage, followed by Cu. In general, the heavy metal contents indicated a moderate degree of ecological damage. Based on the analysis of the semi-variance function, the Cd, Cu, and Ni in the soil were best fit with exponential models, the Zn and Pb were better fit with the Gaussian model, and Cr was consistent with the spherical model. Cd, Cu, Pb, Ni, and Cr had the strong spatial autocorrelation, with Nugget/Sill ratios of 12.1%, 4.6%, 14.9%, 2.6%, and 11.2%, respectively, while the Nugget/Sill ratio of Zn was 48.8%, indicating a medium spatial autocorrelation. Moran's I and Kriging interpolation results found that the heavy metals Cd, Cu, Zn, Pb, Ni, and Cr all had obvious spatial distribution patterns and local spatial aggregation phenomena. The high values of heavy metals in soils were mainly found in Taiyang, Daoshi, Qingliangfeng, Heqiao, and Tuankou, and the probability of the risk for contamination by Cd and Cu was higher in the study area. The high values of Cd, Cu, Zn, Ni, and Cr were mainly related to mining, while Pb was closely related to the application of potassium.

LncRNA HOTAIR alleviates rheumatoid arthritis by targeting miR-138 and inactivating NF-κB pathway.

Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited. Enforced expression of HOTAIR also led to the upregulation of proliferation-related protein Ki67 and proliferating cell nuclear antigen (PCNA). Moreover, a negative correlation was detected between the expression of HOTAIR and microRNA (miR)-138, and the expression of miR-138 was significantly increased in LPS-induced chondrocytes. The effects of HOTAIR over-expression on the proliferation and inflammation were partly reversed by miR-138 overexpression. Furthermore, the overexpression of HOTAIR significantly inhibited the activation of nuclear transcription factor-κB (NF-κB) in LPS-treated chondrocytes by suppressing p65 to cell nucleus, resulting in the down-regulation of IL-1ß and tumor necrosis factor (TNF)-α. In addition, the in vivo experiments exhibited that overexpression of HOTAIR increased cell proliferation and inhibited inflammation in RA rats, which were demonstrated by upregulation of Ki67 and PCNA, reduced CD4+IL-17+,CD4+IL-23+ cells, and down-regulation of p-p65, IL-1ß and TNF-α. In summary, our study suggests HOTAIR plays a protective role in RA by increasing proliferation rate and inhibiting inflammation, which may be related with the regulation of miR-138 expression and NF-κB signaling pathway. These results suggest that the regulation of HOTAIR may be a promising therapeutic strategy for RA.

Acute atorvastatin treatment restores the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats.

BACKGROUND: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats. RESULTS: Compared to control group, infarct size decreased more significantly in atorvastatin+IPC and atorvastatin+IPC+wortmannin groups than IPC or atorvastatin+IPC+PD98059 groups. Phosphorylation of PI3K/Akt was attenuated in atorvastatin + IPC+ wortmannin group, phosphorylation of P42 MAPK/ERK was increased in atorvastatin+IPC and atorvastatin+IPC+wortmannin groups. MATERIALS AND METHODS: Ninety four-weeks old male SD rats fed with cholesterol enriched diet for six weeks were randomized into nine groups (n = 10/group) - sham group, control group, IPC group, atorvastatin group, wortmannin group, PD98059 group, atorvastatin+IPC group, atorvastatin+IPC+wortmannin group and atorvastatin+IPC+PD98059 group. Atorvastatin was administered orally 12 hours before myocardial reperfusion. CONCLUSIONS: Post-translational activation of P42 MAPK/ERK, rather than PI3K/Akt, participates in the net protective effect of IPC and atorvastatin in hyperlipidemia.

Assessment of left ventricular twist mechanics by speckle tracking echocardiography reveals association between LV twist and myocardial fibrosis in patients with hypertrophic cardiomyopathy.

