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Sevoflurane (SEV) has been reported to be an effective neuroprotective agent for cerebral ischemia/reperfusion injury (CIRI). However, the precise molecular mechanisms of Sev preconditioning in CIRI remain largely unknown. Therefore, CIRI model was established via middle cerebral artery occlusion method. SEV was applied before modeling. after successful modeling, lentivirus was injected into the lateral ventricle of the brain. Neurological impairment score was performed in each group, and histopathologic condition, infarct volume, apoptosis, inflammation, oxidative stress, microRNA (miR)-30 c-5p and homeodomain-interacting protein kinase 1 (HIPK1) were detected. Mouse hippocampal neuronal cell line HT22 cells were pretreated with SEV, and the in vitro model was stimulated via oxygen-glucose deprivation and reoxygenation. The corresponding plasmids were transfected, and the cell growth was detected, including inflammation and oxidative stress, etc. The targeting of miR-30 c-5p with HIPK1 was examined. The results clarified that reduced miR-30 c-5p and elevated HIPK1 were manifested in CIRI. SEV could improve CIRI and modulate the miR-30 c-5p-HIPK1 axis in vitro and in vivo, and miR-30 c-5p could target HIPK1. Depressed miR-30 c-5p could eliminate the protection of SEV in vitro and in vivo. Repression of HIPK1 reversed the effect of reduced miR-30 c-5p on CIRI. Therefore, it is concluded that SEV is available to depress CIRI via targeting HIPK1 through upregulated miR-30 c-5p.

BACKGROUND The Picosecond Nd:YAG laser has advantages in skin rejuvenation, which has little damage to surrounding tissues due to the ultra-short pulse width. We perform clinical application of Picosecond Nd:YAG laser's tender skin mode, which could improve the seborrheic dermatitis. MATERIALS AND METHODS Sixty-three subjects with facial seborrheic dermatitis are randomized to be control and observation groups. Records regarding skin subjective improvement, skin barrier function-related data, skin microbial status, and dermoscopy detection of the two patient groups before and after treatments are investigated. RESULTS Improvements of erythema and scales in observation group are significant compared with controls (p

Yan Qu,1 Xien Feng,2 Jin’ning Liang,2 Junru Liu,3 Dong Gao2 1Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, 264003, Shandong, People’s Republic of China; 3Department of Dermatology, Yantai Yuhuangding Hospital Laishan Branch, Yantai, 264003, Shandong, People’s Republic of ChinaCorrespondence: Dong Gao Email gaodong_yhd@163.comObjective: We aimed to investigate picosecond laser effects regarding rat tattoo removals. We systematically detected the metabolic pathways considering tattoo pigment particles in rat models.Materials and Methods: We employed fluorescein to mark the tattoo dye and utilized a pattern needle to prepare tattoo on rat so as to establish the tattoo removal effects of picosecond laser methods employing animal models. We applied a picosecond laser to process the tattoo and observed the effects along with metabolic pathways for tattoo removal via pathology and imaging approaches.Results: Based on the results of characterization, pathology and fluorescence, we discovered that the picosecond laser could effectively remove the pigment particles on rat skin, part of which would be metabolized out of the body through the circulatory system. After picosecond laser treatment, the fluorescence intensity of the rat skin engraved part was gradually weakened. At 8 h after the treatment, the metabolic organs had weak fluorescence, and there was no fluorescence in the metabolic organs at 12 h and 24 h after the treatment.Conclusion: The picosecond laser had perfect tattoo removal effects, which could be utilized as a reference for clinical tattoo removal.Keywords: tattoo, picosecond laser, pattern engraving, dye

Accumulating evidence has demonstrated the vital roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). In this study, we aimed to explore the effect of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) on ALI development. The ALI mice and cell models were constructed using lipopolysaccharide (LPS)-induced method. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, NEAT1, miR-182-5p, and WNT-inducible secreted protein 1 (WISP1) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. The level of lactate dehydrogenase (LDH) and the activity of caspase-3 were measured by specific kits. The interaction between miR-182-5p and NEAT1 or WISP1 was investigated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Protein levels were measured by Western blot assay. NEAT1 level was elevated in LPS-induced ALI mice and LPS-stimulated MH-S cells. LPS treatment repressed MH-S cell viability and promoted apoptosis and inflammation, while NEAT1 silencing restored the impacts. For mechanism analysis, NEAT1 was identified as the sponge for miR-182-5p to positively regulate WISP1 expression. Moreover, NEAT1 knockdown could accelerate cell viability and inhibit cell apoptosis and inflammation in LPS-induced MH-S cells by elevating miR-182-5p and decreasing WISP1 in LPS-exposed MH-S cells. In addition, NEAT1 deficiency blocked the activation of NF-κB pathway caused by LPS in MH-S cells. NEAT1 overexpression restrained cell viability and facilitated cell apoptosis and inflammation in LPS-exposed MH-S cells through miR-182-5p/WISP1 axis.

