Mechanical Stimulation of Anti-Inflammatory and Antioxidant Hydrogels for Rapid Re-Epithelialization.

The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re-epithelialization to restore tissue integrity and function in an adverse environment is challenging. In this work, a long-term anti-inflammatory and antioxidant hydrogel with mechanical stimulation for rapid re-epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, and γ-Fe2O3 nanoparticles is reported. Glycine-modified supramolecular thioctic acid is stable and possesses outstanding mechanical properties. The incorporating γ-Fe2O3 providing the potential contrast function for magnetic resonance imaging observation, can propel hydrogel reconfiguration to enhance the mechanical properties of the hydrogel underwater due to water-initiated release of Fe3+. In vitro experiments show that the hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, and alleviated inflammation. The effect of rapid re-epithelialization is ultimately demonstrated in a long urethral injury model in vivo, and the mechanical stimulation of hydrogels achieves effective functional replacement and ultimately accurate remodeling of the epithelium. Notably, the proposed strategy provides an advanced alternative treatment for patients in need of large-area epithelial reconstruction.

miR-98-5p Prevents Hippocampal Neurons from Oxidative Stress and Apoptosis by Targeting STAT3 in Epilepsy in vitro.

Purpose: Epilepsy is a serious mental disease, for which oxidative stress and hippocampal neuron death after seizure is crucial. Numerous miRNAs are involved in epilepsy. However, the function of miR-98-5p in oxidative stress and hippocampal neuron death after seizure is unclear, which is the purpose of current study. Methods: Magnesium ion (Mg2+)-free solution was used to establish the in vitro epilepsy model in hippocampal neurons. Oxidative stress was exhibited by measuring malondialdehyde (MDA) level and superoxide Dismutase (SOD) activity using enzyme-linked immune sorbent assay (ELISA) kits. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were applied for the examination of neuron viability and apoptosis, respectively. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot were used to evaluate the mRNA and protein levels of miR-98-5p and signal transducer and activator of transcription (STAT3), respectively. The relationship between miR-98-5p and STAT3 was predicted by TargetScan 7.2, and identified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: miR-98-5p was decreased in the in vitro epileptic model of hippocampal neurons induced by Mg2+-free solution, whose overexpression rescued oxidative stress and neuron apoptosis in epileptic model. Moreover, overexpression of STAT3, one downstream target of miR-98-5p, partially eliminated the effects of miR-98-5p mimic. Conclusion: We shed lights on a pivotal mechanism of miR-98-5p in regulating neuron oxidative stress and apoptosis after seizures, providing potential biomarkers for the diagnosis of epilepsy and therapeutic targets for the treatment of epilepsy.

Laparoscopic assisted trans-scrotal orchiopexy versus traditional orchiopexy for inguinal cryptorchidism: a retrospective study based on 154 patients.

BACKGROUND: The purpose of this study was to investigate the clinical effect of laparoscopic assisted trans-scrotal orchiopexy versus traditional orchiopexy for inguinal cryptorchidism. METHODS: A retrospective analysis of cryptorchidism patients who were admitted to our hospital from July 2018 to July 2021. The patients were divided into the laparoscopic assisted trans-scrotal surgery group (n = 76) and the traditional surgery group (n = 78) according to the surgical method. RESULTS: All patients were successfully operated. There was no significant difference in operation time between the laparoscopic assisted trans-scrotal group and the traditional group (P>0.05). Although there was no significant difference in the postoperative hospital stay between the two groups, the time of postoperative hospital stay of the laparoscopic assisted trans-scrotal surgery group was lower than that in the traditional surgery group (P = 0.062). Additionally, there was no significant difference in discharge rate on the first day after surgery between the two groups, but the discharge rate on the first day after surgery was more than 90% in both groups. In terms of postoperative complications, there were no cases of testicular retraction, testicular atrophy, inguinal hernia, or hydrocele that occurred in both groups. There was no significant difference in the incidence of scrotal hematoma between the two groups(P>0.05). Although there was no significant difference in the incidence of poor wound healing between the two groups(P>0.05), the incidence in the laparoscopic assisted trans-scrotal surgery group was lower than that in the traditional surgery group (2.6% vs. 6.4%). CONCLUSION: Laparoscopic assisted trans-scrotal surgery is as safe and effective method as traditional surgery for patients with inguinal cryptorchidism, and could also provide a good appearance.

Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells.

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. In vivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the in vivo knockdown model with isolated primary LCs and in vitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Benchmarking of 5 algorithms for high-resolution genotyping of human leukocyte antigen class I genes from blood and tissue samples.

