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Abstract Background With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. Methods This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. Results After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

We present multi-parameter optimization of a shallow ridge InP-based traveling wave Mach-Zehnder modulator (MZM) for ultra-wide modulation bandwidth by velocity and impedance matching and microwave attenuation minimization. Relationship between MZM microwave loss and p-cladding layer doping profile is quantitatively analyzed and incorporated in device optimization. We propose a systematic analysis methodology allowing the full optimization of an InP shallow ridge MZM capable of 200 Gb/s PAM4 operation, compatible with high-volume low-cost manufacturing. Our design is expected to achieve 4.3 V half-wave voltage and 81 GHz 3-dB bandwidth with simplified fabrication process and improved long-term reliability.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Context Jiedutongluotiaogan formula (JTTF), a traditional Chinese medicine (TCM), could promote islet function. However, the potential effect of JTTF on endoplasmic reticulum stress (ERS) and autophagy have not been reported.Objective This study explores the potential effect of JTTF on ERS and autophagy in the pancreas.Materials and methods The Zucker diabetic fatty (ZDF) rats were randomised into five groups, control, model, JTTF (1, 3, 5 g/kg/day for 12 weeks). LPS induced pancreatic β-cells were treated with JTTF (50, 100, 200 μg/mL). LPS was used to induce pancreatic β-cell injury, with cell viability and insulin secretion evaluated using MTT, glucose-stimulated insulin secretion (GSIS) assays, and PCR. Intracellular Ca2+ concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining.Results Compared with the model group, body weight, FGB, HbA1c, IPGTT, FINs, and HOMA-IR in JTTF treatment groups were significantly reduced. In islets cells treated with JTTF, the pancreatic islet cells in the JTTF group were increased, lipid droplets were reduced, and there was a decrease in Ca2+ (16.67%). After JTTF intervention, PERK, p-PERK, IRE1α, p- IRE1α, ATF6, eIF2α, GRP78, p-ULK1, LC3 and p62 expression decreased, whereas Beclin1and p-mTOR expression increased. In addition, the expression of proteins related to apoptosis in the JTTF groups were lower than those in the control group.Discussion and conclusions JTTF may alleviate pancreatic β-cell injury by inhibiting ER stress and excessive autophagy in diabetic rats. This provides a new direction for treating diabetes and restoring pancreatic dysfunction by TCM.

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

In the process of continuous promotion in the green electricity market, various risks have emerged due to the inherent uncertainty and complex trading environment of the market. Evaluating and controlling the risks through a multi-dimensional evaluation is crucial for the smooth and healthy development of the green electricity market. This work proposes a risk assessment method for the green electricity market based on the multi-dimensional cloud model. First, the comprehensive indicator evaluation system is established for both pre-transaction and post-transaction dimensions by analyzing the operating mechanism of the green electricity market. Second, each dimensional cloud is formed by the evaluation clouds of all indicator levels. The comprehensive risk level cloud is generated based on the indicator values and the evaluation clouds of each indicator. Finally, the sources of market risk are identified, and the corresponding risk management methods are proposed on the basis of the risk evaluation level and membership degree of each indicator. The case study results demonstrate that the proposed method can accurately evaluate and reduce the potential risks existing in the green electricity market through the two-stage detection mechanism.

Abstract Ultrafast Raman fiber laser has been proved to be an effective method to obtain ultrafast optical pulses at special wavelength. Yet, compared with conventional rare-earth doped counterparts, it is challenging for Raman fiber lasers to generate pulses with high pulse energy and short pulse duration. Here, we review three categories of ultrafast Raman fiber laser technologies and give detailed discussions on the advantages and challenges of each. In regards to mode-locking, different saturable-absorbers-based fiber lasers are compared and their common problem resulting from long cavity length are discussed. In terms of synchronously-pumping, several approaches to match the repetition rate of pulsed pump with the length of Raman fiber cavity are discussed, while the technical complexity of each method is analyzed. Moreover, the recently developed technology termed as nonlinear optical gain modulation (NOGM) is introduced, which turns out to be a simple and quality solution to generate high-energy femtosecond pulses with wavelength agility. Compared with the others, NOGM gathers various advantages including simple structure, long-term stability, high pulse energy and short pulse duration, which may effectively promote application expansion of ultrafast Raman fiber laser in the near future.

