B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer.

PURPOSE: The function of B cells in papillary thyroid cancer (PTC) is controversial. The role of B-cell-related tertiary lymphoid structures (TLSs) is still unclear. Whether B cells exert their anti-tumor effect through forming TLS in PTC needs further investigation. METHODS: We detected the percentage of B cells in PTC tissues by multi-parameter flow cytometry. Paraffin-embedded tumor tissues of 125 PTC patients were collected and stained with Haematoxylin-Eosin (H&E) for inflammatory infiltration analysis in combination with clinical features. Multiplexed immunohistochemistry (mIHC) was performed to verify the TLSs in above inflammatory infiltration. Correlation of B cells and TLSs with prognosis was analyzed using the TCGA database. RESULTS: We observed that PTC patients with higher expression of B lineage cell genes had improved survival and the percentage of B cells in the PTC tumor tissues was variable. Moreover, PTC tumor tissues with more B cells were surrounded by immune cell aggregates of varying sizes. We furtherly confirmed the immune cell aggregates as TLSs with different maturation stages. By analyzing PTC data from TCGA database, we found the maturation stages of TLSs were associated with genders and clinical stages among PTC patients. Moreover, patients with high TLSs survived longer and had a better prognosis. CONCLUSION: B cells are associated with the existence of TLSs which have different maturation stages in PTC. Both B cells and TLSs are associated with the survival rate of PTC. These observations indicate that the anti-tumor effects of B cells in PTC are associated with TLSs formation.

[Association between depression and chronic diseases among middle-aged and older Chinese adults].

OBJECTIVE: To examine the association between depressive symptoms and chronic diseases among middle-aged and older Chinese adults within a national investigation. METHODS: Data used in current analysis were obtained from a nationally representative, cross-sectional population-based survey of China health and retirement longitudinal study, which were conducted in 2011 using four-stage probability-proportional-to-size sampling methods. A total of 10 420 participants who were aged 45 years and above from 28 provinces in mainland China were included. Information on demographic characteristics (e.g., age, gender, education level), lifestyle factors (e.g., smoking status and drinking frequency) and chronic diseases (e.g., hypertension, diabetes, and stroke) were collected by well-trained interviewers at the interviewees' homes using a standardized questionnaire. Depressive symptoms were measured using the 10-item version of the center for epidemiological studies depression scale (CESD-10, which was a widely used standard tool in Chinese population, and elevated depressive symptoms were defined by a cut-off ≥10. Multivariate Logistic regression analysis was carried out to assess the association between depressive symptoms and chronic diseases (including hypertension, diabetes, heart disease, dyslipidemia and stroke), adjusting for age, gender, education level, marital status, ethnicity, place of residence, bady mass index (BMI) and other potential confounding factors. RESULTS: Among the 10 420 participants, the mean age was (59.2±9.4) years, and 48.2% of them were men. There were 3 900 (37.4%) participants who had a depression rating score of 10 or greater, indicative of elevated depressive symptoms. The results of multivariate Logistic regression analysis demonstrated that diabetes (OR=1.230, 95%CI: 1.080-1.401), hypertension (OR=1.335, 95%CI: 1.205-1.480), heart disease (OR=1.953, 95%CI: 1.711-2.229), and stroke (OR=2.269, 95%CI: 1.704-3.020) were significantly associated with depressive symptoms (P < 0.05), after full adjustment of age, gender, education level, marital status, ethnicity, residency and other potential confounders. While no significant relationship was found between dyslipidemia and depressive symptoms (P>0.05). The prevalence of elevated depressive symptoms increased parallel with the number of chronic diseases (Ptrend < 0.001). CONCLUSION: Depressive symptoms were significantly associated with chronic diseases (including diabetes, hypertension, heart disease, and stroke), which suggests that psychological factors, such as depressive symptoms should be taken into consideration in the prevention and control of chronic diseases.

[Breast ultrasound optimization process analysis based on breast cancer screening for 1 501 753 rural women in China].

Objective: To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening. Methods: The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children's public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated. Results: A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area (P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area (P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area (P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area (P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area (P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area (P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions: The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

Downregulation of nuclear protein-1 induces cell cycle arrest in G0/G1 phase in glioma cells in vivo and in vitro via P27.

