Treatment of lung cancer by acupuncture combined with medicine based on pathophysiological mechanism: A review.

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.

The impact of support electronegativity on the electrochemical properties of platinum.

Modulating the electronic structure of platinum (Pt) through a support is an important strategy for enhancing its electrocatalytic properties. In this work, to explore the impact of support electronegativity on Pt's catalytic activity for hydrogen evolution, we chose diverse metals with varying electronegativities that are stable in acidic solutions, such as titanium (Ti), molybdenum (Mo), and tungsten (W), as supports. Ti is the optimal support according to density functional theory (DFT) calculations. As expected, the Pt@Ti catalyst demonstrated remarkable efficiency in the hydrogen evolution reaction (HER), displaying a minimal overpotential of 13 mV at -10 mA cm-2, a Tafel slope of 34.5 mV dec-1, and sustained durability over 110 h in a 0.5 M H2SO4 solution. To unravel the metal-support interaction (MSI) between Pt and Ti, a comprehensive exploration encompassing both experimental investigations and DFT calculations was undertaken. The results elucidate that the outstanding HER performance of Pt@Ti stems from robust synergies forged between Pt and Ti atoms within the Ti support. This work not only furnishes a technique for producing electrocatalysts with superior efficiency and stability but also streamlines the process of choosing the most appropriate metal support. Moreover, it enhances comprehension of the interaction between Pt and the metal support.

Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.

BACKGROUND: The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. METHODS: We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. RESULTS: Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. CONCLUSION: Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.

Formononetin, a bioactive isoflavonoid constituent from Astragalus membranaceus (Fisch.) Bunge, ameliorates type 1 diabetes mellitus via activation of Keap1/Nrf2 signaling pathway: An integrated study supported by network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Type 1 diabetes mellitus (T1DM) results from insulin deficiency due to the destruction of pancreatic ß-cells. Previously, our studies showed that inhibition of Keap1/Nrf2 signaling pathway promoted the onset of T1DM, which suggests that finding drugs that can activate the Keap1/Nrf2 signaling may be a promising therapeutic strategy for the T1DM treatment. Astragalus membranaceus (Fisch.) Bunge is a common traditional Chinese medicine that has been frequently applied in Chinese clinics for the treatment of diabetes and other diseases. Formononetin (FMNT), one of the major isoflavonoid constituents isolated from this herbal medicine, possesses diverse pharmacological benefits and T1DM therapeutic potential. However, the exact molecular mechanisms underlying the action of FMNT in ameliorating T1DM have yet to be fully elucidated. AIMS OF THE STUDY: This study is to investigate the regulation of FMNT on the Keap1/Nrf2 signaling pathway to ameliorate T1DM based on network pharmacology approach combined with experimental validation. MATERIALS AND METHODS: A mouse-derived pancreatic islet ß-cell line (MIN6) was used for the in vitro studies. An alloxan (ALX)-induced T1DM model in wild-type and Nrf2 knockout (Nrf2-/-) C57BL/6J mice were established for the in vivo experiments. The protective effects of FMNT against ALX-stimulated MIN6 cell injury were evaluated using MTT, EdU, apoptosis and comet assays. The levels of blood glucose in mice were measured by using a blood monitor and test strips. The protein expression was detected by Western blot analysis. Furthermore, the binding affinity of FMNT to Keap1 was evaluated using cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and solvent-induced protein precipitation (SIP) assay. The interaction pattern between FMNT and Keap1 was assessed by molecular docking and molecular dynamics simulation techniques. RESULTS: Network pharmacology analysis revealed that FMNT exerted its therapeutic effect against T1DM by mainly regulating oxidative stress response-associated signaling molecules and pathways, such as Nrf2 regulating anti-oxidant/detoxification enzymes and Keap1-Nrf2 signaling pathway. The in vivo results showed that FMNT significantly deceased the ALX-induced high blood glucose levels and conversely increased the ALX-induced low insulin contents. In vitro, FMNT markedly protected MIN6 cells from ALX-induced cytotoxicity, proliferation inhibition and DNA damage and reduced the ALX-stimulated cell apoptosis. FMNT also inhibited ALX-induced overproduction of intracellular ROS to alleviate oxidative stress. In addition, FMNT could bind to Keap1 to notably activate the Keap1/Nrf2 signaling to upregulate Nrf2 expression and promote the Nrf2 translocation from the cytoplasm to the nucleus, resulting in enhancing the expression of antioxidant proteins HO-1 and NQO1. Inhibition of Keap1/Nrf2 signaling by ALX was also markedly abolished in the cells and mice exposed to FMNT. Moreover, these effects of FMNT in ameliorating T1DM were not observed in Nrf2-/- mice. CONCLUSIONS: This study demonstrates that FMNT could bind to Keap1 to activate the Keap1/Nrf2 signaling to prevent intracellular ROS overproduction, thereby attenuating ALX-induced MIN6 cell injury and ameliorating ALX-stimulated T1DM. Results from this study might provide evidence and new insight into the therapeutic effect of FMNT and indicate that FMNT is a promising candidate agent for the treatment of T1DM in clinics.

