Effects of evidence-based nursing care interventions on wound pain and wound complications following surgery for finger tendon injury.

We conducted this study aimed to examine the impact of evidence-based nursing interventions on postoperative wound pain and complications after surgery for finger tendon injury. A total of 86 patients treated for finger tendon injuries at our hospital from January 2021 to October 2023 were selected and randomly divided into an experimental group and a control group. The control group received conventional nursing care, while the experimental group received evidence-based nursing interventions. The study compared the postoperative wound pain intensity, incidence of complications and patient satisfaction with nursing care between the two groups. The analysis revealed that compared with conventional care, evidence-based nursing interventions significantly reduced the level of wound pain (p = 0.034) and the incidence of complications (4.65% vs. 18.60%, p = 0.043). It also increased patient satisfaction with the nursing care (97.67% vs. 83.72%, p = 0.026). The study indicates that the application of evidence-based nursing interventions for patients with finger tendon injuries can reduce postoperative wound pain, decrease the incidence of complications and enhance patient satisfaction with nursing care.

Annonaceous Acetogenins Synergistically Inhibit Hepatocellular Carcinoma with Sorafenib.

Sorafenib was first approved as the standard treatment for advanced hepatocellular carcinoma (HCC). Despite providing an advantage in terms of patient survival, sorafenib has shown poor clinical efficacy and severe side effects after long-term treatment. Thus, combination treatment is a potential way to increase the effectiveness and reduce the dose-limiting toxicity of sorafenib. Extracts of the seeds of Annona montana have shown synergistic antitumor activity with sorafenib, and seven annonaceous acetogenins, including three new acetogenins, muricin P (2), muricin Q (3), and muricin R (4), were isolated from the extracts by bioguided fractionation and showed synergy with sorafenib. The structures of these compounds were determined using spectroscopic and chemical methods. Annonacin (1) and muricin P (2), which reduced intracellular ATP levels and promoted apoptosis, exhibited synergistic cytotoxicity with sorafenib in vitro. In vivo, annonacin (1) displayed synergistic antitumor activity by promoting tumor cell apoptosis. Moreover, the potential mechanism of annonacin (1) was predicted by transcriptomic analysis, which suggested that SLC33A1 is a potential target in HCC. Annonacin (1) might be a novel candidate for combination therapy with sorafenib against advanced HCC.

Oxidization and Chain-Branching Reaction for Recycling HDPE and Mixed HDPE/PP with In-situ Compatibilization by Ozone-Induced Reactive Extrusion.

High-density polyethylene (HDPE) and isotactic polypropylene (iPP) are widely used in industrial and residential applications due to their low cost and chemical stability, thus their recycling process can contribute to a circular economy. However, both polymers are non-polar materials, and the incompatibility with most other materials leads to substantially inferior properties of blends. In this work, we propose a flexible compatibilization strategy to improve the compatibility of HDPE/iPP blends. Ozone is adopted to induce reactive extrusion for rapid oxidation of HDPE and chain-branching reactions for both HDPE and HDPE/iPP blends. During extrusion process, ozone oxidizes HDPE effectively in a short time and introduces oxygen-containing groups such as carbonyl and ester groups, which improves the hydrophilicity. The addition of trimethylolpropane triacrylate (TMPTA) could promote branching reaction and facilitate the formation of HDPE-g-iPP copolymers, which improved the compatibility for HDPE/iPP. As a result, the impact strength of ozone-modified HDPE and HDPE/iPP blends increased by 22 % and 82 %, respectively, and the tensile strength also increased. This strategy would have potential applications in the field of sorting-free and solvent-free recycling of waste polyolefin plastics.

[Immunophenotypic and Clinical Characteristics of SET-CAN Fusion Gene Positive Acute Leukemia Patients].

