Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

OBJECTIVES: To construct an intelligent analysis model for classifying fetal orientation during intrapartum ultrasound videos based on multi-feature fusion. METHODS: The proposed model consists of the Input, Backbone Network and Classification Head modules. The Input module carries out data augmentation to improve the sample quality and generalization ability of the model. The Backbone Network was responsible for feature extraction based on Yolov8 combined with CBAM, ECA, PSA attention mechanism and AIFI feature interaction module. The Classification Head consists of a convolutional layer and a softmax function to output the final probability value of each class. The images of the key structures (the eyes, face, head, thalamus, and spine) were annotated with frames by physicians for model training to improve the classification accuracy of the anterior occipital, posterior occipital, and transverse occipital orientations. RESULTS: The experimental results showed that the proposed model had excellent performance in the tire orientation classification task with the classification accuracy reaching 0.984, an area under the PR curve (average accuracy) of 0.993, and area under the ROC curve of 0.984, and a kappa consistency test score of 0.974. The prediction results by the deep learning model were highly consistent with the actual classification results. CONCLUSIONS The multi-feature fusion model proposed in this study can efficiently and accurately classify fetal orientation in intrapartum ultrasound videos.
Humans ; Female ; Ultrasonography, Prenatal/methods* ; Pregnancy ; Fetus/diagnostic imaging* ; Neural Networks, Computer ; Video Recording

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

β-elemene has been observed to exert inhibitory effects on a multitude of tumors,primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis.The present study is designed to elucidate the role and underlying mechanisms of β-elemene in the thera-peutic intervention of non-small cell lung cancer(NSCLC).Both in vitro and in vivo experimental models corroborate the inhibitory potency of β-elemene on NSCLCs.Our findings indicate that β-elemene fa-cilitates the maturation of miR-127-3p by inhibiting CBX8.Functioning as an upstream regulator of MAPK4,miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4,thereby inducing autophagy in NSCLCs.Additionally,β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP.Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4.Taken together,the detailed understanding of the mechanisms through which β-elemene in-duces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.

【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.

Objective:To assess the efficacy of Tamsulosin monotherapy for overactive bladder(OAB)symptoms in benign prostatic hyperplasia(BPH)patients with the prostate volume(PV)<40 ml, and to analyze related factors affecting the efficacy.Methods:300 BPH patients with OAB were enrolled, with an average age of(66.9±7.7)years and the PV<40 ml.Smoking, drinking and other living habits were investigated.Data on the Overactive Bladder Symptom Score(OABSS), International Prostate Symptom Score(IPSS)and Quality of Life Scale(QOLS)were collected before and after 4 weeks of treatment with Tamsulosin 0.2 mg QN.The maximum urine flow rate(Qmax)and bladder residual urine volume(PVR)were measured before and after treatment.OBASS was used as the main assessment parameter to analyze the correlation of efficacy with age, lifestyle, pre-treatment symptom scores, PV, Qmax and PVR.Results:257 patients completed the study, and 169 patients were treated effectively, with an overall effectiveness rate of 65.8%.The effectiveness rates of the mild, moderate and severe OAB groups were 83.6%, 62.4% and 38.5%, respectively, with statistical significance( χ2=13.037, P=0.001).3 patients showed adverse drug reactions, including 2 patients with mild dizziness and 1 patient with nausea.The baseline OABSS score, the proportion of smoking patients and the proportion of drinking patients in the effectively treated OAB group were significantly lower than those in the ineffectively treated group.Multivariate analysis showed that baseline OABSS score( OR=0.735, P<0.001)and smoking( OR=2.111, P=0.029)were correlated with tamsulosin's efficacy in treating BPH patients with OAB with PV<40 ml. Conclusions:The effectiveness rate of Tamsulosin for the treatment of BPH patients with mild OAB with PV<40 ml is high.The baseline OABSS score and smoking are factors affecting the efficacy of Tamsulosin on OAB symptoms in these patients.

