ARHGAP32 as a novel RhoGAP interacting with desmoplakin is required for desmosomal organization and assembly.

Desmosomes play a critical role in maintaining tissue barrier integrity, particularly in mechanically stressed tissues. The assembly of desmosomes is regulated by the cytoskeleton and its regulators, while desmosomes also function as a central hub for regulating F-actin. However, the specific mechanisms underlying the crosstalk between desmosomes and F-actin remain unclear. Here, we identified that ARHGAP32, a Rho GTPase-activating protein, is located in desmosomes through its interaction with DSP via its GAB2-interacting domain (GAB2-ID). We confirmed that ARHGAP32 is required for desmosomal organization, maturation, and length regulation. Notably, loss of ARHGAP32 increased formation of F-actin stress fibers and phosphorylation of Myosin at T18/S19. Inhibition of ROCK1 activity in ARHGAP32 KO cells effectively restored desmosomal organization and the integrity of epithelial cell sheets. Moreover, loss of DSP impaired desmosomal ARHGAP32 while decreased actomyosin contractility. Deletion of the GAB2-ID of ARHGAP32 enhanced its association with RHOA in the cytosol and failed to rescue the desmosomal organization. Collectively, our study unveils ARHGAP32 associates with and regulates desmosomes by interacting with DSP. This interaction potentially facilitates the crosstalk between desmosomes and F-actin.

Exploring the molecular mechanism of ginseng against anthracycline-induced cardiotoxicity based on network pharmacology, molecular docking and molecular dynamics simulation.

BACKGROUND: Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations. RESULTS: Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation. CONCLUSIONS: This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.

Maternal Gestational Diabetes Mellitus and High-Fat Diet Influenced Hepatic Polyunsaturated Fatty Acids Profile in the Offspring of C57BL/6J Mice.

SCOPE: This research examines the effects of maternal high-fat (HF) diet and gestational diabetes mellitus (GDM) on offspring lipid metabolism and polyunsaturated fatty acids (PUFA) profile. METHODS AND RESULTS: GDM is induced using the insulin receptor antagonist S961. Weaning offspring are categorized into HF-GDM, HF-CON, NC-GDM, and NC-CON groups based on maternal diet or GDM. Adult offspring are then grouped into NC-CON-NC, NC-CON-HF, NC-GDM-NC, NC-GDM-HF, HF-CON-NC, HF-CON-HF, HF-GDM-NC, and HF-GDM-HF according to dietary patterns. Gas chromatography determines PUFA composition. Western blot assesses PI3K/Akt signaling pathway-related protein expression. Feeding a normal chow diet until adulthood improves the distribution of hepatic PUFA during weaning across the four groups. PI3K expression is upregulated during weaning in HF-CON and HF-GDM, particularly in HF-CON-NC and HF-GDM-NC, compared to NC-CON-NC during adulthood. Akt expression increases in NC-GDM-NC after weaning with a normal diet. The hepatic PUFA profile in HF-CON-HF significantly distinguishes among the maternal generation health groups. Maternal HF diet exacerbates the combined impact of maternal GDM and offspring HF diet on hepatic PUFA and PI3K/Akt signaling pathway-related proteins during adulthood. CONCLUSIONS: Early exposure to HF diets and GDM affects hepatic PUFA profiles and PI3K/Akt signaling pathway protein expression in male offspring during weaning and adulthood.

Improving Perovskite Solar Cell Performance and Stability via Thermal Imprinting-Assisted Ion Exchange Passivation.

The latest development in perovskite solar cell (PSC) technology has been significantly influenced by advanced techniques aimed at passivating surface defects. This work presents a new approach called thermal imprinting-assisted ion exchange passivation (TIAIEP), which delivers a different approach to conventional solution-based methods. TIAIEP focuses on addressing surface imperfections in solid-state films by using a passivator that promotes ion exchange specifically at the defect sites within the perovskite layer. By adjusting the time and temperature of the TIAIEP process, we achieve substantial enhancement in the creation of a compositional gradient within the films. This optimization slows the cooling rate of hot carriers, leading to minimizing charge recombination and improving the device performance. Remarkably, devices treated with TIAIEP achieve a 22.29% power conversion efficiency and show outstanding stability, with unencapsulated PSCs maintaining 91% of their original efficiency after over 2000 h of storage and 90% efficiency after 1200 h of constant illumination. These results highlight TIAIEP's effectiveness in mitigating surface defects, improving both the photoelectric and stability performance of PSCs, and indicating significant potential for large-scale application in perovskite film passivation, promoting the widespread adoption of this technology.

