The current work screened differentially expressed genes (DEGs) related to advanced clear cell renal cell carcinoma (ccRCC) and found potential biomarkers and drugs for advanced ccRCC. After analyzing GSE53757 and GSE66271, we identified DEGs and performed the functional annotation, pathway enrichment, validation, survival analysis, and candidate drug analysis. We obtained 861 common DEGs from datasets between advanced ccRCC tissues and normal kidney tissues. Besides, we performed functional analysis under ontological conditions and carried out pathway analysis. The five most stable core gene groups and top 10 genes were screened using the Cytoscape software. We performed functional and pathway analyses again and found that the core genes were similar to total DEGs. After verification, the expression trends of the 10 hub genes did not change. Survival analysis showed high expressions of TOP2A, BIRC5, BUB1, MELK, RRM2, and TPX2 genes, suggesting that they might participate in cancer occurrence, migration, and relapse of ccRCC. The gene-drug analysis showed that gallium nitrate, cladribine, and amonafide were strongly associated with RRM2 and TOP2A. We found that RRM2 and TOP2A might be predictive biomarkers and novel targeted therapy for advanced ccRCC. These drugs (gallium nitrate, cladribine, and amonafide) might be used for treating advanced ccRCC.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal-recessive hereditary neuropathy causing congenital loss of pain sensation, thermoception, and perspiration. CIPA sometimes causes destructive spondyloarthropathy, the so-called Charcot spine, because of insensitivity to pain stimuli. Herein, we report a case of CIPA with severe spinal destruction treated by multiple spinal reconstructive surgeries and over 15 years of follow-up. A 15-year-old male patient who had been diagnosed with CIPA at the age of 17 months presented to his previous spine clinic with gait disturbance due to muscle weakness in his lower extremities. Imaging studies revealed that collapsed L3 and L4 vertebral bodies involved the spinal canal, and it was treated by L3-L4 instrumented posterior fusion. Fourteen years after surgery, the patient became unable to walk again due to spinal canal stenosis at the proximal fusion segment. An L2-L3 posterior interbody fusion alleviated his gait ability for 2 years; however, he became unable to stand again because of the collapsed fusion segment that caused severe lumbar kyphosis. Subsequently, a two-staged posterior and anterior fusion surgery from the lower thoracic spine to the pelvis was performed, and spinal fusion and neurological recovery were achieved 3 years after surgery. A kyphotic deformity in patients with CIPA-associated Charcot spine could be favorably treated by a long spinal fusion in combination with a reconstruction of an anterior spinal column. This case report provides a significant lesson for a treatment of CIPA-associated Charcot spine.

Müller-Weiss Disease (MWD) is a rare foot disease with unclear etiology but frequently occurred in women. Due to the resistance to conservative treatment, surgical therapy has gradually occupied a necessary position in the clinical management of MWD. Joint fusion surgery is a commonly used treatment for MWD, which could effectively alleviate pain, correct deformation, and restore function. A total of 12 MWD patients (III-V stage) were enrolled in this study. All patients showed no significant improvement in conservative treatment and further received the triple and talonavicular arthrodesis. All patients were followed up with an average follow-up of 16.8 ± 1.19 months (mean ± SD). The triple and talonavicular arthrodesis significantly ameliorated the pain and walking dysfunction in the affected foot. The American Orthopedic Foot Andankle Society (AOFAS) scores dramatically increased from 43.4 ± 16.1 to 85.3 ± 6.2. Meanwhile, the conducting of triple and talonavicular arthrodesis improved the X-ray length (15.5 ± 0.8 vs. 14.3 ± 0.9 cm) and arch height (18.6 ± 0.9 vs. 10.2 ± 0.7 mm) and reduced the Meary-Tomeno angle (1.3 ± 2.5 vs. 2.14 ± 4.8°). The triple and talonavicular arthrodesis achieved a satisfying therapeutic effect on MWD patients at the III-V stage, which improved patients’ outcomes and the quality of life.

