Bidirectional crosstalk of the cAMP/ROS-dependent signaling pathways in inflammatory macrophage: An activation of formononetin.

Bacterial lipopolysaccharide (LPS) is a toxic stimulant to macrophage inflammation. Inflammation intersects cell metabolism and often directs host immunopathogenesis stress. We aim here at pharmacological discovering of formononetin (FMN) action, to which anti-inflammatory signaling spans across immune membrane receptors and second messenger metabolites. In ANA-1 macrophage stimulated by LPS, and simultaneous treatment with FMN, results show the Toll-like receptor 4 (TLR4) and estrogen receptor (ER) signals, in concert with reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP), respectively. LPS stimulates inactivation of the ROS-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) by upregulating TLR4, but it does not affect cAMP. However, FMN treatment not only activates Nrf2 signaling by TLR4 inhibition, but also it activates cAMP-dependent protein kinase activities by upregulating ER. The cAMP activity gives rise to phosphorylation (p-) of protein kinase A, liver kinase B1 and 5'-AMP activated protein kinase (AMPK). Moreover, bidirectional signal crosstalk is amplified between p-AMPK and ROS, as FMN combinational validation with AMPK activator/inhibitor/target small-interfering RNA or ROS scavenger. The signal crosstalk is well positioned serving as the 'plug-in' knot for rather long signaling axis, and the immune-to-metabolic circuit via ER/TLR4 signal transduction. Collectively, convergence of the FMN-activated signals drives significant reduction of cyclooxygenase-2, interleukin-6 and NLR family pyrin domain-containing protein 3, in LPS-stimulated cell. Although anti-inflammatory signaling is specifically related to the immune-type macrophage, the p-AMPK antagonizing effect arises from FMN combination with ROS scavenger H-bond donors. Information of our work assists in predictive traits against macrophage inflammatory challenges, using phytoestrogen discoveries.

A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP. Here we report a direct sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100 unrelated healthy controls. We detected a heterozygous T to A transition at nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine codon (TCA) to a threonine codon (ACA). No such mutation was detected in the unaffected family members or the 100 unrelated healthy controls. Our results demonstrated a novel missense mutation in MVK gene. This will be valuable for the diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of affected families.

Fibroblasts/three-dimensional scaffolds complexes promote wound healing in rats with skin defects.

We aim to construct a three-dimensional nano-skin scaffold material in vitro and study its promoting effect on wound healing in vivo. In this study, hybrid constructs of three-dimensional (3D) scaffolds were successfully fabricated by combination of type I collagen (COL-1) and polylactic-glycolic acid (PLGA). Fibroblasts and human umbilical cord mesenchymal stem cells (hUCMSCs) were used to implanted into 3D scaffolds and constructed into SD skin scaffolds in vitro. Finally, the fibroblasts/scaffolds complexes were inoculated on the surface of rat wound skin to study the promoting effect of the complex on wound healing. In our study, we successfully built a 3D scaffold, which had a certain porosity. Meanwhile, the content of COL-1 in the cell supernatant of fibroblast/scaffold complexes was increased. Furthermore, the expression of F-actin, CD105, integrin ß, VEGF, and COL-1 was up-regulated in hUCMSC/scaffold complexes compared with the control group. In vivo, fibroblast/scaffold complexes promoted wound healing in rats. Our data suggested that the collagen Ⅳ and vimentin were elevated and collagen fibers were neatly arranged in the fibroblast/scaffold complex group was significantly higher than that in the scaffold group. Taken together, fibroblast/scaffold complexes were expected to be novel materials for treating skin defects.

Diabetes mellitus and increased risk of extrahepatic cholangiocarcinoma: a meta-analysis.

