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Abstract This study aimed to investigate the association between serum chloride levels and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were extracted for analysis. Demographic information, laboratory results, medical histories, vital signs, and prognosis-related data were collected. Cox proportional hazard models were used to assess the relationship between serum chloride levels and 90-day and 365-day mortality. Subgroup analyses were conducted to explore potential interactions between serum chloride levels and various factors. The study included patients with a median age of 72.00 years, of whom 52.39% were male. Higher quartiles of serum chloride levels were associated with significantly lower levels of weight, RBC, platelet, hemoglobin, and other variables (P

Abstract The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia.

Abstract Background Accurate measurement of hemoglobin concentration is essential for various medical scenarios, including preoperative evaluations and determining blood loss. Traditional invasive methods are inconvenient and not suitable for rapid, point-of-care testing. Moreover, current models, due to their complex parameters, are not well-suited for mobile medical settings, which limits the ability to conduct frequent and rapid testing. This study aims to introduce a novel, compact, and efficient system that leverages deep learning and smartphone technology to accurately estimate hemoglobin levels, thereby facilitating rapid and accessible medical assessments. Methods The study employed a smartphone application to capture images of the eye, which were subsequently analyzed by a deep neural network trained on data from invasive blood test data. Specifically, the EGE-Unet model was utilized for eyelid segmentation, while the DHA(C3AE) model was employed for hemoglobin level prediction. The performance of the EGE-Unet was evaluated using statistical metrics including mean intersection over union (MIOU), F1 Score, accuracy, specificity, and sensitivity. The DHA(C3AE) model’s performance was assessed using mean absolute error (MAE), mean-square error (MSE), root mean square error (RMSE), and R^2. Results The EGE-Unet model demonstrated robust performance in eyelid segmentation, achieving an MIOU of 0.78, an F1 Score of 0.87, an accuracy of 0.97, a specificity of 0.98, and a sensitivity of 0.86. The DHA(C3AE) model for hemoglobin level prediction yielded promising outcomes with an MAE of 1.34, an MSE of 2.85, an RMSE of 1.69, and an R^2 of 0.34. The overall size of the model is modest at 1.08 M, with a computational complexity of 0.12 FLOPs (G). Conclusions This system presents a groundbreaking approach that eliminates the need for supplementary devices, providing a cost-effective, swift, and accurate method for healthcare professionals to enhance treatment planning and improve patient care in perioperative environments. The proposed system has the potential to enable frequent and rapid testing of hemoglobin levels, which can be particularly beneficial in mobile medical settings. Trial Registration The clinical trial was registered on the Chinese Clinical Trial Registry (No. ChiCTR2100044138) on 20/02/2021.

Abstract Composed of obesity and lipid parameters, the cardiometabolic index (CMI) has emerged as a novel diagnostic tool. Originally developed for diabetes diagnosis, its application has expanded to identifying patients with cardiovascular diseases, such as atherosclerosis and hypertension. However, the relationship between CMI and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in the US population remains unclear. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020, involving 2996 participants aged 20 years or older. Vibration controlled transient elastography using a FibroScan® system (model 502, V2 Touch) with controlled attenuation parameter measurements identified NAFLD at a threshold of ≥ 274 dB/m, while liver stiffness measurement (LSM) results (median, ≥ 8.2 kPa) indicated fibrosis. A multifactorial logistic regression model explored the relationship between CMI and NAFLD and fibrosis. The effectiveness of CMI in detecting NAFLD and liver fibrosis was assessed through receiver operating characteristic curve analysis. Controlling for potential confounders, CMI showed a significant positive association with NAFLD (adjusted OR = 1.44, 95% CI 1.44–1.45) and liver fibrosis (adjusted OR = 1.84, 95% CI 1.84–1.85). The Areas Under the Curve for predicting NAFLD and fibrosis were 0.762 (95% CI 0.745 ~ 0.779) and 0.664(95% CI 0.633 ~ 0.696), respectively, with optimal cut-off values of 0.462 and 0.527. There is a positive correlation between CMI and NAFLD and fibrosis, which is a suitable and simple predictor of NAFLD and fibrosis.

Abstract Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

Abstract There are few studies on the relationship between dietary habits and asthma–COPD overlap (ACO). In this study, we aimed to investigate the association between dietary inflammation index (DII) score and ACO. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. The DII score was first calculated and the demographic characteristics of the grouping based on the DII quartile were assessed. The weighted logistic regression model was used to study the relationship between DII and ACO. Subgroup analysis was used to further explore the differences in different subgroups. Restricted cubic spline (RCS) plot was used to show the general trend of DII score and disease risk, and threshold effect analysis was used to determine the inflection point. In a comparison of baseline characteristics, the highest ACO prevalence was found in the fourth quartile array of people in DII. An adjusted weighted logistic regression model showed that DII was positively correlated with the incidence of ACO. Subgroup analysis showed that the association was more pronounced in women, non-Hispanics, people with cardiovascular disease, and people without diabetes. The RCS graph shows that overall, the risk of ACO increases with the increase of DII score. Threshold effect analysis showed that the inflection point was 3.779, and the risk was more significant after the DII score was greater than the inflection point value (OR 2.001, 95% CI 1.334–3.001, P

By reviewing the relevant literature in the field of T cell and allergic rhinitis, we determined the development status, study hotspots, and research frontiers viewpoints of this field to provide a reference for researchers and clinical workers. Methods: Web of Science Core Collection (WoSCC) was applied to obtain the studies related to T cells and allergic rhinitis (AR) from 2003 to 2023, and the information extracted from these studies was analyzed using CiteSpace 6.1.R6 and VOSviewer 1.6.18. Results: In total, 1585 articles were collected from WoSCC, with the time set between 2003 and 2023. Overall, a growing number of articles are being published annually. The countries and institutions with the maximum publications volume are China (370, 23.34 %) and Sun Yat-sen University (34, 2.15 %). The biggest contributor to the field was Durham, Stephen R. from the UK (22, 1.39 %). The Journal of Allergy and Clinical Immunology published the most related papers in the field (88, 5.54 %). Immunotherapy, Th cells, and inflammation were found to be the research hotspots in this area of T cells and allergic rhinitis in recent years. Pathway, model, Regulatory T cells (Treg cells), regulatory B cells, immunoglobulin E,and innate lymphoid cells were the current research hotspots in this field. Conclusion: The field of T cell and allergic rhinitis is developing rapidly, and many countries significantly contributed to this field. Most researchers in this field mainly focused on immunotherapy, Th cell, and inflammation. Pathway, model, Treg cell, regulatory B cell, immunoglobulin E,and innate lymphoid cells were the main subject of current research, and future development is expected to occur in this field.