Topical Transdermal Administration of Supramolecular Self-Assembled Carnosine for Anti-Melanin and Anti-Aging.

The structure of natural proteins has inspired the hypothesis that L-carnosine (LC), acetyl carnosine (AC), and decarboxy carnosine (DC) self-assemble into highly bioactive carnosine with supramolecular structures. These structures are proposed to combat skin pigmentation and aging through the coordination of weak interactions between molecules. Simulations are conducted to ascertain the precise free energies of the potential supramolecular structures and to identify the equilibrium structure. The mechanism of transdermal action of supramolecular carnosine is investigated through experiments and molecular dynamics simulations. The results demonstrate that supramolecular carnosine exhibits a more pronounced reactivity with the skin than LC, primarily due to the interaction of AC and DC with the lipid matrix, which reduces interfacial resistance. The anti-photoaging and anti-glycation cell models demonstrate that supramolecular carnosine upregulates the expression of the Nrf2 protein, activates the antioxidant defense system of melanocytes, inhibits the expression of the receptor for advanced glycosylation end products (AGEs), and reduces the level of AGEs in vivo. Moreover, supramolecular carnosine has demonstrated satisfactory whitening efficacy in cells and clinical efficacy tests, thereby underscoring its considerable potential for biomedical and aesthetic applications.

Evaluation of peripheral blood inflammation indexes as prognostic markers for colorectal cancer metastasis.

The aim of this study was to evaluate the prognostic value of peripheral blood inflammation indexes in patients with metastatic Colorectal Cancer (CRC) and to establish a predictive scoring system. A total of 324 CRC patients diagnosed through pathological examination from January 2017 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were included. The prognosis of patients with metastatic CRC was examined, and the correlation between IL-10 expression in pathological tissues and IL-10 expression in serum was analyzed. The results showed that the prognosis of CRC was poorer when metastasis occurred (P < 0.001). Additionally, IL-10 was highly expressed in the metastatic CRC group (P = 0.018), and the expression of IL-10 in pathological tissues of patients with metastatic CRC was positively correlated with the expression of IL-10 in serum (P = 0.037). The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-white blood cell ratio (LWR), aggregate index of systemic inflammation (AISI), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and interleukin-10 (IL-10) were calculated and determined by ROC curve. The critical values were 2.135, 3.735, 353.745, 0.265, 1.025, 52.975, 353.635, and 11.25, respectively. Inflammatory indexes with an AUC of more than 0.6 were selected, and each colorectal cancer patient with any of these risk factors was assigned a score of one. The 324 patients were then divided into two groups: 0-4 for the low-risk group and 4-8 for the high-risk group. The occurrence of distant metastases in the two groups was statistically analyzed. The results showed that the OS and PFS of the low-risk group were significantly superior to those of the high-risk group (P < 0.05). These findings indicate that NLR, LWR, AISI, MLR, SIRI, PNI, ALI, and IL-10 are risk factors for distant metastasis in CRC patients. Therefore, the prediction scores of these indexes can be used to effectively evaluate the prognosis of patients with metastatic CRC.

Unlocking the potential: strategic synthesis of a previously predicted pyrazolate-based stable MOF with unique clusters and high catalytic activity.