Objective The aim of this study was to establish a preoperative prediction method for sparsely granulated (SG) growth hormone (GH) secreting pituitary adenoma, an aggressive tumor subtype with high recurrence risk, in acromegaly patients. Methods Eighty-three patients with GH-secreting pituitary adenomas were included in this study. GH measurements, cytokeratin immunostaining and electron microscopy were performed to detect granulation patterns. Preoperative factors, including general, radiological and endocrinological features and acute octreotide suppression test outcomes, were compared between SG and densely granulated (DG) groups. The predictive capabilities of these features were analyzed using a receiver operating characteristic (ROC) curve, and the most predictive features were combined to establish a grading scale. Results Thirty-nine of the 83 patients had SG GH-secreting pituitary adenomas; 44 had DG tumors. SG tumors tended to occur in younger patients and have larger diameters and volumes, higher Knosp grades, lower GH indexes and normalized insulin-like growth factor-1 (IGF-1) levels, and a lower ∆GH% after octreotide treatment. The tumor size, Knosp grade, GH index and ∆GH% after octreotide treatment had good predictive performance, with area under the curve (AUC) values ranging from 0.70 to 0.80. Combining four parameters, including diameter, Knosp grade, GH index and ∆GH% after octreotide treatment, we established a grading scale for predicting SG GH-secreting pituitary adenomas with an AUC of 0.84 and relatively high sensitivity and specificity. Conclusions We propose a predictive method for distinguishing SG and DG GH-secreting pituitary adenomas preoperatively. This method will help physicians identify candidates for presurgical medical treatment and neurosurgeons determine radical surgical strategies for high-risk tumors.

Objective: The primary purpose of this study was to explore the safety of peripheral intravenous catheter (PIVC) replacement every 96 h compared to that of clinically indicated catheter removal. Methods: A prospective, single-blind, randomized controlled trial was conducted. A random number table method was used. Six hundred patients treated with PIVC intravenous infusion in 10 nursing units of a hospital from September to October 2019 were selected. Sixty were collected from each nursing unit, including 30 in the clinically indicated replacement group and 30 in the routine replacement group. The incidence of phlebitis, catheter-related infection (CRI), occlusion, infiltration, and any form of infusion therapy failure were compared between the two groups. SPSS 23.0 software was used. Results: The dwelling times of PIVC in the clinically indicated replacement group and routine replacement group were significantly different (hours) (83.62 ± 50.08, 69.75 ± 25.54, t = 3.021, p = 0.003). The incidence of any form of infusion therapy failure (RR = 4.448, 95% CI: 3.158–6.265, p Conclusion: Replacement of PIVC every 96 h is safer than clinically indicated.

BACKGROUND Melasma is an acquired refractory pigmentary disorder, which is a skin disease that predominantly affects females. This investigation aims to assess the efficacy of a low-power fractional CO2 laser combined with tranexamic acid (TXA) for melasma topical treatment with MASI and dermoscopy. MATERIALS AND METHODS A randomized comparative split-face study was performed. Each treatment interval was 3 weeks with four times in total. At the same time, we applied TXA solution twice a day. Assessments were made by the MASI score of the melasma area severity index, and the dermoscopy performance was collected and analyzed. RESULTS After treatments, the patient MASI score decreased significantly. Compared with the baseline, the MASI score was significantly lower than that of control group (P

MicroRNAs (miRNAs) modulate a variety of cellular signaling pathways and play a vital role in cell-to-cell communication. The overlapped expression of a certain miRNA is commonly reported to be related to cancers. Therefore, combined detection of multiple miRNAs is of great significance for cancer diagnosis. Herein, we developed a FeII 4L4 tetrahedron-assisted three-way junction (3WJ) probe, which exhibited a higher stability than the normal 3WJ probe, for multiple miRNA detection. In this method, the simultaneous existence of miRNA-21 and miRNA-144 triggers the release of the Y3 sequence in the FeII 4L4 tetrahedron-assisted 3WJ probe, which in turn triggers subsequent CRISPR-Cas12a-assisted rolling circle amplification. Based on this, simultaneous detection of miRNA-21 and miRNA-144 was achieved. Furthermore, we also applied this method to the detection of miRNAs in clinical samples and achieved good agreement with quantitative real-time polymerase chain reaction (qRT-PCR), indicating its significant potentials in early diagnosis and treatment of cancer.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00601-8) contains supplementary material, which is available to authorized users.

