Macrophages in guided bone regeneration: potential roles and future directions.

Guided bone regeneration (GBR) is one of the most widely used and thoroughly documented alveolar bone augmentation surgeries. However, implanting GBR membranes inevitably triggers an immune response, which can lead to inflammation and failure of bone augmentation. It has been shown that GBR membranes may significantly improve in vivo outcomes as potent immunomodulators, rather than solely serving as traditional barriers. Macrophages play crucial roles in immune responses and participate in the entire process of bone injury repair. The significant diversity and high plasticity of macrophages complicate our understanding of the immunomodulatory mechanisms underlying GBR. This review provides a comprehensive summary of recent findings on the potential role of macrophages in GBR for bone defects in situ. Specifically, macrophages can promote osteogenesis or fibrous tissue formation in bone defects and degradation or fibrous encapsulation of membranes. Moreover, GBR membranes can influence the recruitment and polarization of macrophages. Therefore, immunomodulating GBR membranes are primarily developed by improving macrophage recruitment and aggregation as well as regulating macrophage polarization. However, certain challenges remain to be addressed in the future. For example, developing more rational and sophisticated sequential delivery systems for macrophage activation reagents; addressing the interference of bone graft materials and dental implants; and understanding the correlations among membrane degradation, macrophage responses, and bone regeneration.

Feasibility of 2-Point Fixation by Absorbable Plates Using the Transoral Approach in Management of the Zygomatic Complex Fractures.

PURPOSE: The purpose of this study was to retrospectively evaluate the feasibility of 2-point fixation using absorbable plates by the transoral approach in the management of the zygomatic complex (ZMC) fractures. METHODS: Twenty-five patients (15 male and 10 female, age range 16 y to 55 y) with Knight and North Group Ⅲ zygomatic fractures were included in this case series. Open reduction by intraoral approach was performed on these patients, and the fractures were fixed using absorbable plates placed at the zygomaticomaxillary buttress and infraorbital rim. Postoperatively, follow-up was undertaken to evaluate the fracture healing, mouth opening, facial asymmetry, diplopia, and paresthesia. RESULTS: Postoperatively, all patients achieved uneventful healing; facial symmetry and wound healing were achieved, along with sensory recovery involving the infraorbital nerve. Complications such as sensory disturbances, infection, diplopia, malunion, and nonunion were not encountered in these patients. CONCLUSIONS: Two-point fixation using absorbable plates by transoral approach can provide sufficient stabilization for Knight and North Group III zygomatic fractures.

Renal anatomical classification systems cannot predict the occurrence of vascular complications after partial nephrectomy.

OBJECTIVES: To determine the relationship between renal tumor complexity and vascular complications after partial nephrectomy using PADUA, RENAL, and ZS scores. METHODS: Between January 2007 and December 2018, a total of 1917 patients with available cross-sectional imaging were enrolled in the study. Logistic regressions were used to identify independent predictors of vascular complications. RESULTS: Of 1917 patients, 31 (1.6%) developed vascular complications, including 10 females and 21 males. The high-complexity category was significantly associated with a decreased risk of vascular complication in PADUA (OR = 0.256; 95%CI = 0.086-0.762; P = 0.014) and ZS score (OR = 0.279; 95%CI = 0.083-0.946; P = 0.040). Laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were independent risk factors for vascular complications. Meanwhile, the incidence was significantly reduced in the recent 4 years in the high score tumor group alone in PADUA (0.2% [1/474] vs. 2.2% [3/139], P = 0.038) and ZS score (0.2% [1/469] vs. 2.7% [3/112], P = 0.024). In the first 8 years, laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were the only two independent risk factors for vascular complications. In the recent 4 years, only the high-complexity category was significantly associated with a decreased risk of vascular complication in the PADUA score (OR = 0.110; 95%CI = 0.013-0.938; P = 0.044). CONCLUSION: The renal anatomic classification system cannot predict the occurrence of vascular complications after partial nephrectomy.

A novel mini-retractor for retroperitoneal laparoscopic partial nephrectomy.

