Prolactin receptor potentiates chemotherapy through miRNAs-induced G6PD/TKT inhibition in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a notoriously dismal prognosis. As a competitive inhibitor of DNA synthesis, gemcitabine is the cornerstone drug for treating PDAC at all stages. The therapeutic effect of gemcitabine, however, is often hindered by drug resistance, and the underlying mechanisms remain largely unknown. It is unclear whether their response to chemotherapeutics is regulated by endocrine regulators, despite the association between PDAC risk and endocrine deregulation. Here, we show that prolactin receptor (PRLR) synergizes with gemcitabine in both in vitro and in vivo treatment of PDAC. Interestingly, PRLR promotes the expression of miR-4763-3p and miR-3663-5p, two novel miRNAs whose functions are unknown. Furthermore, the analysis of transcriptome sequencing data of tumors from lactating mouse models enriches the PPP pathway, a multifunctional metabolic pathway. In addition to providing energy, the PPP pathway mainly provides a variety of raw materials for anabolism. We demonstrate that two key enzymes of the pentose phosphate pathway (PPP), G6PD and TKT, are directly targeted by miR-4763-3p and miR-3663-5p. Notably, miR-4763-3p and miR-3663-5p diminish the nucleotide synthesis of the PPP pathway, thereby increasing gemcitabine sensitivity. As a result, PRLR harnesses these two miRNAs to suppress PPP and nucleotide synthesis, subsequently elevating the gemcitabine sensitivity of PDAC cells. Also, PDAC tissues and tumors from LSL-KrasG12D/+, LSL-Trp53R172H/+, and PDX1-cre (KPC) mice exhibit downregulation of PRLR. Bisulfite sequencing of PDAC tissues revealed that PRLR downregulation is due to epigenetic methylation. In this study, we show for the first time that the endocrine receptor PRLR improves the effects of gemcitabine by boosting two new miRNAs that block the PPP pathway and nucleotide synthesis by inhibiting two essential enzymes concurrently. The PRLR-miRNAs-PPP axis may serve as a possible therapeutic target to supplement chemotherapy advantages in PDAC.

Prognostic prediction model of colorectal cancer based on preoperative serum tumor markers.

BACKGROUND: Preoperative serum tumor markers not only play a role in the auxiliary diagnosis and postoperative monitoring in colorectal cancer (CRC), but also have been found to have potential prognostic value. AIM: To analyze whether preoperative serum tumor markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), affect the prognosis of CRC. METHODS: This was a retrospective study conducted in a single center. Patients with nonmetastatic CRC who underwent initial surgery between January 2011 and January 2020 were enrolled and divided into development site and validation site groups at a ratio of 7:3. The independent prognostic factors were screened by Cox regression analysis, and finally, a prognostic nomogram model was established. The newly developed model was tested by internal validation. RESULTS: Eventually, 3526 postoperative patients with nonmetastatic CRC were included in the study. There were 2473 patients at the development site and 1056 patients at the validation site. Age (P < 0.01, HR = 1.042, 95%CI = 1.033-1.051), tumor node metastasis (TNM) classification (P < 0.01, HR = 1.938, 95%CI = 1.665-2.255), preoperative CEA (P = 0.001, HR = 1.393, 95%CI = 1.137-1.707) and CA19-9 (P < 0.01, HR = 1.948, 95%CI = 1.614-2.438) levels were considered independent prognostic factors for patients with nonmetastatic CRC and were used as variables in the nomogram model. The areas under the curve of the development and validation sites were 0.655 and 0.658, respectively. The calibration plot also showed the significant performance of the newly established nomogram. CONCLUSION: We successfully constructed a nomogram model based on age, TNM stage, preoperative CEA, and CA19-9 levels to evaluate the overall survival of patients with nonmetastatic CRC.

Predictors of complications after prophylactic ileostomy reversal for rectal cancer: A retrospective study.

