Primary nasopharyngeal carcinoma with cerebrospinal fluid EBV positivity: A case report and mini literature review.

Background: To summarize the diagnosis and treatment of a patient with nasopharyngeal carcinoma and cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) positivity (determined by next-generation sequencing), review the relevant literature, and explore the significance of EBV presence in the CSF of patients with nasopharyngeal carcinoma. Methods: A patient presenting with headache as the initial symptom was diagnosed with nasopharyngeal carcinoma and admitted to the Eighth Medical Center of Chinese PLA General Hospital on March 3, 2021. Available databases were screened for reports on nasopharyngeal carcinoma with EBV-positive CSF and analyzed. The patients' general information, initial symptoms, treatment, and prognosis were subsequently evaluated. Results: EBV-positive CSF is commonly observed in patients with recurrent nasopharyngeal carcinoma. However, no reports of EBV-positive CSF in patients with primary nasopharyngeal carcinoma have been published to date. Conclusion: The presence of EBV in the CSF of patients with recurrent nasopharyngeal carcinoma is indicative of a poor prognosis. Thus, newly diagnosed nasopharyngeal carcinoma patients should undergo a lumbar puncture as soon as possible to have their CSF tested for EBV. Such a measure would promptly predict the prognosis and facilitate the development of a personalized treatment strategy.

Effects of THE PEEP-ZEEP Maneuver in Adults Receiving Mechanical Ventilation: A Systematic Review with Meta-Analysis.

INTRODUCTION: It is important to clarify the secretion clearance and lung-related effects of the PEEP-ZEEP maneuver in adults undergoing mechanical ventilation (MV). There is no published comprehensive meta-analysis of the effects of PEEP-ZEEP in adults receiving MV. OBJECTIVES: The aim of this study was to analyze published randomized controlled trials, investigating the effects of the PEEP-ZEEP maneuver in adults undergoing mechanical ventilation. METHODS: We searched Embase, PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from the date of inception of the databases until 6 May 2023. Quality assessment was using the Cochrane Systematic Assessment Handbook. The GRADE system was used to grade the quality of the evidence. RESULTS: A total of 12 trials were included, and the results of the meta-analysis showed that PEEP-ZEEP was not superior to bag squeezing for the removal of bronchial secretions. One study showed a significant increase in the amount of secretion retrieved with the PEEP-ZEEP when compared with tracheal suctioning. Additionally, PEEP-ZEEP was more effective than bag squeezing at improving oxygen saturation. However, one trial showed that bag squeezing was better at improving dynamic compliance. No other differences were found between PEEP-ZEEP and other techniques, except for one study showing more frequent changes in diastolic blood pressure with PEEP-ZEEP compared with ventilator hyperinflation. CONCLUSION: PEEP-ZEEP was not superior to bag squeezing in removing bronchial secretions. However, it improves oxygen saturation when compared to bag squeezing, and no adverse effects on patients' respiratory systems have yet been observed.

Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus.

PURPOSE: Skeletal muscle insulin resistance (IR) is an important etiology of type 2 diabetes mellitus (T2DM); however, its molecular mechanism is yet to be fully defined. This study attempted to identify the gene expression patterns and molecular disorders in T2DM patients' skeletal muscle samples. METHODS: First, the difference in genetic expression among GSE25462 data was analyzed. Next, PPI network analysis of differential genes was carried out, after which the maladjustment module was identified. Then, an enrichment analysis and gene set enrichment analysis (GSEA) were carried out. Finally, the transcription factors that regulate the modular genes by raid were predicted. RESULTS: Most differentially expressed genes were found to be able to form an interaction network and cluster into 9 modules. These modular genes were shown to possess a significant correlation with immune inflammation and metabolic response. Importantly, the top 15 genes of area under receiver operating characteristic curve (AUC) were identified, and the expression of 10 genes by GSE12643, GSE18732 and GSE29221 was confirmed. The expression and AUC value of ALDH6A1 were then verified according to three sets of data, where ALDH6A1 was found to be negatively correlated with follicular helper T cells. However, among the predicted transcription regulators, HDAC was shown to have a better regulatory effect. CONCLUSION: The findings highlight that the dysregulation of ALDH6A1 expression in IR of T2DM may serve as a potential therapeutic target. ALDH6A1 is involved in the immune inflammation and metabolic pathways.

