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Background Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p Conclusions Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides.

AIM: To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus. METHODS: In our prospective clinical trial, 40 patients (60 eyes) with progressive keratoconus were randomized to undergo corneal cross-linking with transepithelial (TE group, n=30) or epithelium-off (EO group, n=30) keratoconus. Examinations comprised topography, corneal biomechanical analysis and specular microscopy at 6mo postoperatively. RESULTS: The keratometer values were not significantly different between the TE and EO corneal cross-linked groups in different periods (each P>0.05). The corneal thickness of the EO group was greater than that of the TE group at 1wk after the operation (each P

Qian Li,1,2,* Dan-Lei Xiong,3,* Heng Wang,1 Wei-Li Jin,4 Ying-Yu Ma,5 Xiao-Ming Fan1,2 1Graduate Department, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Ultrasound, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 3School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 310018, People’s Republic of China; 4Department of Gastroenterology, Nanxun People’s Hospital (Zhejiang Provincial People’s Hospital Nanxun Branch), Huzhou, 313009, Zhejiang Province, People’s Republic of China; 5Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying-Yu MaKey Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaTel + 86-0571-85893781Email myy011525@163.comXiao-Ming FanGraduate Department, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of ChinaTel + 86-0571-85893291Email fan-xiaoming@163.comPurpose: SLC41A3 is a member of the solute carrier family 41 (SLC41) and is involved in many cellular processes as a magnesium ion transporter. Although it plays an important role in cancer formation and development, the correlation between the expression of SLC41A3 and the occurrence and prognosis of hepatocellular carcinoma (HCC) remains unclear. Therefore, this study was focused on the evaluation of the relationship between SLC41A3 and the development and prognosis of HCC.Patients and Methods: Firstly, we collected the mRNA expression of SLC41A3 in HCC through the platform of Oncomine. Then, the subgroups of HCC were performed by the UALCAN website and the prognosis of HCC was analyzed by Kaplan–Meier Plotter database. Subsequently, immunohistochemistry (IHC) method was used to detect SLC41A3 expression in 323 clinically confirmed HCC samples and 184 non-cancerous liver tissues. Finally, function enrichment analysis was done using the LinkInterpreter module in LinkedOmics, and gene set enrichment analysis (GSEA) was performed using TCGA data set.Results: The Oncomine database and immunohistochemical (IHC) showed higher SLC41A3 expression in HCC tissue compared to normal tissue. The expression of SLC41A3 was significantly correlated with tumor metastasis, Edmondson grade, microvascular invasion, and AFP level. Kaplan–Meier and Cox regression analyses verified that high SLC41A3 expression is a significant prognostic factor for reduced overall survival in HCC patients.Conclusion: Our results demonstrated that high expression of SLC41A3 was the predictor of poor prognosis in HCC patients, suggesting that this protein may be a potential target for HCC therapy.Keywords: HCC, solute carrier 41A3, immunohistochemistry, bioinformatics

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

Clinical scores, molecular markers and cellular phenotypes have been used to predict the clinical outcomes of patients with glioblastoma. However, their clinical use has been hampered by confounders such as patient co-morbidities, by the tumoral heterogeneity of molecular and cellular markers, and by the complexity and cost of high-throughput single-cell analysis. Here, we show that a microfluidic assay for the quantification of cell migration and proliferation can categorize patients with glioblastoma according to progression-free survival. We quantified with a composite score the ability of primary glioblastoma cells to proliferate (via the protein biomarker Ki-67) and to squeeze through microfluidic channels, mimicking aspects of the tight perivascular conduits and white-matter tracts in brain parenchyma. The assay retrospectively categorized 28 patients according to progression-free survival (short-term or long-term) with an accuracy of 86%, predicted time to recurrence and correctly categorized five additional patients on the basis of survival prospectively. RNA sequencing of the highly motile cells revealed differentially expressed genes that correlated with poor prognosis. Our findings suggest that cell-migration and proliferation levels can predict patient-specific clinical outcomes.

Background Several epidemiological studies have investigated the association between whole grains intake and digestive tract cancer risk; however, the results are still controversial. The purpose of this meta-analysis was to assess the association. Methods Studies published before March 2020 were searched in database and other sources. The risk ratio (RR) with the 95% confidence interval (CI) were pooled using fix or random-effects models. Results This meta-analysis included 34 articles reporting 35 studies, 18 studies of colorectal cancer, 11 studies of gastric cancer and 6 studies of esophagus cancer, involving 2,663,278 participants and 28,921 cases. Comparing the highest-intake participants with the lowest-intake participants for whole grains, we found that the intake of whole grains were inversely related to colorectal cancer (RR = 0.89, 95% CI: 0.84–0.93, P P < 0.001), esophagus cancer (RR = 0.54, 95% CI: 0.44–0.67, P < 0.001), respectively. However, subgroup analysis of colorectal cancer found no significant association in the case-control studies and studies of sample size Conclusion This meta-analysis provides further evidence that whole grains intake was associated with a reduced risk of digestive tract cancer. Our result supports the dietary guidelines that increase whole grains intake to reduce the risk of digestive tract cancer.

