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Abstract Proteins that bind to DNA/RNA are typically evolutionarily conserved with multiple regulatory functions in transcription initiation, mRNA translation, stability of RNAs, and RNA splicing. Therefore, dysregulation of DNA/RNA binding proteins such as purine-rich element binding protein alpha (PURα) disrupts signaling transduction and often leads to human diseases including cancer. PURα was initially recognized as a tumor suppressor in acute myeloid leukemia (AML) and prostate cancer (PC). Most recently, several studies have revealed that PURα is dysregulated in multiple cancers, such as breast cancer (BC) and esophageal squamous cell carcinoma (ESCC). The oncogenic or tumor-suppressive functions of PURα are realized via regulating RNA/protein interaction, mRNA translation, formation of stress granules (SGs), and transcriptional regulation of several oncogenes and tumor suppressors. Although DNA/RNA binding proteins are hardly targeted, novel strategies have been applied to identify compounds targeting PURα and have demonstrated promising anti-tumor efficacy in the preclinical study. The present review summarizes the most recently discovered critical roles of PURα in various cancer types, providing an overview of the biomarker and therapeutic target potential of PURα for patients with cancer.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adult, characterized by uncontrolled cell proliferation and strong aggressiveness. Previous studies have found that cyclin-dependent kinase 1(CDK1) are related to tumor growth and metastasis. However, the role of CDK1 in DLBCL is exclusive. This study investigated the clinical implications and expression of CDK1 in DLBCL. Methods Gene expression data for healthy subjects were sourced from the Genotype-Tissue Expression repository. Clinical details and survival statistics of patients with DLBCL were obtained from the Gene Expression Omnibus archive (GSE10846). Patients were categorized based on CDK1 expression levels, and differences in clinical outcomes between the groups were examined. Univariate and multivariate Cox regression analyses were used to ascertain whether CDK1 expression independently predicted DLBCL prognosis. The protein expression of CDK1 was gauged by immunohistochemistry. Additionally, we investigated the effect of CDK1 inhibition on DLBCL cell growth and death using the Cell Counting Kit-8 and flow cytometry. Results In the control group, CDK1 expression was predominantly observed in the hematopoietic and reproductive systems. CDK1 levels in patients with DLBCL were notably elevated compared with those in controls. Significant differences were noted in the lactate dehydrogenase ratio and overall survival based on CDK1 expression. Statistical analyses confirmed that CDK1 was an independent predictor of DLBCL outcomes. Elevated CDK1 protein levels were observed in a significant number of DLBCL samples, in contrast to normal lymph node samples from individuals without lymphoma. The inhibitor Ro-3306 curtails DLBCL cell growth and enhances cell death in vitro. Conclusions Elevated CDK1 levels are correlated with poor prognosis in patients with DLBCL.

Purpose This study explored the association of the elasticity modulus and shear wave velocity (SWV) of the tibialis anterior muscle, as measured by two-dimensional shear wave elastography (2D-SWE), with the intracompartmental pressure (ICP) determined using the Whitesides method in a New Zealand rabbit model of acute compartment syndrome (ACS). Additionally, it evaluated the viability of 2D-SWE as a noninvasive, quantitative tool for the early detection of ACS. Methods An ACS model was established through direct external compression by applying pressure bandaging to the lower legs of 15 New Zealand rabbits using neonatal blood pressure cuffs. Another five animals represented a non-modeled control group. To measure the elasticity modulus and SWV of the tibialis anterior muscles, 2D-SWE was employed. Blood oxygen saturation, serum creatine kinase (CK), and myoglobin levels were monitored. Subsequently, the anterior tibial compartment was dissected, and the tibialis anterior was removed for hematoxylin and eosin staining to assess muscle injury. Results The elasticity modulus and SWV of the tibialis anterior muscle increased with compression duration, as did serum CK and myoglobin levels. ICP was strongly positively correlated with these parameters, particularly mean velocity (r=0.942, P

Abstract Pathological complete response (pCR) serves as a critical measure of the success of neoadjuvant chemotherapy (NAC) in breast cancer, directly influencing subsequent therapeutic decisions. With the continuous advancement of artificial intelligence, methods for early and accurate prediction of pCR are being extensively explored. In this study, we propose a cross-modal multi-pathway automated prediction model that integrates temporal and spatial information. This model fuses digital pathology images from biopsy specimens and multi-temporal ultrasound (US) images to predict pCR status early in NAC. The model demonstrates exceptional predictive efficacy. Our findings lay the foundation for developing personalized treatment paradigms based on individual responses. This approach has the potential to become a critical auxiliary tool for the early prediction of NAC response in breast cancer patients.

Studies suggest that gut dysbiosis occurs in autoimmune neurological diseases, but a comprehensive synthesis of the evidence is lacking. Our aim was to systematically review and meta-analyze the correlation between the gut microbiota and autoimmune neurological disorders to inform clinical diagnosis and therapeutic intervention. We searched the databases of PubMed, Embase, Web of Science, and the Cochrane Library until 1 March 2024 for research on the correlation between gut microbiota and autoimmune neurological disorders. A total of 62 studies provided data and were included in the analysis (n = 3,126 patients, n = 2,843 healthy individuals). Among the included studies, 42 studies provided data on α-diversity. Regarding α-diversity, except for Chao1, which showed a consistent small decrease (SMD = −0.26, 95% CI = −0.45 to −0.07, p < 0.01), other indices demonstrated no significant changes. While most studies reported significant differences in β-diversity, consistent differences were only observed in neuromyelitis optica spectrum disorders. A decrease in short-chain fatty acid (SCFA)-producing bacteria, including Faecalibacterium and Roseburia, was observed in individuals with autoimmune encephalitis, neuromyelitis optica spectrum disorders, myasthenia gravis, and multiple sclerosis. Conversely, an increase in pathogenic or opportunistic pathogens, including Streptococcus and Escherichia-Shigella, was observed in these patients. Subgroup analyses assessed the confounding effects of geography and immunotherapy use. These findings suggest that disturbances of the gut flora are associated with autoimmune neurological diseases, primarily manifesting as non-specific and shared microbial alterations, including a reduction in SCFA-producing bacteria and an increase in pathogenic or opportunistic pathogens.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023410215.

