Feasibility of two-step approach for screening NTRK fusion in two major subtypes of non-small cell lung cancer within a large cohort.

Our objective is to investigate a cost-effective approach to screen for NTRK fusion in the major subtypes of non-small cell lung cancer (NSCLC). Evaluate the concordance between immunohistochemistry (IHC) and next-generation sequencing (NGS), as well as between fluorescence in situ hybridization (FISH) and NGS, to detect any discrepancies in methodological consistency between lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). Analyze the factors influencing IHC results. A cohort of 1654 patients with NSCLC underwent screening for NTRK fusion using whole slide IHC. The positive cases were analyzed by both FISH and NGS. Totally, 57 tested positive for pan-TRK, with positivity rates of 0.68% (10/1467) for LADC and 29.01% (47/162) for LSCC. FISH showed separate NTRK1 and NTRK3 rearrangements in two pan-TRK-positive LADCs, while all LSCCs tested negative. NGS confirmed functional NTRK fusion in two FISH-positive cases: one involving TPM3-NTRK1 and the other involving SQSTM1-NTRK3. A non-functional fusion of NTRK2-XRCC1 was detected in LSCC, while FISH was negative. According to our approach, the prevalence of NTRK fusion in NSCLC is 0.12%. The concordance rate between IHC and RNA-based NGS was 20% (2/10) in LADC and 0% (0/162) in LSCC. When the positive criteria increased over 50% of tumor cells showing strong staining, the concordance would be 100% (2/2). A concordance rate of 100% (2/2) was observed between FISH and RNA-based NGS in LADC. The expression of pan-TRK was significantly correlated with the tumor proportion score (TPS) of PD-L1 (p < 0.05) and transcript per million (TPM) values of NTRK2 (p < 0.05). We recommend using IHC with strict criteria to screen NTRK fusion in LADC rather than LSCC, confirmed by RNA-based NGS directly. When the NGS results are inconclusive, FISH validation is necessary.

Eosinophil Recovery Time Is Associated with Clinical Outcomes in Patients with Type A Acute Aortic Dissection: a Retrospective Cohort Study.

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD.Clinical trial registration number: NCT05409677.

Autophagic-lysosomal damage induced by swainsonine is protected by trehalose through activation of TFEB-regulated pathway in renal tubular epithelial cells.

Swainsonine (SW) is the main toxic component of locoweed. Previous studies have shown that kidney damage is an early pathologic change in locoweed poisoning in animals. Trehalose induces autophagy and alleviates lysosomal damage, while its protective effect and mechanism against the toxic injury induced by SW is not clear. Based on the published literature, we hypothesize that transcription factor EB(TFEB) -regulated is targeted by SW and activating TFEB by trehalose would reverse the toxic effects. In this study, we investigate the mechanism of protective effects of trehalose using renal tubular epithelial cells. The results showed that SW induced an increase in the expression level of microtubule-associated protein light chain 3-II and p62 proteins and a decrease in the expression level of ATPase H+ transporting V1 Subunit A, Cathepsin B, Cathepsin D, lysosome-associated membrane protein 2 and TFEB proteins in renal tubular epithelial cells in a time and dose-dependent manner suggesting TFEB-regulated lysosomal pathway is adversely affected by SW. Conversely, treatment with trehalose, a known activator of TFEB promote TFEB nuclear translocation suggesting that TFEB plays an important role in protection against SW toxicity. We demonstrated in lysosome staining that SW reduced the number of lysosomes and increased the luminal pH, while trehalose could counteract these SW-induced effects. In summary, our results demonstrated for the first time that trehalose could alleviate the autophagy degradation disorder and lysosomal damage induced by SW. Our results provide an interesting method for reversion of SW-induced toxicity in farm animals and furthermore, activation of TFEB by trehalose suggesting novel mechanism of treating lysosomal storage diseases.

Ezrin's role in gastric cancer progression: Implications for immune microenvironment modulation and therapeutic potential.