Background The WD40 protein family member WD repeat domain 5 (WDR5) plays significant roles in the tumorigenesis and development of multiple organ tumours. However, the correlation between WDR5 expression and oesophageal squamous cell carcinoma (ESCC) has not been elucidated. Methods WDR5 mRNA expression data were acquired from The Cancer Genome Atlas (TCGA) database, and the expression and prognostic potential of WDR5 were assessed by immunohistochemistry (IHC) and Western blot. The cell counting kit-8 (CCK-8), colony formation assay and cell cycle evaluation were performed to verify the WDR5 function in vitro. The xenograft model was used to verify WDR5 function in vivo. Results The mRNA and protein expression levels of WDR5 were significantly upregulated in ESCC tissues compared with expression in adjacent normal tissues. Kaplan-Meier analysis showed that high WDR5 expression in ESCC patients was associated with poor overall survival (P=0.004). Multivariate analysis revealed that WDR5 overexpression emerged as an independent predictor of poor overall survival (P=0.013) in ESCC. The in vitro and in vivo experiments revealed that downregulation of WDR5 expression blocked cell proliferation of ESCC. Mechanistically, we found that WDR5 may influence ESCC proliferation by targeting the PI3K/AKT/mTOR signalling pathway. Conclusion Our data demonstrate that overexpression of WDR5 was associated with poor prognosis in patients with ESCC and that WDR5 may act as a potential novel prognostic biomarker for ESCC.

Background Dioxygenase 12-lipoxygenase (12-LOX) plays an important role in tumorigenesis and promotes angiogenesis and proliferation in several tumors, including prostate and breast tumors. Radiotherapy enhances the expression of 12-LOX in esophageal squamous cell carcinoma (ESCC). Two types of macrophages can be found in the tumor microenvironment. The M2 subtype accelerates tumor progression; however, the relationship between 12-LOX and macrophages is not well established. Here, we explore this interaction and its effect on ESCC to induce tumor progression. Methods and Results RT-qPCR and Western blot analyses were used to evaluate the mRNA and protein expression levels of 12-LOX and chemokine (C-C motif) ligand 5 (CCL5) in ESCC after radiotherapy. CCL5 expression was increased by 12-LOX upregulation but was suppressed by the well-established 12-LOX inhibitor, baicalein. Furthermore, CCL5 attracted and repolarized human myeloid leukemia mononuclear cells (THP-1)-derived macrophages. Finally, ESCC co-culture with THP-1-derived macrophages led to a strong cancer migratory capacity. Conclusion Radiation-induced 12-LOX overexpression in ESCC upregulates CCL5 expression, thereby attracting THP-1-derived macrophages and promoting their polarization to the M2 subtype, which enhances cellular metastasis.

Recently, minimally invasive techniques, including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, have been used for the treatment of patients with spontaneous cerebellar hemorrhage (SCH). However, credible evidence is still needed to validate the effects of these techniques. To explore the long-term outcomes of both surgical techniques in the treatment of SCH. Fifty-two patients with SCH who received endoscopic evacuation or MIC evacuation were retrospectively reviewed. Six-month mortality and the modified Rankin Scale (mRS) score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of the different surgical techniques on patient outcomes. In the present study, the mortality rate for the entire cohort was 34.6%. Univariate analysis showed that the surgical technique and preoperative Glasgow Coma Scale (GCS) score affected 6-month mortality. However, no variables were found to be correlated with 6-month mRS scores. Further multivariate analysis demonstrated that 6-month mortality in the endoscopic evacuation group was significantly lower than that in the MIC evacuation group (OR = 4.346, 95% CI 1.056 to 17.886). The 6-month mortality rate in the preoperative GCS 9–14 group was significantly lower than that in the GCS 3–8 group (OR = 7.328, 95% CI 1.723 to 31.170). Compared with MIC evacuation, endoscopic evacuation significantly decreased 6-month mortality in SCH patients. These preliminary results warrant further large, prospective, randomized studies.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury. Electronic supplementary material The online version of this article (10.1007/s12264-020-00505-7) contains supplementary material, which is available to authorized users.

Wilms tumor (WT) is the most common solid childhood tumors all over the world. MicroRNAs (miRs) contribute to tumorigenesis of various cancers through targeting gene. The present study investigated the vital role of miR‐194‐5p and its underlying mechanism in the progression of WT. Immunohistochemistry and quantitative real‐time polymerase chain reaction (qRT‐PCR) assay indicated downregulation of miR194‐5p and upregulation of Crk, in WT tissues compared to adjacent normal tissues. Transfection with miR‐194‐5p mimics into nephroblastoma cells showed a significant decline in cell migration and invasion, which was detected by Transwell assay. Luciferase assay confirmed that Crk was a direct target gene of miR‐194‐5p. More important, the mesenchymal to epithelial transition (EMT) biomarkers containing E‐cadherin, N‐cadherin and Zeb1 were examined by Western blot, and revealed that miR‐194‐5p mimics decreased the levels of N‐cadherin and Zeb1 but increased E‐cadherin, which suggested that miR‐194‐5p inhibited EMT. Crk knockdown could reverse the increased nephroblastoma cell invasion, migration and EMT caused by miR‐194‐5p inhibitor. Interestingly, qRT‐PCR and Western blot analysis showed that overexpression of miR‐194‐5p deactivated HGF/c‐Met/Scr signaling pathway via targeting Crk. In conclusion, miR‐194‐5p inhibited nephroblastoma cell metastasis and EMT in the progression of WT by targeting Crk. Thus, miR‐194‐5p might be a potential target in WT particularly for the prevention of metastasis and EMT.