Enhanced ability of toluene oxidation by controlling inversion degree of spinel composed of only Co, Mn.

Exploring the single relationship between the inversion degree of spinel and its catalytic performance is a great challenge, but has important significance for further structural design and application. A series of CoMn inverse spinels were prepared and the general formula [Formula: see text] was deduced through X-ray diffraction refinement to find a decreased inversion degree x as calcination temperature rose. Catalytic oxidation of toluene showed that higher inversion degree (S-300 with x ≈ 0.95) can reach larger conversion rate (90 % at about 250 °C for 400 ppm toluene) with greater reaction stability (140 h). Density Functional Theory (DFT) calculations on density of states indicated its metallic nature, and found that the strength of O-p and Transition metal-d orbitals at Fermi energy is positively correlated to the inversion degree, meaning stronger electron migration ability. Along with the adsorption calculation analysis that lattice oxygen species are proved to work dominantly (S-300 with lowest adsorption energy but highest performance), this work uncovered a theoretical insight into inverse spinel oxide, to provide the possibility of elevated oxidation ability through structural control.

Artificial intelligence versus radiologist in the accuracy of fracture detection based on computed tomography images: a multi-dimensional, multi-region analysis.

Background: Extremities fractures are a leading cause of death and disability, especially in the elderly. Avulsion fracture are also the most commonly missed diagnosis, and delayed diagnosis leads to higher litigation rates. Therefore, this study evaluates the diagnostic efficiency of the artificial intelligence (AI) model before and after optimization based on computed tomography (CT) images and then compares it with that of radiologists, especially for avulsion fractures. Methods: The digital X-ray photography [digital radiography (DR)] and CT images of adult limb trauma in our hospital from 2017 to 2020 were retrospectively collected, with or without 1 or more fractures of the shoulder, elbow, wrist, hand, hip, knee, ankle, and foot. Labeling of the fracture referred to the visualization of the fracture on the corresponding CT images. After training the pre-optimized AI model, the diagnostic performance of the pre-optimized AI, optimized AI model, and the initial radiological reports were evaluated. For the lesion level, the detection rate of avulsion and non-avulsion fractures was analyzed, whereas for the case level, the accuracy, sensitivity, and specificity were compared among them. Results: The total datasets (1,035 cases) were divided into a training set (n=675), a validation set (n=169), and a test set (n=191) in a balanced joint distribution. At the lesion level, the detection rates of avulsion fracture (57.89% vs. 35.09%, P=0.004) and non-avulsion fracture (85.64% vs. 71.29%, P<0.001) by the optimized AI were significantly higher than that by pre-optimized AI. The average precision (AP) of the optimized AI model for all lesions was higher than that of pre-optimized AI model (0.582 vs. 0.425). The detection rate of avulsion fracture by the optimized AI model was significantly higher than that by radiologists (57.89% vs. 29.82%, P=0.002). For the non-avulsion fracture, there was no significant difference of detection rate between the optimized AI model and radiologists (P=0.853). At the case level, the accuracy (86.40% vs. 71.93%, P<0.001) and sensitivity (87.29% vs. 73.48%, P<0.001) of the optimized AI were significantly higher than those of the pre-optimized AI model. There was no statistical difference in accuracy, sensitivity, and specificity between the optimized AI model and the radiologists (P>0.05). Conclusions: The optimized AI model improves the diagnostic efficacy in detecting extremity fractures on radiographs, and the optimized AI model is significantly better than radiologists in detecting avulsion fractures, which may be helpful in the clinical practice of orthopedic emergency.

