Adverse reactions caused by high serum concentration of linezolid: Two case reports and literature review.

Linezolid is a potent oxazolidinone for the treatment of various gram-positive bacterial infections. However, the drug can cause potential adverse reactions such as thrombocytopenia, hyperlactacidemia and serotonin syndrome, which warrant consideration by the medical team when planning treatment. The existing literature has reported some adverse reactions caused by linezolid, but most of these are based on clinical characteristics and simple treatment measures. Two cases of linezolid overdose resulting in thrombocytopenia, hyperlactacidemia and serotonin syndrome are presented, which were successfully managed with therapeutic drug monitoring. A dose adjustment strategy was adopted to safely and effectively mitigate linezolid-related adverse events.

Dose adjustment strategy of levetiracetam in pregnant patients with epilepsy: Case report and literature review.

RATIONALE: Pregnant patients with epilepsy are prone to preterm delivery, stillbirth, or cesarean section, and their mortality rate is almost 10 times higher than that of normal pregnant women. The potential negative influences of antiepileptic drugs (AEDs) on the fetus are weighed against the necessity for achieving optimal control of seizures. Treatment with AEDs during pregnancy is a major challenge for pregnant women and healthcare teams. PATIENT CONCERNS: This paper reports two cases of young women diagnosed with pregnancy and epilepsy. INTERVENTION: The dose of levetiracetam was adjusted under the guidance of therapeutic drug monitoring to reduce the effects of seizures on the fetus and the incidence of reproductive toxicity caused by adverse drug reactions. OUTCOMES: Epilepsy was well controlled in the two pregnant patients, and the newborns had no genetic disorders. LESSONS: It is recommended to regularly monitor the serum LEV level in pregnant patients with epilepsy. This practice serves as a foundation for adjusting the drug treatment plan and offering more precise guidance for medication management during pregnancy.

Delayed low-dose methotrexate excretion in a rheumatoid arthritis patient: A case report and literature review.

RATIONALE: Low-dose methotrexate has a relatively good safety profile. However, in cases where patients with multiple risk factors, a delayed excretion has been observed, resulting in the occurrence of severe adverse reactions. It is necessary to supervise and intervene throughout the entire process of treating patients with multiple risk factors for methotrexate, and to strengthen the rational application of methotrexate. PATIENT CONCERNS AND DIAGNOSES: A 66-year-old male patient was admitted to our hospital with rheumatoid arthritis and underlying conditions such as chronic obstructive pulmonary disease (COPD). This patient received treatment with low-dose MTX (10 mg/week) and experienced adverse reactions including anemia. He was diagnosed with methotrexate-induced bone marrow suppression. INTERVENTIONS AND OUTCOMES: The therapeutic drug monitoring revealed that the serum drug concentration of methotrexate was at a critical level and the patient was rescue with calcium folinate and other adjuvant therapy such as transfusions of red blood cells, plasma, platelets, oral Yixuesheng tablets and Leucogen tablets. We conducted a 1-month follow-up, and there was no recurrence of bone marrow suppression and anemia. LESSONS: To ensure rational administration of methotrexate, it is important to fully evaluate the clinical manifestations and physical condition of patients and regularly detecting the serum drug concentration of methotrexate when patients with multiple risk factors, Otherwise, even low-dose methotrexate administration may cause delayed excretion, resulting in severe adverse reactions.

Rescue strategies for valproic acid overdose poisoning: Case series and literature review.

Valproic acid (VPA) is a wide-ranging anti-epileptic medication that primarily affects bipolar disorder, mania, and migraine. The leading causes of mortality associated with acute poisoning from VPA are nervous system toxicity, drug-induced shock due to encephalopathy from hyperammonemia, as well as acute liver and kidney failure, and respiratory depression that contribute to hemodynamic instability. Treatment of acute VPA poisoning primarily involves in vitro elimination methods, including hemoperfusion (HP), hemodialysis, and hemofiltration, as well as drug remedies such as L-carnitine and meropenem. Nonetheless, there are conflicting opinions regarding drug usage. This article details the three cases of acute poisoning from VPA. The fundamental approach to treatment employs HP assisted by blood concentration monitoring to alleviate shock and stabilize hemodynamics. This investigation presents guidance for the treatment and management of acute poisoning with VPA in clinical settings.

