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Abstract Background Cholangiocarcinoma is a highly heterogeneous tumor with bile acid metabolism involving in its development. The aim of this study was to characterize bile acid metabolism and identify specific subtypes to better stratify cholangiocarcinoma patients for individualized treatment and prognostic assessment. Methods A total of 30 bile acids were quantified using the ultra-performance liquid chromatography tandem mass spectrometry. Using Consensus clustering, the molecular subtypes related to bile acid metabolism were identified. The prognosis, clinicopathologic characteristics, immune landscape, and therapeutic response were compared between these subtypes. The single-cell RNA sequencing (scRNA-seq) analysis and preliminary cell experiment were also conducted to verify our findings. Results The altered bile acid profile and genetic variation of bile acid metabolism-related genes in cholangiocarcinoma were demonstrated. The cholangiocarcinoma was categorized into bile acid metabolism-active and -inactive subtypes with different prognoses, clinicopathologic characteristics, tumor microenvironments (TME) and therapeutic responses. This categorization was reproducible and predictable. Specifically, the bile acid metabolism-active subtype showed a poor prognosis with an immunosuppressive microenvironment and an inactive response to immunotherapy, while the bile acid metabolism-inactive subtype showed the opposite characteristics. Moreover, the scRNA-seq revealed that immunotherapy altered bile acid metabolism in TME of cholangiocarcinoma. Finally, a prognostic signature related to bile acid metabolism was developed, which exhibited strong power for prognostic assessment of cholangiocarcinoma. Consistently, these results were verified by immunohistochemistry, cell proliferation, migration, and apoptosis assays. Conclusion In conclusion, a novel cholangiocarcinoma classification based on bile acid metabolism was established. This classification was significant for the estimation of TME and prognosis.

Abstract RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy.

Estrogen is a necessary sex steroid and potent neuroprotective hormone. It plays a multifaceted role beyond the reproductive system, extending its influence to the brain, skeletal muscle, and other organs. Estrogen’s role in cognition, mood, autonomic regulation, and neuroprotection involves interactions with neurotransmitters, neuromodulators in a distributed manner. Notably, the impact of estrogen on mitochondrial metabolism in skeletal muscle is particularly significant due to a unique modulated bioenergetic profiles, synaptic plasticity, and neuronal health. The deficiency of estrogen in menopause has been linked to changes in brain structure, connectivity, energy metabolism. Therewith, these are crucial factors in cognitive function and the risk of Alzheimer’s diseases. Besides, it leads to endocrine and metabolic dysfunction, resulting in osteoporosis, metabolic syndrome, and a tendency toward decreased muscle mass and strength. Estrogen’s influence on mitochondrial function is particularly relevant to aging, as it affects the production of ATP and the overall metabolic health of the brain. Estrogen decline in women skeletal muscle mass is usually related to sarcopenia, a prevalent disease observed in vulnerable elderly individuals. Therefore, estrogen is considered to play a crucial role in skeletal muscle homeostasis and motor ability, although the exact mechanism remains unclear. This paper reviews the literature on the impact of estrogen on postmenopausal skeletal muscle diseases and the underlying molecular mechanisms, especially in terms of mitochondrial metabolism. In summary, estrogen plays an important role in the health of skeletal muscle in postmenopausal women, and its impact on mitochondrial function and homeostasis offers potential targets for the development of new strategies to treat sarcopenia.

Medullary Thyroid Carcinoma (MTC), a neuroendocrine malignancy that arises from the calcitonin-secreting parafollicular C-cells of the thyroid, constitutes a minor yet impactful fraction of thyroid malignancies. Distinguished by its propensity for aggressive growth and a pronounced tendency for metastasis, MTC poses formidable obstacles to the early diagnosis and therapeutic intervention. The molecular genetics of MTC, particularly the role of the RET gene and the RAS gene family, have been extensively studied, offering insights into the pathogenesis of the disease and revealing potential therapeutic targets. This comprehensive review synthesizes the latest advancements in the molecular genetics of MTC, the evolution of precision therapies, and the identification of novel biomarkers. We also discuss the implications of these findings for clinical practice and the future direction of MTC research.

ABSTRACT As antimicrobial resistance (AMR) surveillance shifts to genomics, ensuring the quality of whole-genome sequencing (WGS) data produced across laboratories is critical. Participation in genomic proficiency tests (GPTs) not only increases individual laboratories' WGS capacity but also provides a unique opportunity to improve species-specific thresholds for WGS quality control (QC) by repeated resequencing of distinct isolates. Here, we present the results of the EU Reference Laboratory for Antimicrobial Resistance (EURL-AR) network GPTs of 2021 and 2022, which included 25 EU national reference laboratories (NLRs). A total of 392 genomes from 12 AMR-bacteria were evaluated based on WGS QC metrics. Two percent (n = 9) of the data were excluded, due to contamination, and 11% (n = 41) of the remaining genomes were identified as outliers in at least one QC metric and excluded from computation of the adjusted QC thresholds (AQT). Two QC metric correlation groups were identified through linear regression. Eight percent (n = 28) of the submitted genomes, from 11 laboratories, failed one or more of the AQTs. However, only three laboratories (12%) were identified as underperformers, failing across AQTs for uncorrelated QC metrics in at least two genomes. Finally, new species-specific thresholds for “N50” and “number of contigs > 200 bp” are presented for guidance in routine laboratory QC. The continued participation of NRLs in GPTs will reveal WGS workflow flaws and improve AMR surveillance data. GPT data will continue to contribute to the development of reliable species-specific thresholds for routine WGS QC, standardizing sequencing data QC and ensure inter- and intranational laboratory comparability.IMPORTANCEIllumina next-generation sequencing is an integral part of antimicrobial resistance (AMR) surveillance and the most widely used whole-genome sequencing (WGS) platform. The high-throughput, relative low-cost, high discriminatory power, and rapid turnaround time of WGS compared to classical biochemical methods means the technology will likely remain a fundamental tool in AMR surveillance and public health. In this study, we present the current level of WGS capacity among national reference laboratories in the EU Reference Laboratory for AMR network, summarizing applied methodology and statistically evaluating the quality of the obtained sequence data. These findings provide the basis for setting new and revised thresholds for quality metrics used in routine WGS, which have previously been arbitrarily defined. In addition, underperforming participants are identified and encouraged to evaluate their workflows to produce reliable results.

