Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Current advances and future directions in combined hepatocellular and cholangiocarcinoma.

The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.

Both arthroscopic one-step Broström-Gould and Lasso-loop stitch techniques achieved favourable clinical outcomes for chronic lateral ankle instability.

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.

Nomogram for preoperative differentiation of benign and malignant breast tumors using contrast-enhanced cone-beam breast CT (CE CB-BCT) quantitative imaging and assessment features.

PURPOSE: Breast cancer's impact necessitates refined diagnostic approaches. This study develops a nomogram using radiology quantitative features from contrast-enhanced cone-beam breast CT for accurate preoperative classification of benign and malignant breast tumors. MATERIAL AND METHODS: A retrospective study enrolled 234 females with breast tumors, split into training and test sets. Contrast-enhanced cone-beam breast CT-images were acquired using Koning Breast CT-1000. Quantitative assessment features were extracted via 3D-slicer software, identifying independent predictors. The nomogram was constructed to preoperative differentiation benign and malignant breast tumors. Calibration curve was used to assess whether the model showed favorable correspondence with pathological confirmation. Decision curve analysis confirmed the model's superiority. RESULTS: The study enrolled 234 female patients with a mean age of 50.2 years (SD ± 9.2). The training set had 164 patients (89 benign, 75 malignant), and the test set had 70 patients (29 benign, 41 malignant). The nomogram achieved excellent predictive performance in distinguishing benign and malignant breast lesions with an AUC of 0.940 (95% CI 0.900-0.940) in the training set and 0.970 (95% CI 0.940-0.970) in the test set. CONCLUSION: This study illustrates the effectiveness of quantitative radiology features derived from contrast-enhanced cone-beam breast CT in distinguishing between benign and malignant breast tumors. Incorporating these features into a nomogram-based diagnostic model allows for breast tumor diagnoses that are objective and possess good accuracy. The application of these insights could substantially increase reliability and efficacy in the management of breast tumors, offering enhanced diagnostic capability.

Change and pathological significance of glycogen content in oral squamous cell carcinoma and oral submucous fibrosis.

OBJECTIVE: This study aimed to investigate the change and pathological significance of glycogen content in oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). METHODS AND MATERIALS: 13 normal oral mucosa (NOM), 12 OSF mucosa, and 35 pairs of OSCC tissues and their corresponding adjacent mucosa tissues (AT) were collected from Xiangya Hospital for PAS staining to detect glycogen. Transcriptome sequencing data from OSCC were used to compare glycogen metabolism gene expression differences. Kaplan-Meier method was conducted to estimate Recurrence-free survival (RFS). RESULTS: Glycogen levels were lower in OSF than in NOM and lower in OSCC than in AT. Transcriptome sequencing data analysis showed the expression of most glycogenolysis genes was increased and the expression of glycogen synthesis genes including PPP1R3C and GBE1 was decreased in OSCC tissues. High glycogen level was correlated with poor prognosis in OSCC patients under the background of OSF. CONCLUSION: Glycogen may be used as a potential diagnostic biomolecule for OSF and OSCC, as well as a potential prognostic factor for OSCC in the context of OSF.

Clinical Outcomes and Return to Preinjury Sports After Anatomic Reconstruction With a Gracilis Autograft Versus the Modified Broström Procedure in Patients With Generalized Joint Laxity.