BACKGROUND Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. METHODS Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70 grays and 67 grays relative biological effectiveness, respectively. Approximately 53% received IMPT. RESULTS The median follow-up was 23.4 months (range, 1.7-69.3 months) for all patients and 28.1 months (range, 2.3-69.3 months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P

BACKGROUND The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Background Accurate and early diagnosis of residual tumors or intrahepatic recurrences after TACE is critically needed for determining the success of treatments and for guiding subsequent therapeutic planning. This meta-analysis was performed to assess the efficacy of diffusion weighted imaging (DWI) with the quantitative apparent diffusion coefficient (ADC) value in diagnosing residual or recurrent hepatocellular carcinoma after transarterial chemoembolization (TACE). Materials and methods A comprehensive literature search of PubMed, Embase, Web of Science, Scopus and the Cochrane Library database, from inception to July 2019, was conducted to select original studies on diagnosing residual or recurrent HCCs after TACE using DWI sequence with its ADC value. Two researchers independently chose study, extracted data, conducted meta-analysis, and evaluated methodological quality according to Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results Twelve studies comprising 624 patients and 712 tumors were finally included. The pooled sensitivity, specificity and AUC value of DWI in diagnosing residual or recurrent HCCs after TACE were 85% (95%CI: 74–92%), 83% (95%CI: 75–88%) and 0.90 (95%CI: 0.87–0.92), respectively. Residual or recurrent HCCs have significantly lower ADC value than necrotic tumors (MD = -0.48, 95%CI: − 0.69~ − 0.27, P Conclusion This study demonstrated that DWI performed better in diagnosing residual or recurrent HCCs after TACE, and ADC value may serve as alternatives for further evaluation of residual or recurrent leisions in HCC patients after TACE.

Background Radiogenomics explores the association between imaging features and genomic assays to uncover relevant prognostic features; however, the prognostic implications of the derived signatures remain unclear. Purpose To identify preoperative radiogenomic signatures of estrogen receptor-positive breast cancer associated with the Oncotype DX recurrence score (RS) and to evaluate whether they are biomarkers for survival and responses to neoadjuvant chemotherapy (NACT). Materials and Methods In this retrospective multicohort study, three data sets were analyzed. The radiogenomic development data set, with preoperative dynamic contrast-enhanced MRI and RS data obtained between January 2016 and October 2019 was used to identify radiogenomic signatures. Prognostic implications of the imaging signatures were assessed by measuring overall survival and recurrence-free survival in the prognostic assessment data set using a multivariable Cox proportional hazards model. The therapeutic implication of the radiogenomic signatures was evaluated by determining their ability to predict the response to NACT using the treatment assessment data set obtained between August 2015 and March 2019. Prediction performance was estimated by using the area under the receiver operating characteristic curve (AUC). Results The final cohorts included a radiogenomic development data set with 130 women (mean age, 52 years ± 10 [standard deviation]), a prognostic assessment data set with 116 women (mean age, 48 years ± 9), and a treatment assessment data set with 135 women (mean age, 50 years ± 11). Radiogenomic signatures (n = 11) of texture and morphologic and statistical features were identified to generate the predicted RS (R2 = 0.33, P < .001). A predicted RS greater than 29.9 was associated with poor overall and recurrence-free survival (P = .001 and P = .007, respectively); predicted RS was greater in women with a good NACT response (30.51 ± 6.92 vs 27.35 ± 4.04 [responders vs nonresponders], P = .001). By combining the predicted RS and complementary features, the model achieved improved performance in prediction of the NACT response (AUC, 0.85; P < .001). Conclusion Radiogenomic signatures associated with genomic assays provide markers of prognosis and treatment in estrogen receptor-positive breast cancer. © RSNA, 2021 Online supplemental material is available for this article.

BACKGROUND Breast tumor heterogeneity is associated with histological characteristics. However, pharmacokinetic (PK) heterogeneity within tumor might merit further exploration. PURPOSE To enhance the predictive power of molecular subtypes, Ki-67, and tumor grade by analyzing PK heterogeneity within tumor based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). STUDY TYPE Retrospective. POPULATION Two hundred and eight biopsy-proven breast cancer patients, randomly divided into a training cohort (N = 144) and a testing cohort (N = 64). FIELD STRENGTH/SEQUENCE T1 -weighted DCE-MRI at 3.0 T. ASSESSMENT A convex analysis of mixtures-compartmental modeling decomposition method was used to estimate the PK parameter (i.e., the volume transfer constant Ktrans ) in tumor subregions with distinct physiological kinetic patterns, including fast-flow kinetics, slow-flow kinetics, and plasma input. Radiomic features based on the PK parameter were calculated from each tumor subregion. STATISTICAL TESTS The training cohort was used to build random forest classifiers based on the optimal features determined by the 5-fold cross-validation method. The performance was assessed on the testing cohort using the area under the receiver operating characteristic curve (AUC). The AUCs derived from the tumor subregion-based PK parameter were compared with those of the original images of the entire tumor using the DeLong test. A P-value of

OBJECTIVE Complications affect the outcome of patients with cirrhosis. The favorable prognosis of patients with Wilson disease (WD)-related cirrhosis suggests that its complications differ from those of hepatitis B virus (HBV) infection-related cirrhosis. We aimed to delineate the differences in complications between WD-related and HBV-related cirrhosis. METHODS The electronic-medical data from patients with WD-related and HBV-related cirrhosis were extracted and analyzed. RESULTS In total, 211 patients with WD-related cirrhosis and 374 patients with HBV-related cirrhosis were enrolled. Most patients with WD progressed to cirrhosis 10 years. Patients with WD-related cirrhosis had a markedly lower prevalence of ascites (8.5% vs. 38.5%), gastroesophageal varices/variceal bleeding (13.3% vs. 47.6%), renal impairment (0 vs. 7.6%) and primary liver cancer (0 vs. 39.3%; all p

Background Numerous studies and guidelines suggest an outcome detriment from radiation treatment breaks (rTBs) and the need for compensatory dosing in patients with head and neck cancer. Methods In a consecutive cohort of 521 patients with oropharyngeal squamous cell carcinoma (OPSCC), we investigated the impact of rTBs and prolongation of overall treatment time (OTT) on OS, DFS, LRC, and cancer recurrence using competing risk and multivariate analyses. Results Neither OTT prolongation by ≤2 days nor rTBs of ≤3 days were associated with detriments to clinical outcomes. Consecutive breaks of ≥3 days were also not significantly associated with detriment to clinical outcomes. There was significantly increased competing mortality in those with longer breaks. Conclusions In OPSCC patients treated with definitive concurrent chemoradiotherapy, there is no significant association between disease failure and total rTBs of ≤3 consecutive or scattered days. Further investigation is needed for longer breaks.