Abstract Objective Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Hungry bone syndrome (HBS) after parathyroidectomy (PTX) is a serious complication, which can lead to diarrhea, convulsion, arrhythmia and even death. This study was aimed to determine the risk factors for HBS after PTX in dialysis patients with SHPT and construct a nomogram prediction model to predict the incidence of postoperative complications. Methods Clinical data were collected from 80 maintenance hemodialysis (MHD) patients with SHPT who received total PTX in the Second Hospital of Jilin University from January 2018 to September 2021. In line with the inclusion and exclusion criteria, totally 75 patients were finally enrolled for analysis. Patients were divided into two groups for retrospective analysis according to the severity of postoperative HBS, including HBS group and non-HBS (N-HBS) group. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for postoperative HBS. Afterwards, the receiver operating characteristic (ROC) curves were plotted based on the statistical analysis results, aiming to compare the prediction effects of different predicting factors. Finally, the nomogram was established to evaluate the occurrence probability of postoperative complications predicted by the risk factors. Results Among the 75 patients, 32 had HBS (HBS group), while 43 did not have HBS (N-HBS group). Univariate analysis results indicated that, the preoperative intact parathyroid hormone (iPTH) and serum alkaline phosphatase (ALP) levels in HBS group were significantly higher than those in N-HBS group, while preoperative hemoglobin and preoperative albumin (Alb) levels were significantly lower than those in N-HBS group. As discovered by multivariate logistic regression analysis, preoperative iPTH (OR = 1.111, P = 0.029) and ALP (OR = 1.010, P

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a leading public health problem worldwide. Approximately one fourth of patients with nonalcoholic fatty liver (NAFL) progress to nonalcoholic steatohepatitis (NASH), an advanced stage of NAFLD. Hence, there is an urgent need to make a better understanding of NAFLD heterogeneity and facilitate personalized management of high-risk NAFLD patients who may benefit from more intensive surveillance and preventive intervene. Methods In this study, a series of bioinformatic methods were performed to identify NAFLD progression-specific pathways and genes, and three machine learning approaches were combined to construct a risk-stratification gene signature to quantify risk assessment. In addition, bulk RNA-seq, single-cell RNA-seq (scRNA-seq) transcriptome profiling data and whole-exome sequencing (WES) data were comprehensively analyzed to reveal the genomic alterations and altered pathways between distinct molecular subtypes. Results Two distinct subtypes of NAFL were identified with the NAFLD progression-specific genes, and one subtype has a high similarity of the inflammatory pattern and fibrotic potential with NASH. The established risk-stratification gene signature could discriminate advanced samples from overall NAFLD. COL1A2, one key gene closely related to NAFLD progression, is specifically expressed in fibroblasts involved in hepatocellular carcinoma (HCC), and significantly correlated with EMT and angiogenesis in pan-cancer. Moreover, the β-catenin/COL1A2 axis might play a critical role in fibrosis severity and inflammatory response during NAFLD-HCC progression. Conclusion In summary, our study provided evidence for the necessity of molecular classification and established a risk-stratification gene signature to quantify risk assessment of NAFLD, aiming to identify different risk subsets and to guide personalized treatment.

Background: Traditional Chinese medicine injections with invigorating blood circulation (TCMI-IBCs), which have been used as antithrombosis therapies, are widely employed by Chinese clinicians as adjuvant therapy for acute myocardial infarction (AMI).Objective: A Bayesian network meta-analysis was conducted to contrast the effectiveness and safety of four TCMI-IBCs in AMI.Methods: Eight Databases were thoroughly searched before 31 December 2023, for randomized controlled trials (RCTs) focusing on the application of TCMI-IBCs combined with conventional treatments (CT) to treat AMI. All-cause mortality (ACM) was the major endpoint. Secondary outcomes included bleeding events, malignant arrhythmia (MA), recurrent myocardial infarction (RMI), left ventricular ejection fraction (LVEF), and adverse events. Stata17.0 and GeMTC software were employed for Bayesian network meta-analysis.Results: A total of 73 eligible RCTs involving 7,504 patients were enrolled. Puerarin injection (PI), Danhong injection (DI), sodium Tanshinone IIA Sulfonate injection (STSI), and Danshen Chuanxiongqin injection (DCI) combined with CT can significantly reduce the occurrence of ACM and improve LVEF in AMI (P < 0.05), while without significant impact on bleeding events or MA (P > 0.05). STSI + CT would be the optimal treatment strategy in lowering RMI and ACM. DI + CT was the most likely to be the optimal strategy in reducing MA occurrence and improving LVEF. CT was likely the most effective strategy in reducing bleeding events. However, DI + CT exhibited the least favorable safety.Conclusion: TCMI-IBCs + CT had potential benefits in the treatment of AMI. STSI + CT showed the most favorable performance in treating AMI, followed by DI combined with CT.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384067, identifier CRD42022384067.

Background: Traditional Chinese medicine injection for Activating Blood Circulation (TCMi-ABC), which exhibits comparable anticoagulant and antiplatelet effects, is commonly used as an adjuvant treatment for acute myocardial infarction (AMI) in China. Objective: The aim of this study was to conduct a meta-analysis to assess the efficacy and safety of TCMi-ABC in combination with conventional western medicine in reducing mortality associated with AMI. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, EMBASE, Web of Science, CBM, WanFang Data, and CNKI databases. Randomized controlled trials (RCTs) investigating the use of TCMi-ABC (including Danhong injection, sodium tanshinone IIA sulfonate injection, salvia miltiorrhiza ligupyrazine injection, and puerarin injection) for the treatment of AMI were included. The search included studies published from the inception of the databases up to December 2022. Two authors independently screened RCTs, extracted data, and assessed the risk of bias. Meta-analysis was performed using RevMan 5.3 and Stata 17.0. The quality of evidence was evaluated using the GRADE approach. Results: A total of 52 RCTs involving 5363 patients were included in the analysis, none of which described independent testing of the purity or potency of the TCMi-ABC product used. 19/52 reported random sequence generation. All RCTs lack adequate description of allocation concealment. 51/52 failed to assess blinding. The meta-analysis results demonstrated that the combined application of TCMi-ABC, compared with conventional western medicine treatment alone, significantly reduced in-hospital mortality in AMI patients [RR= 0.41, 95% CI (0.29, 0.59), P 0.05). The GRADE evidence quality classification indicated that the evidence for in-hospital mortality, malignant arrhythmia, and adverse events was of moderate quality, while the evidence for LVEF was of low quality. Conclusion: TCMi-ABC demonstrates additional clinical value in reducing mortality and the risk of malignant arrhythmia in patients with AMI. However, further validation of these findings is warranted through high-quality clinical trials due to methodological weaknesses in randomization, blinding, allocation concealment, and insufficient assessing for the purity/potency of herbs and the gram amount of active constituents.Systematic Review Registration: [INPLASY], identifier [INPLASY202170082]

Abstract Steatotic liver disease poses a serious threat to human health and has emerged as one of the most significant burdens of chronic liver disease worldwide. Currently, the research mechanism is not clear, and there is no specific targeted drug for direct treatment. Phosphorylation is widely regarded as the most common type of protein modification, closely linked to steatotic liver disease in previous studies. However, there is no systematic review to clarify the relationship and investigate from the perspective of phosphorylation. Phosphorylation has been found to mainly regulate molecule stability, affect localization, transform molecular function, and cooperate with other protein modifications. Among them, adenosine 5’-monophosphate-activated protein kinase (AMPK), serine/threonine kinase (AKT), and nuclear factor kappa-B (NF-kB) are considered the core mechanisms in steatotic liver disease. As to treatment, lifestyle changes, prescription drugs, and herbal ingredients can alleviate symptoms by influencing phosphorylation. It demonstrates the significant role of phosphorylation as a mechanism occurrence and a therapeutic target in steatotic liver disease, which could be a new star for future exploration.

