Co-delivery of siAEG-1 and doxorubicin to treat osteosarcoma via nanomicelles for azide-alkyne "click" conjugation of poly(l-lysine) dendrons onto Zein.

Astrocyte elevated gene-1 (AEG-1) oncogene is a notorious and evolving target in a variety of human malignancies including osteosarcoma. The RNA interference (RNAi) has been clinically proven to effectively knock down specific genes. To successfully implement RNAi in vivo, protective vectors are required not only to protect unstable siRNAs from degradation, but also to deliver siRNAs to target cells with controlled release. Here, we synthesized a Zein-poly(l-lysine) dendrons non-viral modular system that enables efficient siRNA-targeted AEG-1 gene silencing in osteosarcoma and encapsulation of antitumor drugs for controlled release. The rational design of the ZDP integrates the non-ionic and low immunogenicity of Zein and the positive charge of the poly(l-lysine) dendrons (DPLL) to encapsulate siRNA and doxorubicin (DOX) payloads via electrostatic complexes and achieve pH-controlled release in a lysosomal acidic microenvironment. Nanocomplexes-directed delivery greatly improves siRNA stability, uptake, and AEG-1 sequence-specific knockdown in 143B cells, with transfection efficiencies comparable to those of commercial lipofectamine but with lower cytotoxicity. This AEG-1-focused RNAi therapy supplemented with chemotherapy inhibited, and was effective in inhibiting the growth in of osteosarcoma xenografts mouse models. The combination therapy is an alternative or combinatorial strategy that can produce durable inhibitory responses in osteosarcoma patients.

Identification of a DNA-methylome-based signature for prognosis prediction in driver gene-negative lung adenocarcinoma.

"Driver gene-negative" lung adenocarcinoma (LUAD) was of rare treatment options and a poor prognosis. Presently, for them, few biomarkers are available for stratification analysis to make appropriate treatment strategy. This study aimed to develop a DNA-methylome-based signature to realize the precise risk-stratifying. Here, an Illumina MethylationEPIC Beadchip was applied to obtain differentially methylated CpG sites (DMCs). A four-CpG-based signature, named as TLA, was successfully established, whose prognosis-predicting power was well verified in one internal (n = 78) and other external (n = 110) validation cohorts. Patients with high-risk scores had shorter overall survival (OS) in all cohorts [hazard ratio (HR): 11.79, 5.16 and 2.99, respectively]. Additionally, it can effectively divide patients into low-risk and high-risk groups, with significantly different OS in the diverse subgroups stratified by the standard clinical parameters. As an independent prognostic factor, TLA may assist in improving the nomogram's 5-year OS-predicting ability (AUC 0.756, 95% CI:0.695-0.816), superior to TNM alone (AUC 0.644, 95% CI: 0.590-0.698). Additionally, the relationship of TLA-related genes, TAC1, LHX9, and ALX1, with prognosis and tumour invasion made them serve as potential therapy targets for driver gene-negative LUAD.

Analgesic effect of thoracic paravertebral block on patients undergoing thoracoscopic lobectomy under general anesthesia.

Objective: To investigate the analgesic effect of thoracic paravertebral block (TPVB) in patients undergoing thoracoscopic lobectomy under general anesthesia (GA). Methods: Clinical records of 82 patients who underwent thoracoscopic lobectomy under GA from October 2021 to October 2022 in the General Hospital of Southern Theater Command were retrospectively analyzed. The patients were divided into two groups according to the method of anesthesia used: general anesthesia group (Group-G, n=37), and TPVB plus GA group (Group-T, n=45). The analgesic effect, mean arterial pressure (MAP), heart rate (HR) and the rate of adverse events in both groups were compared. Results: Visual analogue scale (VAS) scores of patients in Group-T at 12h, 24h and 48h after the operation were significantly lower compared to Group-G (P<0.05). MAP and HR the time of tracheal intubation induction (T1), single lung ventilation (T2), skin incision (T3), operation completion (T4), and 20 minutes after the extubation (T5) were lower in both groups compared to T0, and were significantly higher in Group-T compared to Group-G (P<0.05). The rate of adverse events in Group-T was 6.67%, significantly lower compared to Group-G (24.32%) (P<0.05). Conclusions: TPVB combined with GA can improve the analgesic effect, improve MAP and HR during the operation, and reduce the incidence of adverse events in patients undergoing thoracoscopic lobectomy.

