Search

In recent years, unilateral biportal endoscopic spinal surgery has been used for the treatment of lumbar spinal stenosis with good results. Some investigators counted the total incidence of complications in unilateral biportal endoscopic surgery for lumbar spinal stenosis, but none have analyzed the incidence of specific complications. The present study further counted the incidence of specific complications and gave the possible causes of the complications.English databases including PubMed were searched to collect relevant literature on unilateral biportal endoscopic spinal surgery for lumbar spinal stenosis. The inquiry period is from January 1, 2015, to July 1, 2022. The literature was screened, information extracted, and risk of bias evaluated by the researchers, followed by Meta analysis using R4.2.1 and RStudio statistical software.In total, we included 14 studies involving 707 patients. The included studies were retrospective case series, The results of the single-arm rate meta-analysis showed that the total complication rate of unilateral biportal endoscopic surgery treatment of lumbar spinal stenosis was 8.1% (95% confidence interval [CI] [0.060; 0.103]); of which, the highest incidence of dural tear was 4.5% (95% CI [0.030; 0.064]), the incidence of symptomatic postoperative spinal epidural hematoma was approximately 1.1% (95% CI [0.001; 0.027]), the incidence of incomplete decompression was 2.0% (95% CI [0.007; 0.038]), the incidence of transient palsy was 2.6% (95% CI [0.005; 0.057]).The incidence of total complications of unilateral biportal endoscopic surgery for lumbar spinal stenosis was 8.1%, dural tear remained a major complication with an incidence of 4.5%, incomplete decompression was 2.0%, transient palsy was 2.6%, and, unexpectedly, symptomatic postoperative spinal epidural hematoma was only 1.1%.

PDF file - 31K

PDF file - 46K

PDF file - 255K

PDF file - 53K

OCTN2 is a bifunctional transporter that reabsorbs filtered carnitine in a sodium-dependent manner and secretes organic cations into urine as a proton antiport mechanism. We hypothesized that inhibition of OCTN2 by anticancer drugs can influence carnitine resorption. OCTN2-mediated transport inhibition by anticancer drugs was assessed using cells transfected with human OCTN2 (hOCTN2) or mouse Octn2 (mOctn2). Excretion of carnitine and acetylcarnitine was measured in urine collected from mice and pediatric patients with cancer before and after administration of etoposide. Five of 27 tested drugs (50–100 μmol/L) inhibited hOCTN2-mediated carnitine uptake by 42% to 85% (P < 0.001). Of these inhibitors, etoposide was itself a transported substrate of hOCTN2 and mOctn2. Etoposide uptake by hOCTN2 was reversed in the presence of excess carnitine. This competitive inhibitory mechanism was confirmed in an in silico molecular docking analysis. In addition, etoposide inhibited the transcellular apical-to-basolateral flux of carnitine in kidney cells. Etoposide was also associated with a significant urinary loss of carnitine in mice (∼1.5-fold) and in patients with cancer (∼2.4-fold). Collectively, these findings indicate that etoposide can inhibit hOCTN2 function, potentially disturb carnitine homeostasis, and that this phenomenon can contribute to treatment-related toxicities. Mol Cancer Ther; 11(4); 921–9. ©2012 AACR.

PDF file - 107K

PDF file - 172K

Purpose: To compare side-by-side the uptake of sorafenib and sunitinib in vitro by human uptake solute carriers of the SLC22A and SLCO families, the transport by and inhibition of efflux ATP-binding cassette (ABC) transporters, and the role of ABCB1 in the plasma pharmacokinetics and brain penetration of these agents.Experimental Design: Uptake of [3H]sorafenib or [3H]sunitinib was assessed in Xenopus laevis oocytes or mammalian cells transfected with cDNAs coding for human OATP1A2, OATP1B1, OATP1B3, OCT1, OAT2, OAT3, OCTN1, or OCTN2. Efflux and inhibition experiments were conducted in cells transfected with human ABCB1, ABCG2, ABCC2, or ABCC4. In vivo pharmacokinetic studies were done in knockout mice lacking Abcb1-type transporters.Results: Intracellular uptake was not appreciably affected by any of the studied solute carriers and was minute relative to the respective prototypical substrates. Sorafenib and sunitinib showed concentration-dependent (1 and 10 μmol/L), low to moderate affinity for ABCB1 but were not affected by the other ABC transporters. Both agents inhibited all tested ABC transporters. The absence of Abcb1 had no affect on plasma pharmacokinetics, but brain penetration was moderately increased by 1.9- and 2.9-fold for sorafenib and sunitinib, respectively, in knockout animals versus controls.Conclusions: Unlike other tyrosine kinase inhibitors, sorafenib and sunitinib do not appear to rely on active transport to enter the cell nor are they high-affinity substrates for ABC efflux transporters. Based on these characteristics, these two drugs may be less susceptible to transporter-mediated alterations in systemic exposure and transporter-related resistance mechanisms. (Clin Cancer Res 2009;15(19):6062–9)