BACKGROUND: Previous studies have analyzed the risk factors for complications after ileostomy reversal for rectal cancer (RC), but there were significant differences in the reported risk factors for complications after stoma reversal. No studies have analyzed the risk factors for stoma-related complications and overall postoperative complications separately. AIM: To analyze the risk factors for overall complications and stoma-related complications after ileostomy reversal for patients with RC. METHODS: This was a retrospective study of 439 patients who underwent ileostomy reversal at a clinical center and were followed up between September 2012 and September 2022. Continuous variables are expressed as the mean ± SD and were analyzed with independent-sample t tests, while frequency variables are expressed as n (%), and the χ2 test or Fisher's exact test was used. Univariate and multivariate logistic regression analyses were used to identify predictors of overall complications and stoma-related complications. RESULTS: The overall complication rate after ileostomy reversal was 11.4%. Patients with lower preoperative albumin concentration (P < 0.01), greater blood loss (P = 0.017), and longer operative times (P < 0.01) were more likely to experience postoperative complications. The incidence of stoma-related complications was 6.4%. Analysis of the study showed that a higher body mass index (BMI) (P < 0.01), preoperative comorbid hypertension (P = 0.049), time from primary surgery to ileostomy reversal (P < 0.01) and longer operation time (P = 0.010) were more likely to result in stoma-related complications postoperatively. Multivariate logistic regression analysis revealed that a lower preoperative albumin level (P < 0.01, OR = 0.888, 95%CI: 0.828-0.958) was an independent risk factor for overall complications. Moreover, multivariate analysis revealed that BMI (P < 0.01, OR = 1.176, 95%CI: 1.041-1.330) and time from primary surgery to ileostomy reversal (P < 0.01, OR = 1.140, 95%CI: 1.038-1.252) were independent risk factors for stoma-related complications after stoma reversal. CONCLUSION: The preoperative albumin level was a predictor of overall complications. Preoperative BMI and the time from primary surgery to ileostomy reversal were predictors of stoma-related complications.

Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging of pediatric neuroblastoma: a multi-omics parameters method to predict MYCN copy number category.

Background: The MYCN copy number category is closely related to the prognosis of neuroblastoma (NB). Therefore, this study aimed to assess the predictive ability of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomic features for MYCN copy number in NB. Methods: A retrospective analysis was performed on 104 pediatric patients with NB that had been confirmed by pathology. To develop the Bio-omics model (B-model), which incorporated clinical and biological aspects, PET/CT radiographic features, PET quantitative parameters, and significant features with multivariable stepwise logistic regression were preserved. Important radiomics features were identified through least absolute shrinkage and selection operator (LASSO) and univariable analysis. On the basis of radiomics features obtained from PET and CT scans, the radiomics model (R-model) was developed. The significant bio-omics and radiomics features were combined to establish a Multi-omics model (M-model). The above 3 models were established to differentiate MYCN wild from MYCN gain and MYCN amplification (MNA). The calibration curve and receiver operating characteristic (ROC) curve analyses were performed to verify the prediction performance. Post hoc analysis was conducted to compare whether the constructed M-model can distinguish MYCN gain from MNA. Results: The M-model showed excellent predictive performance in differentiating MYCN wild from MYCN gain and MNA, which was better than that of the B-model and R-model [area under the curve (AUC) 0.83, 95% confidence interval (CI): 0.74-0.92 vs. 0.81, 95% CI: 0.72-0.90 and 0.79, 95% CI: 0.69-0.89]. The calibration curve showed that the M-model had the highest reliability. Post hoc analysis revealed the great potential of the M-model in differentiating MYCN gain from MNA (AUC 0.95, 95% CI: 0.89-1). Conclusions: The M-model model based on bio-omics and radiomics features is an effective tool to distinguish MYCN copy number category in pediatric patients with NB.

Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

BACKGROUND: This study aimed to evaluate the safety of enhanced recovery after surgery (ERAS) in elderly patients with gastric cancer (GC). AIM: To evaluate the safety of ERAS in elderly patients with GC. METHODS: The PubMed, EMBASE, and Cochrane Library databases were used to search for eligible studies from inception to April 1, 2023. The mean difference (MD), odds ratio (OR) and 95% confidence interval (95%CI) were pooled for analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores. We used Stata (V.16.0) software for data analysis. RESULTS: This study consists of six studies involving 878 elderly patients. By analyzing the clinical outcomes, we found that the ERAS group had shorter postoperative hospital stays (MD = -0.51, I2 = 0.00%, 95%CI = -0.72 to -0.30, P = 0.00); earlier times to first flatus (defecation; MD = -0.30, I² = 0.00%, 95%CI = -0.55 to -0.06, P = 0.02); less intestinal obstruction (OR = 3.24, I2 = 0.00%, 95%CI = 1.07 to 9.78, P = 0.04); less nausea and vomiting (OR = 4.07, I2 = 0.00%, 95%CI = 1.29 to 12.84, P = 0.02); and less gastric retention (OR = 5.69, I2 = 2.46%, 95%CI = 2.00 to 16.20, P = 0.00). Our results showed that the conventional group had a greater mortality rate than the ERAS group (OR = 0.24, I2 = 0.00%, 95%CI = 0.07 to 0.84, P = 0.03). However, there was no statistically significant difference in major complications between the ERAS group and the conventional group (OR = 0.67, I2 = 0.00%, 95%CI = 0.38 to 1.18, P = 0.16). CONCLUSION: Compared to those with conventional recovery, elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

Early postoperative complications after transverse colostomy closure, a retrospective study.

BACKGROUND: Ostomy is a common surgery usually performed to protect patients from clinical symptoms caused by distal anastomotic leakage after colorectal cancer (CRC) surgery and perforation or to relieve intestinal obstruction. AIM: To analyze the complications after transverse colostomy closure. METHODS: Patients who underwent transverse colostomy closure from Jan 2015 to Jan 2022 were retrospectively enrolled in a single clinical center. The differences between the complication group and the no complication group were compared. Logistic regression analyses were conducted to find independent factors for overall complications or incision infection. RESULTS: A total of 102 patients who underwent transverse colostomy closure were enrolled in the current study. Seventy (68.6%) patients underwent transverse colostomy because of CRC related causes. Postoperative complications occurred in 30 (29.4%) patients and the most frequent complication occurring after transverse colostomy closure was incision infection (46.7%). The complication group had longer hospital stays (P < 0.01). However, no potential risk factors were identified for overall complications and incision infection. CONCLUSION: The most frequent complication occurring after transverse colostomy closure surgery in our center was incision infection. The operation time, interval from transverse colostomy to reversal, and method of anastomosis might have no impact on the postoperative complications. Surgeons should pay more attention to aseptic techniques.

Progression of Notch signaling regulation of B cells under radiation exposure.

With the continuous development of nuclear technology, the radiation exposure caused by radiation therapy is a serious health hazard. It is of great significance to further develop effective radiation countermeasures. B cells easily succumb to irradiation exposure along with immunosuppressive response. The approach to ameliorate radiation-induced B cell damage is rarely studied, implying that the underlying mechanisms of B cell damage after exposure are eager to be revealed. Recent studies suggest that Notch signaling plays an important role in B cell-mediated immune response. Notch signaling is a critical regulator for B cells to maintain immune function. Although accumulating studies reported that Notch signaling contributes to the functionality of hematopoietic stem cells and T cells, its role in B cells is scarcely appreciated. Presently, we discussed the regulation of Notch signaling on B cells under radiation exposure to provide a scientific basis to prevent radiation-induced B cell damage.

Multifunctional nanocomposites mediated novel hydrogel for diabetic wound repair.

The regeneration and repair of diabetic wounds, especially those including bacterial infection, have always been difficult and challenging using current treatment. Herein, an effective strategy is reported for constructing glucose-responsive functional hydrogels using nanocomposites as nodes. In fact, tannic acid (TA)-modified ceria nanocomposites (CNPs) and a zinc metal-organic framework (ZIF-8) were employed as nodes. Subsequent crosslinking with 3-acrylamidophenylboronic acid achieved functional nanocomposite-hydrogels (TA@CN gel, TA@ZMG gel) by radical-mediated polymerization. Compared with a simple physically mixed hydrogel system, the mechanical properties of TA@CN gel and TA@ZMG gel are significantly enhanced due to the intervention of the nanocomposite nodes. In addition, this kind of nanocomposite hydrogel can realize the programmed loading of drugs and release of drugs in response to glucose/PH, to coordinate and promote its application in the regeneration and repair of diabetic wounds and infected diabetic wounds. Specifically, TA@CN gel can remove reactive oxygen species and generate oxygen through its various enzymatic activities. At the same time, it can effectively promote neovascularization, thus promoting the regeneration and repair of diabetic wounds. Furthermore, glucose oxidase-loaded TA@ZMG gel exhibits glucose response and pH-regulating functions, triggering programmed metformin (Met) release by degrading the metal-organic framework (MOF) backbone. It also exhibited additional synergistic effects of antibacterial activity, hair regeneration and systemic blood glucose regulation, which make it suitable for the repair of more complex infected diabetic wounds. Overall, this novel nanocomposite-mediated hydrogel holds great potential as a biomaterial for the healing of chronic diabetic wounds, opening up new avenues for further biomedical applications.

Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma.

Endocrine receptors play an essential role in tumor metabolic reprogramming and represent a promising therapeutic avenue in pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by a nutrient-deprived microenvironment. To meet their ascendant energy demands, cancer cells can internalize extracellular proteins via macropinocytosis. However, the roles of endocrine receptors in macropinocytosis are not clear. In this study, we found that progesterone receptor (PGR), a steroid-responsive nuclear receptor, is highly expressed in PDAC tissues obtained from both patients and transgenic LSL-KrasG12D/+; LSL-Trp53R172H/+; PDX1-cre (KPC) mice. Moreover, PGR knockdown restrained PDAC cell survival and tumor growth both in vitro and in vivo. Genetic and pharmacological PGR inhibition resulted in a marked attenuation of macropinocytosis in PDAC cells and subcutaneous tumor models, indicating the involvement of this receptor in macropinocytosis regulation. Mechanistically, PGR upregulated CDC42, a critical regulator in macropinocytosis, through PGR-mediated transcriptional activation. These data deepen the understanding of how the endocrine system influences tumor progression via a non-classical pathway and provide a novel therapeutic option for patients with PDAC.

Construction and screening of spin-crossover-sponge materials based on iron(II)-triazole coordination polymers.

Iron(II)-triazole coordination polymers have attracted considerable interest for their synthetic versatility, which allows tuning their spin-crossover (SCO) properties. Embedding SCO solid particles in sponge matrices is a simple, powerful, and generic approach to construct processable SCO materials. Here, we have studied a series of magnetic frameworks based on partial ligand substitution by using different chemical mixtures of two organic ligands, yielding four isostructural coordination polymers. The integration of the hygroscopic SCO material has endowed the composite sponge with the ability to capture moisture under ambient conditions. In particular, not only does a spin-crossover transition during absorption occur, but also a color variation has been achieved by varying humidity. The consequences of cooperativity and the exposed surface of the composite sponge on the spin transition were evaluated and the most promising materials among them were screened. This work provides guiding significance for the fabrication and practical application of spin-crossover-sponge materials.

Effect of intraoperative blood loss on postoperative complications and prognosis of patients with colorectal cancer: A meta­analysis.

The purpose of the present study was to evaluate whether the amount of intraoperative blood loss (IBL) affects the complications and prognosis of patients with colorectal cancer (CRC). The PubMed, EMBASE and the Cochrane Library databases were used to search for eligible studies from inception to November 30, 2020. Hazard ratios (HRs) and 95% confidence intervals (Cls) were pooled up. The overall survival (OS) and disease-free survival (DFS) were compared between the larger IBL group and the smaller IBL group. The present study was performed with RevMan 5.3 (The Cochrane Collaboration). A total of seven studies involving 1,540 patients with CRC were included in the present study. The smaller IBL group had a higher rate of OS (HR=1.45, 95% CI=1.17 to 1.8, P=0.0007) and a higher rate of DFS (HR=1.76, 95% CI=1.40 to 2.21, P<0.00001). Furthermore, the larger IBL group had a higher rate of postoperative complications than the smaller IBL group (odds ratio=2.06, 95% CI=1.72 to 2.15, P<0.00001). In conclusion, a smaller IBL was associated with better OS and DFS, and a lower risk of postoperative complications compared with a larger IBL in patients with CRC, suggesting that surgeons should pay more attention during perioperative management and surgical operation to reduce IBL.

Value function assessment to different RL algorithms for heparin treatment policy of patients with sepsis in ICU.