The effect of intravenous and inhalation anesthesia in general on the cognition of elderly patients undergoing non-cardiac surgery: a systematic review and meta-analysis.

Background: Postoperative cognitive dysfunction (POCD) is a postoperative complication that often occurs in the elderly. This systematic review and meta-analysis aimed to compare intravenous anesthetics (propofol) with inhalation anesthetics (sevoflurane) regarding the occurrence of POCD in the elderly who underwent non-cardiac surgery. Methods: The investigators searched for published articles from the PubMed, Embase, Web of Science, Scopus, Cochrane, and Clinicalkey databases. Clinical studies comparing the incidence of POCD in elderly patients undergoing intravenous or inhalation anesthesia in general were selected. Primary outcomes included the occurrence of POCD at 1, 3, and 7 days. The secondary outcomes were the patient's plasma S-100ß protein levels (pg*mL-1) and delayed neurocognitive recovery incidence 5-7 days after surgery. Results: Fifteen studies including 3,817 patients were enrolled in the systematic review. Ten studies involving 1,829 patients were enrolled in the meta-analysis. The results demonstrate that there was no difference between the intravenous and inhalation groups in the incidence of POCD within 1-7 days (95% CI 0.73-1.26, p = 0.77) and the occurrence of delayed neurocognitive recovery 5-7 days after surgery (95% CI -353.15 to -295.44, p = 0.28). Plasma S-100ß protein levels in the intravenous anesthesia group were lower than those in the inhalation group (95% CI 0.48-1.24, p < 0.001). Conclusion: For elderly patients undergoing non-cardiac surgery, inhalation anesthesia was comparable to intravenous anesthesia in terms of the occurrence of short-term POCD. Inhalation anesthesia may cause greater damage to the nervous system, with delayed recovery of cognitive function after 5-7 days showing no difference. Systematic review: identifier (CRD42021251317).

Immune desert in MMR-deficient tumors predicts poor responsiveness of immune checkpoint inhibition.

Background: Although many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved. Materials and methods: Here, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS). Results: In both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition. Conclusion: Our findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.

A Real-Time Respiration Monitoring System Using WiFi Sensing Based on the Concentric Circle Model.

This paper proposes and experimentally validates a novel concentric circle (CC) model for indoor WiFi sensing. By setting the transmitter and receiver together, the perception model becomes concentric circles with equal spacing, eliminating the blind zone and unequal radial sensitivity problems of the Fresnel zone (FZ) model. Then a human respiratory monitoring system is developed based on this model, which executes the following steps: (1) Principal component analysis (PCA) is applied to the channel state information ratio (CSIR) as a preprocessing to extract the components related to human activities. (2) Human presence and respiratory signal detection are adopted to improve monitoring accuracy. (3) The Doppler respiratory frequency is extracted to calculate the respiratory rate. Experimental results show that the CC model achieves high accuracy in velocity measurement with an error of less than 0.4 cm/s. The respiration monitoring system can accurately monitor human respiration with an error of less than 0.7 bpm within 6 m.

Noninvasive prenatal screening in southeast China: clinical application and accuracy evaluation.

OBJECTIVE: To assess the clinical performance of noninvasive prenatal screening (NIPS) for both common trisomy and sex chromosome aneuploidy (SCA). METHODS: We recruited 71,888 pregnant women to undergo NIPS testing from December 2015 to June 2021. Demographic characteristics, diagnostic results, and follow-up outcomes were collected. RESULTS: There were a total of 381 high-risk cases for common trisomy and 343 positive screens for SCA. Invasive prenatal diagnosis (IPD) was performed in 507 (70.0%) participants. The positive predictive value (PPV) was 83.7% for T21, 72.5% for T18, 14.3% for T13, 31.9% for 45,X, 72.0% for 47,XXX, 89.8% for 47,XXY, and 72.2% for 47,XYY, respectively. Logistic regression analysis presented a significant association between Z-score and PPV in common trisomy (P < 0.05) while not in SCA (P > 0.05). PPV in the high-risk group (Z-score ≥ cutoff) was superior to that in the intermediate risk group (3 ≤ Z-score < cutoff) for T21/T18/T13. PPV for 45,X, 47,XXY, and 47,XYY tended to be higher with the increasing Z-score, except for 47,XXX. CONCLUSIONS: NIPS would be a valuable strategy in prenatal screening, while cautions should be kept in mind for subsequent genetic consulting about the risk of Z-score.

