Arthroscopic Repair of Acetabular Cartilage Delamination Using Chondral Nail Fixation in Patients With Femoroacetabular Impingement.

Acetabular cartilage delamination is commonly seen in patients with femoroacetabular impingement (FAI), especially ones with the cam deformity. However, the definition and classification of acetabular cartilage injuries caused by FAI to guide clinical treatment remain controversial. Moreover, treatment of acetabular cartilage damage always causes a dilemma for surgeon during surgery. We believe a reliable repair of the acetabular cartilage delamination will lead to a better long-term outcome for patients with FAI. In this Technical Note, we introduce the chondral nail fixation under hip arthroscopy for treating acetabular cartilage delamination in patients with FAI. This technique contributes to eliminating intra-articular unstable factors, preserving native cartilage as much as possible, and restoring cartilage surface intact at best.

Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Global, regional, and national burden of trachea, bronchus, and lung cancer among women of reproductive age, 1990-2019.

BACKGROUND: Trachea, bronchus, and lung (TBL) cancer has demonstrated a discernible feminization and a tendency towards younger onset in recent decades. Therefore, our objective is to examine the most recent patterns in the worldwide prevalence of TBL among women of reproductive age on a global, regional, and national scale. METHODS: To assess the prevalence trends of TBL in women of reproductive age, we calculated the estimated annual percentage change (EAPC), age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and disability-adjusted life years (DALYs) for 204 countries and territories from 1990 to 2019. These calculations were based on the Global Burden of Disease (GBD) 2019 database. RESULTS: From 1990 to 2019, there was a global increase in the absolute number of incidence cases, deaths, and DALYs of TBL in women of reproductive age. However, the ASIR, ASDR, and age-standardized DALY rates were decreasing over this period, with EAPC of -0.77 (95 % confidence interval [CI]: -1.03 to -0.51), -1.08 (95 % CI: -1.34 to -0.82), and -1.10 (95 % CI: -1.36 to -0.84), respectively. This trend was observed even in regions with higher Socio-Demographic Index (SDI). East Asia consistently had the highest ASIR, ASDR, and age-standardized DALY rate, but there was a decreasing trend. Conversely, Eastern Sub-Saharan Africa displayed an increasing burden pattern. When examining countries individually, Monaco, Greenland, and Palau had the highest ASIR. Moreover, in most countries, the ASIR for TBL increased with age, particularly among women aged 35-49 years. CONCLUSIONS: Despite a global decline in ASIR, ASDR, and age-standardized DALY rates for TBL in women of reproductive age over the past three decades, there is still a troubling increase observed in low- and low-middle SDI regions. It is crucial to implement effective preventive and curative measures in these regions in order to address this concerning trend.

Quantitative assessment whole-rock iron content in magnetite protolith based on terahertz time-domain spectroscopy.

Terahertz time-domain spectroscopy was first used to establish a correlation with the whole-rock iron (TFe) content in different depths of the Bayan Obo protolith. Compared with element content obtained by the traditional method of X-ray fluorescence spectroscopy (XRF), a similar tendency of the absorption coefficient and refractive index is presented. Furthermore, three machine learning algorithms, namely, partial least squares regression (PLSR), random forest (RF), and multi-layer perceptron (MLP), were used to develop a quantitative analytical model for TFe content of the protolith minerals. Among the three algorithms, MLP has the highest detection accuracy, with a model coefficient of determination R 2 reaching up to 0.945. These findings demonstrate that terahertz time-domain spectroscopy can be used to rapidly quantify the TFe elemental content of protolith, providing a method of detecting the content of mineral components.

Predicting the risk of lung cancer using machine learning: A large study based on UK Biobank.

In response to the high incidence and poor prognosis of lung cancer, this study tends to develop a generalizable lung-cancer prediction model by using machine learning to define high-risk groups and realize the early identification and prevention of lung cancer. We included 467,888 participants from UK Biobank, using lung cancer incidence as an outcome variable, including 49 previously known high-risk factors and less studied or unstudied predictors. We developed multivariate prediction models using multiple machine learning models, namely logistic regression, naïve Bayes, random forest, and extreme gradient boosting models. The performance of the models was evaluated by calculating the areas under their receiver operating characteristic curves, Brier loss, log loss, precision, recall, and F1 scores. The Shapley additive explanations interpreter was used to visualize the models. Three were ultimately 4299 cases of lung cancer that were diagnosed in our sample. The model containing all the predictors had good predictive power, and the extreme gradient boosting model had the best performance with an area under curve of 0.998. New important predictive factors for lung cancer were also identified, namely hip circumference, waist circumference, number of cigarettes previously smoked daily, neuroticism score, age, and forced expiratory volume in 1 second. The predictive model established by incorporating novel predictive factors can be of value in the early identification of lung cancer. It may be helpful in stratifying individuals and selecting those at higher risk for inclusion in screening programs.

