Empathy ability and influencing factors among pediatric residents in China: a mixed-methods study.

BACKGROUND: Empathy is one of the fundamental factors enhancing the therapeutic effects of physician-patient relationships, but there has been no relevant research in China on the pediatric resident physicians' capacity for empathy or the influencing factors. METHODS: A mixed-methods study was undertaken. The student version of the Jefferson Scale of Empathy was used to assess 181 postgraduate residents at Shanghai Children's Medical Center and Shanghai Children's Hospital. Differences in empathy ability among pediatric resident physicians of different genders and specialties were analyzed using independent sample t-tests and Mann-Whitney U tests. A one-way analysis of variance was used to analyze the differences in empathy ability at different educational levels and years of medical residency training. Seven third-year postgraduate pediatric residents from Shanghai Children's Medical Center participated in semi-structured interviews exploring the influencing factors. We analyzed the interview transcripts using thematic analysis. RESULTS: The scale was completed by 154 pediatric residents. No statistically significant differences in empathy were found between educational level, postgraduate year, gender, or specialty. The factors influencing empathy in doctor-patient communication included the person who accompanied the child to see the doctor, how the children cooperated with doctors for medical treatment, the volume of pediatric outpatient and emergency visits, and the physician's ability to withstand pressure. All interviewed resident physicians regarded learning empathy as important but rarely spent extra time learning it. CONCLUSIONS: The evaluation results of resident physicians on changes in empathy after improving clinical abilities vary according to their understanding of empathy, and the work environment has an important impact on pediatricians' empathy ability. Their empathy score is relatively low, and this requires exploration and intervention.

Magnetostrictive bi-perceptive flexible sensor for tracking bend and position of human and robot hand.

The sensor that simultaneously perceives bending strain and magnetic field has the potential to detect the finger bending state and hand position of the human and robot. Based on unique magneto-mechanical coupling effect of magnetostrictive materials, the proposed a bi-perceptive flexible sensor, consisting of the Co-Fe film and magnetic sensing plane coils, can realize dual information perception of strain/magnetic field through the change of magnetization state. The sensor structure and interface circuit of the sensing system are designed to provide high sensitivity and fast response, based on the input-output characteristics of the simulation model. An asynchronous multi-task deep learning method is proposed, which takes the output of the position task as the partial input of the bending state task to analyze the output information of the sensor quickly and accurately. The sensing system, integrating with the proposed model, can better predict the bending state and approach distance of human or robot hand.

Genetic spectrum features and diagnostic accuracy of four plasma biomarkers in 248 Chinese patients with frontotemporal dementia.

INTRODUCTION: Frontotemporal dementia (FTD) is characterized by phenotypic and genetic heterogeneities. However, reports on the large Chinese FTD cohort are lacking. METHODS: Two hundred forty-eight patients with FTD were enrolled. All patients and 2010 healthy controls underwent next generation sequencing. Plasma samples were analyzed for glial fibrillary acidic protein (GFAP), α-synuclein (α-syn), neurofilament light chain (NfL), and phosphorylated tau protein 181 (p-tau181). RESULTS: Gene sequencing identified 48 pathogenic or likely pathogenic mutations in a total of 19.4% of patients with FTD (48/248). The most common mutation was the C9orf72 dynamic mutation (5.2%, 13/248). Significantly increased levels of GFAP, α-syn, NfL, and p-tau181 were detected in patients compared to controls (all p < 0.05). GFAP and α-syn presented better performance for diagnosing FTD. DISCUSSION: We investigated the characteristics of phenotypic and genetic spectrum in a large Chinese FTD cohort, and highlighted the utility of plasma biomarkers for diagnosing FTD. HIGHLIGHTS: This study used a frontotemporal dementia (FTD) cohort with a large sample size in Asia to update and reveal the clinical and genetic spectrum, and explore the relationship between multiple plasma biomarkers and FTD phenotypes as well as genotypes. We found for the first time that the C9orf72 dynamic mutation frequency ranks first among all mutations, which broke the previous impression that it was rare in Asian patients. Notably, it was the first time the C9orf72 G4C2 repeat expansion had been identified via whole-genome sequencing data, and this was verified using triplet repeat primed polymerase chain reaction (TP-PCR). We analyzed the diagnostic accuracy of four plasma biomarkers (glial fibrillary acidic protein [GFAP], α-synuclein [α-syn], neurofilament light chain [NfL], and phosphorylated tau protein 181 [p-tau181]) at the same time, especially for α-syn being included in the FTD cohort for the first time, and found GFAP and α-syn had the highest diagnostic accuracy for FTD and its varied subtypes.

