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Introduction: Postoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%-80% within 2 years after local treatment and approximately 90% within 5 years. "Yang-deficient toxic node" is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of "nourishing Qi and warming Yang, strengthening Zhengqi, and detoxifying" can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence. Methods: The study will be a multicenter, randomized, double-blind, placeboparallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. Themain outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1-3 years, cumulative annual survival after 1-3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate. Discussion: There is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery. [ABSTRACT FROM AUTHOR]

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells in the tumor microenvironment (TME) that play critical roles in promoting tumor growth and metastasis. Tumor-associated platelets (TAPs) help cancer cells evade the immune system and promote metastasis. In this paper, we describe the interaction between MDSCs and TAPs, including their generation, secretion, activation, and recruitment, as well as the effects of MDSCs and platelets on the generation and changes in the immune, metabolic, and angiogenic breast cancer (BC) microenvironments. In addition, we summarize preclinical and clinical studies, traditional Chinese medicine (TCM) therapeutic approaches, and new technologies related to targeting and preventing MDSCs from interacting with TAPs to modulate the BC TME, discuss the potential mechanisms, and provide perspectives for future development. The therapeutic strategies discussed in this review may have implications in promoting the normalization of the BC TME, reducing primary tumor growth and distant lung metastasis, and improving the efficiency of anti-tumor therapy, thereby improving the overall survival (OS) and progression-free survival (PFS) of patients. However, despite the significant advances in understanding these mechanisms and therapeutic strategies, the complexity and heterogeneity of MDSCs and side effects of antiplatelet agents remain challenging. This requires further investigation in future prospective cohort studies. [ABSTRACT FROM AUTHOR]

Background: The question of whether flexible sigmoidoscopy (FS) for colorectal cancer (CRC) affects incidence or mortality remains unclear. In this study, we conducted a meta-analysis and systematic review to explore this issue. Methods: A systematic search of PubMed, EMBASE, and ClinicalTrials.gov was performed for cohort studies (CS), case--control studies, and randomized controlled trials (RCTs) of people who underwent FS and reported mortality or incidence of CRC until 11 December 2022. Relative risk (RR) was applied as an estimate of the effect of interest. To combine the RRs and 95% confidence intervals, a random-effects model was used. The quality of the included studies and evidence was assessed by the Newcastle-Ottawa quality assessment scale, the Jadad scale, and the "Grading of Recommendations Assessment, Development and Evaluation System." Results: There were a total of six RCTs and one CS, comprising 702,275 individuals. FS was found to be associated with a 26% RR reduction in CRC incidence (RR, 0.74; 95% CI, 0.66--0.84) and a 30% RR reduction in CRCmortality (RR, 0.70; 95% CI, 0.58--0.85). In the incidence subgroup analysis, FS significantly reduced the incidence of CRC compared with non-screening, usual care, and fecal immunochemical testing. Significance was also shown in men, women, distal site, stages III--IV, ages 55--59, and age over 60. In terms of the mortality subgroup analysis, the results were roughly the same as those of incidence. Conclusion: According to this study, FS might reduce the incidence and mortality of CRC. To confirm this finding, further prospective clinical studies should be conducted based on a larger-scale population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023388925. [ABSTRACT FROM AUTHOR]

