[Role of Flow Cytometry in the Diagnosis of Chronic Myeloid Leukemia].

OBJECTIVE: To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance. METHODS: The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups. RESULTS: The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI. CONCLUSION: The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.

[Nomogram prediction model construction and clinical guidance value of urinary incontinence in benign prostatic hyperplasia after plasma prostatectomy].

OBJECTIVE: To analyze the construction and clinical guiding value of nomogram prediction model for urinary incontinence (UI) after plasma kinetic enucleation of the prostate (PKEP) in patients with benign prostatic hyperplasia（BPH）. METHODS: The clinical data of 250 BPH patients admitted to our hospital from December 2021 to April 2023 were retrospectively analyzed. According to the postoperative UI, they were divided into UI group (n=68) and no-UI group (n=182). The general and clinical data of the two groups were compared, and the influencing factors of postoperative UI in patients with BPH were analyzed by multivariate Logistic regression. Using the "rms" software package in R version 3.5.2, the Nomogram prediction model of UI risk in patients with BPH after operation was drawn, and the diagnostic efficiency of the model was evaluated by the receiver's operating characteristics (ROC) curve. RESULTS: The proportion of patients with age ≥65 years old, diabetes and preoperative UI in UI group was significantly higher than that in no-UI group (P<0.05). The preoperative membranous urethra (MUL) level of patients in UI group was significantly lower than that in no-UI group, and the proportion of bladder dysfunction decompensation, preoperative prostate volume and operation time were significantly higher than those in no-UI group (P<0.05). Multivariate Logistic regression analysis showed that patients' age ≥65 years, diabetes, preoperative UI, bladder dysfunction decompensation, preoperative prostate volume and operation time were the risk factors for postoperative UI in patients with BPH, and the preoperative length of membranous urethra (MUL) was the protective factor for postoperative UI in patients with BPH (P<0.05). The Nomogram prediction model of postoperative UI of patients with BPH was established. The ROC curve analysis showed that the AUC of Nomogram prediction model for predicting postoperative UI of patients with BPH was 0.826 (95% CI 0.798－0.934) (P<0.05). CONCLUSION: Age ≥65 years old, diabetes, preoperative UI, bladder dysfunction decompensation, preoperative prostate volume and operation time are closely related to postoperative UI in patients with BPH. MUL before operation is a protective factor for postoperative UI in patients with BPH. Based on the above factors, it is of certain value to construct Nomogram prediction model in predicting postoperative UI in patients with BPH, which can help predict postoperative conditions of patients and adjust treatment plans in time.

LncRNA FGD5-AS1 enhances the proliferation and stemness of hepatocellular carcinoma cells through targeting miR-223 and regulating the expression of ECT2 and FAT1.

AIM: Hepatocellular carcinoma (HCC) is common and causes many deaths worldwide. The aim of this study is to explore the mechanism by which long non-coding RNA FGD5-AS1 regulates HCC cell proliferation and stemness. METHODS: Tumor and normal adjacent tissues were harvested from HCC patients. Real-time quantitative reverse transcription-PCR was applied to examine the expression of FGD5-AS1, miR-223, Epithelial cell transforming sequence 2 (ECT2) and FAT1. The protein levels of ECT2, FAT1, proliferating cell nuclear antigen (PCNA), OCT4, CD133 and CD90 were analyzed by western blot. The localization of FGD5-AS1 was examined by Fluorescence in situ hybridization. Cell proliferation was analyzed with CCK-8 and colony formation assays. Spheroid formation was used for analyzing cell stemness. Gene interaction was examined by RNA immunoprecipitation and luciferase activity assays. A subcutaneous xenograft mouse model was established to analyze HCC growth and stemness in vivo. Immunohistochemistry staining was used to analyze the expression PCNA and OCT4 in subcutaneous tumors. RESULTS: FGD5-AS1 was upregulated in HCC and its high expression indicated poor prognosis of patients. High expression of FGD5-AS1 enhanced HCC cell proliferation and stemness. Knockdown of FGD5-AS1 restrained tumor growth and stemness in mice. FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC. Both knockdown of miR-223 and overexpression of ECT2 and FAT1 reversed FGD5-AS1 silencing-mediated suppression of HCC cell proliferation and stemness. CONCLUSION: FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC, thus enhancing HCC cell proliferation and stemness. Our study identifies potential prognostic biomarkers and therapeutic targets for HCC.

TREM-1-targeting LP17 attenuates cerebral ischemia-induced neuronal injury by inhibiting oxidative stress and pyroptosis.

