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Tao Zhu,1 Fang Kang,1 Ming-Ming Han,1 Fang He,2 Sen Jiang,2 Li-Na Hao,1 Xiang Huang,1 Juan Li1 1Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Electrophysiology, the First Affiliated Hospital of USTC, Division of life sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Juan Li, Department of anesthesiology, the First Affiliated Hospital of USTC, Division of life sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China, Email huamuzi1999@163.comPurpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM).Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes.Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7± 44.1 and 53.4± 35.4, respectively. Furthermore, the 95% confidence interval of the difference was − 25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P< 0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P< 0.05).Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.Keywords: anesthetics, abnormal muscle response, ciprofol, microvascular decompression

Meng-Meng Han,1,* Wen-Shu Zhao,2,* Xin Wang,2,* Shan He,3 Xiao-Rong Xu,2 Cai-Jing Dang,2 Juan Zhang,2 Jia-Mei Liu,2 Mu-Lei Chen,2 Lin Xu,2 Hua Wang2 1Intensive Care Units, Beijing Longfu Hospital, Beijing, 100010, People’s Republic of China; 2Heart Center and Beijing Key Laboratory of Hypertension Research, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 3Heart Center, Beijing Chaoyang Hospital Jingxi Branch, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Xu; Hua WangHeart Center and Beijing Key Laboratory of Hypertension Research, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaTel +86-10-85231445; +86-10-85231556Email lxdrqw09_dr@163.com; huwsmndr66@yandex.comObjective: This study aimed to find echocardiographic parameters that can predict short- and long-term adverse cardiovascular events in patients with AMI.Methods: A total of 126 patients with AMI admitted to our hospital from July to December 2012 were enrolled in this study. All patients underwent echocardiographic examination within 12 hours after admission and received regular follow-ups until December 2018. The primary endpoint was a composite of the major adverse cardiovascular events (MACEs).Results: In the first year of this study, a primary endpoint occurred in 35 patients and the predictor derived from the echocardiography of 1-year primary endpoint was LVEF< 40% (OR: 9.000, 95% CI 3.242-24.987, p< 0.0001) and the area under the curve (AUC) for the predictor was 0.676 (95% CI 0.561-0.790, p=0.002). For the total 5 years, 57 patients underwent primary endpoint. The results of the 5-year primary endpoint were: E/E’> 15 (OR: 4.094, 95% CI 1.726– 9.710, P=0.001), the wall motion score index was (WMSI)> 1.5 (OR: 12.791, 95% CI 1.511– 108.312, P=0.019), and the AUC was 0.691 (95% CI 0.595– 0.787 P< 0.0001).Conclusion: LVEF is correlated with a short-term outcome (1-year), and WMSI and E/E’ can predict a long-term outcome (5-year) in patients with acute myocardial infarction.Keywords: echocardiography, cardiovascular events, predictors, acute myocardial infarction, wall motion score index

Md Kaosar Yazdani-Ibn-Taz,1 Myint Myint Han,1 Sven Jonuscheit,1 Andrew Collier,1,2 Jane E Nally,1 Suzanne Hagan1 1School of Health and Life Sciences, Glasgow Caledonian University (GCU), Glasgow G4 0BA, UK; 2Diabetes Day Centre, University Hospital Ayr, Ayr KA6 6DX, UK Purpose: The purpose of the study was to assess the relationship between patient-reported severity of dry eye disease (DED), quality of life (QoL), presence of diabetic retinopathy (DR) and length of disease duration in people with type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2).Patients and methods: A survey of 152 people (110 with and 42 without diabetes). All participants completed the Ocular Surface Disease Index (OSDI) and Dry Eye-related Quality of Life Score (DEQS) questionnaires.Results: Forty-four percent of all diabetic subjects reported dry eye symptoms, compared to 29% in the control group. Patients with DM2 reported dry eye symptoms more frequently than those with DM1 (55% and 27% respectively, P=0.001). Dry eye severity was linked to a significant deterioration in QoL in both types of diabetes (DM1, r=0.609 and P=0.036; DM2, r=0.417 and P=0.011). Irrespective of DR, the presence of DED was significantly higher in DM2 compared to DM1 (with DR, P=0.011; without DR, P=0.018).Conclusion: Dry eye symptoms are associated with reduced QoL and are more common in people with DM2 than in DM1, irrespective of DR status. Routine clinical screening for severe DED could potentially allow for a timely and more effective treatment and could contribute to mitigating the dry eye-associated reduction in QoL in those with DM2. Keywords: ocular surface, dry eye, symptoms, retinopathy

