Search

Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database.A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP).ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion.LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.

Galectins are a family of proteins with at least one carbohydrate-recognition domain. Galectins are present in various tissues and organs and participate in different physiological and pathological molecular reactions in vivo. Wound healing is the basic process of traumatic disease recovery. Wound healing involves three overlapping stages: inflammation, proliferation, and remodelling. Furthermore, a comparison of wound healing with the tumour microenvironment revealed that galectin plays a key role in the wound healing process. The current review describes the role of galectin in inflammation, angiogenesis, re-epithelialisation, and fibrous scar formation and evaluates its potential as a therapeutic drug for wounds.

Background: The G protein-coupled receptor P2RY2 protein of the purinergic receptor family is involved in the pathogenesis of Alzheimer’s disease (AD). Naturally occurring antibodies against P2RY2 (NAbs-P2RY2) are present in human plasma, with their clinical relevance in AD unknown. Objective: To explore the alteration of NAbs-P2RY2 in AD patients and its associations with biomarkers and cognition of AD patients. Methods: The levels of naturally occurring antibodies against the four extracellular domains of P2RY2 (NAbs-P2RY2-1, NAbs-P2RY2-2, NAbs-P2RY2-3, and NAbs-P2RY2-4) were measured in the plasma of 55 AD patients, 28 non-AD dementia patients, and 70 cognitively normal participants. The correlations of autoantibody levels with cognitive scale scores, AD plasma biomarkers, and brain amyloid burden were examined. Results: NAbs-P2RY2-1, NAbs-P2RY2-3, and NAbs-P2RY2-4 were reduced in AD patients. Plasma levels of NAbs-P2RY2-2 and NAbs-P2RY2-3 levels were positively associated with cognitive and functional performances. Among these antibodies, plasma NAbs-P2RY2-2 levels were positively associated with plasma amyloid-β 42 levels. While plasma NAbs-P2RY2-3 levels were negatively associated with brain amyloid burden in AD patients. Conclusion: These findings indicate an alteration of humoral immunity against P2RY2 in AD patients. Further mechanistical investigations are needed to reveal the role of NAbs-P2RY2 in the pathogenesis of AD.

To explore its potential causative role in CRC development, we evaluated the colon pathology, mucosa barrier, colon microbiota and host transcriptome profile afterThree groups of mice were compared to reveal the differences,Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group, and AOM/DSS mice withOur study demonstrated that

RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans and the technology, is being leveraged for rapid emergency response. In this report, we assessed immunogenicity, and, for the first time, toxicity, biodistribution and protective efficacy in preclinical models of a two-dose self-amplifying messenger RNA (SAM) vaccine, encoding a prefusion stabilized Spike antigen of SARS-CoV-2 Wuhan-Hu-1 strain and delivered by lipid nanoparticles (LNP). In mice, one immunization with the SAM vaccine elicited a robust Spike-specific antibody response, which was further boosted by a second immunization, and effectively neutralized the matched SARS-CoV-2 Wuhan strain as well as B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) variants. High frequencies of Spike-specific germinal center B, Th0/Th1 CD4, and CD8 T cell responses were observed in mice. Local tolerance, potential systemic toxicity, and biodistribution of the vaccine were characterized in rats. In hamsters, the vaccine candidate was well-tolerated, markedly reduced viral load in the upper and lower airways, and protected animals against disease in a dose-dependent manner, with no evidence of disease enhancement following SARS-CoV-2 challenge. Therefore, the SARS-CoV-2 SAM (LNP) vaccine candidate has a favorable safety profile, elicits robust protective immune responses against multiple SARS-CoV-2 variants, and has been advanced to Phase-1 clinical evaluation (NCT04758962)., Graphical Abstract, Comprehensive preclinical development of a lipid nanoparticle (LNP)-formulated SAM vaccine encoding the prefusion stabilized SARS-CoV-2 Spike full-length antigen is reported. Protective efficacy, immunogenicity, toxicity, and biodistribution assessment of this candidate vaccine in mice, rats, and hamsters showed a favorable safety profile and robust immune responses against SARS-CoV-2 infection and disease.

Single-incision laparoscopic distal pancreatectomy has not been widely applied due to technical challenges and increased operative risks. The newly released da Vinci SP system has been introduced to overcome these limitations and offer improvements for established robotic single-site procedures. We report our experience of robotic single port plus one port distal pancreatectomy using the da Vinci SP system.We performed robotic distal pancreatectomy in three patients using the da Vinci SP surgical system with one additional port used for applying the energy device and stapling. Technical and clinical feasibility were examined.The mean age and body mass index were 70.7 years and 27.8 kg/mRobotic distal pancreatectomy using the da Vinci SP system is safe and feasible, with acceptable perioperative outcomes.