BACKGROUND: Retroperitoneal partial nephrectomy (RLPN) is the premier treatment for localized renal tumors despite narrow operation space. Many efforts have been taken to facilitate the operation of RLPN, but the optimal resolution remains debatable. OBJECTIVE: To explore the feasibility of using Mini-lap to improve workspace and surgical vision in RLPN. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective review of 51 patients who underwent RLPN with Mini-lap from January 2018 to December 2020 was conducted. SURGICAL PROCEDURE: Standard RLPN under three poles was performed in all cases. We highlighted the usage of Mini-lap (Teleflex Minilap percutaneous Surgical System) as a novel retractor in RLPN. OUTCOME AND MEASUREMENTS AND STATICAL ANALYSIS: Demographics, preoperative, intraoperative, and postoperative outcomes were assessed. RESULTS AND LIMITATIONS: All 51 cases completed RLPN with three ports successfully and no conversion to open surgery. The mean diameter of tumors was (3.53 ± 1.05) cm, in which 62.7% (32/51) were located anteriorly. The operation time and warm ischemic time (WIT) were (86.7 ± 15.9) min and (25.6 ± 5) min respectively. Minor complications (Clavien grade 1-2) occurred in 6 cases. The limitations were small sample size, retrospective design, and absence of control. CONCLUSIONS: Mini-lap could be used as a mini-retractor in RLPN, sparing extra assistant ports, expanding workspace, and optimizing vision. PATIENT SUMMARY: With highlights of larger workspace and less instrument interference, mini-lap could be applied in retroperitoneal laparoscopic partial nephrectomy.

Glucopeptide Superstructure Hydrogel Promotes Surgical Wound Healing Following Neoadjuvant Radiotherapy by Producing NO and Anticellular Senescence.

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.

Development and validation of a clinical-radiomics model for prediction of prostate cancer: a multicenter study.

PURPOSE: To develop an early diagnosis model of prostate cancer based on clinical-radiomics to improve the accuracy of imaging diagnosis of prostate cancer. METHODS: The multicenter study enrolled a total of 449 patients with prostate cancer from December 2017 to January 2022. We retrospectively collected information from 342 patients who underwent prostate biopsy at Minhang Hospital. We extracted T2WI images through 3D-Slice, and used mask tools to mark the prostate area manually. The radiomics features were extracted by Python using the "Pyradiomics" module. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for data dimensionality reduction and feature selection, and the radiomics score was calculated according to the correlation coefficients. Multivariate logistic regression analysis was used to develop predictive models. We incorporated the radiomics score, PI-RADS, and clinical features, and this was presented as a nomogram. The model was validated using a cohort of 107 patients from the Xuhui Hospital. RESULTS: In total, 110 effective radiomics features were extracted. Finally, 9 features were significantly associated with the diagnosis of prostate cancer, from which we calculated the radiomics score. The predictors contained in the individualized prediction nomogram included age, fPSA/tPSA, PI-RADS, and radiomics score. The clinical-radiomics model showed good discrimination in the validation cohort (C-index = 0.88). CONCLUSION: This study presents a clinical-radiomics model that incorporates age, fPSA/PSA, PI-RADS, and radiomics score, which can be conveniently used to facilitate individualized prediction of prostate cancer before prostate biopsy.

Preparation of an injectable and photocurable carboxymethyl cellulose/hydroxyapatite composite and its application in cranial regeneration.

Limited bone regeneration, uncontrollable degradation rate, mismatched defect zone and poor operability have plagued the reconstruction of irregular bone defect by tissue-engineered materials. A combination of biomimetic scaffolds with hydroxyapatite has gained great popularity in promoting bone regeneration. Therefore, we designed an injectable, photocurable and in-situ curing hydrogel by methacrylic anhydride -modified carboxymethyl cellulose (CMC-MA) loading with spherical hydroxyapatite (HA) to highly simulate the natural bony matrix and match any shape of damaged tissue. The prepared carboxymethyl cellulose-methacrylate/ hydroxyapatite(CMC-MA/HA) composite presented good rheological behavior, swelling ratio and mechanical property under light illumination. Meanwhile, this composite hydrogel promoted effectively proliferation, supported adhesion and upregulated the osteogenic-related genes expression of MC3T3-E1 cells in vitro, as well as the activity of the osteogenic critical protein, Integrin α1, ß1, Myosin 9, Myosin 10, BMP-2 and Smad 1 in Integrin/BMP-2 signal pathway. Together, the composite hydrogels realized promotion of bone regeneration, deformity improvement, and the enhanced new bone strength in skull defect. It also displayed a good histocompatibility and stability of subcutaneous implantation in vivo. Overall, this study laid the groundwork for future research into developing a novel biomaterial and a minimally invasive therapeutic strategies for reconstructing bone defects and contour deficiencies.

Restoring long-lasting midface volume in the Asian face with a hyaluronic acid filler: A randomized controlled multicenter study.

