The Effect of Cuproptosis-Related Proteins on Macrophage Polarization in Mesothelioma is Revealed by scRNA-seq.

High invasiveness mesothelioma is a malignant tumor of the peritoneum or pleura. The effect of cuproptosis on mesothelioma (MESO) is still unknown, though. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets were used to identify differential genes linked to cuproptosis in mesothelioma. Multigene features were then created to assess the course of the disease. Use single-cell data and in vitro validation to uncover crucial gene regulation mechanisms. In MESO, we found nine differentially expressed genes linked to cuproptosis. Using univariate Cox and LASSO regression techniques, a 3-gene feature (P < 0.05) was created, showing a good predictive potential for survival time. According to the risk score, patients in the low-risk subset had a considerably greater survival rate than those in the high-risk subset (P = 0). The similar survival pattern and prediction performance are also seen in the validation queue. The findings of the drug sensitivity research indicate that in high-risk patients, vinblastine, paclitaxel, gefitinib, and erlotinib are sensitive medications (P < 0.05). Classical monocytes were identified as core cells connected to cuproptosis by the CellChat results. SLC31A1 is implicated in the positive regulation of M2 macrophage polarization, according to cell subtype analysis and in vitro confirmation. Genes linked to cuproptosis have a major influence on tumor immunity and can predict how MESO will progress.

[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

Systematic review and meta-analysis of the interventional effects of resveratrol in a rat model of myocardial ischemia-reperfusion injury.

Objective: To evaluate the intervention effect of resveratrol on rat model of myocardial ischemia-reperfusion injury. Methods: The relevant studies on the intervention of resveratrol on rat models of myocardial ischemia reperfusion injury were searched in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and China Science and Technology Journal Database from the start of database establishment to January 2023. Data were extracted from studies that met the inclusion criteria. The results included electrocardiogram (ECG) and myocardial injury markers: ST changes, cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH); hemodynamic indicators: heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of increase of left ventricular pressure (+dp/dtmax), maximum rate of decrease of left ventricular pressure (-dp/dtmax); oxidative damage indicators: nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA); inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); apoptosis index: B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), cardiomyocyte apoptosis index (AI); heart tissue structure: myocardial infarction size. Finally, a meta-analysis of these results was conducted. The methodological quality of the studies was assessed using the SYRCLE Bias Risk tool. Results: A total of 43 studies were included in the meta-analysis, and the quality of the included studies was assessed. It was found that the evidence quality of these 43 studies was low, and no study was judged to have low risk bias in all risk assessments. The results showed that resveratrol could reduce ST segment, cTn-I, cTn-T, CK, CK-MB, LDH, LVEDP, ROS, MDA, TNF-α, IL-6, AI levels and myocardial infarction size. HR, LVDP, LVSP, +dp/dtmax, NO, Bcl-2, and SOD levels were increased. However, resveratrol had no significant effect on -dp/dtmax and Bax outcome measures. Conclusion: Resveratrol can reduce ST segment in rat model of myocardial ischemia-reperfusion injury, alleviate myocardial injury, improve ventricular systolic and diastolic ability in hemodynamics, reduce inflammatory response and oxidative damage, and reduce myocardial necrosis and apoptosis. Due to the low quality of the methodologies included in the studies, additional research is required.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma lacks ideal diagnostic biomarkers. There is a lack of scientific evaluation of relevant promising biomarkers as well. Therefore this study reanalyzes the related studies of 11 blood biomarkers of HCC, and compares the diagnostic value of these biomarkers for HCC systematically. METHODS: The relevant literatures on the diagnostic value in HCC of 11 blood indexes in recent 5 years were searched in PubMed, Embase, and Cochrane libraries. Data were extracted and analyzed. RESULTS: Finally, 83 literature studies were brought into meta-analysis. The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The AUC and sum of sensitivity and specificity of the combination of AFP and other biomarkers were all significantly higher than that of AFP, including AFP + AFP-L3 + DCP, AFP + DCP, AFP/DCP, AFP + GPC3. Among other biomarkers, the AUC and sum of sensitivity and specificity of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN were significantly higher than that of AFP. In this study, GP73 had the highest sum of sensitivity and specificity (1.78) and AUC (0.95). CONCLUSIONS: The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The combination of AFP and other biomarkers improved the diagnostic efficiency. The diagnostic value of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN was higher than that of AFP. GP73 had the best diagnostic value for HCC with the highest sum of sensitivity and specificity (1.78) and AUC (0.95).KEY MESSAGESThe pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The combination of AFP and other biomarkers improved the diagnostic efficiency of HCC.The diagnostic value of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN was higher than that of AFP.GP73 had the best diagnostic value for HCC.

