Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Multiparametric MR characterization for human epithelial growth factor receptor 2 expression in bladder cancer: an exploratory study.

PURPOSE: To investigate the application value of multiparametric MRI in evaluating the expression status of human epithelial growth factor receptor 2 (HER2) in bladder cancer (BCa). METHODS: From April 2021 to July 2023, preoperative imaging manifestations of 90 patients with pathologically confirmed BCa were retrospectively collected and analyzed. All patients underwent multiparametric MRI including synthetic MRI, DWI, from which the T1, T2, proton density (PD) and apparent diffusion coefficient (ADC) values were obtained. The clinical and imaging characteristics as well as quantitative parameters (T1, T2, PD and ADC values) between HER2-positive and -negative BCa were compared using student t test and chi-square test. The diagnostic efficacy of parameters in predicting HER2 expression status was evaluated by calculating the area under ROC curve (AUC). RESULTS: In total, 76 patients (mean age, 63.59 years ± 12.84 [SD]; 55 men) were included: 51 with HER2-negative and 25 with HER2-positive BCa. HER2-positive group demonstrated significantly higher ADC, T1, and T2 values than HER2-negative group (all P < 0.05). The combination of ADC values and tumor grade yielded the best diagnostic performance in evaluating HER2 expression level with an AUC of 0.864. CONCLUSION: The multiparametric MR characterization can accurately evaluate the HER2 expression status in BCa, which may further guide the determination of individualized anti-HER2 targeted therapy strategies.

A study on combination of non-ablative local RFA with PD-1 and angiogenesis blocking to prolong survival through improvement of immune microenvironment in advanced Hepatocellular Carcinoma.

Radiofrequency ablation (RFA), an effective local treatment method for early-stage Hepatocellular Carcinoma (HCC), combined with PD-1 blocking and anti-angiogenic therapy is being extensively explored in advanced HCC, however, the definite results and underlying mechanisms still remain to be elucidated. Therefore, whether non-ablative RFA-based combined therapy can play a synergistic anti-tumor effect through improving tumor immune microenvironment was investigated by us in HCC mouse models. Our results showed that non-ablative RFA could regulate multilayered immunity, such as inducing immunogenic death of tumor cells, upregulating the secretion of inflammatory cytokines, mainly IFN-γ, TNF-α, and IL-10, and subsequently promoting the infiltration of CD8 + T cells. As a result, a significant synergistic anti-tumor effect was demonstrated in the combination therapy group. Similarly, in the real-world setting, non-curative RFA combined with PD-1 blocking and Lenvatinib for 12 patients with Barcelona Clinic Liver Cancer (BCLC) stage C achieve promising results, with 6.9 months (95 % CI: 3.23-15.73) median progression-free survival (mPFS) and 12.7 months (95 % CI: 7.40-19.73) median overall survival (mOS). The common treatment-related adverse reactions were pneumonia and thyroiditis with low prevalence, both less than grade 3 and manageable by symptomatic treatment. Summarily, local non-ablative RFA should be a clinically preferred strategy in combination with PD-1 blocking and anti-angiogenic therapy, because this more flexible scheme abandons its historical concept of tumor eradication, but fully utilizes the immune regulatory function by inducing immunogenic tumor death and has higher-level of safety. Therefore, this is a two-pronged and highly balanced approach to achieved favorable treatment outcomes, while conclusive evidence is still pending, it can be attempted in the real world anyway.

Anti-glioma effect of paclitaxel mediated by specific mode electroacupuncture stimulation and the related role of the Hedgehog pathway.

INTRODUCTION: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway. METHODS: The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100 Hz, 3 mA, 6-6 s, and 40 min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. RESULTS: SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression. CONCLUSION: SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB.

