[Retracted] MicroRNA­329­3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell cell migration and invasion assay data featured in Figs. 5C and 6C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published elsewhere prior to the submission of this paper to Oncology Reports, or were submitted for consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 2743­2750, 2017; DOI: 10.3892/or.2017.5555].

Reprocessable, Highly Transparent Ionic Conductive Elastomers Based on ß-Amino Ester Chemistry for Sensing Devices.

Ionic conductive elastomers (ICEs) exhibit a compelling combination of ionic conductivity and elastic properties, rendering them excellent candidates for stretchable electronics, particularly in applications like sensing devices. Despite their appeal, a significant challenge lies in the reprocessing of ICEs without compromising their performance. To address this issue, we propose a strategy that leverages covalent adaptable networks (CANs) for the preparation of ICEs. Specifically, ß-amino ester bonds as dynamic motifs are incorporated into a poly(ethylene oxide) network containing lithium bis(trifluoromethane) sulfonimide (LiTFSI) salt. LiTFSI-containing ß-amino ester networks (LBAEs) exhibit superb transparency (94%), thermal stability (>280 °C), and modest conductivity (0.00576 mS·cm-1 at 20 °C), and some LBAEs maintain operational capability across a wide temperature range (-20 to 100 °C). By regulating the lithium salt content, the mechanical properties, conductivities, and viscoelastic behaviors can be tailored. Benefiting from these features, LBAEs have been successfully applied in sensing devices for monitoring human motion (e.g., finger bending, swallowing, and clenching). Notably, even after four reprocessing cycles, LBAEs demonstrate structural integrity and maintain their operational capability. This novel approach represents a promising solution to the reprocessing challenges associated with flexible conductive devices, demonstrating the successful integration of CANs and ICEs.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic ß-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases.

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.

Enhancing cell pyroptosis with biomimetic nanoparticles for melanoma chemo-immunotherapy.

Despite the fact that immunotherapy has significantly improved the prognosis of melanoma patients, the non-response rate of monoimmunotherapy is considerably high due to insufficient tumor immunogenicity. Therefore, it is necessary to develop alternative methods of combination therapy with enhanced antitumor efficiency and less systemic toxicity. In this study, we reported a cancer cell membrane-coated zeolitic imidazole framework-8 (ZIF-8) encapsulating pyroptosis-inducer oxaliplatin (OXA) and immunomodulator imiquimod (R837) for chemoimmunotherapy. With the assistance of DNA methyltransferase inhibitor decitabine (DCT), upregulated Gasdermin E (GSDME) was cleaved by OXA-activated caspase-3, further inducing tumor cell pyroptosis, then localized antitumor immunity was enhanced by immune adjuvant R837, followed by triggering systemic antitumor immune responses. These results provided a proof-of-concept for the use of cell membrane-coated biomimetic nanoparticles as a promising drug carrier of combination therapy and a potential insight for pyroptosis-based melanoma chemo-immunotherapy.

M1 polarization of macrophages promotes stress-induced hair loss via interleukin-18 and interleukin-1ß.

Stress-induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress-induced hair loss was related to an imbalanced immune microenvironment. Screening the skin-infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress-induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress-induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in-vivo and in-vitro studies confirm that NE can induce macrophage polarization toward M1 through the ß-adrenergic receptor, Adrb2. Transcriptome, enzyme-linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase-1 inflammasome signaling and its downstream effector interleukin 18 (IL-18) and interleukin 1 beta (IL-1ß) were significantly upregulated in the NE-treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase-1, IL-18, and IL-1ß. Indeed, IL-18 and IL-1ß treatments lead to apoptosis of HFSCs. More importantly, blocking IL-18 and IL-1ß signals reversed HFSCs depletion in skin organoid models and attenuated stress-induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)-endocrine (NE)-immune (M1 macrophages) axis in stress-induced hair shedding and suggestes that IL-18 or IL-1ß may be promising therapeutic targets.

Design, synthesis and evaluate of indazolylaminoquinazoline derivatives as potent Tropomyosin receptor kinase (TRK) inhibitors.

