Systematic Characterization of the Clinical and Pathological Features of Schwannomas Harboring SH3PXD2A::HTRA1 Fusion.

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

High oxidative stability of a complex fish liver oil nano-capsules in response to long-term storage, and to hyperthermal and sunlight exposure.

BACKGROUND: In this study, a biocompatible nano-carrying platform using chitosan (ChI) and chondroitin sulfate (ChS) was developed for the encapsulation of cobia liver oil (CBLO) to prevent its oxidation and improve its absorption. An ionic gelation method was applied to encapsulate CBLO with different weight ratios (from 1.0 to 1.5) to obtain ChS-ChI nano-capsules (ChS-ChI@CBLO NCs). RESULTS: Morphological observations of the nano-capsules revealed a spherical shape and diameter around 267-381 nm. The maximum loading capacity (LC) and encapsulation efficiency (EE) for ChS-ChI@CBLO NCs estimated by thermogravimetric analysis (TGA) and derivative thermogravimetric (DTG) analysis were 25.7% and 56.2%, respectively. The structural stability of ChS-ChI@CBLO NCs was confirmed through differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis; moreover DSC also further confirmed the oxidative stability of ChS-ChI@CBLO NCs. Fourier-transform infrared (FTIR) spectra confirmed the excellent stability of ChS-ChI@CBLO NCs against high temperature and sunlight exposure. Biocompatibility analysis also verified the non-toxicity of ChS-ChI@CBLO NCs, further indicating safety and potential application in complex-nutritional supplements. CONCLUSION: Nano-degree of ChS-ChI@CBLO NCs has a loading capacity and encapsulation efficiency of around 16.5 ~ 25.7% and 33.4 ~ 56.2%, respectively, for encapsulation of CBLO. Characterization results also indicate that ChS-ChI@CBLO NCs display high oxidative stability against long-term, hyperthermal, and sunlight exposure. Bioassay results confirm that the ChS-ChI@CBLO NCs are safe and non-toxic. This study demonstrates that nano-capsules are also beneficial in preventing sensitive compounds from metamorphosis, and are non-toxic. These materials are suitable for use in the food and pharmaceutical industries. © 2023 Society of Chemical Industry.

Aerobic glycolysis supports hepatitis B virus protein synthesis through interaction between viral surface antigen and pyruvate kinase isoform M2.

As an intracellular pathogen, the reproduction of the hepatitis B virus (HBV) depends on the occupancy of host metabolism machinery. Here we test a hypothesis if HBV may govern intracellular biosynthesis to achieve a productive reproduction. To test this hypothesis, we set up an affinity purification screen for host factors that interact with large viral surface antigens (LHBS). This identified pyruvate kinase isoform M2 (PKM2), a key regulator of glucose metabolism, as a binding partner of viral surface antigens. We showed that the expression of viral LHBS affected oligomerization of PKM2 in hepatocytes, thereby increasing glucose consumption and lactate production, a phenomenon known as aerobic glycolysis. Reduction of PKM2 activity was also validated in several different models, including HBV-infected HepG2-NTCP-C4 cells, adenovirus mediated HBV gene transduction and transfection with a plasmid containing complete HBV genome on HuH-7 cells. We found the recovery of PKM2 activity in hepatocytes by chemical activators, TEPP-46 or DASA-58, reduced expressions of viral surface and core antigens. In addition, reduction of glycolysis by culturing in low-glucose condition or treatment with 2-deoxyglucose also decreased expressions of viral surface antigen, without affecting general host proteins. Finally, TEPP-46 largely suppressed proliferation of LHBS-positive cells on 3-dimensional agarose plates, but showed no effect on the traditional 2-dimensional cell culture. Taken together, these results indicate that HBV-induced metabolic switch may support its own translation in hepatocytes. In addition, aerobic glycolysis is likely essential for LHBS-mediated oncogenesis. Accordingly, restriction of glucose metabolism may be considered as a novel strategy to restrain viral protein synthesis and subsequent oncogenesis during chronic HBV infection.

Thiazide-associated hyponatremia increases the risk of major adverse cardiovascular events among elderly Taiwanese patients.