Metabonomics and pharmacodynamics studies of Gentiana radix and wine-processed Gentiana radix in damp-heat jaundice syndrome rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana radix (GR) and wine-processed Gentiana radix (WGR) have been commonly used in folk medicine for the treatment of bile or liver disorders, including jaundice, hepatitis, swelling and inflammation for thousands of years. However, the therapeutic effects of gentian root (GR) and wine-made gentian root (WGR) treatment on damp-heat jaundice syndrome (DHJS) have not been studied in animal experiments. AIM OF THE STUDY: This study aimed to investigate the protective effects and mechanisms of GR and WGR on DHJS in rats. MATERIALS AND METHODS: In a high-fat and high-sugar diet in a humidified hot environment, hepatic injury induced by giving alpha-naphthalene isothiocyanate (ANIT) in rats were used as a DHJS model. Histological analysis, enzyme-linked immunosorbent assay (ELISA), PCR analysis, and metabolomics were used to elucidate the mechanism of GR and WGR for DHJS. RESULTS: The results indicated that GR and WGR affected DHJS by inhibiting the release of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (D-BIL), total bilirubin (TBIL), total bile acid (TBA), malondialdehyde (MDA), glutathione S-transferase (GST) (P < 0.05). In addition, they significantly reduced the gene expression levels of Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BESP), multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) (P < 0.05). The WGR group improved the above function indicators better than the GR group. GR and WGR could restore 11 potential biomarkers in rats with DHJS tended to return to normal levels, these biomarkers were involved in arachidonic acid metabolism, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, porphyrin and chlorophyll metabolism, retinol metabolism, arginine biosynthesis. The results of the metabolic pathway showed that WGR was significantly better than GR in the improvement of porphyrin and chlorophyll metabolism. CONCLUSIONS: These findings suggest that treatment with GR and WGR has a beneficial effect on DHJS in rats, the major mechanisms may be involved in improving functional indicators of the body and endogenous metabolism, and WGR is more effective than GR. It provides important evidence for the clinical application of GR and WGR in the treatment of DHJS.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events.

BACKGROUND: This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. METHODS: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. RESULTS: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. CONCLUSIONS: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm ­ a muscle that helps with breathing ­ becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specifically for patients who also had heart, blood, or blood vessel disease; patients who had a mental illness; and patients who had MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight hospital stays. Patients with gMG also had four times more overnight hospital stays and two times more hospital day visits when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors also need to control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.

Aconitum coreanum and processed products on its base prevent stroke via the PI3K/Akt and KEAP1/NRF2 in the in vivo study.

Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.

Application of Platysma Myocutaneous Flap in Surgical Repair after T2-3 Glottic Carcinoma Resection.

OBJECTIVE: Numerous methods and materials are available for vertical partial laryngectomy. In this study, the reparative effects of the platysma myocutaneous flap (PMF) and ribbon myocutaneous flap (RMF) on the postoperative voice quality of patients were compared to provide a reference for selecting a method conducive to improving postoperative voice quality. METHODS: A retrospective analysis was performed on patients with unilateral T2-3 glottic carcinoma. Following vertical partial laryngectomy, the defect was repaired with a PMF or simple RMF. Twelve months after surgery, voice quality was assessed according to voice acoustics, aerodynamics, and subjective perceptual evaluation, and glottic morphology was recorded using a laryngeal stroboscopy. RESULTS: A total of 70 patients were identified, including 54 in the PMF group and 16 in the RMF group. The PMF group was superior to the RMF group in terms of voice quality assessed by voice acoustics, aerodynamics, and subjective perceptual evaluation. In the PMF group, 72.2% of patients performed phonation with their vocal cords, and approximately 27.8% of patients were affected by supraglottic compression. In the RMF group, 81.3% of patients were affected by supraglottic compression. No significant difference was found in the 5-year survival rate between the two groups. CONCLUSION: For defect repair following vertical partial laryngectomy, a PMF can allow better postoperative voice quality to be achieved than an RMF because a PMF can provide more tissue (including strap muscle under the flap) for padding, which enables the glottic portion corresponding to the vocal cord to close well. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3181-3186, 2024.