PurposeRecommendations from the National Health Commission of China (NHCC) and the International Ki67 Working Group (IKWG) were issued to guide immunohistochemistry (IHC)-based Ki67 scoring for breast cancer patients in daily clinical practice. They were evaluated in this multi-institutional study alongside the results from the Quantitative Dot Blot (QDB) method.MethodsThree alternative adjacent sections from 40 primary ER+ breast cancer resection blocks were randomly assigned a number from 1 to 120 for Ki67 staining and reviewed by 21 pathologists, while the other three alternative sections were sent for QDB analysis of Ki67 protein levels. Ki67 scores were grouped by 5/30% (IKWG), 10/30% (NHCC) and 20/30% (NHCC appendix 9, NHCCa9), respectively while QDB results were grouped by C5–C95 of 2.31 nmol/g defined in previous study as low-, equivocal-, and high-risk groups.ResultsThe overall Intraclass Correlation Coefficient (ICC) was 0.785 for IHC evaluations from 21 pathologists, with Fleiss Kappa values of 0.555, 0.628, and 0.480 when Ki67 scores were grouped by guidance from IKWG, NHCC, and NHCCa9, respectively. In comparison, the ICC and Fleiss kappa values for the QDB analysis were 0.939 and 0.831, respectively. When IHC and QDB results were cross-referenced, more specimens were grouped as high-risk by QDB than IHC, and NHCCa9 led to the highest percentage of disagreement between the two methods.ConclusionThe IKWG recommendation was harder to achieve categorized agreement among pathologists than the NHCC recommendation, yet it led to the best agreement with the QDB to define the low-risk group. The QDB method offers significantly improved consistency compared to the current IHC-based Ki67 assessment.

BackgroundSmoking is highly prevalent among HIV-infected individuals and is associated with high morbidity and mortality. Studies on smoking among HIV-infected individuals in China, especially compared to uninfected individuals, are scarce.PurposeThis study aimed to investigate and compare the prevalence and factors associated with smoking between HIV-infected and uninfected men in Guilin, China.MethodsA survey was conducted among 1,395 HIV-infected men at Guilin Third People’s Hospital from June to December 2022, with a 1:2 age (±1 year) and education-matched control group of 2,790 HIV-uninfected men, whose data were collected from March to August 2023. Both groups completed an online questionnaire on smoking behaviors and relevant characteristics, with a comparative analysis of associated factors conducted using chi-square tests and multivariable logistic regressions.ResultsThe rates of former smokers were comparable between HIV-infected and uninfected men [12.3% (95% CI: 10.7–13.9%) vs. 12.0% (95% CI: 10.9–13.1%)], but the current smoking rate was significantly higher in the infected group than in the uninfected group [37.6% (95% CI: 35.2–40.0%) vs. 27.6% (95% CI: 25.9–29.3%), p

This study evaluated the effects of four highland barley proteins (HBPs), namely albumin, globulin, gliadin and glutenin, on the retrogradation and in vitro digestion properties of highland barley starch (HBS). The results showed globulin had the most significant effect on inhibiting short-term retrogradation of HBS, which was reflected in the reduction of G' and G''. Compare with HBS, four HBPs could significantly inhibit long-term recrystallization process. For albumin, globulin, gliadin and glutenin, the degree of retrogradation reduced from 51.55 % to 48.20 %, 35.06 %, 42.22 % and 32.63 %, respectively, which was reflected in the decrease of water migration rate, crystal enthalpy, crystallinity and short-range order. It could be found that glutenin had the most significant effect on inhibiting long-term retrogradation of HBS. Moreover, the anti-digestion properties of retrograded HBS with HBPs intervention significantly increased, with glutenin most significantly. Compared with HBS, resistant starch (RS) content increased by 59.76 % at 28 d of retrogradation.

Abstract Protein-encoding circular RNAs (circRNAs) are newly identified RNA molecules characterized by intense interaction with translating ribosome. Emerging evidence has implicated physiological and pathological significance of these non-canonical RNAs, yet a large body of them remains unidentified. Due to limited tools at hand, we developed CircProPlus, an automated computational pipeline for de novo detection of translated circRNAs. In comparison to previously established CircPro, CircProPlus adjusts the overall workflow and integrates more robust implements for achieving easier accessibility, higher flexibility and productivity. In present study, we tested the performance of CircProPlus when using different circRNA-detecting implements (i.e., CIRI2, CirComPara2) in the evaluation of coding ability of circRNAs. Results showed that CirComPara2, a state-of-the-art algorithm, consistently outperformed CIRI2 when coupled with CircProPlus in testing real data collected from different RNA libraries and species, which highlighted its potency in data mining of circRNAs with protein-coding potential.

BackgroundTelemedicine is expanding rapidly, with public direct-to-consumer (DTC) telemedicine representing 70% of the market. A key priority is establishing clear quality distinctions between the public and private sectors. No studies have directly compared the quality of DTC telemedicine in the public and private sectors using objective evaluation methods. ObjectiveUsing a standardized patient (SP) approach, this study aimed to compare the quality of DTC telemedicine provided by China’s public and private sectors. MethodsWe recruited 10 SPs presenting fixed cases (urticaria and childhood diarrhea), with 594 interactions between them and physicians. The SPs evaluated various aspects of the quality of care, effectiveness, safety, patient-centeredness (PCC), efficiency, and timeliness using the Institute of Medicine (IOM) quality framework. Ordinary least-squares (OLS) regression models with fixed effects were used for continuous variables, while logistic regression models with fixed effects were used for categorical variables. ResultsSignificant quality differences were observed between public and private DTC telemedicine. Physicians from private platforms were significantly more likely to adhere to clinical checklists (adjusted β 15.22, P

Introduction: Neuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. Objectives: Here, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. Methods: Bioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. Results: The differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. Conclusion: Our study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.

Abstract Background Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. Results In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin−CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. Conclusions In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice. Graphical abstract

Abstract Background The Chinese government has formulated a series of policies and strengthened training of general practitioners (GPs) to support their role as “gatekeepers” of residents’ health. This study aimed to explore the core competencies of Chinese GPs and develop a competency framework in line with China’s actual conditions, which can provide a more scientific basis for the education, training, and evaluation of GPs. Methods Literature analysis and behaviour event interviews were conducted to build the competency dictionary and the initial version of the competency model. Two rounds of Delphi were performed to gain consensus on the final model. The questionnaire survey was carried out in 10 provinces (municipalities, autonomous regions) of China, and GPs were invited to score the importance of each competency item. The total sample was randomly divided into two groups. One group was for exploratory factor analysis (EFA), and the other was for confirmatory factor analysis (CFA) to examine the scale’s reliability and validity. Results The dictionary of general practitioners’ competency including 107 competency items was constructed. After two rounds of Delphi, a consensus was reached on 60 competencies in 6 domains. A total of 1917 valid questionnaires were obtained in the nationwide survey. The average importance score of all second-level indicators is 4.53 ± 0.45. The Cronbach’s α coefficient is 0.984. The results of the five factors extracted by EFA showing the 68.16% cumulative explained variance variation is considered to be consistent with the six dimensions obtained by Delphi after thorough discussion. The model fitness indexes obtained by CFA were acceptable (χ2/df = 4.909, CFI = 0.869, NFI = 0.841, RMSEA = 0.065). The values of the composite reliability (CR) of the six dimensions were all greater than 0.7 (0.943, 0.927, 0.937, 0.927, 0.943, 0.950), and the average of variance extracted (AVE) were all greater than 0.5 (0.562, 0.613, 0.649, 0.563, 0.626, 0.635). The results showed that the model has good reliability and validity. Conclusion A competency model for GPs suited to China has been developed, which may offer guidance for future training and medical licensing examinations of GPs.