Nuclear protein-1 (NUPR1), also named as p8 or Com1, has been since found overexpressed in several human malignant tumor cells, such as glioma. NUPR1 also regulates cell cycle progression, however, the role of NUPR1 in regulating glioma cell cycle remains poorly understood. Knockdown efficiency of U87 and U251 cells infected with the lentiviral vector was detected by quantitative real-time PCR and western blot in vitro and in vivo. Flow cytometry and western blot were used to explore a mechanism by which NUPR1 modulates cell cycle in U87 and U251 cells. Immunohistochemistry was applied to detect expression levels of P27, CDK2, and cyclin E in human glioma tissues with NUPR1 positive expression and tumorigenesis in nude mice. We confirmed that the downregulation of NUPR1 arrested the cell cycle in the G0/G1 phase in U87 and U251 cells in vitro. Furthermore, the expression level of P27 was increased, and CDK2 and cyclin E were decreased upon silencing NUPR1 expression in vitro and in vivo. In conclusion, the knockdown of NUPR1 induces cell cycle arrest in the G0/G1 phase in glioma cells via P27.

[Effect of ultrasound-guided vacuum-assisted excision verus open surgery for benign phyllodes tumors of breast on postoperative local recurrence].

Objectives: To examine the effect of VAE and open surgery on the postoperativelocal recurrence of benign phyllodes tumors of breast and to investigate the clinical efficacy of VAE in the treatment of benign phyllodes tumors. Methods: The clinical data of 128 patients with benign phyllodes tumors of breast admitted to the Guangdong Women and Children Hospital from January 2013 to January 2018 were retrospectively analyzed. All patients were female, aged (37.7±9.1) years (range: 16 to 56 years). Eighty patients underwent ultrasound-guided VAE (minimally invasive group) and 48 patients underwent open surgery (open group). The t-test, χ(2) test or Fisher exact probability method were used to compare the clinical characteristics of the two groups of patients. Logistic regression was used to analyze the prognostic factors of postoperative local recurrence. Results: The maximum diameter of tumor in the minimally invasive group was smaller than that in the open group ((20.6±7.4) mm vs. (42.0±2.0) mm, t=-7.173, P=0.000). The follow-up time was (36.4±1.8) months (range: 12 to 71 months). There were 7 cases of local recurrences during the follow-up period. The local recurrence rates in the minimally invasive and open groups were 5.0% (4/80) and 6.3% (3/48). The results of multivariate analysis showed that the maximum tumor diameter of 25 mm was an independent prognosis factor for postoperativelocal recurrence (OR=0.122, 95%CI: 0.016 to 0.901, P=0.039). While surgical procedure, age, menopausal status and history of fibroadenomas in the ipsilateral breast is not an independent prognostic factor for postoperative local recurrence. In the minimally invasive surgery group, the local recurrence rates were 2.9% (2/69) and 2/11 in patients with tumor maximum diameters<25 mm and ≥25 mm, respectively. Conclusions: Local recurrence of breast benign phyllodes tumors is closely related to the tumor size. For patients with tumor diameter<25 mm, the postoperative local recurrence rate of VAE is low, which can be used in clinical practice. Intraoperative complete resection to achieve a negative surgical margin should be guaranteed to avoid local recurrence.

Local body cooling to improve sleep quality and thermal comfort in a hot environment.

The effects of local body cooling on thermal comfort and sleep quality in a hot environment were investigated in an experiment with 16 male subjects. Sleep quality was evaluated subjectively, using questionnaires completed in the morning, and objectively, by analysis of electroencephalogram (EEG) signals that were continuously monitored during the sleeping period. Compared with no cooling, the largest improvement in thermal comfort and sleep quality was observed when the back and head (neck) were both cooled at a room temperature of 32°C. Back cooling alone also improved thermal comfort and sleep quality, although the effects were less than when cooling both back and head (neck). Mean sleep efficiency was improved from 84.6% in the no cooling condition to 95.3% and 92.8%, respectively, in these conditions, indicating good sleep quality. Head (neck) cooling alone slightly improved thermal comfort and subjective sleep quality and increased Stage N3 sleep, but did not otherwise improve sleep quality. The results show that local cooling applied to large body sections (back and head) could effectively maintain good sleep and improve thermal comfort in a hot environment.

