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Abstract Background Medication Treatment Satisfaction (M-TS) from the patients’ perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. Methods Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). Results This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. Conclusions Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integrate molecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Aβ1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Aβ1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Aβ1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calcium responses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Aβ1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Aβ in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches.

ObjectiveThe purpose of this meta-analysis was to investigate the effect of high-intensity interval training (HIIT) on arterial stiffness (AS) and vascular function in persons at high risk of cardiovascular disease (CVD).MethodsWe conducted a comprehensive search of randomized controlled trials (RCTs) published in electronic databases (PubMed, Web of Science, Cochrane, Embase, and Ebsco) since their inception through October 2023 to evaluate the effect of HIIT on AS and vascular function in persons at high risk for CVD. The weighted mean difference (WMD) and 95% confidence intervals (95% CI) were calculated, and heterogeneity was assessed using the I2 test.ResultsThis study included 661 participants from 16 studies. HIIT significantly reduced pulse wave velocity (PWV) in persons at high risk for CVD [weighted mean difference (WMD), −0.62; 95% CI, −0.86–−0.38; P

Rhizoctonia cerealis is a soilborne fungus that can cause sharp eyespot in wheat, resulting in massive yield losses found in many countries. Due to the lack of resistant cultivars, fungicides have been widely used to control this pathogen. However, chemical control is not environmentally friendly and is costly. Meanwhile, the lack of genetic transformation tools has hindered the functional characterization of virulence genes. In this study, we attempted to characterize the function of virulence genes by two transient methods, host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS), which use RNA interference to suppress the pathogenic development. We identified ten secretory orphan genes from the genome. After silencing these ten genes, only the RcOSP1 knocked-down plant significantly inhibited the growth of R. cerealis. We then described RcOSP1 as an effector that could impair wheat biological processes and suppress pathogen-associated molecular pattern–triggered immunity in the infection process. These findings confirm that HIGS and SIGS can be practical tools for researching R. cerealis virulence genes. [Graphic: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

ABSTRACT Wheat sharp eyespot caused by Rhizoctonia cerealis is primarily a severe threat to worldwide wheat production. Currently, there are no resistant wheat cultivars, and the use of fungicides is the primary method for controlling this disease. Elucidating the mechanisms of R. cerealis pathogenicity can accelerate the pace of the control of this disease. Long intergenic noncoding RNAs (lincRNAs) that function in plant-pathogen interactions might provide a new perspective. We systematically analyzed lincRNAs and identified a total of 1,319 lincRNAs in R. cerealis. We found that lincRNAs are involved in various biological processes, as shown by differential expression analysis and weighted correlation network analysis (WGCNA). Next, one of nine hub lincRNAs in the blue module that was related to infection and growth processes, MSTRG.4380.1, was verified to reduce R. cerealis virulence on wheat by a host-induced gene silencing (HIGS) assay. Following that, RNA sequencing (RNA-Seq) analysis revealed that the significantly downregulated genes in the MSTRG.4380.1 knockdown lines were associated mainly with infection-related processes, including hydrolase, transmembrane transporter, and energy metabolism activities. Additionally, 23 novel microRNAs (miRNAs) were discovered during small RNA (sRNA) sequencing (sRNA-Seq) analysis of MSTRG.4380.1 knockdown, and target prediction of miRNAs suggested that MSTRG.4380.1 does not act as a competitive endogenous RNA (ceRNA). This study performed the first genome-wide identification of R. cerealis lincRNAs and miRNAs. It confirmed the involvement of a lincRNA in the infection process, providing new insights into the mechanism of R. cerealis infection and offering a new approach for protecting wheat from R. cerealis. IMPORTANCE Rhizoctonia cerealis, the primary causal agent of wheat sharp eyespot, has caused significant losses in worldwide wheat production. Since no resistant wheat cultivars exist, chemical control is the primary method. However, this approach is environmentally unfriendly and costly. RNA interference (RNAi)-mediated pathogenicity gene silencing has been proven to reduce the growth of Rhizoctonia and provides a new perspective for disease control. Recent studies have shown that lincRNAs are involved in various biological processes across species, such as biotic and abiotic stresses. Therefore, verifying the function of lincRNAs in R. cerealis is beneficial for understanding the infection mechanism. In this study, we reveal that lincRNAs could contribute to the virulence of R. cerealis, which provides new insights into controlling this pathogen.