Head-to-head comparison of 18F-FAPI and 18F-FDG PET/CT in staging and therapeutic management of hepatocellular carcinoma.

BACKGROUND: Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has limitations in staging hepatocellular carcinoma (HCC). The recently introduced 18F-labeled fibroblast-activation protein inhibitor (FAPI) has shown promising prospects in detection of HCC lesions. This study aimed to investigate the initial staging and restaging performance of 18F-FAPI PET/CT compared to 18F-FDG PET/CT in HCC. METHODS: This prospective study enrolled histologically confirmed HCC patients from March 2021 to September 2022. All patients were examined with 18F-FDG PET/CT and 18F-FAPI PET/CT within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. RESULTS: A total of 67 patients (57 men; median age, 57 [range, 32-83] years old) were included. 18F-FAPI PET showed higher SUVmax and TBR values than 18F-FDG PET in the intrahepatic lesions (SUVmax: 6.7 vs. 4.3, P < 0.0001; TBR: 3.9 vs. 1.7, P < 0.0001). In diagnostic performance, 18F-FAPI PET/CT had higher detection rate than 18F-FDG PET/CT in intrahepatic lesions [92.2% (238/258) vs 41.1% (106/258), P < 0.0001] and lymph node metastases [97.9% (126/129) vs 89.1% (115/129), P = 0.01], comparable in distant metastases [63.6% (42/66) vs 69.7% (46/66), P > 0.05]. 18F-FAPI PET/CT detected primary tumors in 16 patients with negative 18F-FDG, upgraded T-stages in 12 patients and identified 4 true positive findings for local recurrence than 18F-FDG PET, leading to planning therapy changes in 47.8% (32/67) of patients. CONCLUSIONS: 18F-FAPI PET/CT identified more primary lesions, lymph node metastases than 18F-FDG PET/CT in HCC, which is helpful to improve the clinical management of HCC patients. TRIAL REGISTRATION: Clinical Trials, NCT05485792 . Registered 1 August 2022, Retrospectively registered.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Luteolin exhibits synergistic therapeutic efficacy with erastin to induce ferroptosis in colon cancer cells through the HIC1-mediated inhibition of GPX4 expression.

Colon cancer continues to be a prevalent gastrointestinal malignancy with a bleak prognosis. The induction of ferroptosis, a new form of regulated cell death, has emerged as a potentially effective strategy for the treatment of colon cancer. However, numerous colon cancer cells display resistance to ferroptosis induced by erastin, a well-established ferroptosis inducer. Finding drugs that can enhance the susceptibility of colon cancer cells to erastin is of utmost importance. This study aimed to examine the synergistic therapeutic impact of combining erastin with a bioactive flavonoid compound luteolin on the ferroptosis-mediated suppression of colon cancer. Human colon cancer HCT116 and SW480 cells were used for the in vitro studies and a xenograft of colon cancer model in BALB/c nude mice was established for the in vivo experiments. The results showed that combinative treatment of luteolin and erastin effectively inhibited the viability and proliferation of colon cancer cells. Luteolin and erastin cotreatment synergistically induced ferroptosis, concomitant with a reduction in glutathione and an elevation in lipid peroxides. In vivo, combinative treatment of luteolin and erastin exhibited a pronounced therapeutic effect on xenografts of colon cancer, characterized by a significant induction of ferroptosis. Mechanistically, luteolin in combination with erastin synergistically reduced the expression of glutathione peroxidase 4 (GPX4), an antioxidase overexpressed in colon cancer cells. Furthermore, luteolin and erastin cotreatment significantly upregulated the expression of hypermethylated in cancer 1 gene (HIC1), a transcriptional repressor also recognized as a tumor suppressor. HIC1 overexpression notably augmented the suppression of GPX4 expression and facilitated ferroptotic cell death. In contrast, HIC1 silencing attenuated the inhibition of GPX4 expression and eliminated the ferroptosis. Conclusively, these results clearly demonstrated that luteolin acts synergistically with erastin and renders colon cancer cells vulnerable to ferroptosis through the HIC1-mediated inhibition of GPX4 expression, which may act as a promising therapeutic strategy.