Background: Depression is one of the common complications in patients with postoperative breast cancer (BC). Conventional therapies for postoperative depression of BC always have modest treatment outcomes and undesirable side effects. Clinical practice and many studies have shown that traditional Chinese medicine (TCM) has a good effect on postoperative depression of BC. This meta-analysis aimed to assess the clinical effect of TCM as an add-on treatment for postoperative depression of BC. Methods: A systematic and thorough search was conducted on eight online electronic databases up to 20 July 2022. The control group received conventional therapies, and intervention groups received what control groups received plus TCM treatment. Review Manager 5.4.1 was used for statistical analysis. Results: Nine RCTs involved 789 participants who met the inclusion standards. The results showed the intervention group was better at decreasing the score of the Hamilton rating scale for depression (HAMD) (mean difference, MD = −4.21, 95% CI −5.54 to −2.88) and the self-rating depression scale (SDS) (MD = −12.03, 95% CI −15.94 to −8.13), improving clinical efficacy (RR = 1.25, 95% CI 1.14–1.37), increasing the levels of 5-hydroxytryptamine (5-HT) (MD = 0.27, 95% CI 0.20–0.34), dopamine (DA) (MD = 26.28, 95% CI 24.18–28.77), and norepinephrine (NE) (MD = 11.05, 95% CI 8.07–14.04), and influencing the immune index, including the levels of CD3+ (MD = 15.18, 95% CI 13.61–16.75), CD4+ (MD = 8.37, 95% CI 6.00–10.74), and CD4+/CD8+ (MD = 0.33, 95% CI 0.27–0.39). The level of CD8+ (MD = −4.04, 95% CI −11.98 to 3.99) had no obvious difference between the two groups. Conclusion: The meta-analysis stated that a therapeutic regimen involving TCM could better improve the depression status in postoperative BC. [ABSTRACT FROM AUTHOR]

Changes in cellular metabolism involving fuel sources are well-known mechanisms of cancer cell differentiation in the context of carcinogenesis. Metabolic reprogramming is regulated by oncogenic signaling and transcriptional networks and has been identified as an essential component of malignant transformation. Hypoxic and acidified tumor microenvironment contributes mainly to the production of glycolytic products known as lactate. Mounting evidence suggests that lactate in the tumor microenvironment of colorectal cancer(CRC) contributes to cancer therapeutic resistance and metastasis. The contents related to the regulatory effects of lactate on metabolism, immune response, and intercellular communication in the tumor microenvironment of CRC are also constantly updated. Here we summarize the latest studies about the pleiotropic effects of lactate in CRC and the clinical value of targeting lactate metabolism as treatment. Different effects of lactate on various immune cell types, microenvironment characteristics, and pathophysiological processes have also emerged. Potential specific therapeutic targeting of CRC lactate metabolism is also discussed. With increased knowledge, effective druggable targets might be identified, with the aim of improving treatment outcomes by reducing chemoresistance. [ABSTRACT FROM AUTHOR]

Cancer has become one of the major causes of human death. Several anticancer drugs are available; howeve their use and efficacy are limited by the toxic side effects and drug resistance caused by their continuous application. Many natural products have antitumor effects with low toxicity and fewer adverse effects. Moreover, they play an important role in enhancing the cytotoxicity of chemotherapeutic agents, reducing toxic side effects, and reversing chemoresistance. Consequently, natural drugs are being applied as potential therapeutic options in the field of antitumor treatment. As natural medicinal plants, some components of ginseng have been shown to have excellent efficacy and a good safety profile for cancer treatment. The pharmacological activities and possible mechanisms of action of ginseng have been identified. Its broad range of pharmacological activities includes antitumor, antibacterial, anti-inflammatory, antioxidant, anti-stress, antifibrotic, central nervous system modulating, cardioprotective, and immuneenhancing effects. Numerous studies have also shown that through multiple pathways, ginseng and its active ingredients exert antitumor effects on gastrointestinal (GI) tract tumors, such as esophageal, gastric, colorectal, liver, and pancreatic cancers. Herein, we introduced the main components of ginseng, including ginsenosides, polysaccharides, and sterols, etc., and reviewed the mechanism of action and research progress of ginseng in the treatment of various GI tumors. Further more, the pathways of action of the main components of ginseng are discussed in depth to promote the clinical development and application of ginseng in the field of anti-GI tumors. [ABSTRACT FROM AUTHOR]

