Exploration of the factors affecting different delirium subtypes in hospitalized COVID-19 patients: a multicentre cross-sectional study.

During the COVID-19 pandemic, delirium became a major complication that worsened patient outcomes. However, the factors influencing the severity of delirium in patients with COVID-19 have not been determined. We conducted this study to detect influencing factors associated with subtypes of delirium in patients with COVID-19. We included 1774 adult inpatients with COVID-19 from January to February 2023 at 7 sites in China. And used the 3 min Confusion Assessment Method and the Richmond Agitation-Sedation Scale for site assessment to identify and classify subtypes of delirium. Laboratory data were obtained from the Hospital Information System. After multivariate analysis, hypoactive delirium was significantly associated with age, the serum albumin concentration, frailty and sarcopenia, and health and nutritional status. Mixed delirium was significantly associated with age, D-dimer level, sarcopenia, health status and nutritional status. Additionally, hyperactive delirium was significantly associated with age, procalcitonin levels, frailty status and health status. Our findings suggest that poor nutritional status and low serum albumin concentration can help detect patients at high risk of developing hypoactive and mixed delirium. Additionally, clinical staff should pay more attention to patients with inflammatory conditions to assess and detect delirium because many influencing factors are involved in the common pathological mechanism of inflammation.

Study on chemical characterization and sleep-improvement function of Prunella vulgaris L. based on the functional components.

Prunella vulgaris L. (P. vulgaris) has great application value and development prospects in improving sleep. In this study, we continued to evaluate the sleep-improvement function and mechanism of P. vulgaris from both chemical characterization and function based on sleep-improvement functional ingredients, rosmarinic acid and salviaflaside, screened out in the previous stage as the index components. The chemical constituents of P. vulgaris and its phenolic acid fraction were characterized by the UPLC-MSn technology. The quality of the sleep-improvement phenolic acid fraction of P. vulgaris was scientifically evaluated by fingerprints combined with quantitative analysis of rosmarinic acid and salviaflaside. The function of phenolic acid parts of P. vulgaris in improving sleep was verified by different insomnia models including the PCPA-induced insomnia model and surface platform sleep deprivation model. HE staining was used to observe the effect of P. vulgaris on the morphology of nerve cells in different brain regions. In vivo experiments and molecular docking explored the sedative-hypnotic effects of functional ingredients of P. vulgaris. All these results investigated the material basis and mechanism of P. vulgaris to improve sleep from multiple perspectives, which contribute to providing a basis for the development of functional food to improve sleep.

Alteration of bone microarchitecture in hereditary distal RTA patients with SLC4A1 gene mutation: assessed by HR-pQCT.

CONTEXT: Hereditary distal renal tubular acidosis caused by SLC4A1 gene mutation (SLC4A1-dRTA) is a rare hereditary form of renal tubular acidosis. Rickets or osteomalacia is a common complication of SLC4A1-dRTA, and seriously affects patients' daily life. However, studies on the bone microstructure in SLC4A1-dRTA are limited. OBJECTIVE: This work aimed to evaluate the bone microstructure of SLC4A1-dRTA patients, compared to age- and sex-matched healthy controls and X-linked hypophosphatemic rickets (XLH) patients. METHODS: This was a retrospective study on eleven SLC4A1-dRTA patients. Clinical manifestations, biochemical and radiographical examinations were characterized. Bone microstructure was examined in seven SLC4A1-dRTA patients, seven healthy controls and twenty-one XLH patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Skeletal symptoms, including fracture, bone pain, and lower limb deformity, were presented in 72.7% of SLC4A1-dRTA patients. Short stature was presented in 63.6% of the patients. SLC4A1-dRTA patients had significantly lower volumetric BMD in the distal tibia, and more severe deteriorated trabecular bone in the distal radius and tibia than healthy controls. SLC4A1-dRTA patients had significantly more severe deteriorated trabecular bone in the distal radius and distal tibia compared to XLH patients. With long-term alkaline therapy, SLC4A1-dRTA patients had alleviation in bone pain, increase in height. CONCLUSIONS: Skeletal lesions were common clinical manifestations in SLC4A1-dRTA patients. Compared with XLH, another common type of rickets, SLC4A1-dRTA patients had more severe trabecular bone microstructure damage, further supporting the necessity of early diagnosis and timely treatment of the disease.

PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. METHODS: To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT-qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1's regulation of autophagy in GC. RESULTS: Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. CONCLUSION: PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC.

Trophic transfer of dechloranes in marine food webs in Dalian Bay, China.

Dechloranes, including dechlorane 602 (Dec 602), dechlorane 603 (Dec 603), dechlorane 604 (Dec 604), dechlorane plus (DP, including syn- and anti-DP) and mirex, were determined in marine food web from Dalian Bay, Northeast China to investigate their occurrence andtrophic transfer. In all organisms, the detection rates were Dec 602 (99%) > mirex (95%) > Dec 603 (92%) > anti-DP (91%) > syn-DP (82%) > Dec 604 (9.6%). The concentrations were 0.92-16 ng/g lipid weight (lw) for mirex, 0.53-2.3 ng/g lw for syn-DP, 1.1-4.5 ng/g lw for anti-DP, 0.19-5.0 ng/g lw for Dec 602, 0.26-1.9 ng/g lw for Dec 603 and 0.020-0.33 ng/g lw for Dec 604. Significant positive relationships (p < 0.0001) were observed between lipid normalized concentrations and trophic levels for mirex (R2 = 0.80) and Dec602 (R2 = 0.82) in food webs, with the calculated TMFs values of 3.09 and 3.39, respectively, indicating the trophic magnification potential of these compounds. For syn-DP, anti-DP, Dec 603 and Dec 604, the similar significant relationships were not found, suggesting that these chemicals do not trophic magnification nor trophic dilution in the food web. With low log KOW values for mirex (7.01) and Dec 602 (8.05), these two compounds have the highest magnifications potentials, while the magnification potential of Dec 603, Dec 604 and DP dramatically decreased because of their extremely big log KOW values (higher than 10). The observed fractional abundance of anti-DP (fanti) ranged of 0.58-0.69, closing to the one in Chinese industrial products, indicating DP isomers had not undergone significant differences of physicochemical or biological process in the studied food web.

Effectiveness of silver and iodine dressings on wound healing: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of silver and iodine dressings on healing time, healing rate, exudate amount, pain and anti-infective efficacy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Databases including PubMed, Cochrane Library, Embase, Web of Science and CINAHL were surveyed up to May 2024. ELIGIBILITY CRITERIA: Randomised controlled trials comparing silver and iodine dressings on wound healing in humans. DATA EXTRACTION AND SYNTHESIS: Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data extraction was done independently by two reviewers, with the risk of bias assessed using the Cochrane tool. Narrative synthesis was performed to evaluate the effects of silver and iodine dressings on healing time, healing rate, pain, exudate amount and anti-infective efficacy. Meta-analysis using Review Manager V.5.4 calculated standardised mean differences for healing time and relative risks for rate to quantify the impacts of the treatments. RESULTS: 17 studies (18 articles) were included. The meta-analysis indicated that silver dressings significantly reduced healing time compared with iodine dressings (SMD=-0.95, 95% CI -1.62 to -0.28, I2=92%, p=0.005, moderate-quality evidence), with no significant difference in enhancing healing rate (RR=1.29, 95% CI 0.90 to 1.85, I2=91%, p=0.16, low-quality evidence). Based on low-quality evidence, for exudate amount (3/17), 66.7% (2/3) of the studies favoured silver dressings over iodine in reducing exudate volume. For pain (7/17), 57.1% (4/7) of the studies reported no significant difference between silver and iodine dressings, while 42.9% (3/7) studies indicated superior pain relief with silver dressings. For anti-infective efficacy (11/13), 54.5% (6/11) of the studies showed equivalence between silver and iodine dressings, while 36.4% (4/11) suggested greater antibacterial efficacy for silver. CONCLUSION: Silver dressings, demonstrating a comparable healing rate to iodine dressings, significantly reduce healing time, suggesting their potential as a superior adjunct in wound care. PROSPERO REGISTRATION NUMBER: CRD42020199602.