At present, surgical resection is the most effective method for the treatment of gastric cancer. However, death caused by inoperable metastasis is still very common, despite research in this area. The mechanisms underlying the occurrence, development, and metastasis of gastric cancer are not fully understood. Ezrin, a plasma membrane-microfilament junction participates in a variety of cellular activities and is closely related to tumorigenesis and development. Few studies have explored the relationship between the tumor immune microenvironment and ezrin expression in gastric cancer. In this study, we used proteomic techniques to analyze the differentially expressed proteins between the gastric cancer cell lines MKN-45 and HGC-27 and screened ezrin as the target protein. We collected patient information from The TCGA and GEO databases, and the results showed that ezrin was positively correlated with adverse clinical features. We further explored the relationship between ezrin expression levels, immune microenvironment, and genomic changes. We found that ezrin was involved in immune regulation and genomic instability in gastric cancer. When the expression of ezrin is high, immune cell infiltration also increases. We also predicted that ezrin is closely related to immunotherapy and chemosensitivity. Single-cell transcriptome data showed that the ezrin gene was mainly expressed in B cells and epithelial cells, and the expression of EZR in these epithelial cells was positively correlated with the epithelial-mesenchymal transformation pathway and Pi3k-AKT pathway score. Through functional verification of the stably transfected cell line constructed by lentivirus, the results of the liver metastasis model in nude mice suggested that high expression of ezrin leads to the formation of more metastatic foci. In summary, our results clarify the prognostic, immunological, and therapeutic value of ezrin in gastric cancer and provide a theoretical basis for more accurate treatment.

Microwave hydrothermal sulfuric acid leaching of spent cathode carbon from aluminum electrolysis for high efficiency removal of insoluble calcium fluoride.

Toxic substances, like fluoride salts present in spent cathode carbon (SCC), have been a great risk to the environment and public health. Our approach involves alkali leaching to eliminate soluble fluoride, followed by microwave hydrothermal acid leaching to efficiently remove insoluble CaF2 from SCC. The optimized conditions, including a temperature of 353 K, a solid-liquid ratio of 1:20, and a 60-minute reaction time, resulted in an impressive 95.6 % removal of fluoride from SCC. Various characterization techniques were employed to analyze the composition, micro-morphology, and elemental content of the materials before and after the leaching process. Furthermore, critical process parameters on the leaching separation of insoluble CaF2 during microwave hydrothermal acid leaching were systematically investigated. The study removal mechanism revealed the transformation of insoluble CaF2 in the process of microwave oxidation insertion-hydrothermal acid leaching for SCC. The kinetic characteristics of the two-stage leaching process of CaF2 at different temperatures were analyzed according to the shrinkage kernel model. The results indicate that the two-stage leaching process of CaF2 is affected by mixing control and by diffusion control, severally. The expansion of the graphite flake layer of SCC through oxidative intercalation was identified as a critical process for the thorough removal of CaF2. Microwave hydrothermal acid leaching demonstrated a 17 % improvement over traditional hydrothermal acid leaching within the same reaction time, showcasing a noteworthy enhancement in fluoride removal. Consequently, the microwave oxidizing intercalation-hydrothermal acid leaching treatment of SCC, as explored in this study, offers an effective approach for achieving deep defluoridation of SCC.

Heterogeneity of molecular subtyping and therapy-related marker expression in primary tumors and paired lymph node metastases of small cell lung cancer.