BACKGROUND: Hyaluronic acid (HA) filler treatment is a minimally-invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane® Volyme) is a flexible HA filler suited to contouring and volumizing the midface. METHODS: This randomized, evaluator-blinded, no-treatment controlled study evaluated effectiveness and safety of HAVOL for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HAVOL and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator-assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as ≥1-point improvement from baseline on both sides of the face. RESULTS: HAVOL was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%-79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (≥96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in ≥80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL . Additionally, HAVOL was well tolerated, with no unanticipated related adverse events. CONCLUSIONS: This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.

Metabolomic machine learning predictor for diagnosis and prognosis of gastric cancer.

Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC.

Metabolic heterogeneity in clear cell renal cell carcinoma revealed by single-cell RNA sequencing and spatial transcriptomics.

BACKGROUND: Clear cell renal cell carcinoma is a prototypical tumor characterized by metabolic reprogramming, which extends beyond tumor cells to encompass diverse cell types within the tumor microenvironment. Nonetheless, current research on metabolic reprogramming in renal cell carcinoma mostly focuses on either tumor cells alone or conducts analyses of all cells within the tumor microenvironment as a mixture, thereby failing to precisely identify metabolic changes in different cell types within the tumor microenvironment. METHODS: Gathering 9 major single-cell RNA sequencing databases of clear cell renal cell carcinoma, encompassing 195 samples. Spatial transcriptomics data were selected to conduct metabolic activity analysis with spatial localization. Developing scMet program to convert RNA-seq data into scRNA-seq data for downstream analysis. RESULTS: Diverse cellular entities within the tumor microenvironment exhibit distinct infiltration preferences across varying histological grades and tissue origins. Higher-grade tumors manifest pronounced immunosuppressive traits. The identification of tumor cells in the RNA splicing state reveals an association between the enrichment of this particular cellular population and an unfavorable prognostic outcome. The energy metabolism of CD8+ T cells is pivotal not only for their cytotoxic effector functions but also as a marker of impending cellular exhaustion. Sphingolipid metabolism evinces a correlation with diverse macrophage-specific traits, particularly M2 polarization. The tumor epicenter is characterized by heightened metabolic activity, prominently marked by elevated tricarboxylic acid cycle and glycolysis while the pericapsular milieu showcases a conspicuous enrichment of attributes associated with vasculogenesis, inflammatory responses, and epithelial-mesenchymal transition. The scMet facilitates the transformation of RNA sequencing datasets sourced from TCGA into scRNA sequencing data, maintaining a substantial degree of correlation. CONCLUSIONS: The tumor microenvironment of clear cell renal cell carcinoma demonstrates significant metabolic heterogeneity across various cell types and spatial dimensions. scMet exhibits a notable capability to transform RNA sequencing data into scRNA sequencing data with a high degree of correlation.

Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma.

Background: N6-Methyladenosine (m6A) RNA modification is the most prevalent internal modification pattern in eukaryotic mRNAs and plays critical roles in diverse physiological and pathological processes. However, the expression of m6A regulator YTHDF2, its prognostic value, its biological function, its correlation with tumor microenvironment (TME) immune infiltrates, and related regulatory networks in hepatocellular carcinoma (HCC) remain determined. Methods: TCGA, GTEx, and GEO databases were used to investigate the expression profile of YTHDF2 in HCC. We performed differentially expressed genes (DEGs) analysis and constructed a PPI network to explore the biological processes of YTHDF2 in HCC. Kaplan-Meier curves and Cox regression analysis were used to assess the prognostic value of YTHDF2 and then a clinical prognostic nomogram was constructed. Additionally, ssGSEA was performed to assess the correlation between YTHDF2 and immune infiltration levels. The TISIDB database was applied to explore the expression of YTHDF2 in immune and molecular subtypes of HCC. GSEA identifies the YTHDF2-related signaling pathways. Finally, we utilized miRNet and starBase database to construct regulatory networks for HCC based on lncRNA-miRNA and miRNA-YTHDF2 interactions. Results: YTHDF2 was significantly upregulated in HCC tumor tissues compared with the adjacent normal tissues. HCC patients in the high YTHDF2 expression group had poorer survival. Multivariate Cox analysis suggested that YTHDF2 may be a new independent prognostic indicator for HCC patients, with the prognostic nomogram exhibiting satisfactory results. YTHDF2 expression was significantly correlated with TME immune cell-infiltrating characteristics. Strong correlations were also shown in immune subtypes, molecular subtypes and immune checkpoints. Further analysis revealed that the combination of YTHDF2 expression and immune cell score was considerably associated with survival outcome in HCC patients. GESA analysis demonstrated that high YTHDF2 expression is associated with multiple biological processes and oncogenic pathways. Moreover, 14 possible regulatory networks were constructed, which are associated with HCC progression. Conclusion: Our findings revealed that YTHDF2 may serve as a promising prognostic biomarker for HCC and may regulate the tumor immune microenvironment to provide effective therapeutic strategies.