Digital literacy and farmers' entrepreneurial behavior-Empirical analysis based on CHFS2019 micro data.

Farmers' entrepreneurship is an important engine to comprehensively help promote rural revitalization. Based on data from the China Household Finance Survey (CHFS2019), this paper empirically examines the effect of digital literacy on farmers' entrepreneurial behavior using the Probit model and instrumental variable method; and examines the mediating role of health status in this effect using the mediation effect model, combined with the Sobel and Bootstrap tests. The results of the study showed that (1) digital literacy positively influenced farmers' entrepreneurial behavior at the 1% significant level, and this positive influence showed some differences across gender and age; (2) health status played a mediating effect in the positive influence of digital literacy on farmers' entrepreneurial behavior. Accordingly, policy recommendations are made to foster farmers' digital literacy, encourage farmers' entrepreneurship, and ensure farmers' "digital health" services.

Laparoscopic radical transverse colectomy with transrectal specimen extraction: A novel natural orifice specimen extraction procedure: A case report.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Comparative short-term and survival outcomes of three specimen extraction techniques in laparoscopic low rectal cancer surgery: does it affect ileostomy closure?

INTRODUCTION: This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. MATERIALS AND METHODS: A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. RESULTS: In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P < 0.001), more intraoperative bleeding (P < 0.001), longer length of abdominal incision (P<0.001), longer time to first flatus (P < 0.001), longer time to first defecation (P < 0.001), longer time to first eat (P < 0.001), and longer postoperative hospital stays (P = 0.005) than the EXSI and EVER groups. The primary postoperative complication rate in the EXAI and EVER group was significantly higher than in the EXSI group (P = 0.005). In loop ileostomy closure, EXAI group had significantly longer operative time (P = 0.001), more bleeding volume, and longer postoperative hospital stays (P < 0.001) than the EXSI and EVER groups. For survival outcomes, the 3-year local recurrence-free survival (LRFS) is 92.6% for all patients. The 3-year LRFS for patients in EXAI, EXSI, and EVER were 90.1%, 95.4%, and 92.7%, with P = 0.476. CONCLUSIONS: Our single-center results found that in LAR-PLI surgery for low rectal cancer, the short-term outcomes of specimen extraction through the stoma incision or anus were better than that through the auxiliary incision, but the 3-year LRFS was no statistically different.

Efficient gas chromatographic separation of xylene and other aromatic isomers by using pillar[6]arene-based stationary phase.

The separation of aromatic isomers, in particular xylene isomers, represents a big issue in chemical and petroleum industries, owing to their similar molecular sizes and boiling points. In this work, the investigation ofpillar[6]arene derivative modified by long alkyl chains (P6A-C10) as a stationary phase for high-resolution gas chromatographic (GC) separations of xylene isomers is presented. Pillar[n]arenes are a new class of macrocyclic hosts that can accommodate specific guests due to their highly symmetrical and rigid pillar architectures with π-electron rich cavities. The P6A-C10 column showed high-resolution performance towards xylene isomers, with peculiar advantages if compared with the commercial HP-5, HP-35, DB-17, and PEG-20Mcolumns.A quantum chemistry calculation has been performed, showing a difference in non-covalent interactions with the P6A-C10 pillar framework, which leads to specific selectivity for xylene isomers.Furthermore, the P6A-C10 column exhibited good repeatability.

Development of artificial blood loss and duration of excision score to evaluate surgical difficulty of total laparoscopic anterior resection in rectal cancer.

Purpose: Total laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR. Methods: RC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score. Results: A total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set. Conclusion: This preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

Altered electronic structure of trimetallic FeNiCo-MOF nanosheets for efficient oxygen evolution.

Theoretical calculation results unveil that the reconstructed Co(Ni)OOH on FeNiCo-MOF during OER processes is beneficial to improve the OER activity. Experimentally, to achieve 2D trimetallic FeNiCo-MOF nanosheets, a facile room-temperature dispersion approach is employed. Such 2D nanosheets reveal an OER overpotential as low as 239 mV at 10 mA cm-2 and excellent long-term stability in 1M KOH. Undoubtedly, this work highlights the great potential of directly utilizing MOF nanosheets as OER electrocatalysts.