Objective:To determine the predictive value of preoperative monocyte-to-lymphocyte ratio(MLR) for prognosis in elderly patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy(RNU).Methods:A retrospective study was performed on 168 elderly patients who underwent RNU in Beijing Hospital between March 2004 to February 2019.Males accounted for 44.6% (75 patients) and females 55.4%(93 patients) of the patients. Median age at the time of surgery was 73(69-78) years, and 110 (65.5%) patients suffered from hydronephrosis. There were 147 cases(87.5%)with single tumor, and 21 cases(12.5%)with multiple tumors, including 75(46.6%) cases in renal pelvis or pelvi-ureteric junction, and 93(53.4%)cases in ureter. Open RNU was performed in 106(63.1%) patients, and laparoscopic method in 62(32.9%) patients. The optimal cutoff value of MLR was set as 0.22 by using the median.χ 2 test, which was used to detect the association between MLR(≤0.22 vs.>0.22) and clinicopathological variables. Survival analyses were performed using the Kaplan-Meier method and were compared using the log-rank test. Additional subgroup analyses(low grade vs. high grade) were performed according to pathological grade. Univariate and multivariate analysis by Cox’s proportional hazards model was used to determine the significance of MLR in respect to OS and PFS. Results:The follow-up period ranged from 19.2 to 86.9 months (median 51.9 months). Next, the cohort was divided into 2 groups , including 77 patients with low MLR(≤0.22) and 91 patients with high MLR(>0.22). High MLR was significantly more frequent in male patients(31.2% vs.56.0%), as well as those undergoing laparoscopic surgery (54.5% vs.70.3%)(All P<0.05). Based on a Cox univariate proportional hazards analysis, male gender( HR=1.793, 95% CI 1.003-3.205, P=0.049), presence of lymph node metastasis( HR=6.809, 95% CI 2.124-17.454, P=0.001) and high MLR( HR=2.287, 95% CI 1.259-4.154, P=0.007)were associated with poor OS. Male gender( HR=1.758, 95% CI 1.066-2.902, P=0.027), presence of lymph node metastasis( HR=6.524, 95% CI 2.542-16.748, P<0.001), lymphovascular invasion(LVI) ( HR=2.348, 95% CI 1.139-4.838, P=0.021), high MLR( HR=2.801, 95% CI 1.657-4.735, P<0.001)and PLR( HR=1.663, 95% CI 1.003-2.757, P=0.049) were significantly associated with subsequent PFS. By multivariate analysis, tumor site( HR=2.050, 95% CI 1.079-3.892, P=0.028), lymph node metastasis ( HR=6.641, 95% CI 1.852-23.811, P=0.004) and MLR( HR=2.089, 95% CI 1.062-4.113, P=0.033) were the independent risk factors for OS in elderly patients with UTUC. Tumor side( HR=2.024, 95% CI 1.033-3.965, P=0.040), multifocality ( HR=2.992, 95% CI 1.161-7.713, P=0.023), lymph node metastasis ( HR=6.454, 95% CI 2.026-20.564, P=0.002) and MLR( HR=2.866, 95% CI 1.554-5.284, P=0.001) were associated with PFS.The multivariate analysis of the significant risk factors established a postoperative risk stratification model for OS and PFS. The results showed significant differences among the 3 subgroups of patients with low(0 risk factor), intermediate(1 risk factor), or high risk(2-3 risk factors)(All P<0.05). Conclusion:MLR was an independent risk factor for OS and PFS in elderly patients with UTUC and patients with elevated MLR have worsen prognosis.

Objective:To investigate the value of liver fibrosis serum markers in predicting esophagogastric variceal re-bleeding (EGVR) after laparoscopic splenectomy and azygoportal discon-nection (LSD).Methods:The prospective study was conducted. The clinical data of 155 cirrhotic portal hypertension patients with EGVR after LSD in the Clinical Medical College of Yangzhou University from September 2014 to January 2017 were selected. Observation indicators: (1) grouping situations of the enrolled patients; (2) risk factors analysis for postoperative EGVR; (3) prediction of postoperative EGVR; (4) follow-up. Follow-up was conducted using telephone interview, outpatient examination and hospitalization. Patients were followed up once every 3 months after operation to detect occurrence of EGVR and survival of patient up to January 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data wite skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups were conducted using the chi-square test or Fisher exact probability. Logistic regression model was used for multivariate analysis. The area under curve (AUC) of receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficiency. The Youden index was used to determine the optimal cut-off point. Results:(1) Grouping situations of the enrolled patients. A total of 155 patients were selected for eligibility. There were 106 males and 49 females, aged (53±11)years. Of the 155 patients, there were 21 cases with EGVR in the postoperative 1 year and 134 cases without EGVR in the postoperative 1 year. The protein expression of laminin and collagen Ⅳ were 100.3(range, 16.1?712.2)μg/L and 68.4(range, 35.0?198.8)μg/L in patients with EGVR, vs 35.5(range, 2.0?521.2)μg/L and 43.5(range, 4.3?150.4)μg/L in patients without EGVR, showing significant differences between them ( Z=?4.55, ?4.52, P<0.05). (2) Risk factors analysis for postoperative EGVR. According to the Youden index, the optimal cut-off point of protein expression of laminin and collagen Ⅳ were 64.0 μg/L and 65.0 μg/L, respec-tively. Results of multivariate analysis showed that the protein expression of laminin ≥64.0 μg/L and the protein expression of collagen Ⅳ ≥65.0 μg/L were independent risk factors for postoperative EGVR ( odds ratio=9.69, 8.16, 95 confidence intervals as 3.05?30.82, 2.65?25.15, P<0.05). (3) Prediction of postoperative EGVR. Results of ROC curve showed that the AUC of laminin and collagen Ⅳ in predicting postoperative EGVR was 0.79 (95% confidence interval as 0.66?0.92), with sensi-tivity as 0.62 and specificity as 0.96. (4) Follow-up. All the 155 patients were followed up for 12(range, 1?12)months. During the follow-up, there were 21 of the 155 patients (13.55%) with post-operative EGVR, including 3 cases died of EGVR. Of the 21 patients with postoperative EGVR, there were 6 cases with postoperative EGVR during the first month after operation including 2 cases died, 5 cases with postoperative EGVR at postoperative 1?3 month, 6 cases with postoperative EGVR more than 3 month and less than 6 month after operation and 4 cases with postoperative EGVR at postoperative 6?12 months including 1 case died at postoperative 12 month. Conclusions:Laminin and collagen Ⅳ show satisfactory ability to predict EGVR after LSD.