Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis.

BACKGROUNDS: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. METHODS: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger's test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. RESULTS: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = -5.25, 95% CI: -5.94 to -4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. CONCLUSION: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

Co-morbid intersections of cancer and cardiovascular disease and targets for natural drug action: Reprogramming of lipid metabolism.

Cancer and cardiovascular diseases are major contributors to global morbidity and mortality, and their seemingly separate pathologies are intricately intertwined. In the context of cancer, the cardiovascular disease encompasses not only the side effects arising from anti-tumor treatments but also the metabolic shifts induced by oncological conditions. A growing body of research indicates that lipid metabolic reprogramming serves as a distinctive hallmark of tumors. Furthermore, anomalies in lipid metabolism play a significant role in the development of cardiovascular disease. This study delves into the cardiac implications of lipid metabolic reprogramming within the cancer context, closely examining abnormalities in lipid metabolism present in tumors, cardiac tissue, and immune cells within the microenvironment. Additionally, we examined risk factors such as obesity and anti-tumor therapy. Despite progress, a gap remains in the availability of drugs targeting lipid metabolism modulation for treating tumors and mitigating cardiac risk, with limited advancement seen in prior studies. Here, we present a review of previous research on natural drugs that exhibit both shared and distinct therapeutic effects on tumors and cardiac health by modulating lipid metabolism. Our aim is to provide insights for potential drug development.

Comparative study of different extendable intramedullary rods combined with surgery in the treatment of congenital pseudarthrosis of the tibia.

BACKGROUND: When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture PURPOSE: To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children METHODS: From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. EXCLUSION CRITERIA: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated RESULTS: It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years CONCLUSION: Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research.

METTL3 promotes the osteogenic differentiation of periosteum-derived MSCs via regulation of the HOXD8/ITGA5 axis in congenital pseudarthrosis.

Background: Congenital pseudarthrosis of the tibia (CPT) is a dominant health challenge in pediatric orthopedics. The essential process in the development of CPT is the limited capacity of mesenchymal stem cells (MSCs) derived from CPT to undergo osteogenic differentiation. Our research aimed to elucidate the role and mechanism of methyltransferase-like 3 (METTL3) in the osteogenic differentiation process of CPT MSCs. Methods: The osteogenic differentiation medium was used to culture MSCs, and the detection of osteogenic differentiation was performed using Alizarin Red S and alkaline phosphatase (ALP) assays. Gene or protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, or immunofluorescence (IF) staining. The m6A modification of Homeobox D8 (HOXD8) was verified by methylated RNA immunoprecipitation (MeRIP) assay. Interactions between METTL3 and HOXD8 or HOXD8 and integrin alpha 5 (ITGA5) promoter were validated by the luciferase reporter gene, RIP, and chromatin immunoprecipitation (ChIP) assays. Results: METTL3 overexpression enhanced CPT MSCs' osteogenic differentiation. METTL3 stabilized the HOXD8 in an m6A-dependent manner. Moreover, the overexpressed ITGA5 up-regulated the CPT MSCs' osteogenic differentiation. Further, HOXD8 could transcriptionally activate ITGA5. METTL3 increased the transcription of ITGA5 via HOXD8 to enhance the osteogenic differentiation of CPT MSCs. Conclusion: METTL3 promoted osteogenic differentiation via modulating the HOXD8/ITGA5 axis in CPT MSCs.

Detection of ion cyclotron emission by using an ion cyclotron range of frequency antennas-based diagnostic system in experimental advanced superconducting tokamak.

In the experimental advanced superconducting tokamak (EAST), a novel ion cyclotron range of frequency (ICRF) antenna-based diagnostic system is designed to measure ion cyclotron emission (ICE) driven by high-energy ions. The diagnostic system includes ICRF antenna straps, a three-tune impedance matching system, a coaxial switching system, a direct current block, and a data acquisition and storage system. Using the coaxial switching system, the ICRF antenna can be switched from the heating mode to the coupling mode between two discharges. In the 2023 EAST experiment campaign, core ICE was observed using the ICRF antenna-based diagnostic system during neutron beam injection heating, and the obtained results agreed well with the signal detected by the previous high-frequency B-dot probe-based diagnostic system.

ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

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.

Fusion of airborne multimodal point clouds for vegetation parameter correction extraction in burned areas.

Most experimental studies use unimodal data for processing, the RGB image point cloud cannot separate the shrub and tree layers according to the visible vegetation index, and the airborne laser point cloud is difficult to distinguish between the ground and grass ranges, to address the above problems, a multi-band information image fusing the LiDAR point cloud and the RGB image point cloud is constructed. In this study, data collected from UAV platforms, including RGB image point clouds and laser point clouds, were used to construct a fine canopy height model (using laser point cloud data) and high-definition digital orthophotos (using image point cloud data), and the orthophotos were fused with a canopy height model (CHM) by selecting the Difference Enhancement Vegetation Index (DEVI) and Normalised Green-Blue Discrepancy Index (NGBDI) after comparing the accuracy of different indices. Morphological reconstruction of CHM + DEVI/NGBDI fusion image, remove unreasonable values; construct training samples, using classification regression tree algorithm, segmentation of the range of the burned areas and adaptive extraction of vegetation as trees, shrubs and grasslands, tree areas as foreground markers using the local maximum algorithm to detect the tree apexes, the non-tree areas are assigned to be the background markers, and the Watershed Transform is performed to obtain the segmentation contour; the original laser point cloud is divided into chunks according to the segmented single-tree contour, and the highest point is traversed to search for the highest point, and corrected for the height of the single-tree elevations one by one. Accuracy analysis of the vegetation information extracted by the method with the measured data showed that the improved method increased the overall recall rate by 4.1%, the overall precision rate by 3.7%, the overall accuracy F1 score by 3.9%, and the tree height accuracy by 8.8%, 1.4%, 1.7%, 6.4%, 1.8%, and 0.3%, respectively, in the six sampling plots. The effectiveness of the improved method is verified, while the higher the degree of vegetation mixing in the region the better the extraction effect of the improved algorithm.

Successful reimplantation of extruded bone segment in lower limb open fractures: case report and literature review.

Objective: The aim of this study is to summarize and demonstrate the different sterilization methods and surgical techniques for open fractures with impacted bone segments in the lower limbs. Methods: A retrospective analysis was conducted on the clinical characteristics, treatment methods, and outcomes of a case involving a 10.5 cm extruded segment of the femur in a 9-year-old male with a right femoral comminuted fracture treated at our center. Additionally, a retrospective review and summary were conducted on all reported cases of open fractures with impacted bone segments in the lower limbs. Results: Our center treated a 9-year and 11-month-old male child who presented with a Gustilo type IIIB open fracture of the femur along with a large segment of the femur being ejected as a result of a car accident. The child was resuscitated to correct hypovolemic shock, underwent emergency wound debridement, and had Ilizarov external fixation of the femur. The ejected femur segment was sterilized using ethylene oxide and re-implanted four days after the injury. A literature review showed that out of the cases of open fractures with impacted bone segments in the lower limbs, there were 14 cases involving the femur and 5 cases involving the tibia. Among them, sterilization was performed using povidone-iodine in 6 cases, high-pressure steam sterilization in 3 cases, and other methods including gamma-ray irradiation and soaking in antibacterial solution were used in the remaining cases. In terms of surgical methods, 7 cases were fixed with locking plates, 3 cases were fixed with external fixation devices, 1 case was immobilized in a cast, 1 case was fixed with an intramedullary rod, and 4 cases involved a combination of external fixation and internal fixation. The average time for re-implantation was 7.6 days after the injury. There were no serious complications such as infection or non-union observed in any of the cases during follow-up. Conclusion: Ethylene oxide can be considered a reliable choice for the reimplantation of displaced bone segments in open fractures after sterilization.

