Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-κB/IRF7/JAK-STAT signalling pathway and apoptosis.

1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells.2. The half toxic concentration (CC50) of palmatine was 672.92 µM, the half inhibitory concentration (IC50) of palmatine against IBV was 7.76 µM and the selection index (SI) was 86.74.3. Mode of action assay showed that palmatine was able to directly inactivate IBV and inhibited the adsorption, penetration and intracellular replication of IBV.4. Palmatine significantly upregulated TRAF6, TAB1 and IKK-ß compared with the IBV-infected group, leading to the increased expressions of pro-inflammatory cytokines IL-1ß and TNF-α in the downstream NF-κB signalling pathway.5. Palmatine significantly up-regulated the levels of MDA5, MAVS, IRF7, IFN-α and IFN-ß in the IRF7 pathway, inducing type I interferon production. It up-regulated the expression of 2'5'-oligoadenylate synthase (OAS) in the JAK-STAT pathway.6. IBV infection induced cell apoptosis and palmatine-treatment delayed the process of apoptosis by regulation of the expression of apoptosis-related genes (BAX, BCL-2, CASPASE-3 and CASPASE-8).7. Palmatine could exert anti-IBV activity through regulation of NF-κB/IRF7/JAK-STAT signalling pathways and apoptosis, providing a theoretical basis for the utilisation of palmatine to treat IBV infection.

[Correlation between arousal threshold and occurrence of hypertension in patients with obstructive sleep apnea hypopnea syndrome].

Objective: To investigate the relationship between arousal threshold (ArTH) and hypertension in patients with obstructive sleep apnea hypopnea syndrome (OSA). Methods: This study recruited 648 patients diagnosed with OSA at the Sleep Center of the Second Affiliated Hospital of Soochow University from January 2020 to August 2021, including 569 males and 79 females, aged 42(35,52) years. The basic demographic information and clinical data of all patients were collected, including blood pressure measurement, and relevant questionnaire scores, and nocturnal polysomnography (PSG) parameters. A clinical predictive model based on sleep apnea hypopnea index (AHI), lowest pulse oxygen saturation (LSpaO2) and hypopnea ratio (FHypopneas) was used to access the arousal threshold of OSA patients. Patients were divided into OSA group and OSA with hypertension group according to whether they were combined with hypertension. The differences in the above indexes between the two groups were analyzed to explore the relationship between arousal threshold and hypertension in OSA patients, using a binary logistic stepwise regression analysis. Results: A total of 648 OSA patients were enrolled, including 415 in the OSA with hypertension group and 233 in the OSA group. Compared with OSA group, OSA with hypertension group had older age, higher body mass index (BMI), higher blood pressure at bedtime and at awakening, higher AHI and lower proportion of hypopnea (all P<0.05). There were no significant differences between other general data and PSG parameters (all P>0.05). The proportion of patients with low arousal threshold (AHI<30 events per hour, LSpO2>82.5%, Fhypopneas>58.3%) in OSA with hypertension group was lower, and the proportion of phenotypic patients with low arousal threshold was significantly lower (30.1% vs. 52.4% P<0.001). Binary logistic stepwise regression analysis showed that the high arousal threshold (OR=1.930, 95%CI:1.326-2.808, P=0.001) was an independent risk factor for OSA complicated with hypertension. Conclusion: The arousal threshold is associated with the development of hypertension in OSA patients, and OSA patients with a high arousal threshold have a higher risk of developing hypertension.

Analyzing the incidence of silicosis across various industries in Taiwan: a study of occupational disease surveillance by linking national-based workers' and medicoadministrative databases.

OBJECTIVES: This study aimed to establish an occupational disease surveillance system by identifying high-risk industries for silicosis in Taiwan using a national database linkage approach. METHODS: The study was based on a comprehensive analysis of benefit claims from the National Labor Insurance Research Database and medical records from the National Health Insurance Research Database between 2004 and 2020, providing coverage for more than 88.5% of the workforce and 99.9% of citizens. Silicosis was defined as having received compensation for labor insurance benefits or having received a diagnosis of silicosis (International Classification of Diseases, 10th Revision: J62 or International Classification of Diseases, Ninth Revision: 502). The study used the International Standard Industrial Classification of All Economic Activities for industry-specific classification. Cox proportional hazard models were used to compare the silicosis incidence and risk among each industry and identify high-risk industries for silicosis. RESULTS: This study analyzed 1466 cases of silicosis between 2004 and 2020 and found that 28 industries had incidence rates of over 40 cases per 100,000 workers, indicating more than double the risk of developing silicosis. Of these industries, 14 were considered high risk (relative risk of over four times). Among these, this study identified industries rarely mentioned in the past, such as wholesale of brick, sand, cement, and products, artistic creation, landscape construction, and materials recovery. Stratification by years of work experience reveals those industries such as quarrying of stone, sand, clay, and other mining, construction of buildings, landscape construction, site preparation, foundation and structure construction, building completion and finishing, manufacture of ships, boats, and floating structures, and plumbing, heat, and air conditioning installation display higher hazard ratios for individuals with <10 years of work experience. CONCLUSIONS: The current surveillance system has identified certain industries that are at a higher risk of developing silicosis, which could be used for future occupational epidemiological surveys and targeted preventive measures in these sectors.

