Hepatocellular carcinoma (HCC) is a global public health problem with increased morbidity and mortality. Agrimol B, a natural polyphenol, has been proved to be a potential anticancer drug. Our recent report showed a favorable anticancer effect of agrimol B in HCC, however, the mechanism of action remains unclear. Here, we found agrimol B inhibits the growth and proliferation of HCC cells in vitro as well as in an HCC patient-derived xenograft (PDX) model. Notably, agrimol B drives autophagy initiation and blocks autophagosome-lysosome fusion, resulting in autophagosome accumulation and autophagy arrest in HCC cells. Mechanistically, agrimol B downregulates the protein level of NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1) through caspase 3-mediated degradation, leading to mitochondrial reactive oxygen species (mROS) accumulation and autophagy arrest. NDUFS1 overexpression partially restores mROS overproduction, autophagosome accumulation, and growth inhibition induced by agrimol B, suggesting a cytotoxic role of agrimol B-induced autophagy arrest in HCC cells. Notably, agrimol B significantly enhances the sensitivity of HCC cells to sorafenib in vitro and in vivo. In conclusion, our study uncovers the anticancer mechanism of agrimol B in HCC involving the regulation of oxidative stress and autophagy, and suggests agrimol B as a potential therapeutic drug for HCC treatment.
Designing high-performance polarization-sensitive photodetectors is essential for photonic device applications. Anisotropic one-dimensional (1D) van der Waals (vdW) materials have provided a promising platform to that end. Despite significant advances in 1D vdW photonic devices, their performance is still far from delivering practical potential. Herein, we propose the design of high-performance polarization-sensitive photodetectors using unique 1D vdW materials. By leveraging the chemical vapor transport technique, we successfully fabricate high-quality 1D vdW Nb2Pd1-xSe5 (x = 0.29) nanowires. The 1D vdW Nb2Pd1-xSe5 photodetector exhibits a high mobility of â¼56 cm2/(V s) and superior photoresponse performance, including a high responsivity of 1A/W and an ultrafast response time of â¼8 µs under 638 nm illumination. Moreover, the 1D vdW Nb2Pd1-xSe5 photodetector demonstrates excellent polarization-sensitive photoresponse with a degree of linear polarization (DOLP) up to 0.85 and can be modulated by adjusting the gate voltage, laser power density, and wavelength. Those exceptional performance are believed to be relevant to the symmetry-reduction induced by the partial occupation of Pd sites. This study offers feasible approaches to enhance the anisotropy of 1D vdW materials and the modulation of their polarization-sensitive photoresponse, which may provide deep insights into the physical origin of anisotropic properties of 1D vdW materials.
The sulfate radical (SO4â¢-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4â¢- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.
High-quality cardiopulmonary resuscitation (CPR) and training are important for successful revival during out-of-hospital cardiac arrest (OHCA). However, existing training faces challenges in quantifying each aspect. This study aimed to explore the possibility of using a three-dimensional motion capture system to accurately and effectively assess CPR operations, particularly about the non-quantified arm postures, and analyze the relationship among them to guide students to improve their performance. We used a motion capture system (Mars series, Nokov, China) to collect compression data about five cycles, recording dynamic data of each marker point in three-dimensional space following time and calculating depth and arm angles. Most unstably deviated to some extent from the standard, especially for the untrained students. Five data sets for each parameter per individual all revealed statistically significant differences (p < 0.05). The correlation between Angle 1' and Angle 2' for trained (rs = 0.203, p < 0.05) and untrained students (rs = -0.581, p < 0.01) showed a difference. Their performance still needed improvement. When conducting assessments, we should focus on not only the overall performance but also each compression. This study provides a new perspective for quantifying compression parameters, and future efforts should continue to incorporate new parameters and analyze the relationship among them.
Cardiopulmonary Resuscitation , Data Compression , Humans , Feasibility Studies , Motion Capture , China
Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 µg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1ß, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.