The blood–brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

Background: Fructus cannabis (Hemp seed), the dried and mature fruit of Cannabis sativa L., was reported to have effects against Alzheimer's disease (AD) in different experimental models. However, either chemical composition or mechanisms of action was not clear. Our previous work isolated and identified diverse phenylpropionamides such as cannabisin A-F, caffeoyltyramine and feryroyltyramine from hemp seed, which showed antioxidant and anti-neuroinflammatory activity in cell models. Purpose: To study the anti-AD effect and mechanism of the total phenylpropionamides (TPA) extract from hemp seed using APPswe/PS1dE9 mice model. Methods: TPA extract was prepared via extraction and column chromatography techniques, then analyzed and measured using HPLC, HPLC-MS and Folin-Ciocalteu method. The extract was administered by gavage to APPswe/PS1dE9 mice. The learning memory ability of mice were examined using new object recognition test and Morris water maze. Hematoxylin and Eosin staining was used to observe the morphology of neuronal cells in the hippocampal region of brain tissue; ELISA was used to measure the content of IL-1β, TNF-α, IL-6, superoxide dismutase (SOD), malondialdehyde (MDA) in the brain tissue; the deposition of Aβ protein was measured by immunohistochemistry and Western blotting; the activation of microglia was measured by immunofluorescence. The expression of APP, PS1, SIRT1, and ADAM10 proteins was measured by Western blotting. Results: Folin-Ciocalteu method showed the total phenylpropionamides content was 238.03 μg caffeic acid equivalent /mg TPA. HPLC and HPLC-MS analysis showed the contents of N-trans-caffeoyltyramine, cannabisin A and B were 20.16 μg/mg, 32.16 μg/mg and 214.35 μg/mg, respectively, in TPA extract. TPA treatment significantly increased the survival rate of APP/PS1 mice, improved the learning and memory ability, reversed the neural cell damage in the hippocampal region, and reduced Aβ deposition and activated microglia in brain tissue. Meanwhile, the administration decreased the neuroinflammatory factors TNF-α, IL-6, IL-1β expression, increased antioxidant enzyme SOD activity, and attenuated MDA expression. Western blotting showed that TPA administration increased SIRT1 and ADAM10 protein expression and decreased APP and PS1 protein expression. Conclusion: TPA improved learning memory capacity, increased survival rate, attenuated neuroinflammation, oxidative stress, microglia activation and hippocampal apoptosis, and reduced amyloid deposition via the SIRT1-ADAM10 pathway in APP/PS1 mice.

BackgroundGrip strength has been shown to be associated with chronic renal insufficiency, but the relationship between grip strength and albuminuria has not been confirmed. In this study, we used NHANES data to explore the association between grip strength and albuminuria in a US population.MethodsIn this analytical study, we utilized data sourced from the National Health and Nutrition Examination Survey (NHANES), specifically spanning the years 2011 to 2014. The dataset included 9,638 participants aged 20 years or older. After adjusting for potential confounders, multiple regression models were developed to infer the interrelationship between grip strength and albumin to creatinine ratio (ACR), and subgroup analyses were conducted.ResultsAfter adjusting for all covariates, ACR by 0.49 mg/g [−0.49 (95% CI: −0.93, −0.04)] for each 1 kg increase in grip strength decreased. Subgroup analysis showed that gender, age, hyperlipidemia, hypertension, diabetes mellitus, smoking, alcohol consumption and body mass index did not influence the negative correlation between grip strength and albuminuria.ConclusionThere is a negative correlation between grip strength and albuminuria in the general U.S. population.

With a shortage of organs for transplant, the use of marginal donors can be an effective measure to meet the shortfall. Myelodysplastic syndromes (MDS) are considered an absolute contraindication for organ donation because of the high invasive potential. Currently, organ transplantation from donors with a past history of MDS has not been reported. In this paper, we report the successful clinical experience of one liver transplantation and two kidney transplantations, with organs donated by a 39-year-old patient diagnosed with a past history of MDS following intracranial hemorrhage. Four and a half years after transplantation, the three recipients are all doing well. However, it is still not clear to what extent organs donated by patients with a past history of MDS can be safely transplanted. This report provides support for the careful use of marginal donors. With effective treatment and full peer assessment, livers and kidneys from donors with a past history of MDS may be safely transplanted.

The sudden outbreak of coronavirus disease 2019 (COVID-19) in early 2020 posed a massive threat to human life and caused an economic upheaval worldwide. Kidney transplant recipients (KTRs) became susceptible to infection during the COVID-19 pandemic owing to their use of immunosuppressants, resulting in increased hospitalization and mortality rates. Although the current epidemic situation is alleviated, the long-term existence of COVID-19 still seriously threatens the life and health of KTRs with low immunity. The Omicron variant, a highly infectious but less-pathogenic strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns among transplant physicians regarding managing KTRs diagnosed with this variant. However, currently, there are no clear and unified guidelines for caring for KTRs infected with this variant. Therefore, we aimed to summarize the ongoing research on drugs that can treat Omicron variant infections in KTRs and explore the potential of adjusting immunotherapy strategies to enhance their responsiveness to vaccines. Herein, we discuss the situation of KTRs since the emergence of COVID-19 and focus on various prevention and treatment strategies for KTRs since the Omicron variant outbreak. We hope to assist physicians in managing KTRs in the presence of long-term COVID-19 variants.

Prostatic cancer (PCa) is a common malignant neoplasm in men worldwide. Most patients develop castration-resistant prostate cancer (CRPC) after treatment with androgen deprivation therapy (ADT), usually resulting in death. Therefore, investigating new therapeutic targets and drugs for PCa patients is urgently needed. Nuclear Dbf2-related kinase 1 (NDR1), also known as STK38, is a serine/threonine kinase in the NDR/LATS kinase family that plays a critical role in cellular processes, including immunity, inflammation, metastasis, and tumorigenesis. It was reported that NDR1 inhibited the metastasis of prostate cancer cells by suppressing epithelial-mesenchymal transition (EMT), and decreased NDR1 expression might lead to a poorer prognosis, suggesting the enormous potential of NDR1 in antitumorigenesis. In this study, we characterized a small-molecule agonist named aNDR1, which specifically bound to NDR1 and potently promoted NDR1 expression, enzymatic activity and phosphorylation. aNDR1 exhibited drug-like properties, such as favorable stability, plasma protein binding capacity, cell membrane permeability, and PCa cell-specific inhibition, while having no obvious effect on normal prostate cells. Meanwhile, aNDR1 exhibited good antitumor activity both in vitro and in vivo. aNDR1 inhibited proliferation and migration of PCa cells and promoted apoptosis of PCa cells in vitro. We further found that aNDR1 inhibited subcutaneous tumors and lung metastatic nodules in vivo, with no obvious toxicity to the body. In summary, our study presents a potential small-molecule lead compound that targets NDR1 for clinical therapy of PCa patients.

