Multidisciplinary approach to diagnosis and management of fever of unknown origin: A case report.

INTRODUCTION: Fever of unknown origin (FUO) poses a diagnostic challenge, often requiring a systematic evaluation to uncover its elusive cause. This case study delves into the presentation of a 42-year-old Chinese male with persistent fever, muscle pain, and a perplexing rash. PATIENT CONCERNS: The patient's symptoms included a prolonged fever, chills, muscle pain, and throat discomfort, with a history of pulmonary tuberculosis. Initial diagnoses of upper respiratory infection and unspecified infection were followed by antibiotic treatments, yet the fever persisted, accompanied by an exacerbating rash. DIAGNOSIS: Extensive diagnostic investigations, including laboratory tests, imaging studies, and skin dermoscopy, provided valuable insights. The patient exhibited elevated inflammatory markers, hepatosplenomegaly, lymphadenopathy, and lung nodules. Differential diagnoses included adult-onset Still disease and drug-induced hypersensitivity syndrome. INTERVENTIONS: The patient received a series of antibiotic treatments, which initially had limited success. Upon considering an autoimmune etiology, corticosteroids were introduced, followed by cyclosporine. The patient exhibited a positive response to this immunosuppressive therapy. OUTCOMES: Treatment adjustments were made, and the patient responded positively to a combination of corticosteroids and cyclosporine. His fever subsided, and laboratory markers normalized. One month after discharge, the patient showed continued improvement. CONCLUSION: FUO cases often demand a multidisciplinary approach, considering rare and uncommon diseases. This case underscores the importance of thorough evaluation, collaboration between specialties, and vigilant monitoring of treatment responses. The patient's unique presentation emphasizes the need to consider drug-induced reactions, even when symptoms deviate from typical disease patterns, highlighting the complexities in diagnosing and managing FUO.

Downregulated SIRT6 and upregulated NMNAT2 are associated with the presence, depth and stage of colorectal cancer.

Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide, and is difficult to detect in its early stages. Diagnostic and prognostic biomarkers are required, which may also be the basis for improving the targeted therapy for CRC. Sirtuin 6 (SIRT6) is a member of the sirtuin family of gene regulators, which have specific functions in genomic stability, gene transcription and energy metabolism in tumorigenesis. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is a metabolic enzyme which can be deacetylated by sirtuins. In this study, tissue samples from 29 patients with histologically confirmed CRC of varying grade and stage were studied for SIRT6 and NMNAT2 expression by western blotting and reverse transcription-quantitative polymerase chain reaction. Immunohistochemistry was performed for SIRT6 and NMNAT2 expression in 113 paired (CRC and adjacent) tissue sections. SIRT6 protein and mRNA expression levels were significantly reduced in CRC tissues; NMNAT2 protein and mRNA expression levels were significantly increased in CRC tissues (P<0.01). A negative correlation between the expression of SIRT6 and NMNAT2 in CRC tissue samples was identified (r=-0.246, P<0.01). The reduced expression of SIRT6 and increased expression of NMNAT2 were associated with the tumor depth invasion, stage, differentiation grade (SIRT6 only) and the presence of lymph node metastasis (P<0.05). In conclusion, the findings of the present preliminary study demonstrated that the increased expression of NMNAT2 and reduced expression of SIRT6 may be associated with the progression of CRC. The downregulation of SIRT6 may promote the expression of NMNAT2. Further studies are indicated on the role of NMNAT2 and SIRT6 as potential diagnostic and prognostic biomarkers and as targets for therapy in CRC and other malignant tumors.

Huang Gan Formula Eliminates the Oxidative Stress Effects of Advanced Oxidation Protein Products on the Divergent Regulation of the Expression of AGEs Receptors via the JAK2/STAT3 Pathway.

Chronic kidney disease (CKD) has a high prevalence and low cure rate and represents a significant health issue. Oxidative stress is common in CKD due to metabolic disorders, inflammation, and impaired renal function changing normal proteins into advanced oxidation protein products (AOPPs). Huang Gan formula (HGF) is a new type of traditional Chinese herbal medicine. Although we previously investigated the protective effects of HGF against oxidative stress, the mechanism of HGF in CKD is still not fully understood. In this study, we used western blotting, quantitative polymerase chain reaction, and biochemical assays to show that HGF significantly decreased AOPP-induced oxidative stress damage. Moreover, the protective effects of HGF might be associated with upregulation of the advanced glycation end product receptor 1 (AGE-R1) and downregulation of the receptor for advance glycation end products (RAGE). Treatment with HGF and the Janus kinase 2 (JAK2) inhibitor, AG4-90, significantly attenuated AOPP-induced JAK2/STAT3 protein levels. These findings indicate that HGF inhibits AOPP-mediated biological responses by inactivating the JAK2/STAT3 pathway. In conclusion, HGF eliminated AOPP-induced effects in human mesangial cells (HMCs) by interrupting JAK2/STAT3 signaling, which altered RAGE/AGE-R1 expression and reduced oxidative stress in CKD.

Nicotinamide Mononucleotide Adenylyl Transferase 2: A Promising Diagnostic and Therapeutic Target for Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers all over the world. It is essential to search for more effective diagnostic and therapeutic methods for CRC. Abnormal nicotinamide adenine dinucleotide (NAD) metabolism has been considered as a characteristic of cancer cells. In this study, nicotinamide mononucleotide adenylyl transferases (NMNATs) as well as p53-mediated cancer signaling pathways were investigated in patients with colorectal cancer. The CRC tissues and adjacent normal tissues were obtained from 95 untreated colorectal cancer patients and were stained for expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) and p53. The survival rate was analyzed by the Kaplan-Meier method and the log-rank test. The multivariate Cox proportional hazard regression analysis was conducted as well. Our data demonstrated that expression of NMNAT2 and p53 was significantly higher in CRC tissues, while NMNAT2 expression is in correlation with the invasive depth of tumors and TNM stage. Significant positive correlation was found between the expression of NMNAT2 and the expression of p53. However, NMNAT2 expression was not a statistically significant prognostic factor for overall survival. In conclusion, our results indicated that NMNAT2 might participate in tumorigenesis of CRC in a p53-dependent manner and NMNAT2 expression might be a potential therapeutic target for CRC.