The metal-organic framework (MOF) constructed from [Co4Pz8] clusters (Pz = pyrazolate) and 1,3,5-tris(pyrazolate-4-yl) benzene (BTP3-) ligands was structurally predicted many years ago, and expected to be a promising candidate for various applications owing to its unique clusters and highly open 3D framework structure. However, this MOF has not been experimentally prepared yet, despite extensive efforts were made. In this work, we present the successful construction of this MOF, hereinafter referred to as BUT-124(Co), by adopting a two-step synthesis strategy, involving the initial construction of a template framework (BUT-124(Cd)) followed by a post-synthetic metal metathesis process. The effects of various cobalt sources and solvents were systematically investigated, and an innovative stepwise metathesis strategy was employed to optimize the exchange rates and the porosity of the material. BUT-124(Co) demonstrates high catalytic activity in the oxygen evolution reaction (OER), achieving a competitive performance with an overpotential of 393 mV at a current density of 10 mA cm-2, and also affords remarkable long-term stability during potentiostatic electrolysis in 1 M KOH solution, surpassing the durability of many benchmark catalysts. This work not only introduces a novel MOF material with promising properties but also exemplifies a strategic synthesis approach for pyrazolate-based MOFs, paving the way for advancements in diverse application fields.

mir-744-5p inhibits cell growth and angiogenesis in osteosarcoma by targeting NFIX.

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor that commonly occurs in children and adolescents under the age of 20. Dysregulation of microRNAs (miRNAs) is an important factor in the occurrence and progression of OS. MicroRNA miR-744-5p is aberrantly expressed in various tumors. However, its roles and molecular targets in OS remain unclear. METHODS: Differentially expressed miRNAs in OS were analyzed using the Gene Expression Omnibus dataset GSE65071, and the potential hub miRNA was identified through weighted gene co-expression network analysis. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-744-5p in OS cell lines. In vitro experiments, including CCK-8 assays, colony formation assays, flow cytometry apoptosis assays, and tube formation assays, were performed to explore the effects of miR-744-5p on OS cell biological behaviors. The downstream target genes of miR-744-5p were predicted through bioinformatics, and the binding sites were validated by a dual-luciferase reporter assay. RESULTS: The lowly expressed miRNA, miR-744-5p, was identified as a hub miRNA involved in OS progression through bioinformatic analysis. Nuclear factor I X (NFIX) was confirmed as a direct target for miR-744-5p in OS. In vitro studies revealed that overexpression of miR-744-5p could restrain the growth of OS cells, whereas miR-744-5p inhibition showed the opposite effect. It was also observed that treatment with the conditioned medium from miR-744-5p-overexpressed OS cells led to poorer proliferation and angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, NFIX overexpression restored the suppression effects of miR-744-5p overexpression on OS cell growth and HUVECs angiogenesis. CONCLUSION: Our results indicated that miR-744-5p is a potential tumor-suppressive miRNA in OS progression by targeting NFIX to restrain the growth of OS cells and angiogenesis in HUVECs.

Uromodulin and progression of IgA nephropathy.

Background: This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods: We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results: The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion: The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.

Effect of Various Fruit Extracts on Angiotensin I-Converting Enzyme (ACE) and Kallikrein (KLK) Activities.

Hypertension is one of the main risk factors for cardiovascular disease and causes widespread morbidity and mortality worldwide. The aim of this work was to screen the fruit with high angiotensin I-converting enzyme (ACE) inhibitory activity and kallikrein (KLK) promotion activity by three different extraction methods from 22 kinds of fruits. Results showed that the aqueous extracts of fresh kiwifruit significantly inhibited ACE activity (47.71%), whereas the KLK activity was also inhibited (4.56%). This indicated that the substances inhibiting ACE activity existed in kiwifruit might be small molecular substances such as polyphenols. The nonpolar substance existed in the ethanol extracts of grape inhibited ACE activity significantly. The enzymatic hydrolysates of red grape significantly promoted KLK activity, whereas its ethanol extracts significantly inhibited KLK activity. This results suggested that the components that lower blood pressure and raise blood pressure are generally presented in the same fruit, the former are mostly water-soluble substances, while the latter are generally alcohol-soluble substances. If certain or individual components can be isolated from edible fruits, they may significantly affect blood pressure in humans.

Novel long noncoding lncARF mediated hyperhomocysteinemia-induced atherosclerosis via autophagy inhibition in foam cells.