Background: Specific alterations in human leukocyte antigen class I (HLA-I) loci are associated with clinical outcomes for immune checkpoint inhibitors, which increase the clinical relevance of accurate high-resolution HLA genotyping in immuno-oncology applications. Numerous algorithms have been developed for high- to full-resolution HLA genotyping by next-generation sequencing (NGS) data; however, Sanger sequencing-based typing (SBT) remains the gold standard. With the increasing use of NGS for clinical oncology, it is important to identify the computational tool with comparable performance as the gold standard. This study aimed to benchmark 5 algorithms against SBT for the high-resolution typing of classical HLA-I genes for targeted NGS data from blood and tissue samples. Methods: Paired white blood cell (WBC), plasma, and tissue deoxyribonucleic acid (DNA) samples derived from 22 cancer patients with known HLA genotypes were sequenced using a panel of all the following exons of classical HLA-I genes: HLA-A, HLA-B, and HLA-C. NGS-based genotypes were generated by the 5 different algorithms, including HLA-HD, HLAscan, OptiType, Polysolver, and xHLA. Accuracy was defined as the concordance between the SBT and NGS-based algorithms. Accuracy was computed as the fraction of all the alleles with concordant genotype using the SBT and any of the algorithm over the total number of alleles. Results: In relation to the WBC, plasma, and tissue samples, all 5 algorithms were highly accurate at low-resolution HLA-I genotyping, but had more varied accuracy at high-resolution HLA-I genotyping, particularly in HLA-A. The in-silico analyses revealed that high-resolution genotyping by all 5 algorithms achieved approximately 90% accuracy at sequencing depths of 6,000× - 100× for the WBC samples, at 6,000× - 700× for the plasma samples, and at 1,000× - 100× for the tissue samples. Among the 5 algorithms, HLA-HD was consistently accurate at high-resolution HLA-I genotyping, and had an accuracy of 93.9% for the WBC samples, 87.9% for the plasma samples, and 94.2% for tissue samples even at a 50× sequencing depth. Conclusions: We found that HLA-HD was an accurate algorithm for the high-resolution genotyping of classical HLA-I genes sequenced by our targeted panel, particularly at a sequencing depth ≥300× for blood and tissue samples.

Analysis of a Long Non-coding RNA associated Signature to Predict Survival in Patients with Bladder Cancer.

BACKGROUND: The study aimed to find a potential long non-coding RNA (lncRNA) model related to survival in bladder cancer by analyzing data in The Cancer Genome Atlas (TCGA). METHODS: We downloaded the gene expression data from the TCGA and analyzed the differentially expressed lncRNAs (DELs) between tumor and normal tissues. Patients were divided into training and testing groups, and a prognostic risk score model with lncRNAs was constructed by using data in the training group using multivariate Cox and lasso regression analysis. We divided patients into high-and low-risk groups according to the median value in the lncRNA signature model. Survival and receiver operating characteristic (ROC) curves were visualized in both groups. Further, we validated the model in the testing group. RESULTS: We screened 169 DELs for bladder cancer. The univariate Cox regression analysis showed that 13 lncRNAs were associated with prognosis with a p-value <0.01. We selected 12 of these lncRNAs to perform a multivariate Cox analysis to build the lncRNA signature. The formula with nine lncRNAs, namely, MIR497HG, LINC00968, NALCN-AS1, LINC02321, RNF144A-AS1, MNX1-AS1, FLJ22447, LINC01956, FLJ42969, was significantly related to prognosis. Patients in the high-risk group had a lower survival rate compared with the low-risk group in the training and testing sets (both p-values < 0.05) and the area of the ROC curve was 0.737 and 0.68, respectively. CONCLUSIONS: The study illustrated a significant lncRNA signature and indicated the risk score Cox model could be an important biomarker to predict the prognosis of bladder cancer.

Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489,and TMEM147-AS1,and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.

Laparoscopic transmesenteric pyeloplasty and isthmusectomy for adult horseshoe kidney with recurrent symptomatic hydronephrosis.

INTRODUCTION: There is no consensus for the horseshoe kidneys with recurrent symptomatic hydronephrosis, so we presented our initial experience with a laparoscopic transmesenteric approach. CASE PRESENTATION: Five patients with symptomatic ureteropelvic junction obstruction were identified by computed tomography urography. The laparoscopic transmesenteric approach was performed in such a way that the mesentery of the small intestine was incised along with the blood vessels longitudinally, and the isthmus was isolated to avoid injury to the mesenteric blood supply; then we cut the isthmus using an endostapler. The ureteropelvic junction obstruction was removed via the Anderson-Hynes technique. The operation time was 135-204 min, and the estimated blood loss was 50-120 mL. Patients had a 5.7-day stay postoperatively, there were no other injuries or complications, and ultrasound scans or computed tomography urography showed good postoperative effects. CONCLUSION: Laparoscopic transmesenteric surgery is a feasible and safe procedure for selected cases with horseshoe kidney with recurrent symptomatic hydronephrosis.