Alterations in serum metabolomics during the first seizure and after effective control of epilepsy.

The existing diagnostic methods of epilepsy have great limitations, and more reliable and less difficult diagnostic methods are needed. We collected serum samples of adult patients with first-diagnosed epilepsy (EPs) and seizure control patients (EPRs) for non-targeted metabolomics detection and found that they were both significantly altered, with increased expression of nicotine addiction, linoleic acid metabolism, purine metabolism, and other metabolic pathways. The diagnostic model based on 4 differential metabolites achieved a diagnostic efficiency of 99.4% in the training cohort and 100% in the validation cohort. In addition, the association analysis of oral flora, serum metabolism, and clinical indicators also provided a new angle to analyze the mechanism of epilepsy. In conclusion, this study characterized the serum metabolic characteristics of EPs and EPRs and the changes before and after epilepsy control based on a large cohort, demonstrating the potential of metabolites as non-invasive diagnostic tools for epilepsy.

Piperazine ferulate inhibits diabetic nephropathy by suppressing AGE/RAGE-mediated inflammatory signaling in rats and podocytes.

Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.

Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy.

BACKGROUND: Pancreatic cancer (PC) is characterized by a poor prognosis and limited treatment options. Ferroptosis plays an important role in cancer, SET and MYND domain-containing protein 2 (SMYD2) is widely expressed in various cancers. However, the role of SMYD2 in regulating ferroptosis in PC remains unexplored. This study aimed to investigate the role of SMYD2 in mediating ferroptosis and its mechanistic implications in PC progression. METHODS: The levels of SMYD2, c-Myc, and NCOA4 were assessed in PC tissues, and peritumoral tissues. SMYD2 expression was further analyzed in human PC cell lines. In BxPC3 cells, the expression of c-Myc, NCOA4, autophagy-related proteins, and mitochondrial morphology, was evaluated following transfection with si-SMYD2 and treatment with autophagy inhibitors and ferroptosis inhibitors. Ferroptosis levels were quantified using flow cytometry and ELISA assays. RNA immunoprecipitation was conducted to elucidate the interaction between c-Myc and NCOA4 mRNA. A xenograft mouse model was constructed to validate the impact of SMYD2 knockdown on PC growth. RESULTS: SMYD2 and c-Myc were found to be highly expressed in PC tissues, while NCOA4 showed reduced expression. Among the PC cell lines studied, BxPC3 cells exhibited the highest SMYD2 expression. SMYD2 knockdown led to decreased c-Myc levels, increased NCOA4 expression, reduced autophagy-related protein expression, mitochondrial shrinkage, and heightened ferroptosis levels. Additionally, an interaction between c-Myc and NCOA4 was identified. In vivo, SMYD2 knockdown inhibited tumor growth. CONCLUSIONS: Targeting SMYD2 inhibits PC progression by promoting ferritinophagy-dependent ferroptosis through the c-Myc/NCOA4 axis. These findings provide insights into potential diagnostic and therapeutic strategies for PC.

Causal Effects of Asthma on Upper Airway Diseases and Allergic Diseases: A Two-Sample Mendelian Randomization.