AimsMitochondrial dysfunction contributes to many forms of peripheral and central nervous system degeneration. Therapies that protect mitochondrial number and function have the potential to impact the progression of conditions such as diabetic neuropathy. We therefore assessed indices of mitochondrial function in dorsal root ganglia (DRG) and brain cortex of the Zucker diabetic fatty (ZDF) rat model of type 2 diabetes and tested the therapeutic impact of a neurogenic compound, NSI-189, on both mitochondrial function and indices of peripheral and central neurological dysfunction.Materials and methodsZDF rats were maintained for 16 weeks of untreated diabetes before the start of oral treatment with NSI-189 for an additional 16 weeks. Nerve conduction velocity, sensitivity to tactile and thermal stimuli, and behavioral assays of cognitive function were assessed monthly. AMP-activated protein kinase (AMPK) phosphorylation, mitochondrial protein levels, and respiratory complex activities were assessed in the DRG and brain cortex after 16 weeks of treatment with NSI-189.ResultsTreatment with NSI-189 selectively elevated the expression of protein subunits of complexes III and V and activities of respiratory complexes I and IV in the brain cortex, and this was accompanied by amelioration of impaired memory function and plasticity. In the sensory ganglia of ZDF rats, loss of AMPK activity was ameliorated by NSI-189, and this was accompanied by reversal of multiple indices of peripheral neuropathy.ConclusionsEfficacy of NSI-189 against dysfunction of the CNS and PNS function in type 2 diabetic rats was accompanied by improvement of mitochondrial function. NSI-189 exhibited actions at different levels of mitochondrial regulation in central and peripheral tissues.

Objective: The aim of our study was to evaluate the clinical feasibility and diagnostic value of a new MRI metal artefact reduction pulse sequence called MAVRIC-SL in a 3 T MRI environment. Subjects and methods: Two MAVRIC-SL sequences obtained in 61 patients with symptomatic total hip replacement were compared with standard FSE-STIR sequences optimized for imaging around metal. Artefact size was measured on the slice of greatest extent. Image quality, fat saturation, image distortion, visibility of anatomical structures, and detectability of joint abnormalities were visually assessed and graded on qualitative scales. Differences between MAVRIC-SL and FSE sequences were tested with the Wilcoxon signed-rank test. Results: MAVRIC-SL sequences at 3 T showed significantly smaller metal artefacts compared to FSE-STIR sequences (p < 0.0001). The general image quality of MAVRIC-SL sequences was reduced with regard to spatial resolution, noise and contrast (p = 0.001), and fat saturation (p < 0.0001). The reduction of artefact size and image distortion significantly improved visualization of joint anatomy (p < 0.0001) and diagnostic confidence regarding implant-associated abnormalities (p = 0.0075 to

The objective of this study was to investigate the between autophagy activity and local immune response in hypopharyngeal squamous cell carcinoma (HSCC). Herein, we observed the expression of autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B), CD8 cytotoxic T lymphocytes (CTLs), CD39 (regulatory T cells Tregs) and CD163 (tumor-associated macrophages TAMs) in HSCC, and determined the prognostic roles of CD8 + /CD39 + and CD8 + /CD163 + in patients with HSCC. The expression of light chain 3B (LC3B) and CD8 + /CD39 + was found to be significantly lower in HSCC tissues than in adjacent non-tumor mucosa tissue samples; LC3B expression was positively correlated with the infiltration rate of CD8 + /CD39 + in HSCC. Further studies revealed that the ratio of CD8 + /CD39 + immune cells was negatively correlated with tumor lymph node metastasis and TNM classification, while the ratio of CD8 + /CD163 + immune cells was negatively correlated with TNM classification. Moreover, the expression of LC3B was analyzed and the patients were grouped according to their immune infiltration characteristics. The 5-year cumulative survival rates of LC3B + , CD8 + /CD39 + , and CD8 + /CD163 + patients were significantly higher than those of other group patients. Collectively, our studies indicated that the expression of LC3B in HSCC was correlated with the infiltration ratio of immune cells, and a change in autophagy activity may affect the cellular immunity in HSCC. The ratios of tCD8 + /CD39 + and tCD8 + /CD163 + may serve as prognostic factors for HSCC.

Background: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-331-3p is upregulated in pancreatic cancer and promotes pancreatic cancer cell proliferation and epithelial-to-mesenchymal transition–mediated metastasis by targeting ST7L. However, it is uncertain whether miR-331-3p is involved in drug resistance. Methods: We investigated the relationship between miR-331-3p and pancreatic cancer drug resistance. As part of this, microRNA mimics or inhibitors were transfected into pancreatic cancer cells. Quantitative polymerase chain reaction was used to detect miR-331-3p expression, and flow cytometry was used to detect cell apoptosis. The Cell Counting Kit-8 assay was used to measure the IC50 values of gemcitabine in pancreatic cancer cells. The expression of multidrug resistance protein 1, multidrug resistance-related protein 1, breast cancer resistance protein, β-Catenin, c-Myc, Cyclin D1, Bcl-2, and Caspase-3 was evaluated by Western blotting. Results: We confirmed that miR-331-3p is upregulated in gemcitabine-treated pancreatic cancer cells and plasma from chemotherapy patients. We also confirmed that miR-331-3p inhibition decreased drug resistance by regulating cell apoptosis and multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein expression in pancreatic cancer cells, whereas miR-331-3p overexpression had the opposite effect. We further demonstrated that miR-331-3p effects in drug resistance were partially reversed by ST7L overexpression. In addition, overexpression of miR-331-3p activated Wnt/β-catenin signaling in pancreatic cancer cells, and ST7L overexpression restored activation of Wnt/β-catenin signaling. Conclusions: Taken together, our data demonstrate that miR-331-3p contributes to drug resistance by activating Wnt/β-catenin signaling via ST7L in pancreatic cancer cells. These data provide a theoretical basis for new targeted therapies in the future.