Tropomyosin receptor kinases (TRKs), the superfamily of transmembrane receptor tyrosine kinases, have recently become an attractive method for precision anticancer therapies since the approval of Larotrectinib and Entrectinib by FDA. Herein, we reported the discovery of a series of novel indazolylaminoquinazoline and indazolylaminoindazole as TRK inhibitors. The representative compound 30f exhibited good inhibitory activity against TRKWT, TRKG595R and TRKG667C with IC50 values of 0.55 nM, 25.1 nM and 5.4 nM, respectively. The compound also demonstrated potent superior to Larotrectinib antiproliferative activity against a panel of Ba/F3 cell lines transformed with both NTRK wild type and mutant fusions (IC50 = 10-200 nM). In addition, compound 30f exhibited good in vitro metabolic stability (T1/2 = 73.0 min), indicating that the quinazoline derivatives may have better metabolic stability. Finally, the binding mode of compound 30f predicted by molecular docking well explained the good enzyme inhibitory activity of indazolylaminoquinazoline compounds as TRK inhibitor. Thus, compound 30f can be used as a promising lead molecule for further structural optimization.

Identifying potential ferroptosis key genes for diagnosis and treatment of postmenopausal osteoporosis through competitive endogenous RNA network analysis.

Objective: Postmenopausal osteoporosis (PMOP) is a common systemic metabolic bone disorder that is owing to the reduced estrogen secretion and imbalance of bone absorption and bone formation in postmenopausal women. Ferroptosis has been identified as a novel modulatory mechanism of osteoporosis. Nevertheless, the particular modulatory mechanism between ferroptosis and PMOP is still unclear. The objective of the current investigation was to detect potential biomarkers connected to ferroptosis in PMOP and discover its probable mechanism through bioinformatics. Methods: We downloaded PMOP-related microarray datasets from the database of Gene Expression Omnibus (GEO) and obtained the differentially expressed genes (DEGs). Utilizing bioinformatics analysis, the DEGs were intersected with the ferroptosis dataset to obtain ferroptosis-connected mRNAs. Enrichment analysis employing KOBAS 3.0 was conducted to comprehend the biological functions and enrichment pathways of the DEGs. The generation of the protein-protein interaction (PPI) network was conducted with the aim of identifying central genes. Lastly, the coexpression and competitive endogenous RNA (ceRNA) networks were built using Cytoscape. With the help of external datasets GSE56815 to verify the reliability of the hub genes by plotting ROC curves. Results: We identified 178 DE microRNAs (miRNAs), 138 DE circular RNAs (circRNAs), and 86 ferroptosis-related mRNAs. Enrichment analysis exhibited that mRNAs were primarily connected with the signaling pathways of PI3K/Akt, metabolism, mTOR, FoxO, HIF-1, AMPK, MAPK, ferroptosis, VEGF, and NOD-like receptors. Generation of the PPI network detected eight hub genes. The circRNA/miR-23b-3p/PTEN axis may relieve PMOP by inhibiting ferroptosis through targeting the pathway of PI3K/Akt signaling, which is a vital modulatory pathway for PMOP progression. Moreover, the ROC curves ultimately indicates that the four hub genes have greater diagnostic importance in PMOP samples in contrast to the normal group samples, which may be possible markers for PMOP diagnosis. Conclusions: Bioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management. Moreover, the circRNA/miR-23b-3p/PTEN axis may relieve PMOP by suppressing ferroptosis through targeting the pathway of PI3K/Akt signaling, providing a new avenue to explore the pathogenesis of PMOP.

Triple Hybrid Cellular Nanovesicles Promote Cardiac Repair after Ischemic Reperfusion.