Abstract Objective Lumbosacral vertebral osteoblastic metastasis is treated with percutaneous vertebroplasty (PVP) combined with 125I seed implantation and PVP alone. Compared to PVP alone, we evaluated the effects of combination therapy with PVP and 125I seed implantation on pain, physical condition, and survival and evaluated the clinical value of PVP combined with 125I particle implantation. Methods We retrospectively analyzed 62 patients with lumbosacral vertebral osseous metastases treated at our hospital between 2016 and 2019. All the patients met the inclusion criteria for 125I implantation, and they were randomly divided into a combined treatment group and a pure PVP surgery group. The visual analog pain scale (VAS), Karnofsky Performance Status (KPS), and survival time were recorded at different time points, including preoperative, postoperative 1 day, 1 month, 3 months, 6 months, 12 months, and 36 months in each group. The variation in clinical indicators and differences between the groups were analyzed using SPSS version 20.0. Correlations between different variables were analyzed using the nonparametric Spearman’s rank test. The Kaplan–Meier method was used to estimate the relationship between survival time and KPS score, VAS score, or primary tumor progression, and survival differences were analyzed using the log-rank test. Multivariate analyses were performed using a stepwise Cox proportional hazards model to identify independent prognostic factors. Results Compared to the PVP treatment group, the pain level in the combined treatment group was significantly reduced (P = 0.000), and the patient’s physical condition in the combination treatment group significantly improved. Kaplan–Meier analysis showed that the survival rate of the PVP group was significantly lower than that of the combination group (P = 0.038). We also found that the median survival of patients in both groups significantly increased with an increase in the KPS score (14 months vs. 33 months) (P = 0.020). Patients with more than three transfer sections had significantly lower survival rates than those with one or two segments of the section (P = 0.001). Further, Cox regression analysis showed that age (P = 0.002), the spinal segment for spinal metastasis (P = 0.000), and primary tumor growth rate (P = 0.005) were independent factors that affected the long-term survival of patients with lumbosacral vertebral osseous metastases. Conclusions PVP combined 125I seeds implantation surgery demonstrated superior effectiveness compared to PVP surgery alone in treating lumbosacral vertebral osseous metastases, which had feasibility in the clinical operation. Preoperative KPS score, spine transfer section, and primary tumor growth rate were closely related to the survival of patients with lumbosacral vertebral osteoblastic metastasis. Age, spinal segment for spinal metastasis, and primary tumor growth can serve as prognostic indicators and guide clinical treatment.

ObjectiveAs a spectrum of neurodegenerative conditions, dementia presents a significant challenge to worldwide health. Mild cognitive impairment (MCI) is recognized as the intermediate stage between normal cognitive functioning and dementia. Studies highlight the significant impact of dietary patterns on the management of MCI and dementia. Currently, comprehensive research on dietary patterns specific to MCI and dementia is limited, but bibliometric analysis offers a method to pinpoint essential research directions.MethodsOn November 18, 2023, a search was conducted in the Web of Science Core Collection (WoSCC) for publications on diet and MCI/dementia. Tools such as Rstudio, CiteSpace, and VOSviewer were employed to create a knowledge atlas. This atlas analyzed collaborations, reference co-citations, keyword patterns, and emerging trends.ResultsThe search yielded 1,493 publications on diet and MCI/dementia, indicating a growing interest despite fluctuations. Contributions came from 70 countries/regions and 410 organizations across 456 journals. The USA and China led in publication numbers, with significant contributions from Columbia University and Harvard Medical School. Top authors include Scarmeas Nikolaos, Morris Martha Clare, and Samieri Cecilia. The Ketogenic, Mediterranean, and MIND diets emerged as key dietary patterns for cognitive decline prevention, highlighting the role of genetic factors, especially ApoE polymorphisms, in cognitive deterioration.ConclusionThis study provides core countries, institutions, and authors in the field, and points out the development directions in the field. Future research directions in dietary for MCI and dementia will focus on: (1) the potential effects of the KD in alleviating oxidative stress and modulating gut microbiota in neurodegenerative diseases; (2) how diet influences cognitive health through patterns of ApoE and protein expression; (3) investigating the interactions between gut microbiota and brain function, known as the “gut-brain axis.”

AimTo determine the experiences and needs of palliative care in patients with advanced Parkinson’s disease (PD).MethodsA scoping literature review methodology, as described by the Joanna Briggs Institute, was employed to search for relevant literature. An electronic search of studies published in English was conducted across five databases from inception to 10 September 2023.ResultsThe search yielded a total of 1,205 articles, with 20 meeting the inclusion criteria. The findings were organized into four themes: (1) unmet emotional and informational needs; (2) needs for effective coordination of care; (3) planning for the future; and (4) symptom management. This scoping review highlights the intricate nature of palliative care for patients with PD and sheds light on issues within current palliative care healthcare systems. The findings emphasize the necessity for individualized interventions and services to address the diverse unmet palliative care needs of people with PD.ConclusionThe study reveals the complex landscape of palliative care for individuals with advanced PD, emphasizing the inadequacies within existing healthcare systems. The identified themes underscore the importance of tailored interventions to address the varied unmet palliative care needs of this population.

Abstract Background Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations. Methods This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations. Results Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p

Abstract Aim The aim of the study was to develop and psychologically test the mobile health information‐seeking behaviour (MHISB) questionnaire in people with cancer. Design Instrument development. Methods The study was conducted in three phases in a southeastern city of China from May 2017 to April 2018. In phase one, an item pool was constructed based on a literature review and semistructured interviews. In phase two, expert evaluation and cognitive interviews were used to evaluate the content validity of the questionnaire. In phase three, a cross‐sectional study was conducted with people with cancer. Cronbach's α was calculated for reliability analysis. Validity evaluation included content validity and construct validity. Results The developed MHISB questionnaire has four dimensions (information‐seeking frequency, information‐seeking self‐efficacy, health information evaluation and information‐seeking willingness) and 25 items. Psychometric findings were satisfactory and supported the questionnaire's reliability. Conclusions The construction process of the MHISB questionnaire was scientific and feasible. The MHISB questionnaire had acceptable validity and reliability, and it requires further improvement in future studies.

