LncRNA DANCR regulates osteosarcoma migration and invasion by targeting miR-149/MSI2 axis.

OBJECTIVE: As a new LncRNA, anti-differentiated non-coding RNA (DANCR) plays an important role in tumorigenesis and development, and its molecular mechanism in osteosarcoma is unclear. In this study, by investigating osteosarcoma tissue and cells, we explored the molecular mechanism by which lncRNA DANCR regulates the occurrence and development of osteosarcoma by targeting the miR-149 / MSI2 axis. PATIENTS AND METHODS: In this study, osteosarcoma tissues and adjacent tissues in 109 patients were collected, and the relative expression of DANCR was detected by qPCR. The correlation between DANCR expression and clinical classification was statistically analyzed. In order to explore the potential molecular mechanism of DANCR related to tumor migration and invasion, an overexpression and silencing test was performed on the osteosarcoma cell line Saos-2, and then qPCR method was used to test the expression of miR149, and cell scratch test was used to detect invasion after DANCR silencing and miR149 overexpression. Transwell assay was used to detect the invasion after DANCR silencing and miR149 overexpression. Finally, Western blot was used to verify the expression of MSI2 protein after overexpression and silencing of miR-149. RESULTS: DANCR was significantly up-regulated in both osteosarcoma tissue and cells. The high expression of DANCR was significantly positively correlated with tissue typing and advanced TNM stage. DANCR can significantly reduce the migration and invasion of osteosarcoma cells. miRNA overexpression significantly reduced osteosarcoma cell migration and invasion. When miR-149 was overexpressed, MSI2 protein expression was significantly down-regulated. When miR-149 was silenced, MSI2 protein was significantly up-regulated. CONCLUSIONS: LncRNA DANCR plays an important regulatory role in the occurrence and development of osteosarcoma. It may be used as a potential target in the treatment of osteosarcoma in the future, by targeting the miR-149/MSI2 axis to regulate the occurrence and development of osteosarcoma.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

Prospective randomized controlled trial comparing treatment efficacy and tolerance of picosecond alexandrite laser with a diffractive lens array and triple combination cream in female asian patients with melasma.

BACKGROUND: Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC: fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions. OBJECTIVE: We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma. METHODS: Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals) or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12 and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively. RESULTS: Nine, 11 and 6 participants in groups A1, A2 and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2 and B, the improvement rates at week 20 were 53%, 38% and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores and brown spots after 3 laser sessions (P < 0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles and pores; however, only red areas were significantly different (P < 0.001). All side-effects in the 3 groups were transient and gradually subsided after 1-3 months. CONCLUSION: Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions.

Wound Closure after Thyroid and Parathyroid Surgery: A Meta-Analysis of Randomized Controlled Trials.

AIMS: Wound closure after thyroidectomy and parathyroidectomy is associated with patients' satisfaction, perception of cosmetic appearance, and experience of postoperative pain. Subcutaneous sutures, clips, and tissue adhesive are the three major methods of wound closure. In this study, we conducted a meta-analysis of randomized controlled trials to evaluate the outcomes of these methods. METHODS: Relevant studies published before December 2017 were identified from PubMed, Embase, Cochrane Library, Scopus, and the ClinicalTrials.gov registry. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using random-effect models. The primary outcome was the cosmetic appearance, which was evaluated 4 weeks, 6 weeks, and 6 months after surgery. The secondary outcomes were patient satisfaction, postoperative pain, and complications. RESULTS: A total of nine trials with 612 patients were reviewed. No significant difference was observed in patient satisfaction, postoperative pain, and complications among the wound closure methods. However, according to surgeon assessment, the subcutaneous suture method resulted in a significantly more favorable cosmetic appearance than the clip method (mean difference: -1.47, 95% confidence interval: -2.72 to -0.23). CONCLUSION: In the current study, no differences were found in patient satisfaction and postoperative pain among the subcutaneous suture, clip, and tissue adhesive wound closure methods. However, surgeons provided a more favorable appraisal for the subcutaneous suture method because of the improved cosmetic appearance. The choice of the closure method should be based on surgeon's preference and cost.

