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Purpose Segmentation of the whole breast and fibroglandular tissue (FGT) is important for quantitatively analyzing the breast cancer risk in the dynamic contrast-enhanced magnetic resonance (DCE-MR) images. The purpose of this study is to improve the accuracy and efficiency of the segmentation of the whole breast and FGT in 3-D fat-suppressed DCE-MR images with a versatile deep learning (DL) framework. Methods We randomly collected 100 breast DCE-MR scans from Shanghai Cancer Hospital of Fudan University. The MR scans in the dataset were different in both the spatial resolution and the MR scanners employed. Furthermore, four breast density categories were assessed by radiologists based on Breast Imaging Reporting and Data System (BI-RADS) of American College of Radiology. The dataset was separated into the training and the testing sets, while keeping a balanced distribution of scans with different imaging parameters and density categories. The nnU-Net has been recently proposed to automatically adapt preprocessing strategies and network architectures for a given medical image dataset, thus showing a great potential in the systematic adaptation of DL methods to different datasets. In this study, we applied the nnU-Net to segment the whole breast and FGT in 3-D fat-suppressed DCE-MR images. Five-fold cross validation was employed to train and validate the segmentation method. Results The segmentation performance was evaluated with the volume and surface agreement metrics between the DL-based automatic and the manually delineated masks, as quantified with the following measures: the average Dice volume overlap (0.968 ± 0.017 and 0.877 ± 0.081), the average surface distances (0.201 ± 0.080 mm and 0.310 ± 0.043 mm), and the Pearson correlation coefficient of masks (0.995 and 0.972) between the automatic and the manually delineated masks, as calculated for the whole breast and the FGT segmentation, respectively. The correlation coefficient between the breast densities obtained with the DL-based segmentation and the manual delineation was 0.981. There was a positive bias of 0.8% (DL-based relative to manual) in breast density measurement with the Bland-Altman plot. The execution time of the DL-based segmentation was approximately 20 s for the whole breast segmentation and 15 s for the FGT segmentation. Conclusions Our DL-based segmentation framework using nnU-Net could robustly achieve high accuracy and efficiency across variable MR imaging settings without extra pre- or post-processing procedures. It would be useful for developing DCE-MR-based CAD systems to quantify breast cancer risk and to be integrated into the clinical workflow.

We investigated the effects of botulinum toxin on gait in Parkinson’s disease (PD) patients with foot dystonia. Six patients underwent onabotulinum toxin A injection and were assessed by Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), visual analog scale (VAS) of pain, Timed Up and Go (TUG), Berg Balance Test (BBT), and 3D gait analysis at baseline, 1 month, and 3 months. BFMDRS (p = 0.002), VAS (p = 0.024), TUG (p = 0.028), and BBT (p = 0.034) were improved. Foot pressures at Toe 1 (p = 0.028) and Midfoot (p = 0.018) were reduced, indicating botulinum toxin’s effects in alleviating the dystonia severity and pain and improving foot pressures during walking in PD.

Background: Carcinoembryonic antigen (CEA) is one of the important indexes for the diagnosis and prognosis of gastrointestinal cancer. Systemic inflammatory response (SIR) is closely related to the occurrence and development of gastrointestinal cancer. Methods: A total of 803 patients who underwent radical gastrectomy in Qinghai University Affiliated Hospital from January 2012 to December 2016 were included as training set. Multivariable Cox proportional hazard regression was used to identify associations with outcome of gastric cancer (GC). CNLR was established by combining CEA and the neutrophils to lymphocytes ratio (NLR, a typical parameter in SIR) to generate a novel prognostic score system and its prognostic value was externally validated. Results: Multivariate analysis showed that CEA and NLR were independent prognostic factors for GC patients (both p < 0.05). A higher CNLR was significantly associated with older age, male sex, larger tumor size, vascular invasion and advanced stages (all p < 0.05). Patients with higher CNLR had poor prognosis than those with lower CNLR (p < 0.05). Multivariate analysis showed that CNLR was an independent prognostic factor (p < 0.05). Incorporation of the CNLR into a prognostic model including age and TNM stage generated a nomogram, which predicted accurately 3- and 5-year survival for GC patients. And similar results were obtained in the external validation set. Conclusions: The CNLR prognostic scoring system established by combining CEA and NLR is an independent prognostic factor for GC, which can be incorporated into the traditional TNM staging to improve the prediction of long-term survival outcomes.

Background This study investigated the incidence, radiographic patterns, and relevance to clinical outcome of everolimus-related pneumonitis (ERP) in patients with metastatic breast cancer (MBC). Materials and Methods Data of patients with MBC treated with everolimus who had baseline and at least one follow-up chest computed tomography (CT) were obtained from a medical electronic database system. An independent review of the CT scans of these patients was conducted by two radiologists (NCT 03730428). Log-rank and Cox proportional hazard regression analyses were used for time-to-event analyses. Results ERP was radiographically detected in 45 of 86 patients (52.3%). In more than 80% of these patients, ERP occurred during the first 4 months of everolimus treatment. Only 14 of the 45 patients with ERP were symptomatic (31.1%). Symptoms included cough, fever, and shortness of breath. Bilateral and lower distribution of the pneumonitis was most common. In most of the cases, ground-glass opacities and reticular opacities were noticed. Elderly patients were more likely to develop ERP. Patients with ERP had significantly longer progression-free survival (PFS; 6.8 vs. 4.1 months, p = .024) and overall survival (OS; 42.8 vs. 21.3 months, p = .016). ERP was a predictor of OS improvement confirmed by multivariate Cox analysis (hazard ratio, 0.49; 95% confidence interval, 0.25–0.97; p = .040). Conclusions ERP was noted in half of the patients with MBC treated with everolimus. Our data suggested that ERP was associated with improved prognosis and may be used as a biomarker for the efficacy of everolimus in MBC. Close monitoring, prompt diagnosis, and proper treatment for ERP are essential to maintain the quality of life of patients and achieve maximum treatment benefits. Implications for Practice Everolimus-related pneumonitis (ERP) is one of the most worrying drug adverse events, especially in Asian patients. However, little has been known about the clinical and radiographic details of ERP in patients with metastatic breast cancers (MBCs) treated with everolimus. The present study investigated the clinical characteristics, radiographic patterns, and its correlation with treatment outcome in patients with MBC. ERP was identified in more than half of patients with MBC during everolimus therapy and was associated with improved outcome. Close monitoring and prompt diagnosis and appropriate treatment for ERP are critical for the preservation of patients' quality of life and achievement of maximal treatment benefits.

Purpose To identify MRI-based radiomics signature (Rad-score) as a biomarker of risk stratification for disease-free survival (DFS) in patients with HER2-positive invasive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC) and establish a radiomics-clinicoradiologic-based nomogram that combines Rad-score, MRI findings, and clinicopathological variables for DFS estimation. Patients and Methods A total of 127 patients were divided into a training set and testing set according to the ratio of 7:3. Radiomic features were extracted from multiphase CE-MRI (CEm). Rad-score was calculated using the LASSO (least absolute shrinkage and selection operator) regression analysis. The cutoff point of Rad-score to divide the patients into high- and low-risk groups was determined by receiver operating characteristic curve analysis. A Kaplan-Meier survival curves and the Log rank test were used to investigate the association of the Rad-score with DFS. Univariate and multivariate Cox proportional hazards model were used to determine the association of Rad-score, MRI features, and clinicopathological variables with DFS. A radiomics-clinicoradiologic-based nomogram combining the Rad-score, MRI features, and clinicopathological findings was plotted to validate the radiomic signatures for DFS estimation. Results The Rad-score stratified patients into high- and low-risk groups for DFS in the training set (P

Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson’s disease. In this study, we aimed to identify the gut microbiome associated with Parkinson’s disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson’s disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson’s disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson’s disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease. We developed the first gut microbial gene catalogue associated with Parkinson’s disease. Twenty-five gene markers were identified that distinguished Parkinson’s disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1–96.1%). A highly accurate Parkinson’s disease index, which was not influenced by disease severity or Parkinson’s disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson’s disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4–98.0%), but also in an independent group of 78 patients with Parkinson’s disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0–95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson’s disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson’s disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson’s disease.