Background The epigenetic alteration has an impact on cancer cell cycle regulation. Expression of histone deacetylase 8 (HDAC8) ruled out the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and this is linked with the prognosis of Esophageal cancer (EC) patients. Methods By the immunohistochemical staining, we examined the expression status of HDAC8 and CDKN2A protein of 110 esophageal squamous cell carcinoma (ESCC) patients in the tissue microarray. The nuclear staining intensity was counted by immunoreactivity scoring ranging from 0 to 12 and grouped them into two; weak or non-expression and over-expression. Results The median follow-up duration of our study was 71 months postoperatively. Up-regulation of HDAC8 expression and down-regulation of CDKN2A (p16) indicate decreased 5-year overall survival (OS) (P=0.003) and (P=0.001) respectively and progression-free survival (PFS) (P=0.005, P=0.001) respectively, which are statistically significant and determined by Kaplan-Meier estimates using log-rank test. Consequently, HDAC8 and CDKN2A act as an independent prognostic biomarker, for OS and PFS that analyzed by multivariate cox-regression analysis, HR 1.173 with 95% CI: 0.215–6.416 and P=0.003 and HR 1.217 with 95% CI: 0.224–6.600 and P=0.005 respectively. Spearman rank test establish the negative correlation between HDAC8 and CDKN2A. Conclusions Over-expression of HDAC8 and weak or no expression of CDKN2A have a worse impact on EC patients and indicate poor survival and progression of the disease and act as a promising prognostic parameter.

We sought to assess whether controlled, intraoperative lumbar drainage (LD) of cerebrospinal fluid (CSF) could facilitate resection of pituitary macroadenomas and reduce the rate of CSF leak.A retrospective cohort study from a prospective database was conducted on 189 patients with pituitary macroadenoma who received endoscopic transsphenoidal surgery between 2013 and 2017. Patients were classified into 2 groups: 119 patients received an intraoperative LD (LD group) and 70 patients underwent routine endoscopic surgery without LD (control group). In the LD group, lumbar catheters were placed preoperatively and CSF was drained intermittently during tumor resection. The rates of gross total resection (GTR) and CSF leaks were assessed both intraoperatively and postoperatively.Intraoperative LD was associated with a higher rate of GTR (92.4% in the LD group vs. 78.6% in the control group, P = 0.006), especially in macroadenomas with suprasellar extension (90.3% vs. 75.0%, P = 0.012). Both intraoperative and postoperative CSF leak rates were significantly decreased in the LD group (intraoperative: 10.1% vs. 31.4%, P0.001; postoperative: 3.4% vs. 11.4%, P = 0.035). In functioning adenomas, a better remission rate of excess-hormone secretion was observed in the LD group compared with the controls (89.1% vs. 60.6%, P = 0.001). Patients in the LD group also had an enhanced recovery with a shorter postoperative length of stay (7 days vs. 5 days, P = 0.020).Intraoperative LD may assist surgeons during endoscopic transsphenoidal resection of pituitary macroadenomas by achieving a higher rate of GTR and a lower rate of perioperative CSF leaks. Validation in prospective randomized controlled studies is needed.

Objective: The aim of the present study was to evaluate the effects of ethyl acetate extract of Polygonum orientale L. (POE) on ameliorating postmenopausal osteoporosis in ovariectomized (OVX) rats...

BackgroundChronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH.MethodsThe second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days.DiscussionThis multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH.Trial registrationChiCTR,ChiCTR1900021659. Registered on 3 March 2019,http://www.chictr.org.cn/showproj.aspx?proj=36157.