Abstract Introduction Generative pretrained transformer-4 (GPT-4) has gained widespread attention from society, and its potential has been extensively evaluated in many areas. However, investigation of GPT-4’s use in medicine, especially in the ophthalmology field, is still limited. This study aims to evaluate GPT-4’s capability to identify rare ophthalmic diseases in three simulated scenarios for different end-users, including patients, family physicians, and junior ophthalmologists. Methods We selected ten treatable rare ophthalmic disease cases from the publicly available EyeRounds service. We gradually increased the amount of information fed into GPT-4 to simulate the scenarios of patient, family physician, and junior ophthalmologist using GPT-4. GPT-4’s responses were evaluated from two aspects: suitability (appropriate or inappropriate) and accuracy (right or wrong) by senior ophthalmologists (> 10 years’ experiences). Results Among the 30 responses, 83.3% were considered "appropriate" by senior ophthalmologists. In the scenarios of simulated patient, family physician, and junior ophthalmologist, seven (70%), ten (100%), and eight (80%) responses were graded as “appropriate” by senior ophthalmologists. However, compared to the ground truth, GPT-4 could only output several possible diseases generally without “right” responses in the simulated patient scenarios. In contrast, in the simulated family physician scenario, 50% of GPT-4's responses were “right,” and in the simulated junior ophthalmologist scenario, the model achieved a higher “right” rate of 90%. Conclusion To our knowledge, this is the first proof-of-concept study that evaluates GPT-4’s capacity to identify rare eye diseases in simulated scenarios involving patients, family physicians, and junior ophthalmologists. The results indicate that GPT-4 has the potential to serve as a consultation assisting tool for patients and family physicians to receive referral suggestions and an assisting tool for junior ophthalmologists to diagnose rare eye diseases. However, it is important to approach GPT-4 with caution and acknowledge the need for verification and careful referrals in clinical settings.

The stainless steel/aluminum multilayer composites were prepared by one-step explosive welding using ammonium nitrate explosive with two different thicknesses. The microstructure and mechanical properties of the multilayer composites were examined. There is a thin metallurgical melting zone at each bonding interface, consisting mostly of iron and aluminum elements. However, the micro-crack appears in the second metallurgical bonding zone obtained using the explosive of 24 mm thickness. The micro-hardness values at the four bonding interfaces are higher than those of bulk 1060 aluminum and 304 stainless steel. The yield strength of the multilayer composites obtained in the two cases is higher than that of the original 304 stainless steel while the tensile strength is between those of the original 1060 aluminum and 304 stainless steel. Meanwhile, the tensile strength and yield strength of multilayer composites obtained by explosive welding with explosive of 20 mm thickness are relatively higher.

Abstract Background Contrast staining (CS) on dual-energy CT (DECT) is common after endovascular therapy (EVT) in acute ischemic stroke (AIS). We performed a meta-analysis to investigate the prognostic significance of CS detected by DECT after EVT in AIS. Method MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Scopus databases were searched from inception to July 2023 for publications on the prognostic significance of CS on DECT after EVT in patients with AIS. Prognostic outcomes were hemorrhage transformation (HT) and poor functional outcome (modified Rankin Scale [mRS] Score of 3–6 at the 90-day follow-up). Data are presented as odds ratios (OR) and 95% confidence intervals (CI). Results Eleven studies including 1123 cases of AIS were included. Pooled results indicated a higher risk of HT in patients with CS than in those without CS (OR = 2.22; 95% CI 1.41–3.51, P = 0.001; I 2 = 45.4%). No association between CS and symptomatic HT was observed (OR = 2.10; 95% CI 0.64–6.95, P = 0.223; I 2 = 67.3%). Moreover, there was also higher odds of poor functional outcome in patients with CS than in those without CS (OR = 2.76; 95% CI 1.53–4.97, P = 0.001; I 2 = 44.9%). Conclusions The presence of contrast staining on DECT after EVT is associated with a higher risk of hemorrhage transformation and poor functional outcome. However, further high-quality studies with standardized processes are required to confirm these results.

Background: In computer vision, simultaneously estimating human pose, shape, and clothing is a practical issue in real life, but remains a challenging task owing to the variety of clothing, complexity of deformation, shortage of large-scale datasets, and difficulty in estimating clothing style. Methods: We propose a multistage weakly supervised method that makes full use of data with less labeled information for learning to estimate human body shape, pose, and clothing deformation. In the first stage, the SMPL human-body model parameters were regressed using the multi-view 2D key points of the human body. Using multi-view information as weakly supervised information can avoid the deep ambiguity problem of a single view, obtain a more accurate human posture, and access supervisory information easily. In the second stage, clothing is represented by a PCAbased model that uses two-dimensional key points of clothing as supervised information to regress the parameters. In the third stage, we predefine an embedding graph for each type of clothing to describe the deformation. Then, the mask information of the clothing is used to further adjust the deformation of the clothing. To facilitate training, we constructed a multi-view synthetic dataset that included BCNet and SURREAL. Results: The Experiments show that the accuracy of our method reaches the same level as that of SOTA methods using strong supervision information while only using weakly supervised information. Because this study uses only weakly supervised information, which is much easier to obtain, it has the advantage of utilizing existing data as training data. Experiments on the DeepFashion2 dataset show that our method can make full use of the existing weak supervision information for fine-tuning on a dataset with little supervision information, compared with the strong supervision information that cannot be trained or adjusted owing to the lack of exact annotation information. Conclusions: Our weak supervision method can accurately estimate human body size, pose, and several common types of clothing and overcome the issues of the current shortage of clothing data.

Solid polymer electrolytes (SPEs) are the key components of lithium metal batteries to overcome the obstacle of insecurity in conventional liquid electrolytes; however, the trade-off between their ionic conductivity and mechanical properties remains a significant challenge. In this work, two-dimensional ZSM-5 nanosheets as fillers are incorporated into a poly(ethylene oxide) (PEO) matrix and lithium salts to obtain composite polymer electrolytes (CPEs). The improved physicochemical and electrochemical properties of the CPE membranes are characterized in full detail. Stripping/plating measurements in symmetric Li/Li cells and cyclic charge/discharge tests are performed to investigate the cyclability and stability of the CPEs. All-solid-state LiFePO4/Li batteries deliver excellent cycling performance with an initial discharge capacity of 152.3 mAh g−1 and 91.4% capacity retention after 200 cycles at 0.2 C, with a discharge specific capacity of 118.8 mAh g−1 remaining after 350 cycles at 0.5 C. Therefore, CPEs containing ZSM-5 nanosheets are a promising option for all-solid-state lithium-ion batteries.