To investigate the normal section strength and cracking bending moment of normal concrete–ultra-high-performance concrete (NC-UHPC) composite beams, calculation formulas were established considering the tensile strength of UHPC based on the current railway bridge design code. Using the railway T-beam as a template, prestressed NC-UHPC composite beams with different NC layer heights were built. A static bending test was performed, the pressure of the steel strand and the deflection and strain of the beam were measured, and the evolution of cracks in each beam was observed. The calculation formulas of the normal section strength and cracking bending moment of NC-UHPC composite beam were verified by the test. The results showed that the type of strain was similar to load-deflection curves with increasing load; the bending failure process of the NC-UHPC composite beam showed four obvious stages: elasticity, uniform cracking, crack development, and yield. Cracks in the beam started to appear at stage II, developed rapidly at stage III, and stopped emerging at stage IV. The calculation formulas for the normal section strength and the cracking bending moment of the NC-UHPC composite beam were in good agreement with the test values. Normal concrete with a compressive strength of 80 MPa can replace UHPC for the design of NC-UHPC composite beams.

The advantages of ultraviolet light-emitting diodes (LEDs) inserted with a p-AlGaN layer, whose Al mole composition is less than that of the last barrier, between the last barrier and the electron blocking layer have been investigated by using the Crosslight APSYS programs. The results show that the output power and the internal quantum efficiency of the proposed LEDs are improved. Furthermore, the efficiency droop is also mitigated effectively. Based on the analysis of electrical and optical characteristics, these improvements are mainly attributed to the relatively higher effective barrier height against the escape of electrons and an increased hole concentration in the quantum wells by inserting a hole reservoir near the active region. In addition, the optimized Al mole composition of this inserted layer has been also studied in detail, and the optimized Al mole composition has been achieved.

Abstract To elucidate the currently unknown relationship between hyperthyroidism and osteoarthritis (OA). During 2007–2012, 7,433 participants (hyperthyroidism patients = 125; OA patients = 675) were included in the National Health and Nutrition Examination Survey database. We used a weighted multivariable-adjusted logistic regression analysis to assess the association between hyperthyroidism and OA. We also assessed the causality of that relationship using publicly available genome-wide association study data and three Mendelian randomization (MR) analysis methods. The heterogeneity test, pleiotropy test, and leave-one-out tests were used for sensitivity analysis. In this cross-sectional study, after adjusting for potential confounding factors, we found that hyperthyroidism significantly (P = 0.018) increased the risk of OA (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.2–4.17). Age-stratified analysis revealed that hyperthyroidism was associated with a greater risk of OA in the 60–80-year-old age group (OR = 2.86, 95% CI = 1.46–5.59, P = 0.002), with no significant association in the 18–59-year-old age group (all P > 0.05). The results of the inverse-variance weighting (IVW) analysis showed that hyperthyroidism increased the risk of OA (OR = 1.23, 95% CI = 1.04–1.46; P = 0.017). The weighted median estimator (WME) and MR-Egger method also confirmed this causal association (OR = 1.27 and OR = 1.32, respectively). The sensitivity analysis results confirmed the reliability of this conclusion. In addition, IVW-based reverse-MR analysis revealed that OA did not increase the risk of hyperthyroidism (OR = 1.02, 95% CI = 0.97–1.08; P = 0.449). Hyperthyroidism is associated with an increased risk of OA, but the underlying pathological mechanism still needs to be clarified in future research.

Various material design strategies have been developed to enhance photocatalytic performance of TiO2. However, no report is available on applications of the photopiezocatalysis strategy on TiO2 due to its lack of piezoelectricity. Here we developed a low-temperature molten salt etching process to create rutile TiO2 nanoparticles by etching [MgO6] octahedrons away from MgTiO3 by molten NH4Cl, during which a lattice distortion occurred in TiO2. The lattice distortion broke the structure symmetry of rutile TiO2 and subsequently endowed these rutile TiO2 nanoparticles with an unusual piezoelectric response with the maximum effective piezoelectric coefficient (d33) of ~41.6 pm/V, which had not previously been found in TiO2 photocatalysts. Thus, the photopiezocatalysis strategy was applied for the first time to enhance the photocatalytic performance of these TiO2 nanoparticles. The creation of lattice distortion to induce piezoelectricity could be extended to other photocatalysts that the photopiezocatalysis strategy has not been applied to and may generate novel functionalities for various technical applications.

Abstract The association between the systemic immune-inflammation index (SII) and the risk of sarcopenia has not yet been revealed. The purpose of this study was to investigate the relationship between the SII and sarcopenia in individuals aged 18–59 years. All data for this study are from the National Health and Nutrition Examination Survey (NHANES) database, including 7258 participants (age range: 18–59 years). We divided SII values by quartiles (quartiles 1–4: 0.3–3.1, 3.2–4.4, 4.4–6.2, and 6.2–58.5). We constructed a multivariate logistic regression model to assess the association between the SII and the risk of sarcopenia, and an interaction test was run to test the stability of the model and identify high-risk individuals with sarcopenia. Compared to nonsarcopenia participants, sarcopenia patients had a significantly higher SII value (weighted average: 6.65 vs. 5.16) (P = 0.002). Multivariate logistic regression results showed a positive linear relationship between the SII and sarcopenia (OR [odds ratio] = 1.12, 95% CI [confidence interval] 1.03–1.21). Compared to the quartile 1 group, the quartile 4 group was associated with a higher risk of sarcopenia (OR = 3.94, 95% CI 1.42–10.94). Compared with the quartile 1 group, the OR value of the quartile 2 to quartile 4 groups showed an upwards trend (P trend