Background: This article reports on the bilateral lip mucosa flaps (BLMFs) for reconstruction of the vermilion tubercle of the corrected cleft lip deformity. Methods: From 2005 to 2013, the bilateral mucosa flaps procedures were performed on 34 secondary cleft lip patients (bilateral, n = 25; unilateral, n = 9). We retrospectively reviewed the pre-, intra-, and postoperative data of these 34 cases receiving BLMFs. Results: Satisfactory results were obtained, both cosmetically and functionally, in all 34 patients. Lateral projection measurements of the reconstructive vermilion tubercle showed a mean increase of 151%. There were minimal perioperative complications. The color and texture matched well with the surrounding tissue. The postoperative scars are not remarkable at all. Conclusions: The technique is relatively simple. The BLMFs provided a versatile and reliable option for the reconstruction of the vermilion tubercle from secondary cleft lip deformities.

Metabolomics has focused on toxicological applications to (1) understand the mechanisms of toxicity, (2) identify novel biomarkers of toxicity, and (3) provide in vivo assessment in animal models through simple and fast methods to date. The toxicological effects of nonylphenol (NP) were evaluated after intraperitoneal injection of rats with 0, 50, and 250 mg kg-1 day-1 NP for four consecutive days. In the nontargeted approach, different extraction conditions were introduced to investigate the effects of NP on rats through gas chromatography/mass spectrometry (GC/MS). The GC/MS data obtained were further analyzed with partial least-squares discriminant analysis to compare toxicological effects between control and treated groups. The targeted approach was also used in combination with GC/MS to quantify endocrine hormones and to identify possible biomarkers in rat urine under optimal extraction conditions. In addition, we considered the metabolic trajectory to examine the metabolite profiles and patterns related to steroid metabolism in rats that were treated with NP, considering both treatment amount and time. The data suggest that tetrahydrocorticosterone and 5α-tetrahydrocorticosterone are possible urinary biomarkers of NP-induced toxicity. This metabolomic approach is a promising tool to assist with screening in toxicological studies. [ABSTRACT FROM AUTHOR]

Throughout pregnancy, maternal thyroid-related hormones are transported to the fetus via the placenta to allow normal fetal growth and development and are particularly important in the first and second trimesters of pregnancy. During maternal-fetal transport, in addition to thyroid-related hormones, thyroid-stimulating hormone receptor antibodies and antithyroid drugs can enter the fetus and interfere with development of the fetal thyroid gland and endocrine function, potentially leading to hyperthyroidism or hypothyroidism in the fetus or newborn. Several basic studies have been performed to demonstrate the important role of thyroid-related hormones in fetal and neonatal bone development. Ultrasound can assess neonatal skeletal maturity and bone development safely, rapidly, and effectively. This review aims to communicate the latest knowledge about maternal and fetal thyroid function in both normal and pathological pregnancies and summarize the latest advances in the potential effects of abnormal maternal thyroid function on bone development in the fetus and neonate. Finally, it discusses recent advances in research on ultrasound in the assessment of fetal and neonatal bone development.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

Objective: Our objective is to assess whether the outcome of intrahepatic unresectable or ablative hepatocellular carcinoma (HCC) could be improved by supplemental transarterial chemoembolization (TACE) following initial treatment of TACE with 3-dimensional conformal radiotherapy (3DCRT), compared to TACE followed by 3DCRT alone. Methods: We retrospectively analyzed intrahepatic unresectable or ablative HCC patients who underwent TACE, followed by 3DCRT with or without additional TACE, from June 2010 to December 2016 at our institution. Survival was assessed using the Kaplan-Meier method and compared with the log-rank test. Cox regression analyses were used to identify factors that influenced prognosis. Toxicity profiles were evaluated using CTCAE 4.0. Results: 27 patients received TACE with 3DCRT (TR group) and 11 received additional TACE following TACE and 3DCRT (sandwich group), respectively. The median intrahepatic progression-free survival (IPFS), progression-free survival (PFS), and overall survival (OS) in the TR group and sandwich group were 5.4 months vs. 17 months (P = 0.018), 5.4 months vs. 17 months (P = 0.008), and 13.5 months vs. 29.2 months (P = 0.011), respectively. Multivariate Cox regression demonstrated that TACE followed by radiotherapy alone had a shorter IPFS (HR: 2.516, 95% CI (1.136-5.570), P = 0.023) and PFS (HR: 2.637, 95% CI (1.182-5.880), P = 0.018) compared with the sandwich treatment. Hepatitis B virus reactivation occurred in 1 patient in the sandwich group. Myleosuppresion was considered a grade 3/4 adverse event. Conclusion: Unresectable or ablative HCC patients possibly benefit from the combination of TACE and 3DCRT followed by additional TACE therapy, compared with TACE followed by 3DCRT alone.

