Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics. The supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol (CB[7]‒PEG) has been shown to stabilize insulin formulations by reducing aggregation propensity. Yet prolonged in vivo duration of action, arising from sustained complex formation in the subcutaneous depot, limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a meal. Supramolecular affinity of CB[7] in binding the B1-Phe residue on insulin is central to supramolecular PEGylation using this approach. Accordingly, here we synthesized N-terminal acid-modified insulin analogs to reduce CB[7] interaction affinity at physiological pH and reduce the duration of action by decreasing the subcutaneous depot effect of the formulation. These insulin analogs show weak to no interaction with CB[7]‒PEG at physiological pH but demonstrate high formulation stability at reduced pH. Accordingly, N-terminal modified analogs have in vitro and in vivo bioactivity comparable to native insulin. Furthermore, in a rat model of diabetes, the acid-modified insulin formulated with CB[7]‒PEG offers a reduced duration of action compared to native insulin formulated with CB[7]‒PEG. This work extends the application of supramolecular PEGylation of insulin to achieve enhanced stability while reducing the risks arising from a subcutaneous depot effect prolonging in vivo duration of action.

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. Methods: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. Results: Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. Conclusions The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) is an important basis for judging suspected occupational diseases and occupational contraindications. There are crossing over or overlap between occupational contraindications and diagnostic criteria of poisoning damage. Occupational contraindications have different meanings with the degree and range of common diseases or symptoms and the frequency of physical examination during employment conflicts with the current standard. Based on the practice of occupational health examination in a large population, the present study analyzed relevant articles and put forward some suggestions for revision, in combination with clinical medicine, occupational health standards, and diagnostic standards of occupational diseases. The modification could provide a reference for the revision of Technical Specifications for Occupational Health Surveillance and the practice of occupational health examination.
Humans ; Occupational Health ; Occupational Diseases ; Occupational Health Services ; Workplace ; Reference Standards ; Occupational Medicine

Background/Aims: Growing evidence suggests a negative effect of eosinophilic esophagitis (EoE) on patients’ general health-related quality of life (HRQOL). However, the relevance and use of coping strategies and its relation to (disease specific) HRQOL as well as its determinants have not been studied well. Methods: Adult EoE patients were invited to complete standardized measures on general HRQOL (Short Form-36 Health Survey [SF-36]) and coping strategies (Utrechtse Coping Lijst [UCL]). Scores were compared to general population norms. The disease specific Adult Eosinophilic Esophagitis Quality of Life (EoE-QOL-A) measure was used to assess EoE-HRQOL. Socio-demographic-and clinical factors were also evaluated. Results: In total, 147 adult EoE patients (61% males), age 43 (interquartile range, 29-52) years were analyzed. Mental health-scores (SF-36) were significantly lower in EoE patients, whereas physical health-scores (SF-36) were similar in EoE patients (vs the general population;P = 0.010 and P = 0.240), respectively. The subdomain “disease anxiety” (EoE-QOL-A) was mostly affected, determinants were; female gender, younger age, severe clinical disease activity, higher number of food bolus extraction, and more recent EoE-diagnosis. Less effective coping styles (ie, passive/palliative reaction) were associated with a significant impact on each individual EoE-HRQOLsubdomain as well as lower scores of the Mental Health Component Scale in male EoE patients. Passive reaction in female EoEpatients correlated with impairment of the EoE-HRQOL-domains “emotional impact” and “disease anxiety.” Active problem solving was significantly related to better perception of mental HRQOL (SF-36) in both males and females. Conclusions EoE has a significant negative impact on mental HRQOL, with less effective coping strategies––specifically in males, being a relevant determinant. Thus, a pro-active approach towards coping mechanisms is needed in order to enhance HRQOL and manage patients’ burden of EoE.