Cleidocranial dysplasia (CCD) represents a rare autosomal dominant skeletal dysplasia caused by mutations that induce haploinsufficiency in RUNX2, the important transcription factor of osteoblasts related to bone/cartilage development and maintenance. Clavicular hypoplasia, which involves aberrant tooth/craniofacial bone/skeletal formation, is a feature of classic CCD. RUNX2 mutations can be found in approximately 60-70% of patients with CCD, and around ∼10% of these mutations are microdeletions. The present paper describes the radiological and clinical characteristics of a 5-year-old girl who showed representative CCD features, including extra teeth, aplasia of clavicles, sloping shoulders, marked calvarial hypomineralization, and osteoporosis.We obtained genomic DNA of her family members and performed whole-genome sequencing (WGS) for samples collected from the proband. Quantitative fluorescent PCR (QF-PCR) and specific PCR plus electrophoresis were then performed as validation assays for all participants. In vitro analysis was performed. Luciferase assay for Runx2 transcription activity and evaluation of mRNA levels of Runx2 downstream osteogenic markers were conducted.WGS identified a 11.38-kb microdeletion in RUNX2 comprising 8-9 exons, which was validated by QF-PCR and specific PCR plus electrophoresis. In vitro experiments confirmed the pathogenicity of this variation.The present study identified a 11.38-kb microdeletion in RUNX2 that causes CCD. The deletion in the PST domain of RUNX2 reduces its transcription activity and reduces osteogenic marker levels, eventually decreasing the differentiation of osteoblasts. These findings clarify the role of the CCD-related mechanism in the development of CCD and suggest that it is important to consider copy number variation for the suspected familial patients early.

Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.

Background/aims Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

The purpose of the present review is to analyze and summarize the feasibility, effectiveness, and safety of ultrasound-guided percutaneous microwave ablation (MWA) for adenomyosis according to largest studies available in current literature, so as to provide a more robust foundation for its use in the treatment of patients with this condition.Adenomyosis is a common and frequently occurring gynecological disease. It can lead to clinical symptoms such as dysmenorrhea, menostaxis, menorrhagia, and anemia, and can seriously affect patients' quality of life. Treatments for adenomyosis include drug, minimally invasive, and surgical therapies. Among them, ultrasound-guided percutaneous microwave ablation has become a new hotspot in the minimally invasive treatment of adenomyosis in recent years, with its advantages of small trauma and a good therapeutic effect.Relevant studies were retrieved from the CNKI (Chinese National Knowledge Infrastructure), CQVIP, Wanfang, PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and Google Scholar databases. The retrieval time range was from January 2000 to June 2021. Chinese search terms included "adenomyosis", "microwave ablation", and "ultrasound". English search terms included "microwave ablation", "ultrasound", "(adenomyosis) OR (endometrioma) OR (adenomyoma)".Ultrasound-guided percutaneous microwave ablation therapy is a feasible, safe, and effective technique for the treatment of adenomyosis, and is worthy of clinical application and promotion.

The purpose of this work is to probe into the potential role of long non-coding RNA growth arrest specific transcript 5 (lncGAS5)/ microRNA (miR)-188-5p/SMAD2 axis in MIRI. Through ligating the left anterior descending (LAD) coronary artery, MIRI animal model and hypoxia/reoxygenation (H/R) myocardial injury model in vitro were established. Via adenovirus or plasmid transfection, lncGAS5/MiR-188-5p/SMAD2 expression was up-regulated or down-regulated in the study. RT-qPCR was applied to check LncGAS5/MiR-188-5p/SMAD2 mRNA expression, HE staining for histopathological staining, TUNEL staining and flow cytometry to examine cardiomyocyte apoptotic rate, CCK-8 to check cell viability, ELISA to detect inflammatory factor levels, Western blot to examine Bax, Bcl-2, cleaved caspase-3, NF-κB and SMAD2 expression, and dual luciferase reporter experiment to examine the targeting relationship of miR-188-5p with LncGAS5 and SMAD2. The results indicated that LncGAS5 and SMAD2 were highly expressed in MIRI and miR-188-5p was under-expressed. Silencing LncGAS5 and SMAD2 or overexpressing miR-188-5p could reduce MIRI in myocardial tissue, cardiomyocyte apoptosis, inhibit Bax, cleaved caspase-3 and NF-κB expressions and promote Bcl-2 expression, while reducing inflammatory factors TNF -α, IL-1β and IL-6 levels. Overexpressing LncGAS5 promoted MIRI. Additionally, the impact of silencing LncGAS5 on MIRI could be reversed through inhibiting miR-188-5p. LncGAS5 acted as a sponge of miR-188-5p to target SMAD2 expression. In conclusion, Silencing LncGAS5 is available to improve MIRI through regulating miR-188-5p/SMAD2 axis, and may be used as a potential target for treating MIRI in the future.

Objectives To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC. Methods The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses. Results Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = −0.054; OR = 0.947; 95% confidence interval [CI], 0.925–0.970; P Conclusions The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC.