OBJECTIVE: To analyze the flow immunophenotype and clinical characteristics of leukemia patients with positive SET-CAN fusion gene. METHODS: A total of 7 newly diagnosed acute leukemia patients with SET-CAN fusion gene admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 2016 to February 2020 were collected. Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of SET-CAN fusion gene. The immunophenotype was detected by four-color flow cytometry. The case information of 17 literatures published at home and abroad was extracted for statistical analysis. RESULTS: Among the 7 patients, 2 cases were diagnosed as mixed phenotype acute leukemia (MPAL), 2 cases as acute myeloid leukemia (AML), and 3 cases as T-acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Leukemia cells in bone marrow specimens of all cases expressed or partially expressed CD34, CD33 and CD7. CD5 and cytoplasmic CD3 were expressed in 5 patients except 2 patients diagnosed with AML. Bone marrow and lymph node specimens were both detected in 2 patients, and the immunophenotypes of the two specimens were not completely consistent, with differences in lineage or maturity related markers. Two patients with MPAL showed differentiated response to treatment. One AML patient gave up treatment, and another AML patient with FLT3-ITD gene mutation had a poor prognosis. All three T-ALL/LBL patients maintained a long duration of remission after induced remission, and one case underwent allogeneic hematopoietic stem cell transplantation. CONCLUSIONS: There are common characteristics of immunophenotype in patients with positive SET-CAN fusion gene. Differential expression of immunophenotype in samples from different parts is observed in some cases. The prognosis of these diseases varies.

Promoting reverse cholesterol transport contributes to the amelioration of atherosclerosis by paeoniflorin.

Reverse cholesterol transport (RCT) offers a practical approach to mitigating atherosclerosis. Paeoniflorin, a monoterpenoid glycoside found in plants of the Paeoniaceae family, has shown various effects on cardiovascular and liver diseases. Nevertheless, its impact on atherosclerosis in vivo remains poorly understood. The objective of this study is to examine the effect of paeoniflorin on atherosclerosis using apolipoprotein E-deficient (ApoE-/-) mice and explore the underlying mechanisms, with a specific focus on its modulation of RCT. ApoE-/- mice were continuously administered paeoniflorin by gavage for three months. We assessed lipid parameters in serum and examined pathological changes and gene expressions related to RCT pathways in the aorta, liver, and intestine. In an in vitro study, we utilized RAW264.7 macrophages to investigate the inhibitory effect of paeoniflorin on foam cell formation and its potential to promote RCT. The results revealed that paeoniflorin reduced atherosclerosis, alleviated hyperlipidemia, and mitigated hepatic steatosis. Paeoniflorin may promote RCT by stimulating cholesterol efflux from macrophages via the liver X receptor alpha pathway, enhancing serum high-density lipoprotein cholesterol and apolipoprotein A-I levels, and regulating key genes in hepatic and intestinal RCT. Additionally, treatment ApoE-/- mice with paeoniflorin suppressed the expression of inflammation-related genes, including CD68, tumor necrosis factor alpha, and monocyte chemoattractant protein-1, and mitigated oxidative stress in both the aorta and liver. Our results indicated that paeoniflorin has the potential to be a more effective and safer treatment for atherosclerosis, thanks to its promotion of RCT and its anti-inflammatory and anti-oxidative effects.

DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3Ahigh subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3Ahigh cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3Ahigh tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC.

Isolation of Projection-Specific and Behavior-Relevant Amygdala Circuit for RNA Sequencing.

One of the most sought-after topics in neuroscience is to understand how the environment regulates the activity and function of neural circuitry and subsequently influences relevant behaviors. In response to alterations in the environment, the neural circuits undergo adaptive changes ranging from gene expression changes to altered cellular function. Performing sequencing of the transcriptome involved in these behavior-related circuits will provide clues to accurately dissect the detailed mechanisms of related behavior. Here, we describe methods for marking and collecting the ventral hippocampus-projecting basolateral amygdala neurons, which have been repeatedly implicated in regulation of anxiety-like behavior, and subsequently constructing a library ready for sequencing. Specifically, the reported approaches include adeno-associated virus injection, acute brain slice isolation, cell suspension preparation, cell extraction, and cDNA library construction. By utilizing the techniques described here, researchers can comprehensively investigate the transcriptional levels of neural clusters embedded in particular circuits and discover potential pathogenic and therapeutic targets for behavior-relevant disorders. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Tagging of behavior-related neural circuits Basic Protocol 2: Isolation and capture of fluorescent-positive cells Basic Protocol 3: Foundation of sequencing library.

Analysis of postoperative pregnancy outcome in 180 women with congenital uterine malformation.