BackgroundSerious bacterial infections (SBIs) are linked to unplanned hospital admissions and a high mortality rate. The early identification of SBIs is crucial in clinical practice. ObjectiveThis study aims to establish and validate clinically applicable models designed to identify SBIs in patients with infective fever. MethodsClinical data from 945 patients with infective fever, encompassing demographic and laboratory indicators, were retrospectively collected from a 2200-bed teaching hospital between January 2013 and December 2020. The data were randomly divided into training and test sets at a ratio of 7:3. Various machine learning (ML) algorithms, including Boruta, Lasso (least absolute shrinkage and selection operator), and recursive feature elimination, were utilized for feature filtering. The selected features were subsequently used to construct models predicting SBIs using logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost) with 5-fold cross-validation. Performance metrics, including the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), accuracy, sensitivity, and other relevant parameters, were used to assess model performance. Considering both model performance and clinical needs, 2 clinical timing-sequence warning models were ultimately confirmed using LR analysis. The corresponding predictive nomograms were then plotted for clinical use. Moreover, a physician, blinded to the study, collected additional data from the same center involving 164 patients during 2021. The nomograms developed in the study were then applied in clinical practice to further validate their clinical utility. ResultsIn total, 69.9% (661/945) of the patients developed SBIs. Age, hemoglobin, neutrophil-to-lymphocyte ratio, fibrinogen, and C-reactive protein levels were identified as important features by at least two ML algorithms. Considering the collection sequence of these indicators and clinical demands, 2 timing-sequence models predicting the SBI risk were constructed accordingly: the early admission model (model 1) and the model within 24 hours of admission (model 2). LR demonstrated better stability than RF and XGBoost in both models and performed the best in model 2, with an AUC, accuracy, and sensitivity of 0.780 (95% CI 0.720-841), 0.754 (95% CI 0.698-804), and 0.776 (95% CI 0.711-832), respectively. XGBoost had an advantage over LR in AUC (0.708, 95% CI 0.641-775 vs 0.686, 95% CI 0.617-754), while RF achieved better accuracy (0.729, 95% CI 0.673-780) and sensitivity (0.790, 95% CI 0.728-844) than the other 2 approaches in model 1. Two SBI-risk prediction nomograms were developed for clinical use based on LR, and they exhibited good performance with an accuracy of 0.707 and 0.750 and a sensitivity of 0.729 and 0.927 in clinical application. ConclusionsThe clinical timing-sequence warning models demonstrated efficacy in predicting SBIs in patients suspected of having infective fever and in clinical application, suggesting good potential in clinical decision-making. Nevertheless, additional prospective and multicenter studies are necessary to further confirm their clinical utility.

AbstractCisplatin (DDP) is a potent chemotherapeutic; however, it can also cause acute kidney injury (AKI). Because of the complexity of the toxicity it induces, few effective methods exist for ameliorating any form of DDP-induced AKI. Recent research has suggested that the complement system is a potential molecular target for such amelioration. In the study here, in vivo (male ICR mice) and in vitro (HK-2 cells) models of DDP-induced AKI were established to investigate the potential therapeutic effects of Vitamin D (VD) against this form of AKI. Endpoints assessed in vivo/in vitro included overall renal function, degree of renal damage, and complement receptor C5aR expression using histology, immunohistochemistry, immunofluorescence, RT-PCR, and Western blots. The data indicated that the use of VD treatment could reduce renal pathological damage along with expression of TNFα, IL-1β, IL-18, and C5aR; however, an over-expression of C5aR weakened the protective effects of VD/VD receptor (VDR) against oxidative damage and inflammatory cell infiltration. Using a luciferase reporter gene assay and ChIP analysis, it was demonstrated that C5aR was transcriptionally inhibited by VDR. In conclusion, VD/VDR could delay DDP-induced AKI by inhibiting the expression of C5aR through transcriptional regulation and reducing the production of downstream pro-inflammatory cytokines. The present study revealed the regulatory mechanism of VD/VDR in acute renal inflammation and provides new insights into its therapeutic function in DDP-induced AKI.

Abstract Aim To explore the quality‐of‐life among community‐dwelling older adults in China and to examine the associations between frailty, sociodemographic characteristics and quality‐of‐life. Design A cross‐sectional correlational study was adopted. Methods Questionnaire study of 311 community‐dwelling older adults using the Life Satisfaction Questionnaire and FRAIL scale. Results Highest quality‐of‐life was found for the physical symptoms factor and the lowest for quality of everyday activities/fun. Frailty was associated with total quality‐of‐life and the physical symptoms and sickness impact factors. For total quality‐of‐life, the odds of being in the group with a median score or more decreased for frail older people (OR 0.30) versus non‐frail and increased for those with medical insurance from employer versus basic (OR 2.30) and those doing exercise ≥30 min 3 days/week or more versus less (OR 2.12). Registered nurses caring for community‐dwelling older adults should screen for and prevent frailty and encourage exercise to improve their quality‐of‐life.

Abstract Objective Palliative care (PC) can improve the quality of life of Parkinson’s disease (PD) patients and their carers. However, the impact of PC services on patients with PD remains unclear. This research was conducted to identify the barriers and facilitators influencing PC services for patients with PD based on the Social Ecological Model (SEM) framework. Methods This research was conducted through semi-structured interviews, employing SEM to organize themes and identify potential solutions across multiple levels. Results A total of 29 interviewees (5 PD clinicians, 7 PD registered nurses, 8 patients, 5 caregivers, and 4 policy makers) completed the interviews. Facilitators and barriers were identified according to the levels of the SEM. Several facilitators were identified, i.e., (1) individual level: the critical needs among PD patients and their relatives and the desire for PC knowledge among health professionals; (2) interpersonal level: social support; (3) organizational level: the investments towards systematization of PC; and nurses are the bridge between patients and doctors; (4) community level: the convenience of community services; and hospital-community-family-based services; (5) culture and policy level: existing policy. Conclusion The social-ecological model proposed in this study helps illuminate the complex and multilevel factors that may influence PC delivery to PD patients.

ObjectiveTo investigate development trends and research hotspots of exercise for hypertension research and provide researchers with fresh perspectives for further studies.Materials and methodsArticles and reviews regarding exercise and hypertension spanning May 1st 2003 to May 18th 2023 were retrieved from the Web of Science Core Collection (WOSCC) database. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field.ResultsA total of 1,643 peer-reviewed papers were identified, displaying a consistent increasing trend over time. The most prolific country and institution were Brazil and University of Sao Paulo, respectively. And we identified the most productive author was lrigoyen, Maria Claudia C, while Pescatello Linda S was the most co-cited author. Journal of hypertension was the most prominent journal, and Hypertension was the journal which was the most co-cited. And this field can be divided into 3 research themes: exercise interventions for hypertension, age-specific relevance of exercise for hypertension, and the global burden of hypertension and the role of exercise. According to the result of keywords analysis, epidemiological information, types of exercise, target population, mechanism, and study design are significant research areas. “Resistance training”, “adults”, and “heart rate variability” were identified as the major future research foci.ConclusionsThe findings offer a scientific insight into exercise for hypertension research, presenting researchers with valuable information to understand the current research status, hotspots, and emerging trends for future investigation.

Objective Hypocalcemia after parathyroidectomy (PTX) results in tetany, diarrhea, cardiac arrhythmia, and even sudden death. However, a meta-analysis or systematic evaluation of risk factors with the occurrence and development of hypocalcemia in patients with secondary hyperparathyroidism (SHPT) after PTX has never been performed.Methods A thorough search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE, was performed to retrieve relevant studies from database inception to June 2021. Quality of the included studies was assessed by two independent reviewers using the Newcastle–Ottawa Scale. Review Manager 5.3 and Stata 16.0 were used for meta-analysis. The random-effects model was adopted to calculate the 95% CIs (I2> 50% or p 7 points. Risk factors significantly related to hypocalcemia in patients with SHPT after PTX were preoperative serum calcium (OR 0.19, 95%CI 0.11–0.31), preoperative alkaline phosphatase (ALP) (OR 1.01, 95% CI 1.01–1.02), and preoperative intact parathyroid hormone (iPTH) (OR 1.38, 95%CI 1.20–1.58). Meanwhile, age (OR 0.97, 95%CI 0.87–1.10) was not significantly correlated with hypocalcemia after PTX.Conclusions Based on the current evidence, preoperative serum calcium, preoperative ALP, and preoperative iPTH were significant predictors of hypocalcemia in patients with SHPT after PTX. More attention should be given to patients with these risk factors for the prevention of postoperative hypocalcemia.