A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer.

Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 µg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.

Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolutionize cancer management. Among various types of FAP ligands, peptides and antibodies have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides in tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

Asymmetric synthesis of P-stereogenic phosphindane oxides via kinetic resolution and their biological activity.

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Deep learning-based automated lesion segmentation on pediatric focal cortical dysplasia II preoperative MRI: a reliable approach.

OBJECTIVES: Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II. METHODS: High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance. RESULTS: The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset. CONCLUSION: This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection. CRITICAL RELEVANCE STATEMENT: Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes. KEY POINTS: • Simplified image processing promotes the DL model implemented in clinical practice. • The histopathological confirmed lesion masks enhance the clinical credibility of the AI model. • The voxel-level evaluation metrics benefit lesion detection and clinical decisions.

External treatment of traditional Chinese medicine for cancer pain: A systematic review and network meta-analysis.

BACKGROUND: Cancer pain is one of the most intolerable and frightening symptoms of cancer patients. However, the clinical effect of the three-step analgesic ladder method (TSAL) is not satisfactory. The combination of external treatment of traditional Chinese medicine (TCM) can improve the clinical effect. OBJECTIVE: This study used network meta-analysis to compare the effects of different external treatment methods of TCM combined with TSAL on cancer pain. METHODS: Databases searched by our team included Google Scholar, Web of Science, Scopus, Embase, PubMed, and Cochrane Library. Randomized controlled trials related to the external treatment of TCM combined with TSAL for cancer pain were screened from the establishment of the database till now. The above literature extracted clinical efficacy, NRS score, KPS score, analgesic onset time, and duration as the main results after the screening. The 95% confidence interval (95% CI) of OR value and SMD value was used as the effect index to compare the difference in efficacy of different interventions, and the ranking was conducted. STATA 17.0 software was used for the statistical analysis of the above data. RESULTS: A total of 78 studies were included, including 8 interventions and 5742 participants. Based on ranking probability, the clinical effective rate of manual acupuncture combined with TSAL was the best when the intervention time was set at 4 weeks [OR = 5.42, 95% CI (1.99,14.81)], and the improvement effect on KPS score was also the best [SMD = 0.97, 95% CI (0.61, 1.33)]. Acupoint external application was the best intervention in reducing NRS score [SMD = -1.14, 95% CI (-1.90, -0.93)]. Acupoint moxibustion combined with TSAL was considered to be the most effective intervention to prolong the duration of analgesia [SMD = 1.69, 95% CI (0.84, 2.54)] and shortening the onset time of analgesia [SMD = -3.00, 95% CI (-4.54, -1.47)]. CONCLUSIONS: TSAL combined with manual acupuncture is the best in terms of clinical efficacy and improvement of patients' functional activity status. With the extension of treatment time, the intervention of this kind of treatment on the clinical effect is more pronounced. Acupoint external application also has a unique advantage in reducing the pain level of patients. From the point of view of analgesic duration and duration of analgesia, combined acupoint moxibustion has the best effect.

Is cryoablation still suitable for advanced non-small cell lung cancer after failure of first-line chemotherapy? A multicenter, prospective, randomized-controlled trial of eighty-seven patients.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

[Replication and expression of oncolytic herpes simplex virus type â ¡ in tumors].

This study aimed to measure the duration and replication level of oncolytic herpes simplex virus type 2 (oHSV2) at the tumor injection site in BALB/c mice. Additionally, the expression level of human granulocyte macrophage colony-stimulating factor (hGM-CSF) and HSV-2 antibody in the serum was also measured. High and low doses of oHSV2-Fluc (firefly luciferin, Fluc) were injected into the mice's tumors to track the change and duration of fluorescence expression. The copy number of oHSV2 gene in tumor tissues was determined using quantitative real-time polymerase chain reaction (qPCR). Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of hGM-CSF and HSV-2 antibody in the serum. The tumor volume in the high-dose group was significantly lower than that in the control group (P < 0.01). Intratumor injection of oHSV2-Fluc showed that the carried Fluc could continue to express in the tumor, with fluorescence still detectable at day 11 and declining to undetectable level by day 18. The mRNA expression of oHSV2 was detected in tumor tissues of both high and low dose groups on day 9 using qPCR. ELISA results showed that the levels of HSV2 antibody and hGM-CSF in both high and low dose groups were significantly increased compared to the control group (P < 0.05) after collecting orbital blood. These findings suggest that oHSV2 can replicate in the tumor and sustainably express exogenous factors, thus effectively targeting and killing the tumor. Furthermore, intratumoral injection of oHSV2 resulted in higher levels of hGM-CSF and HSV-2 antibodies found in the mice's serum.