Introduction: The incidence and mortality of gastric cancer ranks among the highest, and the 5-year survival rate of advanced gastric cancer (AGC) is less than 10%. Currently, chemotherapy is the main treatment for AGC, and oxaliplatin is an important part of the commonly used chemotherapy regimen for AGC. A large number of RCTs have shown that Chinese herbal medicine (CHM) combined with oxaliplatin-based chemotherapy can improve objective response rate (ORR) and disease control rate (DCR), reduce the toxic and side effects of chemotherapy. There is currently a lack of systematic evaluation of the evidence to account for the efficacy and safety of CHM combined with oxaliplatin-based chemotherapy in AGC. Therefore, we carried out this study and conducted the sensitivity analysis on the herbal composition to explore the potential anti-tumor efficacy. Methods: Databases of PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Wanfang database, and the Chinese Scientific Journals Database were searched from their inception to April 2022. RCTs evaluating the efficacy of CHM combined with oxaliplatin-based chemotherapy on AGC were included. Stata 16 was used for data synthesis, RoB 2 for quality evaluation of included RCTs, and GRADE for quality of synthesized evidence. Additional sensitivity analysis was performed to explore the potential anti-tumor effects of single herbs and combination of herbs. Results: Forty trials involving 3,029 participants were included. Most included RCTs were assessed as "Some concerns" of risk of bias. Meta-analyses showed that compare to oxaliplatin-based chemotherapy alone, that CHM combined with oxaliplatin-based chemotherapy could increase the objective response rate (ORR) by 35% [risk ratio (RR) = 1.35, 95% confidence intervals (CI) (1.25, 1.45)], and disease control rate (DCR) by 12% [RR = 1.12, 95% CI (1.08, 1.16)]. Subgroup analysis showed that compare to SOX, FOLFOX, and XELOX regimens alone, CHM plus SOX, CHM plus FOLFOX, and CHM plus XELOX could significantly increase the ORR and DCR. Sensitivity analysis identified seven herbs of Astragalus, Liquorice, Poria, Largehead Atractylodes, Chinese Angelica, Codonopsis, and Tangerine Peel with potentials to improve tumor response of oxaliplatin-based chemotherapy in AGC. Conclusion: Synthesized evidence showed moderate certainty that CHM plus oxaliplatin-based chemotherapy may promote improvement in tumor response in AGC. CHM treatment is safe for AGC. Due to the poor quality of included RCTs and small samplesizes, the quality of synthesized evidence was not high. Specific combinations of herbs appeared to produce higher contributions to ORR than the herb individually. Each of this seven above mentioned herbs has been shown in experimental studies to potentially contribute to the improvement of tumor response. To support this conclusion, these seven herbs are worthy of further clinical research. [ABSTRACT FROM AUTHOR]

Recent research unveiled that LINC00857 plays a regulatory role in multiple human cancers, such as lung adenocarcinoma and gastric cancer. Nevertheless, the function of LINC00857 in pancreatic adenocarcinoma (PAAD) remains unclear. This study concentrates on LINC00857 to discuss the relevant molecular mechanism of this gene in PAAD. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were implemented for measuring the expressions of RNAs and proteins. Wound healing and Transwell assays were used to assess cell migration and invasion, and fluorescent in situ hybridization (FISH) to locate LINC00857 in PAAD cells. Additionally, mechanism assays were conducted to validate the interaction between genes. Results indicated that LINC00857 was upregulated in PAAD cells and the knockdown of LINC00857 impeded PAAD cell migration, invasion and epithelialmesenchymal transition (EMT). Further, it was found that LNC00857 regulates CLDN12 expression by targeting miR-150-5p. Moreover, LINC00857 was confirmed to recruit serine/arginine-rich splicing factor 1 (SRSF1) to promote the alternative splicing (AS) targeting CLDN12, affecting the phenotypes of PAAD cells. In addition, the transcription factor ZNF460 was proven to positively regulate LINC00857 expression. To sum up, LINC00857 regulated by ZNF460 upregulates CLDN12 expression by sponging miR-150-5p and recruiting SRSF1 to facilitate the progression of PAAD cells. [ABSTRACT FROM AUTHOR]