The identification of genes to be deleted or amplified is an essential step in metabolic engineering for strain improvement toward the enhanced production of desired bioproducts. In the past, several methods based on flux analysis of genome–scale metabolic models have been developed for identifying gene targets for deletion. Genome–wide identification of gene targets for amplification, on the other hand, has been rather difficult. Here, we report a strategy called flux scanning based on enforced objective flux (FSEOF) to identify gene amplification targets. FSEOF scans all the metabolic fluxes in the metabolic model and selects fluxes that increase when the flux toward product formation is enforced as an additional constraint during flux analysis. This strategy was successfully employed for the identification of gene amplification targets for the enhanced production of the red–colored antioxidant lycopene. Additional metabolic engineering based on gene knockout simulation resulted in further synergistic enhancement of Jycopene production. Thus, FSEOF can be used as a general strategy for selecting genome–wide gene amplification targets in silico. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is exacerbated by injurious mechanical forces that destabilize the pulmonary mechanical microenvironment homeostasis, leading to alveolar dysfunction and exacerbating disease severity. However, given the inherent mechanosensitivity of fibrotic lungs, where type II alveolar epithelial cells (AEC IIs) are subjected to persistent stretching and overactivated myofibroblasts experience malignant interactions during mechanotransduction, it becomes imperative to develop effective strategies to modulate the pulmonary mechanical microenvironment. Herein, cyclo (RGDfC) peptide-decorated zeolitic imidazolate framework-8 nanoparticles (named ZDFPR NPs) are constructed to target and repair the aberrant mechanical force levels in pathological lungs. Specifically, reduces mechanical tension in AEC IIs by pH-responsive ZDFPR NPs that release zinc ions and 7, 8-dihydroxyflavone to promote alveolar repair and differentiation. Meanwhile, malignant interactions between myofibroblast contractility and extracellular matrix stiffness during mechanotransduction are disrupted by the fasudil inhibition ROCK signaling pathway. The results show that ZDFPR NPs successfully restored pulmonary mechanical homeostasis and terminated the fibrosis process in bleomycin-induced fibrotic mice. This study not only presents a promising strategy for modulating pulmonary mechanical microenvironment but also pioneers a novel avenue for IPF treatment., (© 2024 Wiley‐VCH GmbH.)

In the development of asthma, subepithelial fibrosis and vascular proliferation cause airway remodeling and narrowing, leading to disease deterioration and respiratory failure. In the clinic, the treatment of asthma was aimed at reducing the frequency of acute asthma attacks through inhaled corticosteroids (ICSs). However, ICSs cannot prevent the progression into refractory asthma due to the formation of airway remodeling mainly by subepithelial fibrosis and angiogenesis surrounding the tracheal lumen. Herein, we constructed surface-engineered mesenchymal stem cells (MSCs/PVLA) via the bioconjugation of MSCs and reactive oxygen species-responsive polymeric micelles loaded with vactosertib (VST) and linifanib (LFN) for treating refractory asthma through reversing airway remodeling. MSCs/PVLA migrated to the tracheal lumen due to the inflammation tropism of MSCs, and subsequently released VST and LFN could inhibit the formation of airway remodeling by preventing subepithelial fibrosis and angiogenesis. Meanwhile, MSCs reduced inflammatory cell infiltration and cytokine secretion to regulate the pathological microenvironment. Our results suggested that MSCs/PVLA could serve as a promising candidate to prevent disease exacerbations and treat refractory asthma., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study introduced an innovative sequential extraction methodology designed for the efficient recovery of alpha-mangostin (⍺-M) from mangosteen pericarps. Alpha-mangostin, renowned for its pharmacological properties including anti-inflammatory, anti-cancer, and anti-bacterial effects, has garnered significant attention across diverse industries. The proposed method of sequential extraction achieved 73% recovery and a yield of 46.75 mg/g based on the weight/weight percentage of the mass of ⍺-M extracted from the sequence and the mass of raw material. Furthermore, the purity of the dried product was 67.9%. The sequence solvent extraction system, comprising water, hexane, and acetonitrile, plays a pivotal role in enhancing the efficacy of the extraction process. Notably, this methodology offers a cost-effective alternative to conventional extraction methods. It reduces the need for complex equipment and processes, positioning it as a resource-efficient extraction technique in comparison to existing methodologies. This novel sequential extraction method presents a promising avenue for the economical and sustainable recovery of alpha-mangostin (⍺-M) from pericarps., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-β. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Epigenetic regulation plays a central role in the regulation of a number of cellular processes such as proliferation, differentiation, cell cycle, and apoptosis. In particular, small molecule epigenetic modulators are key elements that can effectively influence gene expression by precisely regulating the epigenetic state of cells. To identify useful small-molecule regulators that enhance the expression of recombinant proteins in Chinese hamster ovary (CHO) cells, we examined a novel dual-HDAC/LSD1 inhibitor I-4 as a supplement for recombinant CHO cells. Treatment with 2 μM I-4 was most effective in increasing monoclonal antibody production. Despite cell cycle arrest at the G1/G0 phase, which inhibits cell growth, the addition of the inhibitor at 2 µM to monoclonal antibody-expressing CHO cell cultures resulted in a 1.94-fold increase in the maximal monoclonal antibody titer and a 2.43-fold increase in specific monoclonal antibody production. In addition, I-4 significantly increased the messenger RNA levels of the monoclonal antibody and histone H3 acetylation and methylation levels. We also investigated the effect on HDAC-related isoforms and found that interference with the HDAC5 gene increased the monoclonal antibody titer by 1.64-fold. The results of this work provide an effective method of using epigenetic regulatory strategies to enhance the expression of recombinant proteins in CHO cells. KEY POINTS: • HDAC/LSD1 dual-target small molecule inhibitor can increase the expression level of recombinant monoclonal antibodies in CHO cells. • By affecting the acetylation and methylation levels of histones in CHO cells and downregulating HDAC5, the production of recombinant monoclonal antibodies increased. • It provides an effective pathway for applying epigenetic regulation strategies to enhance the expression of recombinant proteins., (© 2024. The Author(s).)