Introduction: This study aims to explore the effects of combination of laparoscopy and hysteroscopy in pregnancy outcome in women diagnosed with congenital uterine malformation (CUM). The observation criteria include pregnancy rate, misdiagnosis rate, rate of spontaneous abortion and preterm birth rate. Material and methods: A total of 180 patients with congenital uterine malformation, who were treated in our hospital from January 2015 to June 2018, were enrolled in the study. Prior to hospitalization, all the patients had neither a history of genital tract surgery nor endocrine abnormalities, chromosomal abnormalities, immune abnormalities or other factors affecting pregnancy. Furthermore, the ovarian functions were normal, and there were no factors leading to infertility in the male partners. The diagnosis was mainly based on medical history, clinical manifestations, gynecological examinations, and ultrasonography including two-dimensional and three-dimensional ultrasonography, as well as hysterosalpingogram (HSG), magnetic resonance imaging (MRI), hysteroscopy, and/or laparoscopy or surgery. Patients were diagnosed and classified according to the Buttram classification. Results: Among these 180 patients, 37 patients were diagnosed with complete septate uterus, 96 patients had sub-septate uterus, 25 patients had unicornuate uterus, 11 patients were diagnosed with bicornuate uterus, and 11 patients had didelphic uterus. The total number of preoperative pregnancies was 112, including 106 spontaneous abortions, with an abortion rate of 94.64%, and 86 total postoperative pregnancies, among which spontaneous abortions occurred 11 times, with an abortion rate of 12.79%. The difference was statistically significant (p < 0.05). Conclusions: Uterine malformation surgery can significantly improve the reproductive prognosis in patients with CUM.

[Esophageal Angiolipoma:Report of One Case and Literature Review].

Esophageal angiolipoma is a rare disease with unspecific clinical manifestations.This paper reported a case of esophageal angiolipoma confirmed by upper gastrointestinal endoscopy and summarized the clinical manifestations,endoscopic and pathological features,treatment and prognosis of the patients by reviewing the relevant literature,aiming to provide references for clinical diagnosis and treatment of this disease in the future.

TEAD4 predicts poor prognosis and transcriptionally targets PLAGL2 in serous ovarian cancer.

The oncogenic function of TEA domain transcription factor 4 (TEAD4) has been confirmed in multiple human malignancies, while its potential role and regulatory mechanism in serous ovarian cancer progression are left unknown. By the gene expression analyses from Gene Expression Profiling Interactive Analysis (GEPIA) database, TEAD4 expression is shown to be up-regulated in serous ovarian cancer samples. Here, we confirmed the high expression of TEAD4 in clinical serous ovarian cancer specimens. In the following functional experiments, we found that TEAD4 overexpression promoted serous ovarian cancer malignant phenotypes, including proliferation, migration and invasion in serous ovarian cancer SK-OV-3 and OVCAR-3 cells, while TEAD4 knockout exerted the opposite function. The tumor growth inhibition of TEAD4 depletion was also affirmed by a Xenograft model in mice. In addition, this phenotypic deterioration induced by TEAD4 overexpression was diminished by PLAG1 like zinc finger 2 (PLAGL2) silencing. More importantly, combined with the results of the dual-luciferase assay, the transcriptional regulation of TEAD4 on PLAGL2 promoter was evidenced. Our results showed that the cancer-promoting gene TEAD4 was involved in serous ovarian cancer progression via targeting PLAGL2 at the transcriptional level.

Autoimmunity associates with severity of illness in elderly patients with drug-induced liver injury.