Airway Microbiota in Patients With Synchronous Multiple Primary Lung Cancer: The Bacterial Topography of the Respiratory Tract.

Microbes and microbiota dysbiosis are correlated with the development of lung cancer; however, the airway taxa characteristics and bacterial topography in synchronous multiple primary lung cancer (sMPLC) are not fully understood. The present study aimed to investigate the microbiota taxa distribution and characteristics in the airways of patients with sMPLC and clarify specimen acquisition modalities in these patients. Using the precise positioning of electromagnetic navigation bronchoscopy (ENB), we analyzed the characteristics of the respiratory microbiome, which were collected from different sites and using different sampling methods. Microbiome predictor variables were bacterial DNA burden and bacterial community composition based on 16sRNA. Eight non-smoking patients with sMPLC in the same pulmonary lobe were included in this study. Compared with other sampling methods, bacterial burden and diversity were higher in surface areas sampled by bronchoalveolar lavage (BAL). Bacterial topography data revealed that the segment with sMPLC lesions provided evidence of specific colonizing bacteria in segments with lesions. After taxonomic annotation, we identified 4863 phylotypes belonging to 185 genera and 10 different phyla. The four most abundant specific bacterial community members detected in the airway containing sMPLC lesions were Clostridium, Actinobacteria, Fusobacterium, and Rothia, which all peaked at the segments with sMPLC lesions. This study begins to define the bacterial topography of the respiratory tract in patients with sMPLC and provides an approach to specimen acquisition for sMPLC, namely BAL fluid obtained from segments where lesions are located.

Complications of robot-assisted thymectomy: A single-arm meta-analysis and systematic review.

BACKGROUND: Recently, thymectomy using minimally invasive approaches has been increasing with the development of robotic video-assisted thoracoscopic surgery (R-VATS). Although multimodal approach is effective for robot assisted thymectomy, it is necessary to determine the approach (left, right or subxiphoid) associated with the least complications. METHODS: An electronic retrieval from PubMed, Embase, Web of Science, GreyNet International and The Cochrane Library. The single-arm meta-analysis was performed to compare the rate of complications of right- and left-side approaches by R-VATS. RESULTS: A total of 21 studies including 930 patients were identified. The pooled incidence of total complications was 12.2% (confidence interval: 10.0%-14.8%) for all studies. The overall complication rate was 17.3% for the right-side compared with 7.4% for the left side (P < 0.001, odds ratio = 2.484, 1.601-3.852). The pooled incidence of air leak was significantly higher for the right versus left side (5.1% vs. 1.2%, respectively; p = 0.004). The incidence of atrial fibrillation was higher for the right-side compared with the left-side approach (4% vs. 1.2%, respectively; p = 0.004). The open conversion rate was significantly higher for the right versus the left-side (6.5% vs. 2.9%, respectively; p = 0.004). However, there was no significant difference in the pooled incidence of pleural effusion and thoracic duct fistula when comparing the right- and left-side approaches. In subgroup analysis, in the left approach, the incidence of overall complications (28.6% vs. 5.5%, respectively; p = 0.002) and pleural effusion (14.3% vs. 1%, respectively; p = 0.002) was higher for the 'Old Age' group compared with the 'Youth' group; However, In the subgroup analysis of gender, there was no significant difference in the incidence of complications after thymectomy. CONCLUSION: Robotic video-assisted thoracoscopic surgery can be performed on the left- and right-sides; however, complications are minimal with the left-side approach. These data demonstrate that the incidence of overall complications, atrial fibrillation, open conversion ratios, and air leak rate of left-side R-VATS thymectomy are lower than those of right-side. Further subgroup analysis showed that the incidence of postoperative complications was higher in the older group.