We present a deep neural network (DNN) -based model (HubbardNet) to variationally find the ground-state and excited-state wave functions of the one-dimensional and two-dimensional Bose-Hubbard model. Using this model for a square lattice with M sites, we obtain the energy spectrum as an analytical function of the on-site Coulomb repulsion, U, and the total number of particles, N, from a single training. This approach bypasses the need to solve a new Hamiltonian for each different set of values (U,N) and generalizes well even for out-of-distribution (U,N). Using HubbardNet, we identify the two ground-state phases of the Bose-Hubbard model (Mott insulator and superfluid). We show that the DNN-parametrized solutions are in excellent agreement with results from the exact diagonalization of the Hamiltonian, and it outperforms exact diagonalization in terms of computational scaling. These advantages suggest that our model is promising for efficient and accurate computation of exact phase diagrams of many-body lattice Hamiltonians.

BackgroundEpidermal growth factor receptor (EGFR) exon 20 insertion mutations are uncommon EGFR mutations and generally resistant to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). In precision oncology, treatment regimens are tested for improving the clinical outcomes. Zebrafish embryo tumor transplant models are used in cancer research.MethodsWe report two Chinese females who were diagnosed with stage IV lung adenocarcinoma and shown to harbor EGFR exon 20 insertion mutations by next-generation sequencing (NGS). Then, we established lung cancer patient-derived xenografts using a zebrafish model. The tumor cells were isolated from the patient. For case one, tumor cells were collected from lymph node biopsy, while the tumor cells were obtained from the pleural effusion. Zebrafish were inoculated with tumor cells and placed in the culture medium containing the third-generation EGFR-TKI, osimertinib. Fluorescence microscope photographs were used to record the red fluorescence area, which represented the proliferation and migration of tumor cells in the zebrafish.ResultsCase one was diagnosed with lung adenocarcinoma (cT4N3M1b, stage IVB) and had an EGFR exon 20 mutation (p. N771delinsHH [abundance 14.08%]). Tumor cell proliferation and migration were significantly reduced in the osimertinib group compared with the control group. The patient received first-line osimertinib (160 mg). According to RECIST v1.1, she achieved a partial response. Case two had stage IVA lung adenocarcinoma with a pleural effusion. The pleural effusion sample was selected to obtain tumor cells for injection, and the zebrafish lung cancer model was established. The proliferation of tumor cells in the osimertinib group was significantly reduced compared to the control group. The migration of tumor cells was not significantly reduced compared to the control group. The patient also received first-line osimertinib (160 mg). The lung lesions were stable, but the pleural effusion was poorly controlled.ConclusionOur study demonstrates the applicability of a zebrafish embryos model as an innovative platform to targeted drug testing. More precise methods are needed to select treatment options in the future.

Understanding metabolite profiles may aid in providing a reference for individualized treatment using PEG-rhGH. Therefore, this study aimed to evaluate the clinical efficacy of PEG-rhGH in treating GHD patients by using a metabolomic approach. Fifty-seven pediatric participants treated with PEG-rhGH were enrolled (28 GHD patients with high clinical efficacy and 29 GHD patients with lower clinical efficacy). Serum samples from all patients were first collected at baseline for biochemical detection; then metabolite levels were measured using gas chromatography time-of-flight mass spectrometry. The candidates included heptadecanoic acid, stearic acid, 2-hydroxybutyric acid, myristic acid, palmitoleic acid, D-galactose, dodecanoic acid, and oleic acid. The related metabolic pathways involved fatty acid metabolism and energy metabolism. This study suggested that growth gains of PEG-rhGH treatment might be differentiated by altered serum levels of fatty acid. Collectively, the metabolomic study provides unique insights into the use of PEG-rhGH as a therapeutic strategy for individualized treatment.