Background: Generalized joint laxity (GJL) is a risk factor for inferior outcomes after the modified Broström procedure for chronic lateral ankle instability, while anatomic reconstruction with tendons is more inclined to be recommended. However, whether anatomic reconstruction could achieve better results than the modified Broström procedure in patients with GJL is unknown. Purpose: To compare clinical outcomes and return to sports between anatomic reconstruction and the modified Broström procedure in patients with GJL. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with GJL (Beighton score ≥4) who underwent either the modified Broström procedure or anatomic reconstruction with gracilis autografts between 2017 and 2020 were reviewed. Included were 19 patients who underwent anatomic reconstruction (reconstruction group) and 49 patients who underwent the modified Broström procedure (MBP group). Clinical outcomes were compared using the Foot and Ankle Outcome Score (FAOS) and the Karlsson score. The rates of return to preinjury level in high-demand sports, sprain recurrence, and range of motion between the 2 groups were also compared. Results: The mean follow-up duration was 38.3 months in the reconstruction group and 43.7 months in the MBP group. The FAOS and Karlsson scores improved significantly after surgery in both groups (P < .001 for all), with the reconstruction group having significantly higher postoperative FAOS-Sports scores (87.9 ± 8.9 vs 80.5 ± 11.6; P = .015) and Karlsson scores (86.9 ± 6.1 vs 82 ± 8.4; P = .025) than the MBP group. The rate of return to preinjury high-demand sports was higher in the reconstruction group than in the MBP group (73.3% vs 38.9%; P = .034). The MBP group had a significantly higher rate of sprain recurrence (22.4% vs 0%; P = .027). More patients reported dorsiflexion restriction in the reconstruction group (n = 4; 21.1%) than in the MBP group (n = 1; 2%) (P = .019); nonetheless, there was no noticeable effect on daily life and sports. Conclusion: Better clinical outcomes, less sprain recurrence, and a higher rate of return to preinjury high-demand sports were found after anatomic reconstruction with free tendons compared with the modified Broström procedure in patients with GJL. Anatomic tendon reconstruction can be recommended for such patients, especially those participating in high-demand sports.

B1 Power Modification for Amide Proton Transfer Imaging in Parotid Glands: A Strategy for Image Quality Accommodation and Evaluation of Tumor Detection Feasibility.

BACKGROUND: In the application of APTw protocols for evaluating tumors and parotid glands, inhomogeneity and hyperintensity artifacts have remained an obstacle. This study aimed to improve APTw imaging quality and evaluate the feasibility of difference B1 values to detect parotid tumors. METHODS: A total of 31 patients received three APTw sequences to acquire 32 lesions and 30 parotid glands (one patient had lesions on both sides). Patients received T2WI and 3D turbo-spin-echo (TSE) APTw imaging on a 3.0 T scanner for three sequences (B1 = 2 µT, 1 µT, and 0.7 µT in APTw 1, 2, and 3, respectively). APTw image quality was evaluated using four-point Likert scales in terms of integrity and hyperintensity artifacts. Image quality was compared between the three sequences. An evaluable group and a trustable group were obtained for APTmean value comparison. RESULTS: Tumors in both APT2 and APT3 had fewer hyperintensity artifacts than in APT1. With B1 values decreasing, tumors had less integrity in APTw imaging. APTmean values of tumors were higher than parotid glands in traditional APT1 sequence though not significant, while the APTmean subtraction value was significantly different. CONCLUSIONS: Applying a lower B1 value could remove hyperintensity but could also compromise its integrity. Combing different APTw sequences might increase the feasibility of tumor detection.

Antifatigue effects and antioxidant activity in polysaccharide fractions from Chinese yam bulbils.

Polysaccharides are the principal component in Chinese yam (Dioscorea opposita Thunb.) bulbils. The properties and antifatigue of polysaccharides from yam bulbils (PYB) were identified and compared. Their molecular weights (PYB-1 and PYB-2) were approximately 145 and 11 kDa, respectively, with active ß-configurations. Meanwhile, the antifatigue activities of PYBs were tested in mice via exhaustive swimming tests (EST). The EST results indicated that PYB-1 and PYB-2 significantly prolonged swimming time in mice (p < .05). Associated with this increase was a rise in hepatic glycogen content and antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)) activity, along with a decline in blood urea nitrogen, lactic acid, and malondialdehyde levels. The results showed that molecular weight might contribute to the antifatigue effects of PYBs. Additionally, antioxidant tests showed that PYB-1 had stronger free-radical scavenging activity than PYB-2. Taken together, the findings indicated that PYBs exhibited effective antifatigue and antioxidant activities providing additional evidence supporting the use of PYBs as functional food ingredients for relieving fatigue.