Signaling pathways of genetic variants and miRNAs in the pathogenesis of myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder causing muscle weakness and characterized by a defect in synaptic transmission at the neuromuscular junction. The pathogenesis of this disease remains unclear. We aimed to predict the key signaling pathways of genetic variants and miRNAs in the pathogenesis of MG, and identify the key genes among them. METHODS: We searched published information regarding associated single nucleotide polymorphisms (SNPs) and differentially-expressed miRNAs in MG cases. We search of SNPs and miRNAs in literature databases about MG, then we used bioinformatic tools to predict target genes of miRNAs. Moreover, functional enrichment analysis for key genes was carried out utilizing the Cytoscape-plugin, known as ClueGO. These key genes were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then a miRNA-target gene regulatory network was established to screen key genes. RESULTS: Five genes containing SNPs associated with MG risk were involved in the inflammatory bowel disease (IBD) signaling pathway, and FoxP3 was the key gene. MAPK1, SMAD4, SMAD2 and BCL2 were predicted to be targeted by the 18 miRNAs and to act as the key genes in adherens, junctions, apoptosis, or cancer-related pathways respectively. These five key genes containing SNPs or targeted by miRNAs were found to be involved in negative regulation of T cell differentiation. CONCLUSIONS: We speculate that SNPs cause the genes to be defective or the miRNAs to downregulate the factors that subsequently negatively regulate regulatory T cells and trigger the onset of MG.

Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high­fat­diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3­kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate­1 (IRS­1), glucose transporter type 4 (GLUT­4), nuclear factor (NF)­κB and tumor necrosis factor (TNF)­α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high­fat­diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high­dose testosterone treatment. Low­dose testosterone induced upregulation in the levels of IRS­1, AKT, GLUT­4 protein, NF­κB, TNF­α and PI3K, compared with those in the animals fed a high­fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS­1, AKT, GLUT­4, NF­κB, TNF­α and PI3K. Compared with the rats in the high­fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS­1, AKT and GLUT­4, and downregulation of the mRNA levels of NF­κB, TNF­α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS­1, AKT and GLUT­4, and marked increases in the mRNA levels of NF­κB, TNF­α and PI3K, compared with the low dose group. Castration induced marked disorders of glucolipid metabolism and vascular injuries in the pubescent male rats. Low­dose testosterone treatment was found to ameliorate the vascular damage caused by castration via the PI3K/AKT signaling pathway.

Common Immunosuppressive Monotherapy for Graves' Ophthalmopathy: A Meta-Analysis.

BACKGROUND: Several immunosuppressive therapeutic regimens are widely used to treat Graves' ophthalmopathy (GO), including oral glucocorticoids (OGC), intravenous glucocorticoids (IVGC), retrobulbar injections of glucocorticoids (ROGC) and orbital radiotherapy (OR). The priority among these is unknown. This meta-analysis investigated the efficacy and tolerability of the above regimens. METHODS: The PubMed, EMBASE, and Cochrane Library databases and the Chinese Biomedicine Database were searched up to November 18, 2014. Randomized controlled trials (RCTs) comparing monotherapies (OGC, IVGC, ROGC and OR) in patients with moderate-to-severe active GO were selected. The main efficacy measures were the response rate, the standard mean difference (SMD) in the reduction in the clinical activity score (CAS) and the mean difference (MD) in proptosis from baseline to the end of treatment. The main tolerability measure was the risk ratio (RR) for adverse events. The pooled estimates and 95% confidence intervals (95% CIs) were calculated using the RevMan software, version 5.1. RESULTS: Seven published RCTs involving 328 participants were included in the present meta-analysis, including IVGC versus OGC (3 trials), ROGC versus OGC (3 trials) and OR versus OGC (1 trial). IVGC was more effective than OGC in response rate (RR = 1.48, 95% CI = 1.18-1.87) and had an obvious CAS reduction (SMD = 0.69, 95% CI = 0.13-1.25). IVGC caused fewer adverse events than OGC. ROGC and OGC had no statistically significant difference in response rate (RR = 1.16, 95% CI = 0.94-1.42). OR also did not differ significantly compared with OGC (RR = 0.93, 95% CI = 0.54-1.60). ROGC and OR had fewer adverse events, such as weight gain, compared with OGC. CONCLUSIONS: For patients with GO in the moderate-to-severe active phase, current evidence gave priority to IVGC, which had a statistically significant advantage over OGC and caused fewer adverse events. ROGC and OR did not provide greater efficacy than OGC, although better tolerability and fewer adverse events were shown.