Purpose To explore the laparoscopic technique with the retroperitoneal approach for complex adrenal tumors. Patients and methods The clinical data of 11 patients with complex adrenal tumors from July 2017 to July 2018 were analyzed retrospectively. Among them, there were 4 males and 7 females, 4 with adrenal myelolipomas, 3 with adrenal pheochromocytomas, 2 with adrenal cysts, 1 with adrenocortical adenoma and 1 with adrenal ganglioneuroma. The average tumor diameter was 6.5 ± 1.2 cm, and the average age of the patients was 48 ± 13 years. Results All the operations were successfully completed. The average operation time was 95 ± 15 min, the average amount of blood loss was 50 ± 15 mL, and the average postoperative hospital stay was 2.6 ± 1.3 days. No tumor recurrence was found after 1 year of follow-up. Conclusion Retroperitoneal laparoscopic surgery is effective for the treatment of complex adrenal tumors, but it requires good surgical skills. Surgeons skilled in laparoscopic technology can safely carry out retroperitoneal laparoscopic surgery for complex adrenal tumors.

Ferroptosis, a form of regulated cell death caused by lipid peroxidation, was recently identified as a natural tumor suppression mechanism. Here, we show that ionizing radiation (IR) induces ferroptosis in cancer cells. Mechanistically, IR induces not only reactive oxygen species (ROS) but also the expression of ACSL4, a lipid metabolism enzyme required for ferroptosis, resulting in elevated lipid peroxidation and ferroptosis. ACSL4 ablation largely abolishes IR-induced ferroptosis and promotes radioresistance. IR also induces the expression of ferroptosis inhibitors, including SLC7A11 and GPX4, as an adaptive response. IR- or KEAP1 deficiency-induced SLC7A11 expression promotes radioresistance through inhibiting ferroptosis. Inactivating SLC7A11 or GPX4 with ferroptosis inducers (FINs) sensitizes radioresistant cancer cells and xenograft tumors to IR. Furthermore, radiotherapy induces ferroptosis in cancer patients, and increased ferroptosis correlates with better response and longer survival to radiotherapy in cancer patients. Our study reveals a previously unrecognized link between IR and ferroptosis and indicates that further exploration of the combination of radiotherapy and FINs in cancer treatment is warranted.

Background: To investigate ipsilateral breast tumor recurrence (IBTR) in patients who have undergone breast-conserving surgery (BCS) after neoadjuvant systematic therapy (NST). Method: Three hundred and twenty-one patients undergoing BCS after NST and 2,534 patients undergoing initial BCS from June 2008 to June 2017 at Fudan University Shanghai Cancer Center were retrospectively enrolled, and statistical analyses, including propensity score matching, were applied to compare IBTR-free survival. The main factors related to IBTR in the NST group were estimated utilizing univariate and multivariate analyses. Results: After propensity score matching, the 3-year IBTR-free survival rates were 93.7% (95% CI, 90.6–96.8%) in the NST group and 96.9% (95% CI, 94.9–98.9%) in the matched initial BCS group at a median follow-up period of 58 months. IBTR-free survival did not differ statistically between the two groups (P=0.154). According to multivariate analysis in the NST group, tumor-infiltrating lymphocytes (TILs), epidermal growth factor receptor 2 (HER2) status and pathologic ductal carcinoma in situ (DCIS) constituent were the factors related to IBTR after BCS. Conclusions: BCS after NST and initial BCS have equivalent IBTR-free survival. BCS after NST is a safe and effective therapy in terms of IBTR.

Background: To investigate whether the radiomics signature (Rad-score) of DCE-MRI images obtained in triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NAC) is associated with disease-free survival (DFS). Develop and validate an intuitive nomogram based on radiomics signatures, MRI findings, and clinicopathological variables to predict DFS.Methods: Patients (n = 150) from two hospitals who received NAC from August 2011 to May 2017 were diagnosed with TNBC by pathological biopsy, and follow-up through May 2020 was retrospectively analysed. Patients from one hospital (n = 109) were used as the training group, and patients from the other hospital (n = 41) were used as the validation group. ROIs were drawn on 1.5 T MRI T1W enhancement images of the whole volume of the tumour obtained with a 3D slicer. Radiomics signatures predicting DFS were identified, optimal cut-off value for Rad-score was determined, and the associations between DFS and radiomics signatures, MRI findings, and clinicopathological variables were analysed. A nomogram was developed and validated for individualized DFS estimation.Results: The median follow-up time was 53.5 months, and 45 of 150 (30.0%) patients experienced recurrence and metastasis. The optimum cut-off value of the Rad-score was 0.2528, which stratified patients into high- and low-risk groups for DFS in the training group (pConclusion: The Rad-score derived from preoperative MRI features is an independent biomarker for DFS prediction in patients with TNBC to NAC, and the combined radiomics nomogram improved individualized DFS estimation.

Qin Li,1,2,&ast; Qin Xiao,1,2,&ast; Jianwei Li,2,3 Zhe Wang,4,5 He Wang,4,5 Yajia Gu1,2 1Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, People’s Republic of China; 5Human Phenome Institute, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yajia Gu; He Wang Tel +8618017312040Fax +862164174774Email guyajia@126.com; hewang@fudan.edu.cnBackground: To assess the value of radiomics based on multiphases contrast-enhanced magnetic resonance imaging (CE-MRI) for early prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with human epithelial growth factor receptor 2 (HER2) positive invasive breast cancer.Methods: A total of 127 patients with newly diagnosed primary HER2 positive invasive breast cancer underwent CE-MRI before NAT and performed surgery after NAT. Radiomic features were extracted from the 1st postcontrast CE-MRI phase (CE1) and multi-phases CE-MRI (CEm),respectively. With selected features using a forward stepwise regression, 23 machine learning classifiers based on CE1 and CEm were constructed respectively for differentiating pCR and non-pCR patients. The performances of classifiers were assessed and compared by their accuracy, sensitivity, specificity and AUC (area under curve). The optimal machine learning classification was used to discriminate pCR vs non-pCR in mass and non-mass groups, uni-focal and unilateral multi-focal groups, respectively.Results: For the task of pCR classification, 6 radiomic features from CE1 and 6 from CEm were selected for the construction of machine learning models, respectively. The linear SVM based on CEm outperformed the logistic regression model using CE1 with an AUC of 0.84 versus 0.69. In mass and non-mass enhancement groups, the accuracy of linear SVM achieved 84% and 76%. Whereas in unifocal and unilateral multifocal cases, 79% and 75% accuracy were achieved by linear SVM.Conclusion: Multiphases CE-MRI imaging may offer more heterogeneity information in the tumor and provide a non-invasive approach for early prediction of pCR to NAT in patients with HER2-positive invasive breast cancer.Keywords: radiomics, breast cancer, neoadjuvant therapy, machine learning, magnetic resonance imaging