INTRODUCTION: Asthma is associated with upper airway diseases and allergic diseases; however, the causal effects need to be investigated further. Thus, we performed this two-sample Mendelian randomization (MR) analysis to explore and measure the causal effects of asthma on allergic rhinitis (AR), vasomotor rhinitis (VMR), allergic conjunctivitis (AC), atopic dermatitis (AD), and allergic urticaria (AU). METHODS: The data for asthma, AR, VMR, AC, AD, and AU were obtained from large-scale genome-wide association studies summarized recently. We defined single-nucleotide polymorphisms satisfying the MR assumptions as instrumental variables. Inverse-variance weighted (IVW) approach under random-effects was applied as the dominant method for causal estimation. The weighted median approach, MR-Egger regression analysis, MR pleiotropy residual sum and outlier test, and leave-one-out sensitivity analysis were performed as sensitivity analysis. Horizontal pleiotropy was measured using MR-Egger regression analysis. Significant causal effects were attempted for replication and meta-analysis. RESULTS: We revealed that asthma had causal effects on AR (IVW, odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.74-2.14; p < 0.001), VMR (IVW, OR = 1.40; 95% CI, 1.15-1.71; p < 0.001), AC (IVW, OR = 1.65; 95% CI, 1.49-1.82; p < 0.001), and AD (IVW, OR = 2.13; 95% CI, 1.82-2.49; p < 0.001). No causal effect of asthma on AU was observed. Sensitivity analysis further assured the robustness of these results. The evaluation of the replication stage and meta-analysis further confirmed the causal effect of asthma on AR (IVW OR = 1.81, 95% CI 1.62-2.02, p < 0.001), AC (IVW OR = 1.44, 95% CI 1.11-1.87, p < 0.001), and AD (IVW OR = 1.85, 95% CI 1.42-2.41, p < 0.001). CONCLUSIONS: We revealed and quantified the causal effects of asthma on AR, VMR, AC, and AD. These findings can provide powerful causal evidence of asthma on upper airway diseases and allergic diseases, suggesting that the treatment of asthma should be a preventive and therapeutic strategy for AR, VMR, AC, and AD.

Chronic ethanol exposure induces cardiac fibroblast transdifferentiation via ceramide accumulation and oxidative stress.

AIMS: Excessive alcohol consumption is associated with cardiac dysfunction and the development of myocardial fibrosis. In this study, we aimed to investigate the direct impacts of ethanol on myocardial fibroblasts and elucidate the underlying mechanism responsible for chronic ethanol-induced myocardial fibrosis. METHODS: Rat primary cardiac fibroblasts exposed to ethanol for 24 h and C57BL/6J mice fed on Lieber-DeCarli diet to establish an ethanol intoxication model in vitro and in vivo, respectively. Histological analyses, molecular biology techniques, and analytical chemistry methods were then conducted. RESULTS AND CONCLUSION: In vivo and vitro experiments revealed that chronic ethanol exposure induced increased myocardial fibrosis and augmented the transdifferentiation of myocardial fibroblasts. Simultaneously, it elicited an upregulation in the production of long-chain and very-long-chain ceramides in cardiac fibroblasts. The excessive accumulation of ceramide leads to elevated levels of intracellular oxidative stress, culminating in the activation of TGF-ß-SMAD3 signaling and the development of fibrosis. Intervention of these pathways with pharmacological inhibitors in vitro or in vivo inhibited fibrosis. In conclusion, ethanol increased ceramides and reactive oxygen species (ROS) in cardiac fibroblasts, resulting in the activation of TGF-ß-SMAD3 signaling, transdifferentiation of fibroblasts, and myocardial fibrosis.

Effect of the nurse-led Hospital Elder Life Program on delirium reduction among delirious patients with COVID-19: A randomized clinical trial.

