Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database.

Introduction: An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data. Methods: Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers. Results: In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2 months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction. Conclusion: There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab/ipilimumab, and pembrolizumab/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction.

Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0/G1 arrest and mitochondrial apoptosis.

Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ's effects on MM are unclear. We investigated CTZ's effect on MM cell proliferation and apoptosis induction mechanisms. CTZ's effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Multi role ChatGPT framework for transforming medical data analysis.

The application of ChatGPTin the medical field has sparked debate regarding its accuracy. To address this issue, we present a Multi-Role ChatGPT Framework (MRCF), designed to improve ChatGPT's performance in medical data analysis by optimizing prompt words, integrating real-world data, and implementing quality control protocols. Compared to the singular ChatGPT model, MRCF significantly outperforms traditional manual analysis in interpreting medical data, exhibiting fewer random errors, higher accuracy, and better identification of incorrect information. Notably, MRCF is over 600 times more time-efficient than conventional manual annotation methods and costs only one-tenth as much. Leveraging MRCF, we have established two user-friendly databases for efficient and straightforward drug repositioning analysis. This research not only enhances the accuracy and efficiency of ChatGPT in medical data science applications but also offers valuable insights for data analysis models across various professional domains.

Associations between Proton-Pump Inhibitor Usage, Allergy, and Asthma: An Analysis of NHANES 2005-2006.

INTRODUCTION: Acid suppression medications, such as proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists, are commonly prescribed for the treatment of gastroesophageal reflux disease and other gastrointestinal disorders. However, concerns regarding potential long-term side effects are brought up by the overuse of PPIs. This study aimed to investigate the relationship between PPI usage, allergy, and asthma in the general US population. METHODS: Data of individuals aged ≥20 years who had information on PPI use and questionnaires on allergy and asthma in the US National Health and Nutrition Examination Survey (NHANES) 2005-2006 were analyzed. Univariate and multivariable logistic regression analyses were performed to determine the associations between PPI use, prevalent allergy, and asthma. RESULTS: A total of 4,481 participants (representing 198,543,007 US individuals after weighting) were included in the analyses. PPI use was not significantly associated with the presence of allergy or asthma in the general study population after adjustment. However, in females without steroid exposure, PPI use was significantly associated with increased odds of allergy (adjusted odds ratio [aOR] = 1.69, 95% confidence interval [CI]: 1.002-2.86), among which esomeprazole use was significantly associated with increased odds of allergy (aOR = 2.68, 95% CI: 1.30-5.54) and lansoprazole with increased odds of asthma (aOR = 3.44, 95% CI: 1.50-7.87) as compared to no PPI use. Duration of PPI use was not significantly associated with allergy or asthma. CONCLUSIONS: In US women without steroid exposure, PPI use is associated with increased likelihood of prevalent allergy and asthma.

Establishing and applying an adaptive framework for imported malaria: a field practice in Anhui Province, China from 2012 to 2022.

BACKGROUND: Anhui Province is currently facing an increase in imported malaria cases as a result of globalization and international travel. In response, Anhui Province has implemented a comprehensive adaptive framework to effectively address this threat. METHODS: This study collected surveillance data from 2012 to 2022 in Anhui Province. Descriptive statistics were used to analyze the epidemiological characteristics of imported malaria cases. Additionally, multivariate logistic regression was employed to identify factors associated with severe malaria. Documents were reviewed to document the evolution of the adaptive framework designed to combat imported malaria. The effectiveness of the adaptive framework was evaluated based on the rates of timely medical visits, timely diagnosis, and species identification. RESULTS: During the study period, a total of 1008 imported malaria cases were reported across 77 out of 105 counties in Anhui Province, representing a coverage of 73.33%. It was found that 10.52% of imported cases went undiagnosed for more than seven days after onset. The multivariate analysis revealed several potential risk factors for severe malaria, including increasing age (OR = 1.049, 95%CI:1.015-1.083), occupation (waitperson vs. worker, OR = 2.698, 95%CI:1.054-6.906), a longer time interval between onset and the initial medical visit (OR = 1.061, 95%CI:1.011-1.114), and misdiagnosis during the first medical visit (OR = 5.167, 95%CI:2.535-10.533). Following the implementation of the adaptive framework, the rates of timely medical visits, timely diagnosis, and species identification reached 100.00%, 78.57%, and 100.00%, respectively. CONCLUSIONS: Anhui Province has successfully developed and implemented an adaptive framework for addressing imported malaria, focusing on robust surveillance, prompt diagnosis, and standardized treatment. The experiences gained from this initiative can serve as a valuable reference for other non-endemic areas.