The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles.

Pyroptosis is a novel regulated cell death (RCD) mode associated with inflammation and innate immunity. Gasdermin E (GSDME), a crucial component of the gasdermin (GSDM) family proteins, has the ability to convert caspase-3-mediated apoptosis to pyroptosis of cancer cells and activate anti-tumor immunity. Accumulating evidence indicates that GSDME methylation holds tremendous potential as a biomarker for early detection, diagnosis, prognosis, and treatment of tumors. In fact, GSDME-mediated pyroptosis performs a dual role in anti-tumor therapy. On the one side, pyroptotic cell death in tumors caused by GSDME contributes to inflammatory cytokines release, which transform the tumor immune microenvironment (TIME) from a 'cold' to a 'hot' state and significantly improve anti-tumor immunotherapy. However, due to GSDME is expressed in nearly all body tissues and immune cells, it can exacerbate chemotherapy toxicity and partially block immune response. How to achieve a balance between the two sides is a crucial research topic. Meanwhile, the potential functions of GSDME-mediated pyroptosis in anti-programmed cell death protein 1 (PD-1) therapy, antibody-drug conjugates (ADCs) therapy, and chimeric antigen receptor T cells (CAR-T cells) therapy have not yet been fully understood, and how to improve clinical outcomes persists obscure. In this review, we systematically summarize the latest research regarding the molecular mechanisms of pyroptosis and discuss the role of GSDME-mediated pyroptosis in anti-tumor immunity and its potential applications in cancer treatment.

Analysis of clinical features of oxcarbazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis.

Background: Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN. Methods: Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023. Results: A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported. Conclusion: Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.

The signaling pathways of traditional Chinese medicine in treating diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common diabetic microvascular complications that occurs in the eyes and is closely associated with vision loss in working adults. However, the clinical treatment of DR is limited or accompanied by a large number of complications. Therefore, the development of new drugs for the treatment of DR is urgently needed. Traditional Chinese medicine (TCM) is widely used to treat DR in China, and its multi-pathway and multi-level characteristics can effectively address the complex pathogenesis of DR. Growing evidence suggests that inflammation, angiogenesis, and oxidative stress are the core pathological mechanisms in the development of DR. This study innovatively considers the aforementioned processes as the fundamental unit and sheds light on the molecular mechanisms and potential of TCM against DR in terms of signaling pathways. The results showed that NF-κB, MAPK/NF-κB, TLR4/NF-κB, VEGF/VEGFR2, HIF-1α/VEGF, STAT3, and Nrf2/HO-1 are the key signaling pathways for the treatment of DR by TCMs, which involved curcumolide, erianin, quercetin, blueberry anthocyanins, puerarin, arjunolic acid, ethanol extract of Scutellaria barbata D. Don, Celosia argentea L. extract, ethanol extract of Dendrobium chrysotoxum Lindl., Shengpuhuang-tang, and LuoTong formula. The purpose of this review is to update and summarize the signaling pathways of TCM in the treatment of DR and provide ideas for the development of new drugs against DR in the future.

Explore the mechanism of ursolic acid acting on atherosclerosis through network pharmacological and bioinformatics methods.