BackgroundClinically, only a minority of patients benefit from immunotherapy and few efficient biomarkers have been identified to distinguish patients who would respond to immunotherapy. The tumor microenvironment (TME) is reported to contribute to immunotherapy response, but details remain unknown. We aimed to construct a prognostic model based on the TME of lung adenocarcinoma (LUAD) to predict the prognosis and immunotherapy efficacy.MethodsWe integrated computational algorithms to describe the immune infiltrative landscape of LUAD patients. With the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses, we developed a LUAD tumor microenvironment prognostic signature (LATPS). Subsequently, the immune characteristics and the benefit of immunotherapy in LATPS-defined subgroups were analyzed. RNA sequencing of tumor samples from 28 lung cancer patients treated with anti-PD-1 therapy was conducted to verify the predictive value of the LATPS.ResultsWe constructed the LATPS grounded on four genes, including UBE2T, KRT6A, IRX2, and CD3D. The LATPS-low subgroup had a better overall survival (OS) and tended to have a hot immune phenotype, which was characterized by an elevated abundance of immune cell infiltration and increased activity of immune-related pathways. Additionally, tumor immune dysfunction and exclusion (TIDE) score was markedly decreased in the LATPS-low subgroup, indicating an enhanced opportunity to benefit from immunotherapy. Survival analysis in 28 advanced lung cancer patients treated with an anti-PD-1 regimen at Nanfang hospital revealed that the LATPS-low subgroup had better immunotherapy benefit.ConclusionLATPS is an effective predictor to distinguish survival, immune characteristics, and immunotherapy benefit in LUAD patients.

Little is known about the modulatory capacity of the microbiota in early intestinal development. We examined various intestinal models that respond to gut microbial metabolites based on human pluripotent stem cell-derived human intestinal organoids (hIOs): physiologically relevantiin vitro/ifetal-like intestine, intestinal stem cell, and intestinal disease models. We found that a newly isolatediLimosilactobacillus reuteri/istrain DS0384 accelerated maturation of the fetal intestine using 3D hIO with immature fetal characteristics. Comparative metabolomic profiling analysis revealed that the secreted metabolite N-carbamyl glutamic acid (NCG) is involved in the beneficial effect of DS0384 cell-free supernatants on the intestinal maturation of hIOs. Experiments in an intestinal stem cell spheroid model and hIO-based intestinal inflamed model revealed that the cell-free supernatant from DS0384 comprising NCG promoted intestinal stem cell proliferation and was important for intestinal protection against cytokine-induced intestinal epithelial injury. The probiotic properties of DS0384 were also evaluated, including acid and bile tolerance and ability to adhere to human intestinal cells. Seven-day oral administration of DS0384 and cell-free supernatant promoted the intestinal development of newborn mice. Moreover, NCG exerted a protective effect on experimental colitis in mice. These results suggest that DS0384 is a useful agent for probiotic applications and therapeutic treatment for disorders of early gut development and for preventing intestinal barrier dysfunction.

Sequential window acquisition of all theoretical spectra (SWATH) as a typical data-independent acquisition (DIA) strategy is favorable for untargeted metabolomics. It could theoretically acquire product ions of all precursor ions, including precursor ions showing chromatographic peaks of rather poor qualities. However, existing data processing methods present limited capabilities in capturing poor-quality peaks of precursor ions. Thus, although their product ions could be acquired, their precursor ions are absent. Here, we present a new strategy, chromatographic retention behavior-SWATH (CRB-SWATH), that could unbiasedly capture poor-quality peaks and provide high resolutions of multiplexed mass spectroscopy (MS/MS) spectra in SWATH datasets. CRB-SWATH monitors CRBs of SWATH-MS signals under a series of altered elution gradients. As signals of compounds differ from noise by showing CRBs, both the precursor and fragment ions are captured, while ignoring their peak qualities. Moreover, CRB-SWATH offers good chances to resolve highly multiplexed MS/MS spectra in SWATH datasets because precursor ions coeluted in a single elution gradient often present different CRBs. In the untargeted metabolic analysis of Hela cell extracts, CRB-SWATH showed the advantage in exclusively capturing 2645 ions of poor-quality peaks (i.e., tiny peaks, discontinuous ion traces, tailing peaks, zigzag peaks, etc.), accounting for 34.4% of all the untargeted precursor ions extracted. Therein, it is noteworthy that among 2116 negative ions detected in hydrophilic interaction liquid chromatography (HILIC) mode, 1284 poor-quality ion peaks (>60%) were exclusively captured by CRB-SWATH. As CRB-SWATH automatically captures a large sum of true ion peaks of poor qualities, extracts MS/MS spectra of high purities, and provides chromatographic retention behaviors of untargeted metabolites for identification and classification, it could be a useful metabolomics tool for understanding biological phenomena better.

Background Ultrasound is a promising imaging examination for type 2 diabetic peripheral neuropathy (DPN). This study aimed to explore the risk factors of ultrasound diagnostic characteristics in the tibial nerves of patients with type 2 DPN. Methods The Michigan Neuropathy Screening Instrument (MNSI) was used for neuropathy evaluation, and 520 patients with type 2 diabetes were divided into a DPN group and non-DPN (NDPN) group with 2 points as the cut-off value. The two groups were matched at a ratio of 1:1 according to age, BMI, calf circumference, and gender, resulting in 44 matched pairs. The dependent variable was type 2 DPN and the concomitant variables were the width, thickness, cross-sectional area, and unclear honeycomb-like structure of the tibial nerve. A 1:1 matched conditional logistic regression model was established to analyze which ultrasound diagnostic characteristics of the tibial nerve were risk factors for type 2 DPN. Results The thickness (OR =5.176, P=0.043) and cross-sectional area (OR =1.659, P=0.030) of the tibial nerve were risk factors for the diagnosis of DPN, while the width and unclear honeycomb-like structure of the nerve were not (P>0.05). In the diagnosis of DPN, the area under the receiver operating characteristic (ROC) curve of the cross-sectional area of the tibial nerve was 0.747, and the sensitivity, specificity, positive predictive value, and negative predictive value were 61.36%, 95.45%, 93.10%, and 71.20%, respectively. The area under the ROC curve of tibial nerve thickness was 0.867, and the sensitivity, specificity, positive predictive value, and negative predictive value were 81.82%, 90.91%, 90.00%, and 83.30%, respectively. The area under the ROC curve of thickness was larger than that of cross-sectional area of the tibial nerve (z statistic =1.800, P=0.07). Conclusions The thickness and cross-sectional area of the tibial nerve measured by ultrasound are risk factors for type 2 DPN. The diagnostic sensitivity of the thickness is higher than the cross-sectional area, while the diagnostic specificity of the cross-sectional area is higher than the thickness.