Comparison of indirubin concentrations in indigo naturalis ointment for psoriasis treatment: a randomized, double-blind, dosage-controlled trial.

BACKGROUND: Indigo naturalis and its refined formulation, Lindioil, are effective in treating psoriatic symptoms topically. Indirubin is the active ingredient in indigo naturalis. OBJECTIVES: To determine the efficacy and safety of different concentrations of indirubin in Lindioil ointment for treating psoriasis. METHODS: In this randomized, double-blind trial, adult patients presenting with chronic plaque psoriasis for > 1 year and with < 20% of the body surface area (BSA) affected were randomized to apply Lindioil ointment containing 200, 100, 50 or 10 µg g-1 of indirubin twice daily for 8 weeks followed by an additional 12-week safety/extension period. The primary end point was the mean percentage change in Psoriasis Area and Severity Index (PASI) score along with the proportion of participants achieving 75% and 90% reductions in PASI scores (PASI 75 and PASI 90, respectively) from baseline to week 8. RESULTS: The results from week 8 revealed that the 200 µg g-1 group had the greatest reduction in PASI score [69·2%, 95% confidence interval (CI) 55·5-82·8], followed by the 100 µg g-1 group (63·1%, 95% CI 52·8-73·5), the 10 µg g-1 group (53·4%, 95% CI 42·8-64·0) and the 50 µg g-1 group (50·3%, 95% CI 37·4-63·2), with a between-group comparison of P = 0·0445. The group with the highest proportion of the patients achieving PASI 75 (57%, P = 0·0474) and PASI 90 (30%, P = 0·0098) was the 200 µg g-1 group. No severe treatment-related adverse events were reported during the 20-week evaluation. CONCLUSIONS: An amount of 200 µg g-1 of indirubin in Lindioil ointment is the most effective concentration studied so far for treating psoriasis topically, and is safe.

Early improvement in PANSS-30, PANSS-8, and PANSS-6 scores predicts ultimate response and remission during acute treatment of schizophrenia.

OBJECTIVE: PANSS-8 and PANSS-6 are derived from the 30-item Positive and Negative Syndrome Scale (PANSS-30). We investigate whether PANSS-8 or PANSS-6 is a reliable, valid, sensitive to change measure, and scalable, and whether early improvement using them can predict response/remission. METHOD: Data were from 3 trials for 270 schizophrenia inpatients receiving antipsychotics. Internal consistency, validity, sensitivity to change, and scalability using PANSS-30, PANSS-8, and PANSS-6 at each assessment were examined. Early improvement was defined as at least 20% reduction of PANSS-30, PANSS-8, or PANSS-6 scores at week 2. Response was defined as at least 40% reduction of PANSS-30 and remission as a score of PANSS-8 ≤ 3 on each item at endpoint. Receiver operating characteristic analysis was used to determine which rating scale had better discriminative capacity. RESULTS: PANSS-8 and PANSS-6 showed acceptable internal consistency, were highly correlated with PANSS-30, and had sensitivity to change. PANSS-8 and PANSS-6 were scalable at each assessment, except for PANSS-6 at baseline. Early improvement using PANSS-8 or PANSS-6 had comparable predictive values with that of PANSS-30 for response/remission. CONCLUSION: PANSS-8 and PANSS-6 are clinically useful measures. Early improvement, regardless of whether PANSS-30, PANSS-8, or PANSS-6 is used, is a statistically significant predictor of response/remission.

The relationship between high-density lipoprotein cholesterol levels and arterial stiffness in a Taiwanese population.