Left lower lobectomy and systematic lymph node dissection by complete video-assisted thoracic surgery.

A 50-year-old female was administered with left lower lobe lesion for 10 days. A preoperative chest computed tomography (CT) revealed a mass in the left basilar segment of the lung, about 2.1 cm × 1.7 cm in size. Therefore, video-assisted thoracic surgery (VATS) left lower lobectomy was performed. The operation takes 60 minutes. During the operation, the estimated blood loss was 15 mL. The patient was discharged on postoperative day (POD) 6 with no complications. And the pathological results confirmed the diagnosis of adenocarcinoma with no lymph nodes metastasis.

Protein kinase C delta mediated cytotoxicity of 6-Hydroxydopamine via sustained extracellular signal-regulated kinase 1/2 activation in PC12 cells.

OBJECTIVES: The incidence of Parkinson's disease (PD) is increasing as the global population ages. 6-hydroxydopamine (6-OHDA) can induce PD-like neuropathology and biochemical changes in both in vitro and in vivo models. Therefore, clarification of the molecular mechanism of 6-OHDA-induced cell death might contribute to the understanding of the pathogenesis of PD. METHODS: With this goal in mind, we investigated the role of protein kinase C delta (PKC delta) in 6-OHDA-dependent death using the pheochromocytoma cell line, PC12. Cells were treated with 6-OHDA to induce toxicity with or without pretreatment using rottlerin (a PKC delta inhibitor), bisindolylmaleimide I (a general PKC inhibitor), Gö6976 (a PKC inhibitor selective for calcium-dependent PKC isoforms), or phorbol-12-myristate-13-acetate (PMA, a PKC activator). RESULTS: Phorbol-12-myristate-13-acetate decreased cell survival and increased the rate of apoptosis while rottlerin increased cell survival and decreased the rate of apoptosis. In contrast, neither bisindolylmaleimide I nor Gö6976 affected 6-OHDA-induced cell death. Western analysis demonstrated that phosphorylation of PKC delta on Thr 505 as well as extracellular signal-regulated kinase (ERK) phosphorylation increased after exposure to 6-OHDA. This increase in PKC delta phosphorylation was potentiated by PMA. However, rottlerin attenuated the 6-OHDA-stimulated increase in PKC delta and ERK phosphorylation. CONCLUSION: These data suggest that PKC delta, rather than classic-type PKC (alpha, beta1, beta2, gamma), participates in 6-OHDA-induced neurotoxicity in PC12 cells, and PKC delta activity is required for subsequent ERK activation during cell death.

Differential responses to UVB irradiation in human keratinocytes and epidermoid carcinoma cells.

OBJECTIVE: To examine UVB-induced responses in normal human keratinocytes (HaCaT) and epidermoid carcinoma cells (A431) at the cellular and molecular level, and investigated the protective effect of salidroside. METHODS: Cells irradiated by UVB at various dosage and their viability was assessed by MTT assays, cell cycle was analysed by flow cytometry. The expression of NF-κB, BCL-2, and CDK6 after 50 J/m(2) UVB irradiation were detected by RT-PCR and western blotting. RESULTS: Our results confirmed greater tolerance of A341 cells to UVB-induced damage such as cell viability and cell cycle arrest, which was accompanied by differential expression changes in NF-κB, BCL-2, and CDK6. UVB exposure resulted in HaCaT cells undergoing G(1)-S phase arrest. When treated with salidroside, HaCaT survival was significantly enhanced following exposure to UVB, suggesting great therapeutic potential for this compound. CONCLUSION: Taken together, our study suggests that A431 respond differently to UVB than normal HaCaT cells, and supports a role for NF-κB, CDK6, and BCL-2 in UVB-induced cell G(1)-S phase arrest. Furthermore, salidroside can effectively protect HaCaT from UVB irradiation.

The Raf-1 inhibitor GW5074 and the ERK1/2 pathway inhibitor U0126 ameliorate PC12 cells apoptosis induced by 6-hydroxydopamine.