miR-124a enhances therapeutic effects of bone marrow stromal cells transplant on diabetic nephropathy-related epithelial-to-mesenchymal transition and fibrosis.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has been gradually considered as one of the major pathways that causes the production of interstitial myofibroblasts in diseased kidneys. MATERIALS AND METHODS: The study was done to investigate the effect of a bone marrow stromal cell (BMSCs) transplant on rat podocytes and diabetic nephropathy (DN) rats in high-glucose concentration, and to explore the effect of miR-124a on BMSC therapy. High glucose-injured podocytes and streptozotocin-induced DN rats have been respectively used as injury models in in vitro and in vivo studies. Podocyte viability was measured using the Cell Counting Kit-8 assay. Renal pathological examination was observed by HE staining and Masson staining. The messenger RNA and protein levels were determined via real-time polymerase chain reaction and Western blotting, respectively. RESULTS: By mediating the activation of caveolin-1 (cav-1) and ß-catenin and affecting the expression levels of EMT biomarkers including p-cadherin, synaptopodin, fibroblast-specific protein-1, α-smooth muscle actin and snail, our in vitro study confirmed that miR-124a played a significant role in the treatment of high glucose-induced podocyte injury by BMSCs. The therapeutic effects of the BMSC transplant on DN rats were also proved to be further enhanced by miR-124a overexpression in BMSCs, and such a phenomenon was accompanied by the improvement of renal fibrosis and mitigation of DN-related kidney impairment. Regulation of fibronectin, collagen1, and EMT-related proteins was closely implicated with the mechanism, and the activation of cav-1 and ß-catenin was also possibly involved. CONCLUSION: The study demonstrated the pivotal effect of miR-124a on BMSC therapy for DN rats via mitigating EMT and fibrosis. Our results provide a novel insight into how therapeutic effects of BMSCs can be improved at the posttranscriptional level.

Silence of IGFBP7 suppresses apoptosis and epithelial mesenchymal transformation of high glucose induced-podocytes.

Insulin-like growth factor-binding protein 7 (IGFBP7) has been identified as a secreted protein associated with a number of cellular processes. However, the specific regulatory mechanisms of IGFBP7 on podocytes of diabetic nephropathy (DN) are yet to be elucidated. In the present study, podocytes were identified initially via an immunofluorescence assay using an anti-synaptopodin antibody. It was subsequently demonstrated that glucose promoted podocyte proliferation in a time- and dose-dependent manner via MTT assay. In addition, IGFBP7 expression was silenced in podocytes via siRNA, the effects of which were evaluated using western blotting and reverse transcription-quantitative polymerase chain reaction. It was demonstrated that silencing IGFBP7 inhibited apoptosis and epithelial mesenchymal transformation (EMT) of podocytes mediated by high glucose (HG). Transforming growth factor (TGF)-ß1/mothers against decapentaplegic homolog (Smad) signaling was associated with proliferation, apoptotic activities and EMT. Therefore, the expression levels of TGF-ß1/Smad pathway were detected, and it was observed that silencing IGFBP7 suppressed the TGF-ß1/Smad pathway in podocytes induced by HG. These findings suggested that IGFBP7 may serve as a potential therapeutic target for DN.

Mixed PEGylated surfactant modifying system decrease the accelerated blood clearance phenomenon of nanoemulsions in rats.

The accelerated blood clearance (ABC) phenomenon which is induced by repeated injection of poly (ethylene glycol) (PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is necessary to decrease this unexpected immunological response. A novel 4-arm poly (ethylene glycol-5000)4-cholesteryl methyl amide (4-arm PEG5000-CHMA) has been synthesized. The structure of 4-arm PEG5000-CHMA was confirmed by IR and 1H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate (TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000] (mPEG2000-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and mPEG2000-DSPE (CPNE). The plasma levels of TN and anti-PEG IgM antibody were determined by HPLC and ELISA, respectively. The circulation time of the CPNEs were comparable to the mPEG2000-DSPE coated nanoemulsions. Moreover, the ABC phenomenon can be decreased by CPNEs. This study designs a method to decrease the ABC phenomenon and develops a clinical promising nanoemulsion for therapeutic or imaging purpose.

Effects of complement inhibition on the ABC phenomenon in rats.

Researchers reported that intravenously injected PEGylated colloidal drug carriers lose their long-circulating characteristic and accumulated extensively in liver when they are administrated twice in the same animal with certain intervals. This phenomenon was referred to as the "accelerated blood clearance (ABC) phenomenon". Some former studies had found that complement-mediated phagocytosis, activated by antigen-antibody complex, was responsible for inducing the phenomenon. According to the theory, we have used cobra venom factor to deplete complement in vivo and to investigate the effect of complement inhibition on the ABC phenomenon. Rats were administered by injection of cobra venom factor solution to build up the model of complement exhaustion/inhibition, and the effect of the inhibition of complement on ABC phenomenon was carried out. It seemed that inhibition of complement didn't affect the pharmacokinetic of the first infection. By contrast, in rats of which complement had been depleted, the second dose of PEGylated nanoemulsions showed enhanced circulation time compared with normal rats in a complement inhibition-independent manner, but the ABC phenomenon was not completely eliminated. It indicated that complement inhibition could certainly weaken the accelerated clearance; meanwhile, there were other factors causing the ABC effect. These findings provide novel insights into the attenuating of ABC phenomenon and lay foundation for further study of immune mechanism.

Are PEGylated liposomes better than conventional liposomes? A special case for vincristine.