This paper investigates the production scheduling problems of allocating resources and sequencing jobs in the seru production system (SPS). As a new-type manufacturing mode arising from Japanese production practices, seru production can achieve efficiency, flexibility, and responsiveness simultaneously. The production environment in which a set of jobs must be scheduled over a set of serus according to due date and different execution modes is considered, and a combination optimization model is provided. Motivated by the problem complexity and the characteristics of the proposed seru scheduling model, a nested partitioning method (NPM) is designed as the solution approach. Finally, computational studies are conducted, and the practicability of the proposed seru scheduling model is proven. Moreover, the efficiency of the nested partitioning solution method is demonstrated by the computational results obtained from different scenarios, and the good scalability of the proposed approach is proven via comparative analysis.

Saline-alkali soil imposes severe adverse effects on soil utilization and agriculture production worldwide. Amelioration of saline-alkali soil is crucial to ensure global food security and promote sustainable agricultural development. Here, the effects of the combined application of soil amendment desulfurization gypsum (G) and KIA (K, an industrial organic by-product) on soil improvement and plant growth were investigated. Two experiments, a soil column leaching test and a pot experiment for plant growth, were carried out. The results showed that the combined application of G and K reduced soil pH significantly. Although the soil Na+ contents had no change in the combined treatments, the K+, Ca2+ and Mg2+ contents were significantly higher, and the HCO3− and Cl− contents were significantly lower, compared to the control. Furthermore, maize plants exhibited a higher photosynthetic rate and greater dry weight in the combined treatments. Additionally, after plant growth, the soil enzyme activities increased. These results showed that the combined application of G and K could have a more favorable impact on soil improvement by reducing soil pH, enhancing soil ion exchange, increasing soil nutrient contents, and promoting plant growth. Our study suggests that KIA is an effective and eco-friendly soil amendment for improving saline-alkali soil.

The increasing prevalence of harmful algal blooms (HABs) driven by eutrophication, particularly in China’s nearshore waters, is a growing concern. Dinoflagellate Heterocapsa bohaiensis blooms have caused significant ecological and economic damage, as well as mass mortality, in cultivated species. Nutrients are one of the primary inducers of H. bohaiensis blooms. However, the transcriptomic studies of H. bohaiensis remain sparse, and its metabolic pathways are unknown. This study analyzed the transcriptome of H. bohaiensis under varying nutrient conditions (nitrogen at 128, 512, and 880 μM; phosphate at 8, 6, and 32 μM), focusing on differential gene expression. The results indicated that deviations in nutrient conditions (higher or lower N:P ratios) led to a higher number of differentially expressed genes compared to the control (N:P ratios = 27.5), thereby underscoring their pivotal role in growth. Gene Ontology (GO) enrichment analyses showed that nutrient limitation upregulated the biosynthesis and catabolism processes while downregulating the cell cycle and division functions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that, under nitrogen limitation, the proteasome pathways were upregulated, while photosynthesis and carbon fixation were downregulated; under phosphorus limitation, the proteasome pathways were upregulated and nitrogen metabolism was downregulated. These findings suggest that H. bohaiensis adapts to nutrient stress by adjusting its metabolic processes.

Basic leucine zipper (bZIP) transcription factors (TFs) regulate plant development, growth, and secondary metabolism. The formation of red bark of new ornamental cultivar 'Gantong 1' is regulated mainly by anthocyanin anabolism. However, it is unclear whether and which bZIP TFs are involved in this process. We identified 89 genes encoding CcbZIP TFs in Cinnamomum camphora genome that could be divided into 14 subfamilies with similar gene structures and conserved motifs. CcbZIP38 and CcbZIP57 were highly conserved compared to HY5 in Arabidopsis thaliana and they were highly expressed in the bark and leaves of 'Gantong 1' at different stages. The target gene enrichment analysis showed that indicating indirect involvement of CcbZIP38 and CcbZIP57 in the regulation of anthocyanin synthesis. Our study contributes to understanding the molecular mechanism of anthocyanin synthesis regulation by CcbZIP TFs and provides a theoretical basis for genetic improvement of ornamental traits in C. camphora.

Abstract The precise regulation of cellular behaviors within a confined, crowded intracellular environment is highly amenable in diagnostics and therapeutics. While synthetic circuitry system through a concatenated chemical reaction network has rarely been reported to mimic dynamic self‐assembly system. Herein, a catalytic self‐defined circuit (CSC) for the hierarchically concatenated assembly of DNA domino nanostructures is engineered. By incorporating pre‐sealed symmetrical fragments into the preying hairpin reactants, the CSC system allows the hierarchical DNA self‐assembly via a microRNA (miRNA)‐powered self‐sorting catalytic hybridization reaction. With minimal strand complexity, this self‐sustainable CSC system streamlined the circuit component and achieved localization‐intensified cascaded signal amplification. Profiting from the self‐adaptively concatenated hybridization reaction, a reliable and robust method has been achieved for discriminating carcinoma tissues from the corresponding para‐carcinoma tissues. The CSC‐sustained self‐assembly strategy provides a comprehensive and smart toolbox for organizing various hierarchical DNA nanostructures, which may facilitate more insights for clinical diagnosis and therapeutic assessment.

Abstract Background Given the limited success rate and considerable challenges associated with conventional ultrasonography (US) guidance for percutaneous nephrostomy (PCN) in non-hydronephrotic kidneys, this study proposed a solution with ultrasound contrast agent to enhance the success rate and mitigate the difficulties. Materials and Methods From January 2017 to August 2023, a total of thirteen patients diagnosed with non-hydronephrotic kidney were included in the study. Following routine ultrasonography examination, no significant dilatation of the renal collecting system was observed. US-guided percutaneous nephrostomy PCN was performed with the assistance of ultrasound contrast agent (UCA). The patients were subsequently monitored to assess the improvement of symptoms and postoperative recovery. Results The success rate was found to be 100% for all patients (13/13) and kidneys (20/20). The average volume of UCA solution used was 19 ± 6.7 mL (range, 11–35 mL), while the mean duration of the operation was 18.92 ± 8.96 min (range, 7–36 min). A majority of the patients (12/13) underwent a single puncture procedure. Throughout the follow-up period, no serious complications were observed, and surgery resulted in significant alleviation of symptoms in all patients. Conclusion The use of UCA-assisted US guidance PCN has been shown to be effective in achieving urinary diversion and alleviating associated clinical symptoms in non-hydronephrotic kidneys. In comparison to traditional methods, this approach demonstrates a high success rate and safety profile, while also offering a simplified operative procedure. Consequently, it presents a novel method and concept for managing non-hydronephrotic kidneys afflicted by urine leakage.