6-Hydroxydopamine (6-OHDA) is a widely used dopaminergic neurotoxin that leads to cell apoptosis in vivo and in vitro, and is a widely accepted experimental model of neurodegeneration in Parkinson's disease. However, the molecular mechanisms responsible for 6-OHDA-induced cell apoptosis are unclear. We found that the treatment of PC12 cells with 6-OHDA resulted in a significant decrease in cell viability and elevated apoptosis as detected by MTT assay, Hoechst 33258 staining, and flow cytometry. In addition, 6-OHDA induced a time-dependent phosphorylation of ERK1/2 at Thr-202/Tyr-204 and of Raf-1 at Ser-338, but a decreased level of Raf-1 phosphorylation at Ser-259. Phosphorylation of ERK1/2 at Thr-202/Tyr-204 and Raf-1 at Ser-338 were inhibited by the Raf-1 inhibitor GW5074, while the ERK1/2 pathway inhibitor U0126 decreased phosphorylation of ERK1/2. Furthermore, 6-OHDA-induced PC12 cells apoptosis was suppressed by GW5074 and U0126. Our results suggest that GW5074 and U0126 act as neuroprotants against 6-OHDA toxicity in PC12 cells by modulating Raf-1/ERK1/2 signaling systems.

[The clinical observation of conjunctivochalasis crescent conjunctival resection with bipolar coagulation].

OBJECTIVE: To seek safe, effective, economical, simple treatment conjunctivochalasis surgical methods, optimize treatment, evaluation conjunctivochalasis surgical treatment. METHODS: A prospective randomized control study, 60 patients (60 eyes) conjunctivochalasis surgery patients were randomly divided into two groups, one line of bipolar coagulation therapy, another group of crescent conjunctival resection. After comparing the two surgical methods ocular surface disease index (OSDI) points, the degree of relaxation conjunctiva, tear meniscus height, BUT, surgical complications, the operation time to evaluate the two kinds of surgical methods of clinical efficacy. RESULTS: Bipolar coagulation therapy with crescent conjunctival resection in 8 weeks after the OSDI points, loose conjunctiva residual points, tear meniscus, BUT the difference was not statistically significant. 8 weeks after bipolar coagulation complications points lower than the crescent conjunctival resection is low, the difference was statistically significant (t = 4.67, P = 0.029); bipolar coagulation operating time (9.53 ± 3.15) min crescent than conjunctival resection time (18.59 ± 7.68) min short, the difference was statistically significant (t = 13.26, P > 0.01). CONCLUSIONS: Conjunctivochalasis line bipolar coagulation and removal of loose conjunctiva crescent with considerable effect, bipolar coagulation was significantly shorter operative time, a significant reduction in postoperative complications, surgical procedures easier.

Stemness gene expression profile analysis in human umbilical cord mesenchymal stem cells.

Umbilical cord mesenchymal stem cells (UC-MSCs) have several advantages for clinical therapy: the material is easily obtainable, the donation procedure is painless and there is low risk of viral contamination. UC-MSCs play important roles in tissue regeneration, tissue damage repair, autoimmune disease and graft-versus-host disease. In this study, we investigated the normal mRNA expression profile of UC-MSCs, and analyzed the candidate proteins responsible for the signaling pathway that may affect the differentiation characteristics of UC-MSCs. UC-MSCs were isolated by mincing UC samples into fragments and placing them in growth medium in a six-well plate. The immunophenotype characteristics and multilineage differentiation potential of the UC-MSCs were measured by flow cytometry and immunohistochemical assays. In addition, the pathway-focused gene expression profile of UC-MSCs was compared with those of normal or tumorous cells by realtime quantitative polymerase chain reaction. We successfully isolated and cultured UC-MSCs and analyzed the appropriate surface markers and their capacity for osteogenic, adipogenic and neural differentiation. In total, 168 genes focusing on signal pathways were examined. We found that the expression levels of some genes were much higher or lower than those of control cells, either normal or tumorous. UC-MSCs exhibit a unique mRNA expression profile of pathway-focused genes, especially some stemness genes, which warrants further investigation.

[Effects of radiation injury on peripheral blood and liver NO concentration in mice].