Photocatalytic CO2 reduction to valuable chemical compounds could be a promising approach for carbon-neutral practice. In this work, a simple and robust thermal decomposition process was developed with ammonium carbonate ((NH4)2CO3) as both precipitation agent and sacrificial template to produce fine Nb2O5 nanoparticles with the rich existence of surface hydroxyl (–OH) groups. It was found by density functional theory (DFT) calculations and experiments that the rich existence of the surface –OH groups enhanced the adsorption of both reactants (CO2 and H2O molecules) for the photocatalytic CO2 reduction on these fine Nb2O5 nanoparticles, and the highly selective conversion of CO2 to the high-value chemical compound of ethylene (C2H4, ~68 μmol·g−1·h−1 with ~100% product selectivity) was achieved under simulated solar illumination without usage of any sacrificial agents or noble metal cocatalysts. This synthesis process may also be readily applied as a surface engineering method to enrich the existence of the surface –OH groups on various metal oxide-based photocatalysts for a broad range of technical applications.

BackgroundThe incidence and diagnostic rate of rotator cuff tears (RCTs) have increased significantly. The purpose of this study was to investigate and analyze the risk factors for symptomatic RCTs to provide a basis for their prevention and treatment.MethodsWe retrospectively analyzed the relevant clinical indicators of 193 patients with RCTs and 161 patients without RCTs hospitalized with shoulder pain as the main complaint from January 1, 2017, to August 31, 2021. Univariate analysis and multivariate logistic regression analysis were used to analyze the differences in potential risk factors between the two groups.ResultsUnivariate analysis revealed that age (p

Abstract Background Although fisetin may exist widely in many natural herbs, its anti-OP mechanism is still unclear. The aim of this study is to explore the molecular anti-osteoporosis (OP) mechanism of fisetin based on network pharmacology and cell experiments. Methods The target of fisetin was extracted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of OP were obtained by DisGeNET, GeneCards and the Comparative Toxicogenomics Database, and the targets of fisetin in OP were screened by cross-analysis. The protein–protein interaction (PPI) network was constructed by STRING, and the core targets were obtained. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on common targets via the Database for Annotation, Visualization and Integrated Discovery. Finally, an in vitro cell experiment was used to verify the anti-OP effect and mechanism of fisetin. Results There are 44 targets of fisetin related to the treatment of OP. The PPI results suggest that CTNNB1, CCND1, TP53, JUN, and AKT1 are the core targets. A total of 259 biological process, 57 molecular function and 26 cell component terms were obtained from GO enrichment analysis. The results of KEGG pathway enrichment analysis suggested that fisetin treatment of OP may be related to the Wnt signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway and other signaling pathways. In vitro cell experiments showed that fisetin significantly increased the expression levels of ALP, collagen I, osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) (p

The growing complexity of real-world systems necessitates interdisciplinary solutions to confront myriad challenges in modeling, analysis, management, and control. To meet these demands, the parallel systems method rooted in the artificial systems, computational experiments, and parallel execution (ACP) approach has been developed. The method cultivates a cycle termed parallel intelligence, which iteratively creates data, acquires knowledge, and refines the actual system. Over the past two decades, the parallel systems method has continuously woven advanced knowledge and technologies from various disciplines, offering versatile interdisciplinary solutions for complex systems across diverse fields. This review explores the origins and fundamental concepts of the parallel systems method, showcasing its accomplishments as a diverse array of parallel technologies and applications while also prognosticating potential challenges. We posit that this method will considerably augment sustainable development while enhancing interdisciplinary communication and cooperation.

