Inubritantrimers A-D: Trimerized Sesquiterpenoid [4 + 2] Adducts Featuring a Distinctive Spiro-Polycyclic Scaffold from Inula britannica.

Inubritantrimer A (1), a trace trimerized sesquiterpenoid [4 + 2] adduct featuring an unusual exo-exo type spiro-polycyclic scaffold, together with three new endo-exo [4 + 2] adducts, inubritantrimers B-D (2-4), were discovered from the flowers of Inula britannica. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, and ECD approaches. 1 is characterized as a novel exo-exo trimer, synthesized biogenetically from three sesquiterpenoid monomers, featuring a unique linkage of C-11/C-1', C-13/C-3' and C-13'/C-3″, C-11'/C-1″ through a two-step exo [4 + 2] cycloaddition process. Compounds 1-4 exhibited modest cytotoxicity against breast cancer cells with IC50 values in the range of 5.84-12.01 µM.

CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk.

BACKGROUND: This study used bioinformatics combined with statistical methods to identify plasma biomarkers that can predict intracranial aneurysm (IA) rupture and provide a strong theoretical basis for the search for new IA rupture prevention methods. METHODS: We downloaded gene expression profiles in the GSE36791 and GSE122897 datasets from the Gene Expression Omnibus (GEO) database. Data were normalized using the "sva" R package and differentially expressed genes (DEGs) were identified using the "limma" R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used for DEG function analysis. Univariate logistic regression analysis, least absolute shrinkage and selection operator (LASSO) regression modeling, and the support vector machine recursive feature elimination (SVM-RFE) algorithm were used to identify key biomarker genes. Data from GSE122897 and GSE13353 were extracted to verify our findings. RESULTS: Eight co-DEG mRNAs were identified in the GSE36791 and GSE122897 datasets. Genes associated with inflammatory responses were clustered in the co-DEG mRNAs in IAs. CD6 and C-C chemokine receptor 7 (CCR7) were identified as key genes associated with IA. CD6 and CCR7 were upregulated in patients with IA and their expression levels were positively correlated. There were significant differences in the infiltration of immune cells between IAs and normal vascular wall tissues (p < 0.05). A predictive nomogram was designed using this two-gene signature. Binary transformation of CD6 and CCR7 was performed according to the cut-off value to construct the receiver-operating characteristic (ROC) curve and showed a strong predictive ability of the CD6-CCR7 gene signature (p < 0.01; area under the curve (AUC): 0.90; 95% confidence interval (CI): 0.88-0.92). Furthermore, validation of this two-gene signature using the GSE122897 and GSE13353 datasets proved it to be valuable for clinical application. CONCLUSIONS: The identified two-gene signature (CD6-CCR7) for evaluating the risk of IA rupture demonstrated good clinical application value.

Potential Role of Bmal1 in Lipopolysaccharide-Induced Depression-Like Behavior and its Associated "Inflammatory Storm".