The Role of Endoscopic Ultrasound-guided Fine-needle Aspiration of Pelvic Lesions: A Meta-analysis.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a potentially valuable tool for the diagnosis of pelvic lesions. The aim of this meta­analysis was to evaluate the efficacy and feasibility of EUS-FNA in the diagnosis of pelvic lesions. METHODS: We performed a computerized search of PubMed, EMBASE, Cochrane Library, and Science Citation Index, through March 2023. The main outcome measures examined in the meta-analysis were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: We evaluated 22 trials that used surgical pathology or imaging follow-up results as the reference standard. The studies comprised 844 patients. The cumulative sensitivity, specificity, PPV, NPV, and accuracy were 94%, 100%, 100%, 89%, and 96%, respectively. In the subgroup analysis, the prospective studies revealed the cumulative sensitivity, specificity, PPV, NPV, and accuracy were 91%, 100%, 100%, 85%, and 93%, respectively. CONCLUSIONS: In conclusion, we provide evidence that EUS-FNA is a qualitative diagnostic technique with high sensitivity, specificity, PPV, and accuracy. However, its NPV is slightly low, which does not exclude the risk of a missed diagnosis, and more randomized controlled trials or prospective studies are still needed in the future. EUS-FNA is effective and feasible for pelvic space-occupying lesions. This technique has high clinical application value for pelvic lesions.

Return to Sport After Anatomic Lateral Ankle Stabilization Surgery for Chronic Ankle Instability: A Systematic Review and Meta-analysis.

BACKGROUND: Chronic lateral ankle instability that develops after ankle sprains has a severe, negative influence on the patient's lower extremity function. Anatomic repair or reconstruction of the lateral ankle ligament is an effective treatment for people with chronic lateral ankle instability who want to regain their preinjury levels of work and sport. PURPOSE: To determine the rate of return to sport (RTS) and related factors after anatomic lateral ankle stabilization (ALAS) surgery. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: Electronic databases including Medline, Embase, the Cochrane Library, and EBSCO Rehabilitation & Sports Medicine Source were searched from the earliest feasible entrance until August 2021. Articles reporting the number of patients who returned to sport after ALAS surgery and analyzing the relevant factors were included. The results were combined using proportion meta-analyses. RESULTS: A total of 25 publications were reviewed, with a total of 1384 participants. Results showed that 95% of patients (95% CI, 91%-99%) returned to any sport, 83% (95% CI, 73%-91%) returned to their preinjury level of sport, and 87% (95% CI, 71%-98%) returned to competitive sport after surgery. The mean time to RTS was 12.45 weeks (95% CI, 10.8-14.1 weeks). Each decade of age increased the likelihood of RTS failure by 6%, and increases in body mass index (BMI) of 5 kg/m2 raised the risk of RTS failure by 4%. The rate of RTS was higher in professional and competitive athletes (93%; 95% CI, 73%-100%) than in recreational athletes (83%; 95% CI, 76%-89%). Analysis showed no differences for arthroscopy versus open surgery, repair versus reconstruction, and early versus late weightbearing. CONCLUSION: In most cases, patients may return to some kind of sport after ALAS surgery, and some patients RTS at their preinjury level. The relative risk of RTS failure increases according to the magnitude of the increase in age and BMI. Elite athletes are more likely to return compared with nonelite athletes.

COMPARISON OF THE EFFICACY AND SAFETY OF RANIBIZUMAB 0.5 MG VERSUS 1.0 MG WITH PARS PLANA VITRECTOMY FOR THE TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Controlled Trial.

PURPOSE: To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS: This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS: The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION: Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.

Near-infrared-II Ag2S quantum dot probes targeting podoplanin enhance immunotherapy in oral squamous cell carcinoma.