The Correlation Between Low-Dose Radiotherapy Area of the Mediastinum and CD8+T Cells and the Efficacy of Radiotherapy for Non-Small Cell Lung Cancer.

Background: Radiation therapy (RT) can cause changes in peripheral blood immune cells. The relationship between the efficacy of radiation therapy for non-small cell lung cancer (NSCLC) and immune cell changes and the study of how mediastinal radiation dose parameters affect immune cell changes is still unclear. This study aims to analyze the relationship between immune cell changes induced by radiotherapy and the efficacy of NSCLC radiotherapy, as well as the relationship between radiotherapy dose parameters and immune cell changes. Materials and Methods: We retrospectively analyzed the data of NSCLC patients receiving mediastinal radiation therapy from 2020 to 2022. Collect lymphocytes and circulating immune cells within one week before and after radiotherapy and collect the dose-volume parameters of the whole mediastinum in the patient's RT planning system. Analyze the changes in lymphocytes and radiotherapy effects after radiotherapy, and explore the relationship between radiotherapy dose parameters and immune cell changes. Results: A total of 72 patients were enrolled. Compared with before radiotherapy, the proportion of CD3+T cells, CD8+T cells, and CD8/Treg in peripheral blood significantly increased after radiotherapy (P<0.05). The increase in CD8+T cells and CD8/Treg after radiotherapy was correlated with Objective response rate (ORR) (P<0.05). Based on binary logistic univariate and multivariate regression analysis, an increase in CD8+T cells after radiotherapy is an independent predictor of objective tumor response after radiotherapy (OR=12.71, 95% CI=3.64-44.64, P=0.01), and Volume of 200 cGy irradiation (V2) is an independent positive predictor of an increase in CD8+T lymphocyte ratio after radiotherapy (high group, OR=3.40, 95% CI=1.13-10.36, P=0.03). Conclusion: The increase in CD8+T cells after radiotherapy can positively predict the short-term efficacy of radiotherapy. Mediastinal low-dose radiation therapy can increase CD8+T cells, thereby improving the short-term efficacy of radiotherapy. These potentially related mechanisms are worth further verification and exploration.

Magnetic resonance imaging-based Classifications for Symptom of Adenomyosis.

OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810～0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018～12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131～2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.

[Meta-analysis of the role of fibular fixation in tibiofibular fractures].

OBJECTIVE: To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis. METHODS: The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups. RESULTS: A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison. CONCLUSION: Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

Novel Applications of Concentrated Growth Factors in Facial Rejuvenation and Plastic Surgery.

Concentrated growth factor (CGF), which is a third-generation platelet concentrate product, exhibits good potential for repair and regeneration of soft and hard tissues, and has gradually attracted attention in the field of cosmetic plastic surgery. The purpose of this review is to summarize the application and research of CGF in the field of facial rejuvenation and plastic surgery. A comprehensive review of the literature about the applications of CGF in facial rejuvenation and plastic surgery was conducted in PubMed, Ovid MEDLINE, and Web of Science. According to the inclusion and exclusion criteria, a total of 22 articles were included in this review. In recent years, CGF has been applied in many aspects in the field of facial rejuvenation and plastic surgery, including skin photoaging, repairment of soft-tissue defects, rhinoplasty, hair loss, autologous fat transplantation, and scars. In addition, no significant adverse reactions have been reported so far. CGF is rich in high-concentration growth factors, which has great potential and application prospects in facial rejuvenation and plastic surgery. However, the applications of CGF still have some problems, such as the mechanism, time of decomposition, and long-term efficacy and safety, which are needed to be resolved in future.

Prognostic factors in patients with first diagnosis of hepatocellular carcinoma presenting with pulmonary metastasis and construction of a clinical prediction model.