The exact profiles of the clinical symptoms related to the SARS-CoV-2 Omicron variant (B.1.1.529) remain largely uncertain. Therefore, this study aimed to clarify the clinical manifestations of infection with this variant. We enrolled individuals who were tested by quantitative nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test at a large screening center in a city of Japan during the B.1.1.529 Omicron variant wave between January and May 2022, after contact with COVID-19 patients. Swab tests were planned to be performed approximately 4-5 days after contact. The presence of COVID-19-related symptoms was assessed at the swab test site. Among the 2,507 enrolled individuals, 943 (37.6%) were RT-PCR test-positive and 1,564 (62.4%) were test-negative. Among the 943 PCR test-positive participants, the prevalence of the symptoms was as follows: 47.3% with cough, 32.9% with sore throat, 18.4% with fatigability, 12.7% with fever of ≥ 37.5℃, 9.9% with dyspnea, 2.1% with dysosmia, and 1.4% with dysgeusia. The prevalence of cough, sore throat, dyspnea, and fatigability was higher among adults aged ≥ 18 years than among children and adolescents. The prevalence of dysosmia and dysgeusia remarkably decreased during the Omicron wave (1-3%) compared to during the pre-Omicron variant waves (15-25%). In summary, common COVID-19-related symptoms during the Omicron variant wave included cough and sore throat, followed by fatigability, fever, and dyspnea. The prevalence of most of these symptoms was higher in adults than in non-adults. The prevalence of dysosmia and dysgeusia remarkably decreased with the Omicron variant than with pre-Omicron variants.

Ferroptosis, a newly recognized type of programmed cell death, is characterized by lipid peroxidation and implicated in multiple pathophysiological processes. Ferroptosis agonists are attracting tremendous attention for the clinical management of malignancy. We uncovered that rhamnazin exerted its anti-cancer property via reducing cell proliferation and invasion in hepatocellular carcinoma (HCC) cells. The ferroptosis inhibitor ferrostatin-1 (Fer-1) partially reversed rhamnazin-triggered cell proliferation inhibition, indicating that ferroptosis contributed to the inhibitory potency of rhamnazin. Further characterization corroborated that exposure with rhamnazin, reactive oxygen species (ROS) accumulation and lipid peroxidation, and iron content were elevated in HCC cells. Mechanistically, we demonstrated that glutathione peroxidase 4 (GPX4) was involved in rhamnazin-initiated ferroptotic cell death. Overexpression of GPX4 weakened HCC cell ferroptosis caused by rhamnazin. Collectively, these results strongly suggest that rhamnazin exerts a ferroptosis-inducing role in HCC cells by inhibiting GPX4 expression.

Vasohibin-2 (VASH2) is a gene that promotes local angiogenesis. The tubulin carboxypeptidase activity of vasohibin causes detyrosination of alpha-tubulin and may play an important role in the regulation of various phenomena. Pathological and therapeutic angiogenesis are involved in atherosclerotic lesions. This study aimed to investigate whether the expression of VASH2 is associated with peripheral artery disease (PAD) in relation to angiogenesis, tubulin detyrosination, and severity of atherosclerotic lesions. An analysis of femoral and tibial arteries obtained from 86 patients with PAD or abdominal aortic aneurysm (AAA) was performed. The expressions of cluster of differentiation 31, VASH1, VASH2, and detyrosinated alpha-tubulin (DT-tubulin) were examined by immunohistochemistry, and their association with PAD was analyzed. The counts of VASH2 in the tunica media and adventitia in the tibial artery were significantly higher than those in the femoral artery in the PAD (P = 0.005 and P = 0.008, respectively) and AAA (P = 0.002 and P < 0.001, respectively) groups. In the tunica media and adventitia, VASH2 was significantly correlated with DT-tubulin. There was no significant difference in the expression of VASH2 and DT-tubulin in medial smooth muscle cells (McNemar test, P > 0.999). This study revealed the possible involvements of VASH2 in atherosclerosis by two methods—one maybe related to the progression of atherosclerosis by inducing angiogenesis and the second may be related to the decrease in arterial elasticity by increasing DT-tubulin in medial smooth muscle cells.