AbstractTo detect the value of serum interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) at different disease stages. 141 RA patients were randomly obtained and diagnosed in a large tertiary first-class hospital in Jiangxi Province from November 2021 to January 2022. RA was divided into 38 low activity and remission phase (low remission patients), 72 moderate activity patients, 41 high activity patients, according to the disease activity score 28 (DAS28) of RA and 70 healthy controls. IL-17 and TNF-α in serum detected by flow cytometry; DKK-1by ELISA; rheumatoid factor (RF) and C-reactive protein (CRP) by rate scattering turbidimetry; erythrocyte sedimentation rate (ESR) by Widmanstat method; anti-cyclic citrullinated polypeptide antibody (Anti-CCP) by chemiluminescence. The changes among the groups were statistically analysed and evaluated their diagnostic value. ①Anti-CCP, CRP, and ESR levels in the moderate-to-high activity group were higher than controls, while IL-17, TNF-α, and DKK-1levels higher than low remission group, moderate activity group and controls (p

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

ABSTRACTHIV-1 infection is mediated by a viral envelope subsequently binding to CD4 receptor and two main coreceptors, CCR5 (R5) for primary infection and CXCR4 (X4) in chronic infection. Switching from R5 to X4 tropism in HIV-1 infection is associated with increased viral pathogenesis and disease progression. The coreceptor switching is mainly due to variations in the V3 loop, while the mechanism needs to be further elucidated. We systematically studied the determinant for HIV-1 coreceptor switching by substitution of the genes from one R5 and one X4 pseudoviruses. The study results in successfully constructing two panels of chimeric viruses of R5 to X4 forward and X4 to R5 reverse switching. The determinants for tropism switching are the combined substitution of the V3 loop and C4 region of the HIV-1 envelope. The possible mechanism of the tropism switching includes two components, the V3 loop to enable the viral envelope binding to the newly switched coreceptor and the C4 region, to compensate for the loss of fitness caused by deleterious V3 loop mutations to maintain the overall viral viability. The combined C4 and V3 substitution showed at least an eightfold increase in replication activity compared with the pseudovirus with only V3 loop substitution. The site-directed mutations of N425R and S440-I442 with charged amino acids could especially increase viral activity. This study could facilitate HIV-1 phenotype surveillance and select right entry inhibitor, CCR5 or CXCR4 antagonists, for antiviral therapy.

Summary: The blood-brain barrier (BBB) is primarily manifested by a variety of physiological properties of brain endothelial cells (ECs), but the molecular foundation for these properties remains incompletely clear. Here, we generate a comprehensive molecular atlas of adult brain ECs using acutely purified mouse ECs and integrated multi-omics. Using RNA sequencing (RNA-seq) and proteomics, we identify the transcripts and proteins selectively enriched in brain ECs and demonstrate that they are partially correlated. Using single-cell RNA-seq, we dissect the molecular basis of functional heterogeneity of brain ECs. Using integrative epigenomics and transcriptomics, we determine that TCF/LEF, SOX, and ETS families are top-ranked transcription factors regulating the BBB. We then validate the identified brain-EC-enriched proteins and transcription factors in normal mouse and human brain tissue and assess their expression changes in mice with Alzheimer’s disease. Overall, we present a valuable resource with broad implications for regulation of the BBB and treatment of neurological disorders.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10−15 g/L, and the quantitative limit reached 1.0 × 10−13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10−11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10−10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Investigating thermal transport at the Cu/Si interface holds significant importance, as understanding interface thermal conductance is crucial for enhancing materials interface thermal management, designing thermal interface materials, and improving the performance of thermoelectric devices. In this study, we conducted molecular dynamics simulations in conjunction with the Green–Kubo relation to calculate the thermal conductance of the Cu/Si interface. We successfully obtained Cu/Si interface potentials using the lattice inversion method. Our findings revealed that the thermal conductance of the Cu/Si interface is notably influenced by the interface structure. Specifically, the thermal conductance of the Cu(001)/Si(001) interface and the Cu(111)/Si(111) interface are similar, and both are higher than that of the Cu(110)/Si(110) interface. Furthermore, through first-principles calculations of the adhesion energy, we discovered that interface binding strength plays a critical role in determining interface thermal transport properties, and the influence of pressure was also discussed. This study contributes not only to the understanding of the thermal transport mechanisms at the Cu/Si interface but also provides important insights for designing novel interface materials.

Interactions between the novel hypomethylating agent (HMA) thio-deoxycytidine (T-dCyd) and the BCL-2 antagonist ABT-199 (venetoclax) have been examined in human myelodysplastic syndrome (MDS) cells. The cells were exposed to agents alone or in combination, after which apoptosis was assessed, and a Western blot analysis was performed. Co-administration of T-dCyd and ABT-199 was associated with the down-regulation of DNA methyltransferase 1 (DNMT1) and synergistic interactions documented by a Median Dose Effect analysis in multiple MDS-derived lines (e.g., MOLM-13, SKM-1, and F-36P). Inducible BCL-2 knock-down significantly increased T-dCyd’s lethality in MOLM-13 cells. Similar interactions were observed in the primary MDS cells, but not in the normal cord blood CD34+ cells. Enhanced killing by the T-dCyd/ABT-199 regimen was associated with increased reactive oxygen species (ROS) generation and the down-regulation of the anti-oxidant proteins Nrf2 and HO-1, as well as BCL-2. Moreover, ROS scavengers (e.g., NAC) reduced lethality. Collectively, these data suggest that combining T-dCyd with ABT-199 kills MDS cells through an ROS-dependent mechanism, and we argue that this strategy warrants consideration in MDS therapy.

Abstract Neoantigens derived from somatic mutations in cancer cells can induce antigen‐specific T‐cell immune response for cancer immunotherapy. However, the 3D models for assessing neoepitope immunogenicity and efficacy of anti‐tumor T‐cell immune response to neoantigens are less than perfect. Here, a 3D tumor model based on recellularized liver matrix is leveraged with HepG2 cells to investigate T cell cytotoxic reactivity toward hepatocellular carcinoma (HCC) neoantigens. The whole exome sequencing (WES) data of 364 HCC patients in The Cancer Genome Atlas database are collected and 25 highly potential immunogenic neoantigens to human leukocyte antigen (HLA)‐A*02:01 molecule in silico are predicted. Six of the HCC neoantigen candidates are functionally validated with high immunogenicity by measuring cellular interferon‐γ secretion and cytotoxicity during neoantigen‐specific T‐cell immune responses in vitro. Then, the minigene of six functionally identified neoantigen peptides is constructed and the minigene‐modified GFP‐HepG2 cells are generated. Neoantigen‐specific immune response is observed with highly secreted Granzyme B, IFN‐γ, and PD‐1 when targeting the minigene‐modified GFP‐HepG2 cells in the 3D RLM HCC tumor model. Overall, the 3D RLM tumor model provides a novel strategy for preclinical assessment of the efficacy of neoantigen‐specific T cell immune response, which helps develop personalized cancer vaccines and immunotherapy treatments for HCC patients.