BACKGROUND/AIMS: Diabetes mellitus (DM) has been considered to be relevant to an increased risk of several different types of cancers. However, its relationship with extrahepatic cholangiocarcinoma (ECC) remains unclear. METHODOLOGY: To investigate a quantitative assessment of this relationship, we performed a meta-analysis to evaluate the association between diabetes and the risk of ECC. We identified studies by searching Embase (from 1 January 1974 to 30 June 2012), Medline (from 1 January 1966 to 30 June 2012), and the reference lists of related articles. Summary relative risks (RRs) with corresponding 95% CIs were calculated with a random-effects model. RESULTS: A total of 9 articles (4 case-control and 5 cohort studies) were included in this study. Compared with those without DM, individuals with DM had an increased risk of ECC (for case-control studies: summary OR=1.61, 95% CI: 1.05-2.49, p=0.063 for heterogeneity; for cohort studies: summary RR=1.61, 95% CI: 1.14-2.29, p=0.005 for heterogeneity). The funnel plot showed no evidence for publication bias concerning DM and the risk of ECC (Egger's test, p=0.699; Begg's test, p=0.175). CONCLUSIONS: These findings strongly reveal the positive link between DM and the increased risk of ECC.

Distribution pattern of medial group retropharyngeal lymph nodes and its implication in optimizing clinical target volume in nasopharyngeal carcinoma.

Purpose: This study aimed to determine the diagnostic value of diffusion-weighted imaging (DWI) and to elucidate the clinical characteristics of medial group retropharyngeal lymph nodes (RLNs) based on multi-modal imaging. Also, we intended to explore the feasibility of optimizing the CTV60 boundary based on the characteristics of medial group RLNs. Methods: A total of 549 patients with nasopharyngeal carcinoma received magnetic resonance imaging (MRI), DWI, and contrast-enhanced computed tomography (CT) to detect and evaluate clinical characteristics of medial group RLNs. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was utilized to identify fluorodeoxyglucose uptaking and contrast-enhanced CT to ensure the reliability of CTV optimization during radiotherapy. The DESdC (Drinking, Eating, Swallowing Difficulties, and Coughing while Eating or Drinking) score was utilized to evaluate swallowing disability. Results: Fourteen of 549 patients had medial group RLNs with a transverse diameter of 2.0-19.0 mm, which distributed between the upper margin of 1st cervical vertebra (C1) and the upper one-third of C3. Lasso regression and Pearson chi-square test suggested that its occurrence was associated with stage N, bilateral cervical lymph node metastases, especially when the transverse diameter of cervical lymph nodes was > 3 cm. The sensitivity of DWI, T2 STIR, and contrast-enhanced CT was 100%, 57.1%, and 21.4%, respectively. We optimized CTV60 of medial group RLNs from the base of skull to the upper edge of C2 excluding specific cases. For patients with CTV60 optimization, radiation dose and volume of swallowing structures decreased obviously. Based on our radiotherapy strategy on CTV60, acute toxicities of enrolled patients were well tolerated. Ninety-six of 549 patients had scores with DESdC score. Eighty-three patients scored 1, seven patients scored 2, one patient scored 3, and three patients scored 4. The median interval from the onset of symptoms was 72 (4-114) months. The 5-year overall survival, progression-free survival, local recurrence-free survival, and distant metastasis-free survival were 87%, 80%, 93%, and 85%, respectively. None of the patients with regional recurrence happened in the optimized region. Conclusion: DWI possesses superiorities in displaying lymph nodes. Based on the low incidence of the medial RLNs, CTV60 of medial group RLNs from the base of skull to the upper edge of C2 is feasible and has dosimetric advantages for protecting swallowing structures.

Immunotoxicity of 1-methyl-3-octylimidazolium bromide on brocarded carp (Cyprinus carpio L.).

In the present study, the immunotoxicity of 1-methyl-3-octylimidazolium bromide ([C(8)mim]Br) on brocarded carp was evaluated by an acute exposure of 100-300mgL(-1) of [C(8)mim]Br for 7 days. The results showed 300mgL(-1) of [C(8)mim]Br exposure caused activity inhibition of specific and non-specific immune systems, mainly including IgM level, lysozyme activity, and complement C3 content, while 100mgL(-1) of [C(8)mim]Br activated fish immune system during the early periods of exposure (2-5 days). This result indicates that [C(8)mim]Br has immunotoxicity on brocarded carp. Additionally, histological observation revealed that 300mgL(-1) of [C(8)mim]Br-exposure led to remarkable damages to the hepatopancreas, kidney, and spleen of brocarded carp after 7 days of [C(8)mim]Br treatment, although not only change in kidney and spleen somatic indexes was found, but also no swelling or hemorrhage of carp viscera occurred.

The relationship between occupational stressors and insomnia in hospital nurses: The mediating role of psychological capital.