Immunophenotyping of inflammatory dermal infiltrates in Malassezia folliculitis (MF) and pityriasis versicolor (PV) lesions is less reported. Immunohistochemistry was performed on 21 MF lesions, 10 PV lesions, and 10 control skin. CD3+, CD4+, CD8+, CD20+, CD68+, and CD117+ cells were increased in MF compared with PV and normal skin (P Lay Summary Malassezia folliculitis and pityriasis versicolor are common Malassezia-induced superficial mycoses. Their clinicopathological discrepancy may be due to the difference of cellular and humoral immune responses.

Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

Objective: To evaluate the diagnostic efficiency of bronchoalveolar lavage fluid (BALF) for MycobacteriumTuberculosis (MTB) infection using laboratory methods. Methods: A retrospective study was conducted in patients diagnosed with active pulmonary tuberculosis (APTB) and lacking sputum quality/quantity. BALF collected during the operation processes of Electric bronchoscopy were tested using Ziehl-Neelsen staining acid-fast bacilli smear microscopy (Z-N-AFB-SM), GeneXpert MTB/RIF（Xpert），loop-mediated isothermal amplification (LAMP), or culturing with BACTEC™ Mycobacterial Growth Indicator Tube™ 960 (MGIT). Chi-square test was used for statistic analysis. Results: 331 suspected APTB patients were enrolled in this study. 224 of them were sputum-scarce. 89 were sputum-sufficient andnegative in both Z-N-AFB-SM and MGIT 960 testing. Of the sputum sufficient patients, BALF-testing confirmed APTB diagnosis in 20.2% (18/89) via Z-N-AFB-SM, and 53.0% (35/89) via MGIT. The total positive rates of BALF testing via four aforementioned methods were 18.2% (57/313), 66.4% (168/253), 61.0% (83/136) and 48.2% (140/290) respectively. The positive rate of MTB discovered in BALF collected by well-trained respiratory physicians are significantly higher than those collected by anesthetists (χ2=22.48, PConclusion: BALF has a similar sensitivity and specificity for APTB laboratory diagnosis. It can be used as a complementary diagnostic method for APTB when sputum availability is poor. The proficiency of BALF collection is an important factor affecting the detection results.

Annular syphilis may range from mildly raised lesions with scaly borders to verrucous plaques. Localized annular syphilis on the genitalia has been rarely reported in HIV-negative cases. This paper reports a case of annular secondary syphilis on the penis. Dermoscopy showed peripheral dotted and short linear vessels and white scaling with a relatively clear central area in an erythematous annular plaque. Histopathology revealed mild hyperkeratosis, parakeratosis, psoriasiform acanthosis, and focal basal vacuolar degeneration with lichenoid, perivascular, and periadnexal infiltrate of lymphohistiocytes and plasma cells in the superficial dermis. Silver stain showed several spirochetes in the lower epidermis and superficial dermis. Electron microscopy revealed a few intercellular and intracytoplasmic spirochetes in the basal epidermis and free spirochetes in the papillary dermis. Rapid plasma reagin and Treponema pallidum particle agglutination assays were positive. The lesions disappeared after intramuscular benzathine penicillin, with no relapse at six-month follow-up.

Background Heterogeneity is a common finding within tumours. We evaluated the imaging features of tumours based on the decomposition of tumoural dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data to identify their prognostic value for breast cancer survival and to explore their biological importance. Methods Imaging features (n = 14), such as texture, histogram distribution and morphological features, were extracted to determine their associations with recurrence-free survival (RFS) in patients in the training cohort (n = 61) from The Cancer Imaging Archive (TCIA). The prognostic value of the features was evaluated in an independent dataset of 173 patients (i.e. the reproducibility cohort) from the TCIA I-SPY 1 TRIAL dataset. Radiogenomic analysis was performed in an additional cohort, the radiogenomic cohort (n = 87), using DCE-MRI from TCGA-BRCA and corresponding gene expression data from The Cancer Genome Atlas (TCGA). The MRI tumour area was decomposed by convex analysis of mixtures (CAM), resulting in 3 components that represent plasma input, fast-flow kinetics and slow-flow kinetics. The prognostic MRI features were associated with the gene expression module in which the pathway was analysed. Furthermore, a multigene signature for each prognostic imaging feature was built, and the prognostic value for RFS and overall survival (OS) was confirmed in an additional cohort from TCGA. Results Three image features (i.e. the maximum probability from the precontrast MR series, the median value from the second postcontrast series and the overall tumour volume) were independently correlated with RFS (p values of 0.0018, 0.0036 and 0.0032, respectively). The maximum probability feature from the fast-flow kinetics subregion was also significantly associated with RFS and OS in the reproducibility cohort. Additionally, this feature had a high correlation with the gene expression module (r = 0.59), and the pathway analysis showed that Ras signalling, a breast cancer-related pathway, was significantly enriched (corrected p value = 0.0044). Gene signatures (n = 43) associated with the maximum probability feature were assessed for associations with RFS (p = 0.035) and OS (p = 0.027) in an independent dataset containing 1010 gene expression samples. Among the 43 gene signatures, Ras signalling was also significantly enriched. Conclusions Dynamic pattern deconvolution revealed that tumour heterogeneity was associated with poor survival and cancer-related pathways in breast cancer.