Heparin is a critical aspect of managing sepsis after abdominal surgery, which can improve microcirculation, protect organ function, and reduce mortality. However, there is no clinical evidence to support decision-making for heparin dosage. This paper proposes a model called SOFA-MDP, which utilizes SOFA scores as states of MDP, to investigate clinic policies. Different algorithms provide different value functions, making it challenging to determine which value function is more reliable. Due to ethical restrictions, we cannot test all policies on patients. To address this issue, we proposed two value function assessment methods: action similarity rate and relative gain. We experimented with heparin treatment policies for sepsis patients after abdominal surgery using MIMIC-IV. In the experiments, TD(0) shows the most reliable performance. Using the action similarity rate and relative gain to assess AI policy from TD(0), the agreement rates between AI policy and "good" physician's actual treatment are 64.6% and 73.2%, while the agreement rates between AI policy and "bad" physician's actual treatment are 44.1% and 35.8%, the gaps are 20.5% and 37.4%, respectively. External validation using action similarity rate and relative gain based on eICU resulted in agreement rates of 61.5% and 69.1% with the "good" physician's treatment, and 45.2% and 38.3% with the "bad" physician's treatment, with gaps of 16.3% and 30.8%, respectively. In conclusion, the model provides instructive support for clinical decisions, and the evaluation methods accurately distinguish reliable and unreasonable outcomes.

A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation.

The Hippo pathway has important roles in organ development, tissue homeostasis and tumour growth. Its downstream effector TAZ is a transcriptional coactivator that promotes target gene expression through the formation of biomolecular condensates. However, the mechanisms that regulate the biophysical properties of TAZ condensates to enable Hippo signalling are not well understood. Here using chemical crosslinking combined with an unbiased proteomics approach, we show that FUS associates with TAZ condensates and exerts a chaperone-like effect to maintain their proper liquidity and robust transcriptional activity. Mechanistically, the low complexity sequence domain of FUS targets the coiled-coil domain of TAZ in a phosphorylation-regulated manner, which ensures the liquidity and dynamicity of TAZ condensates. In cells lacking FUS, TAZ condensates transition into gel-like or solid-like assembles with immobilized TAZ, which leads to reduced expression of target genes and inhibition of pro-tumorigenic activity. Thus, our findings identify a chaperone-like function of FUS in Hippo regulation and demonstrate that appropriate biophysical properties of transcriptional condensates are essential for gene activation.

Remission of Nonalcoholic Fatty Liver Disease After Radical Surgery in Patients with Colorectal Cancer: A Single-Center Retrospective Study.

Purpose: The purpose of this study was to investigate the relationship between remission of nonalcoholic fatty liver disease (NAFLD) and radical surgery for colorectal cancer (CRC) patients. Methods: From January 2014 to December 2021, data of patients with concurrent CRC and NAFLD who underwent radical surgery in a single-center hospital were retrospectively collected. NAFLD was defined as a mean computed tomography (CT) liver attenuation value of <40 Hounsfield units (HUs). Comparison of preoperative and 1-year postoperative CT images was performed to evaluate the change of NAFLD. Multivariate logistic regression analysis was performed to identify independent predictive factors for NAFLD remission. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS) between the remission group and no remission group. Results: In this study, a total of 55 eligible patients were included. The remission group had 33 (60.0%) patients and the no remission group had 22 (40.0%) patients. The mean preoperative weight was 66.1 ± 9.9 kg. The mean preoperative body mass index (BMI) was 25.4 ± 2.5 kg/m2. We found that the average weight was significantly decreased (P < 0.01), average BMI was significantly decreased (P < 0.01), and HU score was significantly increased (P < 0.01). By comparing baseline characteristics between the remission group and no remission group, we found that the remission group exhibited larger tumor sizes (P = 0.036) than the no remission group. In the multivariate logistic regression analysis, we found that weight change was a predictor for NAFLD (odds ratio = 0.764, 95% confidence interval = 0.618-0.944, P = 0.013). We did not find any statistically significant differences in OS (P = 0.182) or DFS (P = 0.248) between the remission group and no remission group. Conclusions: The NAFLD remission rate reached 60.0% for CRC patients 1 year after radical surgery. In addition, we found that weight change was a predictor of NAFLD remission.

Automated, fast, robust brain extraction on contrast-enhanced T1-weighted MRI in presence of brain tumors: an optimized model based on multi-center datasets.