Acrylic Resins , Dermatitis , Flavanones , Glucosides , Sunburn , Animals , Mice , Humans , Ultraviolet Rays , Interleukin-6 , Tumor Necrosis Factor-alpha , Wound Healing , Interleukin-1beta , Anti-Inflammatory Agents
BACKGROUND: Hemorrhoids are among the most common and frequently encountered chronic anorectal diseases in anorectal surgery. They are venous clusters formed by congestion, expansion, and flexion of the venous plexus in the lower part of the rectum. Mixed hemorrhoids bleed easily and recurrently, and this can result in severe anemia. Hence, they may have a negative effect on the health of the patient and surgical treatment is required. Milligan-Morgan hemorrhoidectomy has been widely used since 1937 for the treatment of grade III and IV hemorrhoids. However, most patients experience different degrees of postoperative pain that may cause anxiety. AIM: To assess the factors influencing pain scores and quality of life (QoL) in patients with mixed hemorrhoids post-surgery. METHODS: The clinical data of patients with mixed hemorrhoids who underwent Milligan-Morgan hemorrhoidectomy were collected retrospectively. The basic characteristics of the enrolled patients with mixed hemorrhoids were recorded, and based on the Goligher clinical grading system, the hemorrhoids were classified as grades III or IV. The endpoint of this study was the disappearance of pain in all patients. Quantitative data were presented as mean ± SD, such as age, pain score, and QoL score. Student's t-test was used to compare the groups. RESULTS: A total of 164 patients were enrolled. The distribution of the visual analog scale pain scores of all patients at 3, 7, 14 and 28 d after surgery showed that post-surgery pain was significantly reduced with the passage of time. Fourteen days after the operation, the pain had completely disappeared in some patients. Twenty-eight days after the surgery, none of the patients experienced any pain. Comparing the World Health Organization Quality of Life - BREF self-reporting questionnaire scores of patients between 14 and 28 d after surgery, we observed that the quality-of-life scores of the patients post-surgery had significantly improved. There were six items that were compared at 14- and 28-d post-surgery. The mean QoL score 28 d after surgery (4.79 ± 0.46) was higher than that at 14 d post-surgery (3.79 ± 0.57). The mean health condition score 28 d after surgery (4.80 ± 0.41) was also higher than that at 14 d post-surgery (4.01 ± 0.62). The mean physical health score 28 d after surgery (32.10 ± 2.96) was significantly higher than that at 14 d post-surgery (23.41 ± 2.85). The mean psychological health score 28 d after surgery (27.22 ± 1.62) was significantly higher than that at 14 d post-surgery (21.37 ± 1.70). The mean social relations score 28 d after surgery (12.21 ± 1.59) was significantly higher than that at 14 d post-surgery (6.32 ± 1.66). The mean surrounding environment score 28 d after surgery (37.13 ± 2.88) was significantly higher than that at 14 d post-surgery (28.42 ± 2.86). The differences in quality-of-life scores at day 14 and day 28 post-surgery were observed to be statistically significant (P < 0.001). CONCLUSION: Milligan-Morgan hemorrhoidectomy can significantly improve the postoperative QoL of patients. Age, sex, and the number of surgical resections were important factors influencing Milligan-Morgan hemorrhoidectomy.
Introduction: Lacticaseibacillus rhamnosus AFY06 (LR-AFY06) is a microorganism isolated from naturally fermented yogurt in Xinjiang, China. Methods: In this study, we investigated the effects and mechanisms of LR-AFY06 in a mouse model of inflammation-associated colon cancer. The mouse model was established by azoxymethane/dextran sulfate sodium (AOM/DSS) induction. The tumor number in intestinal tissues was counted, and the histopathological analysis was performed on colon tissues. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction were performed to measure relevant protein levels in colon tissues. Results: LR-AFY06 treatment alleviated weight loss, increased organ index, reduced intestinal tumor incidence, improved histopathological damage, decreased the levels of inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), nuclear factor κB (NF-κB), and inducible nitric oxide synthase (iNOS) in the serum and colon tissue, downregulated the mRNA expression of inhibitor of NF-κB beta (IκBß), p65, p50, p52, B-cell lymphoma-2 (Bcl-2), and B-cell lymphoma-extra large (Bcl-xL) in colon tissues, and increased the mRNA expression of Bid and caspase-8. The high concentration of LR-AFY06 exerted a better effect than the low concentration; however, the effect was slightly inferior to that of aspirin. Moreover, LR-AFY06 mitigated the intestinal inflammatory process and inhibited intestinal tumor development by regulating the NF-κB and apoptosis pathways. Discussion: The present study indicates the regulatory potential of LR-AFY06 in inflammation-associated colorectal cancer in mice, providing a valuable basis for further research.
Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.
Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.
BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.
Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.
Alzheimer Disease , Cannabidiol , Cognitive Dysfunction , Mice , Animals , Alzheimer Disease/drug therapy , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Brain-Gut Axis , Cognition , Cognitive Dysfunction/drug therapy , Disease Models, Animal
OBJECTIVE: To examine the effects of web neonatal intensive care unit diaries on the mental health, quality of life, sleep quality, care ability, and hormone levels of parents of preterm infants in the neonatal intensive care unit. DESIGN: Prospective randomized controlled parallel-group clinical trial. SETTING: Maternal and Child Health Hospital, Fujian, China. METHODS: The control group received routine neonatal intensive care unit care, while the intervention group received a web neonatal intensive care unit diary based on routine care. Outcomes, including anxiety, depression, and post-traumatic stress disorder symptoms, quality of life, sleep quality, care ability, and cortisol and melatonin levels, were evaluated at T1 (Time 1, before the intervention), T2 (Time 2, immediately after the intervention), and T3 (Time 3, 1 month after the intervention). RESULTS: Seventy pairs of parents of preterm infants in the neonatal intensive care unit were randomly allocated to two groups: intervention (n = 35) and control (n = 35). The anxiety scores in the intervention group were significantly lower at T2 and T3 than those in the control group (P < 0.001). The care ability scores in the intervention group were significantly higher at T2 and T3 (P < 0.001). The prevalence of post-traumatic stress disorder at T3 was significantly different between the groups (P = 0.040). No significant differences were observed in the quality of life or sleep quality between the groups at T2 and T3 (P > 0.05). No significant differences were observed in cortisol and melatonin levels between the groups (P > 0.05). CONCLUSIONS: Web neonatal intensive care unit diaries effectively relieved anxiety symptoms, reduced the prevalence of post-traumatic stress disorder, and enhanced the care abilities of parents of preterm infants in the neonatal intensive care unit. IMPLICATIONS FOR CLINICAL PRACTICE: Web neonatal intensive care unit diary can be considered in clinical practice as a convenient psychological intervention method, especially among parents of preterm infants in the neonatal intensive care unit.
Human activities have strongly impacted the global climate, and during the last few decades the global average temperature has risen at a rate faster than at any time on record. High latitude lakes in the subarctic and arctic permafrost regions have particularly been vulnerable given the "Arctic amplification" phenomenon and acceleration in warming rate in the northern hemisphere (0.2-0.8 °C/decade). This paper presents a comprehensive overview of the last 30 years of research investigating how subarctic and Arctic lakes respond to climate warming. The review focused on studies where remote sensing technology was used to quantify these responses. The difference between summer lake water temperature and air temperature varied between 1.7 and 5.4 °C in subarctic lakes and 2.4-3.2 °C in Arctic lakes. Overall, the freezing date of lake ice is generally delayed and the date of lake thawing occurs earlier. Lake surface area (4-48.5 %), and abundance in the subarctic and Arctic region have increased significantly due to rising temperature, permafrost thawing, increased precipitation and other localized surface disturbances. However, in recent years, instances of lake shrinkage (between -0.4 % and -40 %) have also been reported, likely due to riparian overflow, groundwater infiltration and lateral drainage. Furthermore, in subarctic and Arctic lakes, climate change and permafrost thawing would release CO2 and CH4, and alter carbon dynamics in impacted lakes through various interconnected processes which could potentially affect the quality of carbon (terrestrial, algae) entering a lake system. The review also highlighted a potential intersection between permafrost melting and public health through human exposure to long-buried viruses. Subarctic and arctic ecosystems' responses to climate change will continue to be an area of intense research interest, and this review has highlighted priority areas for research and how remote sensing technologies can facilitate the pursuit of such a research agenda.