Treatment with immune checkpoint inhibitors (ICIs) has considerably improved prognosis in multiple cancers. However, regardless of PD-L1 expression and TMB, better predictive biomarkers are required to identify ICI-responsive patients. We analyzed a pan-cancer cohort as the discovery cohort to identify the role of Max’s giant associated protein (MGA) mutation in the outcome of ICI treatment in different types of cancers. A pooled lung adenocarcinoma (LUAD) cohort was considered as the validation cohort. Another two LUAD cohorts who received conventional treatment were included for prognostic analysis and mechanism exploration. In the discovery cohort, MGA mutation was a favorable survival biomarker for patients with LUAD than in those with other types of cancers. MGA mutation was positively correlated with the TMB score. The results of the validation cohort were consistent with those of the discovery cohort. Patients with MGA mutation in the TMB-low subgroup had longer survival. Two LUAD cohorts who received standard treatment showed that the MGA mutation was not a prognostic biomarker for standard treatment. Mechanically, we found that the co-mutant genes did not affect the prognostic role of MGA mutation. Gene-set enrichment analysis revealed that genes belonging to the immunodeficiency pathway were enriched in the MGA wild-type group in LUAD. Moreover, activated NK cells were more enriched in the MGA mutant LUAD group. In conclusion, our results demonstrated that MGA mutation was an independent predictive biomarker for ICI therapy. These results may provide a novel insight into identifying potential patients with LUAD for ICI therapy.

Aim Helix B-Surface peptide (HBSP) is the latest discovered erythropoietin (EPO) analogue that can retain the activity of EPO. EPO, which is widely used for treating renal anemia, has recently been proved to have protective effects on ischemia-reperfusion injury of brain, heart and kidney. The protective effects of EPO and HBSP on cardiac function were found in rats with myocardial ischemia. However, the effect of HBSP on sepsis-induced renal injury is still unclear. Methods Establishment of rat kidney injury model and treated with HBSP and lipoposaccharide. Renal injury in rats was observed by hematoxylin-eosin staining and injury index score. Levels of serum creatinine (SCr), blood urea nitrogen (BUN) and Cystatin C (Cys C) were detected using fully automatic biochemical analyzer, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β were detected by enzyme-linked immunosorbent assay. Western blot analysis was performed to determine the role of HBSP in phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Results Acute kidney injury (AKI) appeared after modeling, however, HBSP alleviated the pathological conditions of the kidney injury. In addition, HBSP lowered kidney injury index score in the rats, and decreased the levels of SCr, BUN, Cys C, TNF-α, IL-6 and IL-1β, moreover, HBSP also showed the effect of activating PI3K/Akt pathway. Conclusion HBSP alleviated lipoposaccharide-induced AKI and improved kidney function of the rats with sepsis. More importantly, the effects of HBSP on lipoposaccharid-induced AKI were realized via activating PI3K/Akt pathway. The findings in the current study provide new insights into the therapeutic mechanism for treating the disease.

In light of the controversies regarding the surgical treatment of adult Chiari malformation type I (CM-I) with syringomyelia, a retrospective study was conducted to evaluate the safety and efficacy of tonsillectomy followed by modified reconstruction of the cisterna magna with or without craniectomy. Between 2008 and 2017, 78 adult CM-I patients (36 males and 42 females, mean age 40.6 years old) with syringomyelia were treated with posterior fossa decompression (PFD) with tonsillectomy and modified reconstruction of the cisterna magna. Patients were divided into two study groups: group A (n = 40) underwent cranioplasty with replacement of the bone flap; group B (n = 38) underwent suboccipital craniectomy. Neurological outcomes were evaluated by traditional physician assessment (improved, unchanged, and worsened) and the Chicago Chiari Outcome Scale (CCOS). Syringomyelia outcomes were assessed radiologically. The procedure was successfully performed in all patients, and restoration of normal cerebrospinal fluid (CSF) flow was confirmed by intraoperative ultrasonography. The median postoperative follow-up was 20.3 months (range 18–60 months). Clinical improvement was evident in 66 (84.6%) patients, with no significant differences between the two groups (85.0% vs. 84.2%, P = 0.897). According to the CCOS, 36 patients (90.0%) in group A were labeled as “good” outcome, compared with that of 34 (86.8%) in group B (P = 0.734). Improvement of syringomyelia was also comparable between the groups, which was observed in 35 (87.5%) vs. 33 (86.8%) patients (P = 0.887). The postoperative overall (7.5% vs. 23.7%, P = 0.048) and CSF-related (2.5% vs. 18.4%, P = 0.027) complication rates were significantly lower in group A than group B. Tonsillectomy with modified reconstruction of the cisterna magna without craniectomy seems to be a safe and effective surgical option to treat adult CM-I patients with syringomyelia, though future well-powered prospective randomized studies are warranted to validate these findings.

We reported a case of awake surgery for the left frontal low-grade glioma and reviewed the literature on the strategy of awake surgical resection for glioma. The eloquent cerebral areas that are involved in motor, language, memory, and visuospatial functions, which have to be preserved during surgery, is identified through intraoperative use of brain mapping techniques. This technique of combining intraoperative ultrasound and neuronavigation enabled extension of the surgical indications and improved the extent of resection, while minimizing postoperative morbidity and safeguarding the patient's quality of life. This work was approved by the Institutional Review Board of Tangdu Hospital, Fourth Military Medical University, China.

Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.

Objective To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). Methods RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. Results BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. Conclusion BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.

Purpose B-cell lymphoma-2 (Bcl-2) associated athanogene 1 (Bag-1) is a multifunctional protein, and Bag -1 overexpression is associated with progression, metastasis, and drug resistance in lung cancer. This study assessed the effects of Bag-1 siRNA on sensitization of cisplatin on non-small cell lung cancer (NSCLC) cells. Material and methods NSCLC A549 cell line was transfected with Bag-1 or negative control siRNA and then treated with cisplatin for cell viability, CCK-8, LDH, and flow cytometry assays. The Ca2+ levels were analyzed using Fluo-3/AM fluorescence staining, and the protein levels were assessed using Western blot analysis. Results Bag-1 siRNA significantly knocked down Bag-1 expression and inhibited cell invasion versus the negative control siRNA, while Bag-1 silence sensitized cisplatin to induce A549 cells to apoptosis by induction of cell cycle G1 arrest. At protein level, Bag-1 silence reduced the expression ratio of Bcl-2 to Bcl-2 associated X protein (Bax), downregulated activity of the PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways, and potently upregulated the calcium signaling-mediated pathway. Conclusion This study demonstrated that Bag-1 silencing sensitized A549 to cisplatin to enhance A549 cell apoptosis by modified multiple gene pathways. Further study will evaluate the usefulness of Bag-1 siRNA as a potential targeting therapy for NSCLC.

Background Glioma‐related epilepsy (GRE) is defined as symptomatic epileptic seizures secondary to gliomas, it brings both heavy financial and psychosocial burdens to patients with diffuse glioma and significantly decreases their quality of life. To date, there have been no clinical guidelines that provide recommendations for the optimal diagnostic and therapeutic procedures for GRE patients. Methods In March 2017, the Joint Task Force for GRE of China Association Against Epilepsy and Society for Neuro‐Oncology of China launched the guideline committee for the diagnosis and treatment of GRE. The guideline committee conducted a comprehensive review of relevant domestic and international literatures that were evaluated and graded based on the Oxford Centre for Evidence‐Based Medicine Levels of Evidence, and then held three consensus meetings to discuss relevant recommendations. The recommendations were eventually given according to those relevant literatures, together with the experiences in the diagnosis and treatment of over 3000 GRE cases from 24 tertiary level hospitals that specialize in clinical research of epilepsy, glioma, and GRE in China. Results The manuscript presented the current standard recommendations for the diagnostic and therapeutic procedures of GRE. Conclusions The current work will provide a framework and assurance for the diagnosis and treatment strategy of GRE to reduce complications and costs caused by unnecessary treatment. Additionally, it can serve as a reference for all professionals involved in the management of patients with GRE.

Background: We determined to assess the HDAC8 expression in esophageal squamous cell carcinoma (ESCC) patients and prognostic potential though there is only a little research contribution regarding HDAC8 to tumorigenesis of ESCC. Methods: The immunohistochemical expression of HDAC8 was investigated on tissue microarrays (TMAs) from 110 patients with esophageal squamous cell carcinoma.The nuclear staining intensity is calculated by the immune reactivity score ranging from (0-12) and divides them into two groups: no expression group and overexpression. Results: The median follow-up duration was 70 months. Highly regulated HDAC8 protein significantly predicted decreased 5-year overall survival (p = 0.001) and progression-free survival (p = 0.001) demonstrated by the log-rank test. Furthermore, HDAC8 protein acts as an independent prognostic factor for overall survival and progression-free survival, which determined after multivariate analyses. By Receiver operating characteristics (ROC) analysis, the value of HDAC8 was (0.63±0.54,p=0.04) according to advance cancer stage and (0.59±0.06,p=0.04) according to the lymph node status found in the Area under the curve (AUC). Conclusion: HDAC8 protein is highly regulated in ESCC tissues and potential prognostic indicator for diagnosing patients with decreased survival period.