Bioinformatic analysis reveals prognostic value and immunotherapy potential of Siglec-15 in laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is the ultimate common malignant head and neck cancer with dismal prognosis. The expression pattern and clinical significance of Siglec-15 (Sialic acid-binding immunoglobulin-like lectin 15) in LSCC are poorly understood. In order to lay the groundwork for future immune-related research on Siglec-15 in LSCC, we set out to study its expression and prognostic importance in the disease, as well as to use bioinformatics to investigate the immune features modulated by Siglec-15 in LSCC. Methods: ① In order to get the gene expression profile and clinical data for TCGA head and neck cancer (TCGA-HNSC), you may access the relevant data from UCSC xena and use 110 cases of laryngeal cancer as a training set. Two datasets, GSE27020 and GSE25727, were obtained from the GEO databank and utilized as validation sets. These datasets include expression profiles and clinical information. The Siglec-15 gene and immune characteristics were analyzed by bioinformatics methods. ② Retrospectively collected routine paraffin specimens from patients with pathological diagnosis of squamous cell carcinoma from December 2012 to November 2015 in Sun Yat-sen Memorial Hospital and fresh frozen tissue of patients from June 2021 to March 2022. Immunohistochemistry method, immunofluorescence technique and real-time quantitative PCR was used to examine the difference of Siglec-15 appearance in LSCC tissue and adjacent tissue, and its correlation of prognosis, clinic pathological characteristics and CD8+T lymphocyte infiltration. Using human laryngeal cancer cell line (LCC), we studied the influence of Siglec-15 in cell proliferation and invasion. Results: We identified Siglec-15 was upregulated in LSCC. The patients in Siglec-15 high expression group had a poor overall survival (OS) based on the clinical information from TGCA and 111 LSCC patients that hospitalized in Sun Yat-sen Memorial Hospital. The COX regression analysis indicated Siglec-15 as an independent predictor for poor prognosis of LSCC. Bioinformatic analysis suggested that the high expression of Siglec-15 shape an immune suppressive tumor microenvironment (TEM), leading to poor response to immunotherapy in LSCC. Siglec-15 enhanced cell invasion and proliferation, as we showed in vitro. Conclusion: Our study support Siglec-15 as a potential predictor for LSCC prognosis and an attractive target for LSCC immunotherapy.

Radiomics nomogram for predicting disease-free survival after partial resection or radical cystectomy in patients with bladder cancer.

OBJECTIVES: To create a MRI-derived radiomics nomogram that combined clinicopathological factors and radiomics signature (Rad-score) for predicting disease-free survival (DFS) in patients with bladder cancer (BCa) following partial resection (PR) or radical cystectomy (RC), including lymphadenectomy (LAE). METHODS: Finally, 80 patients with BCa after PR or RC with LAE were enrolled. Patients were randomly split into training (n = 56) and internal validation (n = 24) cohorts. Radiomic features were extracted from T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, and apparent diffusion coefficient sequence. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was applied to choose the valuable features and construct the Rad-score. The DFS prediction model was built using the Cox proportional hazards model. The relationship between the Rad-score and DFS was assessed using Kaplan-Meier analysis. A radiomics nomogram that combined the Rad-score and clinicopathological factors was created for individualized DFS estimation. RESULTS: In both the training and validation cohorts, the Rad-score was positively correlated with DFS (P < .001). In the validation cohort, the radiomics nomogram combining the Rad-score, tumour pathologic stage (pT stage), and lymphovascular invasion (LVI) achieved better performance in DFS prediction (C-index, 0.807; 95% CI, 0.713-0.901) than either the clinicopathological (C-index, 0.654; 95% CI, 0.467-0.841) or Rad-score-only model (C-index, 0.770; 95% CI, 0.702-0.837). CONCLUSION: The Rad-score was an independent predictor of DFS for patients with BCa after PR or RC with LAE, and the radiomics nomogram that combined the Rad-score, pT stage, and LVI achieved better performance in individual DFS prediction. ADVANCES IN KNOWLEDGE: This study provided a non-invasive and simple method for personalized and accurate prediction of DFS in BCa patients after PR or RC.