This prospective, observational study was conducted in a university hospital to verify that intraoperative worsening of right ventricular function causes cardiac surgery-associated acute kidney injury. Adult patients undergoing cardiac surgery under mid-sternal incision with cardiopulmonary bypass were included. Echocardiographic right and left ventricular function parameters were measured before and after bypass and compared using the Wilcoxon signed-rank test. Perioperative serum creatinine values at baseline and within the first 48 hours postoperatively were measured for the diagnosis of acute kidney injury. Spearman rank-order correlation (ρ) and receiver operating characteristic analysis were used to reveal relationships. Thirty-four patients were evaluated. Right ventricular ejection fraction (56.2 ± 7.0 vs. 51.6 ± 7.2%; P = 0.0002), right ventricular fractional area change (49.1 ± 6.4 vs. 46.6 ± 5.3%; P = 0.0201; mean ± standard deviation), and left ventricular ejection fraction (57.4 ± 6.1 vs. 51.7 ± 6.2%; P < 0.0001) were significantly decreased. Central venous pressure was significantly increased (7.2 ± 3.5 vs. 9.7 ± 3.7; P = 0.0001). Serum creatinine values increased from 0.82 [0.70-1.08] to 0.99 [0.82-1.54] mg/dL (P < 0.0001; median [interquartile range]). Changes in right ventricular ejection fraction, fractional area change, and right ventricular strain during cardiovascular surgery were significantly correlated with changes in serum creatinine values. Fractional area change exhibited the strongest correlation (ρ = −0.61, P < 0.0001). Change in fractional area change showed an area under the curve of 0.902 and a cutoff value of −2.1, which predicted acute kidney injury with 92% sensitivity, 73% specificity, and 79% accuracy. The functions of both ventricles were decreased after cardiopulmonary bypass. Worsening right ventricular function was independently correlated with postoperative renal dysfunction, and fractional area change was the strongest predictor of cardiac surgery-associated acute kidney injury.

Spinal cord injury (SCI) is commonly associated with neuropathic pain, which affects large population. Thus, the presented investigation evaluates the beneficial effect of epifriedelinol against SCI-associated neuropathic pain. SCI injury was induced in rats by clip-compression and rats were treated with epifriedelinol 100 and 200 mg/kg, i.p. for 21 days after the induction of SCI. The effect of epifriedelinol was assessed on neuropathic pain by mechanical allodynia and locomotor function. Level of inflammatory cytokines were assessed in the neuronal tissue using enzyme linked immunosorbent assay (ELISA) and expression of caspase-3 and Bcl2 protein were assessed by western blot assay. Data of investigation reveals that epifriedelinol reduces mechanical allodynia in SCI injured rats. Moreover, it also improves locomotor function in SCI injured rats. There was significant decrease in level of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in the neuronal tissues of epifriedelinol-treated group than negative control group. Moreover, treatment with epifriedelinol ameliorates the altered expression of caspase 3, Bcl2 and GluN1 and level of glutamate in neuronal tissue of SCI-injured rats. In conclusion, data reveal that epifriedelinol treatment protects neuropathic pain associated with spinal cord injury by downregulating the N-methyl-D-aspartate (NMDA) receptor function.

Liver cancer is one of the most common cancer forms and a significant contributor to global cancer-associated mortality. Hepatitis B virus (HBV) infection contributes enormously to HCC development and progression. Despite this, the molecular basis of liver tumorigenesis is not clear. This work focused on identifying the relevant genetic markers and available drugs for treating HBV-related HCC. Differentially expressed genes (DEGs) from HBV-related HCC samples and corresponding healthy samples were identified from GSE62232 and GSE121248 datasets from the GEO2R repository (Gene Expression Omnibus). The Venn diagram software screened the overlapping DEGs between these two datasets. The DEGs were functionally assessed using protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses by different bioinformatic methods, and hub genes were screened. Hub genes and related drugs were verified by the GEPIA2 (Gene Expression Profiling Interactive Analysis) web server and the Quartata Web online platform. Overall, 116 DEGs (88 up-regulated and 28 down-regulated) related to signal transduction and metabolic pathways were identified. The nine significant target hub genes were TOP2A, RRM2, DTL, ECT2, ASPM, ANLN, BUB1B, CCNB1, and CDK1. Moreover, one screened drug, Fostamatinib, was targeted to CDK1. Our study identified three genes and associated drugs as probable targets for studying HBV-related HCC.

Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients’ outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.