Stroke ranks as the second leading cause of disability and death globally. Trigger receptors expressed on myeloid cells (TREM) -1 are responsible for the activation of the innate immune response and also play a critical role in inflammation. In this study, we reported the contribution of TREM-1 after ischemic damage in a rat middle cerebral artery occlusion (MCAO) model. This study also demonstrated that TREM-1 expression was upregulated following cerebral infarction in rats. TREM-1 inhibition was determined using its selective inhibitor, LP17, which indicated a neuroprotective effect on cerebral infarction damage. The findings revealed that inhibition of TREM-1 by administering LP17 improved cerebral damage and decreased ischemic areas and brain water contents. Moreover, LP17 decreased MCAO-induced microglial activation and neurodegeneration, evidenced by a reduction in the expression of microglial Iba-1 and FJ-B positive cells, and reversed neuronal loss. Besides, the contribution of LP17 to ischemic neuronal damage may be associated with a decrease in the production of pro-inflammatory cytokines, and enhanced production of anti-inflammatory cytokine IL-10. Both in vivo and in vitro studies showed that inhibiting TREM-1 attenuated ROS accumulation, lipid per-oxidation (LPO) contents such as malondialdehyde (MDA) and enhanced the superoxide dismutase (SOD) activity after ischemia. Inhibiting TREM-1 alleviated inflammation and pyroptosis found in MCAO rats. This was achieved through the inhibition of the levels of NLRP3, caspase-1, ASC (an apoptosis-associated speck-like protein containing a CARD) and gasdermin D. These results confirmed that inhibiting TREM-1 protects against ischemia-induced neuronal damage and alleviates microglial mediated neuro-inflammation by reducing oxidative stress and pyroptosis. Therefore, blocking TREM-1 expression provides an effective intervention for improving ischemic stroke.

Memantine ameliorates tau protein deposition and secondary damage in the ipsilateral thalamus and sensory decline following focal cortical infarction in rats.

Previous studies have reported that memantine presents evidence of therapeutic benefits in several animal models of ischemic stroke and neurodegenerative diseases. However, the effect of memantine on secondary damage in the ipsilateral thalamus after focal cortical infarction remains undefined. Present study investigated whether memantine has a protective effect on secondary damage in the ipsilateral thalamus after focal cerebral infarction in rats. At 24 h after distal middle cerebral artery occlusion (MCAO), rats in the memantine and vehicle groups were intraperitoneal injected with memantine and isopycnic vehicle, respectively, was once daily administered for consecutive 7 days. Infarct size was evaluated through Nissl staining and sensory decline determined using adhesive removal test. Secondary thalamic damage was assessed using Nissl staining and immunofluorescence 8 days after MCAO. Immunoboltting was used to identify tau and apoptosis-associated proteins in the ipsilateral thalamus after MCAO. Results revealed that memantine ameliorated sensory decline compared to the vehicle controls. Subsequently, tau phosphorylated at threonine 231 (p-tau-231), glycogen synthase kinase3ßpY216 (GSK3ßpY216) and protein phosphatase 2A (PP2ApY307) were reduced by memantine, causing greater reduction in neuronal loss and inhibition of reactive astrogliosis in the ipsilateral ventroposterior thalamic nucleus (VPN) compared with the vehicle groups. In addition, increase in secondary damage-induced TUNEL-positive cells was blunted by memantine, as demonstrated by the significant reduction in expression of apoptosis-associated proteins. Our results suggest that memantine has a neuro-protective effect on secondary damage in the ipsilateral thalamus following MCAO by inhibiting the activity of GSK3ßpY216/PP2ApY307 and down regulating the levels of p-tau-231 protein.

Effects of a 4-week Omaha System transitional care programme on rheumatoid arthritis patients' self-efficacy, health status, and readmission in mainland China: A randomized controlled trial.

BACKGROUND AND AIM: To our knowledge, the practice of transitional care was not common in mainland China. This study was designed to test the intervention effects of a specific dose (4 weeks) of an Omaha-based system transitional care programme for Chinese patients suffering from rheumatoid arthritis. METHODS: The intervention group adopted a 4-week nurse-led transitional care intervention based on the Omaha System. The control group used a comparable length of routine care. The outcome indexes were a Chinese version of the Arthritis Self-Efficacy Scale-8, Health Assessment Questionnaire-Disability Index, and hospital readmission rates. Data were collected from June 2018 to December 2018. RESULTS: Finally, 88 patients (44 in the intervention group and 44 in the control group) entered the data analysis. Baseline sociodemographic data for both groups were not found to be statistically significant. The self-efficacy and HAQ-DI of the intervention group were significantly different from the control group. Although the readmission rates of the intervention group were lower than that of the control group, it was not statistically significant. CONCLUSIONS: This 4-week transitional care intervention dose is sufficient to provide evidence for improving self-efficacy to implement disease management and enhancing physical function of patients diagnosed with rheumatoid arthritis.

