Expression and Prognosis of Differential Gene Troponin T1 Between Right and Left Colon Cancers.

Colorectal cancer (CRC) is one of the most common digestive tract tumors in humans. At present, many scholars believe that the primary site of the tumor has a direct and profound impact on its curative effect. There are significant differences in the expression of many genes, tumor microenvironment, and prognosis between the left and right colon. However, there is a lack of detailed studies on whether the differentially expressed genes in the left and right colon significantly impact the prognosis of patients with CRC. Troponin T1 (TNNT1) is an important gene that affects the prognosis difference between left and right colon cancer screening from "The Cancer Genome Atlas" database. By analyzing the differential gene expression data and clinical data of the left and right hemicolons in the database, the online prognostic database was used to screen the key molecules that significantly affect the tumor immune microenvironment and patient prognosis and to predict their functions and pathways. Quantitative reverse transcription-polymerase chain reaction was used to verify the expression difference of TNNT1 in CRC cell lines SW480 and HCT116, and normal human colorectal epithelial cell line FHC. The relationship between TNNT1 expression in 88 pairs of CRC samples and clinical information and pathologic parameters of patients with CRC was analyzed to judge the impact of TNNT1 expression on patient survival. Database analysis showed that TNNT1 was significantly overexpressed in CRC, and TNNT1 was one of the main differential genes between left colon cancer (LCC) and right colon cancer (RCC). The expression of TNNT1 was significantly increased in RCC, which could lead to poor prognosis of patients. Quantitative reverse transcription-polymerase chain reaction indicated that the expression of TNNT1 was significantly up-regulated in CRC cell lines SW480 and HCT116. Eighty-eight immunohistochemistry (IHC) of CRC tissues and adjacent tissues suggested that the expression of TNNT1 in CRC was significantly higher than that in normal adjacent tissues. By analyzing the clinical information and pathologic indicators matched with these clinical samples, we found that high TNNT1 expression in the primary tumor location (right colon) and high N stage (N2, N3) were unfavorable factors affecting the prognosis of patients with CRC. Multivariate Cox regression analysis suggested that high expression of TNNT1 may be an independent risk factor for the prognosis of patients with CRC. As one of the main differential genes between LCC and RCC, TNNT1 is representative to some extent. Its high expression may be one of the reasons why the prognosis of patients with RCC is worse than that of patients with LCC.

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

Salidroside induces mitochondrial dysfunction and ferroptosis to inhibit melanoma progression through reactive oxygen species production.

Reactive oxygen species (ROS) induces necroptotic and ferroptosis in melanoma cells. Salidroside (SAL) regulates ROS in normal cells and inhibits melanoma cell proliferation. This study used human malignant melanoma cells treated with SAL either alone or in combination with ROS scavenger (NAC) or ferroptosis inducer (Erastin). Through cell viability, wound healing assays, and a Seahorse analyze found that SAL inhibited cell proliferation, migration, extracellular acidification rate, and oxygen consumption rate. Metabolic flux analysis, complexes I, II, III, and IV activity of the mitochondrial respiratory chain assays, mitochondrial membrane potential assay, mitochondrial ROS, and transmission electron microscope revealed that SAL induced mitochondrial dysfunction and ultrastructural damage. Assessment of malondialdehyde, lipid ROS, iron content measurement, and Western blot analysis showed that SAL activated lipid peroxidation and promoted ferroptosis in A-375 cells. These effects were abolished after NAC treatment. Additionally, SAL and Erastin both inhibited cell proliferation and promoted cell death; SAL increased the Erastin sensitivity of cells while NAC antagonized it. In xenograft mice, SAL inhibited melanoma growth and promoted ROS-dependent ferroptosis. SAL induced mitochondrial dysfunction and ferroptosis to block melanoma progression through ROS production, which offers a scientific foundation for conducting SAL pharmacological research in the management of melanoma.

The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma.

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

Chemotherapy-related symptom networks in distinct subgroups of Chinese patients with gastric cancer.