Impact of immunosenescence and inflammaging on the effects of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells. Although ICIs can potentially treat different types of cancers in various groups of patients, their effectiveness may differ among older individuals. The reason ICIs are less effective in older adults is not yet clearly understood, but age-related changes in the immune system, such as immunosenescence and inflammation, may play a role. Therefore, this review focuses on recent advances in understanding the effects of immunosenescence and inflammation on the efficacy of ICIs.

Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow. The translocation, (t)(4;14), results in high-risk MM with limited treatment alternatives. Thus, there is an urgent need for identification and validation of potential treatments for this MM subtype. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To elucidate the molecular basis and search for potential effective drugs of t(4;14) MM subtype by employing a comprehensive approach. METHODS: The transcriptional signature of t(4;14) MM was sourced from the Gene Expression Omnibus. Two datasets, GSE16558 and GSE116294, which included 17 and 15 t(4;14) MM bone marrow samples, and five and four normal bone marrow samples, respectively. After the differentially expressed genes were identified, the Cytohubba tool was used to screen for hub genes. Then, the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Using the STRING database and Cytoscape, protein-protein interaction networks and core targets were identified. Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis, respectively. RESULTS: In this study, a total of 258 differentially expressed genes with enriched functions in cancer pathways, namely cytokine receptor interactions, nuclear factor (NF)-κB signaling pathway, lipid metabolism, atherosclerosis, and Hippo signaling pathway, were identified. Ten hub genes (cd45, vcam1, ccl3, cd56, app, cd48, btk, ccr2, cybb, and cxcl12) were identified. Nine drugs, including ivermectin, deforolimus, and isoliquiritigenin, were predicted by the Connectivity Map database to have potential therapeutic effects on t (4;14) MM. In molecular docking, ivermectin showed strong binding affinity to all 10 identified targets, especially cd45 and cybb. Ivermectin inhibited t(4;14) MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro. Furthermore, ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14) MM cells. CONCLUSION: Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.

Nucleation-Supersaturation Dual-Drive Crystallization Strategy Enables Efficient Protein Crystallization.

A rational crystallization strategy is essential to obtain high-quality protein crystals, yet the established methods suffer from different limitations arising from the single regulation on either nucleation or supersaturation. Herein, a nucleation-supersaturation dual-driven crystallization (DDC) strategy that realizes synergistic regulation of heterogeneous nucleation sites and solution supersaturation based on dual surface and confinement effects for efficient protein crystallization is reported. This strategy relies on a p(PEGDA-co-DMAA) hydrogel template with pre-filled NaCl under designed concentrations. Once dropping hen egg white lysozyme (HEWL) protein solution on the hydrogel, the wrinkled surface provides numerous nucleation sites, while the internal structure regulates the solution supersaturation in the crystallization region through diffusion. Finally, DDC strategy can create high-quality HEWL crystals with large sizes (100-300 µm), well-defined morphologies (hexagon and tetragon), and a significantly accelerated nucleation time (9-12 times faster than that achieved using the conventional hanging drop method). It also performs well at wider protein concentrations (10-50 mg mL-1 ) and categories (e.g., achieving fast crystallization and large-size crystals of trypsin), therefore demonstrating clear advantages and great potential for efficiently fabricating protein crystals desirable for diverse applications.

Kidney Transplantation and Clinical Outcomes in Patients With Multiple Myeloma: Evidence From the United States Nationwide Inpatient Sample.

PURPOSE: Patients with multiple myeloma (MM) are prone to developing persistent renal insufficiency. Novel therapeutic medications have improved long-term survival, making kidney transplantation (KT) a viable treatment option for MM survivors with end-stage renal disease. This study aimed to investigate the clinical outcomes in patients with MM who have received KT. METHODS: Data from hospitalized patients ≥ 40 years of age with MM in the Nationwide Inpatient Sample 2016-2018 of the United States were queried. Patients were classified as having or not having undergone KT, as well as the stage of chronic kidney disease (CKD) for those who had not received KT. Propensity-score matching (PSM) was applied to balance the characteristics between the groups. Binary logistic regression was utilized to determine the associations between study variables and inhospital mortality, unfavorable discharges, prolonged length of stay (LOS), and major complications. RESULTS: In total, 50,654 hospitalized patients with MM were identified, of whom 165 (0.3%) had received KT and 50,489 had not (5,905 at stage 5 CKD [CKD5D], 11,559 at stage 1-4 CKD [CKD1-4D], and 33,025 who were CKD-free). After PSM, between-group demographic and hospital-related characteristics were balanced. Binary regression analysis revealed that, compared to patients who were CKD-free, patients at CKD5D were significantly more likely to experience a prolonged LOS (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01-1.70) after adjusting for relevant confounders. Furthermore, compared to CKD-free patients, those who underwent KT were significantly more likely to have sepsis (OR, 1.48; 95% CI, 1.02-2.14). However, KT showed no association with the other adverse inpatient outcomes. CONCLUSION: Although KT is not common in MM patients, those who had undergone KT had comparable hospital outcomes to CKD-free patients. These data will help clinicians deliver better consultations to MM patients attempting to receive KT.