Percutaneous microwave ablation versus sclerotherapy for large hepatic hemangioma: a multi-center cohort study.

OBJECTIVE: The study aimed to compare the effectiveness and safety of ultrasound-guided microwave ablation (MWA) and percutaneous sclerotherapy (PS) for the treatment of large hepatic hemangioma (LHH). METHODS: This retrospective study included 96 patients who underwent MWA (n = 54) and PS (n = 42) as first-line treatment for LHH in three tertiary hospitals from January 2016 to December 2021. Primary outcomes were technique efficacy rate (volume reduction rate [VRR] > 50% at 12 months), symptom relief rate at 12 months and local tumor progression (LTP). Secondary outcomes included procedure time, major complications, treatment sessions, cost and one-, two-, three-year VRR. RESULTS: During a median follow-up of 36 months, the MWA group showed a higher technique efficacy rate (100% vs. 90.4%, p = .018) and symptom relief rate (100% vs. 80%, p = .123) than the PS group. The MWA group had fewer treatment sessions, higher one-, two- and three-year VRR, lower LTP rate (all p < .05), longer procedure time and higher treatment costs than the PS group (both p < .001). MWA shared a comparable major complications rate (1.8% vs. 2.4%, p = .432) with PS. After multivariate analysis, the lesion's heterogeneity and maximum diameter >8.1 cm were independent risk factors for LTP (all p < .05). In the PS group, lesions with a cumulative dose of bleomycin > 0.115 mg/cm3 had a lower risk of LTP (p = .006). CONCLUSIONS: Both MWA and PS treatments for large hepatic hemangioma are safe and effective, with MWA being superior in terms of efficacy.

Amide Proton Transfer-Weighted MRI and Diffusion-Weighted Imaging in Bladder Cancer: A Complementary Tool to the VI-RADS.

RATIONALE AND OBJECTIVES: To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted Magnetic Resonance Imaging (MRI) as a means by which to add value to the Vesical Imaging Reporting and Data System (VI-RADS) for discriminating muscle invasive bladder cancer (MIBC) from nonmuscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: This prospective study enrolled participants with pathologically confirmed bladder cancer (BCa) who underwent preoperative multiparametric MRI, including APTw and diffusion-weighted MRI, from July 2020 to January 2023. The exclusion criteria were lesions smaller than 10 mm, missing smooth muscle layer in the operation specimen, neoadjuvant therapy before MRI, inadequate image quality, and malignancy other than urothelial neoplasm. Two radiologists independently assigned the VI-RADS score for each participant. Quantitative parameters derived from APTw and diffusion-weighted MRI were obtained by another two radiologists. Receiver operating characteristic (ROC) curve analysis with the area under the ROC curve (AUC) was performed to evaluate the diagnostic performances of quantitative parameters for discriminating BCa detrusor muscle invasion status. RESULTS: A total of 106 participants were enrolled (mean age, 64 ± 12 years [SD]; 90 men): 32 with MIBC and 74 with NMIBC. Lower apparent diffusion coefficient (ADC) values (0.88 × 10-3 mm2/s ± 0.12 vs. 1.08 × 10-3 mm2/s ± 0.25; P < 0.001) and higher APTw values (6.89% [interquartile range {IQR}, 5.05%-12.17%] vs. 3.61% [IQR, 2.23%-6.83%]; P < 0.001) were observed in the MIBC group. Compared to VI-RADS alone, both APTw (P = 0.003) and ADC (P = 0.020) values could improve the diagnostic performance of VI-RADS in differentiating MIBC from NMIBC. The combination of the three yielded the highest diagnostic performance (AUC, 0.93; 95% CI:0.87,0.97) for evaluating muscle invasion status. The addition of the APTw values to the combination of VI-RADS and ADC values notably improved the diagnostic performance for differentiating NMIBC from MIBC (VI-RADS+ADC vs. VI-RADS+APTw+ADC, P = 0.046). CONCLUSION: MRI parameters derived from APTw and diffusion-weighted MRI can be used to accurately assess muscle invasion status in BCa and provide additional value to VI-RADS.