Abstract Our previous work has shown that d-ribose (RIB)-induced depressive-like behaviors in mice. However, the relationship between variations in RIB levels and depression as well as potential RIB participation in depressive disorder is yet unknown. Here, a reanalysis of metabonomics data from depressed patients and depression model rats is performed to clarify whether the increased RIB level is positively correlated with the severity of depression. Moreover, we characterize intestinal epithelial barrier damage, gut microbial composition and function, and microbiota-gut-brain metabolic signatures in RIB-fed mice using colonic histomorphology, 16 S rRNA gene sequencing, and untargeted metabolomics analysis. The results show that RIB caused intestinal epithelial barrier impairment and microbiota-gut-brain axis dysbiosis. These microbial and metabolic modules are consistently enriched in peripheral (fecal, colon wall, and serum) and central (hippocampus) glycerophospholipid metabolism. In addition, three differential genera (Lachnospiraceae_UCG-006, Turicibacter, and Akkermansia) and two types of glycerophospholipids (phosphatidylcholine and phosphatidylethanolamine) have greater contributions to the overall correlations between differential genera and glycerophospholipids. These findings suggest that the disturbances of gut microbiota by RIB may contribute to the onset of depressive-like behaviors via regulating glycerophospholipid metabolism, and providing new insight for understanding the function of microbiota-gut-brain axis in depression.

Abstract Background Clostridioides difficile is a bacterium that causes antibiotic-associated infectious diarrhea and pseudomembranous enterocolitis. The impact of C. difficile infection (CDI) in China has gained significant attention in recent years. However, little epidemiological data are available from Chongqing, a city located in Southwest China. This study aimed to investigate the epidemiological pattern of CDI and explore the drug resistance of C. difficile isolates in Chongqing. Methods A case-control study was conducted to investigate the clinical infection characteristics and susceptibility factors of C. difficile. The features of the C. difficile isolates were evaluated by testing for toxin genes and using multi-locus sequence typing (MLST). The susceptibility of strains to nine antibiotics was determined using agar dilution technique. Results Out of 2084 diarrhea patients, 90 were tested positive for the isolation of toxigenic C. difficile strains, resulting in a CDI prevalence rate of 4.32%. Tetracycline, cephalosporins, hepatobiliary disease, and gastrointestinal disorders were identified as independent risk factors for CDI incidence. The 90 strains were classified into 21 sequence types (ST), with ST3 being the most frequent (n = 25, 27.78%), followed by ST2 (n = 10, 11.11%) and ST37 (n = 9, 10%). Three different toxin types were identified: 69 (76.67%) were A+B+CDT−, 12 (13.33%) were A−B+CDT−, and 9 (10%) were A+B+CDT+. Although substantial resistance to erythromycin (73.33%), moxifloxacin (62.22%), and clindamycin (82.22%), none of the isolates exhibited resistance to vancomycin, tigecycline, or metronidazole. Furthermore, different toxin types displayed varying anti-microbial characteristics. Conclusions The strains identified in Chongqing, Southwest China, exhibited high genetic diversity. Enhance full awareness of high-risk patients with HA-CDI infection, particularly those with gastrointestinal and hepatocellular diseases, and emphasize caution in the use of tetracycline and capecitabine. These findings suggest that a potential epidemic of CDI may occur in the future, emphasizing the need for timely monitoring.

ABSTRACT Objective To assess the efficacy and safety of immunotherapy for LGI1 antibody encephalitis, and consider the predictors of poor outcomes following immunotherapy. Methods We searched PubMed and Embase for articles reporting the immunotherapy data of anti‐LGI1 encephalitis patients. The proportions of patients with poor outcomes (modified Rankin Scale [mRS] score > 2) at 3 months, 12 months, and the last follow‐up, as well as the odds ratio [OR] of predictors were pooled. Results The review included 162 articles with 1066 patients. The proportion of patients with poor functional outcomes was 21% at 3 months, 14% at 12 months, and 14% at the last follow‐up after receiving immunotherapy. The proportion of patients with reported relapse was 16.6%. The mean duration from onset to the first relapse was 15.6 months. Predictors significantly associated with poor outcomes were age (increase of 1 year), the presence of cognitive impairment, and CSF LGI1 antibody positive. We did not find a statistically significant association between the worst mRS score in the acute phase, the presence of faciobrachial dystonic seizures (FBDS), days from symptom onset to immunotherapy, second‐line treatment, maintenance immunotherapy, or follow‐up time and outcomes. Interpretation Although most patients respond to immunotherapy, a minority of patients still have poor outcomes. Advanced age, cognitive impairment, and CSF LGI1 antibody positive are associated with an increased risk of poor outcomes. However, due to the insufficiency of the data, these conclusions need to be interpreted with caution.

The coexistence of kaposiform hemangioendothelioma (KHE) and capillary malformation (CM) is quite rare, and few relevant studies can be found to confirm whether this phenomenon is accidental. We diagnosed and treated two such patients, revealing interesting phenomena associated with the development of vascular diseases.These cases offer the possibility that the coexistence of KHE and CM is not accidental and open up a new field of research related to pediatric vascular tumors and vascular malformations. Personalization and precision are required in the diagnosis and treatment of such patients, and the present findings provide a reliable theoretical and practical basis for further research on the pathogenesis and therapy of patients with multiple vascular diseases.

The objective of this work is to characterize the anticancer mechanism of platinum nanoparticles coated with polyethylene glycol and conjugated with Rutin (Rutin-PEG-PtNPs) in a breast cancer cell line. PtNPs were synthesized using Dendrobium officinale extract, coated with PEG, conjugated with Rutin, and characterized by the FT-IR, XRD, DLS, and TEM. The viability of the breast cancer cells (MCF-7) and normal breast cells (MCF-10A) after treatment with PEG-PtNPs and Rutin-PEG-PtNPs was studied by the MTT assay. Superoxide dismutase (SOD) and catalase (CAT) activity, MDA level, and LDH leakage in the PEG-PtNPs and Rutin-PEG-PtNPs were measured. The expression of the p53, Bax, Bcl-2, and caspase −8, and −9 genes, as well as the NF-κB and IL-6 levels in the Rutin-PEG-PtNPs treated cells, were investigated by qPCR and ELISA assays. Results demonstrated that the NPs were in a size range of 30 to 60 nm. The Rutin-PEG-PtNPs showed greater cytotoxic effects on breast cancer cells (IC50: 45.5 µg/mL) than normal breast cells (IC50: 69.4 µg/mL). The expression of the p53, Bax, caspase-8, and −9 was upregulated by 1.96, 1.84, 1.31, and 2.79 folds, while the expression of the Bcl-2 was reduced in Rutin-PEG-PtNP-treated cells. The activity of the SOD and CAT decreased, while the LDH leakage and MDA levels increased after treating the cells with Rutin-PEG-PtNPs. Also, the NF-κB and IL-6 levels in the cell cultures treated with Rutin-PEG-PtNPs were reduced by 22.6 and 17.0 %, respectively. Rutin-PEG-Pt indicated promising inhibitory potential against MCF-7 cells.