Value of two-cycle docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy in hypopharyngeal carcinoma.

Various studies have investigated laryngeal function and survival after induction chemotherapy in hypopharyngeal carcinoma, but potential factors to help predict response rates after induction chemotherapy remain unknown. This retro- spective study evaluated which factors are related to an ineffective response to two-cycle docetaxel, cisplatin, and 5-fluoro- uracil (TPF) induction chemotherapy in hypopharyngeal carcinoma to determine potential candidates for this treatment in clinical practice. From Jan 2005 to Dec 2015, 81 patients diagnosed with hypopharyngeal squamous cell carcinoma based on a pathological examination were analyzed. They were administered two-cycle TPF induction chemotherapy, and magnetic resonance imaging was performed before and after induction chemotherapy. The mean survival time was 5.7 years (95% confidence interval, 5.1-6.2 years). The 1, 3, 5 and 6-year survival rates were 98.8%, 80.1%, 64.5%, and 54.2%, respectively. TPF induction chemotherapy was well tolerated; the main adverse effects resolved with symptomatic treatment. A response to TPF induction chemotherapy was associated with lymph node size, tumor grade, invasion region, T stage, and primary tumor. The following issues were significantly associated with an increasing non-response rate to two-cycle induction chemotherapy: increasing lymph node size, moderately differentiated squamous cell carcinoma, invasion of the esophagus along with the thyroid cartilage, and primary tumor in the piriform sinus. Lymph nodes of ≥2.15 cm, moderately differenti- ated tumor grade, or thyroid cartilage invasion were the best cutoff values for patients who did not respond to induction chemotherapy. However, the initial cancer site, cancer stage, and degree of cancer differentiation were not closely related to the efficacy of induction chemotherapy.

[Investigation and analysis of health-related quality of life in myasthenia gravis patients with myasthenia gravis quality of life-15 Chinese version].

OBJECTIVE: To investigate the level and influencing factors of health-related quality of life in myasthenia gravis (MG) patients with myasthenia gravis quality of life-15 (MGQOL-15) Chinese version and to provide corresponding measures in one tertiary hospital of Sichuan Province. METHODS: We collected the general data (gender, age, body mass index BMI, marital status, educational level and employee status), clinical data [Osserman type, myasthenia gravis composite (MGC), other immunopathies, disease duration, frequency of outpatient visits per month, ratio of disease cost to income each month and frequency of symptoms during the past month] and the MGQOL-15 Chinese version from 168 myasthenia gravis patients in one tertiary hospital of Sichuan Province. RESULTS: The mean score of MGQOL-15 was 17.67±12.78. The score of the item "My occupational skills and job status have been negatively affected." was the highest, followed by "I have trouble using my eyes." and "I am frustrated by my MG." Single factor analysis showed that MG patients' QOL were different with different disease severity MGC (F=19.353, P<0.001), ratio of disease cost to income each month (F=5.831, P<0.001) and the frequency of symptoms during the past month (F=9.128,P<0.001). Multiple regression analysis showed that disease severity MGC (ß=0.743,P<0.001), ration of disease cost to income each month (ß=3.347,P<0.001) and the frequency of symptoms during the past month (ß=2.216,P<0.003) were the main predictors of HRQOL in the MG patients. CONCLUSION: Our study showed that the MGQOL-15 is helpful for clinicians to evaluate MG patients' QOL regularly, investigate the influencing factors and implement corresponding interventions the so as to improve the patients' quality of life. Disease severity MGC, ratio of disease cost to income each month and the frequency of symptoms during the past month were the main predictors of MG patients' QOL. Clinicians should pay more attention to MG patients' disease severity MGC and the frequency of symptoms during the past month.