Electronic components are rapidly updated in the context of expanding application requirements, and communication protocols used in combination with various electronic devices are also emerging. On this basis, IoT technology has developed a variety of sensor devices and gateways, which are widely used in cities. In the field of wisdom, applying IoT technology to classrooms can effectively improve the deficiencies of traditional teaching models. Fuzzy control theory is usually based on fuzzy sets in mathematics, and is combined with neural network, genetic and probability algorithms to form a calculation method. Fuzzy calculation has the ability to simplify the system input of a variety of complex variables, and its applications in the field of education are mainly: provide evaluation of teachers' teaching effectiveness. The advancement of science and technology has promoted the change and updating of the teaching mode. With the continuous advancement of basic education curriculum reform and the continuous deepening of classroom teaching reform, classroom teaching is also in urgent need of reform, from traditional classrooms to smart classrooms. Smart classrooms combine advanced technology with teachers' teaching. Through the dynamic data, the analysis instantly understands the student's learning situation, and then integrates it into education and teaching in a targeted manner. This paper conducts a questionnaire survey on the current situation of smart classroom teaching, and summarizes the current teaching problems. Then, combining the Internet of Things, fuzzy control and deep learning technology, from the two aspects of school teachers and students, it is proposed for smart classroom to promote students' learning effect. With its novel and new-style teaching advantages, smart classroom has gradually entered the public's vision and gained the attention and support of the majority of educators. Taking Grand Wisdom Classroom as an example, it uses the “Internet +'' way of thinking and the new generation of information technology such as big data and cloud computing to create intelligent and efficient classrooms, realizing the whole process of application before, during and after class, and promoting the development of students' wisdom. Under the mobile Internet model, students and teachers can communicate anytime and anywhere. Combined with the analysis and application of our big data technology, data-based precision teaching becomes possible. In a real sense, learning before teaching can be realized and teaching can be determined by learning.

Abstract Chemoresistance has long been the bottleneck of ovarian cancer (OC) prognosis. It has been shown that mitochondria play a crucial role in cell response to chemotherapy and that dysregulated mitochondrial dynamics is intricately linked with diseases like OC, but the underlying mechanisms remain equivocal. Here, we demonstrate a new mechanism where CRL4CUL4A/DDB1 manipulates OC cell chemoresistance by regulating mitochondrial dynamics and mitophagy. CRL4CUL4A/DDB1 depletion enhanced mitochondrial fission by upregulating AMPKαThr172 and MFFSer172/Ser146 phosphorylation, which in turn recruited DRP1 to mitochondria. CRL4CUL4A/DDB1 loss stimulated mitophagy through the Parkin-PINK1 pathway to degrade the dysfunctional and fragmented mitochondria. Importantly, CRL4CUL4A/DDB1 loss inhibited OC cell proliferation, whereas inhibiting autophagy partially reversed this disruption. Our findings provide novel insight into the multifaceted function of the CRL4 E3 ubiquitin ligase complex in regulating mitochondrial fission, mitophagy, and OC chemoresistance. Disruption of CRL4CUL4A/DDB1 and mitophagy may be a promising therapeutic strategy to overcome chemoresistance in OC.

Background : Acute myeloid leukemia (AML) is regarded as a haematological malignancy and seriously threatens the public’s health. Circular RNA (circRNA) is gradually confirmed to be involved in the development of AML. The purpose of this study was to disclose the role of circRNA Potassium Voltage-Gated Channel Subfamily Q Member 5 (circ_KCNQ5) in AML.Methods : Quantitative real-time PCR (qPCR) and western blot were used for expression analysis. Colony formation assay, EdU assay and MTT assay were performed to determine cell proliferation. Flow cytometry assay was conducted to determine cell apoptosis. The predicted binding relationship between miR-622 and circ_KCNQ5 or RAS oncogene family member 10 (RAB10) was verified by dual-luciferase reporter assay.Results : The expression of circ_KCNQ5 was increased in bone marrow samples of childhood AML patients and AML cell lines. The knockdown of circ_KCNQ5 largely suppressed AML cell proliferation and promoted cell apoptosis. Circ_KCNQ5 directly bound to miR-622 and inhibited miR-622 expression. The cotransfection of miR-622 inhibitor reversed the effects of circ_KCNQ5 knockdown and thus recovered cell proliferation and depleted cell apoptosis. RAB10 was a target of miR-622, and circ_KCNQ5 bound to miR-622 to increase the expression of RAB10. MiR-622 restoration inhibited AML cell proliferation and induced cell apoptosis, while RAB10 overexpression abolished these effects.Conclusion : Circ_KCNQ5 high expression was associated with childhood AML malignant development, and circ_KCNQ5 participated in AML progression by regulating the miR-622/RAB10 pathway.

In addition to the unprecedented challenges and stressors that university students faced during the COVID-19 pandemic, Asian American students experienced specific hardships due to COVID-19-associated xenophobic attitudes, harassment, and assault against people of Asian complexions. This qualitative study aimed to explore the ways in which Asian American university students’ experiences during the pandemic changed their views of their identities as Asian Americans by analyzing in-depth interviews of four case study participants. Secondary analysis of two waves of interviews, which were conducted during the initial outbreak of the COVID-19 pandemic and during a six-month follow-up, and primary analysis of a newly conducted third wave one year after the initial outbreak yielded 12 themes that captured the essence of the Asian American university students’ experience and redefining of their identity during the pandemic. The four participants identified these themes across four categories: Experiences and Events during the Pandemic; Categorization of Asians in America; Confronting Asian Discrimination; and Renewed Sense of Identity. The longitudinal findings revealed direct experiences and perspectives regarding the influence of the COVID-19 pandemic on Asian communities, as well as the impact of the various social and political events during this time period, such as the Black Lives Matter Movement (2020) and the 2020 US presidential election. The implications, limitations, and future directions are discussed.