A Potent SOS1 PROTAC Degrader with Synergistic Efficacy in Combination with KRASG12C Inhibitor.

AMG510, as the first approved inhibitor for KRASG12C mutation, has shown promising efficacy in nonsmall-cell lung cancer and colorectal cancer harboring KRASG12C mutation. However, the moderate response rate and the rapid emergence of acquired resistance limit the therapeutic potential of AMG510, highlighting the need for the development of combination strategies. Here, we observed the suppression of RAS-MAPK signaling induced by AMG510 was prolonged and enhanced by SOS1 knockdown. Thus, we design, synthesize, and characterize a potent and specific SOS1 degrader 23. Compound 23 showed efficient SOS1 degradation in KRAS-driven cancer cells and achieved significant antiproliferative potency. Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRASG12C mutant cells in vitro and in vivo. Our findings demonstrated that KRASG12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRASG12C inhibitor.

Discrepancies in MR- and CT-Based Femoral Version Measurements Despite Strong Correlations.

PURPOSE: To determine the correlation and classification consistency of femoral version measurements between magnetic resonance (MR) and computed tomography (CT) using 4 commonly used measurement methods. METHODS: A retrospective study was performed on patients with femoroacetabular impingement (FAI) who received preoperative CT and MR imaging assessment of the surgical hip and ipsilateral distal femur. Femoral version was measured using the Murphy method, the oblique method, the Reikerås method, and the Lee method. Intra- and inter-rater agreements were calculated. Linear regression and Bland-Altman analysis were performed for measurements using different imaging modalities and measurement methods. Femoral version measurements within the lower quartile, the middle 2 quartiles, and the upper quartile were classified into different groups based on their percentile within the sample population. Classification consistency rates between modalities and methods were calculated and compared. RESULTS: Fifty-three patients (39.4 ± 9.1 years; 32 female) were included for analysis. Intra- and inter-rater reliability were high for all modalities and methods (intrarater intraclass correlation coefficient [ICC] range, 0.963-0.993; inter-rater ICC range, 0.871-0.960). MR- and CT-based femoral version measurements showed strong correlations for all methods, with the Lee method demonstrating the strongest association (r = 0.904), while the oblique method exhibited the lowest correlation (r = 0.684) (all P < .001). MR-based measurements were smaller than CT-based measurements, with mean differences ranging from 4.5° to 10.3°. Classification consistency between MR and CT ranged from 51% to 74%, whereas the consistency between different measurement methods ranged from 68% to 85%. CONCLUSIONS: While strong correlations were observed between MR- and CT-based femoral version measurements, MR-based measurements were significantly smaller than their CT counterparts. Classification consistency between the modalities was moderate to high. Measurements between different methods showed strong correlations with high consistency rates. LEVEL OF EVIDENCE: Level III, retrospective case series.

First insights into the bioaccumulation, biotransformation and trophic transfer of typical tetrabromobisphenol A (TBBPA) analogues along a simulated aquatic food chain.

Tetrabromobisphenol A (TBBPA) analogues have been investigated for their prevalent occurrence in environments and potential hazardous effects to humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. Using a developed toxicokinetic model framework, we quantified the bioaccumulation, biotransformation and trophic transfer of tetrabromobisphenol S (TBBPS) and tetrabromobisphenol A di(allyl ether) (TBBPA-DAE) during trophic transfer from brine shrimp (Artemia salina) to zebrafish (Danio rerio). The results showed that the two TBBPA analogues could be readily accumulated by brine shrimp, and the estimated bioconcentration factor (BCF) value of TBBPS (5.68 L kg-1 ww) was higher than that of TBBPA-DAE (1.04 L kg-1 ww). The assimilation efficiency (AE) of TBBPA-DAE in zebrafish fed brine shrimp was calculated to be 16.3%, resulting in a low whole-body biomagnification factor (BMF) in fish (0.684 g g-1 ww). Based on the transformation products screened using ultra-high-performance liquid chromatograph-high resolution mass spectrometry (UPLC-HRMS), oxidative debromination and hydrolysis were identified as the major transformation pathways of TBBPS, while the biotransformation of TBBPA-DAE mainly took place through ether bond breaking and phase-II metabolism. Lower accumulation of TBBPA as a metabolite than its parent chemical was observed in both brine shrimp and zebrafish, with metabolite parent concentration factors (MPCFs) < 1. The investigated BCFs for shrimp of the two TBBPA analogues were only 3.77 × 10-10 - 5.59 × 10-3 times of the theoretical Kshrimp-water based on the polyparameter linear free energy relationships (pp-LFERs) model, and the BMF of TBBPA-DAE for fish was 0.299 times of the predicted Kshrimp-fish. Overall, these results indicated the potential of the trophic transfer in bioaccumulation of specific TBBPA analogues in higher trophic-level aquatic organisms and pointed out biotransformation as an important mechanism in regulating their bioaccumulation processes. ENVIRONMENTAL IMPLICATION: The internal concentration of a pollutant in the body determines its toxicity to organisms, while bioaccumulation and trophic transfer play important roles in elucidating its risks to ecosystems. Tetrabromobisphenol A (TBBPA) analogues have been extensively investigated for their adverse effects on humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. This study investigated the bioaccumulation, biotransformation and trophic transfer of TBBPS and TBBPA-DAE in a simulated di-trophic food chain. This state-of-art study will provide a reference for further research on this kind of emerging pollutant in aquatic environments.