Objective: This study aims to identify distinct subgroups among gastric cancer patients undergoing chemotherapy (CTX), delineate associated symptom networks, and ascertain the clinical and sociodemographic variables contributing to diverse symptom patterns. Methods: Conducted in eastern China, our investigation involved gastric cancer patients receiving CTX. We gathered data using the M.D. Anderson Symptom Inventory Gastrointestinal Cancer Module along with clinical and sociodemographic variables. Subgroups were discerned based on symptom severity through latent profile analysis, and subsequent comparisons were made regarding the symptom networks in different subgroups. Results: The analysis encompassed 677 eligible gastric cancer patients, revealing three profiles: "Profile 1: low class" (n = 354, 52.3%), "Profile 2: moderate class" (n = 222, 32.8%), and "Profile 3: all high class" (n = 101, 14.9%). Nausea-vomiting exhibited robust associations in the symptom networks of all subgroups, whereas sadness-distress, and taste change-lack of appetite were notably linked with Profile 1 and Profile 2. Distress emerged as a core symptom in Profile 1, lack of appetite dominated the symptom network in Profile 2, and fatigue attained the highest strength in Profile 3. Distinct symptom profiles were influenced by variables such as education level, CTX combined with surgical or herbal treatment, psychological resilience, and social support. Conclusions: Patients within different subgroups manifest individualized patterns of symptom profiles. Analyzing demographics, disease characteristics, and psychosocial information among diverse subgroups facilitates healthcare providers in devising more personalized and targeted symptom management strategies, thereby alleviating the symptom burden on patients.

Molecular Regulation and Oncogenic Functions of TSPAN8.

Tetraspanins, a superfamily of small integral membrane proteins, are characterized by four transmembrane domains and conserved protein motifs that are configured into a unique molecular topology and structure in the plasma membrane. They act as key organizers of the plasma membrane, orchestrating the formation of specialized microdomains called "tetraspanin-enriched microdomains (TEMs)" or "tetraspanin nanodomains" that are essential for mediating diverse biological processes. TSPAN8 is one of the earliest identified tetraspanin members. It is known to interact with a wide range of molecular partners in different cellular contexts and regulate diverse molecular and cellular events at the plasma membrane, including cell adhesion, migration, invasion, signal transduction, and exosome biogenesis. The functions of cell-surface TSPAN8 are governed by ER targeting, modifications at the Golgi apparatus and dynamic trafficking. Intriguingly, limited evidence shows that TSPAN8 can translocate to the nucleus to act as a transcriptional regulator. The transcription of TSPAN8 is tightly regulated and restricted to defined cell lineages, where it can serve as a molecular marker of stem/progenitor cells in certain normal tissues as well as tumors. Importantly, the oncogenic roles of TSPAN8 in tumor development and cancer metastasis have gained prominence in recent decades. Here, we comprehensively review the current knowledge on the molecular characteristics and regulatory mechanisms defining TSPAN8 functions, and discuss the potential and significance of TSPAN8 as a biomarker and therapeutic target across various epithelial cancers.

Low Bone Mineral Density and the Risk of Benign Paroxysmal Positional Vertigo.

OBJECTIVE: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population-based UK Biobank (UKB) cohort. STUDY DESIGN: Prospective population-based cohort study. SETTING: The UKB. METHODS: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. RESULTS: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow-up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P = .0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P = .0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. CONCLUSION: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV.

Multifunctional cell membranes-based nano-carriers for targeted therapies: a review of recent trends and future perspective.