Background and objectiveWith the development of global population aging, comorbidity (≥2 diseases) is a common health problem among elderly people. Osteoarthritis (OA) and osteoporosis (OP) are common in elderly individuals. There is a lack of drug therapy for OA and OP comorbidities. The purpose of this study was to explore the efficacy and mechanism of Longbie capsule (LBJN), which contains various plant herbs, in treating OA and OP comorbidities (OA + OP) in rats using metabolomics techniques.MethodsWe created an OA + OP rat model through bilateral oophorectomy combined with meniscus instability surgery. Thirty SD rats were randomly divided into five groups (six in each group), namely, the sham group, OA group, OA + OP group, LBJN low-dose group (0.625 g/kg, OA + OP+LB-L group) and LBJN high-dose group (1.25 g/kg, OA + OP+LB-H group). After 8 weeks of intervention, we used micro-CT to detect bone microstructure status, ELISA to measure bone metabolism indicators, and UPLC–MS technology for metabolomics analysis. Finally, the screened differentially expressed metabolites were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and functional enrichment analysis.ResultsThe micro-CT results showed that LBJN significantly improved the bone mineral density (BMD) and bone quality of subchondral bone in OA + OP rats, and LBJN regulated the expression of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRACP) in serum to maintain bone metabolism balance. Metabolomics analysis showed that the metabolic trajectory of OA + OP rats after intervention in the OA + OP+LB-H group showed significant changes, and 107 potential biomarkers could be identified. Among them, 50 metabolites were upregulated (such as zeranol) and 57 were downregulated (such as vanillactic acid). The KEGG functional enrichment results indicated that the differentially expressed metabolites are mainly involved in amino acid metabolism, lipid metabolism, and carbohydrate metabolism. The KEGG pathway enrichment results indicated that LBJN may exert therapeutic effects on OA + OP rats by regulating the cAMP signaling pathway, and the FoxO signaling pathway.ConclusionLBJN can maintain bone metabolism balance by regulating serum lipid metabolism, amino acid metabolism, carbohydrate metabolism, and estrogen, thereby reducing bone loss in subchondral bone, which may be a potential mechanism through which LBJN treats OA + OP.

Knee osteoarthritis (KOA) is a common geriatric disease in middle-aged and elderly people. Its main pathological characteristics are articular cartilage degeneration, changes in subchondral bone reactivity, osteophyte formation at joint edges, synovial disease, ligament relaxation or contracture, and joint capsular contracture. The prevalence rate of symptomatic KOA in middle-aged and elderly people in China is 8.1%, and this is increasing. The main clinical manifestations of this disease are pain and limited activity of the knee joint, which seriously affect the quality of life of patients and may cause disability, posing a huge burden on society and the economy. Although the pathogenesis of KOA is not clear, the treatment of KOA is diverse, and Chinese medicine, which mainly relies on plant-based natural products, has a relatively stable and reliable curative effect. This guideline aims to emphasize the evidence-based staging and stepped treatment of KOA and the therapeutic effect of integrative medicine based on traditional Chinese medicine on KOA. We make recommendations that include the adoption of manual therapy, acupuncture, external application of herbs, herbal plasters, exercise therapy, and other integrative medicine based on traditional Chinese medicine. Users of the above guidelines are most likely to include clinicians and health managers in healthcare settings.

BackgroundResveratrol is a natural polyphenol compound that is widely present in herbal medicines such as Reynoutria japonica Houtt., Veratrum nigrum L., and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data.MethodsThis study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis.ResultsThis meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol ( 0.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats (p = 0.002) but did not improve the whole-body BMD of 3-month-old rats (p = 0.17).ConclusionResveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.

Objective: The therapeutic efficacy and molecular mechanisms of traditional Chinese medicines (TCMs), such as Liuwei Dihuang pills (LWDH pills), in treating osteoporosis (OP) remain an area of active research and interest in modern medicine. This study investigated the mechanistic underpinnings of LWDH pills in the treatment of OP based on network pharmacology, bioinformatics, and in vitro experiments. Methods: The active ingredients and targets of LWDH pills were retrieved through the TCMSP database. OP-related targets were identified using the CTD, GeneCards, and DisGeNET databases. The STRING platform was employed to construct a protein–protein interaction (PPI) network, and core targets for LWDH pills in treating OP were identified. The GO functional and KEGG pathway enrichment analyses for potential targets were performed using the R package “clusterProfiler”. A “drug–target” network diagram was created using Cytoscape 3.7.1 software. The viability of MC3T3-E1 cells was evaluated using the CCK-8 method after treatment with various concentrations (1.25%, 2.5%, 5%, and 10%) of LWDH pill-medicated serum for 24, 48, and 72 h. Following a 48 h treatment of MC3T3-E1 cells with LWDH pill-medicated serum, the protein levels of collagen Ⅰ, RUNX2, Wnt3, and β-catenin were quantified using the Western blot analysis, and the activity of alkaline phosphatase (ALP) was measured. Results: A total of 197 putative targets for LWDH pills for OP treatment were pinpointed, from which 20 core targets were singled out, including TP53, JUN, TNF, CTNNB1 (β-catenin), and GSK3B. The putative targets were predominantly involved in signaling pathways such as the Wnt signaling pathway, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. The intervention with LWDH pill-medicated serum for 24, 48, and 72 h did not result in any notable alterations in the cell viability of MC3T3-E1 cells relative to the control group (all p > 0.05). Significant upregulation in protein levels of collagen Ⅰ, RUNX2, Wnt3, and β-catenin in MC3T3-E1 cells was observed in response to the treatment with 2.5%, 5%, and 10% of LWDH pill-medicated serum in comparison to that with the 10% rabbit serum group (all p < 0.05). Furthermore, the intervention with LWDH pill-medicated serum resulted in the formation of red calcified nodules in MC3T3-E1 cells, as indicated by ARS staining. Conclusions: LWDH pills may upregulate the Wnt/β-catenin signaling pathway to elevate the expression of osteogenic differentiation proteins, including collagen Ⅰ and RUNX2, and to increase the ALP activity in MC3T3-E1 cells for the treatment of OP.