Diplodiscus japonicus and Diplodiscus mehari (Trematoda: Diplodiscidae) are two important parasites in wood frogs, which have large infection rates and essential importance of ecology, economy and society. In this study, the complete mitochondrial (mt) genomes of D. japonicus and D. mehari were sequenced, then compared with other related trematodes in the superfamily Paramphistomoidea. The complete circular mt sequence of D. japonicus and D. mehari were 14,210 bp and 14,179 bp in length, respectively. Both mt genomes comprised 36 functional subunits, consisting of 12 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one non-coding region. The mt genes of D. japonicus and D. mehari were transcribed in the same direction, and the gene arrangements were identical to those of Paramphistomoidea trematodes. In the 12 PCGs, GTG was the most common initiation codon, whereas TAG was the most common termination codon. All tRNAs had a typical cloverleaf structure except tRNA Ser1. A comparison with related Paramphistomoidea trematode mt genomes suggested that the cox1 gene of D. mehari was the longest in these trematodes. Phylogenetic analyses revealed that Paramphistomoidea trematodes formed a monophyletic branch, Paramphistomidae and Gastrothylacidae were more closely related than Diplodiscidae. And the further analysis with Pronocephalata branch found that the flukes parasitic in amphibians (frogs) formed one group, and the flukes from ruminants (cattle, sheep, ect) formed another group. Our study demonstrated the importance of sequencing mt genomes of D. japonicus and D. mehari, which will provide significant molecular resources for further studies of Paramphistomoidea taxonomy, population genetics and systematics.

Abstract Objective We investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN). Methods We selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients. Results Serum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people (P 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group (P

Background: Artificial intelligence (AI) is used in ophthalmological disease screening and diagnostics, medical image diagnostics, and predicting late-disease progression rates. We reviewed all AI publications associated with macular edema (ME) research Between 2011 and 2022 and performed modeling, quantitative, and qualitative investigations.Methods: On 1st February 2023, we screened the Web of Science Core Collection for AI applications related to ME, from which 297 studies were identified and analyzed (2011–2022). We collected information on: publications, institutions, country/region, keywords, journal name, references, and research hotspots. Literature clustering networks and Frontier knowledge bases were investigated using bibliometrix-BiblioShiny, VOSviewer, and CiteSpace bibliometric platforms. We used the R “bibliometrix” package to synopsize our observations, enumerate keywords, visualize collaboration networks between countries/regions, and generate a topic trends plot. VOSviewer was used to examine cooperation between institutions and identify citation relationships between journals. We used CiteSpace to identify clustering keywords over the timeline and identify keywords with the strongest citation bursts.Results: In total, 47 countries published AI studies related to ME; the United States had the highest H-index, thus the greatest influence. China and the United States cooperated most closely between all countries. Also, 613 institutions generated publications - the Medical University of Vienna had the highest number of studies. This publication record and H-index meant the university was the most influential in the ME field. Reference clusters were also categorized into 10 headings: retinal Optical Coherence Tomography (OCT) fluid detection, convolutional network models, deep learning (DL)-based single-shot predictions, retinal vascular disease, diabetic retinopathy (DR), convolutional neural networks (CNNs), automated macular pathology diagnosis, dry age-related macular degeneration (DARMD), class weight, and advanced DL architecture systems. Frontier keywords were represented by diabetic macular edema (DME) (2021–2022).Conclusion: Our review of the AI-related ME literature was comprehensive, systematic, and objective, and identified future trends and current hotspots. With increased DL outputs, the ME research focus has gradually shifted from manual ME examinations to automatic ME detection and associated symptoms. In this review, we present a comprehensive and dynamic overview of AI in ME and identify future research areas.

Abstract Aim To develop self‐management support platform on mobile for Chinese patients with lung cancer. Design A stepwise approach with combination of methods. Methods Literature review was carried out to construct preliminary framework and develop detailed content for self‐management modules. A semistructured interview was conducted to elicit preference in the content and platform of self‐management modules with 15 patients with lung cancer. Delphi study was performed to evaluate and improve the content of modules with 13 experts. A pilot study was conducted to test the mobile health–based self‐management support modules with 13 patients with lung cancer. Results A social network software‐based WeChat public account “Symptom Self‐Management” for patients with lung cancer was developed and preliminarily tested with positive feedback. Three modules were designed and presented, including symptom management (cancer‐related fatigue, cough, dyspnoea, pain, nausea and vomiting), emotion management and role management. Conclusion This study showed that patients with lung cancer have diversified supportive care needs after discharge. A bottom‐up and stepwise approach to develop mobile health–based self‐management support tool has shown to be feasible and valuable. Theory guidance, user requirement exploration, evidence‐based information and expert evaluation are key elements of the process. Implications for Practice The WeChat Public Account “Symptom Self‐Management” could be used as sustainable platform to support patients with lung cancer in dealing with common challenges. It provides professional information, self‐assessment tools, self‐management skills and peer‐support platform. Information presented in both text and audio forms enables patients' easy access to the platform.

Abstract Background Chinese and global populations are aging, and more older people are living in nursing homes in China. However, there is a lack of research measuring nursing home residents’ quality of life (QOL), and especially associations with nursing home types (publicly versus privately run). Therefore, this study aimed to determine the construct validity and internal consistency of the Chinese version of the life satisfaction questionnaire (LSQ-Chinese) and determine the associations between nursing home types (publicly versus privately run), residents’ sociodemographic characteristics, and their QOL. Methods A cross-sectional survey measuring QOL among older people living in nursing homes was conducted (n = 419). Confirmatory factor analysis and Cronbach’s alpha were used to assess the construct validity and reliability of the LSQ-Chinese. In addition, multivariate regression analysis was used to examine these associations. Results Confirmatory factor analysis indicated acceptable goodness-of-fit statistics for the seven-factor LSQ solution. All factors and the total scale had good internal consistency, with Cronbach’s alpha values > 0.70. The two factors with the highest QOL scores (higher scores indicate a more desirable state) were “physical symptoms” and “socioeconomic situation,” and those with the lowest QOL scores were “quality of close-friend relationships” and “quality of daily activities fun”. Residents living in privately run nursing homes had higher LSQ scores overall and for all factors except “physical symptoms” and “sickness impact” compared with publicly run nursing homes. Multivariate analyses indicated that marital status, number of chronic diseases, education level, main source of income, and nursing home type significantly contributed to the variance in the total LSQ scores. The associated sociodemographic variables differed between the factors, and the variable publicly versus privately run was significant for five of the seven factors. Conclusions The LSQ is a suitable instrument for measuring the QOL of Chinese nursing home residents. The total LSQ score was higher among residents in privately run nursing homes than in publicly run ones. According to residents’ needs, staff should work for person-centered activities, and facilitate residents’ social interactions with friends, as both these aspects were scored relatively low.