BACKGROUND: Thiazide-associated hyponatremia (TAH) has been supposed to increase the risk of major adverse cardiovascular events (MACE) in the elderly. Therefore, this study aimed to evaluate the association of TAH with the risk of MACE in elderly Taiwanese patients. METHODS: Data from the longitudinal generation tracking database (LGTD 2010) of the Health and Welfare Data Science Center (HWDC) were retrospectively assessed. The TAH study group was defined as using > 30 cumulative daily defined doses (CDDDs) thiazide diuretics within one year before diagnosis of hyponatremia. The control group (1:3 propensity score matching) had no diagnosis of hyponatremia but had used > 30 CDDDs thiazide diuretics within one year. Data on MACE were extracted using International Classification of Diseases codes. Outcomes were assessed using a multivariable Cox proportional hazard model and Kaplan-Meier analysis. RESULTS: A total of 1155 and 3465 individuals were enrolled in the TAH and the control groups, respectively. The rates of MACE (11.1% vs. 7.3%) and death (22.8% vs.12.2%) were significantly higher in the TAH group than the control group. In the TAH group, the adjusted HRs were 1.29 (CI 1.01 ‒ 1.65) for MACE, 1.39 (CI 1.19 ‒ 1.63) for all-cause death, and 1.61 (CI 0.90 ‒ 2.92) for stroke. CONCLUSION: TAH in patients above 65-years-old is associated with a 29% higher risk of MACE, 39% higher risk of all-cause death, and 61% higher risk of stroke. This work suggests that thiazides prescription in elderly patients should be more careful. However, further research is required to confirm our findings.

Preliminary Prospective Preoperative and Postoperative Evaluation of Median Nerve Stiffness by Using Sonoelastography.

ABSTRACT: Carpal tunnel syndrome is the most common peripheral nerve entrapment syndrome. No previous studies have compared preoperative and follow-up sonoelastography results or investigated the correlation of median nerve stiffness with the subjective/objective outcomes. Therefore, the aim of this study was to compare the preoperative and postoperative elastography after carpal tunnel release and find the correlation with associated subjective/objective outcomes.From May 2017 to March 2020, 32 patients (6 males, 26 females; 34 hands) with carpal tunnel syndrome were enrolled in this prospective study. Demographic data, QuickDASH score (Chinese version), Boston Carpal Tunnel Questionnaire (Chinese version), nerve conduction velocity/electromyography, and median nerve stiffness by sonoelastography were recorded.Comparisons of preoperative and average sonoelastography findings 1.5 years postoperatively showed a significant decrease in stiffness presented by velocity (Vs) (preoperative Vs, 4.63 ± 1.27 m/s, vs postoperative Vs, 3.39 ± 0.59 m/s; P < 0.001). Changes in subjective functional outcomes also showed the same significant trend. Based on the neurophysiologic study, the improvement of nerve conduction study and elastography have the significant correlation.The same trend of preoperative and postoperative changes in median nerve stiffness and subjective questionnaires/objective neurophysiologic studies may imply that sonoelastography can be used to assess the response to surgery in patients with carpal tunnel syndrome.

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Isolinderalactone (ILL), a sesquiterpene isolated from the root extract of Lindera aggregata, has been reported to exhibit anti-proliferative and anti-metastatic activities in various cancer cell lines. However, the mechanisms associated with its antitumor effects on CRC cells remain unclear. ILL treatment significantly suppressed proliferation and induced cell cycle G2/M arrest in CRC cells by inhibiting the expression of cyclin B, p-cdc2, and p-cdc25c and up-regulating the expression of p21. In addition, ILL induced mitochondria-associated apoptosis through the up-regulation of cleaved -caspase-9 and -3 expression. ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine). Furthermore, ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. Application of the ROS scavenger, N-acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL-induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS-mediated signaling in human CRC cells.

Green extraction and purification of chondroitin sulfate from jumbo squid cartilage by a novel procedure combined with enzyme, ultrasound and hollow fiber dialysis.