To investigate whether digital breast tomosynthesis (DBT) and subsequently generated synthesized mammography (SM) images show a better performance than full-field digital mammography (FFDM) images for diagnosing malignant breast lesions. In addition, the radiation doses for SM using different procedures were compared. This prospective study enrolled 212 women (age ≥ 25 years) with clinically suspicious breast lesions. All participants underwent FFDM and DBT with the same breast compression. Finally, 222 lesions were confirmed by pathological analysis. The mammogram results were evaluated according to the BI-RADS criteria and compared with the pathological results. The diagnostic performances, morphological features and average glandular doses (AGDs) were compared. In total, 141 malignant lesions and 81 benign lesions were confirmed by pathological analysis. The overall AGD showed no significant difference between FFDM and DBT. Compared with 2D imaging, the AUC values of FFDM plus DBT and SM plus DBT were both significantly different overall (P = 0.0002) and remained significantly different in dense breasts (P

Background The optimal standard treatment for primary small cell carcinoma of the esophagus (SCCE) remains undetermined. In this study, we conducted two areas of research on SCCE. First, we analyzed differences in SCCE characteristics between Chinese and U.S. patients. Second, we evaluated optimal treatment strategies for SCCE in the Chinese cohort. Methods Data from 137 Chinese SCCE patients collected from two cancer centers in China were compared with 385 SCCE patients registered in the U.S. SEER program. Prognostic factors were further analyzed in the Chinese group. Propensity score matching (PSM) was used to balance baseline features between the groups. Results There were more Chinese SCCE patients with regional stage disease (41.6%) and surgery was the principal local therapy (78.1%), while 51.7% of U.S. patients was at advanced stages and tended to receive radiotherapy as the main therapy (45.2%). Median overall survival (MST) of Chinese patients was 15.0 months, compared with 8.0 months for U.S. patients (P

Background: Multiple system atrophy (MSA) and Parkinson’s disease (PD) have overlapping symptoms, making diagnosis challenging. Short-chain fatty acids (SCFAs) are produced exclusively by gut microbiota and were reduced in feces of MSA patients. However, plasma SCFA concentrations in MSA patients have not been investigated. Objective: We aimed to investigate the plasma SCFAs in MSA patients and to identify the potential differential diagnostic ability. Methods: Plasma SCFA were measured in 25 MSA patients, 46 healthy controls, and 46 PD patients using gas chromatography-mass spectrometry. Demographic and clinical characteristics of the participants were evaluated. Results: Acetic acid concentration was lower in MSA patients than in healthy controls. Acetic acid and propionic acid concentrations were lower in MSA and MSA with predominant parkinsonism (MSA-P) patients than in PD patients. A receiver operating characteristic curve (ROC) analysis revealed reduced acetic acid concentration discriminated MSA patients from healthy controls with 76% specificity but only 57% sensitivity and an area under the curve (AUC) of 0.68 (95% confidence interval (CI): 0.55–0.81). Combined acetic acid and propionic acid concentrations discriminated MSA patients from PD patients with an AUC of 0.82 (95% CI: 0.71–0.93), 84% specificity and 76% sensitivity. Especially, with combined acetic acid and propionic acid concentrations, MSA-P patients were separated from PD patients with an AUC of 0.89 (95% CI: 0.80–0.97), 91% specificity and 80% sensitivity. Conclusion: Plasma SCFAs were decreased in MSA patients. The combined acetic acid and propionic acid concentrations may be a potential biomarker for differentiating MSA patients from PD patients.

Social media listening (SML) is a new process for obtaining information from social media platforms to generate insights into users' experiences and has been used to analyze discussions about a multitude of diseases. To understand Parkinson's disease patients' unmet needs and optimize communication between doctors and patients, social media listening was performed to investigate concerns in Chinese patients. A comprehensive search of publicly available social media platforms with Chinese-language content posted between January 2005 and April 2019 in mainland China was performed using defined Parkinson's disease-related terms. After multiple steps of machine screening were performed, a series of posts were derived. The content was summarized and classified manually to analyze and map psychological insights, and descriptive statistics were applied to aggregate findings. A total of 101,899 patient-related posts formed the basis of this study. The topics mainly focused on motor symptoms (n = 54,983), choice of pharmaceutical drugs (n = 45,203) and non-motor symptoms (n = 44,855). The most common symptoms mentioned were tremor (54.5%), pain (22.9%), and rigidity (22.1%). Psychological burden (51%) and work/social burden (48%) were the most concerning burdens for patients and their families. The compound levodopa (43%) and dopamine agonists (23%) were the most common options for the patients, while concerns about new-generation anti-Parkinson's disease medication increased. The portraits of patients suggested varying characteristics across different periods and advocate for personalized service from doctors. In the management of patients, it is imperative to plan individualized therapy and education strategies as well as strategies for social support.

PurposeTo develop and validate an imaging-radiomics model for the diagnosis of male benign and malignant breast lesions.MethodsNinety male patients who underwent preoperative mammography from January 2011 to December 2018 were enrolled in this study (63 in the training cohort and 27 in the validation cohort). The region of interest was segmented into a mediolateral oblique view, and 104 radiomics features were extracted. The minimum redundancy and maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) methods were used to exclude radiomics features to establish the radiomics score (rad-score). Mammographic features were evaluated by two radiologists. Univariate logistic regression was used to select for imaging features, and multivariate logistic regression was used to construct an imaging model. An imaging-radiomics model was eventually established, and a nomogram was developed based on the imaging-radiomics model. Area under the curve (AUC) and decision curve analysis (DCA) were applied to assess the clinical value.ResultsThe AUC based on the imaging model in the validation cohort was 0.760, the sensitivity was 0.750, and the specificity was 0.727. The AUC, sensitivity and specificity based on the radiomics in the validation cohort were 0.820, 0.750, and 0.867, respectively. The imaging-radiomics model was better than the imaging and radiomics models; the AUC, sensitivity, and specificity of the imaging-radiomics model in the validation cohort were 0.870, 0.824, and 0.900, respectively.ConclusionThe imaging-radiomics model created by the imaging characteristics and radiomics features exhibited a favorable discriminatory ability for male breast cancer.

BACKGROUND: To determine the histopathological and MRI features of BRCA1/2 mutation-associated familial breast cancers compared with those of BRCA1/2 mutation-negative and sporadic breast cancers and to further compare the imaging features of cancers from BRCA1 and BRCA2 mutation carriers according to lesion type on MRI. METHODS: A retrospective review of medical records was conducted to determine tumour clinicopathologic features and MRI characteristics between June 2011 and July 2017, and 93 lesions with BRCA mutations, 93 lesions without BRCA mutations from familial breast cancers and 93 lesions from sporadic breast cancers were included. Histopathologic data, including immunohistochemistry findings and MRI data according to the BI-RADS lexicon, were reviewed. The association between MRI or histopathologic findings and BRCA mutations was analysed. RESULTS: BRCA-positive familial breast cancers had a higher number of IDCs with high nuclear grade and lymph node metastasis (all P