[Applications of high performance liquid chromatography-mass spectrometry in proteomics].

Proteomics profiling plays an important role in biomedical studies. Proteomics studies are much more complicated than genome research, mainly because of the complexity and diversity of proteomic samples. High performance liquid chromatography-mass spectrometry (HPLC-MS) is a fundamental tool in proteomics research owing to its high speed, resolution, and sensitivity. Proteomics research targets from the peptides and individual proteins to larger protein complexes, the molecular weight of which gradually increases, leading to sustained increases in structural and compositional complexity and alterations in molecular properties. Therefore, the selection of various separation strategies and stationary-phase parameters is crucial when dealing with the different targets in proteomics research for in-depth proteomics analysis. This article provides an overview of commonly used chromatographic-separation strategies in the laboratory, including reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), hydrophobic interaction chromatography (HIC), ion-exchange chromatography (IEC), and size-exclusion chromatography (SEC), as well as their applications and selectivity in the context of various biomacromolecules. At present, no single chromatographic or electrophoretic technology features the peak capacity required to resolve such complex mixtures into individual components. Multidimensional liquid chromatography (MDLC), which combines different orthogonal separation modes with MS, plays an important role in proteomics research. In the MDLC strategy, IEC, together with RPLC, remains the most widely used separation mode in proteomics analysis; other chromatographic methods are also frequently used for peptide/protein fractionation. MDLC technologies and their applications in a variety of proteomics analyses have undergone great development. Two strategies in MDLC separation systems are mainly used in proteomics profiling: the "bottom-up" approach and the "top-down" approach. The "shotgun" method is a typical "bottom-up" strategy that is based on the RPLC or MDLC separation of whole-protein-sample digests coupled with MS; it is an excellent technique for identifying a large number of proteins. "Top-down" analysis is based on the separation of intact proteins and provides their detailed molecular information; thus, this technique may be advantageous for analyzing the post-translational modifications (PTMs) of proteins. In this paper, the "bottom-up" "top-down" and protein-protein interaction (PPI) analyses of proteome samples are briefly reviewed. The diverse combinations of different chromatographic modes used to set up MDLC systems are described, and compatibility issues between mobile phases and analytes, between mobile phases and MS, and between mobile phases in different separation modes in multidimensional chromatography are analyzed. Novel developments in MDLC techniques, such as high-abundance protein depletion and chromatography arrays, are further discussed. In this review, the solutions proposed by researchers when encountering compatibility issues are emphasized. Moreover, the applications of HPLC-MS combined with various sample pretreatment methods in the study of exosomal and single-cell proteomics are examined. During exosome isolation, the combined use of ultracentrifugation and SEC can yield exosomes of higher purity. The use of SEC with ultra-large-pore-size packing materials (200 nm) enables the isolation of exosomal subgroups, and proteomics studies have revealed significant differences in protein composition and function between these subgroups. In the field of single-cell proteomics, researchers have addressed challenges related to reducing sample processing volumes, preventing sample loss, and avoiding contamination during sample preparation. Innovative methods and improvements, such as the utilization of capillaries for sample processing and microchips as platforms to minimize the contact area of the droplets, have been proposed. The integration of these techniques with HPLC-MS shows some progress. In summary, this article focuses on the recent advances in HPLC-MS technology for proteomics analysis and provides a comprehensive reference for future research in the field of proteomics.

Unveiling the frontiers of potato disease research through bibliometric analysis.