BACKGROUND Intertrochanteric fracture (ITF) is a common type of injury, and nearly 30% of ITF patients die in the first 12 mo, especially the elderly with limited activity. Tranexamic acid (TXA) has been widely used in reducing traumatic and surgical bleeding, however, the paucity of studies regarding its use in orthopedic trauma surgery has limited its integration into this field, which may benefit most from TXA. The safety of TXA in this group has not achieved a consensus. AIM This meta-analysis was designed to investigate the efficacy and safety of TXA in elderly ITF patients undergoing surgery. METHODS Databases, including Medline and PubMed, were searched for randomized controlled trials (RCTs) that were published before October 2018 and that addressed the efficacy and safety of TXA in patients who underwent ITF surgery. The Consolidated Standards of Reporting Trials 2010 Statement Checklist was used to assess the methodological quality of each study. Trials without and with heterogeneity were compared by fixed-effects analysis and random-effects analysis, respectively. For each study, odds ratio (OR) and 95%CI and mean differences and 95%CI were calculated for dichotomous and continuous outcomes, respectively. The Power and Sample Size Program software was used to calculate power and sample size. Stability of the results was assessed via sensitivity analysis. RESULTS A total of 836 patients from eight RCTs were subjected to meta-analysis. TXA treatment compared with the control group significantly reduced postoperative blood loss (95%CI, -20.83 to -7.93 mL, P < 0.0001), hidden blood loss (95%CI, -213.67 to -64.43 mL, P = 0.0003), and total blood loss (95%CI, -332.49 to -23.18 mL, P = 0.02) by weighted mean differences of -14.38, -139.05, and -177.83 mL, respectively. However, no significant difference was observed between groups for analysis of intraoperative blood loss. The meta-analysis also proved that the usage of TXA in ITFs may not significantly increase the incidence of deep venous thrombosis. Allogeneic blood transfusion data showed that significantly fewer patients in the TXA group (42%) required transfusion than the control group (95%CI, 0.36 to 0.69; P < 0.0001). CONCLUSION In ITF surgery, intravenous administration of TXA reduces the risk of hidden blood loss and the need for allogeneic transfusion, without increasing thrombotic risk.

This study aimed to predict the molecular subtypes of breast cancer via intratumoural and peritumoural radiomic analysis with subregion identification based on the decomposition of contrast-enhanced magnetic resonance imaging (DCE-MRI). The study included 211 women with histopathologically confirmed breast cancer. We utilised a completely unsupervised convex analysis of mixtures (CAM) method by unmixing dynamic imaging series from heterogeneous tissues. Each tumour and the surrounding parenchyma were thus decomposed into multiple subregions, representing different vascular characterisations, from which radiomic features were extracted. A random forest model was trained and tested using a leave-one-out cross-validation (LOOCV) method to predict breast cancer subtypes. The predictive models from tumoural and peritumoural subregions were fused for classification. Tumour and peritumour DCE-MR images were decomposed into three compartments, representing plasma input, fast-flow kinetics, and slow-flow kinetics. The tumour subregion related to fast-flow kinetics showed the best performance among the subregions for differentiating between patients with four molecular subtypes (area under the receiver operating characteristic curve (AUC) = 0.832), exhibiting an AUC value significantly (p

Background Diffuse myocardial interstitial fibrosis (DMIF) is a key factor for heart failure (HF) in diabetic cardiomyopathy. This study examined the accuracy of the qualitative and quantitative evaluation of early DMIF in a type 1 diabetes mellitus (T1DM) mouse model through 7.0 T cardiac magnetic resonance imaging-based T1 mapping.Methods Eight-week-old C57Bl/6J male mice were randomly divided into control (n = 20) and T1DM (n = 30, induced by a low dose streptozotocin dose of 60 mg/kg) groups. The progression of DMIF was examined every 4 weeks until 24 weeks after successful establishment of the model. Cardiac functional and morphological parameters were evaluated through echocardiography by using a high-resolution ultrasound cardiovascular system. A 7.0 T CMR scan was performed using the pre- and post-contrast GRE Look–Locker inversion recovery T1 mapping sequence. The extracellular volume fraction (ECV) was calculated from CMR and hematocrit data. Sirius Red staining was simultaneously performed in each group to detect DMIF and calculate the collagen volume fraction (CVF). Differences in ECV and CVF values between two groups were analyzed using one-way analysis of variance. The correlation between ECV and CVF values was assessed using the Pearson test.Results Six mice were included every 4 weeks in the control and T1DM groups for statistical analysis. Compared with the control group, a progressive decrease in FS, EF, and E/A ratio was observed in the T1DM group. In the T1DM group, both ECV and CVF values were gradually increased during diabetes progression. A marked increase in ECV and CVF values was observed at 12 weeks in the T1DM group than in the control group (ECV: 32.5% ± 1.6% vs 28.1% ± 1.8%, P = 0.002; CVF: 6.9% ± 1.8% vs 3.3% ± 1.1%, P < 0.01). ECV values showed a strong correlation with CVF in the T1DM group (r = 0.856, P < 0.001).Conclusion ECV is a reliable and feasible imaging marker that can be used to quantitatively assess dynamic DMIF changes in T1DM mice. In addition, ECV could accurately detect DMIF in the early stage and thus can be used as an imaging tool for early intervention in T1DM mice in the future.

Breast tumor morphological and vascular characteristics can be changed during neoadjuvant chemotherapy (NACT). The early changes in tumor heterogeneity can be quantitatively modeled by longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is useful in predicting responses to NACT in breast cancer. In this retrospective analysis, 114 female patients with unilateral unifocal primary breast cancer who received NACT were included in a development (n = 61) dataset and a testing dataset (n = 53). DCE-MRI was performed for each patient before and after treatment (two cycles of NACT) to generate baseline and early follow-up images, respectively. Feature-level changes (delta) of the entire tumor were evaluated by calculating the relative net feature change (deltaRAD) between baseline and follow-up images. The voxel-level change inside the tumor was evaluated, which yielded a Jacobian map by registering the follow-up image to the baseline image. Clinical information and the radiomic features were fused to enhance the predictive performance. The area under the curve (AUC) values were assessed to evaluate the prediction performance. Predictive models using radiomics based on pre- and post-treatment images, Jacobian maps and deltaRAD showed AUC values of 0.568, 0.767, 0.630 and 0.726, respectively. When features from these images were fused, the predictive model generated an AUC value of 0.771. After adding the molecular subtype information in the fused model, the performance was increased to an AUC of 0.809 (sensitivity of 0.826 and specificity of 0.800), which is significantly higher than that of the baseline imaging- and Jacobian map-based predictive models (p = 0.028 and 0.019, respectively). The level of tumor heterogeneity reduction (evaluated by texture feature) is higher in the NACT responders than in the nonresponders. The results suggested that changes in DCE-MRI features that reflect a reduction in tumor heterogeneity following NACT could provide early prediction of breast tumor response. The prediction was improved when the molecular subtype information was combined into the model.