INTRODUCTION: Homocysteine (Hcy) is well recognized to be an independent risk factor for atherosclerosis. Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis, while the underlying mechanisms of its involvement in Hcy induced-atherosclerosis remain largely unknown. OBJECTIVES: The primary aim of this study is to assess the role of lncARF (autophagy-related factor induced by Hcy) in Hcy induced-atherosclerosis and related mechanism. METHODS: RNA sequencing of foam cells treated with Hcy revealed a novel specific long noncoding RNA called lncARF. Locked nucleic acid gapmeRs-mediated lncARF knockdown was used to explore the role of lncARF both in vivo and in vitro. Mass spectrometry, RNA pull-down and RNA immunoprecipitation (RIP) assays were employed to uncover a mechanistic role of lncARF. Mass array assay and chromatin immunoprecipitation (ChIP) were used to detect the transcriptional activation of lncARF mediated by transcription factor. Clinically, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of lncARF in atherosclerotic patients with hyperhomocysteinemia (HHcy). RESULTS: We observed that the expression of lncARF was substantially upregulated in atherosclerotic plaques, and knockdown of lncARF decreased the formation of atherosclerotic lesions by promoting autophagy in foam cells. Mechanistically, lncARF physically binds to RRAGD and inhibits its ubiquitination, further activating the PI3K/Akt and MAPK signaling pathways. Moreover, in vitro experiments showed that transcription factor FosB inhibited the binding of DNMT1 at the lncARF promoter, leading to transcriptional activation through DNA hypomethylation. Clinically, lncARF expression was positively correlated with serum Hcy levels, and it could distinguish atherosclerotic patients with HHcy with a high area under the ROC curve, sensitivity and specificity. CONCLUSIONS: Our study highlights the mechanisms of lncARF in protecting against the development of atherosclerosis involving the epigenetic modifications and RRAGD/PI3K/Akt and RRAGD/MAPK signaling pathways, which may provide novel diagnostic biomarkers to improve atherosclerosis treatment.

Acute Neck Pain from Crowned Dens Syndrome: A Case Report and Clinical Insights.

BACKGROUND Crowned dens syndrome (CDS) is a rare condition characterized by deposition of calcium pyrophosphate crystals on the odontoid process of the second cervical vertebra, forming a calcified 'crown', with neck pain being a common symptom. The disorder exhibits unique clinical and radiological features, resembling manifestations of meningitis, such as acute headaches and cervical stiffness. There are few case reports and case series related to CDS. Patients generally respond well to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), although there is a certain rate of recurrence. Since there are few reports of CDS, we sought to publish this case report, aiming of increasing clinicians' awareness and reducing misdiagnosis rates. CASE REPORT A 62-year-old man presented to the Emergency Department with "cutting-like" headaches and neck pain for 2 days, and was subsequently diagnosed with CDS by cervical computed tomography (CT) scan, and hematological tests revealed inflammatory manifestations. He was advised to take oral nonsteroidal anti-inflammatory drugs and to rest; his symptoms improved after 3 days and his neck pain had almost resolved after 2 months. CONCLUSIONS In older patients experiencing new headaches and neck pain, along with increased inflammatory markers, particularly those with a history of pseudogout, the possibility of CDS should be considered. Case reports suggest that oral NSAIDs and short courses of corticosteroids can generally alleviate symptoms. Further research is needed on CDS diagnosis and treatment.

Inhibition of autophagy via 3-methyladenine alleviates the progression of preeclampsia.

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis reveals significant enrichment of genes related to autophagy-related signaling pathways, including the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the mTOR signaling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examine the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviates the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). The findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.

Risk prediction and prognostic analysis of post-implantation syndrome after thoracic endovascular aortic repair.