Inflammation plays an important role in the pathogenesis of depression; however, the underlying mechanisms remain unclear. Apart from the disordered circadian rhythm in animal models and patients with depression, dysfunction of clock genes has been reported to be involved with the progress of inflammation. This study aimed to investigate the role of circadian clock genes, especially brain and muscle ARNT-like 1 (Bmal1), in the linkage between inflammation and depression. Lipopolysaccharide (LPS)-challenged rats and BV2 cells were used in the present study. Four intraperitoneal LPS injections of 0.5 mg/kg were administered once every other day to the rats, and BV2 cells were challenged with LPS for 24 h at the working concentration of 1 mg/L, with or without the suppression of Bmal1 via small interfering RNA. The results showed that LPS could successfully induce depression-like behaviors and an "inflammatory storm" in rats, as indicated by the increased immobility time in the forced swimming test and the decreased saccharin preference index in the saccharin preference test, together with hyperactivity of the hypothalamic-pituitary-adrenal axis, hyperactivation of astrocyte and microglia, and increased peripheral and central abundance of tumor necrosis factor-α, interleukin 6, and C-reactive protein. Moreover, the protein expression levels of brain-derived neurotrophic factor, triggering receptor expressed on myeloid cells 1, Copine6, and Synaptotagmin1 (Syt-1) decreased in the hippocampus and hypothalamus, whereas the expression of triggering receptor expressed on myeloid cells 2 increased. Interestingly, the fluctuation of temperature and serum concentration of melatonin and corticosterone was significantly different between the groups. Furthermore, protein expression levels of the circadian locomotor output cycles kaput, cryptochrome 2, and period 2 was significantly reduced in the hippocampus of LPS-challenged rats, whereas Bmal1 expression was significantly increased in the hippocampus but decreased in the hypothalamus, where it was co-located with neurons, microglia, and astrocytes. Consistently, apart from the reduced cell viability and increased phagocytic ability, LPS-challenged BV2 cells presented a similar trend with the changed protein expression in the hippocampus of the LPS model rats. However, the pathological changes in BV2 cells induced by LPS were reversed after the suppression of Bmal1. These results indicated that LPS could induce depression-like pathological changes, and the underlying mechanism might be partly associated with the imbalanced expression of Bmal1 and its regulated dysfunction of the circadian rhythm.

Revolutionizing Cancer Care: Advances in Carbon-Based Materials for Diagnosis and Treatment.

Cancer involves intricate pathological mechanisms marked by complexities such as cytotoxicity, drug resistance, stem cell proliferation, and inadequate specificity in current chemotherapy approaches. Cancer therapy has embraced diverse nanomaterials renowned for their unique magnetic, electrical, and optical properties to address these challenges. Despite the expanding corpus of knowledge in this area, there has been less advancement in approving nano drugs for use in clinical settings. Nanotechnology, and more especially the development of intelligent nanomaterials, has had a profound impact on cancer research and treatment in recent years. Due to their large surface area, nanoparticles can adeptly encapsulate diverse compounds. Furthermore, the modification of nanoparticles is achievable through a broad spectrum of bio-based substrates, including DNA, aptamers, RNA, and antibodies. This functionalization substantially enhances their theranostic capabilities. Nanomaterials originating from biological sources outperform their conventionally created counterparts, offering advantages such as reduced toxicity, lower manufacturing costs, and enhanced efficiency. This review uses carbon nanomaterials, including graphene-based materials, carbon nanotubes (CNTs) based nanomaterials, and carbon quantum dots (CQDs), to give a complete overview of various methods used in cancer theranostics. We also discussed their advantages and limitations in cancer diagnosis and treatment settings. Carbon nanomaterials might significantly improve cancer theranostics and pave the way for fresh tumor diagnosis and treatment approaches. More study is needed to determine whether using nano-carriers for targeted medicine delivery may increase material utilization. More insight is required to explore the correlation between heightened cytotoxicity and retention resulting from increased permeability.

Bereaved parents' perceptions of memory making: a qualitative meta-synthesis.

OBJECTIVE: This study aims to investigate the experiences of parents who have experienced bereavement in their efforts to preserve memories of their deceased child. METHODS: Employing a qualitative meta-synthesis approach, this study systematically sought relevant qualitative literature by conducting searches across various electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Wiley, up until July 2023. RESULTS: Nine studies are eligible for inclusion and included in the meta-synthesis. Three overarching categories are identified: (1) Affirming the Significance of Memory Making. (2) Best Practices in Memory Making. (3) Barriers to Effective Memory Making. CONCLUSION: Bereaved parents highly value the act of creating lasting memories, emphasizing its profound significance. While forming these memories, it is imperative to offer family-centered care and honor diverse preferences and needs. It is essential to offer effective support to parents, offering them a range of choices. Furthermore, a more comprehensive examination of memory-making practices is required to better understand their influence on parents' recollections of their deceased child.

The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy/nucleophagy cargos in fission yeast.

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeast Schizosaccharomyces pombe, Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 coassembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins.