Background: Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs. This study aimed to identify the clinical characteristics and explore the risk factors associated with the severity of illness in elderly patients with DILI. Methods: In the present study, the clinical characteristics at the time of liver biopsy of consecutive patients with biopsy-proven DILI who presented at our hospital from June 2005 to September 2022 were evaluated. Hepatic inflammation and fibrosis were assessed according to the Scheuer scoring system. The presence of autoimmunity was considered if IgG level >1.1 × ULN (1826 mg/dL), or high titer (>1:80) of ANA, or SMA. Results: In total, 441 patients were enrolled, and the median age was 63.3 years (IQR, 61.0-66.0); 122 (27.7%), 195 (44.2%), or 124 (28.1%) were classified as having minor, moderate, or severe hepatic inflammation, respectively; and 188 (42.6%), 210 (47.6%) or 43 (9.8%) patients presented minor, significant fibrosis or cirrhosis, respectively. Female sex (73.5%) and the cholestatic pattern (47.6%) were dominant in elderly DILI patients. Autoimmunity existed in 201 patients (45.6%). Comorbidities were not directly associated with the severity of DILI. PLT (OR: 0.994, 95% CI: 0.991-0.997; p < 0.001), AST (OR: 1.001, 95% CI: 1.000-1.003, p = 0.012), TBIL (OR: 1.006, 95% CI: 1.003-1.010, p < 0.001), and autoimmunity (OR: 1.831, 95% CI: 1.258-2.672, p = 0.002) were associated with the degree of hepatic inflammation. Meanwhile, PLT (OR: 0.990, 95% CI: 0.986-0.993, p < 0.001), TBIL (OR: 1.004, 95% CI: 1.000-1.007, p = 0.028), age (OR: 1.123, 95% CI: 1.067-1.183, p < 0.001), and autoimmunity (OR: 1.760, 95% CI: 1.191-2.608, p = 0.005) were associated with the stage of hepatic fibrosis. Conclusion: This study revealed that the presence of autoimmunity represents a more serious illness state of DILI, deserving more intensive monitoring and progressive treatment.

Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

The diagnostic value of next-generation sequencing technology in sepsis.

Objective: This study aims to assess the clinical utility of next-generation sequencing (NGS) in sepsis diagnosis. Methods: A prospective study was conducted on patients with a high suspicion of sepsis by unknown pathogens from January 2017 to December 2021. Blood samples were taken from patients to perform NGS, blood culture (BC), leucocyte (WBC), procalcitonin (PCT), creatinine (CREA), Albumin (ALB) and C-reactive protein (CRP) tests. Results: The feedback time for BC was 3~5 days for bacteria and 5~7 days for fungi, while the turnover time for NGS was only 24 h. The clinical diagnosis was considered the "gold standard". 83 patients passed our inclusion criteria and were separated into two groups by clinical diagnosis. 62 met the clinical diagnosis criteria for sepsis and 21 were non-sepsis. The data from the two groups were retrospectively compared and analyzed. Of 62 sepsis in 83 patients, 8(9.64%) were diagnosed by both BC and NGS, 51 (61.45%) by NGS only, 1(1.20%) by BC and 2 (2.41%) by conventional testing only; PCT, CREA, CRP levels and the detection rate of NGS and BC were higher in the sepsis group than in the non-sepsis group, while ALB levels were lower (p<0.05). The logistic regression results in our study revealed that NGS and ALB were independent prediction factors for sepsis (p<0.05), the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of NGS for diagnosing sepsis was 0.857, 95.16% and 76.19%, while ALB was 0.728, 58.06%, 80.95%, respectively. The combination's sensitivity, specificity and AUC of NGS and ALB were 93.55%, 85.71% and 0.935, greater than that of Albumin or NGS only (both p<0.05). Conclusion: NGS can effectively and quickly identify pathogens, thereby emerges as a promising technology for sepsis diagnosis. Combination of NGS and ALB can be used for early screening and is more powerful than NGS or ALB only.

Ovarian mucinous tumor with mural nodules of anaplastic carcinoma: Three case reports.

BACKGROUND: Anaplastic carcinoma mural nodules in ovarian mucinous tumors are very rare. This study aimed to report the morphological characteristics, molecular detection results, clinical treatment and prognosis of three ovarian mucinous tumors with mural nodules of anaplastic carcinoma. CASE SUMMARY: The pathomorphological features, molecular detection results, clinical treatment and prognosis of anaplastic carcinoma mural nodules were described in three cases. In case 1, sarcoma-like mural nodules (SLMNs) coexisted with anaplastic carcinoma mural nodules. No mutation was found in mucinous tumors. KRAS mutation was found in anaplastic carcinoma nodules and heterotypic cells were found in SLMNs. In case 2, KRAS mutation occurred in the mucinous epithelium and BRAF mutation occurred in mural nodules. In case 3, both mural nodules and mucinous tumors had the same KRAS mutation and a morphological transition between them was observed. All three patients died within 2 years, whether receiving chemotherapy or not. CONCLUSION: Anaplastic carcinoma mural nodules may develop from dedifferentiation of mucinous tumors or are unrelated to mucinous tumors.

