Scoparone alleviates nonalcoholic fatty liver disease by modulating the PPARα signaling pathway.

Scoparone (Scop), a natural compound derived from Artemisia capillaris Thunb, has demonstrated efficacy in improving nonalcoholic fatty liver disease (NAFLD). This study aims to explore the underlying mechanism. NAFLD was induced by a high-fat diet in C57BL/6J mice, followed by an 8-week treatment with Scop. The effect of Scop on mice NAFLD was assessed. mRNA sequencing of liver tissues was performed to identify potential targets, which were validated through in vitro experiments using palmitic acid-induced AML12 hepatocytes. The results demonstrated that Scop promoted lipid metabolism, insulin sensitivity, and liver function, and alleviated inflammation in NAFLD mice. mRNA sequencing identified the peroxisome proliferator-activated receptor α (PPARα) signaling pathway as a target of Scop, which was further confirmed by in vivo and in vitro experiments. Molecular docking studies showed that Scop could bind stably to human PPARα. In summary, Scop was proven to alleviate lipid metabolism dysfunction and inflammation by targeting the PPARα signaling pathway, which provides a basis for its potential application in NAFLD treatment.

Simulation of osteotomy in total knee arthroplasty with femoral extra-articular deformity assisted by artificial intelligence: a study based on three-dimensional models.

BACKGROUND: The impact of extra-articular deformities (EADs) on lower limb alignment and collateral ligament integrity during total knee arthroplasty (TKA) poses significant challenges, increasing surgical complexity. Our study aims to evaluate the influence of EADs on mechanical axis alignment and the risk of collateral ligament injury during TKA using an AI-assisted surgical planning system, with the goal of minimizing ligament damage through precise and scientific planning. METHODS: A healthy volunteer underwent CT and MRI scans of the lower limbs. The scan images were imported into Mimics 20.0 software, and the reconstructed models were spatially aligned using 3-maticResearch 11.0 software. Using Unigraphics NX9.0 software, 50 three-dimensional models of femoral lateral joint deformities with varying positions and angles were created. Finally, TKA was simulated using the AI JOINT preoperative planning system. RESULTS: The larger the deformity angle and the closer it is to the knee joint, the more pronounced the deviation of the mechanical axis. During MA-aligned osteotomy, nine types of deformities can damage the collateral ligaments. After adjusting the varus/valgus of the prosthesis within a safe range of 3° and leaving a residual 3° varus/valgus in the lower limb alignment, only the 25° varus and 25° valgus deformities located at 90% of the femoral anatomical axis remain uncorrected. CONCLUSION: For patients with osteoarthritis and concurrent EAD undergoing TKA, using reconstructed 3D models of the collateral ligaments for preoperative planning helps visually assess collateral ligament damage, providing a practical solution. Minimizing intra-articular osteotomies within a safe range and allowing some residual alignment deviation can reduce the risk of collateral ligament injury.

PARP1 acetylation at K119 is essential in regulating the progression and proliferation of cervical cancer cells.

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function.

Comprehensive Analysis of UBE-Related Complications: Prevention and Management Strategies from 4685 Patients.

Unilateral biportal endoscopy (UBE) surgery is a minimally invasive approach for treatment of spinal disorders, which usually requires creation of a working and viewing channel on 1 side. The UBE technique has developed rapidly in China in recent years, and many spine surgeons have started to apply it and have shared the initial clinical research results many times at minimally invasive spine conferences. Unfortunately, these studies actually translated into fewer publications. In addition, most patients have good outcomes after UBE surgery, but a minority still experience UBE surgery-related complications, including epidural hematoma, dural sac tears, retroperitoneal effusions, inadequate decompression, postoperative back pain and headache, early recurrence, iatrogenic spinal instability, anemia, and infection, which can prolong hospital stay and seriously affect patient satisfaction. Therefore, this article reviews the complications of UBE surgery for lumbar degenerative diseases and discusses ways to prevent and handle complications associated with UBE to help spine surgeons make smart treatment decisions.

Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies.

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation.

RAC1 serves as a prognostic factor and correlated with immune infiltration in liver hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (LIHC) has severe consequences due to late diagnosis and the lack of effective therapies. Currently, potential biomarkers for the diagnosis and prognosis of LIHC have not been systematically evaluated. Previous studies have reported that RAC1 is associated with the B cell receptor signaling pathway in various tumor microenvironments, but its relationship with LIHC remains unclear. We investigated the relationship between RAC1 and the prognosis and immune infiltration microenvironment of LIHC, exploring its potential as a prognostic biomarker for this type of cancer. METHODS: In this study, we analyzed data from The Cancer Genome Atlas (TCGA) using the Wilcoxon signed-rank test and logistic regression to assess the association between RAC1 expression and clinical characteristics in LIHC patients. Additionally, Kaplan-Meier and Cox regression methods were employed to confirm the impact of RAC1 expression levels on overall survival. Immunohistochemistry was used to validate RAC1 protein expression in LIHC. We constructed RAC1 knockdown LIHC cells and studied the effects of RAC1 protein on cell proliferation and migration at both cellular and animal levels. RESULTS: RAC1 expression levels were significantly elevated in LIHC tissues compared to normal tissues. High RAC1 expression was strongly associated with advanced pathological stages and was identified as an independent factor negatively affecting overall survival. At both cellular and animal levels, RAC1 knockdown significantly inhibited the proliferation and migration of LIHC cells. Furthermore, RAC1 expression was positively correlated with the infiltration of Th2 cells and macrophages in the tumor microenvironment, suggesting that RAC1 may contribute to the deterioration of the tumor immunosuppressive microenvironment and potentially lead to reduced patient survival. CONCLUSION: These findings indicate that RAC1 expression promotes LIHC proliferation and migration and influences the landscape of immune cell infiltration in the tumor microenvironment. Based on these results, RAC1 is proposed as a potential prognostic biomarker for LIHC, associated with both cancer progression and tumor immune cell infiltration.

Association between physical activity and sedentary behavior and depression in US adults with cardiovascular disease: NHANES 2007-2016.

BACKGROUND: Previous studies reported the effect of physical activity (PA) or sedentary behavior (SB) on increasing occurrence of depression in patients with cardiovascular disease, leading to a higher risk of adverse clinical outcomes. However, the association between the combination of PA and SB and depression in patients with cardiovascular disease remained unstudied. METHODS: Patients with cardiovascular disease (aged ≥18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Multivariable logistic regression was used to investigate the association between PA, SB, and depression. RESULTS: Among the 2585 patients (mean age 64.43 years; 54.65 % male) in this study, the prevalence of depression was 16.40 %. After adjustment for age, gender, race, education level, marital status, poverty income ratio, employment status, smoking, alcohol use, BMI, hypertension, and number of cardiovascular diseases, depression was negatively associated with higher PA (adjusted OR = 0.567, 95 % CI 0.403, 0.799) and positively associated with higher SB (adjusted OR = 1.472, 95 % CI 1.089, 1.990), respectively. The risk of depression associated with higher PA and lower SB was significantly lower (adjusted OR = 0.464, 95 % CI 0.307, 0.702) compared to those with lower PA but higher SB. LIMITATIONS: This was a cross-sectional study with limited ability to make causal inferences. CONCLUSIONS: Our findings indicate that patients with higher PA and lower SB have a lower risk of depression than those with low PA levels and high SB levels. Moving more and sitting less is a potential preventive measure against depression in patients with cardiovascular disease.

Synthetic vectors for activating the driving axis of ferroptosis.

Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIPPCPO) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIPPCPO is found to boost lysosomal Fe2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIPPCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect is observed between LIPPCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIPPCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIPPCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.

Maternal cigarette smoking before or during pregnancy increases the risk of severe neonatal morbidity after delivery: a nationwide population-based retrospective cohort study.