Evidence-based medicine tries to support clinicians through research, integrated with clinical skill and patient values. This pilot study aimed to assess appropriateness and level of evidence of current clinical practices, through evaluating availability and quality of guidelines.A prospective observational study in a large tertiary hospital network was performed, sampling diagnostic and therapeutic interventions in obstetrics and gynaecology. Interventions performed were justified against knowledge in the published literature, and guideline recommended practice. We collected 58 patient observations, 40(69%) in obstetrics, 18(31%) in gynaecology. There were local guidelines relevant in 52%, national in 22%, and international guidelines in 12%. In 50 interventions with available guidelines, 54% provided strong and clear recommendations for practice, and were supported by research-based knowledge. Similarly, 66% of encounters were thought to be in concordance with research-based knowledge.There was good concordance between interventions and guideline recommendations. However, half of guidelines reviewed had limited or no knowledge to justify their recommendations.IMPACT STATEMENTWhat is already known on this subject? Evidence based medicine should aim to improve patient outcomes. However, available trials assessing effectiveness of established practices suggest that they convey little to no benefit to patients. There remains a paucity of evidence for established practices in obstetrics and gynaecologyWhat do the results of this study add? This pilot study assesses the usefulness of interventions in obstetrics and gynaecology and confirms the feasibility of collecting and coding our interventions and clinical practices with a traffic light system.What are the implications of these findings for clinical practice and/or further research? These findings demonstrate the feasibility of our traffic lights grading system within obstetrics and gynaecology. It demonstrates this method is useful to assess what knowledge base is guiding clinical practice, how well practice concords with guidelines and literature, as well as the presence and significance of any gaps in knowledge. These early findings will be used in an expanded study and have implications on the way healthcare effectiveness is evaluated, as well as reducing healthcare expenditure in obstetrics and gynaecology.

Oncotype DX recurrence score (RS) is increasingly used to differentiate patients at high risk of recurrence from those who have low risk of recurrence. Despite the promising value, this genetic technology has disadvantage in its expensive and currently not readily available in most of the institute, which limited the clinical applications in management of breast cancer. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is becoming standard-of-care in breast cancer management. It is of vital importance to predict Oncotype DX RS using radiomics from DCE-MRI to perform a noninvasive evaluation of recurrence in breast cancer. To this end, 131 patients were included in the dataset, of which 13 (9.9%) had a low risk of recurrence (RS

Objectives To evaluate disparity in service quality between second- and third-tier hospitals and explore factors that affect patients' perception of service quality in China. Design Cross sectional study. Setting Twelve hospitals in China. Participants 5714 patients. Intervention None. Main Outcome Measure Total score of the SERVQUAL scale and each of its five dimensions. Results Patients from third-tier hospitals rated significantly higher scores overall and in all the five dimensions of the SERVQUAL scale. Those with lower education, urban residents and those who had higher degree of life satisfaction and attention paid to health perceived higher service quality. Inpatients perceived higher service quality compared with outpatients. Conclusion We found a significant gap in patient's perceived service quality between second- and third-tier hospitals in China. A variety of demographic and personality factors were found to significantly influence patient's perceived service quality.

We describe a 17-year-old man who developed penile annular and scrotal eczematoid syphilids with penile chancre redux. Dermoscopy showed linear-irregular and hairpin vessels with white scales in annular lesions. Histopathology displayed psoriasiform hyperplasia with perivascular lymphoplasmacytic dermal infiltrate. Rapid plasma reagin and Treponema pallidumparticle agglutination assays were positive. The lesions disappeared after intramuscular benzathine penicillin.

The importance of hypoxia in the pathophysiology of inflammatory bowel disease (IBD) is increasingly being realized; also, hypoxia seems to be an important accelerator of brain inflammation, as has been reported by our group and others. IBD is a chronic intestinal disorder that leads to the development of inflammation, which is related to brain dysfunction. However, no studies have reported whether hypoxia is associated with IBD-induced neuroinflammation. Therefore, the objective of the present study was to determine whether hypoxia augments cerebral inflammation in a DSS-induced colitis mouse model. The mouse model was developed using 3% DSS for five days combined with exposure to hypoxic conditions (6,000 m) for two days. Mice were randomly divided into four groups: control group, DSS group, hypoxia group, and DSS plus hypoxia group. The results demonstrated that DSS combined with hypoxia resulted in up-regulation of colonic and plasmatic proinflammatory cytokines. Meanwhile, DSS plus hypoxia increased expression of Iba1, which is a marker of activated microglia, accompanied by increased expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the brain. Moreover, the expression of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5, was markedly downregulated. The current study provides new insight into how hypoxia exposure induces excessive inflammatory responses andpathophysiological consequences in the brain in a DSS-induced colitis model.

We read with interest the article by Lacarrubba et al.1 that offers a valuable review on dermoscopy of genital diseases. However, dermoscopic features of secondary syphilis on genital area have been omitted in the section "Infectious diseases". In addition to the dermoscopic observation of annular secondary syphilis on the penis,2 we have recently encountered another case of secondary recurrent syphilis with localized annular lesions on the penis. These observations could enlarge the dermoscopic feasibility in the dermatological practice.

Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. Furthermore, the changes of gut microbiota in IBD’s patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD. The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD’s remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described. Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD’s remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26, P

Objectives: Acute coronary syndrome (ACS) is an acute disease with high mortality. Although early percutaneous coronary intervention (PCI) is proved to be the practical approach in treating ACS, th...