OBJECTIVES: Existing brain extraction models should be further optimized to provide more information for oncological analysis. We aimed to develop an nnU-Net-based deep learning model for automated brain extraction on contrast-enhanced T1-weighted (T1CE) images in presence of brain tumors. METHODS: This is a multi-center, retrospective study involving 920 patients. A total of 720 cases with four types of intracranial tumors from private institutions were collected and set as the training group and the internal test group. Mann-Whitney U test (U test) was used to investigate if the model performance was associated with pathological types and tumor characteristics. Then, the generalization of model was independently tested on public datasets consisting of 100 glioma and 100 vestibular schwannoma cases. RESULTS: In the internal test, the model achieved promising performance with median Dice similarity coefficient (DSC) of 0.989 (interquartile range (IQR), 0.988-0.991), and Hausdorff distance (HD) of 6.403 mm (IQR, 5.099-8.426 mm). U test suggested a slightly descending performance in meningioma and vestibular schwannoma group. The results of U test also suggested that there was a significant difference in peritumoral edema group, with median DSC of 0.990 (IQR, 0.989-0.991, p = 0.002), and median HD of 5.916 mm (IQR, 5.000-8.000 mm, p = 0.049). In the external test, our model also showed to be robust performance, with median DSC of 0.991 (IQR, 0.983-0.998) and HD of 8.972 mm (IQR, 6.164-13.710 mm). CONCLUSIONS: For automated processing of MRI neuroimaging data presence of brain tumors, the proposed model can perform brain extraction including important superficial structures for oncological analysis. CLINICAL RELEVANCE STATEMENT: The proposed model serves as a radiological tool for image preprocessing in tumor cases, focusing on superficial brain structures, which could streamline the workflow and enhance the efficiency of subsequent radiological assessments. KEY POINTS: • The nnU-Net-based model is capable of segmenting significant superficial structures in brain extraction. • The proposed model showed feasible performance, regardless of pathological types or tumor characteristics. • The model showed generalization in the public datasets.

LLDT-8 ameliorates experimental autoimmune encephalomyelitis by mediating macrophage functions in the priming stage.

Multiple sclerosis (MS) is an inflammatory demyelinating disease in the central nervous system caused by T cell activation mediated by peripheral macrophages, resulting in severe neurological deficits and disability. Due to the currently limited and expensive treatments for MS, we here introduce an economic Chinese medicine extract, (5R)-5-Hydroxytriptolide (LLDT-8), which shows low toxicity and high immunosuppressive activity. We used the widely accepted mouse model of MS, experimental autoimmune encephalomyelitis (EAE), to examine the immunosuppressive effect of LLDT-8 in vivo. Through the RNA-sequence analysis of peripheral macrophages in EAE mice, we discovered that LLDT-8 alleviates the symptoms of EAE by inhibiting the proinflammatory effect of macrophages, thereby blocking the activation and proliferation of T cells. In all, we found that LLDT-8 could be a potential treatment for MS.

Hyperuricemia remission after colorectal cancer surgery for colorectal cancer patients.

The purpose of this study was to investigate whether patients with colorectal cancer (CRC) combined with hyperuricemia remitted 1 year after CRC surgery. CRC patients combined with hyperuricemia who underwent radical surgery were included from a single clinical center from Jan 2016 to Dec 2021. Baseline characteristics was compared between the remission group and the non-remission group. Multivariate logistic regression was used to find the possible predictive factors of hyperuricemia remission. A total of 91 patients were included for data analysis, retrospectively. There were 34 (37.4%) patients in the remission group and 57 (62.6%) patients in the non-remission group. The mean preoperative weight and body mass index (BMI) were 61.2 ± 10.7 (kg) and 24.1 ± 3.3 (kg/m2). 21 (23.1%) patients had a history of drinking. We found that the weight and BMI were not significantly different before and 1 year after CRC surgery (P > 0.05). In contrast, uric acid values were significantly decreased (P < 0.01). Meanwhile, the outcomes showed there were no significant differences in the baseline characteristics between the remission and non-remission groups (P > 0.05). According to multivariate logistic regression, we found that the history of drinking was a predictive factor of hyperuricemia remission (OR = 0.046, 95% CI 0.005-0.475, P = 0.010). CRC patients with hyperuricemia had a 37.4% remission from hyperuricemia 1 year after CRC surgery. Tumor location, tumor stage, and tumor size did not predict the remission of hyperuricemia. Notably, the history of drinking was a predictive factor of hyperuricemia remission.