Cancer poses a significant threat to human health worldwide, and many therapies have been used for its palliative and curative treatments. Vincristine has been extensively used in chemotherapy. However, there are two major challenges concerning its applications in various tumors: (1) Vincristine's antitumor mechanism is cell-cycle-specific, and the duration of its exposure to tumor cells can significantly affect its antitumor activity and (2) Vincristine is widely bio-distributed and can be rapidly eliminated. One solution to these challenges is the encapsulation of vincristine into liposomes. Vincristine can be loaded into conventional liposomes, but it quickly leak out owing to its high membrane permeability. Numerous approaches have been attempted to overcome this problem. Vincristine has been loaded into PEGylated liposomes to prolong circulation time and improve tumor accumulation. These liposomes indeed prolong circulation time, but the payout characteristic of vincristine is severer, resulting in a compromised outcome rather than a better efficacy compared to conventional sphingomyelin (SM)/cholesterol (Chol) liposomes. In 2012, the USA Food and Drug Administration (FDA) approved SM/Chol liposomal vincristine (Marqibo®) for commercial use. In this review, we mainly focus on the drug's rapid leakage problem and the potentially relevant solutions that can be applied during the development of liposomal vincristine and the reason for conventional liposomal vincristine rather than PEGylated liposomes has access to the market.

The anticancer efficacy of pixantrone-loaded liposomes decorated with sialic acid-octadecylamine conjugate.

Based on the knowledge that sialic acid is a critical element for tumor development and its receptors are highly expressed on the tumor-associated macrophages (TAMs) which play important roles in the growth and metastasis of tumors, we synthesized a sialic acid-octadecylamine conjugate (SA-ODA) and anchored it on the surface of pixantrone (Pix)-loaded liposomes, to achieve an improved anticancer effect. Four Pix formulations (Pix-S, Pix-CL, Pix-PL and Pix-SAL represent solution, conventional liposome, stealth liposome, and SA-ODA modified liposome, respectively) were developed, and various parameters, including drug loading, stability, in vitro release, cytotoxicity and pharmacokinetics, were evaluated. The tumor growth inhibition and toxicity studies were performed in S180-bearing Kunming mice. Pix-S exhibited a strong toxicity to the immune system, accelerated the growth of tumors and reduced the lifespan of mice. In contrast, Pix-SAL displayed the strongest anticancer and life-prolonging effects among all of the formulations in this study. More importantly, injection of Pix-SAL induced a phenomenon whereby the cancerous tissues were "shed" from mice, after which the wound healed. We speculate that this special efficacy may be partly due to the killing of TAMs by Pix-SAL. This study suggests that SA-ODA modified liposomes may serve as an effective intravenous delivery vehicle for Pix.

Stability analysis of impulsive control systems with finite and infinite delays.

This paper studies impulsive control systems with finite and infinite delays. Several stability criteria are established by employing the largest and smallest eigenvalue of matrix. Our sufficient conditions are less restrictive than the ones in the earlier literature. Moreover, it is shown that by using impulsive control, the delay systems can be stabilized even if it contains no stable matrix. Finally, some numerical examples are discussed to illustrate the theoretical results.

Retrospective analysis of 56 patients with advanced gastric cancer treated with combination of intravenous and intra-arterial intensified neoadjuvant chemotherapy.

BACKGROUND: Pre-operative chemotherapy has gained widespread interest while treating advanced gastric cancer in eastern countries. However, there is currently no established standard regimen for gastric cancer. The aim of this research was to explore the value of preoperative chemotherapy with a combination of intravenous and intra-arterial intensified chemotherapy in advanced gastric cancer. METHODS: A total of 56 histologically proven gastric cancer patients, who were considered to be stage II or higher with metastatic lymph nodes and with or without distant metastasis (T2-4, N1-3, and M0-1), were treated with a neoadjuvant chemotherapy. Patients received a combination of intravenous 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) on days 1-5, and intra-arterial etoposide (80 mg/m2) and cisplatin (80 mg/m2) on days 6 and 20. After two cycles of preoperative chemotherapy, patients with resectable tumors underwent laparotomy. RESULTS: All patients finished two cycles of chemotherapy. The overall response rate was 78.57% (44 cases), of which 7.14% (four cases) clinical complete response. Forty-six patients underwent resection, including 21 initially unresectable diseases. R0 resection rate for prechemotherapy resectable and unresectable diseases was 96.15% (25/26 cases) and 66.67% (20/30 cases), respectively. Pathological complete response was observed in 8.70% of patients. Toxicity was moderate and there were no chemotherapy-related deaths. With a median follow-up of 31 months (range 6-76 months), the 5-year survival rate for the whole group and patients with initially resectable tumors were 21.8% and 42.3%, respectively. The median survival for initially resectable and unresectable patients were 41 months (95%CI, 31.006-50.994) and 18 months (95%CI, 13.399-22.601; P<0.01), respectively. CONCLUSION: Preliminary results proved that the combined intensive chemotherapy was a safe and promising regimen for pre-operative treatment of advanced gastric cancer.