Background: Diabetic microangiopathy is a type of vascular dysfunction. The effect of type 2 diabetes microangiopathy (DMA) on bone mineral density (BMD) and bone metabolism is still unclear. Objective: A meta-analysis was performed to investigate the effects of microangiopathy on BMD and bone metabolism in type 2 diabetic patients. Methods: We searched the PubMed, Embase, Cochrane Library and CNKI databases to identify observational studies investigating the effects of type 2 diabetes microangiopathy on BMD or bone metabolism. The time limit for the literature retrieval was from the establishment of the database to September 25, 2021. The Newcastle–Ottawa scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the quality of the studies. RevMan 5.3 software was used for the data analysis. Stata 14.0 was used to quantitatively evaluate the publication bias of the outcome indicators. Results: In total, 12 observational studies were included, including 7 cohort studies, 4 case–control studies and 1 cross-sectional study. In total, 2,500 patients with type 2 diabetes were included. Among them, 1,249 patients had microangiopathy (DMA group), and 1,251 patients did not have microangiopathy (control group). The results of the meta-analysis showed that the BMDs of the femoral neck (SMD = −1.34, 95% CI = −2.22 to −0.45, P = 0.003), lumbar spine (SMD = −0.69, 95% CI = −1.31 to −0.08, P = 0.03) and Ward's triangle (SMD = −2.84, 95% CI = −4.84 to −0.83, P = 0.006) in the DMA group were lower than those in the control group. In the comparison of the bone metabolism indexes, the contents of N-terminal propeptide of type I procollagen (P1NP) (SMD = 0.18, 95% CI = 0.03 to 0.32, P = 0.02), osteocalcin (SMD = 6.97, 95% CI = 3.46 to 10.48, P < 0. 0001), parathyroid hormone (PTH) (SMD = 0.38, 95% CI = 0.03 to 0.73, P = 0.03) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.39, 95% CI = 0.03 to 0.75, P = 0.03) in serum from the DMA group were higher than those in serum from the control group. The serum content of 25-hydroxyvitamin D3 (25(OH)D3) (SMD = −0.63, 95% CI = −1.19 to −0.07, P = 0.03) in the DMA group was lower than that in the control group. There was no significant difference in serum alkaline phosphatase (ALP), calcium or phosphorus between the two groups (P > 0.05). Conclusions: Type 2 diabetes microangiopathy can reduce the lumbar spine, femoral neck and Ward's triangle BMD and has a higher risk of osteoporosis or osteoporosis fractures. The levels of P1NP, PTH, CTX and OC in the serum of patients with type 2 diabetes microangiopathy are higher, and the lower 25(OH)D3 content may be a mechanism by which DMA destroys bone metabolism balance.

The coronavirus disease 2019 (COVID-19) pandemic has triggered multiple global healthcare system crises. Apart from the pandemic itself, the travel restriction and social distance policy for the purpose of epidemic control has cast a shadow on the management of cancer survivors. Cancer survivors suffered a double blow from both the epidemic and cancer. To deal with the challenge, we explored a new Internet-based patient management model. This model has overcome the limitation of time and space and thus can help oncologists to provide remote multidisciplinary healthcare services for cancer survivors. These patients can get high-quality cancer management from multidisciplinary experts without too much transportation. This model has been applied in patients with genitourinary cancers and proved to be effective and efficient. Our study demonstrated that more patients benefited from this model during the pandemic of COVID-19, especially in those affected heavily by COVID-19. These results suggested that it can also give insight into the management of other cancer survivors in China. Given the long-term impact of the COVID-19 pandemic, we would like to introduce our new model of healthcare service and the application of Internet-based multidisciplinary management to our global peers and medical industries to help their cancer survivors who are delayed in treatment due to the COVID-19 pandemic.

Abstract A novel arsenic adsorbent with hydrous cerium oxides coated on glass fiber cloth (HCO/GFC) was synthesized. The HCO/GFC adsorbents were rolled into a cartridge for arsenic removal test. Due to the large pores between the glass fibers, the arsenic polluted water can flow through easily. The arsenic removal performance was evaluated by testing the equilibrium adsorption isotherm, adsorption kinetics, and packed-bed operation. The pH effects on arsenic removal were conducted. The test results show that HCO/GFC filter has high As(V) and As(III) removal capacity even at low equilibrium concentration. The more toxic As(III) in water can be easily removed within a wide range of solution pH without pre-treatment. Arsenic contaminated ground-water from Yangzong Lake (China) was used in the column test. At typical breakthrough conditions (the empty bed contact time, EBCT = 2 min), arsenic researched breakthrough at over 24,000 bed volumes (World Health Organization (WHO) suggested that the maximum contaminant level (MCL) for arsenic in drinking water is 10 mg/L). The Ce content in the treated water was lower than 5 ppb during the column test, which showed that cerium did not leach from the HCO/GFC material into the treated water. The relationship between dosage of adsorbents and the adsorption kinetic model was also clarified, which suggested that the pseudo second order model could fit the kinetic experimental data better when the adsorbent loading was relatively low, and the pseudo first order model could fit the kinetic experimental data better when the adsorbent loading amount was relatively high.