Magnesium supplementation enhances insulin sensitivity and decreases insulin resistance in diabetic rats.

OBJECTIVES: Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency. This study aimed to investigate the effects and mechanisms of magnesium supplementation on insulin receptor activity in elderly type 2 diabetes using a rat model and to provide experimental evidence for insulin resistance improvement by magnesium supplementation. MATERIALS AND METHODS: Rat model of type 2 diabetes was developed using a high-fat diet along with low dose streptozotocin (STZ) treatment. Magnesium supplement was given orally by mixing with the high-fat diet. Serum insulin level, insulin sensitivity, and insulin receptor affinity were assessed using radioimmunoassay (RIA). Insulin receptor, insulin receptor substrate (IRS-2), and ß-Arrestin-2 gene and protein expression levels were measured using immunohistochemistry and RT-PCR. Xanthine oxidase assay, thiobarbituric acid reactive substance assay (TCA method), colorimetric assay, and ELISA were used to determine the serum SOD, MDA, T-AOC, and ox-LDL levels, respectively. RESULTS: Magnesium supplementation enhanced insulin sensitivity and decreased insulin resistance in diabetic rats mainly through increasing insulin receptor expression, affinity, and augmenting insulin receptor signaling. Magnesium supplementation also inhibited lipid peroxidation in diabetic rats and protected against pancreatic cell injury in diabetic rats. In addition, we found that ß-arrestin-2 gene expression was suppressed in diabetes, which was possibly attributed to gene methylation modification, as ß-arrestin 2 promotor was rich in methylation-regulating sites. Magnesium supplementation could affect ß-arrestin-2 gene expression and methylation. CONCLUSION: Magnesium supplementation has a positive effect on insulin receptor activity and insulin sensitivity in type 2 diabetes.

The Effect of Dried Beancurd on Bone Mineral Density in Postmenopausal Chinese Women: A 2-Year Randomized Controlled Trial.

Soy foods contain several components such as isoflavones, calcium and protein that potentially modulate bone turnover and increase bone mineral density (BMD) in postmenopausal women. The study is to evaluate the effect of dried beancurd supplementation on skeletal health in postmenopausal Chinese women. Three hundred postmenopausal women aged 50-65 years were assigned into two groups, receiving 100 g dried beancurd or rice cake a day for 2 years. BMD at the lumbar spine and right proximal femur were measured with a dual-energy X-ray absorptiometry. The bone turnover biomarkers of serum alkaline phosphatase (ALP), bone Gla protein (BGP) and urinary N-telopeptide cross-links of collagen normalized for creatinine (NTX/CRT) were also determined. Serum isoflavone concentration was analyzed by high performance liquid chromatography. The 2-year dried beancurd supplementation generated a significant increase in lumbar spine BMD. An obvious decrease was found in urinary NTX/CRT, and a significant increase was detected in serum isoflavone concentration. The dried beancurd supplementation had no effect on changes of right proximal femur BMD and concentrations of serum ALP and BGP. Daily supplementation of dried beancurd could increase BMD of lumbar spine, but does not slow bone loss at right proximal femur in postmenopausal Chinese women.

Evaluation of the Effect of Sprout Soybeans on the Iron Status of Anemic Adolescent Girls in Rural China.

Soybeans are a major source of nonheme iron in Chinese diet. Germination is considered to be effective in improving iron bioavailability in soybeans. The study is to evaluate the effect of sprout soybean supplementation on the iron status of anemic adolescent girls in rural area of China and to compare it with the effect of soybeans. Two hundred and eighty eight adolescent girls were assigned to receive one of three dietary supplements (100 mL) a day for 6 m: 1) rice milk as the control (C); 2) sprout soybean milk (SS); 3) soybean milk (S). In addition to anthropometric measurements, iron status was measured at baseline and at the end of the study. After six months, the concentration of hemoglobin and plasma ferritin of participants in sprout soybean group were 138.6 ± 6.3 g/L and 43.3 ± 12.6 µg/L, significantly higher than those of the control. Significant decreases in the rate of anemia, iron deficiency and free erythrocyte protoporphyrin (FEP) concentration were found both in sprout soybean and soybean group. An obvious decrease in plasma transferritin receptor was found in the sprout soybean group comparing with the control, but not in the soybean group. Small but not significant differences were found in all iron indicators between the sprout soybean and soybean group. Sprout soybeans and soybeans could improve the iron status of anemic adolescent girls. Although sprout soybeans exhibited some priority to soybeans, no absolutely significant difference was found between them.