Nanotechnology has ignited a transformative revolution in disease detection, prevention, management, and treatment. Central to this paradigm shift is the innovative realm of cell membrane-based nanocarriers, a burgeoning class of biomimetic nanoparticles (NPs) that redefine the boundaries of biomedical applications. These remarkable nanocarriers, designed through a top-down approach, harness the intrinsic properties of cell-derived materials as their fundamental building blocks. Through shrouding themselves in natural cell membranes, these nanocarriers extend their circulation longevity and empower themselves to intricately navigate and modulate the multifaceted microenvironments associated with various diseases. This comprehensive review provides a panoramic view of recent breakthroughs in biomimetic nanomaterials, emphasizing their diverse applications in cancer treatment, cardiovascular therapy, viral infections, COVID-19 management, and autoimmune diseases. In this exposition, we deliver a concise yet illuminating overview of the distinctive properties underpinning biomimetic nanomaterials, elucidating their pivotal role in biomedical innovation. We subsequently delve into the exceptional advantages these nanomaterials offer, shedding light on the unique attributes that position them at the forefront of cutting-edge research. Moreover, we briefly explore the intricate synthesis processes employed in creating these biomimetic nanocarriers, shedding light on the methodologies that drive their development.

Mineralocorticoid receptor antagonists for chronic heart failure: a meta-analysis focusing on the number needed to treat.

Aims: Recent studies have shown that mineralocorticoid receptor antagonists (MRAs) can decrease mortality in patients with heart failure; however, the application of MRAs in current clinical practice is limited because of adverse effects such as hyperkalemia that occur with treatment. Therefore, this meta-analysis used the number needed to treat (NNT) to assess the efficacy and safety of MRAs in patients with chronic heart failure. Methods: We meta-analysed randomized controlled trials (RCTs) which contrasted the impacts of MRAs with placebo. As of March 2023, all articles are published in English. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and adverse events. Results: We incorporated seven studies with a total of 9,056 patients, 4,512 of whom received MRAs and 4,544 of whom received a placebo, with a mean follow-up period of 2.1 years. MACE, all-cause mortality, and cardiovascular mortality were all reduced by MRAs, with corresponding numbers needed to treat for benefit (NNTB) of 37, 28, and 34; as well as no impact on MI or stroke. MRAs increased the incidence of hyperkalemia and gynecomastia, with the corresponding mean number needed to treat for harm (NNTH) of 18 and 52. Conclusions: This study showed that enabling one patient with HF to avoid MACE required treating 37 patients with MRAs for 2.1 years. MRAs reduce MACE, all-cause mortality, and cardiovascular death; however, they increase the risk of hyperkalemia and gynecomastia.

Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice.

Background and Aims: Liver fibrosis is the common pathological pathway of chronic liver diseases and its mechanisms of which have not been fully declared. Macrophages play essential roles in progression of liver fibrosis partially by sensing abnormal mechanical signals. The aim of the study is to investigate the functions of macrophage Piezo1, a mechano-sensitive ion channel, in liver fibrosis. Approach and Results: Immunofluorescence in human and murine fibrotic liver samples revealed that expression of macrophage Piezo1 was increased. Myeloid-specific Piezo1 knockout (Piezo1ΔLysM) attenuated liver fibrosis by decreased collagen deposition and epithelial-mesenchymal transition (EMT). In Piezo1ΔLysM mice, less inflammation during development of liver fibrosis was observed by lessened macrophage infiltration, decreased M1 polarization and expression of inflammatory cytokines. RNA-seq data showed macrophage Piezo1 regulated transcription of cathepsin S (CTSS). Piezo1ΔLysM inhibited expression and activity of CTSS in vitro and in vivo and regulated T cell activity. Furthermore, inhibition of CTSS reversed macrophage inflammatory response driven by Piezo1 activation and LPS. Macrophage Piezo1 activation promoted CTSS secretion due to increased activity of Ca2+-dependent calpain protease induced by Ca2+ influx to cleave lysosome-associated membrane protein-1 (LAMP1). Pharmacological inhibition of calpain activity partially blocked Piezo1 mediated CTSS secretion. Conclusions: Macrophage Piezo1 deficiency limits the progression of liver fibrosis by inhibited inflammatory response and decreased secretion of CTSS. These findings suggest that targeting Piezo1 channel may be a potential strategy for treating hepatic fibrosis.

Associations between immune-mediated diseases (IMDs) and the risk of HPV-associated diseases: a UK Biobank cohort analysis.