We describe a field reversed configuration (FRC) experiment featuring in-vessel θ-pinch coils and open-field-line plasmas confined in a tandem mirror. Two FRCs, formed near the west and the east mirror throats of a central cell, are ejected toward the mid-plane for colliding and merging. Each FRC consists of four groups of pulsed power supplies and four groups of coils, having diameters 35, 35, 40, and 45 cm. The rise time of the main reversal field is 7.15 μs, and the maximum voltage is 40 kV with total currents of 416 kA, corresponding to a magnetic field of 1690 G. The total capacitive stored energy is 115.2 kJ. A fast pulse gas injection system was designed and tested to inject neutral gas into the FRC formation region with controlled directions. The successful installation of the θ-pinch coils inside the vacuum vessel offers greater freedom for diagnostics and control instruments as well as preserving magnetic tandem mirror configuration. The magnetic field reversal is confirmed by internal magnetic field measurements. The plasma temperature, density, and lifetime are, respectively, ~100 eV, ~3.0 × 1018 m-3, and ~300 μs for the current operating conditions. [ABSTRACT FROM AUTHOR]

A high voltage pulse generator based on a silicon-controlled rectifier has been designed and implemented for a field reversed configuration experiment. A critical damping circuit is used in the generator to produce the desired pulse waveform. Depending on the load, the rise time of the output trigger signal can be less than 1 µs, and the peak amplitudes of trigger voltage and current are up to 8 kV and 85 A in a single output. The output voltage can be easily adjusted by changing the voltage on a capacitor of the generator. In addition, the generator integrates an electrically floating heater circuit so it is capable of triggering either pseudosparks (TDI-type hydrogen thyratron) or ignitrons. Details of the circuits and their implementation are described in the paper. The trigger generator has successfully controlled the discharging sequence of the pulsed power supply for a field reversed configuration experiment. [ABSTRACT FROM AUTHOR]

Maize (Zea mays) is one of the most important crops worldwide. To understand the biological processes underlying various traits of the crop (e.g. yield and response to stress), a detailed protein-protein interaction (PPI) network is highly demanded. Unfortunately, there are very few such PPIs available in the literature. Therefore, in this work, we present the Protein-Protein Interaction Database for Maize (PPIM), which covers 2,762,560 interactions among 14,000 proteins. The PPIM contains not only accurately predicted PPIs but also those molecular interactions collected from the literature. The database is freely available at http://comp-sysbio.org/ppim with a user-friendly powerful interface. We believe that the PPIM resource can help biologists better understand the maize crop. [ABSTRACT FROM AUTHOR]

Motivation: MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in post-transcriptional regulations as well as other important biological processes. Recently, accumulating evidences indicate that miRNAs are extensively involved in cancer. However, it is a big challenge to identify which miRNAs are related to which cancer considering the complex processes involved in tumors, where one miRNA may target hundreds or even thousands of genes and one gene may regulate multiple miRNAs. Despite integrative analysis of matched gene and miRNA expression data can help identify cancer-associated miRNAs, such kind of data is not commonly available. On the other hand, there are huge amount of gene expression data that are publicly accessible. It will significantly improve the efficiency of characterizing miRNA's function in cancer if we can identify cancer miRNAs directly from gene expression data. Results: We present a novel computational framework to identify the cancer-related miRNAs based solely on gene expression profiles without requiring either miRNA expression data or the matched gene and miRNA expression data. The results on multiple cancer datasets show that our proposed method can effectively identify cancer-related miRNAs with higher precision compared with other popular approaches. Furthermore, some of our novel predictions are validated by both differentially expressed miRNAs and evidences from literature, implying the predictive power of our proposed method. In addition, we construct a cancer-miRNA-pathway network, which can help explain how miRNAs are involved in cancer. [ABSTRACT FROM AUTHOR]