The management of myocardial ischemia/reperfusion (I/R) damage in the context of reperfusion treatment remains a significant hurdle in the field of cardiovascular disorders. The injured lesions exhibit distinctive features, including abnormal accumulation of necrotic cells and subsequent inflammatory response, which further exacerbates the impairment of cardiac function. Here, we report genetically engineered hybrid nanovesicles (hNVs), which contain cell-derived nanovesicles overexpressing high-affinity SIRPα variants (SαV-NVs), exosomes (EXOs) derived from human mesenchymal stem cells (MSCs), and platelet-derived nanovesicles (PLT-NVs), to facilitate the necrotic cell clearance and inhibit the inflammatory responses. Mechanistically, the presence of SαV-NVs suppresses the CD47-SIRPα interaction, leading to the promotion of the macrophage phagocytosis of dead cells, while the component of EXOs aids in alleviating inflammatory responses. Moreover, the PLT-NVs endow hNVs with the capacity to evade immune surveillance and selectively target the infarcted area. In I/R mouse models, coadministration of SαV-NVs and EXOs showed a notable synergistic effect, leading to a significant enhancement in the left ventricular ejection fraction (LVEF) on day 21. These findings highlight that the hNVs possess the ability to alleviate myocardial inflammation, minimize infarct size, and improve cardiac function in I/R models, offering a simple, safe, and robust strategy in boosting cardiac repair after I/R.

Characterization of SARS-CoV-2-specific humoral immunity and associated factors in the healthy population post-vaccination.

OBJECTIVES: To investigate factors that may influence humoral immunity post-vaccination with a COVID-19-inactivated vaccine (SC2IV). METHODS: A total of 1596 healthy individuals from the Seventh Affiliated Hospital, Sun Yat-sen University (1217) and Shenzhen Baotian Hospital (379) were enrolled in this study among which 694 and 218 participants were vaccinated with two-dose SC2IV, respectively. Physical examination indices were recorded. The levels of neutralizing antibody (NA), Spike IgG, receptor-binding domain (RBD) IgG, RBD IgG + IgM + IgA, and nucleocapsid IgG of SARS-CoV-2 were measured by a non-virus ELISA kit. Multiple statistical analyses were carried out to identify factors that influence humoral immunity post-vaccination. RESULTS: The two-dosage vaccination could induce NA in more than 90 % of recipients. The NA has the strongest correlation with anti-RBD IgG. Age is the most important independent index that affects the NA level, while basophil count, creatine kinase-MB, mean corpuscular hemoglobin, the ratio of albumin to urine creatinine, and thyroglobulin antibody have relatively minor contributions. Indices that affect the NA level were different between males and females. Antibodies targeting other epitopes of SARS-CoV-2 were detected in recipients without anti-RBD. CONCLUSIONS: The factors identified in association with the NA level post-vaccination may help to evaluate the protective effect, risk of re-infection, the severity of symptoms, and prognosis for vaccine recipients in clinical.

Erchen decoction alleviates the progression of NAFLD by inhibiting lipid accumulation and iron overload through Caveolin-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.

Photothermal Ferrotherapy - Induced Immunogenic Cell Death via Iron-Based Ternary Chalcogenide Nanoparticles Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS2 , is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS2 possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS2 promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC.

Enhancing Interfacial Stability and Mechanical Strength of a CoSb3-Based Thermoelectric Junction Using Ti-Based Alloy Barrier Layers.

CoSb3-based filled skutterudites (SKDs) are among the most promising materials for power generation. However, the poor interfacial stability and mechanical strength severely limit their practical application when joined with Cu electrodes. In this study, we propose multiphase Ti-based alloy barrier layers for CoSb3-based thermoelectric junctions to prevent the continuous brittle TiCoSb phase formation. Following the principles of coefficient of thermal expansion matching, we designed three types of Ti80-xNbxCo20 (x = 0, 5, and 10, at.%) barrier layers with the thin intermetallic compound (IMC) layers (<20 µm). Transmission electron microscopy analysis revealed that the interfacial microstructure of the Ti75Nb5Co20/Ce-SKD junction comprises Ti5Sb3, Ti5CoSb3, TiCoSb, and TiSb2 phases, as well as unreacted TiCo, Ti2Co, and Ti(Nb)ss phases, demonstrating a uniform staggered distribution state. After aging tests, the IMC thickness increased gradually from 7 to 12 µm, and the interfacial contact resistivity increased from 7.59 to 15.46 µΩ·cm2. A Cu layer was chosen as a buffer during the brazing process to prevent the formation of cracks and holes. After aging for 360 h at 823 K, the shear strength of the brazed joints remained at ∼21 MPa. Our results demonstrate that the Cu/CuSnP/Cu/Ti75Nb5Co20/Ce-SKD brazed joint exhibits excellent interfacial stability and satisfactory mechanical strength.