Chondroitin sulfate (ChS) from marine sources is gaining attention. The purpose of this study was to extract ChS from jumbo squid cartilage (Dosidicus gigas) using ultrasound-assisted enzymatic extraction (UAEE). An ultrasound with protease assistance, including either alcalase, papain or Protin NY100 was used to extract ChS. The results showed that alcalase had the best extraction efficiency. The response surface methodology was employed to evaluate the relationship between extraction conditions and extraction yield of ChS. The ridge max analysis revealed a maximum extraction yield of 11.9 mg ml- 1 with an extraction temperature of 59.40 °C, an extraction time of 24.01 min, a pH of 8.25, and an alcalase concentration of 3.60%. Compared to ethanol precipitation, purification using a hollow fiber dialyzer (HFD) had a higher extraction yield of 62.72% and purity of 85.96%. The structure characteristics of ChS were identified using FTIR, 1 H-NMR, and 13 C-NMR to confirm that the purified ChS structure was present in the form of chondroitin-4-sulfate and chondroitin-6-sulfate. The results of this study provide a green and efficient process for extraction and purification of ChS and are essential for the use of ChS for the development and production of nutrient food products or pharmaceuticals. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05701-7.

Prognostic value of patient-reported outcome measures (PROMs) in adults with non-small cell Lung Cancer: a scoping review.

BACKGROUND: There is growing interest in the collection and use of patient-reported outcome measures (PROMs) to support clinical decision making in patients with non-small cell lung cancer (NSCLC). However, an overview of research into the prognostic value of PROMs is currently lacking. AIM: To explore to what extent, how, and how robustly the value of PROMs for prognostic prediction has been investigated in adults diagnosed with NSCLC. METHODS: We systematically searched Medline, Embase, CINAHL Plus and Scopus for English-language articles published from 2011 to 2021 that report prognostic factor study, prognostic model development or validation study. Example data charting forms from the Cochrane Prognosis Methods Group guided our data charting on study characteristics, PROMs as predictors, predicted outcomes, and statistical methods. Two reviewers independently charted the data and critically appraised studies using the QUality In Prognosis Studies (QUIPS) tool for prognostic factor studies, and the risk of bias assessment section of the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for prognostic model studies. RESULTS: Our search yielded 2,769 unique titles of which we included 31 studies, reporting the results of 33 unique analyses and models. Out of the 17 PROMs used for prediction, the EORTC QLQ-C30 was most frequently used (16/33); 12/33 analyses used PROM subdomain scores instead of the overall scores. PROMs data was mostly collected at baseline (24/33) and predominantly used to predict survival (32/33) but seldom other clinical outcomes (1/33). Almost all prognostic factor studies (26/27) had moderate to high risk of bias and all four prognostic model development studies had high risk of bias. CONCLUSION: There is an emerging body of research into the value of PROMs as a prognostic factor for survival in people with NSCLC but the methodological quality of this research is poor with significant bias. This warrants more robust studies into the prognostic value of PROMs, in particular for predicting outcomes other than survival. This will enable further development of PROM-based prediction models to support clinical decision making in NSCLC.

Simultaneous Paramedian Pedicle Forehead and Free Medial Sural Artery Perforator Flap Reconstruction of a Composite Nasal Defect: A Case Report.

BACKGROUND: Extensive nasal defects after resection of a malignancy are a challenge for all plastic surgeons. Nasal composite tissue defects have to be reconstructed with multiple staging surgeries. A paramedian pedicled forehead flap and free tissue transfer can be used for lining and skin replacement at different stages. In general, free tissue transfer is used for nasal lining and nasal floor reconstruction at the preliminary stage. Several weeks or months later, a paramedian pedicled forehead flap is used to replace the skin. Intermediate stages will also be necessary, and therefore the total therapeutic course is very long. AIM AND OBJECTIVES: The aim of this study was to report the simultaneous use of a paramedian pedicle forehead flap and a free medial sural artery perforator (MSAP) flap to reconstruct a composite nasal defect after wide excision of squamous cell carcinoma. PATIENT: In 2015, a 57-year-old woman with squamous cell carcinoma of the nose underwent tumor wide excision, which caused a composite defect involving multiple nasal subunits (partial tip, dorsum, right sidewall, right ala subunits). She received both a pedicled paramedian forehead flap to replace the skin and an MSAP flap to reconstruct the lining during the same procedure. At the intermediate stage 4 weeks later, the pedicled forehead flap was elevated and tailored. Then, a further 4 weeks later, flap division was performed. RESULTS: The patient received a total of 3 surgical procedures to reconstruct the composite defects of multiple nasal subunits. Nasal reconstruction was done within 2 months. The patient was satisfied with the aesthetic appearance and functional outcome. CONCLUSIONS: Simultaneous paramedian pedicle forehead and free flap reconstruction can provide an effective solution for composite nasal defects. Satisfactory functional and aesthetic results can be achieved.