The boom in cancer immunotherapy has provided many patients with a better chance of survival, but opportunities often come with challenges. Single immunotherapy is not good enough to eradicate tumours, and often fails to achieve the desired therapeutic effect because of the low targeting of immunotherapy drugs, and causes more side effects. As a solution to this problem, researchers have developed several nano Drug Delivery Systems (NDDS) to deliver immunotherapeutic agents to achieve good therapeutic outcomes. However, traditional drug delivery systems (DDS) have disadvantages such as poor bioavailability, high cytotoxicity, and difficulty in synthesis, etc. Herbal Polysaccharides (HPS), derived from natural Chinese herbs, inherently possess low toxicity. Furthermore, the biocompatibility, biodegradability, hydrophilicity, ease of modification, and immunomodulatory activities of HPS offer unique advantages in substituting traditional DDS. This review initially addresses the current developments and challenges in immunotherapy. Subsequently, it focuses on the immunomodulatory mechanisms of HPS and their design as nanomedicines for targeted drug delivery in tumour immunotherapy. Our findings reveal that HPS-based nanomedicines exhibit significant potential in enhancing the efficacy of cancer immunotherapy, providing crucial theoretical foundations and practical guidelines for future clinical applications.

Objective: This study aims to elucidate the mechanism of action and impact of the "Xuanshen Yishen Mixture" (XYM) on hypertension., Methods: Active components were identified and potential targets were predicted using the Traditional Chinese Medicine Systems Pharmacology database. Hypertension-related targets were collected from GeneCards, DRUGBANK, OMIM, TTD, and PharmaGKB databases. Intersections of disease and drug targets were visualized using the R package "VennDiagram". A protein-protein interaction network was established via the STRING database. GO function enrichment and KEGG pathway analyses were conducted using "clusterProfiler", while "Cytoscape" was used to construct a "drug-component-target" network. Additionally, data from 60 patients with essential hypertension from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were retrospectively analyzed. Patients were divided into a control group (n = 30) and an XYM group (n = 30) based on treatment regimen., Results: Sixty active ingredients and 98 related targets were identified from Uncaria, Radix Scrophulariae, and Epimedium in hypertension treatment. Key active components such as quercetin, kaempferol, yohimbine, and beta-sitosterol were pinpointed, with PTGS2, PTGS1, AR, DPP4, and F2 as crucial targets. KEGG pathway analysis highlighted significant pathways including IL-17 signaling, TNF signaling, Relaxin signaling, and HIF-1 signaling. Clinical data indicated that XYM's therapeutic effects are comparable to those of valsartan, which significantly reduced diastolic and systolic blood pressure and demonstrated good biosafety., Conclusions: Uncaria, Radix Scrophulariae, and Epimedium effectively mitigate hypertension through multiple components, targets, and pathways. Additionally, DPP4, IL-17, and TNF-α are identified as potential therapeutic targets for traditional Chinese medicine preparations in hypertension treatment. This study provides a foundation for further investigation into XYM's mechanisms in hypertension management., Competing Interests: None., (AJTR Copyright © 2024.)

Malware classification is a crucial step in defending against potential malware attacks. Despite the significance of a robust malware classifier, existing approaches reveal notable limitations in achieving high performance in malware classification. This study focuses on image-based malware detection, where malware binaries are transformed into visual representations to leverage image classification techniques. We propose a two-branch deep network designed to capture salient features from these malware images. The proposed network integrates faster asymmetric spatial attention to refine the extracted features of its backbone. Additionally, it incorporates an auxiliary feature branch to learn missing information about malware images. The feasibility of the proposed method has been thoroughly examined and compared with state-of-the-art deep learning-based classification methods. The experimental results demonstrate that the proposed method can surpass its counterparts across various evaluation metrics.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment., Significance: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors., (©2024 The Authors; Published by the American Association for Cancer Research.)

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objective: To explore the mediating effect of self-efficacy and coping mode between powerlessness and quality of life in patients with a venous leg ulcer (VLU)., Methods: The authors used a convenience sampling method to select 208 patients with a VLU in four tertiary grade A hospitals in Qingdao and Tianjin from June 2021 to August 2022. Instruments included the Powerlessness Assessment Tool, Venous Leg Ulcer Self-efficacy Tool, Medical Coping Modes Questionnaire, and Venous Leg Ulcer Quality of Life Questionnaire. The authors used descriptive statistics, Pearson correlation, and PROCESS macros for data analysis., Results: The powerlessness score was significantly negatively associated with self-efficacy and confrontation coping mode scores and positively associated with patients' quality-of-life scores. In addition, self-efficacy and confrontation coping modes separately and sequentially mediated the relationship between powerlessness and quality of life., Conclusions: Self-efficacy and confrontation coping mode play important mediating roles between powerlessness and quality of life in patients with VLUs. By decreasing patients' sense of powerlessness, boosting their self-efficacy, and encouraging them to adopt confrontation coping mode, health professionals can improve patients' quality of life., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain., Methods: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents., Results: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling., Conclusions: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Competing Interests: The authors have no financial or conflicts of interest to disclose.