The classification of molecular subtypes and the identification of targetable molecules have been proposed for small cell lung cancer (SCLC) patients. Our aim was to investigate whether the expression of these markers evaluated using lymph node (LN) metastases represents that of primary tumors. We enrolled 46 surgically resected SCLC patients' primary tumors and paired mediastinal LN metastases. The protein expression of subtype-defining markers (ASCL1, NEUROD1, POU2F3, and YAP1) and therapeutic markers (DLL3, MYC, PD-L1, and MHC I) was examined by immunohistochemistry and was correlated with clinicopathological parameters and prognoses. In primary and metastatic tumors, the expression of these markers was 78.3% and 87.0%, 50.0% and 63.0%, 13.0% and 6.5%, 17.4% and 15.2%, 84.8% and 87.0%, 17.4% and 6.5%, 50.0% and 34.8%, and 60.9% and 37.0%, respectively. Positive tumor PD-L1 expression was less present in LN metastases (p = 0.015), and the same was true for MHC I expression (p = 0.036). NEUROD1 and DLL3 expression levels in metastatic tumors were stronger (p < 0.001 and p = 0.002, respectively); conversely, POU2F3, MYC, PD-L1, and MHC I expression levels were weaker (p = 0.018, p = 0.019, p = 0.001, and p < 0.001, respectively). In 15 (32.6%) patients, we observed a change in the molecular subtyping pattern, and a higher number of neuroendocrine (NE)-high phenotype patients were diagnosed when using the LN specimens (91.3% vs. 84.8%). TNM stage and postoperative chemotherapy were independent prognostic factors in surgically resected SCLC patients, and no prognostic differences were found among molecular subtypes. This study highlights the discordance of subtype-specific proteins and therapeutic markers between SCLC primary tumors and LN metastases. Additionally, our findings have therapeutic and prognostic implications and warrant further clinical investigation.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1ß, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

Discovery and optimization of dihydropteridone derivatives as novel PLK1 and BRD4 dual inhibitor for the treatment of cancer.

In this study, we have designed, synthesized and tested three series of novel dihydropteridone derivatives possessing isoindolin-1-one or isoindoline moieties as potent inhibitors of PLK1/BRD4. Remarkably, most of the compounds showed preferable inhibitory activity against PLK1 and BRD4. Compound SC10 exhibited excellent inhibitory activity with IC50 values of 0.3 nM and 60.8 nM against PLK1 and BRD4, respectively. Meanwhile, it demonstrated significant anti-proliferative activities against three tumor-derived cell lines (MDA-MB-231 IC50 = 17.3 nM, MDA-MB-361 IC50 = 8.4 nM, and MV4-11 IC50 = 5.4 nM). Moreover, SC10 exhibited moderate rat liver microsomal stability (CLint = 21.3 µL·min-1·mg-1), acceptable pharmacokinetic profile (AUC0-t = 657 ng·h·mL-1, oral bioavailability of 21.4 %) in Sprague-Dawley rats, reduced hERG toxicity, acceptable PPB and CYP450 inhibition. Further research indicated that SC10 could induce MV4-11 cell arrest at the S phase and apoptosis in a dose-dependent manner. This investigation provided us with an initial point for developing novel anticancer agents as dual inhibitors of PLK1 and BRD4.

Histopathology images-based deep learning prediction of prognosis and therapeutic response in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer characterized by rapid tumor growth and early metastasis. Accurate prediction of prognosis and therapeutic response is crucial for optimizing treatment strategies and improving patient outcomes. In this study, we conducted a deep-learning analysis of Hematoxylin and Eosin (H&E) stained histopathological images using contrastive clustering and identified 50 intricate histomorphological phenotype clusters (HPCs) as pathomic features. We identified two of 50 HPCs with significant prognostic value and then integrated them into a pathomics signature (PathoSig) using the Cox regression model. PathoSig showed significant risk stratification for overall survival and disease-free survival and successfully identified patients who may benefit from postoperative or preoperative chemoradiotherapy. The predictive power of PathoSig was validated in independent multicenter cohorts. Furthermore, PathoSig can provide comprehensive prognostic information beyond the current TNM staging system and molecular subtyping. Overall, our study highlights the significant potential of utilizing histopathology images-based deep learning in improving prognostic predictions and evaluating therapeutic response in SCLC. PathoSig represents an effective tool that aids clinicians in making informed decisions and selecting personalized treatment strategies for SCLC patients.

Clonality Analysis for the Relationship between the Pulmonary Combined Neuroendocrine Carcinoma and "the So-Called Reported Histologic Transformation".