Multiparametric MRI-Based Radiomics Signature with Machine Learning for Preoperative Prediction of Prognosis Stratification in Pediatric Medulloblastoma.

RATIONALE AND OBJECTIVES: Despite advances in risk-stratified treatment strategies for children with medulloblastoma (MB), the prognosis for MB with short-term recurrence is extremely poor, and there is still a lack of evaluation of short-term recurrence risk or short-term survival. This study aimed to construct and validate a radiomics model for predicting the outcome of MB based on preoperative multiparametric magnetic resonance images (MRIs) and to provide an objective for clinical decision-making. MATERIALS AND METHODS: The clinical and imaging data of 64 patients with MB admitted to Shenzhen Children's Hospital from December 2012 to December 2021 and confirmed by pathology were retrospectively collected. According to the 18-month progression-free survival, the cases were classified into a good prognosis group and a poor prognosis group, and all cases were divided into training group (70%) and validation group (30%) randomly. Radiomics features were extracted from MRI of each child. The consistency test, t-test, and the least absolute shrinkage and selection operator were used for feature selection. The support vector machine (SVM) and receiver operator characteristic were used to evaluate the distinguishing ability of the selected features to the prognostic groups. RAD score was calculated based on the selected features. The clinical characteristics and RAD score were included in the multivariate logistic regression, and prediction models were constructed by screening out independent influences. The radiomics nomogram was constructed, and its clinical significance was evaluated. RESULTS: A total of 1930 radiomic features were extracted from the images of each patient, and 11 features were included in the construction of radiomics score after selected. The area under the curve (AUC) values of the SVM model in the training and validation groups were 0.946 and 0.797, respectively. The radiomics nomogram was constructed based on the training cohort, and the AUC values in the training group and the validation group were 0.926 and 0.835, respectively. The results of clinical decision curve analysis showed that a good net benefit could be obtained from the nomogram. CONCLUSION: The radiomics nomogram established based on MRI can be used as a noninvasive predictive tool to evaluate the prognosis of children with MB, which is expected to help neurosurgeons better conduct preoperative planning and patient follow-up management.

The anti-hyperlipidemic effects of Poria cocos (Schw.) Wolf extract: Modulating cholesterol homeostasis in hepatocytes via PPARα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos (Schw.) Wolf (Polyporaceae, P.cocos), which is born on the pine root, has a history of more than two thousand years of medicine in China. P.cocos was first recorded in the Shennong's Herbal Classic, studies have proved its lipid-lowering effect. AIM OF STUDY: The aim of study was to investigate the underlying mechanism of P.cocos extract on hyperlipidemia. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats aged 9-12 weeks were intraperitoneally (IP) injected with Triton-WR 1339 to establish an acute hyperlipidemia model. At 0 h and 20 h after the model was established, low and high doses of P.cocos extract or simvastatin were given twice. After 48 h, the rats were sacrificed, and liver and serum samples were collected for analysis. The cell model was constructed by treating L02 cells with 1% fat emulsion-10% FBS-RPMI 1640 medium for 48 h. At the same time, low and high doses of P.cocos extract and simvastatin were administered. Oil red O staining was used to evaluate the lipid accumulation in the cells, and H&E staining was used to evaluate the liver lesions of rats. Real-time quantitative PCR and western blotting were used to detect the expressions of lipid metabolism-related genes. RESULTS: P.cocos extract relieved lipid accumulation in vitro and alleviated hyperlipidemia in vivo. Both gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα) were shown to be up-regulated by P.cocos extract. Additionally, P.cocos extract down-regulated the expressions of fatty acid synthesis-related genes sterol regulatory element-binding protein-1 (SREBP-1), Acetyl-CoA Carboxylase 1 (ACC1) and fatty acid synthase (FAS), while up-regulated the expressions of cholesterol metabolism-related genes liver X receptor-α (LXRα), ATP-binding cassette transporter A1 (ABCA1), cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein receptor (LDLR), which were reversed by the treatment with the PPARα inhibitor GW6471. CONCLUSION: P.cocos extract ameliorates hyperlipidemia and lipid accumulation by regulating cholesterol homeostasis in hepatocytes through PPARα pathway. This study provides evidence that supplementation with P.cocos extract could be a potential strategy for the treatment of hyperlipidemia.