Identification of Entry Inhibitors against Delta and Omicron Variants of SARS-CoV-2.

Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2.

Quantitation of Nitration, Chlorination, and Oxidation in Hemoglobin of Breast Cancer Patients by Nanoflow Liquid Chromatography Tandem Mass Spectrometry.

Cells are continually exposed to endogenous reactive oxygen, nitrogen, and halogen species, causing damage to biomolecules. Among them, peroxynitrite and hypochlorous acid are not only oxidants but also biological nitrating and chlorinating agents, leading to the formation of 3-nitrotyrosine and 3-chlorotyrosine, respectively, in proteins. 3-Nitrotyrosine has been detected in vivo under several pathophysiological conditions, including breast cancer. Studies show that the concentrations of 3-nitrotyrosine in plasma proteins and platelets were significantly elevated in breast cancer patients. Compared to blood serum albumin, hemoglobin adducts represent biomonitoring of exposure with a longer lifetime. In this study, human hemoglobin was freshly isolated from blood and digested into peptides with trypsin, and the levels of protein adducts, including nitration, nitrosylation, and chlorination of tyrosine as well as oxidation of methionine residues, were simultaneously quantified by nanoflow liquid chromatography nanoelectrospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) with selected reaction monitoring. The results demonstrated that the relative extents of nitration at α-Tyr-42 and ß-Tyr-130, nitrosylation at α-Tyr-24, and chlorination at α-Tyr-24 and ß-Tyr-130 are significantly higher in globin of 25 breast cancer patients compared to those in 25 healthy subjects (p < 0.05). In particular, nitration at α-Tyr-42 and chlorination at α-Tyr-24 showed the area under the receiver operating characteristic curve of >0.8. While the age of the subjects is correlated with the extents of some of these adducts, the body mass index does not have an effect on any of them. Starting with 1 drop of blood, our results indicated that this highly sensitive and specific nanoLC-NSI/MS/MS is useful in investigating the role of reactive nitrogen oxide species and reactive chlorine species in the etiology of breast cancer.

Association between cirrhosis and herpes zoster in a cohort study in Taiwan.

OBJECTIVES: The aim of the study was to assess if an association exists between cirrhosis and herpes zoster in Taiwan. METHODS: A retrospective cohort study was designed to analyse the 2000-2013 claim dataset of 1 million insured residents who were randomly sampled from the Taiwan National Health Insurance Program. In total, 16 190 subjects aged 20-84 years old with newly diagnosed cirrhosis since 2000 to 2012 were identified as the cirrhosis group and 16 190 sex- and age-matched subjects without cirrhosis were selected as the non-cirrhosis group. Both cirrhosis and non-cirrhosis groups were followed until a new diagnosis of herpes zoster was made or until the end of 2013. The multivariable Cox proportional hazard regression model was applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for herpes zoster associated with cirrhosis. RESULTS: The incidence rate of herpes zoster was 1.08-fold greater in the cirrhosis group than the non-cirrhosis group (8.33 vs 7.69 per 1000 person-years, 95%CI 1.02-1.15). After adjusting for confounders, the adjusted HR of herpes zoster was 1.11 (95% CI 1.004-1.24) for the cirrhosis group compared with the non-cirrhosis group. The adjusted HR increased to 1.33 (95% CI 1.02-1.74) for the decompensated cirrhosis group compared with the non-cirrhosis group. CONCLUSIONS: Cirrhosis is associated with a small but significant increase in the risk of herpes zoster. Given that the risk of herpes zoster is small and the expense of herpes zoster vaccination is high, whether cirrhotic persons need to be vaccinated should assess the balance of cost and benefit.