We aimed to investigate whether left ventricular (LV) twist analysis can detect the extent of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). This prospective case-control study recruited 81 consecutive patients with HCM examined between January 2012 and April 2013. Data of 76 patients were analyzed after excluding 5 patients whose echocardiographic images were of poor quality. Healthy volunteers (n = 46) served as controls. Both groups underwent comprehensive echocardiographic examination (i.e., Bas-Rotation, AP-Rotation, LVEF, LADs, IVST, LAVi, E/Em, LVMI, advanced LV-twist analysis by speckle tracking echocardiography) and magnetic resonance imaging. Between-group differences were analyzed by independent t test; logistic regression analysis was performed to identify effect factors. No significant differences were found between baseline characteristics of HCM and control groups (all p > 0.05). HCM patients had significantly higher Bas-Rotation, AP-Rotation, LV Twist, LVEF, LADs, IVST, LAVi, E/Em and LVMI than controls (all p < 0.0001) and significantly lower LVDd and E/A (both p < 0.001). Bas-Rotation, AP-Rotation, LV-Twist, LADs, IVST, LAVi, E/Em and LVMI were significantly higher in HCM patients with fibrosis than in those without fibrosis (p < 0.001), but no significant differences in other echocardiographic parameters were found between those with and without fibrosis. Age, Bas-Rotation, AP-Rotation, LV twist, LADs, IVST, LAVi, E/A, E/Em, and LVMI were significant effect factors for fibrosis. AUROC analysis showed that LV twist had high discriminatory power to detect extent of myocardial fibrosis (AUC 0.996, 95 % CI 0.989-1.004, p < 0.001). Left ventricular twist mechanics are associated with the extent of myocardial fibrosis. LV-twist assessment by STE may be clinically useful.

[Experiment and model simulation of self-purification capacity of nitrogen and phosphorus in Lake Taihu].

A field experiment was carried out in Zhushanhu in September, 2011. On the basis of mass balance, nutrients flow in and out of Zhushanhu and their Digestion-absorption law was illustrated through water quantity-water quality observation of bay heart, bay mouth and rivers around Zhushanhu, which provides basic data for the further research on the self-purification capacity of Lake Taihu. The EcoTaihu model was adopted to simulate the nutrients flow and their self-purification capacity of Lake Taihu. The simulated annual self-purification capacity of total nitrogen and total phosphorus of Zhushanhu was 1 911 t and 116 t, respectively, whereas the observed annual self-purification capacity of total nitrogen and total phosphorus of Zhushanhu was 1 979 t and 119 t, respectively. The model was validated by the observation data. The simulated result showed that the self-purification capacity of total nitrogen of Lake Taihu in year 2006, 2008 and 2010 was 4. 00 x 10(4) t, 4. 27 x 10(4) t and 4. 11 x 10(4) t, respectively, whereas the self-purification capacity of total phosphorus of Lake Taihu in year 2006, 2008 and 2010 was 1.56 x 10(3) t, 1.80 x 10(3) t and 1.71 x 10(3) t, respectively.

[Inhibition of NHE1 down-regulates IL-8 expression and enhances p38 phosphorylation].

This study was purposed to explore the changes of possible angiogenetic factors other than VEGF after inhibition of NHE1 and their related mechanisms. The K562 cells were treated by NHE1 specific inhibitor cariporide, the angiogenesis factors after inhibition of NHE1 were screened by using protein chip, the IL-8 expression level after cariporide treatment was detected by real-time quantitative PCR; the K562 cells with stable interference of NHE1 were constructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cells treated with cariporide was detected by Western blot. After treatment of K562 cells with p38 inhibitor SB203580, the IL-8 expression level was decreased by real-time quantitative PCR. The results of protein chip showed that IL-8 expression decreased after cariporide treatment. Real-time quantitative PCR confirmed this inhibitory effect. The p38 phosphorylation level increased after cariporide treatment. The down-regulation of IL-8 expression induced by cariporide treatment was partially restored after K562 cells were treated with p38 inhibitor SB203580. It is concluded that the inhibition of NHE1 can inhibit IL-8 expression through up-regulation of p38 phosphorylation.

[Effect of DOT1L gene silence on proliferation of acute monocytic leukemia cell line THP-1].

This study was aimed to investigate the influence of short hairpin RNA (shRNA) on proliferation of human leukemia cell line THP-1. The shRNA targeting the site 732-752 of DOT1L mRNA was designed and chemically synthesized, then a single-vector lentiviral, tet-inducible shRNA-DOT1L system (Plko-Tet-On) was generated. Thereafter, the THP-1 cells with lentivirus were infected to create stable cell line with regulatable shRNA expression. The expression of DOT1L in the THP-1 cell line was assayed by RT-PCR. Effect of shRNA-DOT1L on the proliferation of THP-1 cells was detected with MTT method,and the change of colony forming potential of THP-1 cells was analyzed by colony forming unit test. Cell cycle distribution was tested by flow cytometry. The results indicated that the expression of DOT1L was statistically lower than that in the control groups. The proliferation and colony forming capacity of THP-1 cells were significantly inhibited. The percentage of cells at G0/G1 phase increased in THP-1/shRNA cells treated with Dox while the percentage of cells at S phase significantly decreased as compared with that in the control group. It is concluded that the shRNA targeting DOT1L can effectively inhibit the proliferation of acute monocytic leukemia cell line THP-1.