Effects of Baduanjin exercise on patients with chronic nonspecific low back pain and surface electromyography signs of erector spinal muscle: A randomized controlled trial.

BACKGROUND: Chronic nonspecific low back pain (CNLBP) is a common disease usually with lower back muscle fatigue and injuries that may contribute to lumbar muscle imbalance and pain recurrence. This study aimed to examine the effectiveness of Baduanjin exercise on patients of CNLBP and to assess its impact on the surface electromyographic signals of the lumbar erector spinae muscle. METHODS: A total of 60 patients diagnosed with CNLBP were admitted from the Hubei Provincial Hospital of Traditional Chinese Medicine from March 2022 to December 2022. Those patients were randomly allocated into the Baduanjin group (n = 30) or the walking group (n = 30). Both groups received a 4-week intervention, with 5 training sessions per week. The numeric pain rating scale (the minimal clinically important difference = 2.4) and Oswestry Disability Index (the minimal clinically important difference = 13.4), electromyogram signals during lumbar flexion (FLEXAEMG), lumbar extension (EXTAEMG), and maximum lumbar flexion (MAEMG), the ratios of FLEXAEMG to MAEMG and EXTAEMG to MAEMG were collected at Baseline and posttreatment and compared using the Wilcoxon signed-rank test or Mann-Whitney U test. RESULTS: After treatment, the numeric pain rating scale score in the Baduanjin group exhibited a significant decrease compared to baseline (P < .05) and was found to be lower than that of the Walking group (mean difference 2.36; CI 95% -2.323 to -1.742; P = .001). Similarly, the Oswestry disability index in the Baduanjin group demonstrated a reduction compared to baseline (P < .05) and was lower than that of the Walking group (the mean difference 7.59; CI 95% -8.861 to -6.312; P = .001). The FLEXAEMG and EXTAEMG of both groups had a significant increase (P < .05), with the Baduanjin group demonstrating higher levels compared to the Walking group (P < .05). Conversely, the MAEMG of both groups displayed a significant decrease (P < .05), with the Baduanjin group exhibiting lower levels than the Walking group (P < .05). The FLEXAEMG to MAEMG and EXTAEMG to MAEMG in the Baduanjin group increased (P < .05) and were significantly higher than the Walking group (P < .05). CONCLUSION: Baduanjin exercise has shown to be highly effective in reducing low back pain and in promoting lumber dysfunction, due to its ability to improve the strength and flexibility of the lumbar erector spinae muscle.

Genomic profiles of renal cell carcinoma in a small Chinese cohort.

Objectives: Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. Materials and methods: Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed. Results: The most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel. Conclusion: Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.

Hsa_circ_0001162 Inhibition Alleviates High Glucose-Induced Human Podocytes Injury by the miR-149-5p/MMP9 Signaling Pathway.

Emerging evidences suggested that circular RNAs (circRNAs) are involved in diabetic nephropathy (DN). Accumulating evidence had suggested that the degree of podocyte is a major prognostic determinant of DN progression. However, the function and in-depth mechanisms of hsa_circ_0001162 in podocyte injury of DN remain unclear. Hsa_circ_0001162 expression was detected by real-time quantitative PCR (RT-qPCR) in peripheral blood of DN patients and high glucose-induced podocytes injury model. The cell counting kit 8, 5-ethynyl-2'-deoxyuridine, flow cytometry with Annexin V-FITC/PI staining, caspase-3 activity assay Kit, enzyme linked immunosorbent assay (ELISA), RT-qPCR and western blotting were used to evaluate the effect of hsa_circ_0001162 / miR-149-5p / MMP9 axis on high glucose-induced podocyte injury. Mechanistically, dual luciferase reporter was used to confirm the relationship of miR-149-5p and hsa_circ_0001162 or MMP9. Furthermore, RNA-pull down and immunoprecipitation assay were implemented to verify the potential regulatory effects of EIF4A3 on biogenesis of hsa_circ_0001162. Our results showed that hsa_circ_0001162 was highly expressed in peripheral blood of DN patients and high glucose-induced podocytes injury model, and the knockdown of hsa_circ_0001162 increased the proliferation, inhibited the apoptosis, and suppressed inflammatory response in high glucose-induced podocytes injury. Mechanism studies demonstrated that EIF4A3 bound with flanking sequences of hsa_circ_0001162 to promote hsa_circ_0001162 expression, upregulated hsa_circ_0001162 increased the MMP9 expression via sponging miR-149-5p, thus aggravating the high glucose-induced podocytes injury. Overall, our data demonstrated that knockdown of hsa_circ_0001162 inhibited high glucose-induced podocytes injury by regulating miR-149-5p/MMP9 axis, and intervention of hsa_circ_0001162/miR-149-5p/MMP9 axis may be a potentially promising therapeutic strategy for podocyte injury in DN patients.