Elevated ecto-5'-nucleotidase: a missing pathogenic factor and new therapeutic target for sickle cell disease.

Although excessive plasma adenosine is detrimental in sickle cell disease (SCD), the molecular mechanism underlying elevated circulating adenosine remains unclear. Here we report that the activity of soluble CD73, an ectonucleotidase producing extracellular adenosine, was significantly elevated in a murine model of SCD and correlated with increased plasma adenosine. Mouse genetic studies demonstrated that CD73 activity contributes to excessive induction of plasma adenosine and thereby promotes sickling, hemolysis, multiorgan damage, and disease progression. Mechanistically, we showed that erythrocyte adenosine 5'-monophosphate-activated protein kinase (AMPK) was activated both in SCD patients and in the murine model of SCD. AMPK functions downstream of adenosine receptor ADORA2B signaling and contributes to sickling by regulating the production of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), a negative allosteric regulator of hemoglobin-O2 binding affinity. Preclinically, we reported that treatment of α,ß-methylene adenosine 5'-diphosphate, a potent CD73 specific inhibitor, significantly decreased sickling, hemolysis, multiorgan damage, and disease progression in the murine model of SCD. Taken together, both human and mouse studies reveal a novel molecular mechanism contributing to the pathophysiology of SCD and identify potential therapeutic strategies to treat SCD.

Rapid screening and identification of sesquiterpene lactones in Kudiezi injection based on high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry.

Sesquiterpene lactones are considered as the major active compounds in Kudiezi injection in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of sesquiterpene lactones in Kudiezi injection using high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. First, two sesquiterpene lactone reference standards were analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Second, based on extracted ion chromatography (EIC) data-mining method and characteristic fragmentation pathways analysis, sesquiterpene lactones in Kudiezi injection were rapidly screened and identified. Finally, an important parameter Clog P was adopted to discriminate the isomers of sesquiterpene lactones. As a result, 50 sesquiterpene lactones were characterized, including 9 sesquiterpene lactone aglycones, 39 sesquiterpene lactone glycosides, and 2 amino acid-sesquiterpene lactone conjugates. Among them, 13 compounds were tentatively identified as new compounds. The results demonstrated that the established method would be a rapid, effective analytical tool for screening and identification of sesquiterpene lactones in the complex system of natural medicines.

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus.

The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-Kb-restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool. A lower percentile rank indicates higher affinity and higher immune response. In the case of the consensus method, we also evaluated the binding score of peptide-binding affinity by the BIMAS software to confirm that all peptides were able to bind H2-Kb. Second, one novel GP-derived CTL epitope, GP6 aa456-aa463 (ITSLFSLL), was identified in the splenocytes of HTNV-infected mice using the IFN-γ ELISPOT assay. Third, a single peptide vaccine was administered to C57BL/6 mice to evaluate the immunogenic potential of the identified peptides. ELISPOT and cell-mediated cytotoxicity assays showed that this peptide vaccine induced a strong IFN-γ response and potent cytotoxicity in immunized mice. Last, we demonstrated that the peptide-vaccinated mice had partial protection from challenge with HTNV. In conclusion, we identified an H2-Kb-restricted CTL epitope with involvement in the host immune response to HTNV infection.

Analysis of the genetic variants associated with recurrent thromboembolism in a patient with hemoglobin H disease following splenectomy: A case report.

Reports of recurrent thromboembolism in thalassemia, particularly in hemoglobin H (HbH) disease associated with congenital thrombophilic mutations, are scarce. However, several mutations were detected in a 22-year-old woman with HbH disease. The patient experienced the first thrombotic event at the age of 20 years and had four recurrent thromboses in a short time interval, despite receiving anticoagulant treatment. The present study reports a case with six nucleotide substitutions, including a missense 565C>T (Arg189Trp) mutation and two synonymous mutations, 66T>C (Pro22Pro) and 423G>T (Ser141Ser), identified in the protein C gene. The other three mutations, 947G>A (Arg316His), 981A>G (Val327Val), and 775C>A (rs13146272), were identified in the protein S, antithrombin and cytochrome P450, family 4, subfamily V, polypeptide 2 genes, respectively. These findings suggest that if thrombotic events repeatedly occur in a patient with thalassemia, not only the risk factors associated with a hypercoagulable state, but the acquired and congenital thrombophilia should be screened for.