Consumer misestimations of small recurring changes vs. a single large lump sum.

Various decision contexts require the calculation of smaller recurring changes accumulated over time and their comparison to larger one-time changes (e.g., $100 periodic increase in monthly rent every year vs. a $1000 increase in rent at the end of 5 years). In both hypothetical and incentivized studies, we demonstrate an inaccuracy of estimations involving total cumulations of smaller recurring changes and single lump sums. We document this effect when individuals process increasing or decreasing changes in gains or losses (e.g., raises in wages or rent, discounts in membership fees). Importantly, these biases occur even when the changes are provided to the consumers as clear absolute dollar values as opposed to complex percentages. We discuss the theoretical contributions of our study as well as its implications for consumers, managers, and policy makers.

Uncovering the effects and molecular mechanism of Astragalus membranaceus (Fisch.) Bunge and its bioactive ingredients formononetin and calycosin against colon cancer: An integrated approach based on network pharmacology analysis coupled with experimental validation and molecular docking.

Colon cancer is a highly malignant cancer with poor prognosis. Astragalus membranaceus (Fisch.) Bunge (Huang Qi in Chinese, HQ), a well-known Chinese herbal medicine and a popular food additive, possesses various biological functions and has been frequently used for clinical treatment of colon cancer. However, the underlying mechanism is not fully understood. Isoflavonoids, including formononetin (FMNT) and calycosin (CS), are the main bioactive ingredients isolated from HQ. Thus, this study aimed to explore the inhibitory effects and mechanism of HQ, FMNT and CS against colon cancer by using network pharmacology coupled with experimental validation and molecular docking. The network pharmacology analysis revealed that FMNT and CS exerted their anticarcinogenic actions against colon cancer by regulating multiple signaling molecules and pathways, including MAPK and PI3K-Akt signaling pathways. The experimental validation data showed that HQ, FMNT and CS significantly suppressed the viability and proliferation, and promoted the apoptosis in colon cancer Caco2 and HT-29 cells. HQ, FMNT and CS also markedly inhibited the migration of Caco2 and HT-29 cells, accompanied by a marked increase in E-cadherin expression, and a notable decrease in N-cadherin and Vimentin expression. In addition, HQ, FMNT and CS strikingly decreased the expression of ERK1/2 phosphorylation (p-ERK1/2) without marked change in total ERK1/2 expression. They also slightly downregulated the p-Akt expression without significant alteration in total Akt expression. Pearson correlation analysis showed a significant positive correlation between the inactivation of ERK1/2 signaling pathway and the HQ, FMNT and CS-induced suppression of colon cancer. The molecular docking results indicated that FMNT and CS had a strong binding affinity for the key molecules of ERK1/2 signaling pathway. Conclusively, HQ, FMNT and CS exerted good therapeutic effects against colon cancer by mainly inhibiting the ERK1/2 signaling pathway, suggesting that HQ, FMNT and CS could be useful supplements that may enhance chemotherapeutic outcomes and benefit colon cancer patients.

Development of a machine learning algorithm to predict complications of total laparoscopic anterior resection and natural orifice specimen extraction surgery in rectal cancer.

BACKGROUND: Total laparoscopic anterior resection (tLAR) and natural orifice specimen extraction surgery (NOSES) has been widely adopted in the treatment of rectal cancer (RC). However, no study has been performed to predict the short-term outcomes of tLAR using machine learning algorithms to analyze a national cohort. METHODS: Data from consecutive RC patients who underwent tLAR were collected from the China NOSES Database (CNDB). The random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), deep neural network (DNN), logistic regression (LR) and K-nearest neighbor (KNN) algorithms were used to develop risk models to predict short-term complications of tLAR. The area under the receiver operating characteristic curve (AUROC), Gini coefficient, specificity and sensitivity were calculated to assess the performance of each risk model. The selected factors from the models were evaluated by relative importance. RESULTS: A total of 4313 RC patients were identified, and 667 patients (15.5%) developed postoperative complications. The machine learning model of XGBoost showed more promising results in the prediction of complication than other models (AUROC 0.90, P < 0.001). The performance was similar when internal and external validation was used. In the XGBoost model, the top four influential factors were the distance from the lower edge of the tumor to the anus, age at diagnosis, surgical time and comorbidities. In risk stratification analysis, the rate of postoperative complications in the high-risk group was significantly higher than in the medium- and low-risk groups (P < 0.001). CONCLUSION: The machine learning model shows potential benefits in predicting the risk of complications in RC patients after tLAR. This novel approach can provide reliable individual information for surgical treatment recommendations.