Comparison of immunohistochemistry and RT-qPCR for assessing ER, PR, HER2, and Ki67 and evaluating subtypes in patients with breast cancer.

PURPOSE: Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes. METHODS: A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results. RESULTS: The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR. CONCLUSION: Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer.

Treatment optimization for recurrent hepatoblastoma: retrospective study from a hepatoblastoma cohort in Southern China.

PURPOSE: The present study aimed to explore the clinical characteristics and optimal treatments of RHB patients. METHODS: We retrospectively collected 42 RHB cases and 161 primary HB (PHB) cases. Clinical characteristics were compared between RHB and PHB patients. The risk factors related to overall survival (OS) and progression-free survival (PFS) in RHB patients were explored by COX regression analysis. Patients were further divided into curable and refractory subgroup by treatments. Propensity score match (PSM) analysis was performed to match recurrent curable patients from 145 curable PHB patients from the same cohort. PFS was further compared between 34 pairs of primary and recurrent curative HB patients. RESULTS: Recurrence treatment and number of relapsed tumors were significantly related with both OS and PFS of RHB patients (p < 0.05). Chemotherapy regimen alteration was also risk factor of PFS for RHB (HR = 4.26; 95% CI = 1.54-11.78; p = 0.005). RHB patients underwent curable treatment had better prognosis, compared with recurrent refractory subgroup (p < 0.001). Matched curable PHB patients demonstrated no significant difference of 3-year PFS with curable RHB patients (p = 0.540). CONCLUSION: Curable RHB patients might get benefit from surgery or ablation with similar prognosis with primary curable HB patients.

The Impact of Entrepreneurship Competitions on Entrepreneurial Competence of Chinese College Students.

Entrepreneurship competitions are an important way to implement entrepreneurship education in universities and the main way for many students improve their entrepreneurial competence. To clarify the mechanism of the role of entrepreneurship competition on the entrepreneurial competence of university students, based on data from a sample of 170,764 university students from 31 provinces in China, this study constructs a moderated mediation model that focuses on the mediating role of entrepreneurial spirit (ES) in entrepreneurial competition (ECompetition) and entrepreneurial competence (ECompetence) and the moderating role of entrepreneurial practice (EP). The results showed that ECompetition found to have a significant positive predictive effect on ECompetence. ES plays a mediating role in the relationship between ECompetition and competence. The direct predictive effect of ECompetition on ECompetence and the mediating effect of ES on their relationship is moderated by EP. The results provide a new perspective on the impact of entrepreneurship competition on college students' entrepreneurial competence and expands the experiential learning theory in entrepreneurship education.

A whole-slide image (WSI)-based immunohistochemical feature prediction system improves the subtyping of lung cancer.

BACKGROUND: Clinically, accurate pathological diagnosis is often challenged by insufficient tissue amounts and the unaffordability of additional immunohistochemical or genetic tests; thus, there is an urgent need for a universal approach to improve the subtyping of lung cancer without the above limitations. Here we aimed to develop a deep learning system to predict the immunohistochemistry (IHC) phenotype directly from whole-slide images (WSIs) to improve the subtyping of lung cancer from surgical resection and biopsy specimens. METHODS: A total of 1914 patients with lung cancer from three independent hospitals in China were enrolled for WSI-based immunohistochemical feature prediction system (WIFPS) development and validation. RESULTS: The WIFPS could directly predict the IHC status of nine subtype-specific biomarkers, including CK7, TTF-1, Napsin A, CK5/6, P63, P40, CD56, Synaptophysin, and Chromogranin A, achieving average areas under the curve (AUCs) of 0.912, 0.906, and 0.888 and overall diagnostic accuracies of 0.925, 0.941, and 0.887 in the validation datasets of total, external surgical resection specimens and biopsy specimens, respectively. The histological subtyping performance of the WIFPS remained comparable with that of general pathologists (GPs), with Cohen's kappa values ranging from 0.7646 to 0.8282. Furthermore, the WIFPS could be trained to not only predict the IHC status of anaplastic lymphoma kinase (ALK), programmed death-1 (PD-1), and programmed death ligand 1 (PD-L1), but also predict EGFR and KRAS mutation status, with AUCs from 0.525 to 0.917, as detected in separate populations. CONCLUSIONS: In this study, the WIFPS showed its proficiency as a useful complement to traditional histologic subtyping for integrated immunohistochemical spectrum prediction as well as potential in the detection of gene mutations.