Background The life-threatening haemorrhagic complications of pulmonary arteriovenous malformations (PAVMs) are extremely rare, and only described in isolated cases. This study was designed to comprehensively investigate management of ruptured PAVMs. Methods We retrospectively assessed clinical and imaging data of ruptured PAVMs to summarize incidence, clinical characteristics, and outcomes following embolisation between January 2008 and January 2021. Results Eighteen of 406 (4.4%) patients with PAVMs developed haemorrhagic complications. Twelve of 18 patients were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT). Haemorrhagic complications occurred with no clear trigger in all cases. Eight of 18 patients (44.4%) were initially misdiagnosed or had undergone early ineffective treatment. 28 lesions were detected, with 89.3% of them located in peripheral lung. Computed tomography angiography (CTA) showed indirect signs to indicate ruptured PAVMs in all cases. Lower haemoglobin concentrations were associated with the diameter of afferent arteries in the ruptured lesions. Successful embolotherapy was achieved in all cases. After embolotherapy, arterial oxygen saturation improved and bleeding was controlled (P Conclusions Life threatening haemorrhagic complications of PAVMs are rare, they usually occur without a trigger and can be easily misdiagnosed. HHT and larger size of afferent arteries are major risk factors of these complications. CTA is a useful tool for diagnosis and therapeutic guidance for ruptured PAVMs. Embolotherapy is an effective therapy for this life-threatening complication.

Aging is a complex feature and involves loss of multiple functions and nonreversible phenotypes. However, several studies suggest it is possible to protect against aging and promote rejuvenation. Aging is associated with many factors, such as telomere shortening, DNA damage, mitochondrial dysfunction, and loss of homeostasis. The integrity of the cytoskeleton is associated with several cellular functions, such as migration, proliferation, degeneration, and mitochondrial bioenergy production, and chronic disorders, including neuronal degeneration and premature aging. Cytoskeletal integrity is closely related with several functional activities of cells, such as aging, proliferation, degeneration, and mitochondrial bioenergy production. Therefore, regulation of cytoskeletal integrity may be useful to elicit antiaging effects and to treat degenerative diseases, such as dementia. The actin cytoskeleton is dynamic because its assembly and disassembly change depending on the cellular status. Aged cells exhibit loss of cytoskeletal stability and decline in functional activities linked to longevity. Several studies reported that improvement of cytoskeletal stability can recover functional activities. In particular, microtubule stabilizers can be used to treat dementia. Furthermore, studies of the quality of aged oocytes and embryos revealed a relationship between cytoskeletal integrity and mitochondrial activity. This review summarizes the links of cytoskeletal properties with aging and degenerative diseases and how cytoskeletal integrity can be modulated to elicit antiaging and therapeutic effects.

In situ analysis of sweat provides a simple, convenient, cost-effective, and noninvasive approach for the early diagnosis of physical illness in humans and is particularly useful in family care. In this study, a flexible and skin-attachable colorimetric sweat sensor for multiplexed analysis is developed using a simple, cost-effective, and convenient method. The obtained sweat sensor can be used to simultaneously detect glucose, lactate, urea, and pH value in sweat, as well as sweat loss and skin temperature. Only 2.5 μL of sweat is enough for the whole test, and the sweat loss and chemical-sensing results can be read out conveniently by naked eyes or a smartphone. In addition, body temperature can also be detected with an additional electrical circuit. Our sweat sensor provides a new, cost-effective, and convenient approach for in vitro diagnosis of multiple components in sweat, and the easy fabrication and cost-effectiveness make our sensor commercializable in the near future.

Idiopathic ventricular tachycardia (VT) occurs in structurally normal hearts and accounts for a significant number of all types of VT. The genome-wide association study is the most effective strategy for identifying novel genetic variants for common diseases. However, no genome-wide association study has been reported for idiopathic VT.We conducted the first genome-wide association study for idiopathic VT in the Chinese Han population using a discovery population with 246 cases and 648 controls and a replication population with 222 cases and4072 controls. Candidate VT genes were functionally characterized in zebrafish. Real-time RT-PCR analysis was used to determine the effects of candidate genes on expression of ion channels and regulators. Patch-clamping was used to record L-type calcium current from neonatal rat cardiomyocytes with overexpression of candidate genes.We identified 4 significant loci represented by rs78960694 (minor allele frequency [MAF]=5.02% in cases and 1.84% in controls;The first genome-wide association study identifies 4 novel loci and 2 risk genes (