The impacts of ambient temperature and ultraviolet radiation on the incidence of herpes zoster: An ecological study in Taiwan.

The aim of the study was to examine the relationship between ambient temperature, ultraviolet radiation, and the development of herpes zoster in Taiwan. An ecological study was conducted to analyse the database of the Taiwan National Health Insurance Programme. Participants aged ≥20 years with newly diagnosed herpes zoster between 2003 and 2012 were selected for analysis. The monthly incidence rate of herpes zoster was measured between 2003 and 2012. Monthly average ambient temperature in Celsius (°C) between 2003 and 2012 was measured according to the official database of the Central Weather Bureau in Taiwan. Monthly accumulated ultraviolet radiation (MJ m-2 ) between 2003 and 2012 was measured according to the official database of the Environmental Protection Administration in Taiwan. The overall incidence rates of herpes zoster ranged from 2.54 to 5.67 per 10 000 persons per month from 2003 to 2012.The monthly average ambient temperature was higher and the monthly accumulated ultraviolet radiation was stronger from May to October. The incidence rates of herpes zoster seemed to be high during the period of high ambient temperature and strong ultraviolet radiation (from May to October).Whenever ambient temperature increased 1°C per month, the incidence rate of herpes zoster increased by 0.072 per 10,000 persons per month. Whenever ultraviolet radiation increased 1 MJ m-2 per month, the incidence rate of herpes zoster increased by 0.313 per 10 000 persons per month. There is a significant association between ambient temperature, ultraviolet radiation, and the development of herpes zoster in Taiwan. The incidence rate of herpes zoster is high during the period of high ambient temperature and strong ultraviolet radiation. Low ambient temperature and weak ultraviolet radiation might be beneficial for the prevention of herpes zoster.

Distribution of killer cell immunoglobulin-like receptor (KIR) genes in a large, multi-centre cohort of Chinese donors.

BACKGROUND: The killer cell immunoglobulin-like receptor (KIR), which mediates the killing function of NK cells, is an attractive candidate for adoptive cellular therapy. The ethnic distribution for China provides a unique opportunity to investigate KIR gene distribution. AIM: The aim of this study was to explore the relationship between population history and the rapidly evolving KIR genetic diversity. SUBJECTS AND METHODS: 8050 Chinese donors from 184 hospitals were included to analyse frequency, haplotype, and B-content data of 16 KIR genes, by PCR-SSP for KIR genotyping. RESULTS: KIR gene carrier frequencies were found similar to those observed in other studies on Han, but different from Thais, Japanese, Africans, and populations of West Eurasian ancestry. High-frequency KIR genotype profiles found in the present population were consistent with other studies on Han populations but different from those conducted on other cohorts. The majority of our cohort carried group A KIR gene motifs. Additionally, populations with similar geographic locations in China were shown clustered together, while Hainan and Xinjiang provinces were slightly separated from these. CONCLUSION: The distribution of KIR genes varies by geographic region, and different ethnic groups may be a confounding factor of KIR diversity.

Hispolon Induces Apoptosis, Suppresses Migration and Invasion of Glioblastoma Cells and Inhibits GBM Xenograft Tumor Growth In Vivo.

Hispolon, a polyphenol compound isolated from Phellinus linteus, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial-mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.

Risk of herpes zoster among patients with predialysis chronic kidney disease in a cohort study in Taiwan.