Trienomycin A-simplified analogs: Synthesis and anti-neuroinflammatory activity.

A series of novel trienomycin A (TA)-mimetic compounds (5a-p) have been designed, synthesized, and evaluated for their in vitro anti-neuroinflammatory and neuroprotective activities. Among them, compounds 5h, 5n, and 5o exhibits relatively strong NO inhibitory activity in LPS-activated BV-2 cells with the EC50 values of 12.4, 17.3, and 8.9 µM, respectively. Moreover, 5h showed evidently neuroprotective effect against H2O2-induced PC-12 cells without cytotoxicity at 20 µM. Overall, these compounds can provide a better understanding of the structure-activity relationship of TA and furnish research ideas for anti-neuroinflammatory and neuroprotective agents.

Effect of ultrasound-guided lumbar square muscle block on stress response in patients undergoing radical gastric cancer surgery.

BACKGROUND: Radical surgery is a common treatment for patients with gastric cancer; however, it can lead to postoperative complications and intestinal barrier dysfunction. Ultrasound-guided quadratus lumborum block is often used for postoperative analgesia, but its effects on stress response and intestinal barrier function are not well understood. AIM: To investigate the effects of an ultrasound-guided quadratus lumborum block on stress response and intestinal barrier function in patients undergoing radical surgery for gastric cancer. METHODS: A total of 100 patients undergoing radical surgery for gastric cancer were randomly categorized into observation and control groups. Plasma adrenaline and cortisol levels, intestinal mucosal barrier indexes, and complication rates were compared between the two groups before, during, and 1 day after surgery. RESULTS: The observation group had significantly lower plasma adrenaline and cortisol levels during surgery and at 1 day postoperatively than that of the control group (P < 0.05). Additionally, intestinal barrier indexes (endotoxin and D-dimer) at 1 day postoperatively were significantly lower in the observation group than in the control group (P < 0.05). CONCLUSION: Ultrasound-guided quadratus lumborum block could reduce stress response, protect intestinal barrier function, and decrease the incidence of complications in patients undergoing radical surgery for gastric cancer. This technique has the potential for clinical applications.

Effect of Signal Design of Autonomous Vehicle Intention Presentation on Pedestrians' Cognition.

In this study, a method is devised that allows the intentions of autonomous vehicles to be effectively communicated to pedestrians and passengers via an efficient interactive interface. Visual and auditory factors are used as variables to investigate the effects of different autonomous vehicle signal factors on the judgment of pedestrians and to determine the main factors such that the best combination can be proposed. Two visual dimensions (i.e., color and flashing) and three auditory dimensions (i.e., rhythm, frequency, and melody) are used as the experimental signal variables. In addition, deceleration and waiting-to-restart scenarios are investigated. Multiple-choice questions and a subjective cognition scale are used for evaluation. The results show that the combination of green and slow rhythm can be used for the road-user-first case, whereas the combination of red and fast rhythm can be used for the vehicle-first case. Under the same intention, factors of color, flashing, rhythm, and melody are highly similar in terms of the combination mode, except for the frequency. In the deceleration and waiting-to-restart scenarios, the frequencies of the best signal are high and low frequencies, respectively. The results of this study can be used as a reference for the signal design of autonomous vehicles in the future and provide ideas for the interactions between autonomous vehicles and pedestrians.