Background and purposeThe inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury. Wild-type p53-induced protein phosphatase 1 (Wip1), a serine/threonine phosphatase, is expressed in various tissues. A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue; however, its role in the central nervous system (CNS) remains unclear. This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.MethodsA model of middle cerebral artery occlusion and reperfusion was established in mice. CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia. Laser speckle imaging was used to monitor regional cerebral blood flow. Behavioural outcomes were assessed with a TreadScan gait analysis system. TTC staining was used to evaluate the infarct volume, and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia. ELISA was performed to detect the levels of inflammatory factors.ResultsWip1 expression was increased after ischaemia/reperfusion. Wip1-knockout (KO) mice displayed more severe brain injury than wild-type mice, as indicated by aggravated motor dysfunction, greater brain infarct volumes and higher expression of inflammatory cytokines (interleukin-6 and tumour necrosis factor alpha) in the brain. We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models, which all showed activation of microglia/macrophages. Lentivirus-Ppm1d reversed the injury induced by Wip1-KO.ConclusionsOur results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.

We present a 56-year-old woman with metastatic follicular thyroid cancer at the nose tip with I uptake that is clinically rare, mimicking physiological uptake in the nose, a common finding seen after routine I therapeutic imaging. The lesion revealed a metastatic follicular thyroid cancer with I uptake and response to I therapy. Surgical removal, however, was not performed due to cosmetic and functional considerations. Active surveillance is warranted owing to its relative aggressiveness in nature.

Locally recurrent head and neck malignancies after definitive radiation or chemoradiation represent challenging clinical scenarios requiring careful consideration of individualized risks and benefits before deciding upon the next best course of therapy. Herein, a case-based approach to personalized decision making highlights the expert opinions of leaders in head and neck oncology. Topics of interest include optimal candidacy for reirradiation or salvage surgical resection, the judicious use of chemotherapy as induction therapy or as a radiosensitizing agent, the incorporation of immunotherapy into the treatment paradigm for locally recurrent disease, and the impact of various treatment modalities on quality of life and functional outcomes. Interestingly, the lack of consensus among the experts on topics as fundamental as the appropriateness of offering reirradiation at all and as nuanced as target volume delineation for the reirradiated field suggests that there is no straightforward approach in this scenario. Common to all opinions is a desire to maximize the therapeutic ratio for a patient potentially facing a grim prognosis, and honest discussions about goals of care and expectations for post-treatment quality of life should be central to the clinical approach to this and similar cases.

Background Chronic obstructive pulmonary disease (COPD) is a major and growing cause of morbidity and mortality throughout the world. However, there remains a limited understanding of the association between individual socioeconomic status (SES) and COPD diagnosis and treatment worldwide, including in China. This study investigates socioeconomic variations in prevalence, diagnosis, and treatment of COPD in rural China. Methods The present study employed a cross-sectional survey design. The study population was composed of Han majority as well as Na Xi and Bai ethnic minority individuals 35 years of age and older living in Yunnan Province from 2017 to 2019. In total, 7534 individuals consented to participate in the study and complete a structured interview as well as a post-bronchodilator spirometry test. Multivariate logistic regression was used to analyze the association between individual socioeconomic status variables and the prevalence, diagnosis, and treatment of COPD. Results The age-standardized prevalence of COPD in the present study was 14.3%. Prevalence differed by gender: prevalence for men was 17.1%, versus 11.4% for women (P = 0.0001). Overall, levels of diagnosis and treatment of COPD for participants with COPD were 24.2 and 23.1%, respectively. Multivariate logistic regression indicated that higher educational levels and good access to medical services was associated with an overall lower risk of COPD (P = 0.032 vs. P = 0.018) as well as a higher probability of COPD diagnosis among those with COPD (P = 0.0001 vs. P = 0.002). Participants with COPD with higher educational levels (P = 0.0001) and higher annual household incomes (P = 0.0001) as well as good access to medical services (P = 0.016) were more likely to receive COPD medications and treatment than their counterparts. While Na Xi and Bai participants had a higher probability of having COPD (P = 0.0001), they had a lower probability of having received a diagnosis or treatment for COPD than Han participants (P = 0.0001 vs. P = 0.0012). Conclusions Future interventions to further control COPD and improve diagnosis and treatment should focus on ethnic minority communities, and those with low education levels, low annual household incomes, and poor access to medical services.

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes with a number of advanced malignancies. However, diverse immune-related adverse events (iRAEs) occurred with the widespread use of ICIs, some of which are rarely and life-threatening. Here we report a 66-year-old patient with lung adenocarcinoma who received two doses of sintilimab, a human monoclonal antibody against programmed cell death-1 (PD-1), experienced a fatal storm of iRAEs. He was admitted to the intensive care unit (ICU) by immune induced-myositis/myocarditis and rhabdomyolysis. Despite immediate immunosuppressive therapy with methylprednisolone (MP) and immunoglobulin intravenously, he developed into myositis-myasthenia gravis (MG) overlap syndrome complicated with myasthenia crisis. We commenced plasma exchange (PLEX), mechanical ventilation, immunosuppressive therapy, as well as other supportive therapies. Three months later, the patient's serum creatine phosphate kinase (CPK) and anti-acetylcholine receptor antibody (anti-AChR-Ab) returned to normal despite tumor progression. Herein we discuss the incidence, operating mechanism and management strategies of the fatal iRAEs. Early admission to the ICU and multidisciplinary collaborative treatment for unstable patients with iRAEs could help to achieve a favorable outcome.

Objectives Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. Materials and Methods We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. Results Median age was 66 years. Median follow-up for all patients was 6.0 months and 9.7 months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were > 2 year interval from prior RT and 3–4 QS cycles. Median LPFS was 5.1 months with 1-year LPFS 17.7%, and median OS was 6.4 months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS > 70, presence of palliative response and 3–4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n = 18). No Grade 4–5 toxicities were observed. Conclusion Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3–4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS > 70 and proton therapy are associated with survival improvements.