Isolates coproducing serine/metallo-carbapenems are a serious emerging public health threat, given their rapid dissemination and the limited number of treatment options. The purposes of this study were to evaluate the in vitro antibacterial activity of novel β-lactam-β-lactamase inhibitor combinations (BLBLIs) against carbapenem-resistant Klebsiella pneumoniae (CRKP) coproducing metallo-β-lactamase and serine-β-lactamase, and to explore their effects in combination with aztreonam, meropenem, or polymyxin in order to identify the best therapeutic options. Four CRKP isolates coproducing K. pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) were selected, and a microdilution broth method was used to determine their susceptibility to antibiotics. Time-kill assay was used to detect the bactericidal effects of the combinations of antibiotics. The minimum inhibitory concentration (MIC) values for imipenem and meropenem in three isolates did not decrease after the addition of relebactam or varbobactam, but the addition of avibactam to aztreonam reduced the MIC by more than 64-fold. Time-kill assay demonstrated that imipenem-cilastatin/relebactam (ICR) alone exerted a bacteriostatic effect against three isolates (average reduction: 1.88 log10 CFU/mL) and ICR combined with aztreonam exerted an additive effect. Aztreonam combined with meropenem/varbobactam (MEV) or ceftazidime/avibactam (CZA) showed synergistic effects, while the effect of aztreonam combined with CZA was inferior to that of MEV. Compared with the same concentration of aztreonam plus CZA combination, aztreonam/avibactam had a better bactericidal effect (24 h bacterial count reduction >3 log10CFU/mL). These data indicate that the combination of ATM with several new BLBLIs exerts powerful bactericidal activity, which suggests that these double β-lactam combinations might provide potential alternative treatments for infections caused by pathogens coproducing-serine/metallo-carbapenems.

Abstract Background Mitochondrial metabolism has been proposed as an attractive target for breast cancer therapy. The discovery of new mechanisms underlying mitochondrial dysfunction will facilitate the development of new metabolic inhibitors to improve the clinical treatment of breast cancer patients. DYNLT1 (Dynein Light Chain Tctex-Type 1) is a key component of the motor complex that transports cellular cargo along microtubules in the cell, but whether and how DYNLT1 affects mitochondrial metabolism and breast cancer has not been reported. Methods The expression levels of DYNLT1 were analyzed in clinical samples and a panel of cell lines. The role of DYNLT1 in breast cancer development was investigated using in vivo mouse models and in vitro cell assays, including CCK-8, plate cloning and transwell assay. The role of DYNLT1 in regulating mitochondrial metabolism in breast cancer development is examined by measuring mitochondrial membrane potential and ATP levels. To investigate the underlying molecular mechanism, many methods, including but not limited to Co-IP and ubiquitination assay were used. Results First, we found that DYNLT1 was upregulated in breast tumors, especially in ER + and TNBC subtypes. DYNLT1 promotes the proliferation, migration, invasion and mitochondrial metabolism in breast cancer cells in vitro and breast tumor development in vivo. DYNLT1 colocalizes with voltage-dependent anion channel 1 (VDAC1) on mitochondria to regulate key metabolic and energy functions. Mechanistically, DYNLT1 stabilizes the voltage-dependent anion channel 1 (VDAC1) by hindering E3 ligase Parkin-mediated VDAC1 ubiquitination and degradation. Conclusion Our data demonstrate that DYNLT1 promotes mitochondrial metabolism to fuel breast cancer development by inhibiting Parkin-mediated ubiquitination degradation of VDAC1. This study suggests that mitochondrial metabolism can be exploited by targeting the DYNLT1-Parkin-VDAC1 axis to improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC).

Abstract The study of thermoelectric behaviors in miniatured transistors is of fundamental importance for developing bottom-level thermal management. Recent experimental progress in nanothermetry has enabled studies of the microscopic temperature profiles of nanostructured metals, semiconductors, two-dimensional material, and molecular junctions. However, observations of thermoelectric (such as nonequilibrium Peltier and Thomson) effect in prevailing silicon (Si)—a critical step for on-chip refrigeration using Si itself—have not been addressed so far. Here, we carry out nanothermometric imaging of both electron temperature (T e) and lattice temperature (T L) of a Si nanoconstriction device and find obvious thermoelectric effect in the vicinity of the electron hotspots: When the electrical current passes through the nanoconstriction channel generating electron hotspots (with T e~1500 K being much higher than T L~320 K), prominent thermoelectric effect is directly visualized attributable to the extremely large electron temperature gradient (~1 K/nm). The quantitative measurement shows a distinctive third-power dependence of the observed thermoelectric on the electrical current, which is consistent with the theoretically predicted nonequilibrium thermoelectric effects. Our work suggests that the nonequilibrium hot carriers may be potentially utilized for enhancing the thermoelectric performance and therefore sheds new light on the nanoscale thermal management of post-Moore nanoelectronics.

In this study, Co/Cd-MOFs were synthesized via a solvothermal method. The resulting material was subjected to calcination at 900 °C for 2 h and characterized using FT-IR, XRD, and SEM techniques to assess its efficacy in moxifloxacin removal. The experimental findings revealed that the maximum adsorption capacity of Co/Cd-MOFs for moxifloxacin was observed at 350.4 mg/g within a 5 h timeframe. Furthermore, the analysis based on the pseudo-second-order kinetic model demonstrated that the adsorption process adhered to this specific model. Additionally, the adsorption isotherm analysis indicated that Freundlich multilayer adsorption provided the best description of the interaction between moxifloxacin and the Co/Cd-MOF material. These experimental and theoretical results collectively suggest that employing Co/Cd-MOFs as adsorbents holds promise for wastewater treatment applications.

To study the polarization reflection characteristics of metal surfaces, a parameter optimization method for the polarization bidirectional reflection distribution function (pBRDF) model of metal surfaces based on the improved strawberry algorithm has been proposed. Firstly, the light scattering characteristics of metal surfaces were analyzed and a multi-parameter pBRDF model was constructed. Then, the working mechanism of the strawberry optimization algorithm was investigated and improved by introducing the chaotic mapping and Levy flight strategy to overcome the shortcomings, such as low convergence rate and easily falling into local optimum. Finally, the method proposed in this paper was validated by simulating open-source data from references and the obtained ones with a self-built experimental platform. The results show that the proposed method outperforms those by nonlinear least squares, particle swarm optimization and the original strawberry algorithm in fitting the detected degree of polarization (DOP) data, indicating the modeling accuracy was significantly improved and better suited to characterize the polarized reflection properties of metal surfaces.