Stk10 Deficiency in Mice Promotes Tumor Growth by Dysregulating the Tumor Microenvironment.

Serine-threonine kinase 10 (STK10) is a member of the STE20/p21-activated kinase (PAK) family and is predominantly expressed in immune organs. Our previous reports suggested that STK10 participates in the growth and metastasis of prostate cancer via in vitro and in vivo data. However, the correlation between STK10 and the tumor microenvironment (TME) remains unclear. In this study, we assessed the relationship between STK10 and the immune cells in the tumor microenvironment of prostate cancer through bioinformatic analysis, and investigated the role of Stk10 in tumor growth using an Stk10 knockout mouse model. The results showed that STK10 is significantly associated with the tumor-infiltrating immune cells including lymphocytes, neutrophils, macrophages and dendritic cells. The target deletion of host Stk10 results in increased tumor growth, due to decreased activated/effector cytotoxic T lymphocytes (CTLs) and increased vessel density in the TME. In conclusion, we demonstrate that host Stk10 is involved in the host anti-tumor response by modulating the activated tumor-infiltrated CTLs and angiogenesis.

Challenges to Student Interdisciplinary Learning Effectiveness: An Empirical Case Study.

In order to meet industrial demands, some colleges and universities have offered interdisciplinary programs that integrate design, engineering, and business. However, how many changes these programs have brought to students, and whether students participating in these programs have had better interdisciplinary ability than students involved in a single discipline study have always been questions that many researchers want to explore. In a university that offers an interdisciplinary program, we found that there is no significant difference in interdisciplinary integration ability between the students participating in the interdisciplinary program and the students involved in a single discipline study through quantitative comparisons of 91 student questionnaires and analyses of interviews with nine teachers of interdisciplinary courses and other related staff members. This may result from the students' lack of motivation, lack of prior experience, the influence of individual traits, the increase of learning pressure and academic burden, and the interference of disciplinary factors during interdisciplinary learning. The research finding is intended to improve student interdisciplinary learning effectiveness by facilitating interdisciplinary teachers' understanding of the influencing factors of student interdisciplinary learning, and by providing a reference for interdisciplinary teaching design.

Nurses' perceptions of barriers and supportive behaviors in end-of-life care in the intensive care unit: a cross-sectional study.

BACKGROUND AND AIM: Patient deaths are common in the intensive care unit, and a nurse's perception of barriers to and supportive behaviors in end-of-life care varies widely depending upon their cultural background. The aim of this study was to describe the perceptions of intensive care nurses regarding barriers to and supportive behaviors in providing end-of-life care in a Chinese cultural context. METHODS: A cross-sectional survey was conducted among intensive care nurses in 20 intensive care units in 11 general hospitals in central and eastern China. Instruments used in this study were general survey and Beckstrand's questionnaire. Data were collected via online survey platform. Descriptive analysis was used to describe general characteristics of participants and mean and standard deviations of the barriers and supportive behaviors. The mean and standard deviation were used to describe the intensity and frequency of each barrier or supportive behavior following Beckstrand's method to calculate the score of barriers and supportive behaviors. Content analysis was used to analyze the responses to open-ended questions. RESULTS: The response rate was 53% (n = 368/700). Five of the top six barriers related to families and the other was the nurse's lack of time. Supportive behaviors included three related to families and three related to healthcare providers. Nurses in the intensive care unit felt that families should be present at the bedside of a dying patient, there is a need to provide a quiet, independent environment and psychological support should be provided to the patient and family. Nurses believe that if possible, families can be given flexibility to visit dying patients, such as increasing the number of visits, rather than limiting visiting hours altogether. Families need to be given enough time to perform the final rites on the dying patient. Moreover, it is remarkable that nurses' supportive behaviors almost all concern care after death. CONCLUSIONS: According to ICU-nurses family-related factors, such as accompany of the dying patients and acceptence of patient's imminent death, were found the major factors affecting the quality of end-of-life care. These findings identify the most prominent current barriers and supportive behaviors, which may provide a basis for addressing these issues in the future to improve the quality of end-of-life care.