OBJECTIVES: To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases. DESIGN: Retrospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 500 371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex. EXPOSURE: Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively. RESULTS: During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p<0.001; male: HR=1.66, 95% CI=1.41 to 1.97, p<0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95% CI=1.47 to 2.11, p<0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95% CI=3.32 to 11.04, p<0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups. CONCLUSION: In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases.

Analysis of carotid plaque risk factors in a population at high risk of stroke in Yubei District, Chongqing, China.

OBJECTIVE: To establish a scientific foundation for focused stroke prevention and treatment efforts by comprehending the risk variables connected to carotid plaque formation in adults over 40 who are at high risk of stroke in Yubei District, Chongqing, China. METHODS: By comparing the differences in carotid plaque formation between people of different ages, smoking, blood pressure levels, low-density lipoprotein levels, and glycosylated hemoglobin levels, questionnaires and physical exams were performed on a random sample of permanent residents aged 40 years in three communities in Yubei District, Chongqing, China. The goal was to investigate the risk factors associated with carotid plaque formation in the population. RESULTS: The incidence of carotid plaque gradually increased in the study population as age, blood pressure, low-density lipoprotein, and glycosylated hemoglobin levels increased. The difference in carotid plaque formation between people of different ages, smoking, blood pressure levels, low-density lipoprotein levels, and glycosylated hemoglobin levels was statistically significant (p<0.05). The findings of the multifactorial logistic regression analysis revealed that there was a tendency for the risk of developing carotid plaque to rise with age; the risk of developing carotid plaque in hypertensive patients was (OR=1.41,95% CI: 1.03-1.93); the population of smokers was (OR=2.01,95%CI:1.33-3.05); the low-density lipoprotein cholesterol borderline increased group was (OR=1.94,95%CI:1.03-3.66); the low-density lipoprotein cholesterol elevated group was (OR=2.71,95%CI: 1.26-5.84); glycosylated hemoglobin elevated group was (OR=1.40,95%CI: 1.01-1.94) (p<0.05). CONCLUSION: Age, smoking, blood pressure, low-density lipoprotein, and glycosylated hemoglobin are all associated with carotid plaque formation in those over 40 who are at high risk of stroke. As a result, health education for residents needs to be strengthened to raise knowledge of carotid plaque prevention.

Recent advance of small-molecule drugs for clinical treatment of multiple myeloma.

Multiple myeloma (MM) is a hematologic neoplasm of plasma cells that is currently deemed incurable. Despite the introduction of novel immunomodulators and proteasome inhibitors, MM remains a challenging disease with high rates of relapse and refractoriness. The management of refractory and relapsed MM patients remains a formidable task, primarily due to the emergence of multiple drug resistance. Consequently, there is an urgent need for novel therapeutic agents to address this clinical challenge. In recent years, a significant amount of research has been dedicated to the discovery of novel therapeutic agents for the treatment of MM. The clinical utilization of proteasome inhibitor carfilzomib and immunomodulator pomalidomide has been successively introduced. As basic research continues to advance, novel therapeutic agents, including panobinostat, a histone deacetylase inhibitor, and selinexor, a nuclear export inhibitor, have progressed to the clinical trial and application phase. This review aims to furnish a comprehensive survey of the clinical applications and synthetic pathways of select drugs, with the intention of imparting valuable insights for future drug research and development geared towards MM.

Conditioning therapy with N-acetyl-L-cysteine, decitabine and modified BUCY regimen for myeloid malignancies patients prior to allogeneic hematopoietic stem cell transplantation.