The mediating role of resilience in the relationship between stress and psychological distress in parents of children with cancer.

Caring for children with cancer is stressful for parents and leads to psychological distress, which is mainly manifested as depressive symptoms and anxiety. This study explored the mediating role of resilience in the relationship between stress and psychological distress in parents of children with cancer. We recruited 258 parents of children with cancer in three tertiary hospitals in Mainland China. The results revealed that the mediating effect of resilience for the relationships between stress and depressive symptoms and between stress and anxiety accounted for 23.4% and 11.4%, respectively, of the total effect. Resilience was confirmed as a protective factor that can be incorporated into future intervention programmes to improve the psychological well-being of parents of children with cancer. Future studies could develop resilience training programmes to enhance the resilience of parents of children with cancer to alleviate parents' psychological distress.

Correlation analysis of cardiopulmonary exercise test indices and conditions of overweight patients with obstructive sleep apnea: a retrospective study

ABSTRACT BACKGROUND: The cardiopulmonary function of patients with obstructive sleep apnea (OSA) is significantly lower than that of patients with simple snoring and is significantly related to the severity of OSA. Currently, only a few studies have been conducted on cardiopulmonary exercise testing in overweight patients with OSA. OBJECTIVE: To analyze the correlation between cardiopulmonary exercise test (CPET) indices and the condition of overweight patients with OSA. DESIGN AND SETTING: Retrospective study in Guangdong Provincial Hospital of Chinese Medicine. METHODS: This study included 73 hospitalized overweight patients. The patients were divided into no, mild, moderate, and severe OSA groups. Differences in the CPET indices among the four groups were compared. The correlation between the CPET indices and conditions was analyzed. RESULTS: No, mild, moderate, and severe OSA groups had 18 men and 5 women, 11 men and 3 women, 12 men and 2 women, and 21 men and 1 woman, respectively (P > 0.05). No significant difference was observed in resting pulmonary function among the four groups (P > 0.05). In the CPET, the anaerobic threshold, maximum oxygen uptake, and oxygen pulse were significantly lower in the severe OSA group than those in the normal OSA group (P < 0.05). Moreover, CPET indices negatively correlated with the apnea-hypopnea index. CONCLUSION: Changes in CPET indices occurred earlier than changes in resting pulmonary function in patients with OSA. CPET might be a potential method for evaluating the severity of OSA combined with overweight status.

Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats.

BACKGROUND: Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it's often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM: To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS: The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS: 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1ß, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION: These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.

FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation.

Adipose tissue macrophages (ATM) are key players in the development of obesity and associated metabolic inflammation which contributes to systemic metabolic dysfunction. We here found that fibroblast activation protein α (FAP), a well-known marker of cancer-associated fibroblast, is selectively expressed in murine and human ATM among adipose tissue-infiltrating leukocytes. Macrophage FAP deficiency protects mice against diet-induced obesity and proinflammatory macrophage infiltration in obese adipose tissues, thereby alleviating hepatic steatosis and insulin resistance. Mechanistically, FAP specifically mediates monocyte chemokine protein CCL8 expression by ATM, which is further upregulated upon high-fat-diet (HFD) feeding, contributing to the recruitment of monocyte-derived proinflammatory macrophages with no effect on their classical inflammatory activation. CCL8 overexpression restores HFD-induced metabolic phenotypes in the absence of FAP. Moreover, macrophage FAP deficiency enhances energy expenditure and oxygen consumption preceding differential body weight after HFD feeding. Such enhanced energy expenditure is associated with increased levels of norepinephrine (NE) and lipolysis in white adipose tissues, likely due to decreased expression of monoamine oxidase, a NE degradation enzyme, by Fap-/- ATM. Collectively, our study identifies FAP as a previously unrecognized regulator of ATM function contributing to diet-induced obesity and metabolic inflammation and suggests FAP as a potential immunotherapeutic target against metabolic disorders.