PurposeThe goal of the study was to determine the prognostic significance of metabolic parameters in baseline 18F-FDG PET/CT images obtained from patients with angioimmunoblastic T-cell lymphoma (AITL).MethodsForty patients with pathologically diagnosed AITL who had baseline 18F-FDG PET/CT between May 2014 and May 2021 were assessed as part of this study. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and total metabolic tumor volume (TMTV) were obtained and analyzed. In addition, many relevant features were evaluated, including sex, age, staging, International Prognostic Index (IPI), prediction index for T-cell lymphoma (PIT), Ki-67, and so on. Estimates of progression-free survival (PFS) and overall survival (OS) were determined using the log-rank test and Kaplan-Meier.ResultsThe median follow-up was 30.2 months (interquartile range 9.82-43.03). Throughout the follow-up period, 29 (72.5%) deaths occurred and 22 (55.0%) patients made progress. The rates for 2- and 3-year PFS were 43.6% and 26.4%, respectively. The 3- and 5-year OS were 42.6% and 21.5%. For TMTV, TLG, and SUVmax, the cut-off values were 87.0 cm3, 711.1, and 15.8, respectively. Poorer PFS and OS were substantially correlated with high SUVmax and TLG. An increased TMTV suggested a shorter OS. TLG performed independently as OS predictors in multivariate analysis. The risk score for predicting the prognosis of AITL includes the TMTV, TLG, SUVmax, and IPI scores, with 4.5 for TMTV, 2 for TLG, 1.5 for IPI scores, and 1 for SUVmax. Three risk categories of patients with AITL had 3-year OS rates of 100.0%, 43.3%, and 25.0%, respectively.ConclusionBaseline TLG was a strong predictor of OS. Here a new prognostic scoring system for AITL based on the clinical indicators and PET/CT metabolic parameters was constructed, which might make stratification of prognosis easy and also help to individualize treatment.

Membrane viscosity is an important property of cell biology, which determines cellular function, development and disease progression. Various experimental and computational methods have been developed to investigate the mechanics of cells. However, there have been no experimental measurements of the membrane viscosity at high-frequencies in live cells. High frequency measurements are important because they can probe viscoelastic effects. Here, we investigate the membrane viscosity at gigahertz-frequencies through the damping of the acoustic vibrations of gold nanoplates. The experiments are modeled using a continuum mechanics theory which reveals that the membranes display viscoelasticity, with an estimated relaxation time of ca. 5.7+2.4/−2.7 ps. We further demonstrate that membrane viscoelasticity can be used to differentiate a cancerous cell line (the human glioblastoma cells LN-18) from a normal cell line (the mouse brain microvascular endothelial cells bEnd.3). The viscosity of cancerous cells LN-18 is lower than that of healthy cells bEnd.3 by a factor of three. The results indicate promising applications of characterizing membrane viscoelasticity at gigahertz-frequency in cell diagnosis.

Lipopeptide-19, a HIV fusion inhibitor (LP-19), has showed potent anti-HIV activity. However, there is still limited information of the antiviral activity against different subtype clinical isolates and the drug resistance barrier of LP-19. Therefore, 47 HIV clinical isolates were selected for this study. The viral features were identified, in which 43 strains are CCR5 tropisms, and 4 strains are CCR5/CXCR4 tropisms, and there are 6 subtype B’, 15 CRF01_AE, 14 CRF07_BC, 2 CRF08_BC and 10 URF strains. These 47 viruses were used to detected and analyze the inhibitory activities of LP-19. The results showed that the average 50% inhibitory concentration (IC50) and 90% inhibitory concentration (IC90) of LP-19 were 0.50 nM and 1.88 nM, respectively. The average IC50 of LP-19 to B’, CRF01_AE, CRF07_BC, CRF08_BC, and URF strains was 0.76 nM, 0.29 nM, 0.38 nM, 0.85 nM, and 0.44 nM, respectively. C34 and Enfuvirtide (T-20), two fusion inhibitors, were compared on the corresponding strains simultaneously. The antiviral activity of LP-19 was 16.7-fold and 86-fold higher than that of C34 and T-20. The antiviral activity of LP-19, C34, and T-20 were further detected and showed IC50 was 0.15 nM, 1.02 nM, and 66.19 nM, respectively. IC50 of LP-19 was about 7-fold and 441-fold higher compared to C34 and T-20 against HIV-1 NL4-3 strains. NL4-3 strains were exposed to increasing concentrations of LP-19 and C34 in MT-2 cell culture. The culture virus was sequenced and analyzed. The results showed that A243V mutation site identified at weeks 28, 32, 38, and 39 of the cell culture in the gp41 CP (cytoplasmic domain) region. NL4-3/A243V viruses containing A243V mutation were constructed. Comparing the antiviral activities of LP-19 against HIV NL4-3 to HIV strains (only 1.3-fold), HIV did not show drug resistance when LP-19 reached 512-fold of the initial concentration under the drug pressure for 39 weeks. This study suggests that LP-19 has broad-spectrum anti-HIV activity, and high drug resistance barrier.

The neurovascular unit (NVU) plays a critical role in health and disease. In the current review, we discuss the critical role of a class of neural/glial antigen 2 (NG2)-expressing glial cells (NG2-glia) in regulating NVU after acute ischemic stroke (AIS). We first introduce the role of NG2-glia in the formation of NVU during development as well as aging-induced damage to NVU and accompanying NG2-glia change. We then discuss the reciprocal interactions between NG2-glia and the other component cells of NVU, emphasizing the factors that could influence NG2-glia. Damage to the NVU integrity is the pathological basis of edema and hemorrhagic transformation, the most dreaded complication after AIS. The role of NG2-glia in AIS-induced NVU damage and the effect of NG2-glia transplantation on AIS-induced NVU damage are summarized. We next discuss the role of NG2-glia and the effect of NG2-glia transplantation in oligodendrogenesis and white matter repair as well as angiogenesis which is associated with the outcome of the patients after AIS. Finally, we review the current strategies to promote NG2-glia proliferation and differentiation and propose to use the dental pulp stem cells (DPSC)-derived exosome as a promising strategy to reduce AIS-induced injury and promote repair through maintaining the integrity of NVU by regulating endogenous NG2-glia proliferation and differentiation.