To explore the deep mechanisms of ursolic acid (UA) for treating atherosclerosis based on network pharmacology and bioinformatics. UA target genes were derived from traditional Chinese medicine system pharmacology, BATMAN-TCM, and SwissTargetPrediction databases. Atherosclerosis-related genes were derived from genecards, NCBI genes, and OMIM databases. The protein interaction network was constructed through the STRING database, and the hub network was extracted by using the Cytoscape software MCODE app. The enrichment analysis of gene ontology and Kyoto encyclopedia of genes and genomes was performed by the R software clusterProfiler package, and the expression and prognostic value of the hub genes were verified on the data set. Screen the genes for expression and prognosis conclusions, conduct methylation analysis, and ceRNA construction. UA had 145 targets in the treatment of atherosclerosis. The top 7 gene ontology (biological process, molecular function, and cellular component) and pathways related to atherosclerosis were screened out. It is principally involved in biological processes, including response to lipopolysaccharide and regulation of inflammatory response. The main signaling pathways incorporated the TNF signaling pathway and the AGE-RAGE signaling pathway. Androgen receptor (AR) and interleukin-1 beta gene (IL1B) were further screened as core target genes. Methylation analysis demonstrated that the AR methylation level was elevated in the atherosclerotic group. On the contrary, the IL1B methylation level was lower in the atherosclerotic group. The results of the ceRNA analysis indicated that there were 43 targeted miRNAs in AR and 3 miRNAs in IL1B. We speculate that the target genes of UA regulating atherosclerosis are AR and IL1B. The mechanism may be that UA regulates the expression of target genes by regulating the methylation of target genes.

Pyroptosis in renal inflammation and fibrosis: current knowledge and clinical significance.

Pyroptosis is a novel inflammatory form of regulated cell death (RCD), characterized by cell swelling, membrane rupture, and pro-inflammatory effects. It is recognized as a potent inflammatory response required for maintaining organismal homeostasis. However, excessive and persistent pyroptosis contributes to severe inflammatory responses and accelerates the progression of numerous inflammation-related disorders. In pyroptosis, activated inflammasomes cleave gasdermins (GSDMs) and generate membrane holes, releasing interleukin (IL)-1ß/18, ultimately causing pyroptotic cell death. Mechanistically, pyroptosis is categorized into caspase-1-mediated classical pyroptotic pathway and caspase-4/5/11-mediated non-classical pyroptotic pathway. Renal fibrosis is a kidney disease characterized by the loss of structural and functional units, the proliferation of fibroblasts and myofibroblasts, and extracellular matrix (ECM) accumulation, which leads to interstitial fibrosis of the kidney tubules. Histologically, renal fibrosis is the terminal stage of chronic inflammatory kidney disease. Although there is a multitude of newly discovered information regarding pyroptosis, the regulatory roles of pyroptosis involved in renal fibrosis still need to be fully comprehended, and how to improve clinical outcomes remains obscure. Hence, this review systematically summarizes the novel findings regarding the role of pyroptosis in the pathogenesis of renal fibrosis and discusses potential biomarkers and drugs for anti-fibrotic therapeutic strategies.

Identification of GLS as a cuproptosis-related diagnosis gene in acute myocardial infarction.

Acute myocardial infarction (AMI) has the characteristics of sudden onset, rapid progression, poor prognosis, and so on. Therefore, it is urgent to identify diagnostic and prognostic biomarkers for it. Cuproptosis is a new form of mitochondrial respiratory-dependent cell death. However, studies are limited on the clinical significance of cuproptosis-related genes (CRGs) in AMI. In this study, we systematically assessed the genetic alterations of CRGs in AMI by bioinformatics approach. The results showed that six CRGs (LIAS, LIPT1, DLAT, PDHB, MTF1, and GLS) were markedly differentially expressed between stable coronary heart disease (stable_CAD) and AMI. Correlation analysis indicated that CRGs were closely correlated with N6-methyladenosine (m6A)-related genes through R language "corrplot" package, especially GLS was positively correlated with FMR1 and MTF1 was negatively correlated with HNRNPA2B1. Immune landscape analysis results revealed that CRGs were closely related to various immune cells, especially GLS was positively correlated with T cells CD4 memory resting and negatively correlated with monocytes. Kaplan-Meier analysis demonstrated that the group with high DLAT expression had a better prognosis. The area under curve (AUC) certified that GLS had good diagnostic value, in the training set (AUC = 0.87) and verification set (ACU = 0.99). Gene set enrichment analysis (GSEA) suggested that GLS was associated with immune- and hypoxia-related pathways. In addition, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, competing endogenous RNA (ceRNA) analysis, transcription factor (TF), and compound prediction were performed to reveal the regulatory mechanism of CRGs in AMI. Overall, our study can provide additional information for understanding the role of CRGs in AMI, which may provide new insights into the identification of therapeutic targets for AMI.