Background Infectious diseases encompass a large spectrum of diseases that threaten human health, and coinfection is of particular importance because pathogen species can interact within the host. Currently, the antagonistic relationship between different pathogens during concurrent coinfections is defined as one in which one pathogen either manages to inhibit the invasion, development and reproduction of the other pathogen or biologically modulates the vector density. In this review, we provide an overview of the phenomenon and mechanisms of antagonism of coinfecting pathogens involving parasites. Main body This review summarizes the antagonistic interaction between parasites and parasites, parasites and viruses, and parasites and bacteria. At present, relatively clear mechanisms explaining polyparasitism include apparent competition, exploitation competition, interference competition, biological control of intermediate hosts or vectors and suppressive effect on transmission. In particular, immunomodulation, including the suppression of dendritic cell (DC) responses, activation of basophils and mononuclear macrophages and adjuvant effects of the complement system, is described in detail. Conclusions In this review, we summarize antagonistic concurrent infections involving parasites and provide a functional framework for in-depth studies of the underlying mechanisms of coinfection with different microorganisms, which will hasten the development of promising antimicrobial alternatives, such as novel antibacterial vaccines or biological methods of controlling infectious diseases, thus relieving the overwhelming burden of ever-increasing antimicrobial resistance. Electronic supplementary material The online version of this article (10.1186/s40249-019-0560-6) contains supplementary material, which is available to authorized users.

OBJECTIVEAlthough enhanced recovery after surgery (ERAS) programs have gained acceptance in various surgical specialties, no established neurosurgical ERAS protocol for patients undergoing elective craniotomy has been reported in the literature. Here, the authors describe the design, implementation, safety, and efficacy of a novel neurosurgical ERAS protocol for elective craniotomy in a tertiary care medical center located in China.METHODSA multidisciplinary neurosurgical ERAS protocol for elective craniotomy was developed based on the best available evidence. A total of 140 patients undergoing elective craniotomy between October 2016 and May 2017 were enrolled in a randomized clinical trial comparing this novel protocol to conventional neurosurgical perioperative management. The primary endpoint of this study was the postoperative hospital length of stay (LOS). Postoperative morbidity, perioperative complications, postoperative pain scores, postoperative nausea and vomiting, duration of urinary catheterization, time to first solid meal, and patient satisfaction were secondary endpoints.RESULTSThe median postoperative hospital LOS (4 days) was significantly shorter with the incorporation of the ERAS protocol than that with conventional perioperative management (7 days, p < 0.0001). No 30-day readmission or reoperation occurred in either group. More patients in the ERAS group reported mild pain (visual analog scale score 1–3) on postoperative day 1 than those in the control group (79% vs. 33%, OR 7.49, 95% CI 3.51–15.99, p < 0.0001). Similarly, more patients in the ERAS group had a shortened duration of pain (1–2 days; 53% vs. 17%, OR 0.64, 95% CI 0.29–1.37, p = 0.0001). The urinary catheter was removed within 6 hours after surgery in 74% patients in the ERAS group (OR 400.1, 95% CI 23.56–6796, p < 0.0001). The time to first oral liquid intake was a median of 8 hours in the ERAS group compared to 11 hours in the control group (p < 0.0001), and solid food intake occurred at a median of 24 hours in the ERAS group compared to 72 hours in the control group (p < 0.0001).CONCLUSIONSThis multidisciplinary, evidence-based, neurosurgical ERAS protocol for elective craniotomy appears to have significant benefits over conventional perioperative management. Implementation of ERAS is associated with a significant reduction in the postoperative hospital stay and an acceleration in recovery, without increasing complication rates related to elective craniotomy. Further evaluation of this protocol in large multicenter studies is warranted.Clinical trial registration no.: ChiCTR-INR-16009662 (chictr.org.cn)

Objective The main aim of this study was to investigate the association of polymorphisms in long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Methods A total of 245 ESCC patients and 490 gender- and age-matched cancer-free controls were genotyped for four tag single nucleotide polymorphisms (SNPs) of MALAT1 (rs3200401 C > T, rs1122709 C > G, rs664589 C > G, and rs619586 A > G). Statistical analyses including chi-squared test and logistic regression were performed to identify the association between the tag SNPs and risk of ESCC, and false discovery rate (FDR) Results We found that rs3200401 C > T polymorphism of MALAT1 was significantly associated with increased risk of ESCC (CT vs CC: adjusted OR =1.59, 95% CI =1.07-2.35, P=0.021; TT vs CC: adjusted OR =2.27, 95% CI =1.04-4.96, P=0.039; dominant model [CT+TT vs CC]: adjusted OR =1.68, 95% CI =1.16-2.43, P=0.006). In the stratified analysis, rs3200401 TT and CT/TT genotypes were associated with increased risk of ESCC compared with CC genotype in subgroup of never drinking (TT vs CC: adjusted OR =2.34, 95% CI =1.02-5.34, P=0.044; CT/TT vs CC: adjusted OR =1.52, 95% CI =1.02-2.26, P=0.041). However, compared with AA genotype, MALAT1 rs619586 GG was associated with decreased risk of ESCC in ever drinking subgroup (GG vs AA: adjusted OR =0.38, 95% CI =0.15-0.99, P=0.049). The results remained significant after FDR adjustment (FDR value Conclusion Taken together, our findings proposed that polymorphism rs3200401 C > T in MALAT1 gene is associated with increased risk of ESCC. Since the association between rs619586 A > G polymorphism and ESCC risk was not significant after FDR adjustment, there was a minor possibility that rs619586 A > G might be a protective factor for ESCC.