Motivation: MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in post-transcriptional regulations as well as other important biological processes. Recently, accumulating evidences indicate that miRNAs are extensively involved in cancer. However, it is a big challenge to identify which miRNAs are related to which cancer considering the complex processes involved in tumors, where one miRNA may target hundreds or even thousands of genes and one gene may regulate multiple miRNAs. Despite integrative analysis of matched gene and miRNA expression data can help identify cancer-associated miRNAs, such kind of data is not commonly available. On the other hand, there are huge amount of gene expression data that are publicly accessible. It will significantly improve the efficiency of characterizing miRNA's function in cancer if we can identify cancer miRNAs directly from gene expression data. Results: We present a novel computational framework to identify the cancer-related miRNAs based solely on gene expression profiles without requiring either miRNA expression data or the matched gene and miRNA expression data. The results on multiple cancer datasets show that our proposed method can effectively identify cancer-related miRNAs with higher precision compared with other popular approaches. Furthermore, some of our novel predictions are validated by both differentially expressed miRNAs and evidences from literature, implying the predictive power of our proposed method. In addition, we construct a cancer-miRNA-pathway network, which can help explain how miRNAs are involved in cancer. [ABSTRACT FROM AUTHOR]

Keratinocyte growth factor 1 (KGF-1) has proven useful in the treatment of pathologies associated with dermal adnexae, liver, lung, and the gastrointestinal tract diseases. However, poor stability and short plasma half-life of the protein have restricted its therapeutic applications. While it is possible to improve the stability and extend the circulating half-life of recombinant human KGF-1 (rhKGF-1) using solution-phase PEGylation, such preparations have heterogeneous structures and often low specific activities due to multiple and/or uncontrolled PEGylation. In the present study, a novel solid-phase PEGylation strategy was employed to produce homogenous mono-PEGylated rhKGF-1. RhKGF-1 protein was immobilized on a Heparin-Sepharose column and then a site-selective PEGylation reaction was carried out by a reductive alkylation at the N-terminal amino acid of the protein. The mono-PEGylated rhKGF-1, which accounted for over 40% of the total rhKGF-1 used in the PEGylation reaction, was purified to homogeneity by SP Sepharose ion-exchange chromatography. Our biophysical and biochemical studies demonstrated that the solid-phase PEGylation significantly enhanced the in vitro and in vivo biostability without affecting the over all structure of the protein. Furthermore, pharmacokinetic analysis showed that modified rhKGF-1 had considerably longer plasma half-life than its intact counterpart. Our cell-based analysis showed that, similar to rhKGF-1, PEGylated rhKGF-1 induced proliferation in NIH 3T3 cells through the activation of MAPK/Erk pathway. Notably, PEGylated rhKGF-1 exhibited a greater hepatoprotection against CCl4-induced injury in rats compared to rhKGF-1. [ABSTRACT FROM AUTHOR]

As one of fibroblast growth factor (FGF) family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21) was modified with polyethylene glycol (PEGylation) in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus of rhFGF21. The mono-PEGylated rhFGF21 retained the secondary structure, consistent with the native rhFGF21, but its biostabilities, including the resistance to physiological temperature and trypsinization, were significantly enhanced. The in vivo immunogenicity of PEGylated rhFGF21 was significantly decreased, and in vivo half-life time was significantly elongated. Compared to the native form, the PEGylated rhFGF21 had a similar capacity of stimulating glucose uptake in 3T3-L1 cells in vitro, but afforded a significantly long effect on reducing blood glucose and triglyceride levels in the type 2 diabetic animals. These results suggest that the PEGylated rhFGF21 is a better and more effective anti-diabetic drug candidate than the native rhFGF21 currently available. Therefore, the PEGylated rhFGF21 may be potentially applied in clinics to improve the metabolic syndrome for type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

series of polyimides (PIs) with low dielectric constant were synthesized via a polycondensation from two new unsymmetric phthalic-thioether-naphthalic dianhydride isomers which were synthesized from 3- or 4-chlorophthalic anhydride by a four-step procedure. The introduction of the unsymmetric phthalic-thioether-naphthalic dianhydride into polymer backbone is regarded as an effective way to increase the free volume and decrease the intermolecular force and packing ability of the resulting polymers. Thus, the novel PIs exhibit low dielectric constant, low moisture absorption good solubility, high modulus, and high glass transition temperature. The polyimides show good solubility in phenol, dipolar aprotic solvents, and other common organic solvents. In addition, the isomeric effect of 3- and 4-thioether-linked phthalic anhydride on the properties of PIs was discussed. [ABSTRACT FROM AUTHOR]