Objective: Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD), causing great disturbance to patients. The present study investigated the prevalence and the clinical features of constipation in patients with PD and explored the difference between prodromal and clinical constipation of PD.Methods: A total of 186 patients with PD were recruited into this study. Subjective constipation was defined by ROME III criteria. Demographic and PD-related clinical information of the participants were collected. The PD patients were objectively assessed by a spectrum of rating scales of motor symptoms, non-motor symptoms, and quality of life.Results: In total, 51.61% (96/186) of PD patients suffer from constipation. Compared with patients without constipation, the patients with constipation were prone to have restless leg syndrome, depression, and anxiety and have higher scores of the non-motor symptoms scale. Among patients with constipation, 21.88% (21/96) patients had constipation in prodromal stage. Compared with patients with constipation in clinical stage, patients with prodromal constipation had a lower age of constipation onset (56.48 ± 9.63 and 65.26 ± 8.42, χ2 = 4.091, P < 0.001), longer timespan from constipation onset to motor symptom onset (6.62 ± 3.91 and 3.18 ± 2.13, χ2 = −3.877, P = 0.001). Patients with prodromal constipation were predominantly tremor onset (χ2 = 4.405, P = 0.044) and usually had a better quality of life [28 (14.50–37.5) and 40 (25.0–55.0), χ2 = 2.011, P = 0.046]. Depression was the only risk factor of constipation in PD patients. Body mass index, depression, and anxiety were factors that affected the life quality in patients with constipation.Conclusions: Our results supported the high incidence of constipation in patients with PD and that, in some patients, constipation occurred before the onset of motor symptoms. The specific clinical characteristics of patients with constipation and with prodromal constipation help to make early diagnosis, to discover the relationship between constipation and PD, and to further explore the pathogenesis of this degenerative disease.

Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. The interaction between rs11931074 in α-synuclein (SNCA) and α-HCH or β-HCH, respectively, as well as rs16940758 in the microtubule-associated protein tau (MAPT) gene and δ-HCH were related to increased risk of PD. In addition, α-HCH and propanil enhanced the production of reactive oxygen species and decreased of mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

Bone cells in the human body are continuously engaged in cellular metabolism, including the interaction between bone cells, the interaction between the erythropoietic cells of the bone marrow and stromal cells, for the remodeling and reconstruction of bone. Osteoclasts and osteoblasts play an important role in bone metabolism. Diseases occur when bone metabolism is abnormal, but little is known about the signaling pathways that affect bone metabolism. The study of these signaling pathways will help us to use the relevant techniques to intervene, so as to improve the condition. The study of these signaling pathways will help us to use the relevant techniques to intervene, so as to improve the condition. I believe they will shine in the diagnosis and treatment of future clinical bone diseases.

Considering the rapid rise in breast cancer incidence in China and lack of calibrated breast cancer prediction models for the Chinese female population, developing a breast cancer model targeting the Chinese women is necessary. This study aimed at generating a breast cancer risk prediction model for Chinese women. A total of 1079 (85 images contralateral to a cancer and 994 cases without breast cancer) women were recruited from Fudan University Shanghai Cancer Centre. For each case, we collected sixteen demographic variables such as age, BMI, number of children, family history of breast cancer, and age at menarche. Moreover, the dense tissue was automatically segmented by AutoDensity. A set of quantitative features were extracted from the dense area. Using the 80th percentile of intensity values in the dense area, the segmented area was thresholded again and the second set of computer-extracted features was calculated. The features, i.e. the demographic variables, and texture features extracted from the mammographically dense areas of the image, have been fed into an ensemble of 250 decision trees, whose results were combined using RUSBoost. The classifier achieved an AUC of 0.88 (CI: 0.84 - 0.91) for identifying high-risk images. Therefore, adopting such model might lead to the augmentation of discriminatory power of currently-used risk prediction models. However, it should be noted that the cancer cases were retrieved from the diagnostic environment (not screening) and further validation on a dataset from a screening set-up will be required.

A 22-year-old man complained of progressive bilateral blurred vision that had developed 6 years ago. He also noted dispersed scotomas and graying of vison in both eyes, without photopsia, orbital pain, or double vision. He had not seen an ophthalmologist until he could hardly recognize people by appearance 1 week previously. Bilateral optic atrophy (figure, A) was recorded with best-corrected visual acuities of counting fingers OD and 20/400 OS. Perimetry revealed global visual field loss OD and tunnel vision OS (figure, B). He was referred to our neurology clinic, where he reported recurrent mild dull headache from age 10.

Introduction Increasing evidence shows that the PI3K/AKT/mTOR pathway can be activated by a variety of stimulus in immune cells. Schistosomiasis Japonica is a serious threat to human health in some lakes of China. Methods We analyzed the potential associations between the hub gene (PTEN, mTOR, AKT1 and AKT2) polymorphisms of PI3K/AKT/mTOR pathway and S. japonica risk, including infection risk, as well as immunological hepatic fibrosis risk. An immune database named Database of Immune Cell Expression, Expression quantitative trait loci and Epigenomics (DICE) was used to analyze the expression profiles of the hub genes in 15 types of immune cells. Results Of them, two SNPs rs2295080 (mTOR) and rs7254617 (AKT2) were found associated with the risk of infection and fibrosis. We also performed a multivariant Cox regression analysis and found that HBV infection may increase hepatic fibrosis in chronic schistosomiasis patients, instead of genetic polymorphisms on PI3K/AKT/mTOR pathway or any other factors. We also found the expressions of mTOR (RICTOR) and AKT2 in T cells were higher than those in monocyte cells. And, the expressions of PTEN, mTOR (RICTOR) and AKT1 reduced both in activated CD4 T cells and activated CD8 T cells. Conclusions We concluded that rs2295080 may be an important marker in the diagnosis of susceptibility to schistosomiasis infection. But HBV infection not rs2295080 could promote immunological liver damage with fibrosis in patients with chronic schistosomiasis infection.

Maternal exposure to PM2.5 has been associated with abnormal glucose tolerance during pregnancy, but little is known about which constituents and sources are most relevant to glycemic effects. We conducted a retrospective cohort study of 1148 pregnant women to investigate associations of PM2.5 chemical components with gestational diabetes mellitus (GDM) and impaired glucose tolerance (IGT) and to identify the most harmful sources in Heshan, China from January 2015 to July 2016. We measured PM2.5 using filter-based method and analyzed them for 28 constituents, including carbonaceous species, water-soluble ions and metal elements. Contributions of PM2.5 sources were assessed by positive matrix factorization (PMF). Logistic regression model was used to estimate composition-specific and source-specific effects on GDM/IGT. Random forest algorithm was applied to evaluate the relative importance of components to GDM and IGT. PM2.5 total mass and several chemical constituents were associated with GDM and IGT across the early to mid-gestation periods, as were the PM2.5 sources fossil fuel/oil combustion, road dust, metal smelting, construction dust, electronic waster, vehicular emissions and industrial emissions. The trimester-specific associations differed among pollutants and sources. The third and highest quartile of elemental carbon, ammonium (NH4+), iron (Fe) and manganese (Mn) across gestation were consistently associated with higher odds of GDM/IGT. Maternal exposures to zinc (Zn), titanium (Ti) and vehicular emissions during the first trimester, and vanadium (V), nickel (Ni), road dust and fossil fuel/oil combustion during the second trimester were more important for GDM/IGT. This study provides important new evidence that maternal exposure to PM2.5 components and sources is significantly related to elevated risk for abnormal glucose tolerance during pregnancy.