[Alertness and task processing speed impairment status and influencing factors of young-middle aged men with obstructive sleep apnea hypopnea syndrome].

Objective: To investigate the alertness and task processing speed impairment status in young-mild aged men with obstructive sleep apnea hypopnea syndrome (OSAHS), and analyze its influencing factors. Methods: This prospective study recruited 251 snoring patients aged 18 to 59 (38.9±7.6) years in the Sleep Center of the Second Affiliated Hospital of Soochow University from July 2020 to September 2021 and all patients were diagnosed by polysomnography (PSG). Clinical information, Epworth Sleepiness Scale (ESS) and PSG date were collected. All patients were assessed with the Montreal Cognitive Assessment (MoCA) questionnaires, Mini-mental State Examination (MMSE) and Computerized Neurocognitive Assessment System which includes the reaction time of Motor Screening Task (MOT) for alertness, the reaction time of pattern recognition memory (PRM), spatial span (SSP) and spatial working memory (SWM) for task processing speed. Based on AHI tertiles, all patients were divided into Q1 group (AHI<15 times/h, n=79), Q2 group (15 times/h≤AHI<45 times/h, n=88), and Q3 group (AHI≥45 times/h, n=84). The characteristics of clinical information, ESS, PSG parameters and cognitive scores among three groups were compared. Multiple linear stepwise regression was conducted to analyze the influencing factors of cognitive impairment. Results: There were no statistically significant differences in age, years of education, history of smoking and drinking, and past disease history (except for the prevalence of hypertension) among the 3 groups (P>0.05). There were statistically significant among-group differences in the body mass index (BMI), ESS, prevalence of hypertension and complaints of daytime sleepiness (P<0.05). Compared with Q1 and Q2 group, the arousal index (ArI), oxygen desaturation index (ODI),the proportion of non-rapid eye movement phase 1 and 2 (N1+N2) and percentage of total sleep time with oxygen saturation level<90% (TS90) of Q3 group were higher (all P<0.05). In the cognitive assessment, there was no statistically significant difference in the MoCA total and individual scores and MMSE scores among the three groups (P>0.05). Compared with the Q1 group, the task processing speed and alertness were worse in Q3 group, as shown by slower PRM immediate and delayed reaction time, SSP reaction time and MOT reaction time (all P<0.05). The total time of SWM in Q2 group was slower than that in Q1 group (P<0.05). Multiple linear stepwise regression showed that years of education (ß=-40.182, 95%CI:-69.847--10.517), ODI (ß=3.539, 95%CI: 0.600-6.478) were the risk factors of PRM immediate reaction time. Age(ß=13.303,95%CI: 2.487-24.119), years of education(ß=-32.329, 95%CI:-63.162--1.497), ODI (ß=4.515, 95%CI: 1.623-7.407) were the risk factors of PRM delayed reaction time. ODI was the risk factor of SSP reaction time (ß=1.258, 95%CI: 0.379-2.137). TS90 was the risk factor of MOT reaction time (ß=1.796, 95%CI: 0.664-2.928). Conclusions: The early cognitive impairment in young-mild aged OSAHS patients was manifested in decreased alertness and task processing speed, and intermittent nocturnal hypoxia was its influencing factor in addition to age and years of education.

[Analysis of dynamic functional connectivity states and influencing factors of brain network in male patients with obstructive sleep apnea].