BACKGROUND: Video-assisted thoracic surgery (VATS) has been increasingly used in pediatric patients. We evaluated the outcomes of VATS and thoracotomy for pediatric mediastinal tumors. METHODS: A total of 137 patients who underwent surgery for mediastinal tumors at our department from March 2012 to September 2018 were recruited in this retrospective study. Forty-three patients were treated by VATS and ninety-four underwent thoracotomy (two patients who underwent open surgery were excluded from the study because they were lost to follow-up). Data including demographic information, tumor characteristics, operative time, conversion of surgery, blood transfusion, postoperative hospital stay, mortality and recurrence were collected and compared between the two groups. RESULTS: No significant difference was found in gender, age, weight and tumor distribution between the two groups. The number of patients with malignant tumors who underwent thoracotomy was significantly higher than those who received VATS (78.0% vs. 22.0%, P=0.04). Patients received thoracotomy had significantly larger mean tumor diameter than those who underwent VATS (7.6±3.8 vs. 4.4±1.7 cm, P

Saturated fatty acids (SFAs) (the "bad" fat), especially palmitate (PA), in the human diet are blamed for potential health risks such as obesity and cancer because of SFA-induced lipotoxicity. However, epidemiological results demonstrate a latent benefit of SFAs, and it remains elusive whether a certain low level of SFAs is physiologically essential for maintaining cell metabolic hemostasis. Here, we demonstrate that although high-level PA (HPA) indeed induces lipotoxic effects in liver cells, low-level PA (LPA) increases mitochondrial functions and alleviates the injuries induced by HPA or hepatoxic agent carbon tetrachloride (CCl4). LPA treatment in mice enhanced liver mitochondrial activity and reduced CCl4 hepatotoxicity with improved blood levels of aspartate aminotransferase (AST), alanine transaminase (ALT), and mitochondrial aspartate transaminase (m-AST). LPA-mediated mitochondrial homeostasis is regulated by CDK1-mediated SIRT3 phosphorylation, which in turn deacetylates and dimerizes CPT2 to enhance fatty acid oxidation. Thus, an advantageous effect is suggested by the consumption of LPA that augments mitochondrial metabolic homeostasis via CDK1-SIRT3-CPT2 cascade.

While inflammatory bowel disease (IBD) might be a risk factor in the development of brain dysfunctions, the underlying mechanisms are largely unknown. Here, mice were treated with 5% dextran sodium sulfate (DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-α levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSS-induced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis. These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here, we provide new information on the impact of colitis on the outcomes of cortical inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-018-0288-5) contains supplementary material, which is available to authorized users.

Background Serum human epididymis protein 4 (HE4) is a potential marker for endometrial cancer (EC), however, the diagnostic value of HE4 for EC remains controversial. In this study, we performed a meta-analysis to estimate the diagnostic accuracy of serum HE4 for EC. Methods Literature reports of the diagnostic accuracy of serum HE4 for EC were systematically identified using online data-bases. The meta-analysis was performed using STATA 12.0, Meta-Disc 1.4, and Review Manager 5.2. Results A total of 4182 participants and 23 studies were included in our meta-analysis. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.65 (95% CI: 0.56–0.73), 0.91 (95% CI: 0.84–0.95), (95% CI: 4.38–12.64), 0.38 (95% CI: 0.31–0.47), 19.46 (95% CI: 11.61–32.62) and 0.84 (95% CI: 0.81 to 0.87), respectively. Our overall analysis suggested that HE4 is a useful diagnostic marker for EC. Subgroup analysis indicated that studies with benign disease controls showed higher diagnostic accuracies than those with healthy controls. Conclusion Serum HE4 may serve as a potential biomarker for EC diagnosis. Due to certain limitations, this conclusion should to be cautiously interpreted.

Little work has been done on the prediction of papillary thyroid microcarcinoma in female patients who have given birth to children, which may be different from other people. We performed a retrospective review of female patients who underwent thyroidectomy, aiming at identifying special predictors of papillary thyroid microcarcinoma in female patients who have given birth to children. Univariate analysis was used to identify potential covariates for the prediction of papillary thyroid microcarcinoma. Multivariable logistic regression analysis was used to identify independent predictors and construct a regression model based on a training cohort (246 patients) and then the regression model was validated using an independent cohort (80 patients). We found that having not more than one boy, taller-than-wide shape, poorly defined margin, marked hypoechogenicity, and microcalcification were independent risk factors for the papillary thyroid microcarcinoma in multivariate analyses. The combined predictive formula had a high predictive effect for papillary thyroid microcarcinoma (AUC = 0.938 for training cohort and 0.929 for validation cohort, respectively). The combined predictive formula has clinical value in the prognosis of papillary thyroid microcarcinoma and it may be simple and effective to ask fertility condition of patients to increase the US diagnosis accuracy of papillary thyroid microcarcinoma.

Aim The aim of this study was to identify the correlation between health-related quality of life (HRQOL) and risk factors of first-incidence hip fracture in postmenopausal women. Methods This case-control study included 99 postmenopausal women with first-incident hip fracture and 101 women without hip fracture who were matched according to age. Evaluation consisted of clinical factors, 36-item Short-Form Health Survey (SF-36) and dual-energy X-ray absorptiometry for bone mineral density of hip and spine. Results The mean age of patients with an accidental first-incident hip fracture was 78.0 years. Patients with hip fractures had significantly lower scores for SF-36 domains at enrollment and 4-month follow up compared with the controls. Mental health also deteriorated significantly 4 months after hip fracture. Aside from lower HRQOL, clinical factors, including increased body height, no experience with estrogen therapy, rheumatoid arthritis, use of walking aids, less weight-bearing exercise, and diuretics use, were significant risk factors for hip fracture in univariate analysis. After multivariate adjustment, only the use of walking aids and decreased physical component summary were independent risk factors of hip fracture. Besides aging, use of walking aids, weight-bearing exercise, and psychological medication were the main factors affecting HRQOL when considering their relationship with hip fractures. Conclusion The occurrence of first-incidence hip fracture is highly associated with HRQOL. Aside from aging, clinical factors affecting HRQOL correlated with hip fracture incidence. Thus, in elderly women, exercise or physical therapy to improve physical function and mental support is crucial and should be considered the most important factors for first-incidence hip fracture prevention.