The composite of CdTe quantum dots (QDs) with ZIF-8 was elaborately designed and synthesized as an enzyme-free fluorescent probe for the sensitive determination of uric acid (UA), based on the fluorescence detection property of CdTe QDs and the signal amplification function of ZIF-8. The structure and feature of the composite were characterized with transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, and fluorescence spectrometry. With adding UA to the composite, the emission of CdTe QDs reduced due to the inner filter and dynamic quenching effects of UA, and the adsorption ability of ZIF-8 toward UA promoted the response signal of CdTe QDs. On this basis, UA was quantified by the composite in the concentration range 0.05 to 10 μM with excitation/emission wavelength at 287/615 nm, and the detection limit of the composite toward UA was 32 nM. The reproducibility of the composite for determining UA was further evaluated, and the relative standard deviations were below 10.2%. The composite also exhibited the merits of enzyme-free analysis such as low testing cost, short analysis time (1 min), and loose pH condition (application in whole physiological pH range, 5.0 - 8.0). The composite was applied to the determination of UA in human urine with recoveries of spiked samples in the range 99 to 113%.

To describe the ultrasonographic appearance of congenital anaplastic astrocytoma, so as to provide diagnostic clues for it. An updated review of the literature was also carried out.There was a case of fetal anaplastic astrocytoma detected by ultrasound at 37 + 1 weeks of gestation. It showed that a hypoechoic mass was located in the left hemisphere with a relatively clear margin and subtle color flows. Prenatal magnetic resonance imaging (MRI) which was taken subsequently confirmed the result of ultrasound. Intratumoral hemorrhage was observed in later follow-up and further confirmed by histological examination. The fetus was delivered vaginally at 39 + 6 weeks. The infant died 2 h after delivery due to respiration failure. The histological examination confirmed an anaplastic astrocytoma.Congenital anaplastic astrocytoma commonly detected by ultrasound has a relatively better perinatal prognosis, especially compared with glioblastoma. Prenatal ultrasonography diagnosis accurately is of critical importance. The anaplastic astrocytoma should be considered in cases in which fetal images reveal a heterogeneous echogenic mass in the brain, especially in the presence of intratumoral hemorrhage, subtle color flow, and relatively clear margin.

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

Deficits in the clearance of amyloid β-protein (Aβ) play a pivotal role in the pathogenesis of sporadic Alzheimer’s disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aβ phagocytosis function of peripheral monocytes during ageing and in AD patients. A total of 104 cognitively normal participants aged 22–89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson’s disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aβ uptake by blood monocytes was measured and its alteration during ageing and in AD patients were investigated. Aβ1-42 uptake by monocytes decreased during ageing and further decreased in AD but not in PD patients. Aβ1-42 uptake by monocytes was associated with Aβ1-42 levels in the blood. Among the Aβ uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aβ and might be involved in the development of AD. The recovery of the Aβ uptake function by blood monocytes represents a potential therapeutic strategy for AD.

This prospective study aimed to compare the diagnostic accuracy of shear wave elastography (SWE) with that of shear wave dispersion (SWD) in evaluation of hepatic fibrosis in patients with hepatocellular carcinoma before resection.A total of 210 consecutive patients with hepatocellular carcinoma (HCC) who were scheduled to undergo hepatectomy were prospectively enrolled, pre-operative SWE and SWD examinations were performed. Fibrosis staging and necroinflammatory activity were determined histopathologically according to the Scheuer standard. Multivariate linear regression analysis was used to identify factors associated with SWE and SWD values. The performance of SWE and SWD were determined by receiver operating characteristic (ROC) analysis.Both SWE and SWD values of liver were highly correlated with liver fibrosis stage and necroinflammatory activity (p 0.05). Both SWE and SWD values were significantly different among the patients with different stages of liver fibrosis (p 0.001). ROC analysis revealed that SWE that predicted substantial fibrosis (S ≥ 2), severe fibrosis (S ≥ 3) and cirrhosis (S = 4) were 0.895, 0.877 and 0.854, the SWD that predicted substantial fibrosis (S ≥ 2), severe fibrosis (S ≥ 3) and cirrhosis (S = 4) were 0.857, 0.815 and 0.791. SWE had better diagnostic performance than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4).Both SWE and SWD are useful, accurate and non-invasive methods for evaluating hepatic fibrosis in patients with hepatocellular carcinoma adapted to hepatectomy, SWE is a more accurate imaging modality than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4).

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its advanced form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Ceramides have been shown to exacerbate NAFLD development through enhancing insulin resistance, reactive oxygen species production, liver steatosis, lipotoxicity and hepatocyte apoptosis, and eventually causing hepatic inflammation and fibrosis. Emerging evidence indicates that ceramide production in NAFLD is predominantly attributed to activation of the de novo synthesis pathway of ceramides in hepatocytes. More importantly, pharmacological modulation of ceramide de novo synthesis in preclinical studies seems efficacious for the treatment of NAFLD. In this review, we provide an overview of the pathogenic mechanisms of ceramides in NAFLD, discuss recent advances and challenges in pharmacological interventions targeting ceramide de novo synthesis, and propose some research directions in the field.