Comparisons of the efficacy and tolerability of mycophenolate mofetil and azathioprine as treatments for neuromyelitis optica and neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: To research and compare the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD). METHODS: In this observational study, we enrolled patients with NMO/NMOSD who received either MMF or AZA for 6 months or more. We compared the efficacy and tolerability of MMF and AZA as preventive treatments in patients with NMO/NMOSD. RESULTS: Baseline variables between groups were not significantly different. In the MMF-treated (n = 105) and AZA-treated (n = 105) groups, 56.2% and 52.4%, respectively, of patients were relapse-free, and both median annualized relapse rates and Expanded Disability Status Scale scores were lower (P = 0.000). More patients in the AZA than MMF group stopped or switched to another preventive treatment because of adverse effects. The Expanded Disability Status Scale scores at final follow-up were lower in the AZA group than in the MMF group, the duration after treatment was longer in the AZA group than in the MMF group, and more patients in the AZA than MMF group concurrently used prednisone (P < 0.05). Neither the Kaplan-Meier survival estimates (P > 0.05) nor the Cox proportional hazard model (P > 0.05) indicated a significant difference in relapse between MMF- and AZA-treated groups. CONCLUSIONS: Both MMF and AZA were effective in patients with NMO/NMOSD. Fewer and more mild adverse events were attributed to MMF than AZA. The probability of maintaining a relapse-free state was not significantly different between the MMF and AZA groups. However, more effective treatments with more acceptable safety profiles are still needed.

Physiological responses during exposure to carbon dioxide and bioeffluents at levels typically occurring indoors.

Twenty-five subjects were exposed to different levels of carbon dioxide (CO2 ) and bioeffluents. The ventilation rate was set high enough to create a reference condition of 500 ppm CO2 with subjects present; additional CO2 was then added to supply air to reach levels of 1000 or 3000 ppm, or the ventilation rate was reduced to allow metabolically generated CO2 to reach the same two levels (bioeffluents increased as well). Heart rate, blood pressure, end-tidal CO2 (ETCO2 ), oxygen saturation of blood (SPO2 ), respiration rate, nasal peak flow, and forced expiration were monitored, and the levels of salivary α-amylase and cortisol were analyzed. The subjects performed a number of mental tasks during exposures and assessed their levels of comfort and the intensity of their acute health symptoms. During exposure to CO2 at 3000 ppm, when CO2 was added or ventilation was restricted, ETCO2 increased more and heart rate decreased less than the changes that occurred in the reference condition. Exposure to bioeffluents, when metabolically generated CO2 was at 3000 ppm, significantly increased diastolic blood pressure and salivary α-amylase level compared with pre-exposure levels, and reduced the performance of a cue-utilization test: These effects may suggest higher arousal/stress. A model is proposed describing how mental performance is affected by exposure to bioeffluents.

Effects of exposure to carbon dioxide and bioeffluents on perceived air quality, self-assessed acute health symptoms, and cognitive performance.

The purpose of this study was to examine the effects on humans of exposure to carbon dioxide (CO2 ) and bioeffluents. In three of the five exposures, the outdoor air supply rate was high enough to remove bioeffluents, resulting in a CO2 level of 500 ppm. Chemically pure CO2 was added to this reference condition to create exposure conditions with CO2 at 1000 or 3000 ppm. In two further conditions, the outdoor air supply rate was restricted so that the bioeffluent CO2 reached 1000 or 3000 ppm. The same 25 subjects were exposed for 255 min to each condition. Subjective ratings, physiological responses, and cognitive performance were measured. No statistically significant effects on perceived air quality, acute health symptoms, or cognitive performance were seen during exposures when CO2 was added. Exposures to bioeffluents with CO2 at 3000 ppm reduced perceived air quality; increased the intensity of reported headache, fatigue, sleepiness, and difficulty in thinking clearly; and reduced speed of addition, the response time in a redirection task, and the number of correct links made in the cue-utilization test. This suggests that moderate concentrations of bioeffluents, but not pure CO2 , will result in deleterious effects on occupants during typical indoor exposures.

Clinical analysis of Krukenberg tumours in patients with colorectal cancer-a review of 57 cases.