Research on potato diseases had been widely reported, but a systematic review of potato diseases was lacking. Here, bibliometrics was used to systematically analyze the progress of potato disease. The publications related to "potato" and "disease" were searched in the Web of Science (WOS) from 2014 to 2023. The results showed that a total of 2095 publications on potato diseases were retrieved, with the annual publication output increasing year by year at a growth rate of 8.52%. The main countries where publications were issued were the United States, China, and India. There was relatively close cooperation observed between China, the United States, and the United Kingdom in terms of international collaboration, while international cooperation by India was less extensive. Based on citation analysis and trending topics, potential future research directions include nanoparticles, which provides highly effective carriers for biologically active substances due to their small dimensions, extensive surface area, and numerous binding sites; machine learning, which facilitates rapid identification of relevant targets in extensive datasets, thereby accelerating the process of disease diagnosis and fungicide innovation; and synthetic communities composed of various functional microorganisms, which demonstrate more stable effects in disease prevention and control.

Shape-position perceptive fusion electronic skin with autonomous learning for gesture interaction.

Wearable devices, such as data gloves and electronic skins, can perceive human instructions, behaviors and even emotions by tracking a hand's motion, with the help of knowledge learning. The shape or position single-mode sensor in such devices often lacks comprehensive information to perceive interactive gestures. Meanwhile, the limited computing power of wearable applications restricts the multimode fusion of different sensing data and the deployment of deep learning networks. We propose a perceptive fusion electronic skin (PFES) with a bioinspired hierarchical structure that utilizes the magnetization state of a magnetostrictive alloy film to be sensitive to external strain or magnetic field. Installed at the joints of a hand, the PFES realizes perception of curvature (joint shape) and magnetism (joint position) information by mapping corresponding signals to the two-directional continuous distribution such that the two edges represent the contributions of curvature radius and magnetic field, respectively. By autonomously selecting knowledge closer to the user's hand movement characteristics, the reinforced knowledge distillation method is developed to learn and compress a teacher model for rapid deployment on wearable devices. The PFES integrating the autonomous learning algorithm can fuse curvature-magnetism dual information, ultimately achieving human machine interaction with gesture recognition and haptic feedback for cross-space perception and manipulation.

CISD2 regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS.

OBJECTIVES: To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of CISD2 to the onset and progression of PCOS. METHODS: Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage. RESULTS: We found that CISD2, mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, mitophagy, and CISD2 in KGN cells. CISD2 inhibition promoted the increase of mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress. CONCLUSIONS: Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of mitophagy, thus affecting the occurrence and development of PCOS diseases.

Characteristics of lipid metabolism after treatment of colon cancer mice with American ginseng vesicles.

INTRODUCTION: Lipid molecules are present in tumours and play an important role in the anti-inflammatory response as well as in antiviral protection. Changes in the type and location of lipids in the intestine following exposure to environmental stressors play an important role in several disorders, including ulcerative colitis (UC), inflammatory bowel disease (IBD), and colorectal cancer. OBJECTIVES: The aim of this work is to provide a new theoretical basis for tumour initiation and development by accurately measuring the spatial distribution of lipids and metabolites in intestinal tissue. Spatial metabolomics allows the detection of samples with minimal sample volume by label-free imaging of complex samples in their original state. The distribution of lipid molecules in tumours has not been reported, although the distribution of lipid molecules in intestinal tissue has been reported in the literature. METHODS: The range of lipid profiles in colon cancer mouse tumour tissue was compiled using a spatial metabolomics: lipid extraction method. The changes in lipid distribution in two regions after oral administration of American Ginseng (Panax quinquefolius L.) vesicles were also compared. Tumour tissue samples were extracted with 80% methanol-20% formic acid in water. RESULTS: The resulting spatial metabolic profile allowed the identification of seven lipid classes in mouse tumours. The distribution of fibre tissue cells was 23.2% higher than tumour tissue cells, with the exception of the fatty acid (FA) species.

Comprehensive risk factor predictions for 3-year survival among HIV-associated and disseminated cryptococcosis involving lungs and central nervous system.

BACKGROUND: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. METHODS: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. RESULTS: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). CONCLUSIONS: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.

Improving crop health by synthetic microbial communities: Progress and prospects.