Supplementary Data from Interaction of the Multikinase Inhibitors Sorafenib and Sunitinib with Solute Carriers and ATP-Binding Cassette Transporters

Biofilms are multicellular communities with a spatial structure. Different from single-cell scale diffusion in planktonic systems, the diffusion distance becomes the dimension of multicellular clusters in a biofilm. Such differences in diffusion behavior affect the tolerance and response to exogenous stress. Here, we found that at the same doses of exogenous hydrogen peroxide (H 2 O 2 ), planktonic Escherichia coli were completely killed within two hours, whereas the biofilm resumed growth in six hours by building a catalase barrier to block H 2 O 2 penetration, despite the growth burden. Unexpectedly, when we changed the carbon source from glucose to glycerol, H 2 O 2 instantly counterintuitively boosted biofilm growth due to supplemental oxygen, which was the growth-limiting factor. We further demonstrated that the energy metabolism modes determined the growth-limiting factor, which then determined the two patterns of biofilms resistances to H 2 O 2 .

Sepsis is an acute life-threatening disorder associated with multiorgan dysfunction that remains the leading cause of death in intensive care units. As sepsis progresses, it causes prolonged immunosuppression, which results in sustained mortality, morbidity, and susceptibility to secondary infections. Using a mouse model of sepsis, we found that the long noncoding RNA HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1) was highly expressed in mice during the late phase of sepsis. The upregulation of HOTAIRM1 was induced by Notch/Hes1 activation and, moreover, was critical for the formation of an immunosuppressive microenvironment. HOTAIRM1 induced T cell exhaustion by increasing the percentage of PD-1+ T cells and regulatory T cells, accompanied by elevated PD-L1. Blockade of either Notch/Hes1 signaling or HOTAIRM1 inhibited T cell exhaustion in late sepsis, having alleviated lung injury and improved survival of mice. Further mechanistic studies identified HOXA1 as a key transcription factor targeted by HOTAIRM1 to regulate PD-L1 expression in lung alveolar epithelial cells. These results implicated that the Notch/Hes1/HOTAIRM1/HOXA1/PD-L1 axis was critical for sepsis-induced immunosuppression and could be a potential target for sepsis therapies.

Abstract: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction caused by sepsis that manifests as a range of brain dysfunctions from delirium to coma. It is a relatively common complication of sepsis associated with poor patient prognosis and mortality. The pathogenesis of SAE involves neuroinflammatory responses, neurotransmitter dysfunction, blood-brain barrier (BBB) disruption, abnormal blood flow regulation, etc. Neuroinflammation caused by hyperactivation of microglia is considered to be a key factor in disease development, which can cause a series of chain reactions, including BBB disruption and oxidative stress. Metabolic reprogramming has been found to play a central role in microglial activation and executive functions. In this review, we describe the pivotal role of energy metabolism in microglial activation and functional execution and demonstrate that the regulation of microglial metabolic reprogramming might be crucial in the development of clinical therapeutics for neuroinflammatory diseases like SAE.

Background: Several studies have shown that HEIH is overexpressed in a variety of cancers and plays a role as an oncogene in cancer. The present meta-analysis aims to elucidate the relationship between HEIH expression and prognosis and clinicopathological features among cancer patients.Materials and methods: PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI) were employed to assess the relationship between HEIH expression and clinical outcomes and clinicopathological features in cancer patients.Results: The present study finally enrolled 11 studies which included 1227 cancer patients. The combined results indicated that HEIH overexpression was significantly associated with shorter overall survival (OS) (pooled HR=2.03, 95% CI 1.74–2.38, P < 0.00001).Meanwhile, regarding clinicopathology of cancer patients, upregulated HEIH expression was closely related to larger tumor size (OR = 2.65, 95% CI: 1.52–4.65, P = 0.0006), advanced tumor T stage (OR = 2.41, 95 % CI: 1.54–3.77, P = 0.0001), advanced TNM stage (OR = 4.76, 95% CI: 2.73–8.29, P < 0.00001), distant metastasis (OR = 2.94, 95% CI: 1.75–4.96, P < 0.0001) and lymph node metastasis (OR = 2.07, 95% CI: 1.05–4.07, P = 0.04), respectively.Conclusions: High expression of HEIH in some cancers predicts shorter overall survival and higher clinical stage as well as larger tumor size. HEIH has great potential to become a prognostic marker for cancer patients.