This study aimed to establish a predictive model for the risk of post-thoracic endovascular aortic repair (TEVAR) post-implantation syndrome (PIS) in type B aortic dissection (TBAD) patients, assisting clinical physicians in early risk stratification and decision management for high-risk PIS patients. This study retrospectively analyzed the clinical data of 547 consecutive TBAD patients who underwent TEVAR treatment at our hospital. Feature variables were selected through LASSO regression and logistic regression analysis to construct a nomogram predictive model, and the model's performance was evaluated. The optimal cutoff value for the PIS risk nomogram score was calculated through receiver operating characteristic (ROC) curve analysis, further dividing patients into high-risk group (HRG) and low-risk group (LRG), and comparing the short to midterm postoperative outcomes between the two groups. In the end, a total of 158 cases (28.9%) experienced PIS. Through LASSO regression analysis and multivariable logistic regression analysis, variables including age, emergency surgery, operative time, contrast medium volume, and number of main prosthesis stents were selected to construct the nomogram predictive model. The model achieved an area under the curve (AUC) of 0.86 in the training set and 0.82 in the test set. Results from calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated that the predictive model exhibited good performance and clinical utility. Furthermore, after comparing the postoperative outcomes of HRG and LRG patients, we found that the incidence of postoperative PIS significantly increased in HRG patients. The duration of ICU stay and mechanical assistance time was prolonged, and the incidence of postoperative type II entry flow and acute kidney injury (AKI) was higher. The risk of aortic-related adverse events (ARAEs) and major adverse events (MAEs) at the first and twelfth months of follow-up also significantly increased. However, there was no significant difference in the mortality rate during hospitalization. This study established a nomogram model for predicting the risk of PIS in patients with TBAD undergoing TEVAR. It serves as a practical tool to assist clinicians in early risk stratification and decision-making management for patients.

Minimally invasive posterior cervical foraminotomy versus anterior cervical fusion and arthroplasty: Systematic review and updated meta-analysis.

Introduction: This study is a systematic review and meta-analysis that investigates the efficacy of different surgical methods for treating cervical disc herniation or cervical foraminal stenosis. Research question: The research aimed to compare the efficacy of Minimally Invasive Posterior Cervical Foraminotomy (MI-PCF) with anterior approaches, namely Anterior Cervical Discectomy and Fusion (ACDF) and Cervical Disc Arthroplasty (CDA). Material and methods: The study included a comprehensive review of eight articles that compared ACDF and MI-PCF, and four articles that compared CDA to MI-PCF. Results: The results indicated no significant difference in surgical duration, hospital stay, complication rates, and reoperation rates between MI-PCF and ACDF. However, when comparing CDA with MI-PCF, it was found that CDA had a higher complication rate, while MI-PCF had a higher reoperation rate. Discussion and conclusion: Despite these findings, the study recommends MI-PCF as the preferred surgical method for cervical radiculopathy, owing to the advancements in minimally invasive techniques. However, these findings are preliminary, and further research with longer follow-up periods and larger sample sizes is necessary to confirm these findings and to further explore the potential advantages and disadvantages of these surgical methods.

Development of a machine learning-based model to predict major adverse events after surgery for type A aortic dissection complicated by malnutrition.

Objective: This study aims to develop a predictive model for the risk of major adverse events (MAEs) in type A aortic dissection (AAAD) patients with malnutrition after surgery, utilizing machine learning (ML) algorithms. Methods: We retrospectively collected clinical data from AAAD patients with malnutrition who underwent surgical treatment at our center. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we screened for preoperative and intraoperative characteristic variables. Based on the random forest (RF) algorithm, we constructed a ML predictive model, and further evaluated and interpreted this model. Results: Through LASSO regression analysis and univariate analysis, we ultimately selected seven feature variables for modeling. After comparing six different ML models, we confirmed that the RF model demonstrated the best predictive performance in this dataset. Subsequently, we constructed a model using the RF algorithm to predict the risk of postoperative MAEs in AAAD patients with malnutrition. The test set results indicated that this model has excellent predictive efficacy and clinical applicability. Finally, we employed the Shapley additive explanations (SHAP) method to further interpret the predictions of this model. Conclusion: We have successfully constructed a risk prediction model for postoperative MAEs in AAAD patients with malnutrition using the RF algorithm, and we have interpreted the model through the SHAP method. This model aids clinicians in early identification of high-risk patients for MAEs, thereby potentially mitigating adverse clinical outcomes associated with malnutrition.

How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach.

BACKGROUND: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients. AIM: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT. METHODS: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ²-test. RESULTS: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis (n = 1) and pulmonary infections (n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality (n = 1), postoperative pulmonary infections (n = 8), abdominal infection (n = 1), hepatic artery thromboses (n = 3), portal vein thrombosis (n = 1), and intra-abdominal bleeding (n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups (P > 0.05). CONCLUSION: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers.