Analysis of the influencing factors on fine-needle aspiration biopsy results of the thyroid.

Objective: The objective of the study is to analyze the influencing factors on the results of thyroid fine-needle aspiration biopsy (FNAB). Method: A total of 339 patients who underwent FNAB in our hospital from December 2018 to July 2021 were retrospectively selected. The patients were chosen according to the gender ratio, age, and thyroid ultrasound characteristics and were divided into three groups: (1) a 22G needle vacuum aspiration group (Group 1, n = 85), (2) a 22G biopsy needle non-vacuum aspiration group (Group 2, n = 50), and (3) a 25G biopsy needle non-vacuum aspiration group (Group 3, n = 204). Patients in these groups were evaluated for determining the FNAB dissatisfaction rate of pathological samples. A bivariate regression analysis of independent risk factors related to the unsatisfactory pathological diagnosis of samples was performed. Results: The specimen dissatisfaction rates of the three groups were 22/85 (25.9%), 15/50 (30%), and 18/186 (9.7%), respectively. The overall sample dissatisfaction rate was 55/339 (16.2%), and the sample satisfaction rate of Group 3 was higher than that of Groups 1 and 2 (P < 0.05). Logistic bivariate regression analysis showed that the age of the patients and the capillary sampling needles and aspiration methods were two independent risk factors for determining the dissatisfaction rate of FNAB pathological samples. Conclusion: A 25G capillary sampling aspiration biopsy needle was selected to perform FNAB in thyroid nodules without vacuum aspiration, which could effectively improve the accuracy of FNAB results with a high specimen satisfaction rate.

[Changes of intestinal flora in children with acute lymphoblastic leukemia before and after chemotherapy]. / å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— åŒ–ç–—å‰åŽè‚ é“èŒç¾¤å˜åŒ–ç‰¹ç‚¹.

OBJECTIVES: To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. METHODS: Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. RESULTS: The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). CONCLUSIONS: The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.

MDM2-Mediated Ubiquitination of RXRß Contributes to Mitochondrial Damage and Related Inflammation in Atherosclerosis.

A novel function of retinoid X receptor beta (RXRß) in endothelial cells has been reported by us during the formation of atherosclerosis. Here, we extended the study to explore the cellular mechanisms of RXRß protein stability regulation. In this study, we discovered that murine double minute-2 (MDM2) acts as an E3 ubiquitin ligase to target RXRß for degradation. The result showed that MDM2 directly interacted with and regulated RXRß protein stability. MDM2 promoted RXRß poly-ubiquitination and degradation by proteasomes. Moreover, mutated MDM2 RING domain (C464A) or treatment with an MDM2 inhibitor targeting the RING domain of MDM2 lost the ability of MDM2 to regulate RXRß protein expression and ubiquitination. Furthermore, treatment with MDM2 inhibitor alleviated oxidized low-density lipoprotein-induced mitochondrial damage, activation of TLR9/NF-κB and NLRP3/caspase-1 pathway and production of pro-inflammatory cytokines in endothelial cells. However, all these beneficial effects were reduced by the transfection of RXRß siRNA. Moreover, pharmacological inhibition of MDM2 attenuated the development of atherosclerosis and reversed mitochondrial damage and related inflammation in the atherosclerotic process in LDLr-/- mice, along with the increased RXRß protein expression in the aorta. Therefore, our study uncovers a previously unknown ubiquitination pathway and suggests MDM2-mediated RXRß ubiquitination as a new therapeutic target in atherosclerosis.

Optimization of endometrial cancer organoids establishment by cancer-associated fibroblasts.