ABSTRACT Quorum sensing (QS) is a unique mechanism for microorganisms to coordinate their activities through intercellular communication, including four main types of autoinducer-1 (AI-1, namely, N-acyl homoserine lactone [AHL]), AI-2, AI-3, and diffusible signaling factor [DSF]) based on signaling molecules. Quorum quenching (QQ) enzymes can disrupt the QS phenomenon by inactivating signaling molecules. QS is proposed to regulate biofilm formation in extremely acidic environments, but the QS/QQ-related genomic features in most acidophilic bacteria are still largely unknown. Here, genome annotation of 83 acidophiles from the genera Acidithiobacillus, Leptospirillum, Sulfobacillus, and Acidiphilium altogether revealed the existence of AI-1, AI-3, DSF, and AhlD (AHL degradation enzyme). The conservative investigation indicated that some QS/QQ-related proteins harbored key residues or motifs, which were necessary for their activities. Phylogenetic analysis showed that LuxI/R (AI-1 synthase/receptor), QseE/F (two-component system of AI-3), and RpfC/G (two-component system of DSF) exhibited similar evolutionary patterns within each pair. Meanwhile, proteins clustered approximately according to the species taxonomy. The widespread Acidithiobacillus strains, especially A. ferrooxidans, processed AI-1, AI-3, and DSF systems as well as the AhlD enzyme, which were favorable for their mutual information exchange and collective regulation of gene expression. Some members of the Sulfobacillus and Acidiphilium without AHL production capacity contained the AhlD enzyme, which may evolve for niche competition, while DSF in Leptospirillum and Acidithiobacillus could potentially combine with the cyclic diguanylate (c-di-GMP) pathway for self-defense and niche protection. This work will shed light on our understanding of the extent of communication networks and adaptive evolution among acidophiles via QS/QQ coping with environmental changes. IMPORTANCE Understanding cell-cell communication QS is highly relevant for comprehending the regulatory and adaptive mechanisms among acidophiles in extremely acidic ecosystems. Previous studies focused on the existence and functionality of a single QS system in several acidophilic strains. Four representative genera were selected to decipher the distribution and role of QS and QQ integrated with the conservative and evolutionary analysis of related proteins. It was implicated that intra- or intersignaling circuits may work effectively based on different QS types to modulate biofilm formation and energy metabolism among acidophilic microbes. Some individuals could synthesize QQ enzymes for specific QS molecular inactivation to inhibit undesirable acidophile species. This study expanded our knowledge of the fundamental cognition and biological roles underlying the dynamical communication interactions among the coevolving acidophiles and provided a novel perspective for revealing their environmental adaptability.

PurposeTo explore the molecular mechanism of luteolin in the treatment of osteoporosis (OP) by network pharmacological prediction and experimentation.MethodsThe target proteins of luteolin were obtained with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). OP-related proteins were extracted from the Comparative Toxicogenomics Database (CTD) and GeneCards and DisGeNET databases. We imported the common protein targets of luteolin and OP into the STRING database to obtain the relationships between the targets. The common target proteins of luteolin and OP were assessed by KEGG and GO enrichment analyses with the DAVID database. Animal experiments were conducted to verify the effect of luteolin on bone mineral density in ovariectomised (OVX) rats. Finally, the effects of luteolin on key signalling pathways were verified by cell experiments in vitro.ResultsForty-four targets of luteolin involved in the treatment of OP, including key target proteins such as TP53, AKT1, HSP90AA1, JUN, RELA, CASP3, and MAPK1, were screened. KEGG enrichment analysis found that luteolin inhibits OP by regulating the PI3K-Akt, TNF, oestrogen and p53 signalling pathways. The results of animal experiments showed that bone mass in the low-dose luteolin group (Luteolin-L group, 10 mg/kg), high-dose luteolin group (Luteolin-H group, 50 mg/kg) and positive drug group was significantly higher than that in the OVX group (P

Abstract Background The purpose of this case report was to report a case of Cryptococcus laurentii infection in the left knee of a previously healthy 29 year old male patient. Case presentation After an initial misdiagnosis and 7 months of failed treatment, the patient received nearly a month of treatment with voriconazole (200 mg IV q12 h) and knee irrigation with amphotericin B until the infection was controlled. The treatment continued with fluconazole for nearly 7 months and approximately 5 weeks of antibiotic treatment for a skin bacterial coinfection. In the end, the patient’s symptoms disappeared completely, the left knee recovered well, and there was no recurrence of infection. Conclusion The key points of successful treatment in this case were the thorough debridement, the adequate course of knee irrigation with antifungal drugs and more than 6 months of oral antifungal drugs that were able to eradicate the infection.