Objective: To analyze dynamic functional connectivity (dFNC) states and influencing factors of brain network in male patients with obstructive sleep apnea (OSA). Methods: A total of 111 male patients diagnosed with obstructive sleep apnea or presenting with simple snoring, who visited the Sleep Clinic at the Second Affiliated Hospital of Soochow University between August 2020 and December 2021, were prospectively selected for this study. General information was collected, and polysomnography (PSG) was performed. Based on the oxygen desaturation index (ODI), the participants were divided into three groups: primary snoring group (ODI<5 events/hour, n=34), mild to moderate OSA group (5 events/hour≤ODI<30 events/hour, n=43), and sever OSA group (ODI≥30 events/hour, n=34). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Resting-state functional magnetic resonance imaging (fMRI) data were collected and preprocessed. dFNC matrices were constructed using a sliding time window approach. The number of dFNC states was determined using k-means clustering analysis. Three parameters, namely, fractional time (FT), mean dwell time (MDT), and number of transitions (NT), were used to characterize the temporal properties of dFNC states. Differences in the temporal properties of dFNC states among the groups were compared. The correlations between temporal properties and PSG parameters, as well as MoCA and ESS scores, were further analyzed. Multiple stepwise linear regression analysis was performed to identify the influencing factors of the temporal properties of dFNC states. Results: The age of the patients was (40.2±8.6) years (range: 25-65 years). There were no significant differences in age, smoking history and alcohol history, and MoCA scores among the three groups (all P>0.05). Three dFNC states were extracted through k-means clustering analysis: state 1, characterized by strong connections within the visual and sensorimotor networks with a frequency of 31.7% (4 611/14 541); state 2, characterized by strong connections within the default mode network, attention network, and other cognitive networks, with the lowest frequency of 22.1% (3 213/14 541); state 3, characterized by weaker connections across the whole brain, with the highest frequency of 46.2% (6 717/14 541). The FT [0.28 (0.05, 0.35) vs 0.39 (0.26, 0.53)] and MDT [8.20 (4.35, 12.54) vs 11.68 (8.50, 16.69)] of state 2 in the sever OSA group were lower than those in the primary snoring group (both P<0.05), while there were no significant differences in the temporal properties of states 1 and 3 among the three groups (all P>0.05). The FT and MDT of state 2 were correlated with body mass index (BMI), apnea-hypopnea index (AHI), ODI, and minimum oxygen saturation (MinSaO2) (FT: r values were -0.218, -0.230, -0.249, 0.198, respectively; MDT: r values were 0.269, -0.253, -0.265, 0.209, respectively; all P<0.05). There were no significant correlations between the temporal properties and MoCA or ESS scores (all P>0.05). ODI was found to be an influencing factor for the temporal properties of state 2 (FT: ß=-0.225, 95%CI:-0.227 to -0.223; MDT: ß=-0.241, 95%CI:-0.289 to -0.195). Conclusions: Male patients with OSA exhibit alterations in specific temporal properties of brain network dynamic functional connectivity, which are associated with nocturnal oxygen parameters. This may be one of the mechanisms underlying brain functional damage in patients with OSA.

[Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study].

Objective: To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection. Methods: Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A,n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B,n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results: After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A (χ2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% (χ2=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% (χ2=0.992,P=0.319). Conclusions: Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

A systematic review of olfactory related questionnaires and scales.

PURPOSE: Although neglected by science for a long time, the sense of olfaction has received increasing attention from research areas including psychology, neuroscience, clinical medicine and nutrition. With the rise of psychophysical and neuroimaging re- search into olfaction, psychometric tools (e.g. questionnaires and scales) are the basis for the quantitative exploration of inter-in- dividual variability regarding olfactory related responses. The current systematic review is to summarize existing olfaction related questionnaires and/or scales. METHODS: Peer-reviewed literature on scales and questionnaires related to perception of odors were searched from online databa- ses (PubMed, Web of Science and PsycINFO). Twenty-one articles that meet the following criteria were included in the review: "human species", "physical odor stimuli" and "describing the original development of the tool" and "specific focus on olfaction or odor related responses or behaviors". The psychometric properties, advantages and possible disadvantages were discussed. RESULTS: Existing psychometric measures focus on various aspects of olfactory related responses and behaviors, including af- fective experiences of odor perception, awareness and attitude towards olfaction, olfactory function and the quality of life change due to olfactory dysfunction, and the ability to create vivid mental odor images. While most of them have been tested to have good reliability and validity, some were relatively time-consuming due to the number of questionnaire items. Besides, although many measures have been used in clinical populations, few have provided information on the predictive validity regarding effecti- veness of clinical intervention on changes of certain responses or behaviors. SUMMARY: The current review provides an overview of olfactory related questionnaires and scales, highlighting the emotional and affective impact of olfaction and the impact on quality of life due to olfactory dysfunction. With growing interest in olfaction as an important sense, the development and use of psychometrically sound measurements in conjunction with objective assess- ments will advance our understanding of human olfaction and olfactory dysfunction. The review provides a guide for researchers and clinicians alike to select olfactory scales suitable for olfactory research with different experimental purposes and specific samples.