Histologic transformation (HT) is common following targeted therapy in adenocarcinoma. However, whether the transformed tumor is a new component or a combined neuroendocrine carcinoma (C-NEC) remains controversial. We aimed to explore the relationship between pulmonary C-NEC and HT. Macro-dissection was performed on different components of surgically resected C-NEC samples. Molecular alterations and clonal evolution were analyzed using whole exome sequencing (WES). The gene statuses for TP53 and RB1 were determined using immunohistochemistry (IHC) and WES to analyze the relationship between C-NEC and reported HT. Sixteen combined small-cell lung cancer patients and five combined large-cell neuroendocrine carcinoma patients were enrolled. The frequency of p53 and Rb inactivation, assessed using IHC in NEC and non-NEC components, was 76.2/76.2% and 66.7/61.9%, respectively. The expression consistency between the components was 81.0 and 85.7% for p53 and Rb, respectively. The frequencies of TP53, RB1, and EGFR mutations, assessed using WES in NEC and non-NEC components, were 81.0/81.0%, 28.6/28.6%, and 42.9/42.9%, respectively. The concordance rates for TP53, RB1, and EGFR were 90.5, 71.4, and 90.5%, respectively. The consistency rate between IHC and WES was 81.0 and 61.9% for TP53 and RB1, respectively. The different components had a common clonal origin for the 21 C-NECs in the clonal analysis, consistent with previous studies on HT. Our study shows that IHC is more sensitive for Rb detection and C-NEC, and the reported HT may be due to differences in evaluations between pathologist and clinicians. Assessing the p53/Rb and EGFR status for such cases would help in recognizing potential transformation cases or uncovering potential combined components.

Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.

Lipid metabolic diseases have substantial morbidity and mortality rates, posing a significant threat to human health. PPARα, a member of the peroxisome proliferator-activated receptors (PPARs), plays a crucial role in lipid metabolism and immune regulation. Recent studies have increasingly recognized the pivotal involvement of PPARα in diverse pathological conditions. This comprehensive review aims to elucidate the multifaceted role of PPARα in metabolic diseases including liver diseases, diabetes-related diseases, age-related diseases, and cancers, shedding light on the underlying molecular mechanisms and some regulatory effects of natural/synthetic ligands of PPARα. By summarizing the latest research findings on PPARα, we aim to provide a foundation for the possible therapeutic exploitation of PPARα in lipid metabolic diseases.

[The clinical value of recurrent laryngeal nerve dissection in the surgical treatment for congenital pyriform sinus fistula].

Objective:To explore the clinical value of recurrent laryngeal nerve dissection in the surgical treatment for congenital pyriform sinus fistula（CPSF）. Methods:The clinical data of 42 patients with CPSF were retrospectively analyzed. All patients were diagnosed and treated in the First Affiliated Hospital of Guangdong Pharmaceutical University. Results:During the operation, all patients' recurrent laryngeal nerves were dissected successfully, and fistulas were resected completely,no patients had complication of recurrent laryngeal nerve's damage.There were no recurrence cases during the 13 to 48 months of follow-up. Conclusion:The trend of congenital pyriform sinus fistula is closely related to recurrent laryngeal nerve, it's important to dissect the recurrent laryngeal nerve during the operation for congenital pyriform sinus fistula.

Exploring the molecular features and genetic prognostic factors of pulmonary high-grade neuroendocrine carcinomas.