Infrared detection is more and more widely used in the field of non-destructive testing of buildings to detect whether there is a defect on the surface of the building facade. In many cases, it is necessary to obtain more information about the defect, such as the depth of the defect, so as to evaluate the severity of the defect and repair. The theoretical formula of hollowing defect depths was derived in this paper based on the heat transfer characteristics of the intact and defective areas on the building facade, and the influence of defects with different shapes, sizes and cavity thicknesses on the temperature distribution of the building facade was summarized quantitatively. Firstly, the theoretical formula of the hollowing defect depth and the factors affecting the distribution of the temperature gradient on the building facade excited by external thermal source was derived and restricted by the boundary condition. Secondly, three sets of physical building facade models that contained hollowing defects with different shapes, sizes and cavity thicknesses were fabricated and designed, and the experimental platform was built. The infrared thermograms and the temperature characteristic curves of the hollowing defect in a natural light environment were obtained and fitted according to the temperature differences of the defective area, while analyzing the influence of the size, shape and cavity thicknesses on surface temperature distribution. Finally, the theoretical formula of the defect depth that is applicable to the building façade was validated through the experimental simulation of 14 forms of hollowing. The experimental results demonstrated that the revised formula of defect depth is consistent with the actual defect depth, and the three-dimensional positioning of the hollowing defect of the building facade can be effectively carried out and combined with the defect size taken from the obtained infrared thermal image.

Abstract Coverings have an important impact on the output and safety of photovoltaic (PV) modules. However, due to the complex on-site environment and difficult identification, it is difficult to obtain timely and effective cleaning. In this paper, the optical polarization characteristics of fallen leaf are studied to find the difference for the PV modules with or without fallen leaves covered, which is one of the typical coverings, based on the basic theory of polarization imaging. Firstly, a polarimetric imaging platform with a SALSA camera for PV modules is built. Then, several experiments are conducted and the corresponding images of PV modules shaded by heather or camphor leaves are obtained. Finally, shaded by the impacts on the polarization characteristics of the PV module from fallen leaves, the waveband of the incident light, and the observation angle are analyzed. The results show that the optical polarization characteristics of PV modules at bands of 420 nm and 546 nm are significantly different from others, wherever there existed shading leaves or not; The degree of polarization decreases and then increases with the observation angle from 0° to 70° at 9:00–12:00 a.m. on sunny days; At 0° observation angle, the stokes parameter $$S_{0}$$ S 0 of PV modules with or without fallen leaves has the greatest difference. Highlights 1. The influence of fallen leaves on the polarization characteristics of PV modules is studied. 2. The polarization characteristic parameter with the largest difference between the PV modules with and without fallen leaves is obtained. 3. This parameter is more conducive to detecting fallen leaves on the surface of PV modules.

Abstract Objectives Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. Methods A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. Results Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. Conclusions We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

Abstract Background Autoimmune encephalitis (AE) is a group of severe antibody-mediated brain diseases. The understanding of clinical management of AE has developed rapidly. However, the knowledge level of AE and barriers to effective treatment among neurologists remains unstudied. Methods We conducted a questionnaire survey among neurologist in western China on knowledge of AE, treatment practices, and perspectives on barriers to treatment. Results A total of 1113 neurologists were invited and 690 neurologists from 103 hospitals completed the questionnaire with a response rate of 61.9%. Respondents correctly answered 68.3% of medical questions about AE. Some respondents (12.4%) never assayed for diagnostic antibodies if patients had suspected AE. Half (52.3%) never prescribed immunosuppressants for AE patients, while another 7.6% did not know whether they should do so. Neurologists who never prescribed immunosuppressants were more likely to have less education, a less senior job title, and to practice in a smaller setting. Neurologists who did not know whether to prescribe immunosuppressants were associated with less AE knowledge. The most frequent barrier to treatment, according to respondents, was financial cost. Other barriers to treatment included patient refusal, insufficient AE knowledge, lack of access to AE guidelines, drugs or diagnostic test, etc. Conclusion Neurologists in western China lack AE knowledge. Medical education around AE is urgent needed and should be more targeted to individuals with less educated level or working in non-academic hospitals. Policies should be developed to increase the availability of AE related antibody testing or drugs and reduce the economic burden of disease.

Abstract Background Glycyrrhizic acid (GA), a saponin compound often used as a flavoring agent, can elicit anti-inflammatory and anti-tumor effects, and alleviate aging. However, the specific mechanism by which GA alters immune cell populations to produce these beneficial effects is currently unclear. Results In this study, we systematically analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice. Our in vivo results show that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin−CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to S100 calcium-binding protein 8 (S100A8) protein. Overexpression of S100A8 in Lin− CD117+ hematopoietic stem cells enhanced cognition in aged mice and the immune reconstitution of severely immunodeficient B-NDG (NOD.CB17-Prkdcscid/l2rgtm1/Bcgen) mice. Conclusions Collectively, GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.

Abstract Background Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH. Methods Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo. Results PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo. Conclusions Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH.

Abstract Background Noninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV). Methods A retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV. Results In patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters. Conclusion SS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.

Abstract Background Coronary artery aneurysms (CAA) persistence prediction is critical in evaluating Kawasaki disease (KD). This study established a nomogram prediction system based on potential risk factors for assessing the risk of CAA persistence in a contemporary cohort of patients with KD. Methods This cohort comprised 105 patients with KD who had been diagnosed with CAA during the acute or subacute phase by echocardiography. The follow-up duration was at least 1 year. The clinical and laboratory parameters were compared between the CAA regression and persistence groups. Multivariable logistic regression analysis was used to identify the independent risk factors for CAA persistence, which were subsequently used to build the nomogram predictive model. Decision curve analysis was used to assess the net benefits of different nomogram scores. Results Of these patients with CAA, 27.6% of patients presented with persistent lesions. The incidences of CAA persistence were 14.1%, 81.3%, and 100.0% in patients with small, medium, and large aneurysms, respectively. The ratio of neutrophils to lymphocytes, γ-GT, and CAA size at diagnosis were considered as the independent risk factors for CAA persistence in patients with KD. The nomogram predictive models yielded a high capability in predicting CAA persistence, based on either univariable or multivariable analyses-identified parameters, compared with using CAA size as a single predictor. Conclusion The initial ratio of neutrophils to lymphocytes, γ-GT, and CAA size were the independent risk factors for CAA persistence in patients with KD. Nomogram scores could help elevate predictive efficacy in detecting CAA persistence.

Abstract Many complex systems involve interactions between more than two agents. Hypergraphs capture these higher-order interactions through hyperedges that may link more than two nodes. We consider the problem of embedding a hypergraph into low-dimensional Euclidean space so that most interactions are short-range. This embedding is relevant to many follow-on tasks, such as node reordering, clustering, and visualization. We focus on two spectral embedding algorithms customized to hypergraphs which recover linear and periodic structures respectively. In the periodic case, nodes are positioned on the unit circle. We show that the two spectral hypergraph embedding algorithms are associated with a new class of generative hypergraph models. These models generate hyperedges according to node positions in the embedded space and encourage short-range connections. They allow us to quantify the relative presence of periodic and linear structures in the data through maximum likelihood. They also improve the interpretability of node embedding and provide a metric for hyperedge prediction. We demonstrate the hypergraph embedding and follow-on tasks—including quantifying relative strength of structures, clustering and hyperedge prediction—on synthetic and real-world hypergraphs. We find that the hypergraph approach can outperform clustering algorithms that use only dyadic edges. We also compare several triadic edge prediction methods on high school and primary school contact hypergraphs where our algorithm improves upon benchmark methods when the amount of training data is limited.