BACKGROUND AND AIMS: There are few studies on the association between HDL-C levels and arterial stiffness (AS). HDL-C levels vary in males and females, and it is not clear whether the relationship between HDL-C levels and AS is influenced by gender. The purpose of this study was to investigate gender differences in the association between HDL-C levels and AS in adults. METHODS AND RESULTS: After excluding subjects using lipid-lowering agent, 7254 subjects were enrolled. The AS was assessed by measuring the brachial-ankle pulse wave velocity (baPWV) value. The quartiles of HDL-C were <38, 38-45, 45-53 and >53 mg/dL in men and <48, 48-57, 57-69 and >68 mg/dL in women, respectively. In subjects aged <50 years, none of the HDL-C quartiles were associated with baPWV values. In subjects aged ≥50 years, the highest quartile of HDL-C (beta: -37.57, 95% CI: -61.61 to -13.54) was negatively related to baPWV values. When considering gender difference in subjects aged ≥50 years, the highest quartile of HDL-C (Q4 beta: -57.22, 95% CI: -95.63 to -18.81) was inversely associated with baPWV values in women, but none of the HDL-C quartiles were related to baPWV values in men. CONCLUSIONS: A high HDL-C level was associated with a lower risk of AS in subjects aged ≥50 years in women but not in men, although this relationship was not apparent in subjects aged <50 years. The association between HDL-C level and AS is thus influenced by gender in people aged ≥50 years.

Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover.

Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously, consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicate that TH/PINK1/Parkin pathway has a critical role in protecting hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of TH facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T3 constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.

Are bilateral decubitus views necessary in assessing for vertebral compression fractures using DXA vertebral fracture assessment?

The purpose of this study is to assess the differences in VFA diagnostic accuracy when using bilateral decubitus views and whether diagnostic accuracy is affected by scoliosis. Our findings show that the current practice of performing only one side is valid; however, bilateral views can improve specificity in scoliosis. INTRODUCTION: The diagnostic accuracy of vertebral fracture assessment (VFA) can be influenced by poor patient position and scoliosis. This study aims to assess the differences in VFA diagnostic accuracy for right and left lateral decubitus views and the effect of scoliosis. METHODS: One hundred fourteen postmenopausal women received right and left lateral thoracolumbar spine dual-energy VFA and radiography. Cobb angles were measured from the posteroanterior absorptiometry image, and lumbar spine radiography was the standard reference for vertebral fracture and also provides the levels investigated. McNemar's test was used to compare accuracy between the two decubitus position and Fisher's exact test was used for patients with and without scoliosis. RESULTS: Forty-two vertebral fractures (VFs) were identified. There was no significant difference in sensitivity (p = 0.125) or specificity (p = 0.866) between the left lateral decubitus (64.3, 97.2%) and right lateral decubitus (76.2, 91.1%), respectively, views. Scoliotic patients had a significantly worse specificity (92.7 vs 98.1%, p = 0.003) than patients without scoliosis; however, a combination of both decubitus positions significantly improved specificity (p < 0.001). CONCLUSION: Right and left side lateral decubitus views have excellent agreement with radiography and similar diagnostic accuracy in the detection of VFs. Thus, the current practice of performing only one side is valid. With scoliosis, bilateral decubitus views can improve the specificity of detecting VF; however, this would increase radiation dose.

A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function.

BACKGROUND: Mutations in the DNAJB6 gene have been identified as a rare cause of dominantly inherited limb-girdle muscular dystrophy or distal-onset myopathy. MATERIALS AND METHODS: Exome sequencing was performed to investigate a Taiwanese family with a dominantly inherited distal-onset myopathy. Functional effects of the causal mutation were investigated in vitro. RESULTS: Exome sequencing of the two affected individuals in this family identified a heterozygous mutation, c.287C>T (p.Pro96Leu) in the DNAJB6 gene, which co-segregated with the myopathy within all 12 family members. Notably, this mutation is novel and localizes within the glycine and phenylalanine-rich (G/F) domain and alters an amino acid residue previously reported with a different mutation. Furthermore, immunofluorescence analyses and filter trap assay demonstrated that the c.287C>T (p.Pro96Leu) mutation possessed a dominant negative effect on the anti-aggregation function of DNAJB6 protein. CONCLUSION: This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy.

EGF-mediated inhibition of ubiquitin-specific peptidase 24 expression has a crucial role in tumorigenesis.