In this work, a five-parameter jerk system with one hyperbolic sine nonlinearity is proposed, in which $ \varepsilon $ is a small parameter, and $ a $, $ b $, $ c $, $ d $ are some other parameters. For $ \varepsilon = 0 $, the system is $ Z_{2} $ symmetric. For $ \varepsilon \neq {0} $, the system loses the symmetry. For the symmetrical case, the pitchfork bifurcation and Hopf bifurcation of the origin are studied analytically by Sotomayor's theorem and Hassard's formulas, respectively. These bifurcations can be either supercritical or subcritical depending on the governing parameters. In comparison, it is much more restrictive for the origin of the Lorenz system: Only a supercritical pitchfork bifurcation is available. Thus, the symmetrical system can exhibit very rich local bifurcation structures. The continuation of local bifurcations leads to the main contribution of this work, i.e., the discovery of two basic mechanisms of chaotic motions for the jerk systems. For four typical cases, Cases A–D, by varying the parameter $ a $, the mechanisms are identified by means of bifurcation diagrams. Cases A and B are $ Z_{2} $ symmetric, while Cases C and D are asymmetric (caused by constant terms). The forward period-doubling routes to chaos are observed for Cases A and C; meanwhile, the backward period-doubling routes to chaos are observed for Cases B and D. The dynamical behaviors of these cases are studied via phase portraits, two-sided Poincaré sections and Lyapunov exponents. Using Power Simulation (PSIM), a circuit simulation model for a chaotic jerk system is created. The circuit simulations match the results of numerical simulations, which further validate the dynamical behavior of the jerk system.

Objectives: This study aims to investigate the function of the protein arginine methyltransferase 5 (PRMT5) and fibroblast growth factor receptor 3 (FGFR3)/Akt signaling axis in the epithelial-mesenchymal transition (EMT) of human lung cancer. Methods: The mRNA and protein expression levels of PRMT5, FGFR3, p-Akt, and EMT markers are determined by quantitative real-time PCR and Western blotting, respectively; the expression and localization of PRMT5, p-Akt, and proliferating cell nuclear antigen are detected by immunofluorescence; the human lung cancer cell proliferation is measured by MTS assay. Results: PRMT5 and FGFR3 are highly expressed in human lung cancer tissues and are closely related to lymphatic metastasis. Moreover, down-regulation of PRMT5 by lentivirus-mediated shRNAs or inhibition of PRMT5 by specific inhibitors attenuates FGFR3 expression, Akt phosphorylation, and lung cancer cell proliferation. Further studies show that silencing PRMT5 impairs EMT-related markers, including vimentin, collagen I, and β-catenin. Conversely, ectopic expression of PRMT5 increases FGFR3 expression, Akt phosphorylation, and EMT-related markers, suggesting that PRMT5 regulates metastasis probably through the FGFR3/Akt signaling axis. Conclusion: PRMT5/FGFR3/Akt signaling axis controls human lung cancer progression and metastasis and also implies that PRMT5 may serve as a prognostic biomarker and therapeutic candidate for treating lung cancer.

Background: In addition to intrahepatic angiogenesis, patients with cholestasis cirrhosis develop extrahepatic vasculature disorders and functional disturbances of multiple organ systems. Without effective intervention, these vascular disorders will eventually turn into multiple organs vascular syndromes, including the brain, lung and other organ systems. However, studies on the pathogenesis of vascular alterations among extrahepatic organ disturbances are still carried out separately, which hampered the successful translation of preclinical studies to the human setting and required further mechanistic insight into these complications. This study aims to investigate the relationship between extrahepatic angiogenesis and multiple organ impairment, and whether the vascular endothelial growth factor (VEGF) family members and their receptors are involved in this process. Methods: Pathological changes of the multiple organs were determined by histopathological and immunohistochemical staining in the established common bile duct ligation (CBDL) rats, and angiogenesis was estimated by microvessel density (MVD). Levels of the VEGF family members and their receptors in the serum and organ tissues were also measured by using enzyme-linked immunosorbent assays. Results: The MVD and VEGF family members and their receptors were significantly increased in CBDL rats with multiple organ injury, especially in the liver, lung and cerebral cortex. Meanwhile, we noticed moderate elevation of soluble receptor of the vascular endothelial growth factor-1 (sFlt-1) in the liver, lung, and cerebral cortex, whereas the levels of placental growth factor (PLGF) increased significantly. Conclusions: Extrahepatic angiogenesis may represent a common pathophysiological basis for multiple organ dysfunction and the sFlt-1/PLGF ratio could offer an avenue for further studies to target extrahepatic angiogenesis in cholestatic cirrhosis.

In order to establish a standardized method that can quickly and nondestructively identify the color changes in the process of mutton roasting, this study combined three algorithms (mean value algorithm, K-means algorithm and K-means+image noise reduction algorithm) based on machine vision technology to make the color recognition colourimetric card and carried out online monitoring of the color of roasted mutton. The results showed that the colorimetric cards made by the three algorithms could show the color changes in the process of mutton roasting. In order to clarify the accuracy of the three colorimetric cards, K-medoids algorithm combined with sensory experiment was used to verify the accuracy of color recognition of the colorimetric cards. The verification results of colourimetric card recognition accuracy using K-medoids algorithm showed that the accuracy of mean algorithm was 85.60%, that of K-means algorithm was 95.70%, and that of K-means algorithm+image noise reduction algorithm was 93.40%. The verification results of sensory experiments showed that the recognition accuracy of mean algorithm, K-means algorithm and K-means algorithm+image noise reduction algorithm were 67.32%, 73.71% and 68.74% respectively, the comparison showed that the color recognition accuracy of colourimetric card made by K-means algorithm was the highest for roasted mutton. The study proved that the colorimetric card can be used as the color evaluation criterion and provides guidance for barbecue meat processing. It had a good application prospect.

A 66 years old male was admitted to our hospital after a serious car accident. The patient presented with severe shock after admission. After the examination, the patient was diagnosed with hemopneumothorax and myocardial contusion, accompanied by spleen rupture. After emergency surgery and a series of symptomatic treatments, the patient’s condition gradually stabilized. One week later, the patient suddenly presented with severe shock. Massive hemothorax was found on the left side of the chest. Surgical exploration revealed cardiac rupture and accidental absence of congenital pericardium. According to the literature review, congenital absence of pericardium (CAP) is relatively rare. Although there are certain imaging features, the clinical diagnosis is very difficult. However, this patient did not show the characteristics in the literature and had some other atypical features. The role of CAP in the occurrence and development of the patient’s heart injury and rupture is worthy of discussion. What we learned from this case is that we should look for potential risks in the telltale signs of a patient’s condition.

The atypical Markov decision processes (MDPs) are decision-making for maximizing the immediate returns in only one state transition. Many complex dynamic problems can be regarded as the atypical MDPs, e.g., football trajectory control, approximations of the compound Poincaré maps, and parameter identification. However, existing deep reinforcement learning (RL) algorithms are designed to maximize long-term returns, causing a waste of computing resources when applied in the atypical MDPs. These existing algorithms are also limited by the estimation error of the value function, leading to a poor policy. To solve such limitations, this paper proposes an immediate-return algorithm for the atypical MDPs with continuous action space by designing an unbiased and low variance target Q-value and a simplified network framework. Then, two examples of atypical MDPs considering the uncertainty are presented to illustrate the performance of the proposed algorithm, i.e., passing the football to a moving player and chipping the football over the human wall. Compared with the existing deep RL algorithms, such as deep deterministic policy gradient and proximal policy optimization, the proposed algorithm shows significant advantages in learning efficiency, the effective rate of control, and computing resource usage.