TTF1-NPs Induce ERS-Mediated Apoptosis and Inhibit Human Hepatoma Cell Growth In Vitro and In Vivo.

Previous studies have shown that 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone (TTF1) is the primary anticancer constituent of the traditional Chinese medicinal plant Sorbaria sorbifolia (SS), which has been applied to treat cancer in China. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of small-molecule TTF1 nanoparticles (TTF1-NPs). The effects of TTF1-NPs on cell growth and apoptosis were investigated using human hepatoma cells. The molecular changes associated with the effects of TTF1-NPs were analyzed by immunocytochemistry and Western blot analysis. The in vivo effect of TTF1-NPs was investigated using the HepG2 tumor xenograft model. We found that TTF1-NPs exhibited antitumor effects in vitro accompanied by induction of apoptosis in human hepatoma cells. Mechanistically, our data showed that TTF1-NPs induced apoptosis via endoplasmic reticulum stress (ERS) pathway in hepatoma cells. Moreover, inhibition of ERS activation blocked TTF1-NP-induced apoptosis in HepG2 cells. Finally, TTF1-NPs inhibited the growth of HepG2 xenograft tumors. Taken together, our results demonstrated that TTF1-NP-induced apoptosis was mediated at least in part by the ERS pathway and thus inhibited hepatoma tumor growth.

A Small Indel Mutant Mouse Model of Epidermolytic Palmoplantar Keratoderma and Its Application to Mutant-specific shRNA Therapy.

Epidermolytic palmoplantar keratoderma (EPPK) is a relatively common autosomal-dominant skin disorder caused by mutations in the keratin 9 gene (KRT9), with few therapeutic options for the affected so far. Here, we report a knock-in transgenic mouse model that carried a small insertion-deletion (indel) mutant of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), corresponding to the human mutation KRT9/c.500delAinsGGCT (p.Tyr167delinsTrpLeu), which resulted in a human EPPK-like phenotype in the weight-stress areas of the fore- and hind-paws of both Krt9(+/mut) and Krt9(mut/mut) mice. The phenotype confirmed that EPPK is a dominant-negative condition, such that mice heterozygotic for the K9-mutant allele (Krt9(+/mut)) showed a clear EPPK-like phenotype. Then, we developed a mutant-specific short hairpin RNA (shRNA) therapy for EPPK mice. Mutant-specific shRNAs were systematically identified in vitro using a luciferase reporter gene assay and delivered into Krt9(+/mut) mice. shRNA-mediated knockdown of mutant protein resulted in almost normal morphology and functions of the skin, whereas the same shRNA had a negligible effect in wild-type K9 mice. Our results suggest that EPPK can be treated by gene therapy, and this has significant implications for future clinical application.

Eukaryotic translation initiation factor 5A2 regulates the migration and invasion of hepatocellular carcinoma cells via pathways involving reactive oxygen species.

Eukaryotic translation initiation factor 5A2 (eIF5A2) has been identified as a critical gene in tumor metastasis. Research has suggested that reactive oxygen species (ROS) serve as signaling molecules in cancer cell proliferation and migration. However, the mechanisms linking eIF5A2 and ROS are not fully understood. Here, we investigated the effects of ROS on the eIF5A2-induced epithelial-mesenchymal transition (EMT) and migration in six hepatocellular carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell migration assays, wound-healing assays, and immunofluorescence analysis were used. The protein levels of eIF5A2 in tumor and adjacent tissue samples from 90 HCC patients with detailed clinical, pathological, and clinical follow-up data were evaluated. Overexpression of eIF5A2 was found in cancerous tissues compared with adjacent tissues. We found that eIF5A2 overexpression in HCC was associated with reduced overall survival. Knockdown of eIF5A2 and intracellular reduction of ROS significantly suppressed the invasion and metastasis of HCC cells. Interestingly, N1-guanyl-1, 7-diaminoheptane (GC7) suppressed the intracellular ROS levels. After blocking the EMT, administration of GC7 or N-acetyl-L-cysteine did not reduce cell migration further. Based on the experimental data, we concluded that inhibition of eIF5A2 alters progression of the EMT to decrease the invasion and metastasis of HCC cells via ROS-related pathways.

[Mechanism of TTF1-NP induced implanted hepatoma tumor apoptosis in nude mice by endoplasmic reticulum stress pathway].