Conditioning therapy is an essential procedure prior to hematopoietic stem cell transplant (HSCT), imposing a great impact on the outcomes of recipients. We performed a prospective randomized controlled trial to assess the outcome of HSCT recipients with myeloid malignancies after receiving the conditioning therapy consisting of modified BUCY (mBUCY), N-acetyl-L-cysteine (NAC), and decitabine. Enrolled patients were randomly allocated to either Arm A (decitabine, day -12 to -10; NAC, day -9 to +30; mBUCY, day -9 to -2), or Arm B (mBUCY regimen followed by stem cells infusion). Seventy-six patients in Arm A and 78 patients in Arm B were finally evaluated. The results showed platelet recovery accelerate in Arm A, with more patients achieving a platelet count of ≥50 × 109 /L than Arm B at day +30 and +60 (p = .004 and .043, respectively). The cumulative incidence of relapse is 11.8% (95% CI 0.06-0.22) in Arm A, and 24.4% (95% CI 0.16-0.35) in Arm B (p = .048). The estimated 3-year overall survival rate was 86.4% (±4.4%) and 79.9% (±4.7%) in 2 arms, respectively (p = .155). EFS at 3 years was 79.2% (±4.9%) in Arm A and 60.0% (±5.9%) in Arm B (p = .007). Intracellular reactive oxygen species (ROS) level was found to be reversely correlated with platelet recovery, and fewer patients in Arm A displayed excessive ROS within hematopoietic progenitor cells compared to Arm B. In conclusion, the addition of decitabine and NAC to mBUCY is a feasible and promising conditioning therapy for myeloid malignancies patients.

Clinical characteristics and prognostic significance of DNA methylation regulatory gene mutations in acute myeloid leukemia.

BACKGROUND: DNA methylation is a form of epigenetic modification that regulates gene expression. However, there are limited data on the comprehensive analysis of DNA methylation regulated gene mutations (DMRGM) in acute myeloid leukemia (AML) mainly referring to DNA methyltransferase 3α (DNMT3A), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), and Tet methylcytidine dioxygenase 2 (TET2). RESULTS: A retrospective study of the clinical characteristics and gene mutations in 843 newly diagnosed non-M3 AML patients was conducted between January 2016 and August 2019. 29.7% (250/843) of patients presented with DMRGM. It was characterized by older age, higher white blood cell count, and higher platelet count (P < 0.05). DMRGM frequently coexisted with FLT3-ITD, NPM1, FLT3-TKD, and RUNX1 mutations (P < 0.05). The CR/CRi rate was only 60.3% in DMRGM patients, significantly lower than in non-DMRGM patients (71.0%, P = 0.014). In addition to being associated with poor overall survival (OS), DMRGM was also an independent risk factor for relapse-free survival (RFS) (HR: 1.467, 95% CI: 1.030-2.090, P = 0.034). Furthermore, OS worsened with an increasing burden of DMRGM. Patients with DMRGM may be benefit from hypomethylating drugs, and the unfavorable prognosis of DMRGM can be overcome by hematopoietic stem cell transplantation (HSCT). For external validation, the BeatAML database was downloaded, and a significant association between DMRGM and OS was confirmed (P < 0.05). CONCLUSION: Our study provides an overview of DMRGM in AML patients, which was identified as a risk factor for poor prognosis.