Crop health directly affects yields and food security. At present, agrochemicals such as fertilizers and pesticides are mainly used in agricultural production to promote crop health. However, long-term excessive utilization of agrochemicals will damage the ecological environment of farmlands and increase the safety risk of agricultural products. It is urgent to explore efficient and environment-friendly agricultural products. Rhizosphere microbiome are considered as the second genome of plants, which are closely related to crop health. Understanding the key functional microbes, microbe-microbe interactions, and plant-microbe interactions are fundamental for exploring the potential of beneficial microbes in promoting crop health. However, due to the heterogeneity and complexity of the natural environment, stimulating the function of indigenous microorganisms remains uncertain. Synthetic microbial community (SynCom) is an artificial combination of two or more different strain isolates of microorganisms, with different taxonomic, genetic, or functional characteristic. Because of the advantages of maintaining species diversity and community stability, SynCom has been widely applied in the fields of human health, environmental governance and industrial production, and may also have great potential in promoting crop health. We summarized the concept and research status of SynCom, expounded the principles and methods of constructing SynCom, and analyzed the research on the promotion of crop health by exploring the mechanism of plant-microbe interactions, promoting plant growth and development, and improving stress resistance. Finally, we envisaged the future prospects to guide the using SynCom to improve crop health.

Bismuth-Doped Carbon Dots Decorated Escherichia coli for Enhanced Hydrogen Production.

Photosynthetic inorganic biohybrid systems (PBSs) combining an inorganic photosensitizer with intact living cells provide an innovative view for solar hydrogen production. However, typical whole-cell biohybrid systems often suffer from sluggish electron transfer kinetics during transmembrane diffusion, which severely limits the efficiency of solar hydrogen production. Here, a unique biohybrid system with a quantum yield of 8.42% was constructed by feeding bismuth-doped carbon dots (Bi@CDS) to Escherichia coli (E. coli). In this biohybrid system, Bi@CDS can enter the cells and transfer the electrons upon light irradiation, greatly reducing the energy loss and shortening the distance of electron transfer. More importantly, the photocatalytic hydrogen production of the E. coli-Bi@CDs biohybrid system reached up to 0.95 mmol within 3 h under light irradiation (420-780 nm, 2000 W m-2), which is 1.36 and 2.38 times higher than that in the E. coli-CDs biohybrid system and the E. coli system, respectively. In addition, the mechanism of enhanced hydrogen production was further explored. It was found that the accelerated decomposition of glucose, the accelerated production of pyruvate, the inhibition of lactic acid, and the increase of formic acid were the reasons for the increase of hydrogen production. This work provides a novel strategy for improving the hydrogen production in photosynthetic inorganic biohybrid systems.

A Self-Healing Conductive Elastomer Based on a Polymerizable Deep Eutectic Solvent.

Conductive elastomers are extensively used in electronics; however, they are prone to mechanical damage, have shortened service life, and cause environmental pollution and resource waste under the influence of external factors. Therefore, conductive elastomers with rapid self-healing properties are crucial for solving these problems. To that end, a conductive elastomer based on a polymerizable deep eutectic solvent as the matrix is developed in this study. The contents of certain small molecules and conductive particles are adjusted to yield a conductive elastomer with excellent comprehensive performance. The elastomer exhibited noteworthy fracture strength (15.7 MPa), ultrahigh fracture elongation (2400%), excellent light transmittance (95.6%), and remarkable self-healing characteristics, with complete electrical healing achieved within 0.6 s, ≈63% strain, and ≈64% stress recovered within 1 min, and healing efficiency close to 99% realized within 24 h. By leveraging these properties, the elastomer is used to construct a sensor that exhibited a gauge factor of ≈0.574 in the strain range 0-2400% and excellent stability. Moreover, the CCK-8 toxicity test and fluorescence staining experiment have demonstrated that conductive elastomers have excellent cell compatibility and also have excellent potential in the field of biomedicine. In particular, the sensor is effectively applied in human motion detection, health monitoring.

Ginseng-derived nanoparticles reprogram macrophages to regulate arginase-1 release for ameliorating T cell exhaustion in tumor microenvironment.

BACKGROUND: Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear. METHODS: The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry. RESULTS: GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8+ T cells expansion. CONCLUSIONS: By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment.

SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer.

Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

The application of rapid response team in category 1 emergency caesarean section teaching for OBGYN residents in the delivery room.