Molecular research on large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) has progressed significantly. However, there are still fewer molecular markers related to prognostic/therapeutic strategies for these conditions compared to those for adenocarcinoma. We therefore investigated the molecular characteristics of neuroendocrine carcinomas (NECs). We enrolled patients surgically diagnosed with NECs between 2011 and 2019, with complete follow-up records. All were analyzed using whole exome sequencing and p53/Rb immunohistochemistry (IHC). A total of 92 cases, comprising 45 pure SCLC, 15 combined SCLC, 27 pure LCNEC, and 5 combined LCNEC, were included. TP53 (78.3%) and RB1 (34.8%) were the most common molecular alterations, followed by KMT2D, LRP1B, FAT3, NCOR2, SPTA1, and NOTCH1. The mutation frequency for EGFR was 10.9%. Sixteen patients with LCNEC who had TP53/RB1 co-alterations were SCLC-like, while the remaining were NSCLC-like. There was no statistically significant difference between the groups regarding overall survival (OS; p = 0.458) and progression-free survival (PFS; p = 0.157). The frequency of the loss of Rb expression by IHC in SCLC-like LCNEC was 100%. Significant pathway alterations unique to SCLC included Notch and AMPK, while HIF-1 was enriched exclusively in LCNEC. NCOR2 mutation was linked to worse OS (p = 0.029) and PFS (p = 0.015), while wild-type SPTA1 was associated with poor PFS (p = 0.018). IHC for Rb was reliable for predicting LCNEC molecular subtypes, indicating its clinical value. NCOR2 and SPTA1 alterations were identified as prognostic factors that may provide therapeutic targets for patients with NEC.

Molecular subtypes, predictive markers and prognosis in small-cell lung carcinoma.

AIMS: A new molecular subtype classification was proposed for small-cell lung carcinoma (SCLC). We aimed to further validate the classification in various SCLC patient samples using immunohistochemistry (IHC) to highlight its clinical significance. METHODS: We analysed the protein expression of four subtype (achaete-scute family BHLH transcription factor 1 (ASCL1), neuronal differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3) and Yes1-associated transcriptional regulator (YAP1)) and two predictive markers (delta-like ligand 3 (DLL3) and MYC) using IHC in 216 specimens from 195 SCLC patients, including 21 pairs of resected biopsy tumours. Associations among molecular subtypes, clinicopathological features and prognostic implications were also explored. RESULTS: The ASCL1, NEUROD1, POU2F3, YAP1, DLL3 and MYC-positive expression rates were 70.3%, 56.9%, 14.9%, 19.0%, 75.4% and 22.6%, respectively. DLL3 expression had positive and negative associations with that of ASCL1 and POU2F3/YAP1, respectively, whereas MYC had the opposite effect. Strong associations of ASCL1 (Ρ=0.8603, p<0.0001), NEUROD1 (Ρ=0.8326, p<0.0001), POU2F3 (Ρ=0.6950, p<0.0001) and YAP1 (Ρ=0.7466, p<0.0001) expressions were detected between paired resected biopsy tumours. In addition to SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), unsupervised hierarchical cluster analyses identified a fourth, quadruple-negative SCLC subtype (SCLC-QN) characterised by the low expression of all four subtype-specific proteins, and 55.4% (n=108), 27.2% (n=53), 11.8% (n=23) and 5.6% (n=11) were categorised as SCLC-A, SCLC-N, SCLC-P and SCLC-QN, respectively. Significant enrichment of SCLC-P in the combined SCLC cohort was observed, and adenocarcinoma was more prevalent in SCLC-A, while large-cell neuroendocrine carcinoma was more commonly seen in SCLC-P. No survival difference was found among molecular subtypes. CONCLUSIONS: Our results provide clinical insights into the diagnostic, prognostic and predictive significance of SCLC molecular subtype classifications.

Design and Synthesis of 1,3,5-Triazines or Pyrimidines Containing Dithiocarbamate Moiety as PI3Kα Selective Inhibitors.

Recent studies have shown that phosphoinositide 3-kinase (PI3K) plays a vital role in cell division, and it has become a therapeutic target for many cancers. In this paper, some new 1,3,5-triazine or pyrimidine skeleton derivatives containing dithiocarbamate were designed and synthesized based on the reasonable drug design strategy from the previously effective compound 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK-474), in order to get effective selective PI3Kα inhibitors that have not been reported in the literature. In addition, the inhibitory activities of these compounds on PI3Kα and two tumor cell lines in vitro (HCT-116, U87-MG) were evaluated. The representative compound 13 showed a half-maximal inhibitory concentration (IC50) value of 1.2 nM for PI3Kα and an exciting kinase selectivity. Compound 13 displayed strong efficacy in HCT-116 and U87-MG cell lines with IC50 values of 0.83 and 1.25 µM, respectively. In addition, compound 13 induced obvious tumor regression in the U87-MG cell line xenografts mouse model, with no obvious signs of toxicity after intraperitoneal injection at a dose of 40 mg/kg. Compound 13 can be an effective selective inhibitor of PI3Kα, and it provides patients with an opportunity to avoid the side effects related to the wider inhibition of the class I PI3K family.