CD22 has been suggested to contribute to Alzheimer’s disease (AD) pathogenesis by inhibiting microglial amyloid β (Aβ) phagocytosis. Soluble CD22 (sCD22) generated by cleavage from cell membranes may be a marker of inflammation and microglial dysfunction; but alterations of sCD22 levels in AD and their correlation with AD biomarkers remain unclear. Plasma sCD22 levels were measured in cognitively normal non-AD participants and patients with preclinical AD and AD dementia from a Chinese cohort and the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Plasma sCD22 levels were elevated in patients with preclinical and dementia AD. Plasma sCD22 levels were negatively correlated with cerebrospinal fluid (CSF) Aβ42 levels and Aβ42/Aβ40, and positively correlated with CSF phosphorylated tau levels and brain Aβ burden, but negatively correlated with cognitive function. Moreover, higher plasma sCD22 levels were associated with faster cognitive decline during follow-up. These findings suggest that CD22 plays important roles in AD development, and that sCD22 is a potential biomarker for AD.

Depression, a mood disorder, affects one in fifteen adults, has multiple risk factors and is associated with complicated underlying pathological mechanisms. P-coumaric acid (p-CA), a phenolic acid, is widely distributed in vegetables, fruits and mushrooms. P-CA has demonstrated a protective role against oxidative stress and inflammation in various diseases, including cardiovascular disease, diabetes and cancer. In the current study, we investigated the protection of p-CA against depression and memory impairment in a corticosterone (CORT)-induced chronic depressive mouse model. CORT administration resulted in depression-like behaviors and memory impairment. P-CA treatment alleviated CORT-induced depression-related behaviors and memory impairment. Network pharmacology predicted that p-CA had multiple targets and mediated various signaling pathways, of which inflammation-associated targets and signaling pathways are predominant. Western blotting showed CORT-induced activation of the advanced glycation end product (AGE)-receptor of AGE (RAGE) (AGE-RAGE) signaling and increased expression of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFα) in the hippocampus, while p-CA treatment inactivated AGE-RAGE signaling and decreased the levels of IL-1β and TNFα, suggesting that protection against depression and memory impairment by p-CA is mediated by the inhibition of inflammation, mainly via the AGE-RAGE signaling pathway. Our data suggest that p-CA treatment will benefit patients with depression.

Objectives:There have been reports on re-detectable positive nucleic acid tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recovered coronavirus disease (COVID-19) patients. In this study, we look at the clinical characteristics, possible causes, pathogenesis, and infectivity of re-detectable positive patients and provide up-to-date information to public health policy planners and clinicians.Methods:By consulting the latest research data and related progress data of re-detectable positive patients, this study addresses the implications that this special group brings to clinical work and disease prevention and control.Results:We discuss in detail the phenomenon of re-detectable positive nucleic acid tests for recovered patients. There are many possible causes of a re-detectable positive, but there is no 1 factor that can fully explain this phenomenon.Conclusions:It can’t be completely ruled out that the re-detectable positive patients are infectious. We should be alert to these re-detectable positive patients becoming chronic virus carriers, and virus serological IgM and IgG antibody tests should be added before patient discharge. It is urgent to find a more powerful evidence-based and virological basis for the integrity of viral ribonucleic acid and the variation of viral virulence with time through cell experiments in vitro and animal experiments in vivo.

Background IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. Methods Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. Results Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the “Jang & Kim's modified anatomical classification,” 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010–4.433]). Conclusions This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

Background Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. Methods Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. Results A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). Conclusions IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Background When a hepatic tumor is deeply located in segments 7 and 8 around the right hepatic vein (RHV), right hemihepatectomy (RH) could be excessive owing to the resection of large tumor-free segments. This study aimed to evaluate the feasibility and safety of bisegmentectomy 7–8 (S7–8) and to compare its surgical outcomes with those of RH. Materials and methods Consecutive patients who underwent S7–8 and RH were enrolled in this study. In the S7–8 group, 14 patients with an obvious inferior right hepatic vein (IRHV) (median: 6 mm; range: 3.6–8.8 mm) underwent S7–8 without hepatic vein reconstruction. RHV reconstruction was performed in six patients without an IRHV, involving direct anastomosis of the RHV in five patients and reconstruction using a cryo-preserved iliac vein in one patient. Results A total of 61 patients were included (20 in S7–8 group; 41 in RH group). No significant differences were observed other than higher a model of end-stage liver disease score in the RH group than in the S7–8 group (7 [6–20] vs. 6 [6–9], P = 0.003). Post-hepatectomy liver failure including severe grades was more frequent in the RH group (43.9% vs. 10%, P = 0.008). In the S7–8 group, two patients with direct RHV reconstruction had RHV anastomosis obstruction, and eventually required insertion of a metallic stent. However, computed tomography performed 4 weeks after the operation showed intact venous outflow of the right liver in the S7–8 group. Conclusion S7–8 can be performed safely in selected patients with a thick IRHV. For patients with no obvious IRHV, RHV reconstruction could be a good surgical strategy to retain venous outflow of the right liver with feasible outcomes.