Abstract Background Early diagnosis of medically intractable epilepsy is challenging in clinical work. P-glycoprotein (P-gp) is one of the most important multidrug efflux transporters, which has been demonstrated to contribute to the drug resistance of intractable epilepsy. The present study was aimed to explore the diagnostic value of microRNAs (miRNAs) targeting P-gp for medically intractable epilepsy. Methods Thirty-six patients with intractable epilepsy and 36 epilepsy patients responsive to anti-epilepsy drugs, who visited Jinshan Hospital of Fudan University from September 2014 to September 2016, were enrolled in this study. Clinical information of the patients was obtained by retrospectively reviewing medical records. MiRNAs with differential serum expression between the two groups of patients were detected by microarray assay. Meanwhile, miRNAs that were confirmed to regulate P-gp in vitro by western blot were selected for further validation. In the validation phase, reverse transcription quantitative PCR (RT-qPCR) was conducted to confirm the differential expression of the candidate miRNAs in the epilepsy cohorts. Receiver operating characteristic (ROC) curve analysis was carried out to evaluate the diagnostic value of the miRNAs for intractable epilepsy. Results Three miRNAs including miR-6514-3p, miR-6076-5p, and miR-6855-3p were identified to be candidate miRNAs by microarray assay. The results of western blotting validated that miR-146a-5p and miR-138-5p could regulate P-gp expression in vitro, so they were included in the candidate miRNAs for further validation. In the validation phase, the results of RT-qPCR indicated that compared with drug-responsive patients, the patients with intractable epilepsy showed decreased level of miR-138-5p and increased level of miR-146a-5p. The results of ROC curve analysis indicated that miR-138-5p (AUC = 0.877) and miR-146a-5p (AUC = 0.866) had high diagnostic value for intractable epilepsy. In addition, the miR-panel composed of miR-138-5p and miR-146a-5p showed higher diagnostic value (AUC = 0.926) than the miRNAs selected by microarray assay. Conclusions Our results indicated that the dysregulated miR-138-5p and miR-146a-5p which target P-gp expression have high potential as peripheral biomarkers for medically intractable epilepsy.

Objective To investigate the tolerance and efficacy of HIFU ablation for uterine fibroids with a non-perfused volume ratio (NPVR) ≥ 90%.Methods A prospective cohort study of 2411 patients from 20 clinical centers was available. Contrast-enhanced MRI was used to assess the non-perfused volume ratio (NPVR). The International Society of Interventional Radiotherapy (SIR) complication grading system was used as the tolerance index. Uterine Fibroids-related Symptoms-Quality of Life (UFS-QoL) was used to evaluate the efficacy.Results A total of 1352 patients underwent USgHIFU ablation treatment enrolled, NPVR was median 91.9% (IQR, 81.4%,100.0%). There was 761 case (56.3%) in the NPVR ≥ 90% group in which 17.5% case experienced SIR-B abdominal pain, 591 cases (43.7%) in NPVR < 90% group in which 9.3% case had SIR-B abdominal pain. There were statistically differences in the improvement degree of UFS at 12 months among the four subgroups (NPVR < 70%, 70%–80%, 80%–90%, 90%–100%) (all p

In this paper, we investigate the stability of highly nonlinear hybrid neutral pantograph stochastic differential equations (NPSDEs) with general decay rate. By applying the method of the Lyapunov function, the pth moment and almost sure stability with general decay rate of solution for NPSDEs are derived. Finally, an example is presented to show the effectiveness of the proposed methods.

Abstract Background Has the medical arms race (MAR) increased healthcare expenditures? Existing literature has yet to draw a consistent conclusion. Hence, this study aims to reexamine the relationship between the MAR and medical expenses by the data from public hospitals in Shenzhen, China, during the period of 2009 to 2013. Methods This study’s data were collected through panel datasets spanning 2009 to 2013 from the Shenzhen Statistical Yearbook, Shenzhen Health Statistical Yearbook, and annual reports from the Shenzhen Municipal Health Commission. The Herfindahl–Hirschman index and hierarchical linear modeling were combined for empirical analysis. Results The MAR’s impact on medical examination fees differed during the inpatient and outpatient stages. Further analysis verified that the MAR had the most significant impact on outpatient examination fees. Due to the characteristics of China’s medical system, government regulations in the healthcare market may consequently accelerate the MAR among public hospitals. Strict government regulations on the medical system have also promoted increased medical examination costs to some extent. Once medical service prices are under strict administrative control, only drug and medical examination fees are the primary forms of extra income for hospitals. After the proportion of drug fees is further regulated, medical examinations will then become another staple method to generate extra revenue. These have distorted Chinese public hospitals’ medical fees, which completely differ from those in other countries. Conclusion The government should confirm that they have allocated sufficient financial investments for public hospitals; otherwise, the competition among hospitals will transfer the burden to patients, and especially to those who can afford to pay for care. A core task for public hospitals involves providing safer, less expensive, and more reliable medical services.

A photovoltaic cell defect polarization imaging small target detection method based on improved YOLOv7 is proposed to address the problem of low detection accuracy caused by insufficient feature extraction ability in the process of small target defect detection. Firstly, polarization imaging technology is introduced, using polarization degree images as inputs to enhance the edge contour information of YOLOv7 for detecting small targets; then, the COT self-attention mechanism is added to reconstruct the SPPCSPC module to improve YOLOv7’s ability to capture and fuse small target features in complex backgrounds; next, the normalized Wasserstein distance (NWD) is used to replace the traditional loss function based on intersection over union (IoU) metric, reducing the boundary offset between the prior box and the closest real target box in the prediction process of the object detection model and reducing the sensitivity of the YOLOv7 network to small object position deviations; finally, by constructing a shortwave infrared polarization imaging system to obtain polarization images of photovoltaic cells and detect small targets with scratch defects in photovoltaic cells, the applicability and effectiveness of the proposed method are verified. The results show that the proposed method has good recognition ability for small target defects in photovoltaic cells. By applying the constructed dataset, the detection accuracy reaches 98.08%, the recall rate reaches 95.06% and the mAP reaches 98.83%.