Laser polishing is an emerging efficient technique to remove surface asperity without polluting the environment. However, the insufficient understanding of the mechanism of laser polishing has limited its practical application in industry. In this study, a dual-beam laser polishing experiment was carried out to reduce the roughness of a primary Ti6Al4V sample, and the polishing mechanism was well studied using simulation analysis. The results showed that the surface roughness of the sample was efficiently reduced from an initial 10.96 μm to 1.421 μm using dual-beam laser processing. The simulation analysis regarding the evolution of material surface morphology and the flow behavior of the molten pool during laser the polishing process revealed that the capillary force attributed to surface tension was the main driving force for flattening the large curvature surface of the molten pool at the initial stage, whereas the thermocapillary force influenced from temperature gradient played the key role of eliminating the secondary roughness at the edge of the molten pool during the continuous wave laser polishing process. However, the effect of thermocapillary force can be ignored during the second processing stage in dual-beam laser polishing. The simulation result is well in agreement with the experimental result, indicating the accuracy of the mechanism for the dual-beam laser polishing process. In summary, this work reveals the effect of capillary force and thermocapillary force on molten pool flows during the dual-beam laser polishing processes. Moreover, it is also proved that the dual-beam laser polishing process can further reduce the surface roughness of a sample and obtain a smoother surface.

A noise-like pulse (NLP) thulium-doped fiber laser based on single-wall carbon nanotubes (SWCNTs) has been proposed and demonstrated in this paper, which the microfiber decorated with SWCNTs work as a saturable absorber to generate an ultrafast pulse. The length of the cavity is 12 m, corresponding to the fundamental frequency of 17.2 MHz. NLP with a duration of 643 fs can be obtained at 1965 nm under the signal-to-noise ratio of 56 dB. This work may assist us to better understand the dynamic characteristic of NLP with the help of materials and offer a fine laser source to the subsequent applications just like the generation of supercontinuum.

ObjectiveLarge pneumothorax is a rare but dangerous complication following thoracic and lumbar tumor surgery. There is little discussion about the features of large pneumothorax following spinal tumor surgery. The purpose of this study was to analyze the characteristics of postoperative pneumothorax, identify factors related to large pneumothorax, and propose a management algorithm for prevention, diagnosis, and treatment.MethodsIncluded in this retrospective study were 118 patients who developed pneumothorax after receiving thoracic and lumbar tumor surgery between January 2015 and October 2021. A measurement of lung compression ≥20% on chest CT or x-ray was defined as large pneumothorax, and potential risk factors for large pneumothorax were identified by univariate analysis.ResultsSpinal tumor history and intraoperative blood loss were risk factors for large pneumothorax. The common symptoms of postoperative pneumothorax were chest pain, chest tightness and dyspnea. The mean longest transverse diameter of tumors was 6.63 ± 2.4 cm. En bloc resection was performed in 70 patients, with a mean operation time of 6.9 ± 2.5 h and mean intraoperative blood loss of 1771 ± 1387 ml. The most common pathologies were chondrosarcoma, giant cell tumors of bone, and neurogenic tumors.ConclusionDuring surgery, an artificial dura mater patch and a prolene suture can be used to repair the pleural and lung defects. We recommend chest CT as the preferred method for identifying postoperative pneumothorax. If a patient presents severe dyspnea, a large pneumothorax or concurrent pleural effusion, application of chest drainage is strongly recommended.

Abstract Background Gene therapy shows great promise for a broad array of diseases. However, we found that hypoxic tumor microenvironment (TME) exerted significant inhibitory effects on transfection efficiency of a variety of gene vectors (such as Lipo 2000 and PEI) in an oxygen-dependent manner. Solid tumors inevitably resulted in acute hypoxic areas due to the rapid proliferation of tumor cells and the aberrant structure of blood vessels. Thus, the hypoxic TME severely limited the efficiency and application of gene therapy. Methods In our previous study, we constructed endoplasmic reticulum-targeted cationic liposomes, PAR-Lipo, which could effectively deliver genes and ensure high transfection efficiency under normoxia. Unsatisfactorily, the transfection efficiency of PAR-Lipo was rather poor under hypoxia. We believed that reoxygenation was the most direct and effective means to rescue the low transfection under hypoxia. Hence, we fabricated liposomes modified with perfluorooctyl bromide (PFOB@Lipo) to load oxygen and deliver it to tumor sites, which effectively alleviated the hypoxic nature of tumor. Then PAR-Lipo were applied to mediate high-efficiency delivery of tumor suppressor gene pTP53 to inhibit tumor progression. Results The results showed that such staged strategy augmented the expression of P53 protein in tumors and extremely suppressed tumor growth. Conclusion This work was the first attempt to utilize an oxygen nanocarrier to assist the therapeutic effect of gene therapy under hypoxia, providing a new reference for gene therapy in malignant tumors. Graphical Abstarct

BackgroundSome degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform.MethodsThe PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed.ResultsA total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto’s thyroiditis (HT) and hypothyroid groups, but not in the Graves’ disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found.ConclusionsPLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022341823.

Summary: Background: Accurate identification of ovarian cancer (OC) is of paramount importance in clinical treatment success. Artificial intelligence (AI) is a potentially reliable assistant for the medical imaging recognition. We systematically review articles on the diagnostic performance of AI in OC from medical imaging for the first time. Methods: The Medline, Embase, IEEE, PubMed, Web of Science, and the Cochrane library databases were searched for related studies published until August 1, 2022. Inclusion criteria were studies that developed or used AI algorithms in the diagnosis of OC from medical images. The binary diagnostic accuracy data were extracted to derive the outcomes of interest: sensitivity (SE), specificity (SP), and Area Under the Curve (AUC). The study was registered with the PROSPERO, CRD42022324611. Findings: Thirty-four eligible studies were identified, of which twenty-eight studies were included in the meta-analysis with a pooled SE of 88% (95%CI: 85–90%), SP of 85% (82–88%), and AUC of 0.93 (0.91–0.95). Analysis for different algorithms revealed a pooled SE of 89% (85–92%) and SP of 88% (82–92%) for machine learning; and a pooled SE of 88% (84–91%) and SP of 84% (80–87%) for deep learning. Acceptable diagnostic performance was demonstrated in subgroup analyses stratified by imaging modalities (Ultrasound, Magnetic Resonance Imaging, or Computed Tomography), sample size (≤300 or >300), AI algorithms versus clinicians, year of publication (before or after 2020), geographical distribution (Asia or non Asia), and the different risk of bias levels (≥3 domain low risk or < 3 domain low risk). Interpretation: AI algorithms exhibited favorable performance for the diagnosis of OC through medical imaging. More rigorous reporting standards that address specific challenges of AI research could improve future studies. Funding: This work was supported by the Natural Science Foundation of China (No. 82073647 to Q-JW and No. 82103914 to T-TG), LiaoNing Revitalization Talents Program (No. XLYC1907102 to Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (No. M0268 to Q-JW and No. M0952 to T-TG).