In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting cellular apoptosis and increasing cellular proliferation. Epidermal growth factor (EGF) treatment, and the KrasG12D and EGFRL858R mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604. Knockdown of USP24 decreases Bax and p300 levels, and reduces Ku70 acetylation, thereby preventing cancer cell apoptosis. In addition, knockdown of USP24 increases cell cycle progression by enhancing the G1-S transition and metaphase-anaphase transition. The molecular mechanism involves a decrease in the USP24 level, which reduces the expression of E2F4 and its partner TFDP1, and thus increases the G1/S transition. In conclusion, the USP24 level was decreased during the early stage of cancer and the mitotic stage of the cell cycle to regulate its substrates p300, Bax, E2F4 and securin, resulting in decreased cell apoptosis and increased cell cycle progression and, thus, cancer formation.

Hepatocarcinogenesis in transgenic mice carrying hepatitis B virus pre-S/S gene with the sW172* mutation.

Hepatitis B virus (HBV) carrying the rtA181T/sW172* mutation conferred cross-resistance to adefovir and lamivudine. Cell-based and clinical studies indicated that HBV carrying this mutation had an increased oncogenic potential. Herein, we created transgenic mouse models to study the oncogenicity of the HBV pre-S/S gene containing this mutation. Transgenic mice were generated by transfer of the HBV pre-S/S gene together with its own promoter into C57B6 mice. Four lines of mice were created. Two of them carried wild-type gene and produced high and low levels of HBV surface antigen (HBsAg) (TgWT-H and L). The other two carried the sW172* mutation with high and low intrahepatic expression levels (TgSW172*-H and L). When sacrificed 18 months after birth, none of the TgWT mice developed hepatocellular carcinoma (HCC), whereas 6/26 (23.1%) TgSW172*-H and 2/24 (8.3%) TgSW172*-L mice developed HCC (TgWT vs TgSW172*; P=0.0021). Molecular analysis of liver tissues revealed significantly increased expression of glucose-regulated protein 78 and phosphorylated extracellular signal-regulated kinases 1 in TgSW172* mice, and decreased expression of B-cell lymphoma-extra large in TgSW172*-H mice. Higher proportion of apoptotic cells was found in TgSW172*-H mice, accompanied by increased cyclin E levels, suggesting increased hepatocyte turnover. Combined analysis of complimentary DNA microarray and microRNA array identified microRNA-873-mediated reduced expression of the CUB and Sushi multiple domains 3 (CSMD3) protein, a putative tumor suppressor, in TgSW172* mice. Our transgenic mice experiments confirmed that HBV pre-S/S gene carrying the sW172* mutation had an increased oncogenic potential. Increased endoplasmic reticulum stress response, more rapid hepatocyte turnover and decreased CSMD3 expression contributed to the hepatocarcinogenesis.

Increased serum interleukin-6, not minimal hepatic encephalopathy, predicts poor sleep quality in nonalcoholic cirrhotic patients.

BACKGROUND: Sleep-wake disturbances are common in patients with cirrhosis and have a considerable effect on health-related quality of life; however, the underlying mechanism behind the phenomenon is unclear. Cytokines are involved in the mediation of signalling pathways regulating fibrogenesis, leading to cirrhosis. In addition, increased cytokines could contribute to sleep disturbances. AIM: To determine the relationship between pro-inflammatory cytokines and sleep disturbance in cirrhotic patients. METHODS: Ninety-eight nonalcoholic cirrhotic patients without overt hepatic encephalopathy were enrolled in this cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Psychometric Hepatic Encephalopathy Score (PHES) was used to examine cognitive performance and define minimal hepatic encephalopathy (MHE). The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the mood status of the patients. Pro-inflammatory cytokines that include interleukin 6 (IL-6) and tumour necrosis factor-α, as well as HBV-DNA or HCV-RNA levels were determined in patients. RESULTS: A total of 56 (57%) cirrhotic patients were identified as 'poor' sleepers (PSQI > 5). After multivariate analysis, IL-6 (P = 0.001) and HADS scores (P = 0.002) were found to be independent predictive factors of poor sleep quality. No significant relationships were observed between the sleep indices and the presence of MHE. HCV-RNA, but not HBV-DNA, viraemia was associated with sleep disturbance in cirrhotic patients. CONCLUSIONS: Sleep disturbance is found commonly in cirrhotic patients and a high serum IL-6 level is predictive of poor sleep quality. Minimal hepatic encephalopathy by itself may not contribute to sleep dysfunction in cirrhotic patients.