Cymbaria daurica L.: A Mongolian herbal medicine for treating eczema via natural killer cell-mediated cytotoxicity pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbaria daurica L. (C. daurica) is a perennial herb known commonly as "Xinba" (Chinese) and "Kanba-Arong" (Mongolian). In Mongolia, it is used as a traditional medicine to treat eczema and other skin diseases due to its anti-swelling, anti-inflammatory, anti-hemorrhagic, and anti-itching properties. However, the potential mechanism of action for eczema treatment has not been reported. AIM OF THE STUDY: To investigate the effect of C. daurica on 1-chloro-2,4-dinitrobenzene (DNCB)-induced eczema in rats and the associated action mechanism. MATERIALS AND METHODS: Qualitative analysis of C. daurica was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on information obtained from compound identification and relevant literature, the possible targets of C. daurica against eczema were analyzed using network pharmacology and molecular docking methods. The DNCB-induced eczema rat models were treated with different dosages of C. daurica extract (10, 50, and 250 mg/mL per day), and the therapeutic effects subsequently evaluated based on the degree of skin inflammation, spleen index, and hematoxylin and eosin staining (H&E staining). Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were used to analyze the relevant target effects. The C. daurica mechanism of action on eczema was verified by animal experiments. High-performance liquid chromatography (HPLC) was carried out to determine the content of active ingredients in C. daurica. In addition, the physicochemical properties of the extract were evaluated. RESULTS: Our analysis of the 173 targets included in the protein-protein interaction (PPI) network identified tumor necrosis factor (TNF) and interleukin 2 (IL-2) as key targets involved in the treatment of eczema with C. daurica extract. Furthermore, the 173 targets were associated with the natural killer cell-mediated cytotoxicity pathway. Our results showed that C. daurica significantly reduced IL-2 and TNF-α serum levels in eczema rat models (P < 0.0001); thus, playing an important role in the anti-inflammatory response. Furthermore, according to the p-value, RT-qPCR and western blotting showed that the expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Vav guanine nucleotide exchange factor (Vav), and growth factor receptor-bound protein 2 (Grb2) changed in the skin of the eczema model rats after treatment with the C. daurica extract. CONCLUSION: Our study confirms that C. daurica can inhibit SHP-1, Vav, and Grb2 expression; thereby, inhibiting the natural killer cell-mediated cytotoxicity pathway. These results provide insight into the mechanism of C. daurica in treating eczema.

Effects of modified Huangqi Chifeng decoction on the IL-17 signaling pathway in an IgA nephropathy rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A nephropathy (IgAN) is an immune-related primary glomerular disease prevalent worldwide, with complicated clinical manifestations and an unclear pathogenesis. IgAN is the main cause of chronic renal failure and places a significant burden on patients and society. The modified Huangqi Chifeng decoction (MHCD) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. AIM OF THE STUDY: Based on the findings of previous network pharmacology-related method-based studies, this study aimed to further explore the mechanism of action of MHCD for IgAN treatment. MATERIALS AND METHODS: IgAN rat model was established by bovine serum protein + carbon tetrachloride + lipopolysaccharide. After successful modeling, the rats in the original model group were divided into 5 group: model group, telmisartan group, and MHCD high-, medium- and low-dose groups by random number table (n = 10 respectively). The corresponding drugs were applied for 8 weeks, and the experiment lasted for 21 weeks. At the end of the experiment, 24h urine protein quantification, serum biochemistry and IL-6 and IL-17A levels were measured. The pathological changes of kidney were observed by light microscope, immunofluorescence microscope and the changes of glomerular ultrastructure were observed by transmission electron microscope. The expression levels of IL-17 signaling pathway related proteins (HSP90, MMP9, NF-κB P65 and p-NF-κB P65) were detected by Western Blot and immunohistochemistry. RESULT: Telmisartan and MHCD treatment can reduce the 24h urinary protein level and improved blood stasis states of IgAN rats, alleviate the renal pathological injury, decrease the serum levels of IL-6, IL-17A and the expression levels of HSP90, MMP9 and p-NF-κB P65 related proteins in IL-17 signaling pathway. CONCLUSION: MHCD can down-regulate the expression of IL-17 signaling pathway-related factors in IgAN model rats, improve the state of blood stasis, and alleviate the pathological damage of kidney in rats.

Phosphate-solubilizing microorganisms regulate the release and transformation of phosphorus in biochar-based slow-release fertilizer.

Coupling phosphate-solubilizing microorganisms (PSM) can improve the availability of phosphorous (P) in biochar-based slow-release P fertilizers (BPF). However, the mechanism in release and transformation of P in BPF regulated by PSM is still unclear. Herein, the biocompatibility and the adhesion behaviors of BPF and PSM (Enterobacter hormaechei Rs-198) in soil were firstly studied, and a 90 days' laboratory-scale soil incubation experiment of BPF and Rs-198 was performed to study the transformation of P of BPF. The results show that BPF has a good biocompatibility for Rs-198 due to its low aromaticity, graphitization and free radicals' content (0.084 mg/g). Rs-198 are adhered to the surface of BPF in soil due to the high negative secondary energy minimum and low total interaction energy between Rs-198 and BPF. Available P in the incubation of BPF and Rs-198 (BR treatment) is significantly higher than that of the incubation of BPF (BF treatment) at initial 60 days. However, the content of available P in BR treatment is much lower compared with that in BF treatment on day 90, which is attributed to the entrapment of released P from BPF by Rs-198 and the formation of polyphosphate (polyP) rather than bound with soil mineral. Overall, this study presents new insights into the transformation of P in BPF regulated by PSM.