Flower-like cobalt–molybdenum mixed-oxide microspheres (CoMo-FMs) with hierarchical architecture were successfully synthesized via a hydrothermal process and subsequent calcination step. The characterization results show that CoMo-FMs were assembled from ultrathin mesoporous nanosheets with thicknesses of around 4.0 nm, providing the composite with a large pore volume and a massive surface area. The synthesized CoMo-FMs were employed as catalysts for the aerobic oxidative desulfurization (AODS) of fuel, and the reaction results show that the optimal catalyst (CoMo-FM-2) demonstrated an outstanding catalytic performance. Over CoMo-FM-2, various thiophenic sulfides could be effective removed at 80–110 °C under an atmospheric pressure, and a complete conversion of sulfides could be achieved in at least six consecutive cycles without a detectable change in chemical compositions. Further, the catalytic mechanism was explored by conducting systemic radical trapping and transformation experiments, and the excellent catalytic performance for CoMo-FMs should be mainly due to the synergistic effect of Mo and Co elements.

Opisthorchiosis is a parasitic liver disease found in mammals that is widespread throughout the world and causes systemic inflammation. Praziquantel remains the drug of choice for the treatment of opisthorchiosis, despite its many adverse effects. An anthelmintic effect is attributed to the main curcuminoid of Curcuma longa L. roots—curcumin (Cur)—along with many other therapeutic properties. To overcome the poor solubility of curcumin in water, a micellar complex of curcumin with the disodium salt of glycyrrhizic acid (Cur:Na2GA, molar ratio 1:1) was prepared via solid-phase mechanical processing. In vitro experiments revealed a noticeable immobilizing effect of curcumin and of Cur:Na2GA on mature and juvenile Opisthorchis felineus individuals. In vivo experiments showed that curcumin (50 mg/kg) had an anthelmintic effect after 30 days of administration to O. felineus-infected hamsters, but the effect was weaker than that of a single administration of praziquantel (400 mg/kg). Cur:Na2GA (50 mg/kg, 30 days), which contains less free curcumin, did not exert this action. The complex, just as free curcumin or better, activated the expression of bile acid synthesis genes (Cyp7A1, Fxr, and Rxra), which was suppressed by O. felineus infection and by praziquantel. Curcumin reduced the rate of inflammatory infiltration, whereas Cur:Na2GA reduced periductal fibrosis. Immunohistochemically, a decrease in liver inflammation markers was found, which is determined by calculating the numbers of tumor-necrosis-factor-positive cells during the curcumin treatment and of kynurenine-3-monooxygenase-positive cells during the Cur:Na2GA treatment. A biochemical blood test revealed a normalizing effect of Cur:Na2GA (comparable to that of curcumin) on lipid metabolism. We believe that the further development and investigation of therapeutics based on curcuminoids in relation Opisthorchis felineus and other trematode infections will be useful for clinical practice and veterinary medicine.

Abstract Background Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2. Methods We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated. Results After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs. Conclusions hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.

Abstract. Background. In spite of a growing number in the use of percutaneous coronary intervention (PCI) in China, the mortality of acute myocardial infarction (AMI) has not decreased. Traditional Chinese medicine injections for Activating Blood Circulation (TCMi-ABC), equivalent effect of anticoagulation or antiplatelet, are widely used in China; however, the improvement of fatality towards AMI is unclear. Therefore, we intend to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCMi-ABC in treatment with AMI. Methods. Based on the “National Medical Products Administration of China,” TCMi-ABC with AMI treatment indication will be selected, including Danhong injection, Sodium Tanshinone IIA Sulfonate injection, Danshen Chuanxiongqin injection, and Puerarin injection. Randomized controlled studies will be searched from as follows: PubMed, Embase, the CENTRAL in Cochrane Library, Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Data Knowledge Service Platform. Two researchers will work independently on literature selection, data extraction, and quality assessment. The outcomes focus on the effects of TCMi-ABC on fatality of patients with AMI in hospitalization and in the long term, the incidence of malignant arrhythmia, left ventricular ejection fraction, and adverse events. RevMan 5.4.1 software was used for mate analysis. Results. This study will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the efficacy and safety of TCMi-ABC for AMI. Conclusion. This study will provide high-quality evidence for treatment of AMI with TCMi-ABC in terms of efficacy and safety, which may help clinicians make a better complementary treatment schedule of patients with AMI.

Diabetic nephropathy is a serious complication of diabetes. Hyperoside has been widely reported to ameliorate diabetes-associated disease. The current study is designed to explore the mechanism of hyperoside in diabetic nephropathy. In the present study, high glucose was used to treat podocytes. Diabetic nephropathy mice models were established by high-fat feeding followed by multiple low dose injections of streptozocin. Western blot analysis was conducted for detection of extracellular matrix accumulation, inflammatory response and cell apoptosis. We found out that hyperoside improved high glucose-induced cell injury. Additionally, hyperoside prevented mice with diabetic nephropathy from diabetic symptoms and renal dysfunction. Mechanistically, hyperoside inhibited the mRNA and protein expression of APC. MiR-499–5p was found to be an upstream negative mediator of APC, and hyperoside induced the upregulation of miR-499–5p. MiR-499–5p bound with the 3’ untranslated region of APC to inhibit its expression. Finally, rescue assays revealed that the suppressive effects of miR-499–5p overexpression on renal dysfunction were rescued by upregulation of APC in mice with diabetic nephropathy. In conclusion, these findings indicated that hyperoside ameliorates diabetic nephropathy via targeting the miR-499–5p/APC axis, suggesting that hyperoside may offer a potential tactic for diabetic nephropathy treatment.