Comparison of nocturia response to desmopressin treatment in elderly men with and without nocturnal polyuria in real-life practice.

OBJECTIVES: To evaluate the safety and efficacy of low-dose desmopressin in elderly men with and without nocturnal polyuria (NP) in real-life practice. METHODS: Patients with lower urinary tract symptoms (LUTS)/ benign prostate hyperplasia (BPH) who were≧ 65 years old with refractory nocturia were enrolled in this study. We retrospectively analysed elderly men treated with adding desmopressin to current medications for nocturia according to category of the baseline nocturnal urine volume. The 48-h frequency volume chart (FVC), International Prostate Symptom Score (IPSS) and quality of life (QoL) were initially assessed and re-evaluated 12 weeks later. Serum sodium level was checked 1 week, 4 weeks, and 12 weeks after initiation of desmopressin therapy or suspected hyponatremia event. The mean change in numbers of nocturnal voids was evaluated for efficacy of treatment. RESULTS: A total of 136 patients were included with 55 in non-NP group and 81 in NP group. Hypertension was more common in NP group in regard of comorbidities. During treatment period, there were significant reductions of nocturnal voids from 4.22 ± 1.38 to 2.31 ± 0.98 (p < 0.001) in non-NP group and from 4.52 ± 1.23 to 2.07 ± 0.89 (p < 0.001) in NP group. The reduction in nocturnal voids was more significant in NP group (2.44 ± 1.15 vs. 1.91 ± 1.48, p = 0.003). The mean decrease in serum sodium levels were 3.89 ± 1.22 mmol/l (p < 0.001) in non-NP group and 4.69 ± 3.5 mmol/l (p < 0.001) in NP group at the extreme value. CONCLUSIONS: Long-term treatment with low-dose desmopressin is safe and effective for nocturia with or without NP in elderly patients with LUTS/BPH during real-life practice. Patients should be well informed about the disease and are closely followed.

Interaction between hepatic membrane type 1 matrix metalloproteinase and acireductone dioxygenase 1 regulates hepatitis C virus infection.

Membrane type 1 matrix metalloproteinase (MT1-MMP) binds to and regulates the function of tetraspanin-enriched microdomains. It also physically interacts with claudin-1 and acireductone dioxygenase 1 (ADI1), both associated with hepatitis C virus (HCV) cell entry. Here, we examined hepatic expression of MT1-MMP, ADI1 and claudin-1 as well as their physical interaction in relation to serum or intrahepatic HCV-RNA levels. A total of 104 liver biopsies obtained from chronic hepatitis C patients and 84 liver tissues obtained from noncancerous parts of surgically removed HCV-related hepatocellular carcinoma were analysed. Positive cytoplasmic ADI1 in liver biopsies was associated with higher serum HCV-RNA levels (P = 0.009). Positive MT1-MMP and ADI1 interaction assessed by co-immunoprecipitation was associated with lower tissue HCV-RNA levels (P = 0.009). Hepatic HCV-RNA levels were positively associated with ADI1 levels in the MT1-MMP and ADI1 co-immunoprecipitates (P = 0.030). Overexpression of MT1-MMP in Huh7.5 cells suppressed cell entry of HCV pseudoparticles as well as HCVcc infection. The suppression effect could be reversed by co-expression of ADI1 in a dose-dependent manner. In summary, clinical and cell-based experiments suggested that physical interaction between MT1-MMP and ADI1 led to suppression of HCV infection. This inhibitory effect could be reversed by ADI1 overexpression.

Quality of life in cervical cancer treated with systematic nerve-sparing and modified radical hysterectomies.

