The patient developed lumbar pain and discomfort 2 years ago due to housework. The symptoms were improved after massage treatment at a local clinic, and then the above symptoms recurred. The patient came to the Department of Acupuncture and Massage Rehabilitation of the First Affiliated Hospital of Shaanxi University of Chinese Medicine because of "repeated back pain for 2 years, accompanied by left lower limb pain aggravated for 2 days", and was diagnosed as lumbar disc herniation. The treatment plan was mainly electric acupuncture, supplemented by traditional Chinese medicine hot compress powder. After 2 weeks of treatment, the patient's lumbar symptoms basically recovered, and were significantly better than before treatment.
Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), is an active monomer obtained by modifying the structure of paeoniflorin (Pae). CP-25 can alleviate the course of adjuvant arthritis (AA) rats by regulating immune inflammatory response and reducing bone damage. In addition, our research has found that immune cells are important target cells for its anti-inflammatory and immunomodulatory effects. Therefore, it is of great significance to study the pharmacokinetics of CP-25 in immune cells. The aim of this study was to investigate the absorption and efflux of CP-25 in plasma and peripheral blood mononuclear cells (PBMCs) of rats. We established a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to rapidly determine CP-25 in plasma and PBMC of rat. We found that the transport amount of CP-25 in PBMC gradually decreased with the increase of time, and reached equilibrium after 1 h. Moreover, there is a certain correlation between the concentration of CP-25 in plasma and the concentration of CP-25 in PBMC. In addition, we used several transporter inhibitors to study their effects on the efflux of CP-25 in PBMC. The efflux of CP-25 in PBMC increased with the increase of time in the first 30 min, and the efflux of CP-25 decreased gradually after 30 min. Furthermore, after multiple administration of 50 mg/kg in rats, concentration of CP-25 in PBMC is similar to the change of concentration of CP-25 in plasma. Our results suggest that CP-25 may enter PBMC by passive transport, and P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) may be involved in the efflux of CP-25 in PBMC. This research provides a basis and guidance for further study of the clinical application of CP-25.
Background: Studies of patients with bullous pemphigoid treated with dupilumab were often reported recently, including clinical trials, case series and case reports. To our knowledge, there is no prior meta-analytic evidence regarding efficacy and safety of dupilumab in the treatment of bullous pemphigoid. This study aimed to conduct a systematic review and meta-analysis about efficacy and safety of dupilumab in treating bullous pemphigoid.Methods: Electronic databases (accessed till 8 September 2022) were searched systematically for studies assessing the efficacy and safety of dupilumab for bullous pemphigoid. A fixed-effect model was used in this research; primary outcomes included were objective response rate (ORR, defined as complete response [CR] or partial response [PR]) and rate of adverse events (AEs). The Registration number was INPLASY20221100599 (https://inplasy.com).Findings: A total of 5 studies involving 62 patients with bullous pemphigoid were included for the meta-analysis. The pooled analyses revealed that dupilumab treatment in patients yielded an 80% ORR (95% confidence interval [CI], 65%–92%); the CR and PR rate were 62% (95%CI, 46%–77%) and 12% (95%CI, 3%–25%), respectively. Additionally, the pooled incidence of AEs was 12% (95%CI, 4%–22%).Interpretation: This research was the first meta-analysis of the efficacy and safety of dupilumab for bullous pemphigoid. Approximately 80% of BP patients treated with dupilumab could have a complete clearance of skin blisters, with or without pruritus. Complete clearance of the disease was achieved in 62% of patients. About 12% of patients have treatment-related mild AEs. The research showed that dupilumab performed well in terms of efficacy and safety. In fact, bullous pemphigoid can be expected to be a new indication for dupilumab.Funding Information: This study was supported by the Teaching Reform Project of Postgraduate Education at the University Level of Hebei Medical University (No.2022-20).Declaration of Interests: Guoqiang Zhang has received a grant from Teaching Reform Project of Postgraduate Education at the University Level of Hebei Medical University (No.2022-20). All other authors have no conflicts of interest to declare.
Abstract Background Lung cancer has been the leading cause of tumor related death, and 80%~85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. Methods Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. Results Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. Conclusions Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.
Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC) curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA) and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.