Objective: Tyloxapol is a non-ionic surfactant with diverse pharmacological effects including anti-inflammatory, anti-malignant tumor and antioxidant activities. However, the effect of tyloxapol on osteoclastogenesis has not been elucidated. In this study, we intended to clarify the effect of tyloxapol on RANKL-stimulated osteoclastogenesis and the molecular mechanism both ex vivo and in vivo. Methods: In vitro osteoclastogenesis assay was performed in BMMs and Raw 264.7 cells. The mature osteoclasts were visualized by TRAP staining. The osteoblsats were visualized by alkaline phosphatase (ALP) staining and Von Kossa staining. To assess whether tyloxapol inhibited the function of mature osteoclasts, F-actin belts and pit formation assays were carried out in BMMs. To evaluate the effect of tyloxapol on post-menopausal osteoporosis, the OVX mouse model were utilized. The bone tissue TRAP staining was used to evaluate the osteoclast activity in vivo. The von kossa staining and micro computed tomography were used to evaluate the histomorphometric parameters. The Goldner's staining was used to evaluate the osteoblast activity. The expression of osteoclastogenesis-associated markers were evaluated by Real-time PCR. The NF-κB and NFATc1 transcriptional activities were illustrated utilizing the assay of luciferase reporter. The effect of tyloxapol pretreatment on IκBa degradation and p65 phosphorylation was evaluated using Western bloting assay. The effect of tyloxapol pretreatment on p65 nuclear translocation was evaluated utilizing immunofluorescence. The effect of tyloxapol pretreatment on the phosphorylatio of ERK, p38 and JNK was examined utilizing Western bloting assay. Results: In our research, we found that tyloxapol suppresses RANKL-stimulated osteoclastogenesis in a dose dependent manner and in the initial stage of osteoclastogenesis. Through F-actin belts and pit formation assays, we found that tyloxapol had the ability to inhibit the function of mature osteoclasts in vitro. The results of animal experiments demonstrated that tyloxapol inhibits OVX-induced bone mass loss by inhibiting the activity of osteoclasts but had a limited effect on osteoblastic differentiation and mineralization. Molecularly, we found that tyloxapol suppresses RANKL-stimulated NF-κB activation through suppressing degradation of IκBα, phosphorylation and nuclear translocation of p65. At last, MAPK signaling pathway was also suppressed by tyloxapol in dose and time-dependent manners. Conclusion: Our research illustrated that tyloxapol was able to suppress osteoclastogenesis in vitro and ovariectomized-induced bone loss in vivo by restraining NF-κB and MAPK activation. This is pioneer research could pave the way for the development of tyloxapol as a potential therapeutic treatment for osteoporosis. The translational potential of this article: This study explores that tyloxapol, also known as Triton WR-1339, may be a drug candidate for osteoclastogenic sicknesses like osteoporosis. Our study may also extend the clinical therapeutic spectrum of tyloxapol.

Abstract Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUCROC: 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUCROC: 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

On the basis of the photoelectric properties and hydrophilicity and multimode interference of Graphene Oxide (GO), this study proposes an all-fiber humidity sensor. Two core-offset regions are constructed with a fiber fusion splicer, and a GO film is coated on a single-mode fiber (SMF) between the core-offset regions to form a humidity-sensitive Mach–Zehnder interference structure. As the external humidity environment changes, the refractive index of the GO changes, and the light in the SMF is modulated by humidity. External humidity is measured by detecting the changes in the wavelength of the transmission spectrum of the sensing structure. A saturated salt solution is used to build a stable humidity environment. The sensitivity of the sensor is 0.05 nm/% relative humidity (RH) at 35.3%–95.8% RH, and the linear relationship between the characteristic wavelength and RH is 88%. In addition, the linear relationship between the light intensity and the RH of the sensor at a single wavelength at 1571 nm is analyzed, and the linearity is 97.45%. According to this finding, photoelectric conversion is used to convert the light intensity signal into a voltage signal. The data are processed by a computer to achieve the real-time and visual monitoring of the humidity environment. The fiber optic humidity sensor proposed in this work has a simple structure, simple production, low cost, and high sensitivity. This work provides a new method for humidity sensing.

Purpose To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China. Methods We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age: below 60 years (non-elderly group, n = 5923) and at least 60 years (elderly group, n = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the t-test and chi-square test. Results Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders (p

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the world. The downregulation of farnesoid X receptor (FXR) is frequently founded in CRC patients. The current study found that the decreased expression of FXR in colorectal cancer leads to disorders of bile acids (BAs) metabolism. The altered BAs profile shaped distinct intestinal flora and positively regulated secretory immunoglobulin A (sIgA). The dual regulation of BAs and sIgA enhanced adhesion and biofilm formation of enterotoxigenic Bacteroides fragilis (ETBF), which has a colorectal tumorigenesis effect. The abundance of ETBF increased significantly in intestinal mucosa of colitis-associated cancer (CAC) mice, and finally promoted the development of colorectal cancer. This study suggests that downregulation of FXR in CRC results in BAs dysregulation, and BAs have strong effects on sIgA and gut flora. The elevated BAs concentration and altered gut microbiome are risk factors for CRC.

Lupus nephritis (LN) is a significant cause of various acute and chronic renal diseases, which can eventually lead to end-stage renal disease. The pathogenic mechanisms of LN are characterized by abnormal activation of the immune responses, increased cytokine production, and dysregulation of inflammatory signaling pathways. LN treatment is an important issue in the prevention and treatment of systemic lupus erythematosus. Mesenchymal stem cells (MSCs) have the advantages of immunomodulation, anti-inflammation, and anti-proliferation. These unique properties make MSCs a strong candidate for cell therapy of autoimmune diseases. MSCs can suppress the proliferation of innate and adaptive immune cells, such as natural killer cells (NKs), dendritic cells (DCs), T cells, and B cells. Furthermore, MSCs suppress the functions of various immune cells, such as the cytotoxicity of T cells and NKs, maturation and antibody secretion of B cells, maturation and antigen presentation of DCs, and inhibition of cytokine secretion, such as interleukins (ILs), tumor necrosis factor (TNF), and interferons (IFNs) by a variety of immune cells. MSCs can exert immunomodulatory effects in LN through these immune functions to suppress autoimmunity, improve renal pathology, and restore kidney function in lupus mice and LN patients. Herein, we review the role of immune cells and cytokines in the pathogenesis of LN and the mechanisms involved, as well as the progress of research on the immunomodulatory role of MSCs in LN.

Adamantinoma is a locally aggressive or malignant tumor, accounting for

Cancer proteomics has become a powerful technique for characterizing the protein markers driving transformation of malignancy, tracing proteome variation triggered by therapeutics, and discovering the novel targets and drugs for the treatment of oncologic diseases. To facilitate cancer diagnosis/prognosis and accelerate drug target discovery, a variety of methods for tumor marker identification and sample classification have been developed and successfully applied to cancer proteomic studies. This review article describes the most recent advances in those various approaches together with their current applications in cancer-related studies. Firstly, a number of popular feature selection methods are overviewed with objective evaluation on their advantages and disadvantages. Secondly, these methods are grouped into three major classes based on their underlying algorithms. Finally, a variety of sample separation algorithms are discussed. This review provides a comprehensive overview of the advances on tumor maker identification and patients/samples/tissues separations, which could be guidance to the researches in cancer proteomics.

Satellite remote sensing images contain adequate ground object information, making them distinguishable from natural images. Due to the constraint hardware capability of the satellite remote sensing imaging system, coupled with the surrounding complex electromagnetic noise, harsh natural environment, and other factors, the quality of the acquired image may not be ideal for follow-up research to make suitable judgment. In order to obtain clearer images, we propose a dual-path adversarial generation network model algorithm that particularly improves the accuracy of the satellite remote sensing image super-resolution. This network involves a dual-path convolution operation in a generator structure, a feature mapping attention mechanism that first extracts important feature information from a low-resolution image, and an enhanced deep convolutional network to extract the deep feature information of the image. The deep feature information and the important feature information are then fused in the reconstruction layer. Furthermore, we also improve the algorithm structure of the loss function and discriminator to achieve a relatively optimal balance between the output image and the discriminator, so as to restore the super-resolution image closer to human perception. Our algorithm was validated on the public UCAS-AOD datasets, and the obtained results showed significantly improved performance compared to other methods, thus exhibiting a real advantage in supporting various image-related field applications such as navigation monitoring.