Category 1 cesarean section (CS) can be a life-saving procedure when there is immediate threat to the life of the woman or fetus. However, category 1 CS is a challenge for obstetrics and gynecology residents, and it is necessary to establish an effective and straightforward teaching strategy. This study aimed to evaluate the efficiency of rapid response team (RRT) on category 1 CS teaching for obstetrics and gynecology residents in the delivery room. A total of 142 residents who underwent standardized residency training programs in the delivery room were divided into a RRT teaching group and a traditional response (TR) teaching group. In the RRT teaching group, Category 1 emergency CS teaching was started and explored by rapid response team. The training included both theoretical and practical components. After the training, decision-to-delivery interval (DDI), neonatal Apgar score, operation time and rate of postpartum hemorrhage were compared. A questionnaire on the subjective assessment of various aspects of the program was conducted at the end of the training period. The DDI in minutes in the RRT teaching group (n = 72) was significantly shorter than that of the TR teaching group (n = 70) (11.83 ±â€…4.16 vs 13.56 ±â€…5.47, P = .0364). The score of satisfaction from residents in the RRT teaching group was significantly higher than that of the TR group [7 (6, 9) vs 9 (7, 10), P = .0154]. Compared with the TR teaching group, more residents thought their clinical skills have been improved (94.29% vs 100%, P = .0396) and willing to recommend their training method to others (91.43% vs 100%, P = .0399) in the RRT teaching group. However, no significant differences were observed in the incidence of postpartum hemorrhage between the 2 groups. RRT teaching is beneficial in the standardized training and teaching of residents in the delivery room. It improves the DDI of category 1 emergency cesarean section and the degree of satisfaction.

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND AND AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID. METHODS: In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022. RESULTS: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%). INTERPRETATION: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

Clinical features of progressive supranuclear palsy.

Background: Progressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China. Method: Clinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD. Results: Throughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD. Conclusion: PSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.

Exosomal ACADM sensitizes gemcitabine-resistance through modulating fatty acid metabolism and ferroptosis in pancreatic cancer.

This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms through RNA-sequencing and mass spectrometry. We sought to understand the connection between the exosomal Medium-chain acyl-CoA dehydrogenase (ACADM) level and the reaction to gemcitabine in vivo and in patients with PC. We employed loss-of-function, gain-of-function, metabolome mass spectrometry, and xenograft models to investigate the effect of exosomal ACADM in chemoresistance in PC. Our results showed that the molecules involved in lipid metabolism in exosomes vary between PC cells with different gemcitabine sensitivity. Exosomal ACADM (Exo-ACADM) was strongly correlated with gemcitabine sensitivity in vivo, which can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. Moreover, ACADM was found to regulate the gemcitabine response by affecting ferroptosis through Glutathione peroxidase 4 (GPX4) and mevalonate pathways. It was also observed that ACADM increased the consumption of unsaturated fatty acids and decreased intracellular lipid peroxides and reactive oxygen species (ROS) levels. In conclusion, this research suggests that Exo-ACADM may be a viable biomarker for predicting the responsiveness of patients to chemotherapy.

Lung cancer-derived exosomal miR-132-3p contributed to interstitial lung disease development.

PURPOSE: Interstitial lung diseases (ILDs) have high morbidity and mortality and poor prognosis. The significance of microRNAs (miRNAs) was highlighted in ILDs development. Currently, we attempted to confirm the functions of lung cancer-derived exosomal miR-132-3p and reveal the underlying mechanism. METHOD: Characteristics of exosomes were verified by transmission electron microscope (TEM), nanoparticle tracking analysis, and Western blot assay. Exosome uptake for the normal human lung fibroblasts (NHLF) was assessed using a PKH67 staining assay. MTT and colony formation assays were applied to examine the proliferation abilities of NHLF. The interaction between miR-132-3p and sprouty1 (SPRY1) was confirmed by a luciferase reporter assay. RESULTS: Lung cancer-derived exosomes promoted normal human lung fibroblast activation. Exosome inhibitor GW4869 reversed the effects of Exo on NHLF. Subsequently, miR-132-3p in lung cancer-derived exosomes activated the normal human lung fibroblast and promoted interstitial lung disease development ex vivo. Next, SPRY1 was verified to be the binding protein of miR-132-3p, and sh-SPRY1 abrogated the effects of the miR-132-3p inhibitor on NHLF. CONCLUSION: Exosomal miR-132-3p from A549 cells accelerated the development of interstitial lung disease through binding to SPRY1, which might serve as an important target for ILDs.