Abstract Background Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA. Methods The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation. Results Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: − 0.31; 95% confidence interval (CI): − 0.55 to − 0.06; P = 0.01 0.05). Conclusions Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.

Acidiferrobacter spp. are facultatively anaerobic acidophiles that belong to a distinctive Acidiferrobacteraceae family, which are similar to Ectothiorhodospiraceae phylogenetically, and are closely related to Acidithiobacillia class/subdivision physiologically. The limited genome information has kept them from being studied on molecular taxonomy and environmental adaptation in depth. Herein, Af. thiooxydans ZJ was isolated from acid mine drainage (AMD), and the complete genome sequence was reported to scan its genetic constitution for taxonomic and adaptative feature exploration. The genome has a single chromosome of 3,302,271 base pairs (bp), with a GC content of 63.61%. The phylogenetic tree based on OrthoANI highlighted the unique position of Af. thiooxydans ZJ, which harbored more unique genes among the strains from Ectothiorhodospiraceae and Acidithiobacillaceae by pan-genome analysis. The diverse mobile genetic elements (MGEs), such as insertion sequence (IS), clustered regularly interspaced short palindromic repeat (CRISPR), prophage, and genomic island (GI), have been identified and characterized in Af. thiooxydans ZJ. The results showed that Af. thiooxydans ZJ may effectively resist the infection of foreign viruses and gain functional gene fragments or clusters to shape its own genome advantageously. This study will offer more evidence of the genomic plasticity and improve our understanding of evolutionary adaptation mechanisms to extreme AMD environment, which could expand the potential utilization of Af. thiooxydans ZJ as an iron and sulfur oxidizer in industrial bioleaching.

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.

Due to the contrast of X-ray images being low, significant elements including organs, bones, and nodules are very difficult to identify, so contrast enhancement is necessary. In this paper, an X-ray image enhancement algorithm based on adaptive gradient domain guided image filtering is proposed. The amplification factor in the gradient domain guided image filtering needs to be set manually; it needs to constantly adjust the parameters to achieve the best enhancement effect, and this also increases the computational complexity. In order to solve this problem, an adaptive amplification factor is defined in this paper, and the proposed algorithm is applied to the X-ray image enhancement. Experimental results demonstrate that the proposed method is superior to state-of-the art algorithms in terms of detail enhancement and edge-preserving.

Myocardial infarction (MI) is a deadly disease that threatens human life worldwide, and it is essential to save threatened lives with early detection of MI. The electrocardiogram (ECG), which records the electrical activity presented in the heart, is used for the prevention and treatment of heart disease such as MI. However, it remains a challenge to visually interpret the ECG signals because of their small amplitude and duration. Inspired by the development in computer vision, we try to explore a novel approach for automatic detection of MI by imaging ECG signals without noise removal. In this paper, the ECG time series is first transformed into images using the Gramian Angular Difference Field (GADF) method. Subsequently, the processed images are subjected to the principal component analysis network (PCANet) to extract sparse high-dimensional features, which are easy to perform well in linear classifiers. We carried out several sets of experiments to test the effectiveness of our algorithm. The overall accuracy of 99.49%, the sensitivity of 99.78%, and the specificity of 98.08% are achieved in class-oriented experiments using original ECG beats. The accuracy even rises over 1% compared with the denoising one; Moreover, we also achieved favorable performance for the patient-specific experiment (accuracy of 93.17%, sensitivity of 93.91%, and specificity of 89.20%). The results of the experiments indicate that our model is an effective way to detect MI using raw ECG signals.

BackgroundBeta-blocker (BB) is suggested to have anticancer efficacy. However, the potential influence of BB use on overall survival (OS) in patients with lung cancer remains undetermined. We aimed to evaluate the above relationship in an updated meta-analysis.MethodsObservational studies comparing OS between users and non-users of BB with lung cancer were identified by search of PubMed, Embase, and Cochrane's Library. A random-effect model was used to pool the results.ResultsTen retrospective cohort studies with 30870 patients were included. Overall, BB use was not associated with significantly improved OS in lung cancer (hazard ratio [HR] = 1.02, 95% confidence interval [CI]: 0.98 to 1.06, p = 0.33) with moderate heterogeneity (I2 = 29%). Stratified analyses showed similar results in patients with non-small cell lung cancer and small cell lung cancer, in studies with BB use before and after the diagnosis of lung cancer, and in studies with or without adjustment of smoking. Use of BB was associated with improved OS in patients with stage III lung cancer (HR = 0.91, 95% CI: 0.85 to 0.98, p = 0.02) and in patients that did not receive surgery resection (HR = 0.78, 95% CI: 0.64 to 0.96, p = 0.02), while use of non-selective BB was associated with worse OS (HR = 1.14, 95% CI: 1.01 to 1.28, p = 0.03).ConclusionsThis meta-analysis of retrospective cohort studies does not support a significant association between BB use and improved OS in lung cancer.