Depression is a common mental health disorder. With current depression detection methods, specialized physicians often engage in conversations and physiological examinations based on standardized scales as auxiliary measures for depression assessment. Non-biological markers-typically classified as verbal or non-verbal and deemed crucial evaluation criteria for depression-have not been effectively utilized. Specialized physicians usually require extensive training and experience to capture changes in these features. Advancements in deep learning technology have provided technical support for capturing non-biological markers. Several researchers have proposed automatic depression estimation (ADE) systems based on sounds and videos to assist physicians in capturing these features and conducting depression screening. This article summarizes commonly used public datasets and recent research on audio- and video-based ADE based on three perspectives: Datasets, deficiencies in existing research, and future development directions., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: In response to the growing challenges posed by an aging society, a telemedicine system was developed specifically for older adults postoperative patients, and its effectiveness was thoroughly investigated., Methods: Between May 2020 and May 2022, a total of 88 older adults postoperative patients were enrolled and randomly allocated into an experimental group and a control group. The experimental group received telemedicine services after discharge, while the control group received conventional medical services following the traditional protocol. One month after discharge, various indicators were evaluated for both groups, including number of visits, medical expenditures, postoperative recovery, anxiety, depression and satisfaction., Results: The number of visits and medical expenditures of the experimental group were less than those of the control group [1 (0, 1) vs. 1 (1, 2), Z  = -3.977, p  < 0.001; 25.25 (0.00, 277.40) yuan vs. 174.65 (49.63, 446.10) yuan, Z  = -2.150, p  = 0.032]. In both groups, there were 2 cases of incision infection, respectively. No significant difference was observed between the two groups (Fisher χ 2 , p = 0.259). In both groups, there was no instance of incision bleeding, incision dehiscence, readmission, or reoperation. Additionally, there was no significant difference in physical status between the two groups at discharge and after discharge (66.06 ± 8.92 vs. 65.45 ± 7.39 t = 0.287, p = 0.775; 73.33 ± 9.97 vs. 70.91 ± 7.50, t = 1.202, p = 0.235). And there was no significant difference in the change of physical status between the two groups after discharge [10.00 (0.00, 10.00) vs. 5.00 (0.00, 10.00), Z = -1.077, p = 0.281]. There was no significant difference in body weight change between the two groups after discharge [1.05 (0.38, 1.60) Kg vs. 0.80 (0.50, 1.43) Kg, Z = -0.265, p = 0.791]. There was no significant difference in the levels of anxiety and depression between the two groups at discharge (45.64 ± 8.10 vs. 44.60 ± 8.24, t = 0.520, p = 0.604, 48.33 ± 8.46 vs. 47.50 ± 6.85, t = 0.418, p = 0.677). But the levels of anxiety and depression in the experimental group were lower than those in the control group after discharge (34.92 ± 7.38 vs. 39.03 ± 8.42, t  = -2.183, p  = 0.032, 37.86 ± 7.29 vs. 41.93 ± 7.13, t  = -2.281, p  = 0.025); The change of anxiety level and depression level of the experimental group were more than those of the control group [-10.00 (-11.25, -8.75) vs. -5.00 (-7.81, -3.75), Z = -5.277, p < 0.001; -10.00 (-12.50, -7.50) vs. -5.00 (-7.75, -3.44), Z = -4.596, p < 0.001]. The level of satisfaction regarding medical services, daily care, and psychological comfort was higher in the experimental group compared to the control group [3 (3, 3.25) vs. 2 (1, 2), Z  = -5.931, p  < 0.001; 3 (3, 4) vs. 3 (2, 3), Z  = -2.286, p  = 0.022; 2 (1, 3) vs. 1 (0.75, 2), Z  = -2.081, p  = 0.037]., Conclusion: In the context of an aging society, telemedicine system can offer improved healthcare to older adults postoperative patients. This includes benefits such as reducing number of visits, saving medical expenditures, enhancing psychological comfort and daily care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chang, Han, Hu, Lin and Gu.)

In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug-loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG-E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG-E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl 4 models after tail vein injection of MUA/Y. Overall, this work reveals a macrophage-focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Moyamoya disease (MMD) is a cerebrovascular disease with unknown cause. Patients with MMD disease usually experience transient neurological events (TNEs) after revascularization surgery. This retrospective single-center study was aimed to explore the risk factors of postoperative TNEs after surgical revascularization in patients with MMD., Methods: We selected 324 patients who underwent surgical revascularization between January 2017 and September 2022 in our center. The perioperative characteristics of the patients were recorded and the outcome was TNEs after surgery. An analysis of risk factors contributing to postoperative TNEs by using logistic regression model., Results: Three hundred twelve patients were enrolled, and the incidence of postoperative TNEs was 34% in our study. Males were more likely to suffer from postoperative TNEs (OR = 2.344, p = 0.002). Preoperative ischemic presentation (OR = 1.849, p = 0.048) and intraoperative hypotension (OR = 2.332, p = 0.002) were associated with postoperative TNEs. Compared to patients with blood type O, patients with blood type A (OR = 2.325, p = 0.028), B (OR = 2.239, p = 0.027) and AB (OR = 2.938, p = 0.019) had a significantly higher incidence of postoperative TNEs. A risk prediction model for postoperative TNEs was established, and the established risk prediction area under the receiver operating characteristic curve (ROC) of the model was 0.741., Conclusions: Males, preoperative ischemic presentation and intraoperative hypotension were associated with postoperative TNEs. We also found a possible link between postoperative TNEs and ABO blood types after surgical revascularization for moyamoya patients., (© 2023. The Author(s).)