This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson's disease (PD) reflected by fractional anisotropy (FA), addressing clinical profiles and methodology-related heterogeneity. Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls (HC) using the anisotropic effect size-signed differential mapping. A total of 808 patients with PD and 760 HC coming from 27 databases were finally included. Subgroup analyses were conducted considering heterogeneity with respect to medication status, disease stage, analysis methods, and the number of diffusion directions in acquisition. Compared with HC, patients with PD had decreased FA in the left middle cerebellar peduncle, corpus callosum (CC), left inferior fronto-occipital fasciculus, and right inferior longitudinal fasciculus. Most of the main results remained unchanged in subgroup meta-analyses of medicated patients, early stage patients, voxel-based analysis, and acquisition with 30 diffusion directions. The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex. The cerebellum and CC, associated with typical motor impairment, showed the most consistent FA decreases in PD. Medication status, analysis approaches, and the number of diffusion directions have an important impact on the findings, needing careful evaluation in future meta-analyses.
Anisotropy ; Brain/diagnostic imaging* ; Corpus Callosum ; Diffusion Tensor Imaging ; Humans ; Parkinson Disease/diagnostic imaging* ; White Matter/diagnostic imaging*

Alanine Transaminase ; Animals ; Carbon Tetrachloride ; Gastrointestinal Microbiome ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Quinazolines

Adolescent ; Adult ; Child ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Male ; Manufacturing Industry ; Noise, Occupational ; Occupational Exposure ; Surveys and Questionnaires ; Young Adult

Introduction: Both short and long PFNA are employed to treat intertrochanteric fractures. Controversy exists in the choice between the two nails as each implant has specific characteristics and theoretical advantages. This retrospective study seeks to examine the operative complication rates and clinical outcomes of short versus long (Proximal Femoral Nail Antirotation) PFNA in the treatment of intertrochanteric fractures. Materials and methods: Between July 2011 and February 2015, 155 patients underwent PFNA insertion. The decision on whether to use a short or long PFNA nail, locked or unlocked, was determined by the attending operating surgeon. Visual Analogue Pain Score (VAS) Harris Hip Scores (HHS), Short-form 36 Health Questionnaire (SF-36) and Parker Mobility Scores (PMS) were collected at six weeks, six months and one year post-operatively. Results: A total of 137 (88.4%) patients were successfully followed-up. Forty-two (30.7%) patients received a short PFNA. The patients were similar in baseline characteristics of age, gender, and comorbidities. Operative time was significantly longer in the short PFNA group (62 ±17 mins) versus the long PFNA group (56±17). While the patients in both groups achieved improvement in all outcome measures, there was no significant difference between the groups in terms of HHS (61.0 ±16.0 vs 63.0 ±16.8, p=0.443), PMS (2.3±1.5 vs 2.7±2.1, p=0.545) and VAS (1.7±2.9 vs 1.8 ±2.2 p=0.454). There were 3 (7.1%) and 7 (7.4%) complications in the short versus long PFNA group, respectively. Conclusion: Both short and long PFNA had similar clinical outcomes and complication rates in the treatment of intertrochanteric fractures in an Asian population.

Current treatment of vitiligo is still a great challenge, since most cases of vitiligo have variable re-pigmentation outcomes due to their unpredictable responses to existing therapeutic regimens. There is an urgent need to identify this re-pigmentation process and to develop novel therapies. This review illustrates the most current research and latest understanding of vitiligo skin re-pigmentation and related regulatory mechanisms. Literature was collected from PubMed until January 2020, using the search terms including "vitiligo," "re-pigmentation," "phototherapy," "narrow-band ultraviolet B, " "excimer," "fractional carbon dioxide laser," and "melanocyte stem cells." Literature was mainly derived from English articles. Article type was not limited. Emerging evidence suggests that patients with vitiligo present various re-pigmentation patterns following ultraviolet B phototherapy, which relies on different cell reservoirs from the perilesional margins and/or from uninvolved hair follicles to replenish functional melanocytes that are lost in vitiliginous skin. The following events are likely to be involved in this re-pigmentation process, including: 1) changes in the paracrine secretion and distribution of transforming growth factor-β1 in the bulge area and in the epidermis; 2) the enhanced transfer of dermal pro-melanogenic growth factors to the epidermis; and 3) the induction of a C-X-C motif chemokine ligand (CXCL) 12-enriched micro-environment that efficiently recruits CXCR4- or CXCR7-positive melanocytes. Ongoing studies on the cellular and molecular events underlying vitiligo re-pigmentation will help design new therapeutic strategies to improve treatment outcomes.