BACKGROUND/OBJECTIVE: Patients on chronic dialysis are at risk of developing herpes zoster, but little systematic research focuses on the association between predialysis chronic kidney disease and herpes zoster. The objective of the study was to explore the association between predialysis chronic kidney disease and herpes zoster in Taiwan. METHODS: A nation-based retrospective cohort study was performed using the 2005-2012 database of the Taiwan National Health Insurance Program. There were 16 655 subjects aged 20-84 years with newly diagnosed predialysis chronic kidney disease as the study group and 33 310 randomly selected subjects without chronic kidney disease as the comparison group. Both groups were matched with sex, age, comorbidities and the year of the index date. The incidence rates of herpes zoster in both groups were calculated. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for herpes zoster associated with predialysis chronic kidney disease. RESULTS: The overall incidence rate of herpes zoster was 1.4-fold higher in the predialysis chronic kidney disease group than that in the non-chronic kidney disease group (8.76 vs 6.27 per 1000 person-years, 95% CI 1.27-1.54; P < .001). After controlling for co-variables, the adjusted HR of herpes zoster was 1.38 (95% CI 1.25-1.53; P < .001) for subjects with predialysis chronic kidney disease compared with non-chronic kidney disease subjects. The adjusted HR increased to 1.65 for subjects with predialysis chronic kidney disease and with any comorbidity (95% CI 1.42-1.92; P < .001). CONCLUSIONS: Patients with predialysis chronic kidney disease correlate with approximately 1.4-fold increased hazard of developing herpes zoster.

The Synergistic Anti-Cancer Effects of NVP-BEZ235 and Regorafenib in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual PI3K/mTOR inhibitor BEZ235 in the human HCC cell lines (n = 3). The combined treatment with BEZ235 and regorafenib enhanced the inhibition of cell proliferation and increased the expression of cleaved caspase-3 and cleaved PARP in HCC cells. Moreover, the combined treatment suppressed HCC cell migration and invasion in the transwell assay. Further, the Western blot analyses confirmed the involvement of epithelial-mesenchymal transition (EMT)-related genes such as slug, vimentin, and matrix metalloproteinase (MMP)-9/-2. Additionally, the proteinase activity of MMP-9/-2 was analyzed using gelatin zymography. Furthermore, the inhibition of phosphorylation of the Akt, mTOR, p70S6K, and 4EBP1 after combined treatment was validated using Western blot analysis. Therefore, these results suggest that the combined treatment with BEZ235 and regorafenib benefits patients with HCC.

Association of dietary patterns with depressive symptoms in Chinese postmenopausal women.

Many components in diet have regulated oxidative stress, inflammatory reaction and even balance oestrogen levels. Because these factors are closely associated with depressive symptoms in postmenopausal women, it is considered that dietary factors are able to prevent and control depressive symptoms. On the other hand, a dietary pattern that considers the correlations and synergies between foods and nutrients is expected to have a greater impact on disease risk. The aim of the present study is to evaluate whether dietary patterns are associated with depressive symptoms in Chinese postmenopausal women. A cross-sectional study of 2051 postmenopausal women (mean age: 58·8 (sd 7·4) years) was conducted in Tianjin, China. Dietary consumption was assessed by a valid self-administered FFQ. Principal component analysis was used to derive three major dietary patterns: 'healthy', 'sweets' and 'traditional Tianjin' from eighty-eight food items. Depressive symptoms were assessed using the Zung Self-Rating Depression Scale, and cut-off point of 48 indicating serious depressive symptoms. The association between quartile of dietary patterns and depressive symptoms was assessed using multiple logistic regression analysis. The multivariable-adjusted OR of having depressive symptoms for increasing quartile of dietary patterns were as follows: healthy, 1·00, 0·79 (95 % CI 0·49, 1·28), 0·62 (95 % CI 0·37, 1·04) and 0·57 (95 % CI 0·33, 0·97); sweets, 1·00, 0·75 (95 % CI 0·42, 1·3), 1·08 (95 % CI 0·64, 1·81) and 1·66 (95 % CI 1·03, 2·71); and traditional Tianjin, 1·00, 1·02 (95 % CI 0·58, 1·79), 0·96 (95 % CI 0·54, 1·71) and 2·53 (95 % CI 1·58, 4·16), respectively. The present study demonstrated that a healthy dietary pattern was inversely associated with depressive symptoms. On the contrary, greater adherence to sweets and traditional Tianjin dietary patterns was associated with a higher prevalence of depressive symptoms.