Development of nomogram and discussion of radiotherapy effect for osteosarcoma survival.

This study aimed to develop a predictive system for prognostic evaluation of osteosarcoma patients. We obtained osteosarcoma sample data from 1998 to 2016 using SEER*Stat software version 8.3.8, and established a multivariable Cox regression model using R-4.0.3 software. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The diagnosis of the model was completed through influential cases, proportionality, and multicollinearity. The predictive ability of the model was tested using area under the curve (AUC), calibration curves, and Brier scores. Finally, the bootstrap method was used to internally verify the model. In total, data from 3566 patients with osteosarcoma were included in this study. The multivariate Cox regression model was used to determine the independent prognostic variables. A nomogram and Kaplan-Meier survival curve were established. The AUC and Brier scores indicated that the model had a good predictive calibration. In addition, we found that the radiotherapy appears to be a risk factor of patients with osteosarcoma and made a discussion. We developed a prognostic evaluation system for patients with osteosarcoma for 1-, 3-, and 5-year overall survival with good predictive ability using sample data extracted from the SEER database. This has important clinical significance for the early identification and treatment of high-risk groups of osteosarcoma patients.

Landscape and clinical impact of NOTCH mutations in newly diagnosed acute myeloid leukemia.

BACKGROUND: NOTCH mutations (NOTCHmut ) are recognized as major oncogenic drivers associated with controversial clinical impact on T-cell acute lymphoblastic leukemia (T-ALL), whereas their clinical value on acute myeloid leukemia (AML) is poorly defined. METHODS: A study involving 878 consecutive newly diagnosed patients with AML was undertaken in an institution with available clinical data to unravel the impact of NOTCHmut on prognosis. RESULTS: In the study, NOTCHmut were discovered in 3.6% (32/878) of included patients with AML and composed substitution-missense, frameshift mutation, substitution-nonsense, and insertion-in frame. These mutations were more commonly associated with low platelet (29 vs 42 × 109 /L, p = .024) count and coexisted with BCOR/BCORL1 (15.6% vs 3.2%, p = .001), DNMT3A (28.1% vs 12.5%, p = .021), and MPL (9.4% vs 0.8%, p = .004) mutations compared with NOTCH wild-type (NOTCHwt ). No significant difference was observed in treatment responses between NOTCHmut and NOTCHwt . The presence of NOTCHmut was associated with worse overall survival ([OS], 1 year-OS: 68.0% vs 84.2%; 3 year-OS: 48.3% vs 59.6%; p = .059) and relapse-free survival ([RFS], 1 year-RFS: 78.3% vs 85.4%; 3 year-RFS: 54.5% vs 76.9%; p = .018), especially within the European Leukemia Net 2017 intermediate-risk group. Furthermore, allogeneic hematopoietic stem cell transplantation might abrogate the dismal impact of NOTCHmut on RFS. In multivariate analysis, NOTCHmut were found to be an independent factor negatively influencing RFS (hazard ratio, 2.153; 95% CI, 1.166-3.975; p = .014). CONCLUSION: This study suggests that NOTCHmut may serve as an indicator for poor prognosis of AML. PLAIN LANGUAGE SUMMARY: Although NOTCH mutations (NOTCHmut ) are well studied in T-cell acute lymphoblastic leukemia (T-ALL), less is known about their incidence and prognostic implications in acute myeloid leukemia (AML). A total of 878 newly diagnosed patients with AML was retrospectively analyzed; it was found that the frequency of NOTCHmut was relatively low but was associated with an adverse prognosis.