An attack of congestive heart failure (CHF) can cause symptoms such as difficulty breathing, dizziness, or fatigue, which can be life-threatening in severe cases. An electrocardiogram (ECG) is a simple and economical method for diagnosing CHF. Due to the inherent complexity of ECGs and the subtle differences in the ECG waveform, misdiagnosis happens often. At present, the research on automatic CHF detection methods based on machine learning has become a research hotspot. However, the existing research focuses on an intra-patient experimental scheme and lacks the performance evaluation of working under noise, which cannot meet the application requirements. To solve the above issues, we propose a novel method to identify CHF using the ECG-Convolution-Vision Transformer Network (ECVT-Net). The algorithm combines the characteristics of a Convolutional Neural Network (CNN) and a Vision Transformer, which can automatically extract high-dimensional abstract features of ECGs with simple pre-processing. In this study, the model reached an accuracy of 98.88% for the inter-patient scheme. Furthermore, we added different degrees of noise to the original ECGs to verify the model’s noise robustness. The model’s performance in the above experiments proved that it could effectively identify CHF ECGs and can work under certain noise.

Cardiovascular disease is the leading cause of death worldwide. Immediate and accurate diagnoses of cardiovascular disease are essential for saving lives. Although most of the previously reported works have tried to classify heartbeats accurately based on the intra-patient paradigm, they suffer from category imbalance issues since abnormal heartbeats appear much less regularly than normal heartbeats. Furthermore, most existing methods rely on data preprocessing steps, such as noise removal and R-peak location. In this study, we present a robust classification system using a multilevel discrete wavelet transform densely network (MDD-Net) for the accurate detection of normal, coronary artery disease (CAD), myocardial infarction (MI) and congestive heart failure (CHF). First, the raw ECG signals from different databases are divided into same-size segments using an original adaptive sample frequency segmentation algorithm (ASFS). Then, the fusion features are extracted from the MDD-Net to achieve great classification performance. We evaluated the proposed method considering the intra-patient and inter-patient paradigms. The average accuracy, positive predictive value, sensitivity and specificity were 99.74%, 99.09%, 98.67% and 99.83%, respectively, under the intra-patient paradigm, and 96.92%, 92.17%, 89.18% and 97.77%, respectively, under the inter-patient paradigm. Moreover, the experimental results demonstrate that our model is robust to noise and class imbalance issues.

Cardiovascular disease (CVD) has become one of the most serious diseases that threaten human health. Over the past decades, over 150 million humans have died of CVDs. Hence, timely prediction of CVDs is especially important. Currently, deep learning algorithm-based CVD diagnosis methods are extensively employed, however, most such algorithms can only utilize one-lead ECGs. Hence, the potential information in other-lead ECGs was not utilized. To address this issue, we have developed novel methods for diagnosing arrhythmia. In this work, DL-CCANet and TL-CCANet are proposed to extract abstract discriminating features from dual-lead and three-lead ECGs, respectively. Then, the linear support vector machine specializing in high-dimensional features is used as the classifier model. On the MIT-BIH database, a 95.2% overall accuracy is obtained by detecting 15 types of heartbeats using DL-CCANet. On the INCART database, overall accuracies of 94.01% (II and V1 leads), 93.90% (V1 and V5 leads) and 94.07% (II and V5 leads) are achieved by detecting seven types of heartbeat using DL-CCANet, while TL-CCANet yields a higher overall accuracy of 95.52% using the above three leads. In addition, all of the above experiments are implemented using noisy ECG data. The proposed methods have potential to be applied in the clinic and mobile devices.

In the past decades, the electrocardiogram (ECG) has been investigated as a promising biometric by exploiting the subtle discrepancy of ECG signals between subjects. However, the heart rate (HR) for one subject may vary because of physical activities or strong emotions, leading to the problem of ECG signal variation. This variation will significantly decrease the performance of the identification task. Particularly for short-term ECG signal without many heartbeats, the hardly measured HR makes the identification task even more challenging. This study aims to propose a novel method suitable for short-term ECG signal identification. In particular, an improved HR-free resampling strategy is proposed to minimize the influence of HR variability during heartbeat processing. For feature extraction, the Principal Component Analysis Network (PCANet) is implemented to determine the potential difference between subjects. The proposed method is evaluated using a public ECG-ID database that contains various HR data for some subjects. Experimental results show that the proposed method is robust to HR change and can achieve high subject identification accuracy (94.4%) on ECG signals with only five heartbeats. Thus, the proposed method has the potential for application to systems that use short-term ECG signals for identification (e.g., wearable devices).