Long intergenic noncoding RNA LINC01287 drives the progression of cervical cancer via regulating miR-513a-5p/SERP1.

Cervical cancer is one of the most frequent types of cancer in women, which is characterized by high invasion and metastatic tendency in its advanced stage. Emerging evidence indicated that long non-coding RNAs (LncRNAs) are involved in the pathogenesis of cervical cancer. LINC01287 has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, up until now, whether LINC01287 is associated with the initiation and development of cervical cancer remains largely unknown. In the present study, expression levels of LINC01287, miR-513a-5p and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA were quantified utilizing qRT-PCR. A series of functional experiments including CCK-8 assay, colony formation assay, transwell assay, flow cytometry, and tumor xenograft growth of cervical cancer cells were performed for studying the effects of LINC01287. The luciferase reporter assay, pull-down assay, and western blot were used to confirm the downstream targets of LINC01287 and miR-513a-5p. The results demonstrate that LINC01287 was highly expressed in cervical cancer tissue samples and cell lines. High LINC01287 predicts a poor prognosis for cervical cancer patients. Additional gain- and loss-of-function experiments demonstrated that silencing LINC01287 inhibited cervical cancer cells proliferation, colony formation, migration, apoptosis in vitro and retarded tumor growth and metastasis in vivo. Furthermore, the dual-luciferase reporter gene system and RNA pulldown assay validated that LINC01287 positively regulated SERP1 expressions by sponging miR-513a-5p, and LINC01287 inhibited cervical cancer progression by regulating miR-513a-5p/SERP1 axis. In conclusion, the current study first identified that LINC01287/miR-513a-5p/SERP1 axis played an important role in cervical cancer progression. LINC01287 might be a prognostic biomarker and a target for new therapies in patients with cervical cancer.

The incidence of gestational diabetes mellitus among women with polycystic ovary syndrome: a meta-analysis of longitudinal studies.

BACKGROUND: Previous studies have shown that polycystic ovary syndrome is a predictor of gestational diabetes mellitus, but we do not know exactly how many polycystic ovary syndrome patients may develop gestational diabetes mellitus. Currently, the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome varies greatly across studies, ranged from 4.12% to 59.50%. Besides, many factors have been found to be related to the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, but the results among different studies are not consistent. The possible causes of inconsistencies between the current estimates were unclear. This review aimed at exploring the pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, summarizing possible causes of the inconsistencies in the current estimates, try to provide a reference for prevention of gestational diabetes mellitus and polycystic ovary syndrome in the future. METHODS: Systematic searches of different databases (including EMBASE, Web of Science, MEDLINE, The Cochrane Library, CNKI and PubMed) were conducted for studies published until 31 May 2021. Statistical analyses were performed using R software, the pooled incidence of gestational diabetes mellitus among polycystic ovary syndrome patients was combined using random effects model. Cochrane's "Tool to Assess Risk of Bias in Cohort Studies" was used for quality assessment. RESULTS: Twenty-two longitudinal studies were included. A total of 24,574 women with polycystic ovary syndrome were identified in the 22 articles, of which 4478 were reported with gestational diabetes mellitus. The pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome was 20.64%, with a 95% CI of 14.64% to 28.30%. In the meta-regression model, several variables including age, area, quality score and sample size were suggested as significant sources of heterogeneity, accounted for 77.57% of the heterogeneity across studies. CONCLUSIONS: Evidence in this review suggests that gestational diabetes mellitus were common among women with polycystic ovary syndrome. More research is needed to found effective interventions for preventing gestational diabetes mellitus among women with polycystic ovary syndrome.