Background: Nurses have a high incidence of insomnia. Insomnia not only damages the physical and mental health of nurses, but also reduces their productivity and quality of care, ultimately affecting patient care. Over the past 30 years, a large number of epidemiological surveys have shown that insomnia in nurses is associated with occupational stress. As an external feature of the role of a nurse, occupational stress is difficult to alter in a short period of time. Therefore, it is necessary to discuss the complex mediating variables in the relationship between occupational stress and insomnia in nurses in order to find different ideas to address the problem of insomnia caused by occupational stress. Psychological capital, the positive psychological strength of an individual, has been widely used in previous reports as a mediating variable between occupational stress and adverse psychological problems. Objective: This study aimed to explore the mediating effect of psychological capital on occupational stressors and insomnia among Chinese nurses. Methods: The Strengthening the Reporting of Observational Studies in Epidemiology statement was referred to conduct the study. A cross-sectional stratified sampling method was used to recruit 720 participants from a tertiary hospital in Jinan, Shandong province, located in the east of China, from June to August 2019. Questionnaires were used to obtain data on demographic variables, psychological capital, occupational stressors, and insomnia. Results: The study findings revealed that work settings [department (F = 3.08, p = 0.006), working hours per week (t = -2.03, p = 0.043) and shift work (t = 3.66, p < 0.001)], decision latitude (r = -0.25, p < 0.001), psychological job demand (r = 0.15, p < 0.001), social support (r = -0.31, p < 0.001), and psychological capital (r = -0.40, p < 0.001) were differentially associated with insomnia experiences. This cross-sectional survey showed that psychological capital has significant mediation effects on the relationship between occupational stressors and insomnia. In the model of decision latitude - psychological capital - insomnia, the mediating effect was-0.04 (95%CI: -0.07 ~ -0.02), accounting for 50.0% of the total effect; In the model of job demands - psychological capital - insomnia, the mediating effect was 0.03 (95%CI: 0.01 ~ 0.06), accounting for 25.0% of the total effect; In the model of social support - psychological capital - insomnia, the mediating effect was -0.11 (95%CI: -0.16 ~ -0.07), accounting for 39.0% of the total effect. Conclusion: Psychological capital not only had a direct effect on both occupational stressors and insomnia, but also played mediating roles in relationship between occupational stressors and insomnia. It has been suggested that nurses themselves and nursing managers should improve the psychological capital of nurses by various means to alleviate the effects of occupational stress on nurses' insomnia.

Liver fibrosis and hepatic stellate cells improvement of chronic hepatitis C patients by interferon-beta-1a with or without sustained viral response.

BACKGROUND/AIMS: We aimed to assess liver fibrosis in biopsies from patients with chronic hepatitis C and relationship to different responses to interferon-beta-la. METHODOLOGY: 21 patients with chronic hepatitis C were divided into two groups randomly and treated with recombinant human interferon-beta-la (IFN-B-1a) or IFN-beta-1a plus ribavirin (RBV) for 24 weeks, then followed up for another 24 weeks. 42 liver biopsies of 21 patients before and after treatment respectively were evaluated on conventional histological assessment. Then we studied 21 patients liver biopsies by immunohistochemical analysis of alpha-smooth muscle actin (alpha-SMA) and collagen type III. RESULTS: A significant improvement in HAI fibrosis staging was detected after therapy in all sustained viral responders (SVR) and non-responders (NR) patients. The percentages of cases with HAI scores and fibrosis staging decreased obviously were 100.0% and 71.4% in SVR patients and 50.0% and 42.9% in NR patients. The patients with combination therapy or normal ALT on 48w would more often receive the HAI and fibrosis staging decrease. The significantly lower alpha-SMA-positive HSCs and mean expression level of collagen type III were detected in the post-treatment biopsies. The HAI, alpha-SMA, collagen type III values were significantly correlated with the values of the semiquantitative indexes of fibrosis. CONCLUSIONS: IFN-beta-1a therapy is effective for patients with chronic hepatitis C on liver histology regardless of viral response. The alpha-SMA-positive HSCs and collagen type III expression are responsible for liver fibrosis.

[Effect of pegylated interferon beta-1a therapy on the liver fibrosis in chronic hepatitis C: a semi-quantitative analysis].