Development and validation of a clinical-radiomics model to predict recurrence for patients with hepatocellular carcinoma after curative resection.

PURPOSE: Recurrence is the leading cause of death in hepatocellular carcinoma (HCC) patients with curative resection. In this study, we aimed to develop a preoperative predictive model based on high-throughput radiomics features and clinical factors for prediction of long- and short-term recurrence for these patients. METHODS: A total of 270 patients with HCC who were followed up for at least 5 years after curative hepatectomy between June 2014 and December 2017 were enrolled in this retrospective study. Regions of interest were manually delineated in preoperative T2-weighted images using ITK-SNAP software on each HCC tumor slice. A total of 1197 radiomics features were extracted, and the recursive feature elimination method based on logistic regression was used for radiomics signature building. Tenfold cross-validation was applied for model development. Nomograms were constructed and assessed by calibration plot, which compares nomogram-predicated probability with observed outcome. Receiver-operating characteristic was then generated to evaluate the predictive performance of the model in the development and test cohorts. RESULTS: The 10 most recurrence-free survival-related radiomics features were selected for the radiomics signatures. A multiparametric clinical-radiomics model combining albumin and radiomics score for recurrence prediction was further established. The integrated model demonstrated good calibration and satisfactory discrimination, with the area under the curve (AUC) of 0.864, 95% CI 0.842-0.903, sensitivity of 0.889, and specificity of 0.644 in the test set. Calibration curve showed good agreement concerning 5-year recurrence risk predicted by the nomogram. In addition, the AUC of 1-, 2-, 3-, and 4-year recurrence was 0.935 (95% CI 0.836-1.000), 0.861 (95% CI 0.723-0.999), 0.878 (95% CI 0.762-0.994), and 0.878 (95% CI 0.762-0.994) in the test set, respectively. CONCLUSIONS: The clinical-radiomics model integrating radiomics features and clinical factors can improve recurrence predictions beyond predictions made using clinical factors or radiomics features alone. Our clinical-radiomics model is a valid method to predict recurrence that should improve preoperative prognostic performance and allow more individualized treatment decisions.

Raw Pinelliae Rhizoma: examination of sedative and hypnotic effects in mice and chemical analysis.

PURPOSE: Raw "Pinelliae Rhizoma" (RPR) is widely used in Chinese clinics to treat insomnia. This study investigated its underlying sedative and hypnotic mechanisms and main active components. METHODS: A locomotor activity test was used to evaluate the sedative effects of RPR at three dosages (0.2 g/mL, 0.4 g/mL, and 0.8 g/mL) in mice. Polysomnography was used to assess its ability to improve sleep. Ultra-performance liquid chromatography/time of flight/mass spectrometry (UPLC-TOF-MS) analysis was used to identify the potential active components of RPR. RESULTS: Mice in the RPR groups were less active than mice in the vehicle group; this difference was greatest in the 0.8 g/mL RPR group. Compared with the vehicle, 0.8 g/mL RPR increased the duration of rapid eye movement (REM) sleep in the dark phase. In addition, the duration of wakefulness in the 0.8 g/mL RPR group decreased with increasing durations of nonrapid eye movement (NREM) and REM sleep. Compared with diazepam, 0.8 g/mL RPR increased REM sleep duration in both the light and dark phases and increased the number of transitions both from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 33 RPR constituents, including 15 alkaloids, were identified. CONCLUSION: The results preliminarily indicated that RPR exerts sedative and hypnotic effects in mice, mainly leading to improvements in REM sleep. These effects are possibly due to the alkaloid constituents of RPR.