Background Standardized mortality ratio (SMR) is the most frequently used index in Parkinson's disease (PD) survival survey. However, there is little SMR data in PD from China. Objective To examine the outcome, including overall and cause-specific mortality, of PD patients subsequent to 10 years of surveillance in Shanghai, China. This is an extension study of our previous investigation on mortality. Methods One hundred fifty-seven PD patients recruited from the movement disorder clinic of Rui Jin Hospital in 2006 were followed up until December 31, 2016 or death, representing a follow-up period of up to 10 years. Overall and cause-specific standardized mortality ratios (SMR) were calculated, and predictors for survival at disease onset were estimated. Results Thirty one patients had died by December 31, 2016, and the SMR at 10 years of follow-up was 0.87 (0.59–1.25). The primary direct cause of death was respiratory disease (SMR = 3.52, 95% CI 1.98–5.78). Employing Cox's proportional hazard modeling, postural instability gait disorder (PIGD) type and older age at onset predicted poor survival in this cohort. Conclusions This finding confirms the similar survival of patients with PD to the control population in the post-levodopa era. PIGD type and older age at onset had a negative impact on survival.

Background: Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. Objective: To investigate the effect of G lucidum on osteosarcoma cells and its mechanism. Methods: Osteosarcoma MG63 and U2-OS cells were treated with G lucidum, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of G lucidum on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. Results: G lucidum inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that G lucidum suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, G lucidum blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Conclusions: Our results suggest that G lucidum broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.

The aim of this study was to perform a cross-cultural adaption of the KOOS into Chinese and to evaluate its psychometric properties in patients with anterior cruciate ligament reconstruction (ACL reconstruction) in mainland China.A cross-sectional study.Patients completed the Chinese version of the KOOS and the SF-36 questionnaire three times. We evaluated the reliability, checked the validity, and assessed the responsiveness.A total of 42 patients who had undergone ACL reconstruction.The results of the questionnaire survey.The Chinese version of the KOOS was well accepted, with ideal test-retest reliability and internal consistency. The test-retest reliability was significant, with high ICC values ranging from 0.888 to 0.941. Additionally, we found that the internal consistency was adequate, with Cronbach's alpha coefficient ranging from 0.740 to 0.975. All a priori hypotheses were supported by a high correlation between the KOOS and SF-36. Furthermore, responsiveness was demonstrated since the ES and SRM between subscales following ACL reconstruction was found in the expected pattern.The Chinese version of the KOOS showed psychometric properties demonstrating acceptable reliability and validity similar to the original version. We conclude that the Chinese version is a reliable and valid instrument for research and clinical assessments of ACL reconstruction patients in mainland China.Ziel dieser Studie war die Durchführung einer interkulturellen Adaptation des KOOS ins Chinesische und die Auswertung der psychometrischen Eigenschaften des Fragebogens bei Patienten mit Rekonstruktion des vorderen Kreuzbandes (VKB-Rekonstruktion) in Festlandchina.Querschnittsstudie.Die Patienten füllten die chinesische Version der Fragebögen KOOS und SF-36 dreimal aus. Wir untersuchten die Reliabilität, überprüften die Validität und beurteilten die Änderungssensitivität.Insgesamt 42 Patienten, bei denen eine VKB-Rekonstruktion durchgeführt worden war.Die Ergebnisse der Fragebogenerhebung.Die chinesische Version des KOOS wurde gut aufgenommen und zeigte eine ideale Test-Retest-Reliabilität sowie interne Konsistenz. Die Test-Retest-Reliabilität war signifikant und es wurden hohe ICC-Werte zwischen 0,888 und 0,941 ermittelt. Des Weiteren wurde eine adäquate interne Konsistenz mit einem Cronbach-Alpha-Koeffizienten zwischen 0,740 und 0,975 festgestellt. Alle A-priori-Hypothesen wurden durch eine hohe Korrelation zwischen KOOS und SF-36 untermauert. Außerdem wurde eine Änderungssensitivität nachgewiesen, da die Kennwerte ES und SRM zwischen den Subskalen nach VKB-Rekonstruktion dem erwarteten Muster folgten.Die chinesische Version des KOOS zeigte psychometrische Eigenschaften, die auf eine mit der Originalversion vergleichbare akzeptable Reliabilität und Validität schließen lassen. Daraus folgern wir, dass es sich bei der chinesischen Version um ein zuverlässiges und valides Instrument für Forschungszwecke und zur klinischen Beurteilung von Patienten mit VKB-Rekonstruktion in Festlandchina handelt.

Background The differential diagnosis of Parkinson’s disease (PD) and multiple system atrophy (MSA) remains a challenge, especially in the early stage. Here, we assessed the value of transcranial sonography (TCS) to discriminate non-tremor dominant (non-TD) PD from MSA with predominant parkinsonism (MSA-P). Methods Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study. All the patients were followed up for at least 2 years to confirm the initial diagnosis. Patients with at least one substantia nigra (SN) echogenic size ≥18 mm2 were classified as hyperechogenic, those with at least one SN echogenic size ≥25 mm2 was defined as markedly hyperechogenic. Results The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients (74.1% vs. 38.4%, p

Aim To determine whether breast cancer survivors (BCS) at work following the diagnosis and/or treatment of breast cancer, in a rapidly developing country such as China experience similar to return to work challenges as reported in nations with established return to work (RTW) policy and procedures for employees with cancer. Methods Semi-structured interviews were conducted with 16 BCS who returned to work following diagnosis and/or primary cancer treatment. An Interpretative Phenomenological Analysis was used to investigate responses. Results Three recurring themes emerged: (1) challenges at work related to residual effects of diagnosis and/or primary treatment; (2) positive and negative responses from employers and/or supervisors; and (3) positive and negative responses from co-workers/colleagues. Although several participants experienced a high level of workplace support, there was a subgroup that did report challenges related to symptom burden, cognitive limitations, and both positive and negative responses by employers and co-workers were reported. Conclusions Findings indicate similar challenges in BCS who RTW during and/or following cancer treatment in both rapidly developing and developed nations. Results suggest that regardless of the existence of workplace policies and practices related to RTW for workers with a history of cancer, a subgroup of BCS experience similar challenges when returning to work. These findings highlight the international nature of RTW challenges and suggest the need for more global efforts to develop and evaluate workplace interventions to assist with these similarities.

PURPOSE Understanding the association of iris colour and myopia may provide further insights into the role of the wavelength of lights in the pathophysiology of myopia. We aim to assess the association of iris colour and myopia in a school-based sample of Chinese students. METHODS Two thousand three hundred and forty-six Year 7 students from 10 middle schools (93.5% response rate) aged 13-14 years in Mojiang, a small county located in Southwestern China, participated in the study. We obtained standardised slit lamp photographs and developed a grading system assessing iris colour (higher grade denoting a darker iris). Refractive error was measured after cycloplegia using an autorefractor by optometrists or trained technicians. An IOLMaster (www.zeiss.com) was used to measure ocular biometric parameters including axial length (AL). RESULTS Of all the study participants, 693 (29.5%) were affected by myopia with the prevalence estimates being higher in girls (36.8%; 95% confidence interval [CI]: 34.0, 39.6) than in boys (22.8%; 95% CI: 20.4, 25.1) (p

Background and Aims Accurate prediction of the response to preoperative chemoradiotherapy (CRT) potentially assists in the individualized selection of treatment. Endorectal US (ERUS) is widely used for the pretreatment staging of rectal cancer, but its use for preoperatively predicting the effects of CRT is not well evaluated because of the inflammation, necrosis, and fibrosis induced by CRT. This study assessed the value of sequential ERUS in predicting the efficacy of preoperative CRT for locally advanced rectal cancer. Methods Forty-one patients with clinical stage II/III rectal adenocarcinoma were enrolled prospectively. Radiotherapy was delivered to the pelvis with concurrent chemotherapy of capecitabine and oxaliplatin. Total mesorectal excision was performed 6 to 8 weeks later. EUS measurements of primary tumor maximum diameter were performed before (ERUS1), during (ERUS2), and 6 to 8 weeks after (ERUS3) CRT, and the ratios of these were calculated. Correlations between ERUS values, tumor regression grade (TRG), T down-staging rate, and pathologic complete response (pCR) rate were assessed, and survival was analyzed. Results There was no significant correlation between ERUS2/ERUS1 and TRG. The value of ERUS3/ERUS1 correlated with pCR rate and TRG but not T down-staging rate. An ERUS3 value of 6.3 mm and ERUS3/ERUS1 of 52% were used as the cut-off for predicting pCR, and patients were divided into good and poor prognosis groups. Although not statistically significant, 3-year recurrence and survival rates of the good prognosis group were better than those of the poor prognosis group. Conclusions Sequential ERUS may predict therapeutic efficacy of preoperative CRT for locally advanced rectal cancer. (Clinical trial registration number: NCT01582750.)