OBJECTIVE: To access the effect of pegylated interferon (PEGIFN) beta-1a on the reduction of liver fibrosis in chronic hepatitis C (HVC). METHODS: Twenty-one patients with chronic HVC were divided into two groups randomly and treated with recombinant human PEGIHN-beta-1a (n = 13) or PEGIHN-beta-1a plus ribavirin (RBV) (n = 8) for 24 weeks, and then followed up for another 24 weeks. The clinical manifestations were observed and the clinical effects were evaluated. Biopsy was conducted before and after the treatment to analyze the histological activity index (HAI) and staging of fibrosis according the modified Knodell scoring system. Immunohistochemical analysis was used to examine the levels of alpha-smooth muscle actin (alpha-SMA), marker of activation of hepatic stellate cells (HSCs), and collagen type III in the HSCs. RESULTS: Sustained viral response (SVR) was achieved in 7 patients, and end-of-treatment virologic response (ETVR) was achieved in 9 patients. The HAI after treatment was 4.3 +/- 2.2, significantly lower than that before treatment (6.6 +/- 2.2, t = 4.77, P < 0.01). The fibrosis score after treatment was 1.1 +/- 1.1, significantly lower than that before treatment (1.7 +/- 1.2, t = 1.92, P < 0.05). The alpha-SMA score after treatment was 14 +/- 8, significantly lower than that before treatment (20 +/- 11, t = 2.15, P < 0.05). The integrated light density of collagen type III after treatment was 10 +/- 10, significantly lower than that before treatment (16 +/- 12, t = 1.83, P < 0.05). The improvement levels of fibrosis, alpha-SMA score, and integrated light density of collagen type III of the patients with SVR were all better than those of the patients without SVR; however, the differences were all not significant. The patients with combination therapy, female patients, and the patients with the HCV RNA < 2 x 10(6) copies/ml before treatment all showed higher levels in histology response. HAI, alpha-SMA level, and collagen type III values were all significantly correlated with the values of the semiquantitative indexes of fibrosis (all P < 0.01). CONCLUSION: Resisting hepatitis virus C and inhibiting and reversing the fibrotic progress, IFN-beta-1a therapy improves the liver histology of chronic HVC regardless of the viral response.

Downregulation of miR-335-5p by Long Noncoding RNA ZEB1-AS1 in Gastric Cancer Promotes Tumor Proliferation and Invasion.

Recently, long noncoding RNAs (lncRNAs) have emerged as new gene regulators and prognostic biomarkers in several cancers, including gastric cancer (GC). In this study, we investigate the role of lncRNA ZEB1 antisense1 (ZEB1-AS1) on GC progression. In the present study, we found that ZEB1-AS1 expression was upregulated in GC tissues and cell lines. High ZEB1-AS1 expression was significantly correlated with advanced TNM stage, lymph node metastasis, and poor overall survival in GC patients. ZEB1-AS1 suppression reduced GC cell proliferation and invasion in vitro. Tumor formation assay in nude mice showed that ZEB1-AS1 inhibition suppressed GC cell growth. Quantitative real-time PCR showed that miR-335-5p expression was downregulated and negatively correlated with ZEB1-AS1 expression in GC tissues. And miR-335-5p expression was directly regulated by ZEB1-AS1. Furthermore, we found that inhibition of miR-335-5p abrogated the suppression of proliferation and invasion of GC cells induced by ZEB1-AS1 depletion. Collectively, ZEB1-AS1 is critical for the proliferation and invasion of GC cells by regulating miR-335-5p. Our findings indicated that ZEB1-AS1 might offer potential novel therapeutic targets for GC patients.

Genomic risk variants at 3q22.3 are associated with keloids in a Chinese Han population.