This study evaluated the effects of four highland barley proteins (HBPs), namely, albumin, globulin, gliadin and glutenin, on the short-term retrogradation of highland barley starch (HBS). The findings reveal that HBPs could reduce the viscosity, storage modulus and hardness of HBS, with albumin and globulin showing more prominent effects. Furthermore, with the addition of HBPs, the loss tangent (tan δ) of HBS loss increased from 0.07 to 0.10, and the enthalpy of gelatinization decreased from 8.33 to 7.23. The degree of retrogradation (DR%) of HBS was 5.57%, and the DR% decreased by 26.65%, 38.78%, 11.67% and 20.29% with the addition of albumin, globulin, gliadin and glutenin, respectively. Moreover, the relative crystallinity (RC) and the double helix structures were inhibited with the HBPs’ incorporation. Meanwhile, the HBPs also could inhibit water migration and improve the structure of HBS gels. In summary, HBPs could inhibit the retrogradation behavior of HBS, which provides new theoretical insights for the production studies of highland barley foods.

Abstract Background Consultation length, the time a health provider spend with the patient during a consultation, is a crucial aspect of patient-physician interaction. Prior studies that assessed the relationship between consultation length and quality of care were mainly based on offline visits. Research was lacking in E-consults settings, an emerging modality for primary health care. This study aims to examine the association between consultation length and the quality of E-consults services. Methods We defined as standardized patient script to present classic urticaria symptoms in asynchronous E-consults at tertiary public hospitals in Beijing and Hangzhou, China. We appraised consultation length using six indicators, time waiting for first response, time waiting for each response, time for consultation, total times of provider’s responses, total words of provider’s all responses, and average words of provider’s each response. We appraised E-consults services quality using five indicators building on China’s clinical guidelines (adherence to checklist; accurate diagnosis; appropriate prescription; providing lifestyle modification advice; and patient satisfaction). We performed ordinary least squares (OLS) regressions and logistic regressions to investigate the association between each indictor of consultation length and E-consults services quality. Results Providers who responded more quickly were more likely to provide lifestyle modification advice and achieve better patient satisfaction, without compromising process, diagnosis, and prescribing quality; Providers who spent more time with patients were likely to adhere to clinical checklists; Providers with more times and words of responses were significantly more likely to adhere to the clinical checklist, provide an accurate diagnosis, appropriate prescription, and lifestyle modification advice, which achieved better satisfaction rate from the patient as well. Conclusions The times and words that health providers provide in E-consult can serve as a proxy measure for quality of care. It is essential and urgent to establish rules to regulate the consultation length for Direct-to-consumer telemedicine to ensure adequate patient-provider interaction and improve service quality to promote digital health better.

IntroductionKaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly with a poor prognosis. There is no standard treatment, and drug therapies are the most common therapeutic method. However, some patients' symptoms become gradually aggravated despite medical treatment. Splenectomy may be an alternative option when pharmacological therapies are ineffective.Materials and MethodsWe reviewed and evaluated the cases of 3 patients with KLA who ultimately underwent splenectomy. Results: The lesions were diffusely distributed and involved the lungs and spleens of the 3 patients. Laboratory examinations revealed that all three patients had thrombocytopenia and reduced fibrinogen levels. All patients underwent symptomatic splenectomy after the medication failed. Surprisingly, their symptoms greatly improved. Histopathological investigation of the splenic lesions of the three patients confirmed the diagnosis of KLA. Immunohistochemical staining showed positivity for CD31, CD34, podoplanin, Prox-1 and angiopoietin 2 (Ang-2).DiscussionThis study aimed to review the features of KLA patients treated by splenectomy and explore the underlying link between splenectomy and prognosis. The reason for the improvement after splenectomy may be related to increased Ang-2 levels and platelet activation in patients with KLA. Future research should seek to develop more targeted drugs based on molecular findings, which may give new hope for the treatment of KLA.

Abstract Background Acute respiratory distress syndrome (ARDS) causes significant mortality in young children with certain diseases. Early diagnosis and treatment can reduce infant mortality. Here, we report a rare case of exome sequencing in the early diagnosis of immunodeficiency in an infant. Case presentation A four-month-old full-term male infant presented with severe shortness of breath, hypoxemia, and unexplained parenchymal lung lesions. A series of examinations were performed to search for potential culprit viruses but negative results were obtained with the only exception being the rhinovirus that tested positive. The child’s family history revealed he had a brother who died of severe infection at the age of two years. We performed an exome sequencing analysis and a mutation analysis of CD40LG to obtain genetic data on the patient. Besides, we used flow cytometry to measure the CD40LG expression levels of activated T cells. A retrospective review of all the CD40LG mutant-induced X-linked hyper IgM syndromes (XHIGM) had been conducted to assess the differences between clinical and genetic molecular features. Finally, a regular intravenous immunoglobulin (IVIG) regimen led to steady breathing, the correction of hypoxemia, and a progressive improvement of lung CT scans. During follow-up, the patient received an IVIG regimen and his CT images improved. Moreover, his parents took advantage of pre-implantation genetic testing with in vitro fertilization to have a healthy twin offspring who did not carry such a mutation according to the early exome sequencing for the proband. Compared with other CD40LG mutant cases in our center, this proband displayed a normal plasma immunoglobulin level and he should be the youngest infant to have a molecular diagnosis of XHIGM. Conclusion Usually, XHIGM would not be suspected with a normal plasma immunoglobulin concentration. However, as we could not identify a potential comorbidity or risk factor, exome sequencing helps target this patient's real facts. Thus, this case report calls for exome sequencing to be performed in the case of unexplained infections when immunodeficiency is suspected after general immunological tests, especially for cases with a contributive family history among infants as the maternal transfused immunoglobulin might mask immune deficiency.

Abstract This study investigates the predictability of a fixed uncertainty index (UI) for realized variances (volatility) in the international stock markets from a high-frequency perspective. We construct a composite UI based on the scaled principal component analysis (s-PCA) method and demonstrate that it exhibits significant in- and out-of-sample predictabilities for realized variances in global stock markets. This predictive power is more powerful than those of two commonly employed competing methods, namely, PCA and the partial least squares (PLS) methods. The result is robust in several checks. Further, we explain that s-PCA outperforms other dimension-reduction methods since it can effectively increase the impacts of strong predictors and decrease those of weak factors. The implications of this research are significant for investors who allocate assets globally.

AIM: To assess the changes in the peripapillary vasculature and macular thickness after cataract surgery using two phacoemulsification systems with optical coherence tomography angiography (OCTA). METHODS: Fifty-two eyes of 52 patients with age-related cataract were randomized into two groups for phacoemulsification: Infiniti group (26 patients) using the Infiniti phacoemulsification system with gravity-fluidics and Centurion group (26 patients) using the Centurion phacoemulsification system with active-fluidics. The peripapillary vessel density (PVD) and macular thickness were examined using OCTA at baseline and at 1d, 1 and 3mo after cataract surgery. RESULTS: In the Infiniti group, the PVD was significantly reduced at 1d after the cataract surgery (P0.05). In the Centurion group, the VD and thickness in the optic papilla and macula did not significantly change in all regions during the follow-up (all P>0.05). The best-corrected visual acuity (BCVA) significantly improved in both groups postoperatively (P