Identifying the cancer-associated fibroblast signature to predict the prognosis and immunotherapy response in patients with lung squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment that contribute toward the development of tumors. This study aimed to establish a new algorithm based on CAF scores to predict the prognosis and immunotherapy response in patients with lung squamous cell carcinoma (LUSC). The RNA-seq data of LUSC patients were obtained from two databases and merged after removing inter-batch differences. The CAF-related data for each sample were obtained through three different algorithms. Consistency cluster analysis was performed to obtain different CAF clusters, which were analyzed to identify differentially expressed genes. These were subjected to uniform cluster analysis to obtain different gene clusters. The Boruta algorithm was used to calculate the CAF score. Three CAF clusters and two gene clusters were obtained, all of which differed in their patient prognoses and the content of infiltrating immune cells. Patients with high CAF scores exhibited worse overall survival, higher expression of biomarkers related to immune checkpoints and immune activity, and lower tumor mutation burden. The CAF score could also predict the immunotherapy response of patients. This study suggests that the CAF score can accurately predict the prognosis and immunotherapy response of LUSC patients.

Multiparametric MRI-based VI-RADS: can it predict 1- to 5-year recurrence of bladder cancer?

OBJECTIVES: To evaluate whether Vesical Imaging-Reporting And Data System (VI-RADS) scores based on multiparametric MRI (mp-MRI) can predict bladder cancer (BCa) recurrence. METHODS: In this retrospective study, 284 patients with pathologically confirmed bladder neoplasms from November 2011 to October 2020 were included. Two radiologists blindly and independently scored mp-MRI scans according to VI-RADS. Scoring inconsistency was resolved in consensus. The latest follow-up was completed in December 2022. Pearson's correlation analyses, independent-sample t-tests, and receiver operating characteristic analyses were performed to assess the efficacy of VI-RADS score for the 1- to 5-year recurrence prognostication. RESULTS: Based on the latest follow-up, 37 (of 284, 13.0%), 69 (of 284, 24.3%), 70 (of 234, 29.9%), 72 (of 190, 37.9%), and 63 (of 135, 46.7%) patients had cancer recurrence at 1- to 5-year follow-up, respectively. VI-RADS scores showed significantly intergroup differences between recurrent and nonrecurrent cases during 1- to 4-year surveillance (p < 0.05). The recurrence-free survival was significantly higher in patients with VI-RADS scores of 1 or 2, compared to those with scores of 3, 4, or 5 (p < 0.05). Areas under the receiver operating characteristic curves for 1- to 5-year recurrence prediction were 0.744, 0.686, 0.656, 0.595, and 0.536, respectively. VI-RADS score of 3 or more was the threshold for 1-year recurrence assessment, and VI-RADS more than 3 was the cutoff for 2-year recurrence prediction. CONCLUSION: VI-RADS score has potential in preoperative prognostication of BCa recurrence, but its predictive power decreases over time. CLINICAL RELEVANCE STATEMENT: VI-RADS has potential in bladder cancer recurrence assessment, but its prognostic value decreases over time. Patients with VI-RADS ≥ 3 may be more likely to recur in 1 or 2 years postoperatively, thus should be performed with intensive surveillances. KEY POINTS: • VI-RADS scores had significant differences in 1- to 4-year recurrent and nonrecurrent patient groups. • Patients with VI-RADS scores of ≤ 2 showed more favorable recurrence-free survival outcomes. • The prognostic value of VI-RADS score decreased over time for bladder cancer recurrence prediction.