Molecular subtype expression and genomic profiling differ between surgically resected pure and combined small cell lung carcinoma.

A new molecular subtype classification method has been proposed for small cell lung carcinoma (SCLC). However, little is known about the differences between the pure (P-SCLC) and combined subtypes (C-SCLC). We aimed to compare the molecular subtype expression and genomic profiling in terms of clinical relevance between the two groups. 154 surgically resected SCLCs were analyzed for protein expression of four subtypes (ASCL1, NEUROD1, POU2F3, and YAP1) and two predictive markers (DLL3 and MYC) by immunohistochemistry (IHC). We also performed whole exome sequencing of 60 samples to examine genomic profiles. A total of 113 patients with P-SCLC and 41 with C-SCLC were included. In P-SCLC and C-SCLC, the expression of these markers was 78.8% and 41.5%, 98.2% and 97.6%, 42.5% and 51.2%, 38.9% and 85.4%, 85.0% and 68.3%, and 24.8% and 34.1%, respectively. ASCL1 and DLL3 were highly expressed in P-SCLC (p = 0.000 and p = 0.021, respectively), and YAP1 expression was significantly enriched in C-SCLC (p = 0.000). NGS results, including 45 P-SCLCs and 15 C-SCLCs, indicated that EGFR gene mutations were mostly observed in C-SCLCs (p = 0.000). C-SCLC showed higher CNA burden and wGII than P-SCLC (p < 0.01 and p < 0.05); conversely, P-SCLC had higher TMB burden and SDI (p < 0.05 and p < 0.05). YAP1 expression was associated with poor prognosis in P-SCLC but with favorable prognosis in C-SCLC. P-SCLC and C-SCLC are heterogeneous diseases characterized by different molecular subtype expressions and genomic profiles. Our data provide a basis for adopting histological subtype-based treatments, and further prospective studies are required to confirm our conclusions.

Deep learning prediction model for central lymph node metastasis in papillary thyroid microcarcinoma based on cytology.

Controversy exists regarding whether patients with low-risk papillary thyroid microcarcinoma (PTMC) should undergo surgery or active surveillance; the inaccuracy of the preoperative clinical lymph node status assessment is one of the primary factors contributing to the controversy. It is imperative to accurately predict the lymph node status of PTMC before surgery. We selected 208 preoperative fine-needle aspiration (FNA) liquid-based preparations of PTMC as our research objects; all of these instances underwent lymph node dissection and, aside from lymph node status, were consistent with low-risk PTMC. We separated them into two groups according to whether the postoperative pathology showed central lymph node metastases. The deep learning model was expected to predict, based on the preoperative thyroid FNA liquid-based preparation, whether PTMC was accompanied by central lymph node metastases. Our deep learning model attained a sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and accuracy of 78.9% (15/19), 73.9% (17/23), 71.4% (15/21), 81.0% (17/21), and 76.2% (32/42), respectively. The area under the receiver operating characteristic curve (value was 0.8503. The predictive performance of the deep learning model was superior to that of the traditional clinical evaluation, and further analysis revealed the cell morphologies that played key roles in model prediction. Our study suggests that the deep learning model based on preoperative thyroid FNA liquid-based preparation is a reliable strategy for predicting central lymph node metastases in thyroid micropapillary carcinoma, and its performance surpasses that of traditional clinical examination.

Prognostic values of long noncoding RNA in bone metastasis of prostate cancer: A systematic review and meta-analysis.