BACKGROUND: A Krukenberg tumour (KT) is defined as an ovarian metastasis from a gastrointestinal adenocarcinoma and suggests a terminal condition. This study aimed to identify the prognostic factors affecting the survival of patients with KTs of colorectal origin who receive cytoreductive surgery. METHODS: Medical records of patients who had received cytoreductive surgery and had been pathologically diagnosed with KT of colorectal origin in two centres were reviewed. Information about the patients' clinicopathological features and follow-up visit were collected. Factors influencing patient survival were analysed. RESULTS: Fifty-seven patients were included in this study. The median survival time was 35 months. Five-year overall survival was 25%. Patients who had recurrence 2 years after resection of the primary tumour, achieved complete cytoreduction, had metastases confined to the pelvis, had no lymph node involvement, and received systemic chemotherapy had a significantly longer median survival than those who had recurrence at the same time as resection of the primary tumour (P = 0.027), received incomplete cytoreduction (P < 0.001), had metastases beyond the pelvis (P < 0.001), had lymph node involvement (P = 0.011), and did not receive systemic chemotherapy (P = 0.006) on log-rank test. Less extensive metastatic disease, achievement of complete cytoreduction, and use of systemic chemotherapy were significantly associated with improved prognosis on multivariate analysis. CONCLUSIONS: Cytoreductive surgery may confer survival benefits in patients with KTs of colorectal origin who attain complete cytoreduction and whose metastases are confined to the pelvis and when combined with active systemic chemotherapy.

[Association between efficacy and molecular subtypes in breast cancer patients receiving neoadjuvant chemotherapy].

OBJECTIVE: To investigate the association between pathological complete response (pCR), clinicopathological characteristics and clinical outcomes in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: Medical records of 221 patients who underwent neoadjuvant chemotherapy for breast cancer between January 2006 and December 2008 were retrospectively reviewed. Their clinicopathological features, response to neoadjuvant chemotherapy, survivals and prognostic factors were then analyzed. RESULTS: The total pCR rate was 11.3% (25/221). The rate of pCR was 0%(0/12), 5.7%(6/106), 7.4%(2/27) and 16.9%(11/65) in the luminal A, luminal B, HER-2, and Basal-like subtypes, respectively. Statistically significant association was found between the pCR rate and the molecular substypes of breast cancer(P<0.05). The median 5-year disease free survival and the 5-year overall survival were 72 months and 79 months. The 5-year disease free survival rate and 5-year overall survival rate were 61.1% and 71.9% in all the 221 patients. The 5-year disease free survival rates of pCR and non-pCR patients were 84.0% and 58.2%, and the 5-year overall survival rates of pCR and non-pCR patients were 96.0% and 68.9%, respectively(P<0.05 for all). The multivariate survival analysis showed that clinical and pathological node stage and pCR are independent prognostic factors for the 5-year disease-free survival and 5-year total survival in patients with neoadjuvant chemotherapy (P<0.05 for both). CONCLUSIONS: pCR is more frequently observed in HER-2 and basal-like breast cancer subtypes compared with the luminal breast cancer subtype. The status of clinical and pathological node status and pCR are independent prognostic factors in patients treated with neoadjuvant chemotherapy.

[Interleukin-20 and interleukin-22 in pleural effusion].

OBJECTIVE: To investigate the concentrations and clinical significance of interleukin (IL)-20 and IL-22 in pleural effusion with various etiologies. METHODS: Pleural effusion (PE) and corresponding serum samples were obtained from 88 patients from Wuhan Tuberculosis Prevention and Control Institute from June 2011 to June 2013. There were 27 cases with malignant pleural effusion, 24 with tuberculous pleural effusion, 17 with bacterial pleural effusion and 20 with transudativeeffusion. The pleural and serum levels of IL-20 and IL-22 were determined by sandwich enzyme-linked immunosorbent assays (ELISA). RESULTS: (1) Except for transudativeeffusion, the concentration of IL-20 in malignant pleural effusion (36.8±5.1) ng/L, tuberculous pleural effusion (34.8±6) ng/L, bacterial pleural effusion (41.7±20.2) ng/L, were significantly higher than that of the corresponding serum concentration (29.7±5.97) ng/L, (27.3 ±6.7) ng/L, (25.6±4.7) ng/L (t=5.044, 3.804, 3.452, P<0.05). However, the concentration of IL-20 in pleural effusions of different causes showed no significant difference; malignant (36.8±5.1) ng/L, tuberculous(34.8±6.0) ng/L, bacterial (41.7±20.2) ng/L, transudate (34.1±7.3) ng/L (P>0.05). The concentration of IL-22 (median, quartiles) in tuberculouseffusion was 146.1 (39.8) ng/L and bacterial effusion 59.6 (484.3) ng/L was significantly higher than those in the corresponding serum concentrations 18.7 (9.8) ng/L, 15.7 (17.2) ng/L (Z value respectively -3.971, -3.290, P<0.05). The concentration of IL-22 in tuberculous pleural effusion, bacterial pleural effusion, transudative pleural effusion was significant higher than those in malignant pleural effusion respectively (all P<0.001). (2)The concentrations of IL-22 in malignant pleural effusion was correlated positively with those in serum (r=0.729, P<0.001). (3) With a cut-off value of 19.7 ng/L, pleural IL-22 exhibited a high sensitivity and specificity of 95.1% (39/41) and 88.9%(24/27) respectively, when used for distinguishing infectious pleural effusion (including tuberculous and bacterial effusion) from malignant pleural effusion (P<0.001). CONCLUSIONS: Higher levels of IL-22 in tuberculous and bacterial pleural effusion were found when compared with corresponding serum levels and might be involved in the pathogenesis of infectious pleural effusion. Pleural IL-22 measurement provided reliable diagnostic efficiency for distinguishing infectious from malignant pleural effusion.

Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection.

Transforming growth factor (TGF)-ß, type I receptor (TßRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1-4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.

Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells.

Treatment of primary biliary cirrhosis (PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells (Treg ) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8(+) T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-ßRII) mice to recombination-activating gene (Rag)1(-/-) recipients. We then used this robust established adoptive transfer system and co-transferred CD8(+) T cells from dnTGF-ßRII mice with either C57BL/6 or dnTGF-ßRII forkhead box protein 3 (FoxP3(+) ) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-ßRII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57BL/6 Treg versus dnTGF-ßRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-ßRII mice. Our data reflect the therapeutic potential of wild-type CD4(+) FoxP3(+) Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC.

X-ray tomography for structural analysis of microstructured and multimaterial optical fibers and preforms.

Specialty optical fibers, in particular microstructured and multi-material optical fibers, have complex geometry in terms of structure and/or material composition. Their fabrication, although rapidly developing, is still at a very early stage of development compared with conventional optical fibers. Structural characterization of these fibers during every step of their multi-stage fabrication process is paramount to optimize the fiber-drawing process. The complexity of these fibers restricts the use of conventional refractometry and microscopy techniques to determine their structural and material composition. Here we present, to the best of our knowledge, the first nondestructive structural and material investigation of specialty optical fibers using X-ray computed tomography (CT) methods, not achievable using other techniques. Recent advances in X-ray CT techniques allow the examination of optical fibers and their preforms with sub-micron resolution while preserving the specimen for onward processing and use. In this work, we study some of the most challenging specialty optical fibers and their preforms. We analyze a hollow core photonic band gap fiber and its preforms, and bond quality at the joint between two fusion-spliced hollow core fibers. Additionally, we studied a multi-element optical fiber and a metal incorporated dual suspended-core optical fiber. The application of X-ray CT can be extended to almost all optical fiber types, preforms and devices.

Serum secretory phospholipase A2-IIa (sPLA2-IIA) levels in patients surviving acute myocardial infarction.

BACKGROUND: The increase of secretory phospholipase A2-IIa (sPLA2-IIa) in culprit coronary lesions is associated with myocardial infarction, and the increase of sPLA2-IIa in peripheral plasma levels has a significant risk and prognostic value in patients with coronary artery disease. Little is known about the prognostic significance of elevated serum sPLA2-IIa in post-acute myocardial infarction (post-AMI) patients. OBJECTIVES: The present study is designed to investigate the potential association between serum sPLA2-IIa and prognosis in post-acute myocardial infarction (post-AMI) patients. PATIENTS AND METHODS: From Oct 1998 to Sep 2008, a total of 964 post-AMI patients with serum samples collected in the convalescent stage were studied. Serum levels of sPLA2-IIa were measured by ELISA. According to the optimal cut-off value for sPLA2-IIa concentration, patients were then divided into 2 groups. Categorical variables were compared between the 2 groups using the χ2 test. All continuous variables are described as mean ± SD and were compared using Student's t-test. Statistical associations between clinicopathological observations and sPLA2-IIa levels were determined using the Mann-Whitney U test. The clinical value of sPLA2-IIa level as a prognostic parameter was evaluated using the Cox's proportional hazards model. RESULTS: During a median follow-up period of 1,462 days, 123 patients (12.7%) had adverse events (all-cause mortality, n=52; non-fatal MI, n=31; readmission for heart failure [HF], n=40). Patients were divided into 2 groups according to a serum sPLA2-IIa level of 360 ng/dl, which was determined to be the optimal cut-off for discriminating all-cause mortality based on the maximum value of the area under the receiver operating characteristic curve. Patients with elevated sPLA2-IIa (> 360 ng/dl, n=164) had a significantly higher prevalence of death (18.3% [30/164] vs. 2.75% [22/800] p < 0.001) and readmission for HF (14% [23/164/ vs. 2.1% [17/800], p < 0.0001), but not of non-fatal MI (4.88% [8/164]vs. 2.87% [23/800], p = 0.096), compared to those with sPLA2-IIa < 360 ng/dl. Multivariate Cox regression analysis indicated that elevated serum sPLA2-IIa was associated with an increased risk of mortality and readmission for HF. CONCLUSIONS: Elevated serum sPLA2-IIa during the convalescent stage of AMI predicted long-term mortality and readmission for HF after survival discharge in the post-AMI patients.