Entrepreneurship Education, Psychological Cognition, and Entrepreneurship Activities: An Analysis Based on a Fuzzy-Set Qualitative Comparative Analysis.

At present, research in the field of college students' entrepreneurship has proliferated, but these studies tend to analyze the net benefits of various factors on entrepreneurial activities, which are affected by the configuration effects of multiple factors; hence, it remains unclear whether entrepreneurial education can make graduates more efficient to started their own companies. To fill this gap in the literature, drawing on general systems theory and using fuzzy-set qualitative comparative analysis (fsQCA), we take 1,87,914 undergraduate and junior college students from 1,231 colleges and universities in China as a sample to explore the relationships among the five conditions in the entrepreneurship education environment and cognitive level (i.e., the quality of staff, subject curriculum, entrepreneurial competition, intentions, and opportunity identifications) and entrepreneurial activities. The fsQCA results show that none of these factors are sufficient for entrepreneurial activity. In contrast, three combinations of the five conditions (i.e., co-creation type, competition-oriented environment, and entrepreneurship education that fits under the guidance of entrepreneurial intention) can produce high entrepreneurial activity, as well as substitution and complementarity among the various elements within the configuration. These results show that the combined effect of the five conditions is more conducive to the entrepreneurial activities of college students. Finally, after a discussion of the study's findings, theoretical, and practical contributions are analyzed with regard to the field of entrepreneurship in Chinese colleges, and alternative options indicate that college students are more likely to become entrepreneurs in the future.

Design, synthesis and biological evaluation of combretastatin A-4 sulfamate derivatives as potential anti-cancer agents.

A series of combretastatin A-4 (CA-4) sulfamate derivatives were synthesized and their structure-activity relationship on tubulin, arylsulfatase and tumor cell antiproliferation inhibition was studied. Among them, compound 16a showed excellent potency as well as CA-4 under the same conditions against six tumor cells including HTC-116, HeLa, HepG2, MGC803, MKN45 and MCF-7 cells, respectively. Molecular docking revealed that several important hydrogen bond interactions were formed between the sulfamate group of 16a and the colchicine binding site of tubulin and steroid sulfatase respectively. Although compound 16a was less active than CA-4 in regard to its in vitro activity as an inhibitor of tubulin polymerization, it was effective as an inhibitor of arylsulfatase. This novel combretastatin A-4 sulfamate derivative has the potential to be developed as a dual inhibitor of tubulin polymerization and arylsulfatase for cancer therapy.

Ecust004 Suppresses Breast Cancer Cell Growth, Invasion, and Migration via EMT Regulation.

PURPOSE: Erianin is a small chemical compound extracted from Dendrobium chrysotoxum and has excellent antineoplastic effects against a variety of cancers. Combretastatin A-4 (CA4) is the most effective member of natural phenolic stilbene compounds isolated from the African willow tree Combretum caffrum. Ecust004 (Chemical Formula: C18H21NO7S) is a drug candidate optimized from structure-activity relationship studies of the sulfamate derivatives of Erianin and CA4, which has better bioavailability and pharmacokinetic profiles than Erianin and CA4. METHODS: To investigate the antitumor activity of Ecust004 in different types of breast cancer cells, MDA-MB-231 and MCF7 cells were treated with Ecust004. MTT and CCK8 were used to determine the effects of Ecust004 on cell proliferation. Wound-healing and Transwell assays were used to evaluate the migration and invasion level of cells treated with Ecust004. The expression of genes and proteins associated with epithelial-mesenchymal transition was detected by RT-PCR and Western blotting. In vivo studies further clarified the functional effects of Ecust004. RESULTS: Ecust004 treatment decreased the growth and proliferation of MDA-MB-231 and MCF7 cells at a lower dosage than Erianin. In addition, compared to Erianin and CA4, Ecust004 can better inhibit the invasion and migration of MDA-MB-231 and MCF7 cells. Accordingly, the expression of genes associated with epithelial-mesenchymal transition, such as E-cadherin and vinculin, was increased. Finally, compared with Erianin and CA4, Ecust004 exhibited a better anti-tumor activity in vivo. CONCLUSION: Ecust004 inhibits the proliferation, invasion, and migration of breast cancer cells, and therefore represents a potential agent for development as an antitumor drug.