BACKGROUND: The association of maternal cigarette smoking during pregnancy with severe neonatal morbidity (SNM) is still inconclusive. We aimed to examine the associations of the timing and the intensity of maternal cigarette smoking with infant SNM in the USA. METHODS: We used birth certificate data of 12 150 535 women aged 18-49 years who had live singleton births from the 2016-2019 US National Vital Statistics System. Women self-reported the daily number of cigarettes they consumed before pregnancy and in each trimester of pregnancy. Composite SNM was defined as one or more of the following complications: assisted ventilation immediately following delivery, assisted ventilation for >6 hours, neonatal intensive care unit admission, surfactant replacement therapy, suspected neonatal sepsis, and seizure. RESULTS: Maternal cigarette smoking either before pregnancy or during any trimester of pregnancy significantly increased the risk of infant SNM, even at a very low intensity (ie, 1-2 cigarettes per day). For example, compared with women who did not smoke before pregnancy, the adjusted odds ratios and 95% confidence intervals (OR, 95% CI) of composite SNM in the newborn from women who smoked 1-2, 3-5, 6-9, 10-19, and ≥20 cigarettes per day before pregnancy were 1.16 (1.13 to 1.19), 1.22 (1.20 to 1.24), 1.26 (1.23 to 1.29), 1.27 (1.25 to 1.28), and 1.31 (1.30 to 1.33), respectively. Furthermore, smokers who stopped smoking during pregnancy still had a higher risk of composite SNM than never smokers before and throughout pregnancy. CONCLUSIONS: Maternal cigarette smoking before or during pregnancy increased the risk of infant SNM, even at a low dose of 1-2 cigarettes/day. Interventions should emphasise the detrimental effects of even light smoking before and during pregnancy.

A Controllability Reinforcement Learning Method for Pancreatic Cancer Biomarker Identification.

Pancreatic cancer is one of the most malignant cancers with rapid progression and poor prognosis. The use of transcriptional data can be effective in finding new biomarkers for pancreatic cancer. Many network-based methods used to identify cancer biomarkers are proposed, among which the combination of network controllability appears. However, most of the existing methods do not study RNA, rely on priori and mutations information, or can only achieve classification tasks. In this study, we propose a method combined Relational Graph Convolutional Network and Deep Q-Network called RDDriver to identify pancreatic cancer biomarkers based on multi-layer heterogeneous transcriptional regulation network. Firstly, we construct a regulation network containing long non-coding RNA, microRNA, and messenger RNA. Secondly, Relational Graph Convolutional Network is used to learn the node representation. Finally, we use the idea of Deep Q-Network to build a model, which score and prioritize each RNA with the Popov-Belevitch-Hautus criterion. We train RDDriver on three small simulated networks, and calculate the average score after applying the model parameters to the regulation networks separately. To demonstrate the effectiveness of the method, we perform experiments for comparison between RDDriver and other eight methods based on the approximate benchmark of three types cancer drivers RNAs.

Advanced tumor organoid bioprinting strategy for oncology research.

Bioprinting is a groundbreaking technology that enables precise distribution of cell-containing bioinks to construct organoid models that accurately reflect the characteristics of tumors in vivo. By incorporating different types of tumor cells into the bioink, the heterogeneity of tumors can be replicated, enabling studies to simulate real-life situations closely. Precise reproduction of the arrangement and interactions of tumor cells using bioprinting methods provides a more realistic representation of the tumor microenvironment. By mimicking the complexity of the tumor microenvironment, the growth patterns and diffusion of tumors can be demonstrated. This approach can also be used to evaluate the response of tumors to drugs, including drug permeability and cytotoxicity, and other characteristics. Therefore, organoid models can provide a more accurate oncology research and treatment simulation platform. This review summarizes the latest advancements in bioprinting to construct tumor organoid models. First, we describe the bioink used for tumor organoid model construction, followed by an introduction to various bioprinting methods for tumor model formation. Subsequently, we provide an overview of existing bioprinted tumor organoid models.

Linking industrial emissions and dietary exposure to human burdens of polychlorinated naphthalenes.