The aim of this study was to compare the quality of life (QoL) between cervical cancer patients treated with systematic nerve-sparing radical hysterectomy (SNSRH) and modified radical hysterectomy (MRH). A total of 127 patients with early cervical cancer treated with radical hysterectomy (RH) were included in the study. The patients were divided into two groups: MRH group (n = ) and SNSRH group (n = ). The patients' QoL scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 questionnaire (Chinese version). The overall QoL scores were no different between the SNSRH and MRH groups in preoperative period (P > 0.05). In postoperative period, the overall QoL score in SNSRH group was slightly lower than that in MRH group at different follow-up time, but there was no difference between two groups (P > 0.05). Patients with early cervical cancer subjected to SNSRH or MRH are satisfied with their overall QoL scores. QoL may be negatively impacted by the cancer itself, surgery and adjuvant therapy.

Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer

Purpose: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. Materials and methods: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. Results: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPKsignaling pathway and PPAR signaling pathway. Conclusions: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress (AU)

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Incidence and antiviral response of hepatitis C virus reactivation in lupus patients undergoing immunosuppressive therapy.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease and usually requires immunosuppressive therapy, which is a major cause of viral reactivation. The incidence and antiviral response in SLE patients with hepatitis C virus (HCV) reactivation is unclear and needs to be investigated. METHODS: One hundred and sixty-six SLE patients with antibody to HCV (anti-HCV) status were retrospectively reviewed regarding the events of HCV reactivation. Patients with HCV reactivation were treated with pegylated interferon plus ribavirin treatment. The virological response and relapse rate were evaluated. RESULTS: Twenty-six patients were positive for anti-HCV. During a mean 8.4 years of follow-up, 10 (38.5%) cases developed HCV reactivation. No clear relationship was noted between immunosuppressive therapy and the HCV reactivation. Eight patients underwent antiviral therapy and the rapid virological response (RVR), early virological response, and sustained virological response (SVR) rates were 37.5%, 87.5%, and 75.0%, respectively. However, late relapse (reappearance of HCV RNA in serum after archiving SVR) was found in two (33.3%) of six patients achieving SVR. The two cases were HCV genotype 1 b concurrent with corticosteroid treatment. CONCLUSIONS: HCV reactivation in anti-HCV-positive SLE patients was possibly associated with glucocorticoids. The virological response to interferon plus ribavirin treatment is not inferior to the general population. However, monitoring HCV RNA after SVR is necessary for patients concurrent with corticosteroid treatment due to the risk of late relapse.

IFI27, a novel epidermal growth factor-stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes.

OBJECTIVES: IFI27 is highly expressed in psoriatic lesions but its function has not been known. The present study aimed to explore its role in proliferation of epidermal keratinocytes. MATERIALS AND METHODS: IFI27 knockdown and over-expression in keratinocytes were used to compare their proliferation, by MTT assay, apoptosis (by annexin V binding) and cell cycle progression by flow cytometry. Formation of cyclin A/CDK1 complex was examined by a co-immunoprecipitaion method. Anti-proliferation effects of IFI27 were also examined in vivo by topical application of IFI27 siRNA on imiquimod-induced psoriatic lesions, in a mouse model. RESULTS: Epidermal growth factor was demonstrated to increase IFI27 expression by prolonging half-life of IFI27 protein. The IFI27 knockdown in keratinocytes reduced the proliferation rate, but had no effect on apoptosis nor on apoptosis-related genes. Interestingly, IFI27 knockdown resulted in S-phase arrest that was found to be associated with increased Tyr15 phosphorylation of CDK1, reduced CDC25B and reduced formation of cyclin A/CDK1 complex. In addition, IFI27 knockdown was also shown to activate p53 by Ser15 phosphorylation and increase p21 expression. Topical application of IFI27 siRNA on imiquimod-induced psoriatic lesion in a mouse model reduced epidermal thickness, formation of rete ridges and PCNA expression. CONCLUSIONS: Our study demonstrates for the first time, that cell function of IFI27 is involved in proliferation of skin keratinocytes both in vitro and in vivo. It suggests that IFI27 might be a suitable target for development of a novel anti-psoriasis therapy.