P38 Mitogen-activated Protein Kinase and Parkinson's Disease.

Parkinson's disease, the second major neurodegenerative disease, has created a great impact on the elder people. Although the mechanisms underlying Parkinson's disease are not fully understood, considerable evidence suggests that neuro-inflammation, oxidative stress, mitochondrial dysfunction, cell proliferation, differentiation and apoptosis are involved in the disease. p38MAPK, an important member of the mitogen-activated protein family, controls several important functions in the cell, suggesting a potential pathogenic role in PD. This review provides a brief description of the role and mechanism of p38MAPK in Parkinson's disease.

Characteristics of clinical drugs for elderly chronic heart failure complicated with different degrees of renal insufficiency.

OBJECTIVE: To investigate the characteristics of clinical therapeutic drugs in elderly chronic heart failure (CHF) patients complicated with different degrees of renal insufficiency. METHODS: The elderly patients who were hospitalized from October 2010 to October 2015 in our hospital due to CHF for the first time were selected by means of retrospective case collection. The glomerular filtration rate was estimated by using the Modification of Diet in Renal Disease (MDRD) Study equation. The patients were divided into a group with normal renal function, a group with slight decrease in renal function, and a group with moderate and severe decrease in renal function. Statistical analysis was made to compare the characteristics of clinical drugs for the three groups. RESULTS: Compared with the normal renal function group and the slight decrease group, ACEIs and ß-blockers were less used in the moderate and severe decrease group, but diuretics and spironolactone were more used (P<0.05). Compared with the normal renal function group, the use rate of ACEIs was low whereas that of diuretics was high (P<0.05). CONCLUSION: ACEIs and ß-blockers were barely employed to treat elderly CHF patients complicated with renal insufficiency, but diuretics and spironolactone were frequently utilized.

Intravenous injections of the oncolytic virus M1 as a novel therapy for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells. Knocking down ZC3HAV1 (ZAP), an antiviral factor in ISGs, restores M1 virus reactivity in resistant cells, and overexpressing ZAP partially reverses M1 virus-induced decreases in cell viability in sensitive cells. In orthotopic MIBC mice, tail vein injections of M1 significant inhibit tumor growth and prolong survival period, antitumor effects of M1 are stronger than those of the first-line chemotherapy agent cisplatin (CDDP). Treated tumors display enhanced cleaved-caspase-3 signals, which are representative of cell apoptosis, and decreased Ki-67 signals, which are representative of cell proliferation. Moreover, tissue microarray (TMA) analyses of clinical tumor specimens revealed that up to 45.6% of cases of MIBC presented with low ZAP expression, a finding that is prevalent in advanced MIBC. Our results indicate that the oncolytic virus M1 is a novel agent capable of functioning as a precise and effective therapy for MIBC.

Antihyperglycemic and Antihyperlipidemic Effects of Low-molecular-weight Carrageenan in Rats.

This study investigated the antihyperglycemic and antihyperlipidemic effects of low-molecular-weight carrageenan (LC) on rats fed a high-fat diet. Wistar rats were divided into five groups: normal control group (NC), high-fat diet control group (HC), carrageenan-treated control group (CC), 1% LC group (1% LC), and 3% LC-groups (3% LC). Body weight, food intake, fecal weight, blood glucose, and serum lipid levels were measured. After 30 days, body weight significantly decreased in the LC-treated groups than in the HC group. Moreover, in the LC-treated groups, postprandial blood glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels decreased, whereas high-density lipoprotein cholesterol (HDL-C) levels increased. From this study, our data suggest that LC has antihyperglycemic and hypolipidemic effects when compared to carrageenan, likely related to its increased absorption due to its lower molecular weight.

Gold-chrysophanol nanoparticles suppress human prostate cancer progression through inactivating AKT expression and inducing apoptosis and ROS generation in vitro and in vivo.