Oral colon-targeting preparation can achieve targeted drug release in the lesion site and have a great application prospect. In this study, we presented the principle of particle design in the field of materials science into the preparation of colon-targeting preparation. Enzymatic Pulsatilla saponins Colon-targeting composite Microparticles (EPCM) were prepared by mechanical grinding without any organic solvent. Firstly, Response Surface Methodology (RSM) designed by Box-Behnken was used to optimize the preparation process of EPCM, and the structure of EPCM was characterized. All-Atomic and Molecular Dynamics (AAMD) was used to calculate the compatibility between drugs and coating materials before and after release, so as to explain the principle of colon- targeted drug release in this method. Then, colon-targeting characteristics of EPCM in vitro and in vivo were investigated by experiments. Finally, the pharmacodynamics effects of this composite microparticles on Ulcerative Colitis (UC) induced by DSS in C57BL/6 mice were evaluated. The results demonstrated that the colon-targeting composite microparticles could be prepared by mechanical grinding based on particle design principle. The composite microparticles have appropriate colon-targeting drug release performance in vitro and in vivo, and have good anti-ulcerative colitis effect. This study provides a new idea for the preparation of oral colon-targeting preparation of Traditional Chinese medicine, and has evident reference value for the study of coating isolation and powder modification of traditional Chinese medicine for other purposes.

Abstract Background Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a public health concern. This study aimed to compare the clinical outcomes of patients with nonurinary source bacteraemia caused by ESBL-producing Escherichia coli (E. coli) or Klebsiella pneumoniae (ESBL-producing EK) receiving β-lactam/β-lactamase inhibitor combinations (BLICs) versus carbapenem treatment and assess the risk factors of mortality with these two drugs. Methods We conducted a retrospective single-centre study of adult hospitalised patients with ESBL-producing EK bloodstream infection (BSI) from nonurinary source at our centre over a 4-year period. One hundred and eighty patients who received BLICs or carbapenems were included in the analysis. The outcome variables were 14-day treatment failure and 30-day mortality. For more reliable results, propensity score analysis was performed to compare the efficacy of the two drugs and analyse their risk factors for 30-day mortality. Results Out of 180 patients, 114 received BLICs, and 66 received carbapenem therapy. Compared to carbapenem-treated patients, those treated with BLICs were older and had higher age-adjusted Charlson comorbidity index, but they had shorter stay in the hospital. Additionally, their Pitt bacteraemia score, SOFA score, rate of leukaemia, and immune compromise were lower. After propensity score matching (PSM), the baseline characteristics of patients in the two treatment groups were balanced. BLICs were associated with a higher 14-day treatment failure rate (20.6%, 13/63) than carbapenems (16.3%, 7/43), although the difference was not significant in either univariate analysis (P = 0.429) or multivariate analysis (P = 0.122). And the 30-day mortality rate in BTG (11.1%, 7/63) and CTG (11.6%, 5/43) did not significantly differ (univariate analysis, P = 0.926; multivariate analysis, P = 0.420). In the multivariate analysis, after PSM, leukaemia was the only independent predictor of mortality in both BTG and CTG. Conclusions Our study showed that BLICs had higher 14-day treatment failure rate compared with carbapenems, although there were no statistically significant differences because of the small number of patients, therefore, further evaluation of the efficacy of BLICs is needed.

ABSTRACT: Objectives: We aimed to determine the clinical impact of inappropriate empirical antibiotic treatment (IEAT) compared with appropriate empirical antibiotic treatment (AEAT) in hospitalised patients with urinary tract infections (UTIs) caused by Escherichia coli (E. coli). Methods: This retrospective cohort study included adult patients with a primary diagnosis of UTI who were treated with empirical antibiotics at a tertiary hospital in southern China over a 2-year period. Clinical data of patients who received IEAT were compared with those of patients receiving AEAT. We used multivariable logistic regression to identify the predictors for receiving IEAT and the risk factors affecting clinical outcomes. Results: A total of 213 patients were enrolled (median age, 61 years), of whom 103 (48.4%) received IEAT. IEAT was associated with empirical use of fluoroquinolones, male sex and age-adjusted Charlson comorbidity index (aCCI) score >6. Hospital length of stay (LOS) was longer for patients who received IEAT than for those who received AEAT (13.6 ± 8.6 days vs. 10.8 ± 7.9 days; P = 0.008). IEAT was an independent risk factor for longer LOS along with aCCI score ≥2, lung disease and cardiac disease. Conclusion: Empirical use of fluoroquinolones for UTIs should be avoided, especially in male patients with aCCI score >6. Improved empirical antimicrobial therapy may have a beneficial impact in reducing bacterial resistance and healthcare costs by decreasing the LOS. Therefore, interventions to promote in-depth antibiotic stewardship programmes in China are needed.

CRF07_BC is one of the most prevalent HIV-1 strains in China, which contributes over one-third of the virus transmissions in the country. In general, CRF07_BC is associated with slower disease progression, while the underlying mechanisms remain unclear. Our study focused on envelope proteins (Env) and its V3 loop which determine viral binding to co-receptors during infection of cells. We studied a large dataset of 3,937 env sequences in China and found that CRF07_BC had a unique profile of predominantly single CCR5 tropism compared with CCR5 and CXCR4 dual tropisms in other HIV-1 subtypes. The percentages of the CXCR4-tropic virus in B (3.7%) and CRF01_AE (10.4%) infection are much higher than that of CRF07_BC (0.1%), which is supported by median false-positive rates (FPRs) of 69.8%, 25.5%, and 13.4% for CRF07_BC, B, and CRF01_AE respectively, with a cutoff FPR for CXCR4-tropic at 2%. In this study, we identified the first pure CXCR4-tropic virus from one CRF07_BC-infected patient with an extremely low CD4+T cell count (7 cells/mm3). Structural analysis found that the V3 region of this virus has the characteristic 7T and 25R and a substitution of conserved “GPGQ” crown motif for “GPGH”. This study provided compelling evidence that CRF07_BC has the ability to evolve into CXCR4 strains. Our study also lay down the groundwork for studies on tropism switch, which were commonly done for other HIV-1 subtypes, for the long-delayed CRF07_BC.