Background: Epileptogenesis was the latency period of epilepsy. Neuronal damage and subsequent inflammatory response were the basic mechanisms of epileptogenesis. From now on, there was still no effective drugs to prevent the process of epileptogenesis. Yingqiao San, a famous classic prescription over 400 years in China, was widely used in sorts of infectious disease. In preclinical study of childhood epilepsy complicated with upper respiratory tract infections, we found that YQS can not only reduce the frequency of respiratory tract infections, but also decrease the frequency and duration time of seizures, and can alleviate sterile inflammation to some extent. HMGB1, an important late mediator in sterile inflammation, has been seem as a potential target of epileptogenesis. So we hypothesized that YQS had effect of antiepileptogenic, may be related to inhibit the translocation of HMGB1 and modulate neuroinflammation.Methods: The pilocarpine-induced status epileptic model was adopted to induce brain injury model in mice. Observation and sampling were performed at 7 days, 14 days and 28 days. The number of seizures, duration time of seizures, mortality rate and the appearance of brain were employed to determine the anti-seizure effects of YQS. The Nissl staining, FJB staining were employed to determine the neuroprotective of YQS. The double immunofluorescent staining were employed to observe inflammatory response and the location of HMGB1 in glia cells. The Western blot and immnuohistochemical staining were used to calculate the quantitative and qualitative of HMGB1 to detect the translocation of HMGB1 and the expression of HMGB1/TLR4 signaling pathway. Results: It was found that YQS can effectively decrease the frequency of seizures, shorten duration time of seizures, reduce the mortality of mice and alleviate brain edema. YQS can significantly attenuate neuronal damage and inhibit the activation and proliferation of microglia and astrocytes with time-dependent. Moreover, YQS can modulate the subsequent inflammatory response by inhibiting HMGB1 translocation and regulating the expression of HMGB1/TLR4 signaling pathway.Conclusions: YQS can prevent the process of epileptogensis. Its neuroprotective and anti-inflammatory effects on epileptogenesis may mediate by inhibiting HMGB1 translocation and modulating neuroinflammation. It can still be used as an adjunctive therapy for treatment of epilepsy.

Emerging evidence suggests that pyroptosis is involved in sepsis. However, the role of neutrophil pyroptosis in sepsis and the mechanisms remains elusive. We find that N-acetyltransferase 10 (NAT10), an acetyltransferase responsible for the N4-acetylation of Cytidine (ac4C) in mRNA, is significantly downregulated in neutrophils from septic mice. Neutrophil-specific over-expression of NAT10 improves the survival and ameliorates lung injury in septic mice by inhibiting neutrophil pyroptosis. Notably, UNC-52-like kinase 1 (ULK1) is identified as the target of NAT10 in neutrophils. The decreased expression of NAT10 resultes in the decay of ULK1 transcripts and therefore the reduced expression of ULK1. As a regulator of STING phosphorylation, the loss of ULK1 enhances the activation of STING-IRF3 signaling and subsequently the elevated pyroptosis-inducing NLRP3 inflammasome in neutrophils. While over-expression of NAT10 restrains pyroptosis in neutrophils as well as septic lethality in mice by reversing the ULK1-STING-NLRP3 axis. The decreased expression of NAT10 are also observed in sepsis patients and its correlation with clinical severity is found. Collectively, our findings disclose that NAT10 is a negative regulator of neutrophil pyroptosis and its downregulation contributes to the progress of sepsis by exacerbating pyroptosis via the ULK1-STING-NLRP3 axis, therefore revealing a potential therapeutic target for sepsis.

Several studies showed that LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) is overexpressed in a variety of cancers and plays a role as an oncogene in cancer. The present meta-analysis aims to elucidate the relationship between LOXL1-AS1 expression and prognosis and clinicopathological features among cancer patients.PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. Pooled odds ratios (ORs) and hazard ratios with a 95% confidence interval (CI) were employed to assess the relationship between LOXL1-AS1 expression and clinical outcomes and clinicopathological features in cancer patients.The present study finally enrolled 8 studies which included 657 cancer patients. The combined results indicated that the overexpression of LOXL1-AS1 was significantly associated with shorter overall survival (pooled hazard ratio = 1.99, 95% CI 1.49-2.65, P .00001). Meanwhile, regarding clinicopathology of cancer patients, the upregulation of LOXL1-AS1 expression was closely related to lymph node metastasis (yes vs no OR = 4.01, 95% CI: 2.02-7.96, P .0001) and distant metastasis (yes vs no OR = 3.04, 95% CI: 1.82-5.06, P .0001), respectively.High expression of LOXL1-AS1 in some cancers predicts shorter overall survival, distant metastasis, and lymph node metastasis. LOXL1-AS1 shows great promise as a prognostic biomarker in cancer patients.