Predicting MYCN amplification in paediatric neuroblastoma: development and validation of a 18F-FDG PET/CT-based radiomics signature.

OBJECTIVES: To develop and validate an 18F-FDG PET/CT-based clinical-radiological-radiomics nomogram and evaluate its value in the diagnosis of MYCN amplification (MNA) in paediatric neuroblastoma (NB) patients. METHODS: A total of 104 patients with NB were retrospectively included. We constructed a nomogram to predict MNA based on radiomics signatures, clinical and radiological features. The multivariable logistic regression and the least absolute shrinkage and selection operator (LASSO) were used for feature selection. Radiomics models are constructed using decision trees (DT), logistic regression (LR) and support vector machine (SVM) classifiers. A clinical-radiological (C-R) model was developed using clinical and radiological features. A clinical-radiological-radiomics (C-R-R) model was developed using the C-R model of the best radiomics model. The prediction performance was verified by receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) in the training and validation cohorts. RESULTS: The present study showed that four radiomics signatures were significantly correlated with MNA. The SVM classifier was the best model of radiomics signature. The C-R-R model has the best discriminant ability to predict MNA, with AUCs of 0.860 (95% CI, 0.757-0.963) and 0.824 (95% CI, 0.657-0.992) in the training and validation cohorts, respectively. The calibration curve indicated that the C-R-R model has the goodness of fit and DCA confirms its clinical utility. CONCLUSION: Our research provides a non-invasive C-R-R model, which combines the radiomics signatures and clinical and radiological features based on 18F-FDGPET/CT images, shows excellent diagnostic performance in predicting MNA, and can provide useful biological information with stratified therapy. CRITICAL RELEVANCE STATEMENT: Radiomic signatures of 18F-FDG-based PET/CT can predict MYCN amplification in neuroblastoma. KEY POINTS: • Radiomic signatures of 18F-FDG-based PET/CT can predict MYCN amplification in neuroblastoma. • SF, LDH, necrosis and TLG are the independent risk factors of MYCN amplification. • Clinical-radiological-radiomics model improved the predictive performance of MYCN amplification.

Extrahepatic Angiogenesis: A Potential Common Pathophysiological Basis of Multiple Organ Dysfunction in Rats with Cholestasis Cirrhosis.

BACKGROUND: In addition to intrahepatic angiogenesis, patients with cholestasis cirrhosis develop extrahepatic vasculature disorders and functional disturbances of multiple organ systems. Without effective intervention, these vascular disorders will eventually turn into multiple organs vascular syndromes, including the brain, lung and other organ systems. However, studies on the pathogenesis of vascular alterations among extrahepatic organ disturbances are still carried out separately, which hampered the successful translation of preclinical studies to the human setting and required further mechanistic insight into these complications. This study aims to investigate the relationship between extrahepatic angiogenesis and multiple organ impairment, and whether the vascular endothelial growth factor (VEGF) family members and their receptors are involved in this process. METHODS: Pathological changes of the multiple organs were determined by histopathological and immunohistochemical staining in the established common bile duct ligation (CBDL) rats, and angiogenesis was estimated by microvessel density (MVD). Levels of the VEGF family members and their receptors in the serum and organ tissues were also measured by using enzyme-linked immunosorbent assays. RESULTS: The MVD and VEGF family members and their receptors were significantly increased in CBDL rats with multiple organ injury, especially in the liver, lung and cerebral cortex. Meanwhile, we noticed moderate elevation of soluble receptor of the vascular endothelial growth factor-1 (sFlt-1) in the liver, lung, and cerebral cortex, whereas the levels of placental growth factor (PLGF) increased significantly. CONCLUSIONS: Extrahepatic angiogenesis may represent a common pathophysiological basis for multiple organ dysfunction and the sFlt-1/PLGF ratio could offer an avenue for further studies to target extrahepatic angiogenesis in cholestatic cirrhosis.