Relationships between toxic pollutant emissions during industrial processes and toxic pollutant dietary intakes and adverse health burdens have not yet been quantitatively clarified. Polychlorinated naphthalenes (PCNs) are typical industrial pollutants that are carcinogenic and of increasing concern. In this study, we established an interpretable machine learning model for quantifying the contributions of industrial emissions and dietary intakes of PCNs to health effects. We used the SHapley Additive exPlanations model to achieve individualized interpretability, enabling us to evaluate the specific contributions of individual feature values towards PCNs concentration levels. A strong relationship between PCN dietary intake and body burden was found using a robust large-scale PCN diet survey database for China containing the results of the analyses of 17,280 dietary samples and 4480 breast milk samples. Industrial emissions and dietary intake contributed 12 % and 52 %, respectively, of the PCN burden in breast milk. The model quantified the contributions of food consumption and industrial emissions to PCN exposure, which will be useful for performing accurate health risk assessments and developing reduction strategies of PCNs.

Frontiers in CAR-T cell therapy for autoimmune diseases.

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has demonstrated significant success in treating cancers. The potential of CAR-T cells is now being explored in the context of autoimmune diseases. Recent clinical trials have shown sustained and profound elimination of autoreactive B cells by CAR-T cells, leading to promising autoimmune disease control with minimal safety concerns. These encouraging results have inspired further investigation into CAR-T cell applications for a broader range of autoimmune diseases and the development of advanced cell products with improved efficacy and safety. In this review, we discuss the mechanisms by which CAR-T cells target autoimmune conditions, summarize current preclinical models, and highlight ongoing clinical trials, including CAR-T therapy design, clinical outcomes, and challenges. Additionally, we discuss the limitations and future directions of CAR-T therapy in the treatment of autoimmune diseases.

Atmospheric emissions of particulate matter-bound heavy metals from industrial sources.

Although industrial activities are significant contributors to atmospheric releases of particulate matter (PM) and associated toxic substances that lead to adverse human health effects, a knowledge gap exists concerning the human health risk resulting from such activities owing to lack of evaluation of industrial emissions. Here, we comprehensively characterized and quantified PM from 118 full-scale industrial plants. The dominant (97.9 %) PM showed diameters of <2.5 µm; 79.0 % had diameters below 1 µm. Annual atmospheric releases of Fe and heavy metals (As, Cd, Cr, Cu, Ni, Pb, Zn) contained in fine PM from these global industrial activities are estimated to be 51,161 t and 69,591 t, respectively. Emissions of heavy metals from these industries cause increased cancer risk, estimated to range from 1461 % to 50,752 %. Five crystalline compounds (ZnO, PbSO4, Mn3O4, Fe3O4, Fe2O3) that can indicate specific industrial sources are identified. Global annual emissions of these toxic compounds in fine PM from the industrial sources are estimated to be 78,635 t. The Global South displayed higher emissions than the Global North. These results are significant for recognizing regional health risks of industrial emissions.

Atmospheric emissions of hexachlorobutadiene in fine particulate matter from industrial sources.

Hexachlorobutadiene (HCBD) is a concerning chemical that is included in the United States Toxic Substances Control Act, and the Stockholm Convention. Knowledge of the sources of HCBD is insufficient and is pivotal for accurate inventory and implementing global action. In this study, unintentional HCBD release and source emission factors of 121 full-scale industrial plants from 12 industries are investigated. Secondary copper smelting, electric arc furnace steelmaking, and hazardous waste incineration show potential for large emission reductions, which are found of high HCBD emission concentrations of > 20 ng/g in fine particulate matter in this study. The highest HCBD emission concentration is observed for the secondary copper smelting industry (average: 1380 ng/g). Source emission factors of HCBD for the 12 industries range from 0.008 kg/t for coal fire power plants to 0.680 kg/t for secondary lead smelting, from which an estimation of approximately 8452.8 g HCBD emissions annually worldwide achieved. The carcinogenic risks caused by HCBD emissions from countries and regions with intensive 12 industrial sources are 1.0-80 times higher than that without these industries. These results will be useful for formulating effective strategies of HCBD control.