Dopamine agonists (DAs) play important roles in the treatment of Parkinson's disease (PD). Currently, it is thought that genetic variations in the genes encoding dopamine receptors (DR) are important factors in determining inter-individual variability in drug responses. To investigate the association between Dopamine receptor D type 2 (DRD2) dinucleotide short tandem repeat (CAn-STR) and Dopamine receptor D type 3 (DRD3) Ser9Gly polymorphisms and the risk of PD, as well as the possible reasons for PD patients using different doses of DAs, we recruited 168 idiopathic PD patients and 182 controls. There were no significant differences in DRD2 CAn-STR and DRD3 Ser9Gly genotypes (p = 0.184, p = 0.196) or in allele frequencies (p = 0.239, p = 0.290) between PD patients and controls. There was no association between DRD2 CAn-STR polymorphism and doses of DAs. Among three different DRD3 Ser9Gly genotypes (Ser/Ser, Ser/Gly, Gly/Gly), patients carrying Gly/Gly genotype used higher doses of DAs than patients with Ser/Gly and Ser/Ser genotypes (p = 0.001). In pramipexole subgroup, the Gly/Gly group took more pramipexole than the other genotype groups (p

// Hengyi Gao 1,2,4 , Feng Zhu 2 , Min Wang 2 , Hang Zhang 2 , Dawei Ye 3 , Jiayin Yang 4 , Li Jiang 5 , Chang Liu 5 , Renyi Qin 2 , Lunan Yan 4 and Guangqin Xiao 2,4 1 Department of General Surgery, Guizhou Provincial People’s Hospital, Guiyang, China 2 Department of Hepato-Pancreato-Biliary Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3 Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 4 Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China 5 Department of State Key Laboratory of Biotherapy and Pathology, West China Hospital of Sichuan University, Chengdu, China Correspondence to: Guangqin Xiao, email: // Keywords : hepatocellular carcinoma, liver fibrosis, hepatitis B virus, preoperatively, noninvasive Received : June 03, 2016 Accepted : December 05, 2016 Published : December 19, 2016 Abstract Background: Advanced liver fibrosis can result in serious complications (even patient’s death) after partial hepatectomy. Preoperatively percutaneous liver biopsy is an invasive and expensive method to assess liver fibrosis. We aim to establish a noninvasive model, on the basis of preoperative biomarkers, to predict liver fibrosis in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection. Methods: The HBV-infected liver cancer patients who had received hepatectomy were retrospectively and prospectively enrolled in this study. Univariate analysis was used to compare the variables of the patients with mild to moderate liver fibrosis and with severe liver fibrosis. The significant factors were selected into binary logistic regression analysis. Factors determined to be significant were used to establish a noninvasive model. Then the diagnostic accuracy of this novel model was examined based on sensitivity, specificity and area under the receiver-operating characteristic curve (AUC). Results: This study included 2,176 HBV-infected HCC patients who had undergone partial hepatectomy (1,682 retrospective subjects and 494 prospective subjects). Regression analysis indicated that total bilirubin and prothrombin time had positive correlation with liver fibrosis. It also demonstrated that blood platelet count and fibrinogen had negative correlation with liver fibrosis. The AUC values of the model based on these four factors for predicting significant fibrosis, advanced fibrosis and cirrhosis were 0.79-0.83, 0.83-0.85 and 0.85-0.88, respectively. Conclusion: The results showed that this novel preoperative model was an excellent noninvasive method for assessing liver fibrosis in HBV-infected HCC patients.

This study aims to evaluate the expression of the antioncogene phosphatase and tensin (PTEN) homologue and survivin, a protein encoded by the anti-apoptotic gene baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5), in the progression of cervical neoplasia and to elucidate the relationship between PTEN and survivin expression based on clinicopathological features in squamous cell carcinoma of the uterine cervix. A total of 20 patients with cervical ectropion and squamous metaplasia, 30 with cervical intraepithelial neoplasia, and 49 with cervical squamous cell carcinoma were enrolled in the study. Immunohistochemical staining was performed to detect PTEN and survivin expression in each group. Normal cervical epithelium from 10 people served as the control. Results showed that PTEN expression progressively decreased with the continuum from normal epithelium to squamous cell carcinoma (P0.05), whereas survivin expression progressively increased (P0.05). Furthermore, positive PTEN immunostaining was associated with clinical stage and tumour size (P0.05). The level of PTEN expression in the metastatic pelvic lymph node group was significantly lower compared with the non-metastatic pelvic lymph node group (P0.01). Positive PTEN immunostaining was not associated with age or degree of differentiation (P0.05). Positive survivin immunostaining was associated with clinical stage and tumour size (P0.05). Survivin-positive expression in the metastatic pelvic lymph node group was significantly higher compared with the nonmetastatic pelvic lymph node group (P0.01). No obvious relationship was found between survivin expression and patient age (P0.05). PTEN expression negatively correlated with survivin expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma (P0.01). PTEN and survivin expression correlated with incidence and progression of uterine cervical cancer. Positive expression levels of PTEN and survivin provide potential evaluation indices for early diagnosis and prognosis of uterine cervical cancer, and these biomarkers are also potentially promising therapeutic targets.

Background and objective To explore the alterations of microbial 16s ribosomal (rRNA) gene in the feces and blood of Chinese patients with multiple system atrophy (MSA) and its relationships with clinical features. Methods 40 MSA patients (MSA-P/MSA-C: 23/17) and their healthy spouses were recruited. Fecal and blood microbiota were investigated by high-throughput IllUmina Miseq sequencing targeted on the V3-V4 functional region of 16s rRNA gene. The relationships between microbiota and clinical characteristics were analyzed. Results The abundances of Lactobacillus, Gordonibacter, Phascolarctobacterium, and Haemophilus in feces and abundances of Leucobacter, and Bacteroides in blood were different between MSA patients and healthy controls (HC). Combining the taxa from feces and blood, six genera were identified to be predictive of MSA, achieving an area under the curve (AUC) of 0.853. The abundances of Phascolarctobacterium and Ruminococcus in feces were lower in MSA-P than those in MSA-C. The abundances of Blastococcus, Bacillus, and Acinetobacter in blood were different between MSA subtypes. These five genera differentiated MSA subtypes with an AUC of 0.898. Functional predictions indicated that gene functions involving biosynthetic metabolism and bacterial secretion systems were significantly different between the MSA and HC. The differential genera were associated with disease duration, anxiety, and autonomic dysfunctions. Conclusions We confirmed the alterations of microbial 16s rRNA gene in the feces and blood occurs in Chinese patients with MSA. Microbiota dysbiosis was related to MSA clinical manifestations. Elucidating these differences in microbiomes will be helpful to improve our knowledge of the microbiota in the pathogenesis of MSA.