Controlled releasing of regulations remains the most convenient method to deliver various drugs. In the present study, we precipitated gold nanoparticles with chrysophanol. The gold-chrysophanol into poly (DL-lactide-co-glycolide) nanoparticles was loaded and the biological activity of chrysophanol nanoparticles on human LNCap prostate cancer cells, was tested to acquire the sustained releasing property. The circular dichroism spectroscopy indicated that chrysophanol nanoparticles effectively resulted in conformational alterations in DNA and regulated different proteins associated with cell cycle arrest. The reactive oxygen species (ROS), apoptosis, cell cycle, DNA damage, Cyto-c and caspase-3 activity were analyzed, and the expression levels of different anti- and pro-apoptotic were studied using immunoblotting analysis. The cytotoxicity assay suggested that chrysophanol nanoparticles preferentially killed prostate cancer cells in comparison to the normal cells. Chrysophanol nanoparticles reduced histone deacetylases (HDACs) to suppress cell proliferation and induce apoptosis by arresting the cell cycle in sub-G phase. In addition, the cell cycle-related proteins, including p27, CHK1, cyclin D1, CDK1, p-AMP-activated protein kinase (AMPK) and p-protein kinase B (AKT), were regulated by chrysophanol nanoparticles to prevent human prostate cancer cell progression. Chrysophanol nanoparticles induced apoptosis in LNCap cells by promoting p53/ROS crosstalk to prevent proliferation. Pharmacokinetic study in mice indicated that chrysophanol nanoparticle injection showed high bioavailability compared to the free chrysophanol. Also, in vivo study revealed that chrysophanol nanoparticles obviously reduced tumor volume and weight. In conclusion, the data above suggested that chrysophanol nanoparticles might be effective to prevent human prostate cancer progression.

Sesquiterpenoids from the twigs and leaves of Fokienia hodginsii.

A rare carotane-type sesquiterpenoid, forkienin A (1), a new eudesmane-type sesquiterpenoid, forkienin B (2), and a new natural eudesmane-type sesquiterpenoid, forkienin C (3), were isolated from the twigs and leaves of Fokienia hodginsii, along with eight known sesquiterpenoids. The structures of the new compounds were elucidated on the basis of their spectroscopic analysis, including 1D and 2D NMR methods. All compounds were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.

Slope stability analysis using limit equilibrium method in nonlinear criterion.

In slope stability analysis, the limit equilibrium method is usually used to calculate the safety factor of slope based on Mohr-Coulomb criterion. However, Mohr-Coulomb criterion is restricted to the description of rock mass. To overcome its shortcomings, this paper combined Hoek-Brown criterion and limit equilibrium method and proposed an equation for calculating the safety factor of slope with limit equilibrium method in Hoek-Brown criterion through equivalent cohesive strength and the friction angle. Moreover, this paper investigates the impact of Hoek-Brown parameters on the safety factor of slope, which reveals that there is linear relation between equivalent cohesive strength and weakening factor D. However, there are nonlinear relations between equivalent cohesive strength and Geological Strength Index (GSI), the uniaxial compressive strength of intact rock σ ci , and the parameter of intact rock m i . There is nonlinear relation between the friction angle and all Hoek-Brown parameters. With the increase of D, the safety factor of slope F decreases linearly; with the increase of GSI, F increases nonlinearly; when σ ci is relatively small, the relation between F and σ ci is nonlinear, but when σ ci is relatively large, the relation is linear; with the increase of m i , F decreases first and then increases.

[Clinical significance of ID4 methylation detection by quantitative methylation-specific PCR in acute leukemia].

The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (<1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

[Efficacy and safety analysis of interferon combined with imatinib in treating chronic myeloid leukemia].

Imatinib has been recognized as the frontline therapy drug in chronic myeloid leukemia (CML), however, only limited patients could achieve complete molecular remission (CMR). Recent clinical and basic proofs indicated an improved treatment outcome by the combination of interferon and Imatinib. This study was purposed to evaluated systematically the efficacy and safety of interferon plus Imatinib in patients with CML. Data from relative clinical trials were from clinical trial of gov and Cochrane Collaboration. A comprehensive literature search was performed from data bases such as pubMed and EM. The results indicated that 7 clinical trials and 12 research papers met the criteria enrolled in study, included 697 cases in total. The combination group had higher complete cytogenetic remission (CCgR) rate than imatinib alone at 6 months (58% vs 42%; P = 0.0001) and 12 months (74% vs 68%; P = 0.004). The major molecular remission (MMR) rate was also higher in the combination group at 6 months (58% vs 34%; P = 0.0001) and 12 months (66% vs 47%; P < 0.0001). Furthermore, compared with single drug, the combination group had superior CMR rate at 6 months (13% vs 2%; P = 0.0002) and 12 months (14% vs 5%; P = 0.0009). The major adverse effects of combination therapy were rash, asthenia, edema and musculoskeletal events, and combination therapy was more prone to inducing neutropenia, thrombocytopenia and mild anemia. It is concluded that compared with Imatinib alone, the combination of interferon and Imatinib has better clinical efficacy in treating CML with earlier cytogenetic and molecular remission. It is also a safe therapy in spite of slightly weaker tolerance than single drug therapy.