Traditional Chinese exercises (TCEs) have a positive effect on glycemic control and hemoglobin A1c (HbA1c), but there is no consensus on the benefits of TCEs for patients with prediabetes.The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes.Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions.The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs.Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and INine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = -0.73, 95% confidence interval (CI) [-0.97, -0.50], P 0.00001; Baduanjin: SMD = -0.83, 95% CI [-1.13, -0.53], P 0.00001; 6 month treatment: SMD = -0.73, 95% CI [-1.20, -0.26], P = 0.002. (2) 2hPBG: SMD = -0.75, 95% CI [-0.94, -0.57], P 0.00001; Baduanjin: SMD = -0.62, 95% CI [-0.91, -0.32], P 0.00001; 6 month treatment: SMD = -0.91, 95% CI [-1.39, -0.44], P = 0.0002. (3) HbA1c: SMD = -0.56, 95% CI [-0.89, -0.23], P = 0.00008; Baduanjin: SMD = -0.46, 95% CI [-0.83, -0.08], P = 0.02; 6 month treatment: SMD = -0.77, 95% CI [-1.24, -0.29], P = 0.002.TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied.

Attention based end-to-end speech synthesis achieves better performance in both prosody and quality compared to the conventional "front-end"-"back-end" structure. But training such end-to-end framework is usually time-consuming because of the use of recurrent neural networks. To enable parallel calculation and long-range dependency modeling, a solely self-attention based framework named Transformer is proposed recently in the end-to-end family. However, it lacks position information in sequential modeling, so that the extra position representation is crucial to achieve good performance. Besides, the weighted sum form of self-attention is conducted over the whole input sequence when computing latent representation, which may disperse the attention to the whole input sequence other than focusing on the more important neighboring input states, resulting in generation errors. In this paper, we introduce two localness modeling methods to enhance the self-attention based representation for speech synthesis, which maintain the abilities of parallel computation and global-range dependency modeling in self-attention while improving the generation stability. We systematically analyze the solely self-attention based end-to-end speech synthesis framework, and unveil the importance of local context. Then we add the proposed relative-position-aware method to enhance local edges and experiment with different architectures to examine the effectiveness of localness modeling. In order to achieve query-specific window and discard the hyper-parameter of the relative-position-aware approach, we further conduct Gaussian-based bias to enhance localness. Experimental results indicate that the two proposed localness enhanced methods can both improve the performance of the self-attention model, especially when applied to the encoder part. And the query-specific window of Gaussian bias approach is more robust compared with the fixed relative edges.

Background A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. Methods We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. Results Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P

Pineoblastoma is a rare pediatric cancer induced by germline mutations in the tumor suppressors RB1 or DICER1. Presence of leptomeningeal metastases is indicative of poor prognosis. Here we report that inactivation of Rb plus p53 via a WAP-Cre transgene, commonly used to target the mammary gland during pregnancy, induces metastatic pineoblastoma resembling the human disease with 100% penetrance. A stabilizing mutation rather than deletion of p53 accelerates metastatic dissemination. Deletion of Dicer1 plus p53 via WAP-Cre also predisposes to pineoblastoma, albeit with lower penetrance. In silico analysis predicts tricyclic antidepressants such as nortriptyline as potential therapeutics for both pineoblastoma models. Nortriptyline disrupts the lysosome, leading to accumulation of non-functional autophagosome, cathepsin B release and pineoblastoma cell death. Nortriptyline further synergizes with the antineoplastic drug gemcitabine to effectively suppress pineoblastoma in our preclinical models, offering new modality for this lethal childhood malignancy., Pineoblastoma is a rare pediatric cancer. Here, the authors present inactivation of Rb plus p53 via a WAP-Cre transgene induces metastatic pineoblastoma resembling human disease, and using this model, predict tricyclic antidepressants as a potential therapy for pineoblastoma, supported by their pre-clinical model.

Triboelectric nanogenerator (TENG) has been proven effective in converting biomechanical energy into electrical energy, which is expected to be a new energy supply device for wearable electronics and can be utilized as a self-powered sensor. In this work, we have developed a flexible, eco-friendly, and multifunctional fish gelatin based triboelectric nanogenerator (FG-TENG) composed of fish gelatin (FG) film and poly(tetrafluoroethylene)/poly(dimethylsiloxane) (PTFE/PDMS) composite film. The open-circuit voltage (Voc), short-circuit current (Isc), and output power density of this FG-TENG could reach up to 130 V, 0.35 μA, and 45.8 μW cm-2, respectively, which were significantly higher than those of TENGs based on other commonly used positive friction materials such as aluminum foil, poly(ethylene terephthalate) (PET), and print paper. The superior performance of the FG-TENG is attributed to the strong electron-donating ability of the FG during the triboelectric process. The generated electric energy was high enough to light up 50 commercial light-emitting diodes (LEDs) directly. Importantly, owing to the high stability and excellent sensitivity of the FG-TENG, it has been used as a self-powered sensor for real-time monitoring of the human physiological signals such as finger touch, joint movement, and respiration. Furthermore, to expand the usages in real-life applications, a foldable FG-TENG was fabricated by adopting the Miura folding to monitor human movements in real time. This work provides an economical, simple, and environmental-friendly approach to fabricate a biomechanical energy harvester, which has a great potential in powering next-generation wearable electronics and monitoring human physiological signals.