[Clinicopathological characteristics and prognosis of IgG4-related kidney disease].

The clinical data of 18 patients with biopsy-proven IgG4-related kidney disease (IgG4-RKD) in Peking University First Hospital from Jananuary 2012 to Jananuary 2017 were analyzed retrospectively. The prevalence of elevated IgG4 and hypocomplement C3 were commonly found. Acute kidney disease accounted for 9 cases. Pathological examination showed IgG4 associated tubulointerstitial nephritis, with IgG4-ANCA or anti-PLA2R associated crescentic nephritis in 3 cases, and membranous nephropathy in 2 cases. Patients with erythrocyte sedimentation rate>60 mm/1 h had higher acute tubulointerstitial injury scores. Improved renal function was observed in 15 patients under immunosuppressive therapy. But 3 patients relapsed during follow-up. IgG4-RKD with concurrent glomerulopathy is not uncommon. Biopsy-based kidney examination is recommended.

[Proactive cognitive psychiatry while aging]. / Proactieve cognitieve psychiatrie bij het ouder worden.

BACKGROUND: COGNITIVE SYMPTOMS ARE COMMONLY REPORTED IN PATIENTS WITH UNIPOLAR OR BIPOLAR MOOD DISORDER. THE PREVALENCE OF COGNITIVE SYMPTOMS INCREASES WITH AGEING. THE PRESENCE AND EXTENT OF COGNITIVE SYMPTOMS HAS A DIRECT NEGATIVE IMPACT ON RECOVERY OF THE PSYCHIATRIC ILLNESS AND QUALITY OF LIFE.
AIM: IMPROVING OUTCOME OF OLDER PATIENTS WITH A UNIPOLAR OR BIPOLAR MOOD DISORDER.
METHOD: REVIEW OF AVAILABLE INTERVENTIONS TO IMPROVE COGNITIVE FUNCTIONING DIRECT OR INDIRECT.
RESULTS: STRATEGY TRAINING, TRAINING OF COGNITIVE FUNCTIONS AND PHYSICAL EXERCISE HAVE SHOWN TO BE EFFECTIVE TO IMPROVE COGNITIVE FUNCTIONING AND ITS POSSIBLE ADVANTAGES FOR PSYCHIATRIC POPULATIONS ARE CURRENTLY STUDIED IN THE NETHERLANDS. TREATMENT OF COMORBID INSOMNIA BY COGNITIVE BEHAVIORAL THERAPY MAY IMPROVE COGNITIVE FUNCTIONING INDIRECTLY BY DISCONTINUATION OF SLEEP MEDICATION, IMPROVEMENT OF SLEEP AND MOOD RELATED COGNITIVE SYMPTOMS.
CONCLUSION: A PROACTIVE APPROACH, INCLUDING SCREENING AND TREATMENT OF COGNITIVE SYMPTOMS BEFORE IMPAIRMENT OCCURS, IS WARRANTED TO OPTIMIZE OUTCOME OF THE AGEING PSYCHIATRIC PATIENT. TIJDSCHRIFT VOOR PSYCHIATRIE 63(2021)2, 120-124.

[Quantitative measurement of cross-sectional area of small pulmonary vessels in pulmonary embolism].

Objective: The relationship between the percentage of total cross-sectional area (% CSA) of small pulmonary vessels for the lung area in CTPA and the right ventricular function parameters in patients with pulmonary embolism. Methods: 120 patients with PE and 72 healthy subjects underwent CTPA and all date were analyzed Retrospectively. The main pulmonary artery diameter (mPA), the ratio of the main pulmonary artery to the ascending aorta diameter (rPA), right ventricle/left ventricular diameter ratio (RVd/LVd), and the pulmonary artery obstruction index (PAOI) in the PE group were measured for all subjects. The %CSA<5 mm(2) and 5-10 mm(2) for the lung area (%CSA(<5) and %CSA(5-10)) of small pulmonary vessels were measured with Image J image-processing program. According to the risk stratification of the 2018 Guidelines for the Diagnosis and Treatment of Pulmonary Thromboembolism, PE patients were divided into medium-high risk group (RVd/LVd>1) and low-risk group (RVd/LVd<1). The indexes of PE in medium-high risk group, low risk group and control group were compared by ANOVA, and the indexes among PE subgroups were compared by independent sample t-test. Spearman correlation method was used to analyze the correlation between %CSA and right ventricular function parameters of PE patients. Results: %CSA(<5) of medium-high risk group, low-risk group and control group were (0.69±0.19)%, (0.95±0.27)% and (0.99±0.30)% (P<0.01), respectively. %CSA(5-10) of three groups were (0.63±0.15)%, (0.84±0.18)%, and (0.85±0.25)% (P<0.01), respectively; %CSA(<5) and %CSA(5-10) of medium-high risk group were lower than low-risk group and control group. %CSA(<5) and %CSA(5-10) in PE patients correlated negatively with RVd/LVd, rPA and mPA (r=-0.545/-0.549, -0.235/-0.352, -0.239/-0.298, respectively). Conclusion: The measurement of % CSA<(5) and %CSA (5-10) in CTPA were negatively correlated with RVd/LVd in patients with pulmonary embolism, which indirectly reflected the severity of the pulmonary embolism patients.

Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study.

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

Breast cancer survivors: return to work and wage loss in selected hospitals in Malaysia.

PURPOSE: This study aimed, firstly, to assess the determinants of return to work (RTW), secondly, to explore the amount of annual wage loss, and finally, to discover the determinants of wage loss among breast cancer (BC) survivors. METHODS: A cross-sectional study design was used in this research. The data was collected via interview using a validated questionnaire. Logistic regression models were developed to discover the significant determinants of RTW and of wage loss among BC survivors. RESULTS: A total of 256 BC survivors were included in this study. The analysis showed that there was a 21% loss of or reduction in mean income within 1 year after diagnosis. The significant predictors of RTW are being a government employee, having reduced wages or wage loss, and if the case had been diagnosed 1 year or more ago. Being a private sector employee and having a late stage of cancer was a barrier to RTW. The main risk factors for reduced wages or wage loss were belonging to the age group of 40-59 years, being of Chinese or Indian ethnicity, having low educational status, and not returning to work. However, belonging to the higher monthly income group (earning > RM 2000) is a protective factor against the risk of reduced wages or wage loss. CONCLUSIONS: Non-RTW and wage loss after diagnosis of BC may result in the survivors experiencing a significant financial burden. Assessment of these patients is becoming more crucial because more women participate in the workforce in Malaysia nowadays and because BC is managed using multiple treatment modalities with their consequences could lead to long absences from work.

Experimental study on TGF-ß1-mediated CD147 expression in oral submucous fibrosis.

OBJECTIVE: Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remains largely unknown. METHODS: In this study, we investigated the expression of CD147 and transforming growth factor ß1 (TGF-ß1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-ß1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-ß1 or LY2157299, an inhibitor of TGF-ß1 receptor and arecoline stimulation. RESULTS: We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-ß1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-ß1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-ß1 down-regulated CD147 expression. CONCLUSION: Our findings suggest arecoline promotes CD147 expression via the TGF-ß1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

A new clinical staging system for esophageal cancer to predict survival after definitive chemoradiation or radiotherapy.

This study is to evaluate the prognostic value of a new clinical staging system for esophageal cancer to predict survival after (chemo)radiotherapy. This retrospective study enrolled 444 patients with esophageal squamous cell carcinoma who underwent definitive intensity-modulated radiotherapy with or without chemotherapy between January 2008 and May 2014. A clinical staging system based on the gross tumor volume and maximum diameter of metastatic lymph nodes was developed and the prognostic value of this staging system was compared with that of the 8th edition of American Joint Committee on Cancer TNM staging system. The 3-year survival rate in the whole group was 44.5%. Multivariate analysis showed that gross tumor volume and maximum diameter of metastatic lymph nodes were independent prognostic factors. According to the proposed clinical staging system, the 3-year survival curves of each T, N, and TNM stage were well segregated. On the other hand, 3-year survival rates based on the 8th edition of cTNM staging system were similar between cT3 and cT4, cN1 and cN2, cN2, and cN3, III and IVa stages.The proposed clinical staging system appears to be a simple and accurate predictor of outcome in patients with esophageal squamous cell carcinoma who underwent definitive (chemo) intensity-modulated radiotherapy.

Structural correlates of trait impulsivity in patients with bipolar disorder and healthy controls: a surface-based morphometry study.