Clinical therapeutic effect of self-prescribed Sanhanchushi Tongbi on lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) commonly occurs during spinal surgery; LDH is on the increase in younger patients and is classified as "paralysis" and "back pain." Sanhanchushi Tongbi (SPST) is a customized prescription. It disperses cold, relieves pain, removes cold from the meridians and viscera, and treats neuropathic pain. However, few studies have investigated its mechanism of pain relief. AIM: To observe the clinical therapeutic effects on LDH treated with self-prescribed SPST. METHODS: A total of 211 patients with LDH syndrome were divided into two groups: 107 patients in the control group were treated with conventional massage combined with traction, and 104 patients in the observation group were treated with a combination of the control regimen and self-prescribed oral SPST. The patients were treated for 4 wk. Indices of traditional Chinese medicine (TCM) syndrome score and serum inflammatory factor levels were measured. RESULTS: After therapy, the TCM syndrome score in the observation group was significantly lower than that in the control group (P < 0.05). The main symptoms, clinical signs, daily activities, and Japanese Orthopedic Association scores in the observation group were significantly higher than those in the control group after therapy (P < 0.05). The levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein were lower in the observation group than in the control group (P < 0.05). In the observation group, superoxide dismutase levels were significantly higher, whereas malondialdehyde levels were significantly lower, compared with the control group (P < 0.05). The overall efficacy rate in the observation group was 96.15%, which was substantially higher than that in the control group (88.79%; P < 0.05). CONCLUSION: Self-prescribed SPST can reduce the levels of inflammatory and pain-causing factors as well as lumbar pain in patients with LDH.

Adherence and persistence among people with type 2 diabetes newly initiating oral semaglutide versus DPP-4is in a US real-world setting.

AIMS: To investigate real-world treatment adherence and persistence in people with type 2 diabetes newly initiating oral semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), or a dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: This retrospective cohort study used the Merative™ MarketScan® Commercial and Medicare databases. Index date was the first fill for the cohort medication. Adherence was defined as proportion of days covered (PDC) over the 12-month post-index period ('adherent' = ≥0.8). Persistence was number of days until discontinuation, based on a 45-day gap. Results were compared between cohorts using inverse probability treatment weighting. RESULTS: Oral semaglutide (n=5485) and DPP-4i (n=4980) cohorts had similar percentages of people who were adherent (PDC ≥0.8; 41.6 % vs. 42.9 %; P = 0.182) and persistent for ≥9 months (45.0 % vs. 46.3 %; P = 0.185). The DPP-4i cohort used significantly more anti-diabetic medication (ADM) classes over the post-index period (mean±SD: 2.6±1.0 vs. 2.9±1.1, P < 0.001), with 23.2 % filling a GLP-1 RA in the post-period. CONCLUSIONS: Adherence and persistence were similar between cohorts. However, there are potential benefits to prescribing oral semaglutide over DPP-4is, including reduced need for additional ADM.

Pathophysiological Relevance and Therapeutic Outlook of GPR43 in Atherosclerosis.

Atherosclerosis (AS) is an inflammatory arterial disorder that occurs due to the deposition of the excessive lipoprotein under the artery intima, mainly including low-density lipoprotein (LDL) and other apolipoprotein B-containing lipoproteins. G protein-coupled receptors (GPCRs) play a crucial role in transmitting signals in physiological and pathophysiological conditions. GPCRs recognize inflammatory mediators, thereby serving as important players during chronic inflammatory processes. It has been demonstrated that free fatty acids can function as ligands for various GPCRs, such as free fatty acid receptor (FFAR)1/GPR40, FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120, and the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). This review discusses GPR43 and its ligands in the pathogenesis of AS, especially focusing on its distinct role in regulating chronic vascular inflammation, inhibiting oxidative stress, ameliorating endothelial dysfunction and improving dyslipidemia. It is hoped that this review may provide guidance for further studies aimed at GPR43 as a promising target for drug development in the prevention and therapy of AS.