This study was designed to investigate the effect of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle(TTF1-NP) on inducing apoptosis of implanted tumour cells in nude mice and the mechanism of endoplasmic reticulum stress pathway. The implanted hepatoma model was established in nude mice, and used to test the drug TTF1-NP in five groups(vehicle, 5 µmol·kg(-1) TTF1-NP, 10 µmol·kg(-1) TTF1-NP, 20 µmol·kg(-)1TTF1-NP and adriamycin). The nude mice were killed after the treatment to determine the tumor growth inhibition rate(IR). Morphological changes of implanted tumor cells were observed by HE staining; apoptosis of tumor cells was detected by TUNEL; the protein expression of GRP78, p-JNK and caspase 12 were analyzed using immunocytochemistry staining and Western blotting. We tested the effects of TTF1-NP on implanted Hep G-2 cell tumor growth in nude mice. TTF1-NP-treated mice showed volume of tumor smaller than that of the vehicle-treated mice. The tumor mass of the TTF1-NP-treated mice were significantly reduced than those of the vehicle-treated mice. In addition, the tumor growth rate of the TTF1-NP-treated mice was significantly lower than that of the vehicle-treated mice, and the tumor growth inhibition ratio of the TTF1-NP-treated mice was significantly higher than that of the vehicle-treated mice. TTF1-NP exhibited an inhibitory effect on implanted tumor cells in the model. The IR was 51.2%, 54.2%, 61.8% and 65.9%, respectively. In comparison with the vehicle group, the treated groups exhibited alteration in cell morphology and apoptosis of tumor cells, and expression of GRP78, p-JNK and caspase 12, which were observed by immunocytochemistry staining and Western blotting. Taken together, our results suggest that TTF1-NP induces apoptosis of implanted tumor cells in nude mice and the main mechanism is related to activation of endoplasmic reticulum stress.

A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree.

AIM: To identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD). METHODS: A southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members. RESULTS: The results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation. CONCLUSION: All modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.

MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury.

A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.

A meta-analysis of glutathione S-transferase M1 and T1 genetic polymorphism in relation to susceptibility to nasopharyngeal carcinoma.

OBJECTIVE: To investigate the relationship between glutathione S-transferase M1 (GSTM1), and T1 (GSTT1) genetic polymorphism and susceptibility to nasopharyngeal carcinoma (NPC) using meta-analysis method. METHODS: Data of published case-control studies on the relationship between GSTT1, GSTM1 genetic polymorphism and susceptibility to NPC were collected from EMBASE, PubMed, Web of Science, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, and Wanfang Database. Meta-analysis was conducted using Revman 5.2 software. RESULTS: Nine studies were included for meta-analysis with a total of 1295 cases of NPC patients and 1967 control individuals. Meta-analysis showed that the risk of NPC was significantly higher in population with GSTM1 gene deletion (OR=1.43, 95% CI: 1.42-1.65; P<0.001). Similarly, the risk of NPC was significantly higher in Chinese population with GSTM1 gene deletion (OR=1.38, 95% CI: 1.18-1.62; P<0.001). We did not find association between GSTT1 gene deletion and NPC risk not only in total population (OR=1.32, 95% CI: 0.92-1.87; P=0.12), but in Chinese population (OR=1.41, 95% CI: 0.97-2.04; P=0.07). CONCLUSION: GSTM1 genetic polymorphism, but GSTT1, is associated with susceptibility to NPC.

Matrix metalloproteinase 2 (MMP2) protein expression and laryngeal cancer prognosis: a meta analysis.

OBJECTIVE: To investigate the protein expression of matrix metalloproteinase 2 (MMP2) and its clinical significance in laryngeal cancer. METHODS: A comprehensive search for the related literature published in China and other countries was conducted in a variety of databases, including MEDLINE, Embase, China Academic Journals Full-text Database, Wanfang Data and VIP Database. A total of seven case-control studies were included in the final systematic assessment. A meta-analysis software program was used to statistically analyze the raw data from each study for the calculation of the pooled odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The meta-analysis indicated that, compared with normal laryngeal tissue, the MMP2 protein was highly expressed in the laryngeal cancer tissue [OR=21.67; 95% CI: 11.61-40.43; P<0.001]. Compared with highly differentiated laryngeal cancer, the MMP2 protein expression level was higher in the moderately and poorly differentiated laryngeal cancers [OR=0.25; 95% CI: 0.13-0.46; P<0.001]. Compared with laryngeal cancers without lymph node metastasis, the laryngeal cancers with lymph node metastasis exhibited a greatly elevated MMP2 protein expression [OR=0.25; 95% CI: 0.14-0.46; P<0.001]. CONCLUSION: High protein expression levels of MMP2 may play an important role in the tumorigenesis, progression and prognosis of laryngeal cancer.