Diversity of killer cell immunoglobulin-like receptor genes in the Bai ethnic minority of Yunnan, China.

Killer cell immunoglobulin-like receptors (KIRs), expressed in both natural killer (NK) cells and a subset of T cells, represent a family of both inhibitory and activating receptors that can regulate NK and T cells upon interacting with human leucocyte antigen (HLA) class I molecules on target cells. The number and distribution of KIR genes vary between individuals and populations from different geographical regions and ethnic origins. In this study, we investigated KIR gene frequencies and genotype diversities of 13 KIR genes, 2 pseudogenes, expressed and non-expressed forms of KIR2DL5 and the two subtypes, full-length and deleted forms, of KIR2DS4 in 100 unrelated healthy individuals of the Bai population, living in the Dali Bai autonomous prefecture in the Yunnan province. All individuals were typed positive for the three framework loci KIR3DL3, 2DL4 and 3DL2, as well as for three non-framework genes KIR2DL1, 2DL3 and the pseudogene KIR2DP1. The gene frequencies of the other KIR genes ranged from 7%-95%. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that they display a wide range of LD. χ² analysis among non-ubiquitous genes, using the KIR gene frequency data from our study population, as well as from previously published population data, was conducted and revealed significant differences in the KIR2DL1, 2DL2, 3DL1 and KIR2DS1 genes. The results of the present study can be valuable for enriching the Chinese ethnic gene information resources of the KIR gene pool, for anthropological studies, as well as for KIR-related disease research.

Effects of thermal discomfort in an office on perceived air quality, SBS symptoms, physiological responses, and human performance.

UNLABELLED: The effects of thermal discomfort on health and human performance were investigated in an office, in an attempt to elucidate the physiological mechanisms involved. Twelve subjects (six men and six women) performed neurobehavioral tests and tasks typical of office work while thermally neutral (at 22°C) and while warm (at 30°C). Multiple physiological measurements and subjective assessment were made. The results show that when the subjects felt warm, they assessed the air quality to be worse, reported increased intensity of many sick building syndrome symptoms, expressed more negative mood, and were less willing to exert effort. Task performance decreased when the subjects felt warm. Their heart rate, respiratory ventilation, and end-tidal partial pressure of carbon dioxide increased significantly, and their arterial oxygen saturation decreased. Tear film quality was found to be significantly reduced at the higher temperature when they felt warm. No effects were observed on salivary biomarkers (alpha-amylase and cortisol). The present results imply that the negative effects on health and performance that occur when people feel thermally warm at raised temperatures are caused by physiological mechanisms. PRACTICAL IMPLICATIONS: This study indicates to what extent elevated temperatures and thermal discomfort because of warmth result in negative effects on health and performance and shows that these could be caused by physiological responses to warmth, not by the distraction of subjective discomfort. This implies that they will occur independently of discomfort, i.e. even if subjects have become adaptively habituated to subjective discomfort. The findings make it possible to estimate the negative economic consequences of reducing energy use in buildings in cases where this results in elevated indoor temperatures. They show clearly that thermal discomfort because of raised temperatures should be avoided in workplaces.