Background: The knowledge of 3-dimensional scapular kinematics is essential for understanding the pathological lesions of the shoulder and elbow in throwing athletes. Many studies about alterations of the resting scapular position, dynamic scapular motion, or scapular dyskinesis (SD) have been conducted, yet none of them have identified a consistent pattern of altered scapular kinematics in throwing athletes. Hypothesis/Purpose: To analyze the 3-dimensional scapular kinematics of dominant and nondominant arms in baseball players with a pathological condition of the shoulder or elbow. Study Design: Cross-sectional study. Methods: Bilateral scapular positions, consisting of upward rotation (UR), superior translation (ST), internal rotation (IR), protraction (PRO), and anterior tilting (AT) with an arm at rest and at 150° forward elevation, were measured among 319 baseball players with SD using 3-dimensional computed tomography. Angular values of scapula were compared between dominant and nondominant arms with statistical analysis. Level of Evidence: Level III, diagnostic study. Results: The scapular position of dominant arms showed significantly more AT, less ST at rest and more UR and IR and less ST, PRO, and AT at 150° full forward elevation compared with the nondominant arms. The magnitude of mean change of UR, IR, PRO, and AT during arm elevation increased significantly between the paired arms (P value: UR, ST, PRO, and AT: Conclusion: When compared with the nondominant arms, UR, AT, and PRO with the arm at 150° forward elevation of dominant symptomatic arms in baseball players tilted toward positive compensation, whereas IR altered toward negative decompensation. In addition, the angular increment of the scapula increased significantly in dominant symptomatic arms compared with the nondominant arms.

Cerebrospinal fluid (CSF) biomarkers are essential for the accurate diagnosis of Alzheimer’s disease (AD), yet their measurement levels vary widely across centers and regions, leaving no uniform cutoff values to date. Diagnostic cutoff values of CSF biomarkers for AD are lacking for the Chinese population. As a member of the Alzheimer’s Association Quality Control program for CSF biomarkers, we aimed to establish diagnostic models based on CSF biomarkers and risk factors for AD in a Chinese cohort. A total of 64 AD dementia patients and 105 age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study cohort were included. CSF Aβ42, P-tau181, and T-tau levels were measured by ELISA. Combined biomarker models and integrative models with demographic characteristics were established by logistic regression. The cutoff values to distinguish AD from CN were 933 pg/mL for Aβ42, 48.7 pg/mL for P-tau181 and 313 pg/mL for T-tau. The AN model, including Aβ42 and T-tau, had a higher diagnostic accuracy of 89.9%. Integrating age and APOE ε4 status to AN model (the ANA’E model) increased the diagnostic accuracy to 90.5% and improved the model performance. This study established cutoff values of CSF biomarkers and optimal combined models for AD diagnosis in a Chinese cohort.

As enzymes in the outer membrane of the mitochondrion, monoamine oxidases (MAOs) can catalyze the oxidative deamination of monoamines in the human body. According to different substrates, MAOs can be divided into MAO-A and MAO-B. The imbalance of the MAO-A is associated with neurological degeneration, while excess MAO-B activity is closely connected with Parkinson's disease (PD) and Alzheimer's disease (AD); therefore, detection of MAOs is of great significance for the diagnosis and treatment of these diseases. This work reports the multiplexed detection of MAO-A and MAO-B using paper-based devices based on chemiluminescence (CL). The detection limits were 5.01 pg/mL for MAO-A and 8.50 pg/mL for MAO-B in human serum. In addition, we used paper-based devices to detect MAOs in human cells and tissue samples and found that the results of paper-based detection and Western blotting (WB) showed the same trend. While only one antibody can be incubated on the same membrane by WB, multiple antibodies incubated on the same paper enabled simultaneous detection of MAO-A and MAO-B by paper-based devices. The paper-based assay could be used for preliminary early screening of clinical samples for MAOs and can be extended as an alternative to WB for multiplexed detection of various proteins in disease cell or tissue samples.

Trans-urocanic acid (trans-UCA) is an isomer of cis-UCA and is widely distributed in the brain, predominantly in the hippocampus and prefrontal cortex. Previous studies have investigated the role of trans-UCA in non-spatial memory; however, its influence on spatial memory remains unclear. In the present study, network pharmacology strategy and behavioral testing were used to evaluate the role of trans-UCA in spatial memory and predict its possible mechanism. The results showed that there are 40 intersecting targets between trans-UCA and spatial memory identified by several databases and Venn diagram, indicating that trans-UCA may be involved in spatial memory. Behavioral results show that trans-UCA facilitates spatial working memory in the Y-maze test as well as spatial recognition memory acquisition, consolidation and retrieval in an object location recognition (OLR) task. Furthermore, PPI (protein-protein interaction) network analysis, GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses show that the molecular mechanisms underlying the enhancing effect of trans-UCA on spatial memory are mainly associated with the regulation of insulin, mitogen-activated protein kinase (MAPK) and nuclear factor Kappa B (NF-κB) signaling pathways, serotonergic synapse and arginine and proline metabolism. The results of this study suggest that trans-UCA facilitates spatial memory in the Y-maze test and OLR task and may offer therapeutic potential for Alzheimer's disease (AD). The underlying mechanisms predicted by network pharmacology should be further verified.

Multifunctional fluorescent probes have received increasing attention for the sake of atom economy and high-density integration. Herein, CdTe quantum dots (QDs) modified with Eu