Partial epithelial-mesenchymal transition (pEMT) plays a vital role in oral squamous cell carcinoma (OSCC) cervical lymph node metastasis and tumor immune escape as an immune barrier. However, targeted interventions for pEMT have yet to be established. In this study, we generated an αPDPN-Ag2S probe by modifying a Podoplanin(PDPN) monoclonal antibody on the surface of near infrared (NIR)-II Ag2S quantum dots (QDs) with carboxyl groups through an amide reaction. Then, we evaluated its in vivo targeting ability, therapeutic efficacy of eliminating pEMT using αPDPN-Ag2S-mediated NIR-II photoimmunotherapy (PIT) and biological safety. Here, we found that pEMT is related to CD8 + T-cell infiltration in our human OSCC tissue microarray. Compared with PdpnWT SCC7, the slower growth rate of subcutaneous graft tumors implanted with PdpnKD SCC7 was associated with a change in the tumor immune microenvironment (TIM) in an immunocompetent C3H/HeJ mouse model. In vitro, αPDPN-Ag2S plus NIR 808 nm laser irradiation induced SCC7 cell death. In vivo, NIR-II imaging results show that the αPDPN-Ag2S probe has a good active-targeting ability in a 4-nitroquinoline 1-oxide (4NQO)-induced C57 mouse OSCC model and C3H/HeJ SCC7 subcutaneous graft tumor model. Elimination of pEMT cells by NIR-II αPDPN-Ag2S probe-mediated PIT significantly reversed the local immunosuppressive tumor microenvironment and enhanced PD-1 immunotherapy efficacy. The safety profiles of αPDPN-Ag2S in BALB/c mice were also acceptable. Thus, αPDPN-Ag2S has important clinical translational value in predicting the risk of cervical lymph node metastasis. Importantly, our study proposed a new way to improve the efficacy of tumor immunotherapy.

T1 and T2 mapping for identifying malignant lymph nodes in head and neck squamous cell carcinoma.

BACKGROUND: This study seeks to assess the utility of T1 and T2 mapping in distinguishing metastatic lymph nodes from reactive lymphadenopathy in patients with head and neck squamous cell carcinoma (HNSCC), using diffusion-weighted imaging (DWI) as a comparison. METHODS: Between July 2017 and November 2019, 46 HNSCC patients underwent neck MRI inclusive of T1 and T2 mapping and DWI. Quantitative measurements derived from preoperative T1 and T2 mapping and DWI of metastatic and non-metastatic lymph nodes were compared using independent samples t-test or Mann-Whitney U test. Receiver operating characteristic curves and the DeLong test were employed to determine the most effective diagnostic methodology. RESULTS: We examined a total of 122 lymph nodes, 45 (36.9%) of which were metastatic proven by pathology. Mean T2 values for metastatic lymph nodes were significantly lower than those for benign lymph nodes (p < 0.001). Conversely, metastatic lymph nodes exhibited significantly higher apparent diffusion coefficient (ADC) and standard deviation of T1 values (T1SD) (p < 0.001). T2 generated a significantly higher area under the curve (AUC) of 0.890 (0.826-0.954) compared to T1SD (0.711 [0.613-0.809]) and ADC (0.660 [0.562-0.758]) (p = 0.007 and p < 0.001). Combining T2, T1SD, ADC, and lymph node size achieved an AUC of 0.929 (0.875-0.983), which did not significantly enhance diagnostic performance over using T2 alone (p = 0.089). CONCLUSIONS: The application of T1 and T2 mapping is feasible in differentiating metastatic from non-metastatic lymph nodes in HNSCC and can improve diagnostic efficacy compared to DWI.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration.

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.

Free-Breathing StarVIBE Sequence for the Detection of Extranodal Extension in Head and Neck Cancer: An Image Quality and Diagnostic Performance Study.