A keloid is the process of skin healing, collagen synthesis and metabolism of the loss of normal control in a sustained hyperactive state, resulting in excessive proliferation of collagen fibers. A large-scale genome-wide association study (GWAS) has identified multiple single nucleotide polymorphisms (SNPs) in the 3q22.3 loci that are associated with keloids in a Japanese population. However, the associations of SNPs in 3q22.3 with keloids were not confirmed in a selected Chinese population by a replication study. Thus, in the present study, the relationships between keloids and 3q22.3 were assessed in another independent Chinese Han population, including 309 keloid patients and 1080 control subjects. The results displayed that rs940187 was associated with keloids (OR=1.88, 95% CI 1.27-2.78, P=1.35E-3) and remained significant after Bonferroni's correction for multiple testing, while rs1511412 showed only a trend association (OR=2.23, 95% CI 1.09-4.55, P=0.02) with keloids. In addition, we subsequently checked the annotation datasets for rs940187 with eQTLs and obtained two hits, trans-proteins SLC7A9 and LEMD3, with significant P values less than 1e-4. In summary, genomic risk variants at 3q22.3 are associated with keloids in a Chinese Han population and contribute to the development and deterioration of the keloids, together with environmental factors.

A retrospective dosimetry study of intensity-modulated radiotherapy for nasopharyngeal carcinoma: radiation-induced brainstem injury and dose-volume analysis.

BACKGROUND: Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term complications. Patients who develop severe radiation-induced brainstem injuries have a poor prognosis due to the lack of effective medical therapies. However, the relationship between brainstem injury and radiation volume dose is unknown. In this study, we found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. METHODS: A retrospective analysis was performed on a consecutive cohort of 327 patients with NPC receiving IMRT from May 2005 to December 2014. Dose-volume data and long-term outcome were analyzed. RESULTS: The median follow-up duration was 56 months (range, 3-141 months), and six with T4 and two with T3 patients had radiation-induced brainstem injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The latency period of brainstem injury ranged from 9 to 58 months, with a median period of 21 months. The Cox regression analysis showed that brainstem radiation toxicity was associated with the T4 stage, D2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the Dmax, D1%, D0.1cc, and D1cc of the brainstem were significant predictors of brainstem injury. The area under the ROC curve for these five parameters was 0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were deemed as the radiation dose limit. CONCLUSIONS: Radiotherapy-induced brainstem injury was uncommon in patients with NPC who received definitive IMRT. Multiple dose-volume data may be the dose tolerance of radiation-induced brainstem injury.

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B.

AIM: To study the relationship between hepatitis B virus (HBV) DNA levels and liver histology in patients with chronic hepatitis B (CHB) and to determine the prevalence and characteristics of hepatitis B e antigen (HBeAg) negative patients. METHODS: A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status. The correlation between serum HBV DNA levels and liver damage (liver histology and biochemistry) was explored. RESULTS: Of the 213 patients with serum HBV DNA levels higher than 10(5) copies/mL, 178 (83.6%) were HBeAg positive, 35 (16.4%) were HBeAg negative. The serum HBV DNA levels were not correlated to the age, history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse (ALT), aspartate aminotransferase (AST) in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST, while serum DNA levels correlated with ALT (r=0.351, P=0.042). The grade (G) of liver disease correlated with ALT and AST (P<0.05, r=0.205, 0.327 respectively) in HBeAg positive patients. In HBeAg negative patients, correlations were shown between ALT, AST and the G (P<0.01, and r=0.862, 0.802 respectively). HBeAg negative patients were older (35 +/- 9 years vs 30 +/- 9 years, P<0.05 ) and had a longer history of HBV infection (8 +/- 4 years vs 6 +/- 4 years, P<0.05) and a lower HBV DNA level than HBeAg positive patients (8.4 +/- 1.7 Log HBV DNA vs 9.8 +/- 1.3 Log HBV DNA, P<0.001). There were no significant differences in sex ratio, ALT and AST levels and liver histology between the two groups. CONCLUSION: Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA more than 10(5) copies/mL. Compared to HBeAg positive patients, HBeAg negative patients are older and have a lower HBV DNA level and a longer HBV infection history. There is no significant difference in sex ratio, ALT and AST levels and liver histology between the two groups.

Basic Transcription Factor 3 Is Required for Proliferation and Epithelial-Mesenchymal Transition via Regulation of FOXM1 and JAK2/STAT3 Signaling in Gastric Cancer.

Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3) plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregulation of BTF3 reduced cell proliferation, induced S and G2/M cell cycle arrest, and increased apoptosis. Knockdown of BTF3 significantly reduced the expression of Forkhead box M1 (FOXM1). Upregulation of FOXM1 significantly inhibited the decrease in cell proliferation due to BTF3 silencing, S and G2/M cell cycle arrest, and increase in apoptosis. Knockdown of BTF3 decreased Ki-67 and PCNA expression, whereas it increased p27 expression, which was inhibited by upregulation of FOXM1. Knockdown of BTF3 significantly decreased the ability to invade and migrate. Moreover, knockdown of BTF3 increased E-cadherin expression, whereas it decreased N-cadherin and ZEB2 expression, indicating a decrease in epithelial-mesenchymal transition (EMT). Phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) was significantly inhibited by knockdown of BTF3. IL-6-stimulated phosphorylation of STAT3 and JAK2 markedly suppressed inhibition of EMT due to BTF3 silencing. Silencing of BTF3 decreased tumor volume and weight and reduced peritoneal nodules in implanted tumors. Our findings provide a novel understanding of the mechanism of GC and highlight the important role of BTF3/FOXM1 in tumor growth and BTF3/JAK2/STAT3 in EMT and metastasis.

Analysis of quality of life and influencing factors in 197 Chinese patients with port-wine stains.

Port-wine stains (PWS) are congenital capillary malformations, usually occurring on the face, neck, and other exposed parts of the skin, that have serious psychological and social impact on the patient. Most researchers focus on the treatment of PWS, but the quality of life (QoL) of PWS patients is seldom researched. The objective of this study is to evaluate the QoL of patients with PWS on exposed parts and explore the factors influencing the QoL of PWS patients. The QoL of 197 cases with PWS on exposed parts were prospectively studied using the Dermatology Life Quality Index questionnaire (DLQI), and the factors influencing the patients' QoL were analyzed by single-factor analysis and multiple-factor logistic regression analysis. The reliability and validity of the QoL of PWS patients were then assessed by DLQI. A total of 197 valid questionnaires were collected. The DLQI scores in PWS cases ranged from 2 to 16, with 2 to 5 in 52.29% (103/197), 6 to 10 in 42.13% (83/197), and 11 to 20 in 5.58% (11/197). The main score elements of the DLQI focused on symptoms and feelings, daily activities, and social entertainment. Single-factor analysis and multiple-factor logistic regression analysis showed that the main influencing factors were female sex, skin hypertrophy, and lesion area >30 cm. The inter-item correlation averaged 47.46% and the Cronbach α was 0.740, indicating high internal consistency. Correlation of the 6 dimensions of the DLQI questionnaires with the total scores showed that the Spearman correlation coefficient r ranged from 0.550 to 0.782 (P < .001), with symptoms and feelings having a correlation coefficient of 0.782 and a high correlation with total scores. This study shows that PWS has mild to moderate influence on the QoL of most patients, mainly on daily activities, social entertainment, and feelings.

NEDD4 single nucleotide polymorphism rs2271289 is associated with keloids in Chinese Han population.

Keloids are abnormally raised fibroproliferative lesions that usually occur following cutaneous traumas. Recently, a large-scale genome-wide association study (GWAS) has identified multiple single nucleotide polymorphisms (SNPs) in three genetic loci that are associated with keloids in Japanese population. Subsequently, two reported loci 1q41 (rs873549 and rs1442440) and 15q21.3 (rs2271289) for keloids were confirmed in selected Chinese population. The association of these SNPs with clinical features of keloids, has not yet been studied. To explore the role of these SNPs in the pathogenesis of keloids, we performed a case-controlled study in another independent Chinese Han population to analyze the correlation between 4 SNPs (rs873549, rs2118610, rs1511412, rs2271289) and keloids phenotypes. 309 keloids patients and 1080 control subjects were included. The results showed that, in the dominant mode of inheritance, the minor allele T of SNP rs2271289 had significantly higher odd ratios (ORs) in the severe keloid group compared with both the controls and the mild keloid group. The ORs were maintained after Bonferroni's correction (OR: 4.09, 95% CI: 1.78-9.37, P-value 3.25E-04). The ratio of the severe: mild OR for rs2271289 (dominant model) is (4.73/1.84=2.57). Similar associations in SNP rs2271289 were seen for groups with no family history and multiplesite compared with the control groups. No associations between keloid number, family history or severity relative to the controls were observed for the other three SNPs. Our data support that rs2271289 is strongly associated with severe keloids and might contribute to the complexity of clinical features of keloids.

LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma.

We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients.

[Thirteen to fourteen years' follow-up of patients with hepatitis C].

OBJECTIVE: To investigate the clinical outcomes and hepatic histology of patients with hepatitis C. METHODS: Nine patients with hepatitis, 4 males and 5 females, aged 44 +/- 7, who were infected during transfusion or blood donation underwent follow-up for 13 approximately 14 years: liver histological examination by biopsy, ultrasonography, biochemical examination of alanine transaminase (ALT), apartate aminotransferase (AST), and total bilirubin (TBIL), serum anti-HCV by ELISA, and HCV RNA quantification by PCR. RESULTS: ALT were higher than the normal value at every time point and HCV RNA remained positive (3.57 x 10(8) approximately 7.21 x 10(9) copies/L) in all patients. Ultrasonography showed mild and moderate hepatitis (3 and 6 cases respectively). The modified histological activity indices (HAI) were 5.0 approximately 8.5 and the fibrosis scores were 1 approximately 4. The ALT value was higher in the moderate cases than in the mild cases, and higher in those with higher HAI. The viral load was higher in the patients infected by the virus of the genotype 1b than in the patients infected by the virus of the genotype 2. CONCLUSION: The clinical outcomes and hepatic histology of patients with hepatitis C seem not very severe.

Clinical and epidemiological analysis of keloids in Chinese patients.

Keloids are common abnormally raised fibroproliferative lesions that can occur following even minor cutaneous trauma. There are limited data on Chinese patients with keloids, and the purpose of our study was to investigate the clinical and epidemiological features of keloids in Chinese patients. Assessment was performed by unified, designed questionnaires. A total of 715 patients were enrolled and statistical analysis and heritability were performed using EPI INFO 6.0, SPSS13.0 and Falconer's method. Keloids occurred typically between the ages of 10 and 30 years, and the mean age of initial onset was 21.14 ± 13.45 years in females and 22.55 ± 11.36 years in males. The difference in the mean age of onset was not significant between males and females (p > 0.05). A greater severity of keloids was observed in the positive history family group than in the negative history family group, and this difference was statistically significant (χ (2) = 10.889, p < 0.05). The formation of keloids in multiple anatomical sites was found to be significant in the positive family history group. This difference was statistically significant (χ (2) = 15.47, p < 0.001). The prevalence of keloids in first-, second- and third-degree relatives of the proband with keloids was 7.62, 0.38 and 0.035 %, respectively. These results were higher than those in controls and the difference of the prevalence rates of first- and second-degree relatives between probands and controls was significant (χ (2) = 224.63 and 12.078, respectively, p < 0.001). The heritability of keloids in first-, second- and third-degree relatives was 72.45, 40.55 and 17.07 %, respectively. Our findings revealed that the most severe forms of keloids were observed in the probands with positive family history, and the heritability in first-degree relatives of probands was 72.45 %. It is certain, therefore, that genetic factors play a role in the hereditary composition of keloids.

Detection of a novel missense mutation in the mevalonate kinase gene in one Chinese family with DSAP.

Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis and a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. Recently, the mevalonate kinase (MVK) gene has been identified as a candidate gene responsible for DSAP and multiple mutations have been reported. Here, we report identification of a novel missense mutation in the MVK gene in a Chinese family with DSAP. A 50-year-old male was diagnosed as proband of DSAP based on the clinical and histological findings, which show numerous hyperpigmented macules by physical examination and cornoid lamella by skin biopsy. Similar skin symptoms were also observed in his father, who died many years ago. We prepared genomic DNA from the proband, unaffected individuals from his family members, as well as 100 unrelated healthy controls. PCR was then conducted using the above genomic DNA as template and the MVK gene-specific primers. The PCR product was subjected to direct sequencing and the sequence was compared to that of MVK gene within the NCBI database. We detected a heterozygous C to G transition at nucleotide 643 in exon 7 of MVK gene of the proband. This will result in an amino acid change at codon 215 (P.Arg215Gly.), which is from an arginine codon (CGA) to a Glycine codon (GGA). We did not detect any mutation in the unaffected family members or the 100 unrelated healthy controls, demonstrating that this is a novel missense mutation in MVK gene and therefore, contributes to the molecular diagnosis of DSAP.