Fission Yeast Autophagy Machinery.

Autophagy is a conserved process that delivers cytoplasmic components to the vacuole/lysosome. It plays important roles in maintaining cellular homeostasis and conferring stress resistance. In the fission yeast Schizosaccharomyces pombe, autophagy is important for cell survival under nutrient depletion and ER stress conditions. Experimental analyses of fission yeast autophagy machinery in the last 10 years have unveiled both similarities and differences in autophagosome biogenesis mechanisms between fission yeast and other model eukaryotes for autophagy research, in particular, the budding yeast Saccharomyces cerevisiae. More recently, selective autophagy pathways that deliver hydrolytic enzymes, the ER, and mitochondria to the vacuole have been discovered in fission yeast, yielding novel insights into how cargo selectivity can be achieved in autophagy. Here, we review the progress made in understanding the autophagy machinery in fission yeast.

A comparative study on ultrasound-guided elite, Mammotome, and core needle biopsy for diagnosing malignant breast masses.

Introduction: The present study aims to clarify the advantages and disadvantages of elite biopsy, to provide a reference for selecting the puncture method. Material and methods: A total of 802 patients with a BI-RADS grade ≥ 4, as evaluated by the molybdenum target, and measurable lesions revealed by colour Doppler ultrasound, who were admitted at our department from January 2017 to January 2018, were enrolled in the present study. These patients were randomly divided into three groups: elite, Mammotome and core needle biopsy groups. The pathological underestimation rate, diagnostic accordance rate, haematoma incidence rate, and costs of these three biopsy methods were compared. Results: The difference in diagnostic accordance rates between the elite biopsy group and core needle biopsy group was statistically significant (98.9% vs. 94.7%, p = 0.003), as well as between the Mammotome biopsy group and core needle biopsy group (99.6% vs. 94.7%, p < 0.001). The difference in pathological underestimation rates between the elite biopsy group and core needle biopsy group was statistically significant (7.2% vs. 37.3%, p < 0.001), as well as between the Mammotome biopsy group and core needle biopsy group (1.6% vs. 7.2%, p < 0.001). The difference between the Mammotome biopsy group and elite biopsy group was not statistically significant. The incidence of haematoma in the Mommotome, elite, and core needle groups was 15.9%, 13%, and 21.7%, respectively (13% vs. 21.7%, p = 0.021). Conclusions: Elite biopsy has a low rate of pathological underestimation and low incidence of haematoma, can improve the breast conserving rate, and has an affordable cost. As a biopsy method with high accuracy, safety, and economy, elite biopsy can be widely used in clinics.

Targeting mitochondria for cancer photodynamic therapy.

Cancer remains a health-related concern globally. The application of light to be used as therapeuticagent including cancer has been used for several thousand years. Photodynamic therapy (PDT) is a modern, non-invasive therapeutic modality for the treatment of various cancers and infections by bacteria, fungi, and viruses. Mitochondria are subcellular, double-membrane organelles that have a role in cancer and anticancer therapy. Mitochondria play a key role in regulation of apoptosis and these organelles produce most of the cell's energy which enhance its targeting objective. The role of mitochondria in anticancer approach is achieved by targeting its metabolism (glycolysis and TCA cycle) and apoptotic and ROS homeostasis. The role of mitochondria-targeted cancer therapies in photodynamic therapy have proven to be more effective than other similar non-targeting techniques. Particularly in PDT, mitochondria-targeting sensitizers are important as they have a crucial role in overcoming the hypoxia factor, resulting in high efficacy. IR-730 and IR-Pyr are the indocyine derivatives photosensitizers that play a crucial role in targeting mitochondria because of their better photostability during laser irradiation. Clinical and pre-clinical trials are going on this approach to target different solid tumors using mitochondrial targeted photodynamic therapy.