Purpose: To describe and assess the results of reconstruction of large, full-thickness defects of the central or medial lower eyelid using a semicircular skin flap, rotation of the remnant lateral eyelid, and a lateral tarsoconjunctival flap., Methods: The surgical approach is described, and the authors performed a retrospective chart review of consecutive patients between 2017 and 2023 reconstructed with this technique. Outcomes were assessed for size of eyelid defect, vision, subjective symptoms, facial and palpebral aperture symmetry, eyelid position and closure, corneal examination, surgical complications, and need for subsequent surgical intervention. Postoperative appearance was graded on malposition, distortion, asymmetry, contour deformity, and scarring (MDACS)., Results: Charts of 45 patients were identified. The average size of the lower eyelid defect was 18 mm (ranging from 12 to 26 mm). Facial and palpebral aperture symmetry were acceptable and all patients had preserved visual acuity and eyelid position and closure. The MDACS cosmetic score was perfect (0) in 15.6% (7/45) of eyelids, good (1-4) in 80.0% (36/45) of eyelids, and mediocre (5-14) in 4.4% (2/45) of eyelids. Second stage reconstruction was not necessary in 32 (71.1%) cases. There were no serious surgical complications, but minor complications included redness of the eyelid margin and pyogenic granulomas., Conclusions: Medial rotation of the remnant lower eyelid with a lateral semicircular skin and muscle flap over a lateral tarsoconjunctival flap was very effective in this series. Benefits include scarring within the facial skin tension lines, maintained vision throughout the recovery period, no eyelid retraction, and often single stage reconstruction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Pulmonary fibrosis (PF) is an age-related interstitial lung disease that results in notable morbidity and mortality. The Food and Drug Administration-approved drugs can decelerate the progression of PF; however, curing aged patients with severe fibrosis is ineffective because of insufficient accumulation of these drugs and wide necrocytosis of type II alveolar epithelial cells (AEC IIs). Here, we constructed a mesenchymal stem cell (MSC)-based nanoengineered platform via the bioconjugation of MSCs and type I collagenase-modified liposomes loaded with nintedanib (MSCs-Lip@NCAF) for treating severe fibrosis. Specifically, MSCs-Lip@NCAF migrated to fibrotic lungs because of the homing characteristic of MSCs and then Lip@NCAF was sensitively released. Subsequently, Lip@NCAF ablated collagen fibers, delivered nintedanib into fibroblasts, and inhibited fibroblast overactivation. MSCs differentiated into AEC IIs to repair alveolar structure and ultimately promote the regeneration of damaged lungs in aged mice. Our findings indicated that MSCs-Lip@NCAF could be used as a promising therapeutic candidate for PF therapy, especially in aged patients.

Background: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications., Aim: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes., Methods: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet β-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs., Results: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet β-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-β compared with that of NCs; a notable difference in HOMA-β was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-β, and fasting glucose/insulin ratio when compared with NCs., Conclusion: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Advanced gastric cancer is a highly thrombogenic cancer per Khorana score. Recent clinical practice guidelines suggest primary outpatient thromboprophylaxis (POTP) for patients with a Khorana score ≥2. We performed an updated meta-analysis to evaluate the benefit of POTP in patients with gastric cancer and gastroesophageal junction cancers receiving chemotherapy. Randomized controlled trials with reduction in venous thromboembolism (VTE) as a primary or secondary endpoint were incorporated. A total of 631 patients from subgroups of three randomized controlled trials were included. The VTE incidence was 1.6% and 5.1% in POTP and control groups, respectively (risk ratio 0.31; confidence interval 0.11 to 0.83; P  = 0.02), with a number needed to treat of 29 to prevent one VTE event. Even though the recent clinical practice guidelines suggest POTP in patients with gastric cancer and gastroesophageal junction cancers, our meta-analysis findings do not support the routine use of POTP in those patients., Competing Interests: This study was presented as a poster presentation at the annual meeting of the American Society of Hematology in New Orleans in December 2022. The authors report no funding or conflicts of interest., (Copyright © 2023 Baylor University Medical Center.)

Epithelioid sarcoma is a rare soft tissue neoplasm of uncertain differentiation that typically affects the distal extremities. Primary orbital epithelioid sarcoma is rare, and no reports exist characterizing metastases of this tumor to the orbit and ocular adnexa. In this article, the authors describe a rare case of eyelid metastasis in a 47-year-old man with epithelioid sarcoma of the right fibula diagnosed 16 months earlier who was otherwise doing well on the adjuvant tazemetostat therapy. In addition, the authors perform a retrospective review of cases of primary orbital epithelioid sarcoma reported in the literature, of which 4 patients responded favorably to surgical excision whereas 2 others eventually died as a direct result of their disease., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 μg/mL) group at 125 μg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

As the prevalence of diabetes rises, the use of antidiabetic drugs becomes more frequent. Thus, focusing on the effects of these drugs on water-sodium balance and electrolyte regulation is necessary. This review discusses the effects and the mechanisms behind them. Several sulfonylureas, such as chlorpropamide, methanesulfonamide, and tolbutamide, exhibit water-retaining properties. Other sulfonylureas, such as glipizide, glibenclamide, acetohexamide, and tolazamide, are not antidiuretic or even diuretic. Numerous clinical studies showed that metformin can reduce serum magnesium concentrations and may have an effect on the cardiovascular system, but the specific mechanism remains to be discussed. Different opinions exist about the mechanisms of thiazolidinedione-induced fluid retention. Sodium-glucose cotransporter 2 inhibitors can cause osmotic diuresis and natriuresis and elevated serum potassium and magnesium concentrations. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors can enhance urine sodium excretion. At the same time, increased urinary sodium caused by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors reduce blood pressure and plasma volume, thereby protecting the heart. Insulin has a sodium-retaining effect and is also associated with hypokalemia, hypomagnesemia, and hypophosphatemia. Several of the aforementioned pathophysiological changes and mechanisms have been discussed, and conclusions have been drawn. However, further investigation and discussion are still warranted.