(1) Background: This study aims to evaluate the image quality of abnormal cervical lymph nodes in head and neck cancer and the diagnostic performance of detecting extranodal extension (ENE) using free-breathing StarVIBE. (2) Methods: In this retrospective analysis, 80 consecutive head and neck cancer patients underwent StarVIBE before neck dissection at an academic center. Image quality was compared with conventional VIBE available for 28 of these patients. A total of 73 suspicious metastatic lymph nodes from 40 patients were found based on morphology and enhancement pattern on StarVIBE. Sensitivity (SN), specificity (SP), and odds ratios were calculated for each MR feature from StarVIBE to predict pathologic ENE. (3) Results: StarVIBE showed significantly superior image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) for enlarged lymph nodes compared to VIBE. The MR findings of "invading adjacent planes" (SN, 0.54; SP, 1.00) and "matted nodes" (SN, 0.72; SP, 0.89) emerged as notable observations. The highest diagnostic performance was attained by combining these two features (SN, 0.93; SP, 0.89). (4) Conclusions: This study confirms that StarVIBE offers superior image quality for abnormal lymph nodes compared to VIBE, and it can accurately diagnose ENE by utilizing a composite MR criterion in head and neck cancer.

Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in OSCC is still unaccomplished. Similarly, the mechanism of how 5mC and 5hmC collectively lead to abnormal gene expression in OSCC is largely unexplored. Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized 5mC- and 5hmC-profiles at single-nucleotide resolution in paired primary OSCC samples and their normal adjacent tissues (NATs). We also analyzed the effect of 5mC- and 5hmC-modifications on differential gene expression in OSCC using multi-omics analysis. Results: An overall reduction of both 5mC and 5hmC in various genomic regions have been observed in OSCC samples. At promoter regions, a total of 6,921 differentially methylated regions and 1,024 differentially hydroxymethylated regions were identified in OSCC. Interestingly, compared to bidirectional modification with 5mC and 5hmC, unidirectional modification with 5mC and 5hmC at the promoters is associated with bigger change in the gene expression. Additionally, genes bearing unidirectional modification with 5mC and 5hmC at the promoters are enriched in signaling pathways like cell proliferation, cell differentiation, and receptor tyrosine kinase pathway that are essential for the tumorigenesis. Finally, the grouped expression signature of top 20 genes bearing promoter-unidirectional-modification with 5mC and 5hmC tends to correlate with the clinical outcome of certain subtypes of head and neck squamous cell carcinoma. Conclusion: Using parallel WGBS and oxWGBS analyses, we observed an overall reduction of 5mC- and 5hmC-modifications at various genomic regions in OSCC. Unidirectional modification with 5mC and 5hmC at the promoters is associated with enhanced changes in gene expression in OSCC tissues. Furthermore, such differentially expressed genes bearing unidirectional modifications with 5mC and 5hmC at the promoters might have clinical relevance to the outcome of OSCC.

Imaging of Angiogenesis in White Matter Hyperintensities.

Background White matter hyperintensities (WMHs) are areas of increased signal intensity on T2-weighted magnetic resonance imaging (MRI). WMH penumbra may be a potential target for early intervention in WMHs. We explored the relationship between angiogenesis and WMH penumbra in patients with WMHs. Methods and Results Twenty-one patients with confluent WMHs of Fazekas grade ≥2 were included. All the participants underwent 68Ga-NOTA-PRGD2 positron emission tomography/magnetic resonance imaging. WMH penumbra was analyzed with masks created for the WMH and 7 normal-appearing white matter layers; each layer was dilated away from the WMH by 2 mm. Angiogenesis array and ELISA were used to detect the serum levels of angiogenic factors, inflammatory factors, HIF-1 alpha, and S100B. Fourteen patients with increased 68Ga-NOTA-PRGD2 maximum standardized uptake (>0.17) were classified into group 2. Seven patients with maximum standardized uptake ≤0.17 were classified as group 1. WMH volume and serum levels of integrin αvß3, vascular endothelial growth factor receptor 22, and interleukin-1ß tended to be higher in group 2 than in group 1. In group 2, 68Ga-NOTA-PRGD2 uptake was significantly increased at the border between the WMH and normal-appearing white matter than in WMHs (P=0.004). The structure penumbra, defined by fractional anisotropy, was wider in group 2 (8 mm) than in group 1 (2 mm). The cerebral blood flow penumbra was 12 mm in both groups. Angiogenesis showed a correlation with reduced cerebral blood flow and microstructure integrity. Conclusions Our study provides evidence that angiogenesis occurs in the WMH penumbra. Further studies are warranted to verify the effect of angiogenesis on WMH growth.