The number and health burden of Parkinson’s disease increase rapidly in China. It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030. In this review, we present an overview of epidemiology and health economics status of Parkinson’s disease across China and discuss the risk factors of Parkinson’s disease and related complications. From the view of clinical research, we also discuss the current status of clinical trials, diagnostic biomarkers, treatment of Parkinson’s disease, tertiary network and post-occupation education in Chinese Parkinson’s disease clinics. Electronic supplementary material The online version of this article (10.1186/s40035-019-0162-z) contains supplementary material, which is available to authorized users.

Objective Resting tremor may compound the effects of bradykinesia to further prolong the initiation of voluntary movement in patients with Parkinson's disease (PD). However, the interaction between resting tremor and voluntary movements in these PD patients has not been well understood. Recently, we demonstrated that cutaneous afferents evoked by surface stimulation of superficial radial nerve can inhibit resting tremor effectively. The inhibition appears to take effect via spinal interneuronal pathways. This study evaluates how evoked cutaneous afferents would impact the performance of voluntary movements in PD subjects when tremor is inhibited. Approach Ten PD patients with tremor and eight age-matched control subjects were recruited to participate in this study. Both groups of subjects performed fast reaching movements, while cutaneous stimulation was delivered during reaching tasks on or off randomly. Kinematic performance, such as reaction time (RT), movement time (MT), and movement variability, as well as muscle synergy of tasks were evaluated and compared to assess the impact of evoked cutaneous afferents on movement performances. Main results Results indicated that the cutaneous stimulation significantly reduced RT in PD patients by 17.7%; but had an insignificant effect on RT in control subjects. Cutaneous stimulation, however, caused a significantly longer MT both in control subjects (8.6%) and in PD subjects (15.7%). Movement variability was not significantly altered in both groups of subjects by the cutaneous stimulation. Muscle synergy analysis revealed that cutaneous stimulation affected the power spectral densities (PSD) of time profiles of muscle synergies more significantly than the vector patterns of synergies in both control subjects and PD subjects. Significance These findings provide evidence that tremor increases the RT of voluntary motor control in PD patients, and demonstrate that cutaneous stimulation reduces the RT of voluntary movements significantly, in addition to suppressing tremor, yet without interrupting voluntary control of movements.

Background A large population of patients with Parkinson’s disease (PD) displays the symptom of resting tremor. However, the extent that resting tremor may affect the performance of movement control has not been evaluated specifically. This study aims at establishing methods to quantitatively evaluate motor performance in PD patients with tremor, and at analyzing the interfering effects of tremor on control of reaching movements. Methods Ten PD patients with tremor and Ten healthy control subjects were recruited to participate in this study. All patients and healthy control subjects performed point-to-point reaching movements with their tremor affected arm or preferred arm. We verified that a smoothing model of minimum-jerk trajectory (MJT) can be used to extract voluntary movement trajectory from tremor-corrupted movement trajectory in the reaching tasks by the patients. Performance indices of reaction time (RT) and movement time (MT) of reaching movements by the PD subjects with tremor were evaluated using MJT trajectories. Differences of RT and MT between the recorded trajectories and MJT in PD and control subjects were calculated to investigate the extent that tremor may affect their motor performance. Linear mixed-effects model was used to identify the contributions of tremor, bradykinesia and rigidity to the performance indices of RT and MT based on UPDRS scores. The power spectrum densities (PSD) of tremor were also evaluated using hand velocities to represent tremor intensity and to analyze their correlations with RT and MT. Results The MJT model demonstrated good fit to recorded trajectory with a more consistent estimation of motor performance for both PD and control subjects. The RT and MT of patients were found to be 43.4 and 79.5% longer respectively than those of healthy control subjects. Analysis of the linear mixed-effects model was not able to reveal that tremor, bradykinesia and rigidity each had a significant contribution to RT or MT in PD patients with tremor. However, the PSD of tremor was found to correlate significantly to RT, but not to MT, in both linear regression and linear mixed-effects model. Conclusions The minimum-jerk trajectory and power spectrum densities are effective quantitative tools for evaluating motor performance for PD patients with tremor. Resting tremor is one of the factors prolonging the initiation of voluntary reaching movement in these patients.

Resting tremor affects voluntary reaching movements in patients with Parkinson’s disease (PD). Previously, we found that cutaneous afferents evoked by electrically simulating the superficial radial nerve could inhibit tremor activity [3]. Yet, the mechanism that cutaneous stimulation affects tremor as well as voluntary movements remains unclear. In this paper, we used the method of muscle synergy analysis to further investigate the muscle activation patterns of tremor and reaching movements. Three PD patients with tremor dominant symptom participated in this preliminary study. The patients performed targeted reaching movements with no visual feedback of their hands, while transcutaneous electrical stimulation was delivered to inhibit tremor activity. Kinematics and EMGs of six muscles were recorded during resting and reaching tasks. Muscle synergy analysis was performed with data during resting and task stages with and without cutaneous stimulation. Results showed that during resting state the time profiles of muscle synergy in the tremor cycle displayed two main alternating components that were distributed to antagonistic muscle pairs in upper arm, forearm and wrist. Cutaneous stimulation affected the vector patterns and time profiles of muscle synergies for tremor and reaching movements differently. Our results indicate that muscle synergies are sensitive to central descending drives of muscles, as well as evoked peripheral afferents.

Background. Characteristics of mammographic density for Chinese women are understudied. This study aims to identify factors associated with mammographic density in China using a quantitative method.Methods. Mammographic density was measured for a total of 1071 (84 with and 987 without breast cancer) women using an automatic algorithm AutoDensity. Pearson tests examined relationships between density and continuous variables and t-tests compared differences of mean density values between groupings of categorical variables. Linear models were built using multiple regression.Results. Percentage density and dense area were positively associated with each other for cancer-free (r=0.487, pConclusion. This is the first time that mammographic density was measured by a quantitative method for women in China and identified associations should be useful to health policy makers who are responsible for introducing effective models of breast cancer prevention and diagnosis.

This study compares dosimetric parameters in these following 3 neoadjuvant chemoradiotherapy (NCRT) methods in treating locally advanced esophagus cancer: helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). It is aimed to ascertain the efficient technique that kept high target coverage and availed the dose sparing of bone marrow (BM). This research collected data on 11 patients from October 2014 to June 2017 who received NCRT for pathologically confirmed esophageal cancer. The prescription doses to the planning target volume (PTV) were all given as 60 Gy (2 Gy per fraction, 5 days a week). Three physicists via Varian Eclipse Treatment Planning System and Accuray planning stations redesigned 5 radiotherapy plans (fixed 5-field IMRT, fixed 7-field IMRT, 2-arc VMAT, 3-arc VMAT, and TOMO) for each of the patients. At the end of the planning, we then appraised the dosimetric quality based on the PTV parameters and the doses to organs at risk (OARs). In the study VMAT reached the highest conformity index (CI; 2 arcs VMAT: 0.74 ± 0.10; 3 arcs VMAT: 0.78 ± 0.07; p< 0.05), and IMRT the lowest homogeneity index (HI; fivefields IMRT: 0.12 ± 0.03; sevenfields IMRT: 0.10 ± 0.02; p< 0.05). Besides, 7 fields IMRT (0.10 ± 0.02) achieved superior HI to that of 5 fields IMRT (0.12 ± 0.03, p< 0.01). TOMO (p< 0.05) and VMAT (p< 0.05) were both significantly superior to IMRT in terms of the dose to lung (V5, V10, V15, V20, and V30). These 5 radiation techniques were similar regarding the dose to heart (V5, V20, and V30), but IMRT (5 fields IMRT: 19.27 ± 5.33; 7 fields IMRT: 20.05 ± 4.19) significantly raised the dose to the V50 of the heart when compared to VMAT (2 arcs VMAT: 16.6 ± 5.68; 3 arcs VMAT: 15.04 ± 5.75; p< 0.05) and TOMO (15.05 ± 4.7, p< 0.05). VMAT reduced the dose to BM (V5, V10, V20, and V30) as compared to TOMO (p< 0.05) and IMRT (p< 0.05). The CI of VMAT was the supreme one in those of the techniques in this study, so was the HI of IMRT. VMAT also provided another advantage that it reduced the dose to the BM. TOMO ameliorated the dose sparing of the lung, but the dose that the BM absorbed from TOMO was of some concern about BM toxicity.