Introduction: Recent studies have shown that long non-coding RNAs are closely related to the occurrence and development of prostate cancer bone metastasis, and can be used as biomarkers to predict the prognosis of patients. Therefore, this study aimed to systematically evaluate the relationship between the expression levels of long non-coding RNAs and the prognosis of patients. Methods: The studies of lncRNA in prostate cancer bone metastasis from Pubmed, Cochrane library, Embase, Ebsco, Web of science, Scopus, Ovid databases were analyzed, and Stata 15 was used for meta-analysis. Associations between lncRNA expression and patients' overall survival (OS) and bone metastasis-free survival (BMFS) were assessed by correlation analysis with pooled hazard ratios (HR) and 95% confidence intervals (CI). Furthermore, the results were validated using GEPIA2 and UALCAN, online database based on TCGA. Subsequently, the molecular mechanisms of the included lncRNAs were predicted based on the LncACTdb 3.0 database and the lnCAR database. Finally, we used clinical samples to validate lncRNAs that were significantly different in both databases. Results: A total of 5 published studies involving 474 patients were included in this meta-analysis. The results showed that lncRNA overexpression was significantly associated with lower OS (HR = 2.55, 95% CI: 1.69 - 3.99, p < 0.05) and lower BMFS (OR = 3.16, 95% CI: 1.90 - 5.27, p < 0.05) in patients with prostate cancer bone metastasis. Based on validation from the GEPIA2 and UALCAN online databases, SNHG3 and NEAT1 were significantly up-regulated in prostate cancer. Further functional prediction showed that the lncRNAs included in the study were involved in regulating the occurrence and development of prostate cancer through the ceRNA axis. The result of clinical samples showed that SNHG3 and NEAT1 were expressed in prostate cancer bone metastasis at higher levels than in primary tumors. Conclusions: LncRNA can be used as a novel predictive biomarker for predicting poor prognosis in patients with prostate cancer bone metastasis, which is worthy of clinical validation.

Nickel-promoted Electrocatalytic Graphitization of Biochars for Energy Storage: Mechanistic Understanding using Multi-scale Approaches.

Owing to high-efficiency and scalable advantages of electrolysis in molten salts, electrochemical conversion of carbonaceous resources into graphitic products is a sustainable route for achieving high value-added carbon. To understand the complicated kinetics of converting amorphous carbon (e.g. carbonized lignin-biochar) into highly graphitic carbon, herein this study reports the key processing parameters (addition of Ni, temperature and time) and multi-scale approach of nickel-boosted electrochemical graphitization-catalysis processes in molten calcium chloride. Upon both experiments and modellings, multi-scale analysis that ranges from nanoscale atomic reaction to macroscale cell reveal the multi-field evolution in the electrolysis cell, mechanism of electrochemical reaction kinetics as well as pathway of nickel-boosted graphitization and tubulization. The results of as-achieved controllable processing regions and multi-scale approaches provide a rational strategy of manipulating electrochemical graphitization processes and utilizing the converted biomass resources for high value-added use.

Deep Learning-Based Classification and Targeted Gene Alteration Prediction from Pleural Effusion Cell Block Whole-Slide Images.

Cytopathological examination is one of the main examinations for pleural effusion, and especially for many patients with advanced cancer, pleural effusion is the only accessible specimen for establishing a pathological diagnosis. The lack of cytopathologists and the high cost of gene detection present opportunities for the application of deep learning. In this retrospective analysis, data representing 1321 consecutive cases of pleural effusion were collected. We trained and evaluated our deep learning model based on several tasks, including the diagnosis of benign and malignant pleural effusion, the identification of the primary location of common metastatic cancer from pleural effusion, and the prediction of genetic alterations associated with targeted therapy. We achieved good results in identifying benign and malignant pleural effusions (0.932 AUC (area under the ROC curve)) and the primary location of common metastatic cancer (0.910 AUC). In addition, we analyzed ten genes related to targeted therapy in specimens and used them to train the model regarding four alteration statuses, which also yielded reasonable results (0.869 AUC for ALK fusion, 0.804 AUC for KRAS mutation, 0.644 AUC for EGFR mutation and 0.774 AUC for NONE alteration). Our research shows the feasibility and benefits of deep learning to assist in cytopathological diagnosis in clinical settings.