Identification of immunity-related lncRNAs and construction of a ceRNA network of potential prognostic biomarkers in acute myeloid leukemia.

Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis. Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed. Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified. Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.

[Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients].

OBJECTIVE: To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients. METHODS: Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM. RESULTS: 36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients. CONCLUSION: Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

[Clinical Research Advances of Duodenal-Type Follicular Lymphoma--Review].

Duodenal-type follicular lymphoma (DFL) is a unique subtype of follicular lymphoma (FL), which often involves the second portion of duodenum (descending part of duodenum). Due to its specific pathological features, such as lack of follicular dendritic cells meshwork and disappearance of activation-induced cytidine deaminase expression, DFL presents an inert clinical course and is often confined to the intestinal tract. Inflammation-related biomarkers suggest that the microenvironment may play a likely role in the pathogenesis and favorable prognosis of DFL. Since patients generally have no obvious clinical symptoms and low progression rate, the treatment regimen for DFL is mainly observation and waiting (W&W) strategy. This study will review the latest research progress of epidemiology, diagnosis, treatment and prognosis of DFL in recent years.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.

Background: Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods: This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results: Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (ß Value 0.081; 95% CI, -1.012 to 3.657; P = 0.265) or discharge (ß Value 0.114; 95% CI, -0.723 to 6.408; P = 0.117). d-dimer (ß Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (ß Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (ß Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (ß Value -0.206; 95% CI, -6.248 to -1.197; P = 0.004), LDH (ß Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (ß Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (ß Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, P = 0.018; Z=-2.010, P = 0.044) and a shorter hospital stay (Z=-2.735, P = 0.006; Z=-3.858, P < 0.001). Conclusions: In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

[Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes].

OBJECTIVE: To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes. METHODS: The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score. RESULTS: A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect. CONCLUSION: Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Study on the hypolipidemic effect of Inonotus obliquus polysaccharide in hyperlipidemia rats based on the regulation of intestinal flora.

The purpose of this study was to observe the effect of Inonotus obliquus polysaccharide (IOP) on blood lipids and its regulation on the intestinal flora in hyperlipidemia rats, and explore the modern biological connotation of IOP in reducing blood lipids. In this study, we obtained the crude IOP by the water extraction and alcohol precipitation method, and then classified it by DEAE ion-exchange chromatography to obtain the acidic I. obliquus polysaccharide (IOP-A). After the administration of the IOP-A, the serum TC, TG, and LDL-C levels were significantly lower, while the serum HDL-C levels were significantly higher. The expression of CYP7A1 protein was considerably increased, whereas the expression of SREBP-1C protein was considerably decreased in the rat hepatic tissue. In addition, the IOP-A could significantly alleviate the hepatocyte fatty degeneration in the liver lobule of rats. We believe that the IOP-A can affect the composition of intestinal flora by reducing the relative abundance of Firmicutes and increasing the relative abundance of Bacteroidetes. These findings indicated that the IOP-A can regulate the dyslipidemia of hyperlipidemia rats, and its mechanism may be through regulating the CYP7A1 and SREBP-1C expression in the metabolism of lipids, and correcting the imbalance of intestinal flora structure caused by a high-fat diet.

A case of diffuse large B-cell lymphoma with interstitial pneumonia.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving "full coverage" treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Combination of two target agonists of the thrombopoietin and thrombopoietin receptor in the treatment of elderly patients with refractory immune thrombocytopenia.

Immune thrombocytopenia (ITP) is common in the elderly. Because of the coexistence of multiple diseases, there are many reservations regarding corticosteroid use in the elderly. Thrombopoietin (TPO) and its analogs can promote platelet production, but it is often difficult to correct TP in a short period. Recombinant human TPO (rh-TPO) acting on the cell membrane and the small-molecule TPO-receptor (MPL) agonist acting on the transmembrane receptor may have synergistic effects and accelerate platelet production because of different sites of action in the signaling pathway. In this study, two elderly patients with refractory ITP were successfully treated with two TPO-MPL signaling pathway agonists: recombinant human thrombopoietin (rh-TPO) and eltrombopag. This combination is safe with rapid and lasting effects. However, in elderly patients with refractory, recurrent, and glucocorticoid contraindications, the combination of different TPO agonists' clinical efficacy and adverse reactions needs to be further evaluated.