In some areas where routine screening for hepatocellular carcinoma is not available, 30% of HCC patients present with extra-hepatic metastases at the first visit. The most common metastatic organ among them is the lung. The factors influencing the prognosis of this particular subgroup are questions that deserve to be explored. We screened the patients using the SEER database. After exclusion, 989 patients with first diagnosis of hepatocellular carcinoma with lung metastasis were included in this study. Based on Cox regression, the random forest and stepwise methods were applied to screen out risk factors that independently affect the overall survival or disease-specific survival of HCCPM patients and construct prognostic models, respectively. The data were set as training and validation sets, and the reliability and accuracy of the models were verified in different data sets using time-dependent ROC curves with decision curves. We found that the clinical factors affecting the overall survival of HCCPM patients were age grouping, chemotherapy, AJCC T-stage, pathologic grading, and surgery. The clinical factors affecting disease-specific survival in patients with hepatocellular carcinoma pulmonary metastases were age grouping, marital status, AJCC T-stage, pathological grading, and surgery. For the OS model for the training cohort, the 6-month AUC = 0.695, 12-month AUC = 0.692, and 18-month AUC = 0.72. While the DSS model for the training cohort resulted in a 6-month AUC = 0.671, 12-month AUC = 0.671, and 18-month AUC = 0.635. In this study, we developed and validated a model of prognostic risk factors for patients with lung metastases from hepatocellular carcinoma. Our prognostic model can prospectively predict the prognostic status of patients and improve clinical efficiency.

Magnetic Resonance Imaging-Based Classification Systems for Informing Better Outcomes of Adenomyosis After Ultrasound-Guided High-Intensity Focused Ultrasound Ablating Surgery.

BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes. STUDY TYPE: Retrospective. POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy). FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences. ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant. RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Colorectal liver metastases: Correlations of contrast-enhanced ultrasound features with tumor clinicopathological factors and clinical outcomes following conversion therapy.

OBJECTIVE: To explore the prognostic impact of contrast-enhanced ultrasound (CEUS) features for initially unresectable colorectal liver metastases (CLMs) in a clinical setting of conversion therapy. METHODS: Between March 2015 and November 2020, consecutive patients with CLMs who received conversion treatment were prospectively enrolled. All participants underwent liver CEUS at baseline. The primary endpoint was conversion resection rate (R0 and overall resection). Secondary endpoints were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS: 104 participants who completed conversion treatment were included. CEUS enhancement pattern was correlated with index lesion (size and echogenicity), primary (site, differentiation, perineural invasion, and RAS genotype) and serum (CA19-9 level) characteristics (P = <0.001-0.016). CEUS enhancement pattern was significantly associated with R0 resection rate, ORR, PFS, and OS (P = 0.001-0.049), whereas enhancement degree was associated with PFS and OS (P = 0.043 and 0.045). Multivariate analysis showed that heterogeneous enhancement independently predicted R0 and overall resection (P = 0.028 and 0.024) while rim-like enhancement independently predicted ORR and OS (P = 0.009 and 0.026). CONCLUSION: CEUS enhancement pattern was significantly associated with tumor characteristics and clinical outcomes following conversion therapy, and thus might be of prognosis impact for initially unresectable CLMs.

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults.

Purpose: We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort. Methods: This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (µm) were measured on the OCT tool. Results: Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults. Conclusion: Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.

A novel CPT1A covalent inhibitor modulates fatty acid oxidation and CPT1A-VDAC1 axis with therapeutic potential for colorectal cancer.

Colorectal cancer (CRC) is a common and deadly disease of the digestive system, but its targeted therapy is hampered by the lack of reliable and specific biomarkers. Hence, discovering new therapeutic targets and agents for CRC is an urgent and challenging task. Here we report that carnitine palmitoyltransferase 1A (CPT1A), a mitochondrial enzyme that catalyzes fatty acid oxidation (FAO), is a potential target for CRC treatment. We show that CPT1A is overexpressed in CRC cells and that its inhibition by a secolignan-type compound, 2,6-dihydroxypeperomin B (DHP-B), isolated from the plant Peperomia dindygulensis, suppresses tumor cell growth and induces apoptosis. We demonstrate that DHP-B covalently binds to Cys96 of CPT1A, blocks FAO, and disrupts the mitochondrial CPT1A-VDAC1 interaction, leading to increased mitochondrial permeability and reduced oxygen consumption and energy metabolism in CRC cells. We also reveal that CPT1A expression correlates with the survival of tumor-bearing animals and that DHP-B exhibits anti-CRC activity in vitro and in vivo. Our study uncovers the molecular mechanism of DHP-B as a novel CPT1A inhibitor and provides a rationale for its preclinical development as well as a new strategy for CRC targeted therapy.