Discovery of novel CXCR4 inhibitors for the treatment of inflammation by virtual screening and biological evaluation.

C-X-C chemokine receptor type 4 (CXCR4) exerts considerable influence on the pathogenesis of inflammatory disorders and offers a potent avenue for drug intervention. This research utilizes a hybrid virtual screening methodology constructed using computer-aided drug design to discover novel CXCR4 inhibitors for the treatment of inflammation. First, a compound library was screened by Lipinski's five rules and adsorption, distribution, metabolism, excretion and toxicity properties. Second, the HypoGen algorithm was used in constructing a 3D-QSAR pharmacophore model and verify it layer by layer, and the obtained optimal pharmacophore 1 (Hypo 1) was used as a 3D query for compound screening. Then, hit compounds were obtained through molecular docking (Libdock and CDOCKER). The toxicity of the compounds to MDA-MB-231 cells was evaluated in vitro, and their binding affinity to the target was evaluated according to how they compete with 12G5 antibody for CXCR4 on the surfaces of the MDA-MB-231 cells. Compound Hit14 showed the strongest binding affinity among the hit compounds and inhibited cell migration and invasion in Matrigel invasion and wound healing assay at a concentration of 100 nM, demonstrating a better effect than AMD3100. Western Blot experiments further showed that Hit14 blocked the CXCR4/CXCL12-mediated phosphorylation of Akt. Meanwhile, cellular thermal displacement assay analysis showed that CXCR4 protein bound to Hit14 had high thermal stability. Finally, through in vivo experiments, we found that Hit14 inhibited mouse ear inflammation and reduced ear swelling and damage. Therefore, Hit14 is a promising drug for the further development of CXCR4 inhibitors for inflammation treatment.

Risk factors for endoscopic postoperative recurrence in patients with Crohn's Disease: a protocol for systematic review and meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic condition characterized by a high recurrence rate after surgery, which seriously affects the quality of life of patients. Many studies have explored the risk factors for the recurrence of CD after surgery, there is a lack of meta-analysis focusing on endoscopic postoperative recurrence (ePOR) as a clinical outcome. Therefore, this paper aims to identify the risk factors for ePOR in CD patients through systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for related literature from inception to 17th October 2023. Two researchers independently screened the literature and extracted information. Data analysis was performed using Stata18.0. RESULTS: Twenty-three papers were included, with 5 case-control studies and 18 cohort studies. The National Institutes of Health quality assessment tool rated 17 studies as good and 6 studies as fair. The sample size of the 23 studies ranged from 40 to 346, and the number of patients with ePOR ranged from 23 to 169. The results of multivariate meta-analysis showed that smoking [OR = 2.06, 95% CI (1.65, 2.57), P = 0.0001], previous ileocolonic resection [OR = 1.71, 95% CI (1.23, 2.38), P = 0.002], disease localization at ileocolic resection [OR = 2.68, 95% CI (1.38, 5.22), P = 0.004], perianal disease [OR = 1.47, 95% CI (1.07, 2.03), P = 0.017], and anastomotic scattered ulcer [OR = 3.39, 95% CI (1.83, 6.28), P = 0.001] were risk factors for ePOR in CD patients. Postoperative prophylactic medication [OR = 0.53, 95% CI (0.38,0.75), P = 0.0001] was a protective factor for ePOR in CD patients. CONCLUSIONS: This systematic review identified multiple factors for ePOR in CD patients, as well as a protective factor. However, the number of articles included was limited. More high-quality clinical studies are required to further validate the conclusions. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023483671).

RP11-874 J12.4 promotes erlotinib resistance in non-small cell lung cancer via increasing AXL expression.