BACKGROUND: Dual-layer spectral-detector dual-energy computed tomography angiography (DLCTA) can distinguish components of carotid plaques. Data on identifying symptomatic carotid plaques in patients using DLCTA are not available. METHODS AND RESULTS: In this prospective observational study, patients with carotid plaques were enrolled and received DLCTA. The attenuation for both polyenergetic image and virtual monoenergetic images (40, 70, 100, and 140 keV), as well as Z-effective value, were recorded in the noncalcified regions of plaques. Logistic regression models were used to assess the association between attenuations of DLCTA and the presence of symptomatic carotid plaques. In total, 100 participants (mean±SD age, 64.37±8.31 years; 82.0% were men) were included, and 36% of the cases were identified with the symptomatic group. DLCTA parameters were different between 2 groups (symptomatic versus asymptomatic: computed tomography [CT] 40 keV, 152.63 [interquartile range (IQR), 70.22-259.78] versus 256.78 [IQR, 150.34-408.13]; CT 70 keV, 81.28 [IQR, 50.13-119.33] versus 108.87 [IQR, 77.01-165.88]; slope40-140 keV, 0.91 [IQR, 0.35-1.87] versus 1.92 [IQR, 0.96-3.00]; Z-effective value, 7.92 [IQR, 7.53-8.46] versus 8.41 [IQR, 7.94-8.92]), whereas no difference was found in conventional polyenergetic images. The risk of symptomatic plaque was lower in the highest tertiles of attenuations in CT 40 keV (adjusted odds ratio [OR], 0.243 [95% CI, 0.078-0.754]), CT 70 keV (adjusted OR, 0.313 [95% CI, 0.104-0.940]), Z-effective values (adjusted OR, 0.138 [95% CI, 0.039-0.490]), and slope40-140 keV (adjusted OR, 0.157 [95% CI, 0.046-0.539]), with all P values and P trends <0.05. The areas under the curve for CT 40 keV, CT 70 keV, slope 40 to 140 keV, and Z-effective values were 0.64, 0.61, 0.64, and 0.63, respectively. CONCLUSIONS: Parameters of DLCTA might help assist in distinguishing symptomatic carotid plaques. Further studies with a larger sample size may address the overlap and improve the diagnostic accuracy.
Carotid Artery Diseases , Plaque, Atherosclerotic , Male , Humans , Middle Aged , Aged , Female , Computed Tomography Angiography/methods , Signal-To-Noise Ratio , Tomography, X-Ray Computed/methods , Carotid Artery Diseases/diagnostic imaging , Retrospective Studies , Radiographic Image Interpretation, Computer-Assisted/methods
INTRODUCTION: Several studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis because of its strong immunosuppressive potency and low toxicity profile. Enteric-coated mycophenolate sodium (EC-MPS) was introduced to reduce gastrointestinal adverse reactions of MMF. This study will evaluate the efficacy and safety of EC-MPS combined with glucocorticoid in patients with active and non-life-threatening microscopic polyangiitis (MPA). METHODS AND ANALYSIS: This study is a multicentre, open-label, randomised controlled, non-inferiority trial. A total of 110 patients with active and non-life-threatening MPA from 11 hospitals in Shanxi Province of China will be recruited and randomised in a 1:1 ratio to receive either EC-MPS or CYC. All patients will receive the same glucocorticoid plan. We will compare oral EC-MPS (720-1440 mg/day) with intravenous pulsed CYC (7.5-15 mg/kg) administered for 3-6 months. All patients will be switched from their assigned treatment (EC-MPS or CYC) to oral azathioprine (2 mg/kg/day) after remission has been achieved, between 3 and 6 months. Azathioprine will be continued until the study ends at 18 months. The primary end point of efficacy is the remission rate at 6 months. Follow-up will continue for 18 months in order to detect an influence of induction regimen on subsequent relapse rates. ETHICS AND DISSEMINATION: This study has received approval from the Ethics Committee of the Second Hospital of Shanxi Medical University (2022YX-026). All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The results of this trial will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200063823.
Microscopic Polyangiitis , Mycophenolic Acid , Humans , Azathioprine , Cyclophosphamide , Glucocorticoids , Immunosuppressive Agents/adverse effects , Multicenter Studies as Topic , Mycophenolic Acid/adverse effects , Randomized Controlled Trials as Topic , Remission Induction , Equivalence Trials as Topic
Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.
BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.
Health Literacy , Telemedicine , Humans , Adolescent , Adult , Digital Health , Cross-Sectional Studies , Surveys and Questionnaires , Internet , China
Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH.