Background Public health emergencies have challenged the public health emergency management systems (PHEMSs) of many countries critically and frequently since this century. As the world’s most populated country and the second biggest economy in the world, China used to have a fragile PHEMS; however, the government took forceful actions to build PHEMS after the 2003 SARS outbreak. After more than one decade’s efforts, we tried to assess the improvements and problems of China’s PHEMS between 2002 and 2012. Methods We conducted two rounds of national surveys and collected the data of the year 2002 and 2012, including all 32 provincial, 139 municipal, and 489 county CDCs. The municipal and county CDCs were selected by systematic random sampling. Twenty-one indicators of four stages (preparation, readiness, response and recovery) from the National Assessment Criteria for CDC Performance were chosen to assess the ten-year trends. Results At the preparation stage, organization, mechanisms, workforce, and stockpile across all levels and regions were significantly improved after one decade’s efforts. At the readiness stage, the capability for formulating an emergency plan was also significantly improved during the same period. At the response stage, internet-based direct reporting was 98.8%, and coping scores were nearly full points of ten in 2012. At the recovery stage, the capabilities were generally lower than expected. Conclusions Due to forceful leadership, sounder regulations, and intensive resources, China’s PHEMS has been improved at the preparation, readiness, and response stages; however, the recovery stage was still weak and could not meet the requirements of crisis management and preventive governance. In addition, CDCs in the Western region and counties lagged behind in performance on most indicators. Future priorities should include developing the recovery stage, establishing a closed feedback loop, and strengthening the capabilities of CDCs in Western region and counties.

The kidney is vulnerable to hypoxia-induced injury. One of the mechanisms underlying this phenomenon is cell apoptosis triggered by hypoxia-inducible factor-1- α (HIF-1α) activation. MicroRNA-210 (miR-210) is known to be induced by HIF-1α and can regulate various pathological processes, but its role in hypoxic kidney injury remains unclear. Here, in both rat systemic hypoxia and local kidney hypoxia models, we found miR-210 levels were upregulated significantly in injured kidney, especially in renal tubular cells. A similar increase was observed in hypoxia-treated human renal tubular HK-2 cells. We also verified that miR-210 can directly suppress HIF-1α expression by targeting the 3′ untranslated region of HIF-1α mRNA in HK-2 cells in severe hypoxia. Accordingly, miR-210 overexpression caused significant inhibition of the HIF-1α pathway and attenuated apoptosis caused by hypoxia, while miR-210 knockdown exerted the opposite effect. Taken together, our findings verify that miR-210 is involved in the molecular response in hypoxic kidney lesions in vivo and attenuates hypoxia-induced renal tubular cell apoptosis by targeting HIF-1α directly and suppressing HIF-1α pathway activation in vitro.

Inflammatory linear verrucous epidermal nevus and linear psoriasis are sometimes hard to differentiate clinically and pathologically. Although immunohistochemical expression of keratin 10 (K10), K16, Ki-67, and involucrin may be useful for differentiating both entities, these results have been reported in only a few cases. We collected data from 8 patients with inflammatory linear verrucous epidermal nevus, 11 with psoriasis vulgaris, and 8 healthy controls and evaluated immunohistochemical expression of Ki-67, K16, involucrin, and filaggrin among them. Ki-67 and K16 overexpression was similar in inflammatory linear verrucous epidermal nevus and psoriasis vulgaris compared with normal skin. Although staining for involucrin showed discontinuous expression in parakeratotic regions in 4 inflammatory linear verrucous epidermal nevus cases, it was continuous in the other 4 cases and in all psoriasis vulgaris cases. Filaggrin expression was present in hyperkeratotic regions but scarce in parakeratotic areas in both inflammatory linear verrucous epidermal nevus and psoriasis vulgaris. The immunostaining pattern of Ki-67, K16, involucrin, and filaggrin may be insufficient to discriminate inflammatory linear verrucous epidermal nevus from psoriasis vulgaris.

Aim: This study developed and validated a non-invasive scoring model to predict 1-year hepatitis B e antigen (HBeAg) seroconversion in response to nucleos(t)ide analog (NA) treatment in NA-naïve patients with HBeAg-positive chronic hepatitis B (CHB). Methods: Baseline data from 1014 patients visiting the outpatient and inpatient clinics of Beijing Ditan Hospital, Capital Medical University, China between October 2008 and April 2015 were included. These patients received NAs for HBeAg-positive CHB. The patients were assigned randomly to the derivation (n = 710) and validation (n = 304) cohorts in a 7:3 ratio. A prediction scoring model was established based on univariate and multivariate Cox proportional hazards regression analyses to identify independent prediction factors. In the derivation cohort, the odds ratio of the predictors were converted to integer risk scores by rounding the quotient from dividing the odds ratio, and the final score was the sum of these values. The predictive accuracy of the scoring model was further assessed using Harrell’s concordance index (C-index). Results: The 1-year cumulative HBeAg seroconversion rates were 11.83% and 8.55% in the derivation and validation cohorts, respectively. In the derivation cohort, baseline pretreatment alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), globulin (GLO), and quantitative HBeAg (qHBeAg) levels were independently associated with HBeAg seroconversion and were included in the scoring system. The model had good discrimination in the derivation and validation cohorts (C-index = 0.750, 95% confidence interval 0.694–0.806 and C-index = 0.776, 95% confidence interval 0.698–0.855, respectively). The prediction scores ranged from 0 to 4; scores of 0–1 and 2–4 identified patients with lower and higher levels of HBeAg seroconversion, respectively. Kaplan–Meier analysis was used to determine the 1-year cumulative HBeAg seroconversion rates in the two groups (scores of 0–1 and 2–4) of the primary cohort, and log-rank tests revealed a significant difference (4.87% vs. 20.9%, p