Abstract Background Multiple myeloma (MM) is a prevalent hematological malignancy. Long noncoding RNAs are correlated with the development of MM. In this project, the function of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in MM and the potential mechanistic pathway were explored. Methods The expression of OIP5-AS1, microRNA (miR)-27a-3p and tuberous sclerosis 1 (TSC1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Bromodeoxyuridine (BrdU) staining. And cell apoptosis was evaluated by flow cytometry assay. Cell metastasis was assessed utilizing transwell assay. Western blot analysis was employed to detect protein level. The target relation between miR-27a-3p and OIP5-AS1 or TSC1 was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Tumor xenograft assay was conducted to measure the function of OIP5-AS1 in vivo. Results The expression levels of OIP5-AS1 and TSC1 were decreased in MM, whereas miR-27a-3p was upregulated. High level of OIP5-AS1 could predict favourable prognosis of MM patients. Overexpression of OIP5-AS1 inhibited cell viability, colony formation ability, migration and invasion, induced cell cycle arrest in G1 phase and apoptosis of MM cells in vitro as well as repressed tumorigenesis in vivo. MiR-27a-3p was a target of OIP5-AS1, and reversed the impact of OIP5-AS1 on MM cells. MiR-27a-3p directly targeted TSC1. Silencing of miR-27a-3p repressed MM progression by elevating TSC1 expression. OIP5-AS1 upregulated TSC1 by sponging miR-27a-3p. Conclusion OIP5-AS1 repressed multiple myeloma progression by regulating miR-27a-3p/TSC1 axis.

Nuclear power, as a low-carbon, stable, and efficient energy, plays an important role in replacing fossil fuels in the development of a globally sustainable energy system. However, nuclear power has deviated from the path to achieve the Sustainable Development Goals of the United Nations. The path of sustainable nuclear power for China was proposed based on an analysis of the development of global nuclear power and the situation in China, using advanced operation concepts and intelligent collaboration technology to change the labor-centered operation mode. It serves as a model for other countries with a labor-centered nuclear power operation mode and an aging society seeking to achieve carbon neutrality through the use of nuclear power around the world.

Objective Acute pulmonary embolism (APE) is a serious complication after off-pump coronary artery bypass grafting (OPCABG). We aimed to analyze the risk factors for APE in patients with OPCABG. Methods In this retrospective, observational study, patients with OPCABG who were treated in our hospital from 1 January 2018 to 31 March 2020 were included. The basic characteristics of patients and results of preoperative laboratory examinations were collected and analyzed. Results A total of 707 patients with OPCABG were included and the incidence of APE was 3.21%. Left ventricular ejection fraction (LVEF), a history of smoking, number of bypass grafting, duration of surgery, and age were significant risk factors for APE in patients with OPCABG. The areas under the curves of LVEF, number of bypass grafting, duration of surgery, and age were 0.773, 0.759, 0.738, and 0.723, respectively. The cutoff values of LVEF, number of bypass grafting, duration of surgery, and age were 59.84, 3.18, 237.42, and 73.28, respectively. Conclusions LVEF, a history of smoking, number of bypass grafting, duration of surgery, and age may be risk factors for APE in patients with OPCABG. Early measures should be taken to target these risks to prevent APE.

Monotonic classification is a special task in machine learning and pattern recognition. As to monotonic classification, it is assumed that both features and decision are ordinal and there is the monotonicity constraints between the features and decision. Little work has been focused on feature selection for this type of tasks although a number of feature selection algorithms have been introduced for nominal classification problems. However these techniques can not be applied to monotonic classification as they do not consider the monotonicity constraints. In this work, we present a technique to compute the quality of features for monotonic classification. Using gradient directing search method, this method trains a feature weight vector by maximizing the fuzzy monotonic dependency, which was defined in fuzzy preference rough sets. We conduct some experiments to compare the classification performances of the proposed method with some other techniques. The experimental results show the effectiveness of the proposed algorithm.