Combination treatment with sorafenib and wh-4 additively suppresses the proliferation of liver cancer cells.

Sorafenib is currently used to treat hepatocellular carcinoma (HCC). However, the development of chemoresistance to sorafenib is a major limitation for sorafenib-based therapy in patients with HCC. In the present study, the effect of the combination therapy of sorafenib and wh-4 on the proliferation of liver cancer cells was investigated. The results showed that sorafenib with wh-4 additively suppressed the proliferation of liver cancer cells. The colony formation of liver cancer cells decreased significantly in response to the combination treatment of sorafenib with wh-4, and it also induced the apoptosis of liver cancer cells. Western blot analysis demonstrated decreased expression of Bcl2, and increased expression of Bax in liver cancer cells treated with a combination of sorafenib and wh-4. Moreover, the migration of liver cancer cells was inhibited. The combination treatment of sorafenib with wh-4 reduced the expression levels of ABCB1 and ABCG2 which are responsible for resistance. Finally, STAT3 overexpression abolished the proliferation inhibition effect of sorafenib with wh-4 on liver cancer cells, and sorafenib and wh-4 suppressed the proliferation of liver cancer cells by STAT3 pathway. Together, these results suggest that sorafenib-wh4 combination treatment is a potential novel therapeutic approach to suppress the proliferation of liver cancer cells.

Preoperative high lymphocyte-to-monocyte ratio is associated with intraoperative type I endoleak in patients with TAA with TEVAR.

OBJECTIVES: Various inflammatory factors are closely associated with the incidence of thoracic aortic aneurysms (TAAs). Furthermore, the severity of inflammation is closely related to the absolute value and proportion of each leukocyte subgroup. Only few reports have analyzed the importance of lymphocyte-monocyte ratio (LMR) as a potential inflammatory marker in vascular diseases. Therefore, we aimed to investigate the effect of peripheral blood LMR on thoracic endovascular aortic repair (TEVAR) in patients with TAA. METHODS: A retrospective study of the clinical data collected in our hospital between January 2016 and January 2021 was performed on 162 patients with TAA treated with TEVAR, based on the inclusion and exclusion criteria for patient selection. Based on whether the patient had the clinical symptoms at admission and the occurrence of type I endoleaks during operation, patients were divided into two groups, respectively: an intraoperative type I endoleak group (n = 34) and a group without intraoperative type I endoleak (n = 128), and a group with clinical symptoms (n = 31) and a group without clinical symptoms (n = 131). The clinical data of these two groups were compared, the free from second intervention rates related to endoleak and the preoperatively LMR of the two groups was calculated. LMR was calculated preoperatively. Receiver-operating characteristic curve analysis was used to determine the cut-off for preoperative LMR values. Based on the cut-off point, patients were divided into a high LMR group (n = 34) and a low LMR group (n = 128). The clinical data of the two groups were compared, and further stratified analysis was performed. RESULTS: A total of 162 patients were included in the analysis. All patients were successfully implanted with a thoracic aorta stent graft. The preoperative LMR level and postoperative endoleak-related secondary intervention rate were higher in the type I endoleak group than those in the group without intraoperative type I endoleaks. The preoperative C-reactive protein (CRP) level of patients with TAA with clinical symptoms was higher than that of asymptomatic patients. There was a negative correlation between preoperative CRP and LMR levels. In addition, in symptomatic or asymptomatic patients, the LMR level was associated with the occurrence of intraoperative type I endoleaks. After excluding the influence of type of endografts, our results showed that the clinical symptoms did not affect the occurrence of the intraoperative type I endoleak, and patients with intraoperative type I endoleak had a higher rate of postoperative secondary intervention. CONCLUSION: Patients with TAA with type I endoleaks during TEVAR had an increased rate of secondary intervention related to endoleaks. Patients with TAA with high LMR levels before TEVAR were more likely to have endoleaks during operation.