Objective Gut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia. Background AD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans. New/Updated Hypothesis We hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly. Major Challenges for the Hypothesis The diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies. Linkage to Other Major Theories Escherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram-negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood-brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.

// Xin Wang 1 , Jing Jin 1 , Yong Yang 1 , Wen-Yang Liu 1 , Hua Ren 1 , Yan-Ru Feng 1 , Qin Xiao 2 , Ning Li 1 , Lei Deng 1 , Hui Fang 1 , Hao Jing 1 , Ning-Ning Lu 1 , Yu Tang 1 , Jian-Yang Wang 1 , Shu-Lian Wang 1 , Wei-Hu Wang 1 , Yong-Wen Song 1 , Yue-Ping Liu 1 and Ye-Xiong Li 1 1 Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 2 Department of Radiation Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan, P. R. China Correspondence to: Jing Jin, email: // Keywords : upper rectal cancer, nomogram, recursive partitioning analysis, adjuvant chemoradiotherapy, adjuvant chemotherapy Received : February 04, 2016 Accepted : July 09, 2016 Published : July 19, 2016 Abstract Purpose: The role of adjuvant chemoradiotherapy (ACRT) or adjuvant chemotherapy (ACT) in treating patients with locally advanced upper rectal cancer (URC) after total mesorectal excision (TME) surgery remains unclear. We developed a clinical nomogram and a recursive partitioning analysis (RPA)-based risk stratification system for predicting 5-year cancer-specific survival (CSS) to determine whether these individuals require ACRT or ACT. Materials and Methods:This retrospective analysis included 547 patients with primary URC. A nomogram was developed based on the Cox regression model. The performance of the model was assessed by concordance index (C-index) and calibration curve in internal validation with bootstrapping. RPA stratified patients into risk groups based on their tumor characteristics. Results: Five independent prognostic factors (age, preoperative increased carcinoembryonic antigen and carcinoma antigen 19-9, positive lymph node [PLN] number, tumor deposit [TD], pathological T classification) were identified and entered into the predictive nomogram. The bootstrap-corrected C-index was 0.757. RPA stratification of the three prognostic groups showed obviously different prognosis. Only the high-risk group (patients with PLN ≤ 6 and TD, or PLN > 6) benefited from ACRT plus ACT when compared with surgery followed by ACRT or ACT, and surgery alone (5-year CSS: 70.8% vs . 57.8% vs . 15.6%, P < 0.001). Conclusions: Our nomogram predicts 5-year CSS after TME surgery for locally advanced rectal cancer and RPA-based stratification indicates that ACRT plus ACT post-surgery may be an important treatment plan with potentially significant survival advantages in high-risk URC. This may help to select candidates of adjuvant treatment in prospective studies.

Matrix metalloproteinases (MMPs) are closely associated with tumor proliferation, invasion and metastasis. In this study, we determined the MMPs expression and their clinical significances in gastric cancer (GC). We first extensive studied MMPs expression in GC in The Cancer Genome Atlas (TCGA) RNA sequence database and found MMP16 was candidate biomarker in GC. Then we validated clinical significance of MMP16 mRNA expression in 167 GC by RT-PCR. Survival analysis showed that high expression of MMP16 indicated poor overall and disease free survival (P

Introduction It is well known that α-synuclein (SNCA) and microtubule associated protein (MAPT) genes predispose individuals to develop Parkinson's disease (PD). However, whether these genes contribute to differences in the variable progression observed in PD is obscure. This study aims to evaluate the association of common variants in SNCA (rs11931074, rs894278) and MAPT (rs242557_H1c haplotype, rs3744456) genes with the severity and duration of motor and cognitive performance. Methods 296 Chinese patients with PD were recruited from Shanghai Ruijin Hospital. Motor performance was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS-III) and Hoehn &Yahar (H&Y) stages and cognitive performance using the Mini-Mental Status Examination (MMSE). Genetic associations were analysed using general linear modelling for severity and Cox regression analysis for duration to motor (UPDRS-III≥36 or H&Y ≥ 3, average duration 13 years) and cognitive (MMSE Results The severity of motor function associated with synergic interaction of SNCA (rs11931074) and MAPT (rs3744456) (p ≤ 0.05) while longer survival to the motor cutoff associated with SNCA (rs11931074/T, HR = 0.4, p = 0.03). Increased severity of cognitive function associated with MAPT (H1c haplotype, p = 0.05) with none of the risk alleles chosen associated with survival to the cognitive cutoff (p > 0.05). Conclusion Our findings add further data showing that common variants in SNCA and MAPT genes contribute to variability in progression of PD, with SNCA variants associating with motor progression while MAPT variants associated with clinical severity.

Transcranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD.A total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients.Two hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity.This is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.

The elevation of neutrophil-lymphocyte ratio (NLR) has adverse effects on the prognosis of patients with hepatocellular carcinoma (HCC) who have received liver transplantation (LT). The Hangzhou criteria are set for selecting HCC patients for LT. The present study aimed to establish a set of new criteria combining the NLR and Hangzhou criteria for selecting HCC patients for LT.Receiver operating characteristic (ROC) analysis was done to determine the optimal NLR threshold. Univariate and multivariate analyses were made to evaluate the factors affecting the outcomes of HCC patients after LT. We also proposed new criteria consisting of the elevated NLR and Hangzhou criteria. ROC analysis was carried out to validate the feasibility of the new criteria.Three hundred and five HCC patients were included in this study. The mean follow-up time of these patients was 5.4 years. Of the 305 patients, 197 (64.6%) showed elevated NLRs (NLR4). The recurrence-free survival rates of the patients with elevated NLRs at 1, 3 and 5 years were lower than those of the patients with normal NLRs (NLR ≤ 4) (50.1%, 21.7% and 20.2% vs 80.5%, 58.7% and 56.4%, respectively; P0.001). The overall survival rate was lower in the patients with elevated NLR than in those with normal NLR at 1, 3 and 5 years (60.8%, 27.0% and 22.5% vs 78.4%, 51.1% and 47.8%, respectively; P0.001). Multivariate analysis demonstrated that an NLR4 (P = 0.034), total tumor size8 cm (P = 0.005), alpha-fetoprotein level400 μg/L (P = 0.007) and the presence of vascular invasion (P = 0.003) were independent predictors of HCC recurrence in post-transplant patients. We proposed a set of new criteria based on the elevated NLR and Hangzhou criteria. A ROC analysis demonstrated that the patients with scores ≥ 1 had an area under the curve of 0.764.The criteria combining the elevated NLR and Hangzhou criteria can be used to select patients with HCC for LT.