Most endometrial cancers (EC) are diagnosed at an early stage with a favorable prognosis. However, for patients with advanced or recurrent disease, the chemotherapy response rate and overall survival remain poor. A novel in vitro model, tumor organoids, has important value in providing a more individualized treatment plan for tumor patients. However, the slow growth of the established EC organoid seriously hinders the application of EC organoids. Cancer-associated fibroblasts (CAFs), the main component of tumor stroma, have been reported to promote the proliferation of endometrial cancer cell lines and primary endometrial cancer cells in vivo and in vitro. Therefore, we optimized the current endometrial cancer organoid by introducing CAFs isolated from EC lesions. Here we developed long-term expandable organoids from endometrial cancer lesions, which show disease-associated traits and cancer-linked mutations. Based on the co-culture of CAFs and endometrial cancer organoids, we found that CAFs could promote the growth of endometrial cancer organoids, might by secreting factors according to the result that CAFs could also promote the growth. Our research provided a more promising model for the basic and preclinical study of endometrial cancer.

Activating PGC-1α-mediated signaling cascades in the aorta contributes to the amelioration of vascular senescence and atherosclerosis by 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glycoside.

BACKGROUND: 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glycoside (TSG), the main active polyphenolic component of Polygonum multiflorum, possesses many pharmacological activities. Its anti-aging effect influences a variety of tissues with diverse mechanisms. However, the effectiveness and exact mechanisms of TSG against vascular senescence in atherosclerosis remain unclear. The present study is aimed to investigate the effects of TSG against vascular senescence in atherosclerosis both in vivo and in vitro, and the possible underlying mechanisms focusing on aortic peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated signaling cascades which have never been studied. METHODS: In vivo, 12-mo-old male LDLr-/- mice were randomly separated into control, high-fat diet (HFD), and TSG -treatment groups. At the end of the 12 weeks, the blood samples and aorta tissues of mice were collected for further analysis. In vitro, to mimic the condition of endothelial senescence in hyperlipidemic mice, human aortic endothelial cells (HAECs) were incubated with oxidized low-density lipoprotein (ox-LDL) to induce senescence. RESULTS: TSG administration improved lipid profiles, ameliorated HFD-exacerbated vascular senescence and atherosclerosis. The protective effect of TSG via inhibiting telomere malfunction, oxidative stress, and mitochondrial damage was found both in vivo and in vitro. Notably, TSG administration increased aortic PGC-1α mRNA and protein expression along with the regulation of its targeted genes TERT, NRF1, TFAM, Mn-SOD, and catalase. Further, by using PGC-1α siRNA in ox-LDL-treated HAECs, it is proved that TSG reduced endothelial senescence, telomere malfunction, oxidative stress, and mitochondrial damage at least partly through activating the PGC-1α pathway. CONCLUSIONS: These results provide new evidence for TSG in the treatment of atherosclerosis and the activation of aortic PGC-1α is involved in its beneficial effects.

Prediction of biochemical nonresolution in patients with chronic drug-induced liver injury: A large multicenter study.

BACKGROUND AND AIMS: To clarify high-risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI. APPROACH AND RESULTS: Retrospectively, 3655 of 5326 patients with chronic DILI were enrolled from nine participating hospitals, of whom 2866 underwent liver biopsy. All of these patients were followed up for over 1 year and their clinical characteristics were retrieved from electronic medical records. The endpoint was BNR, defined as alanine aminotransferase or aspartate aminotransferase >1.5× upper limit of normal or alkaline phosphatase >1.1× ULN, at 12 months from chronic DILI diagnosis. The noninvasive high-risk factors for BNR identified by multivariable logistic regression were used to establish a nomogram, which was validated in an independent external cohort. Finally, 19.3% (707 of 3655) patients presented with BNR. Histologically, with the increase in liver inflammation grades and fibrosis stages, the proportion of BNR significantly increased. The risk of BNR was increased by 21.3-fold in patients with significant inflammation compared to none or mild inflammation (p < 0.001). Biochemically, aspartate aminotransferase and total bilirubin, platelets, prothrombin time, sex, and age were associated with BNR and incorporated to construct a nomogram model (BNR-6) with a concordance index of 0.824 (95% CI, 0.798-0.849), which was highly consistent with liver histology. These results were successfully validated both in the internal cohort and external cohort. CONCLUSIONS: Significant liver inflammation is a robust predictor associated with biochemical nonresolution. The established BNR-6 model provides an easy-to-use approach to assess the outcome of chronic DILI.