OBJECTIVE: To study the effect of radiation injury on nitric oxide (NO) concentration in mouse peripheral blood and liver. METHODS: NIH mice were subjected to gamma-ray exposure at 9.0 Gy and transferred immediately in room temperature condition. NO concentrations in the liver and peripheral blood were examined before and at different time points after the exposure. RESULTS: Compared to that before exposure, NO concentration in the peripheral blood and liver significantly increased after gamma-ray exposure. NO concentration in the peripheral blood began to increase 3 h after the exposure, but that in the liver increased till 6 h after the exposure. CONCLUSION: Radiation can cause the increase of NO concentration in the peripheral blood and liver, but different tissues may exhibit different response intensities to radiation.

[Serum resistin concentration and insulin resistance in obese children].

OBJECTIVE: Obesity is an important risk factor of insulin resistance and type 2 diabetes. Adipocyte is a cell that can actively secrete a series of factors to regulate the pathway responsible for energy balance. Resistin is one of these factors. The purpose of this study was to investigate possible correlation between resistin and certain parameters, including body parameters and other parameters of glucose metabolism and roles of resistin in hyperinsulinemia or insulin resistance in obese children. METHODS: The serum resistin concentration was measured in 34 obese children (18 boys, 16 girls; age 8.9-15.9 years) and 31 normal subjects (16 boys, 15 girls; age 7.8-14.5 years) by using ELISA. Anthropometric parameters, fasting glucose and insulin were measured in all subjects. Insulin resistance was assayed by homeostasis model assessment ratio (HOMA-R). Beta cell function was determined by using homeostasis model assessment beta cell (HOMA-beta). Correlation analysis was performed between resistin and other parameters. RESULTS: (1) The serum resistin concentration (common logarithmic transformation) was 3.1 +/- 0.5 in obese subjects and 2.7 +/- 0.8 in normal subjects. (P < 0.05). (2) The serum resistin concentration was not significantly correlated with sex, age, systolic and diastolic blood pressures, but was positively correlated with BMI, percent body fat (BF%), waist-hip ratio (WHR) (r = 0.299, r = 0.304, r = 0.322, P < 0.01); and positively correlated with fasting glucose, insulin, HOMA-R (r = 0.299, r = 0.303, r = 0.324, P < 0.05), but not significantly correlated with HOMA-beta. (3) Multiple linear regression analysis showed that only HOMA-R was the factor that significantly influenced resistin, R(2) = 0.105, the standard partial coefficient was 0.279 (P < 0.01). CONCLUSIONS: The serum resistin concentration in obese children were higher than that in normal children. The serum resistin concentration significantly correlated with the degree of obesity and the distribution of fat. Resistin is probably related to occurrence of hyperinsulinemia and/or insulin resistance in obese children.

[Epidemiological investigation on congenital heart disease in several regions of Yunnan province].

OBJECTIVE: To investigate the distribution of congenital heart disease (CHD) aged 3 - 18 in several regions of Yunnan province. METHODS: Cross-rectional studies were carried out among 48 638 children from Xishuangbanna, Dali, Baoshan Longling, Luxi Mangshi and Gejiu in Yunnan province with stratified, clustered sampling. RESULTS: The overall morbidity of CHD was 5.08 per thousand with 5.09 per thousand in males and 5.07 per thousand in females. Morbidity rates in different regions were 2.75 per thousand in Xishuangbanna, 7.85 per thousand in Dali, 9.59 per thousand in Baoshan Long ling, 4.80 per thousand in Gejiu, 16.99 per thousand in Luxi Wuchalu. However, in the same area, rates were different among different residents:3.25 per thousand in Gejiu, and was 9.10 per thousand in Laochang stannum mine, 11.20 per thousand in Datunxuanchang; 5.74 per thousand at the city of Baoshan Longling, 11.35 per thousand at countryside; 4.90 per thousand at the city of Dali, 8.71 per thousand at countryside; 1.69 per thousand at the city of Xishuangbanna, 4.40 per thousand at country. Morbidity rates in different ethnic groups were as follows: 5.39 per thousand in Dai, 6.83 per thousand in Jinuo, 0 per thousand in Hani, 8.12 per thousand in Bai, 14.18 per thousand in Jingpo. CONCLUSION: There were significant regional and ethnic differences seen in Yunnan on the mobidity of CHD which was different from the domestic literature reported.