How Entrepreneurship Education at Universities Influences Entrepreneurial Intention: Mediating Effect Based on Entrepreneurial Competence.

Research shows that entrepreneurial activities significantly promote economic development, which enhances the importance of the innovative entrepreneurial potential of college students. This study analyzes the effect of entrepreneurship education on entrepreneurial intention from the perspective of planned behavior theory. By examining the significant role of entrepreneurship education at colleges and universities on economic and social development, we established a conceptual model. To understand the relationship between entrepreneurship education and entrepreneurial intention, the hypotheses propose the intermediary role of entrepreneurial ability, and the study provides evidence from China the relationship between entrepreneurship education and entrepreneurial intention. Improving entrepreneurial intention and encouraging college students to establish businesses through entrepreneurship education in universities is crucial. This study proposes a hypothetical model of the relationship between entrepreneurial competence and entrepreneurial intention in entrepreneurship education at universities. Using a questionnaire survey of college students with practical experience in the Yangtze River Delta of China, the bootstrap method in the SPSS macro program process software verifies the hypotheses. The results show that entrepreneurial teaching, business plan competition, and entrepreneurial practice support positively affect entrepreneurial competence. In addition, entrepreneurial competence plays an intermediary role in the relationship between entrepreneurial teaching, business plan competition, entrepreneurship practice support, and entrepreneurial intention. Entrepreneurship education improves the ability to establish a business in the present and in entrepreneurial activities in the future. Entrepreneurial competence obtained through entrepreneurship education continuously affects entrepreneurial intention.

A Two-Step Phenotypic Parameter Measurement Strategy for Overlapped Grapes under Different Light Conditions.

Phenotypic characteristics of fruit particles, such as projection area, can reflect the growth status and physiological changes of grapes. However, complex backgrounds and overlaps always constrain accurate grape border recognition and detection of fruit particles. Therefore, this paper proposes a two-step phenotypic parameter measurement to calculate areas of overlapped grape particles. These two steps contain particle edge detection and contour fitting. For particle edge detection, an improved HED network is introduced. It makes full use of outputs of each convolutional layer, introduces Dice coefficients to original weighted cross-entropy loss function, and applies image pyramids to achieve multi-scale image edge detection. For contour fitting, an iterative least squares ellipse fitting and region growth algorithm is proposed to calculate the area of grapes. Experiments showed that in the edge detection step, compared with current prevalent methods including Canny, HED, and DeepEdge, the improved HED was able to extract the edges of detected fruit particles more clearly, accurately, and efficiently. It could also detect overlapping grape contours more completely. In the shape-fitting step, our method achieved an average error of 1.5% in grape area estimation. Therefore, this study provides convenient means and measures for extraction of grape phenotype characteristics and the grape growth law.

Deep learning-based six-type classifier for lung cancer and mimics from histopathological whole slide images: a retrospective study.

BACKGROUND: Targeted therapy and immunotherapy put forward higher demands for accurate lung cancer classification, as well as benign versus malignant disease discrimination. Digital whole slide images (WSIs) witnessed the transition from traditional histopathology to computational approaches, arousing a hype of deep learning methods for histopathological analysis. We aimed at exploring the potential of deep learning models in the identification of lung cancer subtypes and cancer mimics from WSIs. METHODS: We initially obtained 741 WSIs from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) for the deep learning model development, optimization, and verification. Additional 318 WSIs from SYSUFH, 212 from Shenzhen People's Hospital, and 422 from The Cancer Genome Atlas were further collected for multi-centre verification. EfficientNet-B5- and ResNet-50-based deep learning methods were developed and compared using the metrics of recall, precision, F1-score, and areas under the curve (AUCs). A threshold-based tumour-first aggregation approach was proposed and implemented for the label inferencing of WSIs with complex tissue components. Four pathologists of different levels from SYSUFH reviewed all the testing slides blindly, and the diagnosing results were used for quantitative comparisons with the best performing deep learning model. RESULTS: We developed the first deep learning-based six-type classifier for histopathological WSI classification of lung adenocarcinoma, lung squamous cell carcinoma, small cell lung carcinoma, pulmonary tuberculosis, organizing pneumonia, and normal lung. The EfficientNet-B5-based model outperformed ResNet-50 and was selected as the backbone in the classifier. Tested on 1067 slides from four cohorts of different medical centres, AUCs of 0.970, 0.918, 0.963, and 0.978 were achieved, respectively. The classifier achieved high consistence to the ground truth and attending pathologists with high intraclass correlation coefficients over 0.873. CONCLUSIONS: Multi-cohort testing demonstrated our six-type classifier achieved consistent and comparable performance to experienced pathologists and gained advantages over other existing computational methods. The visualization of prediction heatmap improved the model interpretability intuitively. The classifier with the threshold-based tumour-first label inferencing method exhibited excellent accuracy and feasibility in classifying lung cancers and confused nonneoplastic tissues, indicating that deep learning can resolve complex multi-class tissue classification that conforms to real-world histopathological scenarios.

Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice.

Farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has emerged as a potential therapy for nonalcoholic fatty liver disease (NAFLD). However, the side effects of OCA may limit its application in clinics. We identified previously that isotschimgine (ITG) is a non-steroidal FXR selective agonist and has potent therapeutic effects on NAFLD in mice. Here, we aimed to evaluate the therapeutic effects of ITG on nonalcoholic steatohepatitis (NASH) and fibrosis in mice. We used methionine and choline deficient (MCD) diet-induced NASH mice, bile duct ligation (BDL), and carbon tetrachloride (CCl4 )-treated hepatic fibrosis mice to investigate the effects of ITG on NASH, fibrosis, and cholestatic liver injury. Our results showed that ITG improved steatosis and inflammation in the liver of MCD diet-fed mice, as well as alleviated fibrosis and inflammation in the liver of CCl4 -treated mice. Furthermore, ITG attenuated serum bile acid levels, and reduced vacuolization, inflammatory infiltration, hepatic parenchymal necrosis, and collagen accumulation in the liver of BDL mice. Mechanistically, ITG increased the expression of FXR target genes. These data suggest that ITG is an FXR agonist and may be developed as a novel therapy for NASH, hepatic fibrosis, or primary biliary cholangitis.

FDG PET/CT Findings of Melanoma in a Renal Allograft.

Renal melanoma is rare. We present a case with FDG-avid melanoma arising from renal allograft. This case indicates that melanoma can occur in the allograft, and it should be considered as a differential diagnosis of focal abnormal FDG uptake in the renal allograft.

EFEMP1 as a Potential Biomarker for Diagnosis and Prognosis of Osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. Our previous study revealed an association between the level of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) and the invasion, metastasis, and poor prognosis of OS. However, the exact correlation between the serum EFEMP1 level and OS diagnosis and progression was unclear. This study is aimed at determining the value of the serum EFEMP1 level in the diagnosis and prognosis of OS. Fifty-one consecutive OS patients were prospectively registered in this study. The serum EFEMP1 levels were measured using ELISA at diagnosis, after neoadjuvant chemotherapy, and before and after surgical treatment. Sixty-nine healthy subjects in the control group, nine patients with chondrosarcoma, and 12 patients with giant cell tumor of the bone were also enrolled in this study. Surgical orthotopic implantation was used to generate a mouse OS model, and the correlation between the circulating EFEMP1 levels and tumor progression was examined. Then, OS patients had significantly higher mean serum EFEMP1 levels (7.61 ng/ml) than the control subjects (1.47 ng/ml). The serum EFEMP1 levels were correlated with the Enneking staging system (r = 0.32, P = 0.021) and lung metastasis (r = 0.50, P < 0.001). There was also a correlation between the serum EFEMP1 level and EFEMP1 expression in the respective OS samples (r = 0.49, P < 0.001). Additionally, patients with either chondrosarcoma or giant cell tumor of the bone had significantly higher serum EFEMP1 levels than OS patients. Surgical and chemotherapeutic treatment led to an increase in the serum EFEMP1 levels. Then, the destruction of bone tissues might be one of the factors about the EFEMP1 levels. In the mouse OS model, the serum EFEMP1 level was correlated with tumor progression. Our results suggested that serum EFEMP1 levels might be used to distinguish OS patients from healthy controls and as an indicator for OS lung metastasis. Serum EFEMP1 levels could serve as a new and assisted biomarker for the auxiliary diagnosis and prognosis of OS.