A randomized prospective trial of an ostomy telehealth intervention for cancer survivors.

BACKGROUND: Cancer survivors with ostomies face complex challenges. This study compared the Ostomy Self-Management Telehealth program (OSMT) versus attention control usual care (UC). METHODS: Three academic centers randomized participants. OSMT group sessions were led by ostomy nurses and peer ostomates (three for ostomates-only, one for support persons, and one review session for both). Surveys at baseline, OSMT completion, and 6 months were primary outcome patient activation (PAM), self-efficacy (SE), City of Hope quality of life-Ostomy (COH-O), and Hospital Anxiety and Depression Scale (HADS). Surveys were scored per guidelines for those completing at least two surveys. Linear mixed effects models were used to select potential covariates for the final model and to test the impact of OSMT within each timeframe. RESULTS: A total of 90 OSMT and 101 UC fulfilled analysis criteria. Arms were well-matched but types of tumors were unevenly distributed (p = .023). The OSMT arm had a nonsignificant improvement in PAM (confidence interval [CI], -3.65 to 5.3]; 4.0 vs. 2.9) at 6 months. There were no significant differences in other surveys. There was a significant OSMT benefit for urinary tumors (four SE domains). Higher OSMT session attendance was associated with post-session improvements in five SE domains (p < .05), two COH-O domains (p < .05), and HADS anxiety (p = .01). At 6 months, there remained improvements in one SE domain (p < .05), one COH-O domain (p < .05), and HADS anxiety (p < .01). CONCLUSIONS: No clear benefit was seen for the OSMT intervention, although there may be an advantage based on type of tumor. Benefit with greater session attendance was also encouraging. PLAIN LANGUAGE SUMMARY: Cancer patients with ostomies have many challenges. We tested a telehealth curriculum compared to usual care. There are indications of benefit for the program for those that attend more sessions and those with urostomies.

Patterns of Failure in Metastatic NSCLC Treated With First Line Pembrolizumab and Use of Local Therapy in Patients With Oligoprogression.

INTRODUCTION: The patterns of failure (POF) for metastatic non-small-cell lung cancer (mNSCLC) treated with immunotherapy are not well established. METHODS: We conducted a retrospective cohort study of mNSCLC that received first-line pembrolizumab with or without chemotherapy at a single academic center from 2015 to 2021. We defined POF with 2 classifications: 1) local, regional, or distant failure, or 2) failure in existing lesions, new lesions, or a combination. Oligoprogression was defined as disease progression (PD) in ≤3 sites of failure. Overall survival (OS) was measured via Kaplan-Meier and modelled with Cox regression. RESULTS: Of 298 patients identified, 198 had PD. Using POF classification 1, most failures were distant (43.9%) or a combination of locoregional and distant (34.4%). For POF classification 2, failures occurred in a combination of new and existing lesions (45.0%), existing lesions alone (33.3%), or in new lesions only (21.7%). Oligoprogression occurred in 39.9% (n = 79) cases. Median OS was higher in the following: PD in existing lesions vs. new or new + existing lesions (28.7 vs. 20.2 vs. 13.9 months, P < .001) and oligoprogression vs. polyprogression (35.1 vs. 12.2 months, P < .001). In oligoprogression, median OS was better for those who received radiation to all sites of PD (62.2 months) than for those who changed systemic therapy (22.9 months, P = .007). On multivariable analysis, radiation for oligoprogression (HR 0.35, 95% CI: 0.20-0.62, P < .001) was associated with improved OS. CONCLUSIONS: In mNSCLC treated with pembrolizumab, oligoprogression is relatively common. Randomized data are needed to define the benefits of radiation in oligoprogressive mNSCLC.

Development of high-performance point-of-care aqueous VEGF detection system and proof-of-concept validation in RVO patients.

OBJECTIVES: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients. METHODS: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed. RESULTS: The automatic MPCLEIA system was able to provide results in 45 min with only 20 µL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category. CONCLUSIONS: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.