Mutual communication between radiosensitive and radioresistant esophageal cancer cells modulates their radiosensitivity.

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.

Emerging technologies for engineering of extracellular vesicles.

Extracellular vesicles (EVs) are lipid-bilayer membrane-enclosed vesicles that are secreted by all cell types. Natural EVs contain biological information such as proteins, nucleic acids, and lipids from their parent cells. Therefore, EVs have been extensively studied as diagnostic biomarkers and therapeutic tools under normal and pathological conditions. However, some drawbacks, including low yield, poor therapeutic effects, lack of imaging, and targeting capacity of natural EVs, still need to be improved. Emerging engineering technologies have rendered EVs new properties or functionalities that broadened their applications in the biomedical field. Herein, in this review, we gave a brief overview of advanced strategies for EV engineering. We focused on pre-treatment of parent cells to regulate their released EVs. Meanwhile, we summarized and discussed the direct modification of EVs to achieve drug loading, imaging, and targeting functionalities for downstream applications.

Implantable magnetically-actuated capsule for on-demand delivery.

Many implantable drug delivery systems (IDDS) have been developed for long-term, pulsatile drug release. However, they are often limited by bulky size, complex electronic components, unpredictable drug delivery, as well as the need for battery replacement and consequent replacement surgery. Here, we develop an implantable magnetically-actuated capsule (IMAC) and its portable magnetic actuator (MA) for on-demand and robust drug delivery in a tether-free and battery-free manner. IMAC utilizes the bistable mechanism of two magnetic balls inside IMAC to trigger drug delivery under a strong magnetic field (|Ba| > 90 mT), ensuring precise and reproducible drug delivery (9.9 ± 0.17 µg per actuation, maximum actuation number: 180) and excellent anti-magnetic capability (critical trigger field intensity: ∼90 mT). IMAC as a tetherless robot can navigate to and anchor at the lesion sites driven by a gradient magnetic field (∇ Bg = 3 T/m, |Bg| < 60 mT), and on-demand release drug actuated by a uniform magnetic field (|Ba| = âˆ¼100 mT) within the gastrointestinal tract. During a 15-day insulin administration in vivo, the diabetic rats treated with IMAC exhibited highly similar pharmacokinetic and pharmacodynamic profiles to those administrated via subcutaneous injection, demonstrating its robust and on-demand drug release performance. Moreover, IMAC is biocompatible, batter-free, refillable, miniature (only Φ 6.3 × 12.3 mm3), and lightweight (just 0.8 g), making it an ideal alternative for precise implantable drug delivery and friendly patient-centered drug administration.

Machine learning-derived identification of tumor-infiltrating immune cell-related signature for improving prognosis and immunotherapy responses in patients with skin cutaneous melanoma.

BACKGROUND: Immunoblockade therapy based on the PD-1 checkpoint has greatly improved the survival rate of patients with skin cutaneous melanoma (SKCM). However, existing anti-PD-1 therapeutic efficacy prediction markers often exhibit a poor situation of poor reliability in identifying potential beneficiary patients in clinical applications, and an ideal biomarker for precision medicine is urgently needed. METHODS: 10 multicenter cohorts including 4 SKCM cohorts and 6 immunotherapy cohorts were selected. Through the analysis of WGCNA, survival analysis, consensus clustering, we screened 36 prognostic genes. Then, ten machine learning algorithms were used to construct a machine learning-derived immune signature (MLDIS). Finally, the independent data sets (GSE22153, GSE54467, GSE59455, and in-house cohort) were used as the verification set, and the ROC index standard was used to evaluate the model. RESULTS: Based on computing framework, we found that patients with high MLDIS had poor overall survival and has good prediction performance in all cohorts and in-house cohort. It is worth noting that MLDIS performs better in each data set than almost all models which from 51 prognostic signatures for SKCM. Meanwhile, high MLDIS have a positive prognostic impact on patients treated with anti-PD-1 immunotherapy by driving changes in the level of infiltration of immune cells in the tumor microenvironment. Additionally, patients suffering from SKCM with high MLDIS were more sensitive to immunotherapy. CONCLUSIONS: Our study identified that MLDIS could provide new insights into the prognosis of SKCM and predict the immunotherapy response in patients with SKCM.