Ca A Fe4As4 with A = K, Rb, and Cs are close to the doped 122 system, and the parent material can reach a superconducting transition temperature of 31-36 K without doping. To study the role of alkali metals, we investigated the induced hole doping and chemical pressure effects as a result of the introduction of alkali metals using density-functional-based methods. These two effects can affect the superconducting transition temperature by changing the number of electrons and the structure of the FeAs conductive layer, respectively. Our study shows that the dxz and dyz orbitals, which are degenerate in CaFe2As2, become nondegenerate in Ca A Fe4As4 due to two nonequivalent arsenic atoms (As1 and As2). The unusual oblate ellipsoid hole pocket at Γ point in Ca A Fe4As4 results from a divalent cation Ca 2 + replaced by a monovalent cation A + . It shows one of the main differences in fermiology compared to a particular form of CaFe2As2 with reduced 1144 symmetry, due to the enhancement of As2-Fe hybridization. The unusual band appears in CaFe2As2 (1144) and gradually disappears in the change of K to Cs. Further analysis shows that this band is contributed by As1 and has strong dispersion perpendicular to the FeAs layer, suggesting that it is related to the peculiar van Hove singularity below the Fermi level. In addition, various aspects of CaFe2As2 (1144) and Ca A Fe4As4 in the ground state are discussed in terms of the influence of hole doping and chemical pressure.

Pancreatic fibrosis is mainly manifested by imbalance in extracellular matrix (ECM) homeostasis due to excessive deposition of collagen in pancreas by activated pancreatic stellate cells (PSCs). Recently, some drugs have exhibited therapeutic potentials for the treatment of pancreatic fibrosis; however, currently, no effective clinical strategy is available to remodel imbalanced ECM homeostasis because of inferior targeting abilities of drugs and collagen barriers that hinder the efficient delivery of drugs. Herein, we design and prepare collagen-binding peptide (CBP) and collagenase I co-decorated dual drug-loaded lipid nanoparticles (named AT-CC) for pancreatic fibrosis therapy. Specifically, AT-CC can target fibrotic pancreas via the CBP and degrade excess collagen by the grafted collagenase I, thereby effectively delivering all-trans-retinoic acid (ATRA) and ammonium tetrathiomolybdate (TM) into pancreas. The released ATRA can reduce collagen overproduction by inhibiting the activation of PSCs. Moreover, the released TM can restrain lysyloxidase activation, consequently reducing collagen cross-linking. The combination of ATRA and TM represses collagen synthesis and reduces collagen cross linkages to restore ECM homeostasis. The results of this research suggest that AT-CC is a safe and efficient collagen-targeted degradation drug-delivery system for reversing pancreatic fibrosis. Furthermore, the strategy proposed herein will offer an innovative platform for the treatment of chronic pancreatitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The authors describe a case of Kimura disease (KD) affecting the lacrimal gland, the ipsilateral periorbita, and the contralateral earlobe. The authors also review the literature for characteristics and outcomes of KD affecting the periorbita or earlobe., Methods: The authors review retrospectively a single chart and abstract data from the English language literature., Results: A 15-year-old Samoan male presented with a left upper eyelid mass and later the contralateral earlobe and ipsilateral periorbita. Surgical resection was partially effective and normal vision and eye motility were maintained. Histopathology was consistent with KD. Thirty-seven cases of periorbital KD were identified in the literature. The average age of patients with periorbital KD was 31.9 years (standard deviation: 17.8 years), with 81.1% (30/37) of patients being male and 69.4% (25/36) Asian. Over half of periorbital KD patients had lacrimal gland involvement (51.3%; 19/37). Fifteen patients were initially treated with surgery; 3 (20%) had recurrence of the disease. Another 15 patients were initially treated with corticosteroids; 12 (80%) had recurrence of the disease. Ophthalmologic data, when reported, demonstrated that, most patients had no visual (77.8%; 14/18 patients) or motility disturbances (82.4%; 14/17 patients) but most had proptosis 71.4% (10/14). Only 4 cases of earlobe involvement in KD were identified, all in women., Conclusions: In the literature, orbital KD was rare but often affected the lacrimal gland and caused proptosis, commonly in young adult Asian males. Vision and extraocular motility were usually normal. Earlobe involvement was very rare. This unique case of KD that affected the orbit and contralateral earlobe corroborates the prior literature that KD is prone to recurrence but may not adversely affect vision or extraocular motility., Competing Interests: The authors have no financial or conflicts of interest to disclose. This manuscript has not been previously presented at a local or international conference. Gavin Herbert Eye Institute is a recipient of an institutional Research to Prevent Blindness grant., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)