EGFR tyrosine kinase inhibitor (TKI) resistance is a major challenge for EGFR-mutant non-small cell lung cancer (NSCLC) treatment. Our previous work revealed that overexpression of AXL promoted EGFR-TKI resistance through epithelial-mesenchymal transition (EMT) in a subset of NSCLC patients. Compared with erlotinib resistant and sensitive cells, RP11-874 J12.4 was upregulated in erlotinib-resistant NSCLC cells (HCC827-ER3). Interestingly, the expression of RP11-874 J12.4 positively correlated with AXL. Besides, RP11-874 J12.4 promotes NSCLC cell proliferation and metastasis in vitro. Mechanistically, RP11-874 J12.4 promoted AXL expression through sponge with miR-34a-5p, which was reported to inhibit the translation of AXL mRNA. Meanwhile, the expression of RP11-874 J12.4 in lung cancer tumors were higher than the adjacent tissue, and those patients with high expression of RP11-874 J12.4 showed a poor prognosis in clinical. High expression of RP11-874 J12.4 might be a biomarker for NSCLC patients with erlotinib resistance. These findings reveal a novel insight into the mechanism of erlotinib resistance in NSCLC, and it might be a promising target for the diagnosis and treatment of NSCLC.

TIPRL, a Potential Double-edge Molecule to be Targeted and Re-targeted Toward Cancer.

The target of rapamycin (TOR) proteins exhibits phylogenetic conservation across various species, ranging from yeast to humans, and are classified as members of the phosphatidylinositol kinase (PIK)-related kinase family. Multiple serine/threonine (Ser/Thr) protein phosphatases (PP)2A, PP4, and PP6, have been recognized as constituents of the TOR signaling pathway in mammalian cells. The protein known as TOR signaling pathway regulator-like (TIPRL) functions as a regulatory agent by impeding the activity of the catalytic subunits of PP2A. Various cellular contexts have been postulated for TIPRL, encompassing the regulation of mechanistic target of rapamycin (mTOR) signaling, inhibition of apoptosis and biogenesis, and recycling of PP2A. According to reports, there has been an observed increase in TIPRL levels in several types of carcinomas, such as non-small-cell lung carcinoma (NSCLC) and hepatocellular carcinomas (HCC). This review aims to comprehensively examine the significance of the Tor pathway in regulating apoptosis and proliferation of cancer cells, with a specific focus on the role of TOR signaling and TIPRL in cancer.

Exploration of the Long-term Prognostic Value of Cholangioscopy Combined with Minimally Invasive Abdominal Surgery in Reducing the Possibility of Stone Recurrence in Elderly Patients with Gallstones.

Objective: To observe the effect of cholangioscopy (CS) combined with minimally invasive abdominal surgery on prognosis stone recurrence in elderly patients (≥60 years old) with gallstones (GS). Methods: One hundred and fourteen GS patients admitted to The First Hospital of Nanchang between August 2018 and December 2021 were selected for the study, and they were randomly divided into the control group (n=57) and the observation group (n=57). The control group was treated with open surgery, while the observation group was given CS combined with minimally invasive stone removal surgery. Inter-group comparisons were made regarding operation time, intraoperative blood loss, postoperative intestinal function recovery, hospitalization time, clinical efficacy, and postoperative complication rate. Pain intensities before and, 4, 24, 48, and 72 hours after surgery were assessed using the Visual Analogue Score. After a 1-year post-discharge follow-up, the stone recurrence rate was counted, and the Gastrointestinal Quality-of-Life Index evaluated the quality of life. Results: There was no difference in operation time between the two groups (P > .05), but intraoperative blood loss, recovery time of intestinal function, hospitalization time, and complication rate were all lower in the observation group than in the control group (P < .05). In addition, the clinical efficacy of the observation group was better, and postoperative pain was lower (P < .05). In the prognostic follow-up, it was seen that the observation group had a lower stone recurrence rate (3.51%) and better quality of life (P < .05). Conclusions: CS combined with minimally invasive abdominal surgery is effective and safe in treating patients with GS and can validly reduce the prognosis risk of recurrent stones in patients, which deserves popularization in clinical use.