The preliminary development and clinical verification of the positive index score scale of "Heart Arthralgia Syndrome".

BACKGROUND: In recent years, the age of onset for coronary heart disease (CHD) has become one of the leading causes of death worldwide. The medical treatments occasionally cause side effects; therefore, there is still an urgent need to develop new therapeutic modalities for CHD in clinical practice. "Heart Arthralgia Syndrome (HAS)" is a general term for CHD with arthralgia symptoms proposed by our team based on clinical experience. At present, there is little in-depth research on the treatment of HAS by TCM. Pick Complex Therapy (PCT) is an innovative and developed theory of collateral acupuncture therapy for HAS. METHODS: We collected data from 276 patients who met the criteria for (coronary heart disease with numbness of neck, shoulder, waist, and leg). We selected 24 diagnostic criteria for HAS by means of multiple methods, including Cronbach's α coefficient, retest reliability, subjective evaluation, discrete trend, Pearson's rank correlation coefficient and factor analysis method. We thereafter evaluated the reliability, validity and responsiveness of the scale. In the clinical validation phase, we verified whether the preliminary developed positive index (PI) scale can guide clinical practice. Forty (40) patients with HAS were selected in the study. SPSS23.0 statistical software was used for statistical processing and analysis. RESULTS: Assessment results of the initial PI scale for HAS: the average time to complete the scale was 7.47 ± 3.59 minutes. Cronbach's α coefficient for the initial table was 0.711, the retest reliability was 0.897, the Kaiser-Meyer-Olkin test result was 0.844, and the Bartlett test result was 2502.300. Following maximum variance rotation analysis, the cumulative variance contribution rate was determined to be 66.605%. In the clinical validation phase of the PI scale, we tested 40 patients before and after the PCT treatments. After 3 measurements, the correlation between the PI scale for HAS and the angina pectoris grading scoring method table decreased gradually. The last 2 measurement results of study indicated that there was a significant correlation between the PI scale and thrombin time, while physical and chemical examination showed no significant changes. CONCLUSION: The PI scale for HAS can be widely used in the clinic as a preliminary evaluation tool for guiding PCT.

Effects of once-weekly glucagon-like peptide-1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin-angiotensin system.

AIM: To investigate the potential mechanism of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD). METHODS: We searched both Chinese and English databases for randomized controlled trials related to once-weekly GLP-1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP-1 RA. The underlying mechanism was analysed by network pharmacology. RESULTS: In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non-fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once-weekly GLP-1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low-density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin-angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched. CONCLUSIONS: Our study suggests that once-weekly GLP-1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin-angiotensin system. However, further research is needed to confirm these findings and determine cause and effect.

Identifying subgroups of patients with type 2 diabetes based on real-world traditional chinese medicine electronic medical records.

Introduction: Type 2 diabetes (T2D) is a multifactorial complex chronic disease with a high prevalence worldwide, and Type 2 diabetes patients with different comorbidities often present multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of the clinical Type 2 diabetes population to help identify more accurate disease subtypes for personalized treatment. Methods: Here, utilizing the traditional Chinese medicine (TCM) clinical electronic medical records (EMRs) of 2137 Type 2 diabetes inpatients, we followed a heterogeneous medical record network (HEMnet) framework to construct heterogeneous medical record networks by integrating the clinical features from the electronic medical records, molecular interaction networks and domain knowledge. Results: Of the 2137 Type 2 diabetes patients, 1347 were male (63.03%), and 790 were female (36.97%). Using the HEMnet method, we obtained eight non-overlapping patient subgroups. For example, in H3, Poria, Astragali Radix, Glycyrrhizae Radix et Rhizoma, Cinnamomi Ramulus, and Liriopes Radix were identified as significant botanical drugs. Cardiovascular diseases (CVDs) were found to be significant comorbidities. Furthermore, enrichment analysis showed that there were six overlapping pathways and eight overlapping Gene Ontology terms among the herbs, comorbidities, and Type 2 diabetes in H3. Discussion: Our results demonstrate that identification of the Type 2 diabetes subgroup based on the HEMnet method can provide important guidance for the clinical use of herbal prescriptions and that this method can be used for other complex diseases.