Efficacy and safety of compound kushen injection for treating advanced colorectal cancer: A protocol for a systematic review and meta-analysis.

Introduction: Compound Kushen Injection (CKI) is a traditional Chinese medicine extracted from Sophora flavescens Aiton and Heterosmilax japonica Kunth. Widely utilized in China for the comprehensive treatment of colorectal cancer (CRC), this study aims to systematically assess the efficacy and safety of CKI when combined with chemotherapy for the treatment of advanced CRC, based on available data. Methods: Randomized controlled trials investigating the efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC will be comprehensively searched from databases, including PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang, Chinese Biomedicine Database Searches, Chinese Clinical Trial Registry, and ClinicalTrials.gov until November 2022. Two independent reviewers will screen the studies, assess the risk of bias, and extract data in duplicate. The ROB2 tool will be employed to assess the quality of included studies. Stata 16 will be used for data analysis, and publication bias will be assessed using funnel plots and Egger's test. The quality of evidence will be evaluated according to GRADE, and trial sequence analysis (TSA) will be utilized to calculate the final total sample size required for the meta-analysis. The results of this systematic review will be published in a peer-reviewed journal. The proposed review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022380106). Discussion: This systematic review will integrate current evidence on CKI in advanced CRC and analyze the clinical efficacy and safety of CKI combined with different chemotherapy regimens, providing valuable guidance on the use of CKI in CRC patients.

Multifaceted role of microRNAs in gastric cancer stem cells: Mechanisms and potential biomarkers.

MicroRNAs (miRNAs) have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells (CSCs). The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells (GCSCs). Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs. This review summarizes the coding process and biological functions of miRNAs and demonstrates their role and efficacy in gastric cancer (GC) metastasis, drug resistance, and apoptosis, especially in the regulatory mechanism of GCSCs. It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis, apart from the initial formation of GC. It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC. We believe that this review may help in designing novel therapeutic approaches for GC.

Study on the mechanism of MDSC-platelets and their role in the breast cancer microenvironment.

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.

Tumor-draining lymph nodes: opportunities, challenges, and future directions in colorectal cancer immunotherapy.

Tumor-draining lymph nodes (TDLNs) are potential immunotherapy targets that could expand the population of patients with colorectal cancer (CRC) who may benefit from immunotherapy. Currently, pathological detection of tumor cell infiltration limits the acquisition of immune information related to the resected lymph nodes. Understanding the immune function and metastatic risk of specific stages of lymph nodes can facilitate better discussions on the removal or preservation of lymph nodes, as well as the timing of immunotherapy. This review summarized the contribution of TDLNs to CRC responses to immune checkpoint blockade therapy, local immunotherapy, adoptive cell therapy, and cancer vaccines, and discussed the significance of these findings for the development of diagnostics based on TDLNs and the potential implications for guiding immunotherapy after a definitive diagnosis. Molecular pathology and immune spectrum diagnosis of TDLNs will promote significant advances in the selection of immunotherapy options and predicting treatment efficacy.

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy.

BACKGROUND: The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. METHODS: The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. RESULTS: PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. CONCLUSIONS: Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.

Conventional HE staining combined with two special staining methods to identify antemortem stab wound in case with highly decomposed mutilated corpses.

This study aims to identify an antemortem neck stab wound on a highly decomposed, headless and mutilated body by conventional hematoxylin-eosin (HE) staining combined with Ponceau-Victoria blue B staining (P-VB staining) and Masson staining. Specifically, a tissue sample was excised from the skin and muscle tissue at the junction of the normal and brownish discolored areas around the suspected stabbing tract of the left neck, in the upper and lower wound-clavicle-shoulder region. Conventional HE staining only provides a morphological and structural outline of the tissue, with both the injury hemorrhage and local connective tissue appearing eosinophilic pink. However, P-VB staining shows obvious contrast between the injury hemorrhage and connective tissue, with the former appearing yellow-green and the latter appearing orange-red. Similarly, Masson staining of the injury hemorrhage and connective tissue contrast clearly with purple-red and dark blue, respectively. Therefore, our study highlights that conventional HE staining with the combination of P-VB staining and Masson staining allowed for a clearer and corroborated identification of antemortem injury and hemorrhage from the stab wound in highly decomposed mutilated corpses.

Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4microsphere-doped hydrogel.

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Drug monomers from Salvia miltiorrhiza Bge. promoting tight junction protein expression for therapeutic effects on lung cancer.

Salvia miltiorrhiza Bge. is a traditional Chinese medicine (TCM) that has been used for treatment of various diseases, including cancer by activating blood circulation and removing blood stasis. Tanshinone (TanIIA) and cryptotanshinone (CPT) are major lipophilic compounds extracted from the root of Salvia miltiorrhiza Bge., which are considered to be the effective compounds affecting the efficacy of the anti-tumor therapy of Salvia miltiorrhiza Bge. We have explored the mechanism of CPT and TanIIA exerting inhibition in non-small cell lung cancer (NSCLC) to provide experimental data support for guiding the translational development and clinical application of anti-tumor components of TCM. The subcutaneous tumor model and in vitro culture model of A549 cells was constructed to evaluate CPT and TanIIA's tumour-inhibitory effect respectively. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to CPT and TanIIA treatment. qRT-PCR and Western blot were used to explore the mechanism of CPT and TanIIA intervention on NSCLC. Both CPT and TanIIA significantly inhibited the proliferation of A549 tumor cells and tumor growth in animal models. After intervention, the migration ability decreased and the level of apoptosis increased. RNA-seq results showed that both CPT and TanIIA could cause gene differential expression, miR-21-5p as one of the most significant gene expression differences between the two groups, and could act on cell connectivity. CPT and TanIIA play a regulatory role in regulating tight junction proteins (Occludin and ZO1), and Occludin mRNA and protein levels were reduced in an in vitro miR-21-5p overexpression A549 cell model. The mechanisms may be related to the reduction of miR-21-5p expression to increase the level of promoted tight junction protein expression for the purpose of inhibiting proliferation and invasion of NSCLC.

Hepatic venous gas secondary to pulmonary barotrauma: rat model study.

Intrahepatic gas (IHG) is commonly observed during early postmortem examinations of humans with upper or lower airway obstructions. We conducted a study to test the hypothesis that intrapulmonary gas could retrogradely spread to the hepatic vein following pulmonary barotrauma (PB). To establish a rat model of pulmonary barotrauma, we utilized a controllable pressure-vacuum pump to apply airway pressure (40, 60, or 80 mmHg). The rats were dissected directly at the end of the experiment, and histological analysis was performed through microscopic examination of the rats. Additionally, the rats were ventilated with meglumine diatrizoate under pressures of 160 and 250 mmHg to observe the signal dynamic diffusion using X-ray fluoroscopy examination. Rats exhibited classical changes associated with PB, such as alveolar rupture, pulmonary interstitial emphysema, and hemorrhage, as well as IHG characterized by the presence of gas in the hepatic vein and hepatic sinusoids. Air emboli were not observed in the liver in any of the 40 mmHg groups. However, they were observed in the liver in the 60 and 80 mmHg groups, the amount and size of air emboli in the 80 mmHg group were greater than those in the 60 mmHg group (p < 0.05). The 80 mmHg group presented radial grape-like bubbles in the centrilobular portion of the liver accompanied by congestion in the peripheral region of the hepatic lobule. X-ray fluoroscopy examination revealed a gradual enhancement of dynamic contrast medium signals from the lung to the inferior vena cava and then to the liver. Our findings indicate that pulmonary barotrauma can lead to the retrograde spread of intrapulmonary gas to the hepatic vein. When it is clear that no decomposition of the body has occurred, the presence of IHG serves as a novel indicator for the diagnosis of obstructive pulmonary disease or obstruction in the upper or lower airway.

Novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives as potential anticancer agents.

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.