CD1 is an MHC class I-like molecule that has been conserved throughout mammalian evolution. Unlike MHC class I molecules, CD1 can present unique nonprotein antigens to T cells. The murine CD1 locus contains two highly homologous genes, CD1d1 and CD1d2. CD1d1 is essential for the development of a major subset of NK T cells that promptly secrete IL-4 following activation. However, the function of CD1d2 has not yet been demonstrated. In the present study, we examined the expression of CD1d2 in CD1d1-deficient (CD1d1 degrees) mice with the anti-CD1 Ab 3H3. Unlike CD1d1, which is expressed by all lymphocytes, CD1d2 can be detected only on the surface of thymocytes. To determine whether CD1d2 can select a unique subset of NK T cells, we compared the remnant population of NK T cells in CD1d1 degrees and CD1d1, CD1d2-double deficient (CD1d1 degrees CD1d2 degrees) mice. No significant difference in the number of NK T cells and cytokine secretion capacity can be detected between CD1d1 degrees and CD1d1 degrees CD1d2 degrees mice, indicating that CD1d2 cannot substitute for CD1d1 in NK T cell development. The inability of CD1d2 to select NK T cells is not due to the structural constraints of CD1d2 since CD1d2-transfected cells can be recognized by both NK T cell hybridomas and freshly isolated NK T cells. Given the structural similarities, it is possible that the low levels of surface expression and limited tissue distribution of CD1d2 may prevent it from functioning in the selection and expansion of NK T cells.
Cancer remains one of the top culprits causing disease-related deaths. A lack of effective multi-cancer therapeutic targets has limited the prolongation of cancer patients' survival. Therefore, it is important to explore novel oncogenic genes or versatile targets and perform a comprehensive analysis to assess their roles in the process of tumorigenesis. OSBPL3 protein is an intracellular lipid receptor of the oxysterol-binding protein superfamily, which participates in some pathological and physiological processes in tumor progression. However, its clinical roles and potential mechanisms in cancers remain unknown. Thus, we aimed to systematic explore the potential oncogenic roles of OSBPL3 across thirty-three tumors using multiple web-based and publicly available tools, including the Cancer Genome Atlas, Gene Expression Omnibus, Genotype-Tissue Expression, cBioPortal, and Human Protein Atlas database. OSBPL3 is highly expressed in major subtypes of cancers, distinctly associated with the prognosis of tumor patients. We observed X676_splice/V676G alteration in the oxysterol domain and frequent mutations of OSBPL3 involve cell survival in skin cutaneous melanoma. We also first presented that the expression of OSBPL3 was associated with tumor mutational burden (TMB) in nine cancer types. Additionally, OSBPL3 shows an enhanced phosphorylation level at S426, S251, and S273 loci within the pleckstrin homology domain in multiple tumors, such as breast cancer or lung adenocarcinoma. And OSBPL3 expression was associated with active immune cells (CD8+ T cells) and cancer-associated fibroblasts in breast cancer, colon adenocarcinoma, and kidney renal clear cell carcinoma and immune checkpoint genes in more than 30 tumors, but weakly associated with immune suppressive cells (myeloid-derived suppressor cells, T regulatory cells). Moreover, protein processing and mRNA metabolic signaling pathways were involved in the functional mechanisms of OSBPL3. Our study first demonstrated that a novel agent OSBPL3 plays an important role in tumorigenesis from the perspective of publicly available databases and clinical tumor samples in various cancers, which comprehensively provide insights into its biological functions and may be helpful for further investigation.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths, worldwide, and its prognosis is unfavorable. The aim of this study was to detect serum miR-101 levels in NSCLC patients and investigate its potential diagnostic and prognostic value. A total of 93 patients with NSCLC, 40 cases with various benign lung disease, and 55 healthy volunteers, were enrolled. Quantitative RT-PCR was performed to determine relative serum miR-101 levels in our participants. Decreased serum miR-101 expression was observed in patients with NSCLC and was closely associated with aggressive clinical characteristics. In addition, a significant increase in serum miR-101 levels was found in 36 NSCLC cases after tumor resection. Moreover, receiver-operating characteristic (ROC) curve analysis showed that serum miR-101 was an effective indicator for NSCLC diagnosis. Furthermore, Kaplan-Meier survival curve analysis revealed that low serum miR-101 expression predicted poor overall survival and disease-free survival. Finally, multivariate analysis confirmed serum miR-101 expression was an independent prognostic factor for NSCLC patients. In conclusion, serum miR-101 might serve as a potential biomarker for detection and prognosis evaluation of NSCLC.
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