BACKGROUND: Patients with bipolar disorder (BD) frequently exhibit impulsive behaviors independent of their mood state, and trait impulsivity is increasingly recognized as a crucial BD biomarker. This study aimed to investigate structural correlates of trait impulsivity measured using the Barratt Impulsiveness Scale (BIS) in healthy controls (HCs) and patients with BD. METHOD: We recruited 59 patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched HCs (33.9 ± 7.4 years). Participants underwent structural magnetic resonance imaging and clinical evaluations, and their BIS scores were evaluated. An automated surface-based method (FreeSurfer) was used to measure cortical thickness and generate thickness maps for each participant. Brain-wise regression analysis of the association between cortical thickness and BIS scores was performed separately for BD and HC groups by using a general linear model. RESULTS: Patients with BD obtained significantly higher BIS scores than HCs. In HCs, higher BIS scores were associated with a thinner cortex in the left inferior, middle and medial frontal cortices. By contrast, in BD patients, higher BIS scores were associated with a thicker cortex in the right insula. Patients with BD showed a thinner cortex than HCs in all these four structures. CONCLUSIONS: The findings indicate that the left prefrontal cortex plays a cardinal role in trait impulsivity of healthy individuals. Patients with BD have a different structural correlate of trait impulsivity in the right insula. However, the use of various psychotropics in patients with BD may limit our interpretation of BD findings.

[Clinicopathologic and prognosis features of Claudin-low breast cancers].

Objective: To investigate the clinicopathologic and prognostic features of Claudin-low breast cancers (CLBC). Methods: Tissue microarray sections were scored semiquantitatively for the immunohistochemical expression of claudin-1, -3, -4, -7 and -8 in 233 cases of invasive breast cancers collected from Qingdao Central Hospital from January 2010 to December 2011. Results: The expression rate of Claudin-3 (72/212, 33.9%) and -4 (56/212, 45.2%) was most similar, and Claudin-4 showed the highest expression. Twenty one cases (21/212, 9.0%) were diagnosed as CLBC, with triple-negative breast cancer (TNBC) accounted for the highest proportion (11/21, 52.4%). Among the CLBC cases, the invasive carcinoma no special type (66.7%, 14/21) and metaplastic carcinoma (14.3%, 3/21) were mostly seen, while metaplastic squamous carcinoma did not show Claudin-low pattern. Compared to the non CLBC in this cohort, CLBC had higher proportion of histologic grade 3 and tumors larger than 2 cm, and the proportions were slightly lower than TNBC. Patients with CLBC had lower 5 year disease-free(P>0.05) and overall survival rates(P=0.018). Conclusion: CLBC shows distinct clinicopathologic and prognostic features comparing to other subtypes, and is associated with poor prognosis.

Endovascular Stent Graft Repair is an Effective and Safe Alternative Therapy for Arteriovenous Graft Pseudoaneurysms.

OBJECTIVE/BACKGROUND: Pseudoaneurysm formation occurs in 2-10% of hemodialysis arteriovenous grafts (AVGs). Surgical repair often requires pseudoaneurysm resection, interposition graft placement, and insertion of a catheter as a bridge. Endovascular stent graft repair is a controversial alternative therapy. This study was performed to examine the effectiveness and mid-term outcomes of stent graft repair for AVG pseudoaneurysms. METHODS: All patients who had undergone stent graft repair for AVG pseudoaneurysms between December 2012 and July 2015 were identified from hospital medical records for retrospective analysis. Outcome measures were technical success, early and late complications, and primary and secondary patency rates. RESULTS: A total of 37 stent graft repairs of AVG pseudoaneurysms were performed in 35 patients (42.9% men; mean age 66.9 years). The mean time from AVG creation to pseudoaneurysm repair was 69 months. The indications of treatment (as per the institutional policy) were large pseudoaneurysm (56.7%), impending rupture (27.1%), and bleeding (16.2%). Mean pseudoaneurysm diameter was 23.0 mm. The most common diameter and length of stent graft used were 7 mm (67.6%) and 50 mm (48.6%), respectively. Technical success was 100%. Only one early complication occurred after stent graft repair, which was due to recurrence of the pseudoaneurysm as a result of a short landing zone. Late complications included infection (17.1%) and thrombosis (37.1%). The 1, 6, and 12 month primary patency rates were 89.2%, 55.5%, and 22.0%, respectively. The 1, 6, and 12 month secondary patency rates were 100%, 88.6%, and 78.6%, respectively. The median follow up was 12.3 months. CONCLUSIONS: The study demonstrates that endovascular stent graft repair is an effective and safe alternative therapy for AVG pseudoaneurysms. However, the rate of thrombosis and infection was high and needs to be balanced against open surgery in future studies.