BACKGROUND: Infectious diseases, such as COVID-19, are high-risk factors for delirium. However, the implementation of nonpharmacological interventions faces major challenges during an infectious disease pandemic. AIMS: To evaluate the effect of the nurse-led Hospital Elder Life Program (NL-HELP) on delirium reduction among delirious patients with COVID-19. DESIGN: A single-blind randomized clinical trial. METHODS: This study recruited 122 delirious patients with COVID-19 from internal medicine wards at West China Hospital in China between January 30 and March 31, 2023. Participants were randomized to the NL-HELP group (n = 62) or the usual care group (n = 60). Patients in the intervention group received the NL-HELP protocol three times daily for 7 days. Patients in the control group received usual care. The primary outcome was the absence/presence of delirium during the intervention period measured by the 3-min Diagnostic Confusion Assessment Method. RESULTS: Fewer patients remained delirious in the NL-HELP group than in the control group. There were significantly more delirium-free days in the NL-HELP group than in the usual care group. There were no statistically significant differences between the two groups in terms of delirium severity, length of hospital stay, delirium at 30 days after discharge, 30-day readmission, 30-day mortality, physical function or quality of life. CONCLUSIONS: This study demonstrated that NL-HELP could reduce the presence of delirium in delirious patients. No effect was observed in terms of shortening the length of hospital stay, reducing 30-day mortality, or improving quality of life. IMPACT: NL-HELP may be effective in reducing the presence of delirium in delirious patients. Further research is needed to determine whether the NL-HELP can improve patient outcomes (e.g. mortality and quality of life) in a larger study. PATIENT OR PUBLIC CONTRIBUTION: Caregivers of delirious patients were invited to provide intervention strategies to prevent or abate delirium, including environmental management, orientation communications and identification of alert signs. TRIAL REGISTRATION: This study was prospectively registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/) Identifier: ChiCTR2300067874.

Can board of directors' faultlines improve corporate innovation performance? Evidence from China.

Innovation, which is a pivotal force behind the sustained growth of enterprises, has garnered significant attention across various industries. As the epicenter of corporate decision-making, the board of directors plays a pivotal role in allocating resources and overseeing the execution of strategy. Consequently, it inevitably impacts the innovation capabilities of a business. Previous research has focused primarily on single board member characteristics, such as age, gender, tenure, and educational qualifications, overlooking the cumulative influence of multiple attributes. Therefore, this study aims to investigate the impact of faultlines arising from the intersection of these characteristics within a board on innovation performance. Using panel data from China's A-share listed companies from 2010 to 2021, this research constructs a framework to analyze board faultlines based on gender, age, education, director tenure, independence status, and occupational background. A comprehensive examination reveals a positive association between board faultlines and innovation performance, indicating that diversity within a board can foster enhanced innovative outputs. These findings persist even after rigorous robustness tests, including two-stage instrumental variable regression using lagged innovation performance as well as when substituting explanatory variables and sample intervals. Further analysis reveals that the influence of board faultlines on innovation performance is significant only under certain contextual conditions: when equity concentration is low, industry competition is intense, and risk aversion is greater. This study offers valuable insights for optimizing board membership configurations and thus, ultimately, enhancing the innovation capabilities of enterprises.

Complementary therapy with Chinese aromatic herbs to promote awakening in a comatose patient: A case report.

RATIONALE: Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be "resuscitation with aromatics" based on traditional Chinese medicines theory. PATIENT CONCERNS: A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury. DIAGNOSES: Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease. INTERVENTIONS: According to the patient's condition, we use the Chinese aromatic herbs as a complementary therapy. OUTCOMES: Following a month-long administration, the patient's consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background. LESSONS: The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient's consciousness and EEG background. This could be attributed to the herbs' inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.

CRISPR/Cas13a-based genome editing for establishing the detection method of H9N2 subtype avian influenza virus.

Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature.

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

A novel costimulatory molecule gene-modified leukemia cell-derived exosome enhances the anti-leukemia efficacy of DC vaccine in mouse models.

OBJECTIVES: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models. METHODS: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCsLEX-8086). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCsLEX8086 in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCsLEX8086 in animal models. RESULTS: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCsLEX8086 significantly activated CD8+ T cells and boosted the CTL response in vitro. More importantly, DCsLEX-8086 effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCsLEX-8086 promoted the proportion of CD4+ T cells, CD8+ T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCsLEX-8086 showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments. CONCLUSION: The results suggested that DCsLEX-8086 induces a more effective anti-leukemia immunity compared to DCsLEX-null in vivo and in vitro. DCsLEX-8086 might achieve antitumor effects by elevating the numbers of CD4+ T cells, CD8+ T cells, and M1 macrophages in tumors. Our findings indicate that DCsLEX-8086 could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.