Osteoarthritis (OA) is a chronic disease that seriously impairs people’s physical function and quality of life. Triptolide (TP), as a promising anti-inflammatory drug for the treatment of OA, has limited clinical application due to its severe systemic toxicity, poor solubility and rapid elimination in the body. To extend its application prospect for OA treatment. We have developed a liposome-loaded dissolving microneedle (DMN) system, which can effectively deliver poorly water-soluble TP and improve OA symptoms. To incorporate TP into DMNs, triptolide liposome (TP-Lipo) with entrapment efficiency of 90.25% was prepared by ethanol injection. Subsequently, TP-Lipo was concentrated by ultrafiltration tube and mixed with hyaluronic acid solution to prepare DMNs, TP-Lipo-loaded DMNs (TP-Lipo@DMNs) showed sufficient mechanical and insertion properties to penetrate about 200 μm of rat skin. The drug distribution in vivo showed that TP-Lipo@DMNs had a slow-release effect compared with intra-articular injection. In vivo pharmacodynamic research showed that TP-Lipo@DMNs significantly reduced knee joint swelling and the level of inflammatory cytokines (TNF-α, IL-1β, IL-6). Micro-CT and histological evaluation showed that TP-Lipo@DMNs effectively reduced cartilage destruction and alleviated OA symptoms. These results support that TP@Lipo@DMNs may be a promising option for OA treatment.

BackgroundThe endoplasmic reticulum oxidoreductin-1-like (ERO1L) gene encodes an endoplasmic reticulum luminal localized glycoprotein known to associated with hypoxia, however, the role of ERO1L in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in lung adenocarcinoma (LUAD).MethodsIn this study, raw datasets (including RNA-seq, methylation, sgRNA-seq, phenotype, and survival data) were obtained from public databases. This data was analyzed and used to explore the biological landscape of ERO1L in immune infiltration. Expression data was used to characterize samples. Using gene signatures and cell quantification, stromal and immune infiltration was determined. These findings were used to predict sensitivity to immunotherapy.ResultsThis study found that ERO1L was significantly overexpressed in LUAD in comparison to normal tissue. This overexpression was found to be a result of hypomethylation of the ERO1L promoter. Overexpression of ERO1L resulted in an immune-suppressive TIME via the recruitment of immune-suppressive cells including regulatory T cells (Tregs), cancer associated fibroblasts, M2-type macrophages, and myeloid-derived suppressor cells. Using the Tumor Immune Dysfunction and Exclusion (TIDE) framework, it was identified that patients in the ERO1Lhigh group possessed a significantly lower response rate to immunotherapy in comparison to the ERO1Llow group. Mechanistic analysis revealed that overexpression of ERO1L was associated with the upregulation of JAK-STAT and NF-κB signaling pathways, thus affecting chemokine and cytokine patterns in the TIME.ConclusionsThis study found that overexpression of ERO1L was associated with poor prognoses in patients with LUAD. Overexpression of ERO1L was indicative of a hypoxia-induced immune-suppressive TIME, which was shown to confer resistance to immunotherapy in patients with LUAD. Further studies are required to assess the potential role of ERO1L as a biomarker for immunotherapy efficacy in LUAD.

Background and Purpose: As a rare lesion secondary to brain trauma, traumatic intracranial aneurysms (TICAs) lead to high mortality and morbidity, and multiple treatment modalities have been applied for TICAs. All patients diagnosed with TICAs in our institution from 2010 to 2020 were included in the report, and their clinical features, treatment, and outcomes are described in detail. The purpose of this study is to illustrate the characteristic of different therapeutic methods of TICAs, and focus on the endovascular treatment.Methods: A total of 20 patients were included in this study. The 3 patients who declined treatment all died. Five of the other 17 patients were treated surgically, including clipping, wrapping, and trapping with or without EC-IC high-flow bypass, with only 1 case of parent artery preservation. Twelve patients underwent endovascular treatment, including bare coil embolization (1 case), stent-assisted coiling (2 cases), balloon-assisted coils/Onyx glue embolization (1 case) and covered stents (8 cases), with only 1 case of parent artery sacrifice.Results: 20 patients were included in the present study with 17 males, and the mean of age on 27 years (IQR: 22, 44 years). Eight patients presented with epistaxis, followed by 5 patients with coma, 3 patients with visual defects and 2 patients with CSF leakage. There were 18 TICAs located at the internal carotid artery (ICA); The other 2 TICAs located at pericallosal artery and A1 segment anterior cerebral artery (ACA). One case of diplopia occurred due to sacrifice of the ICA. Occlusion of the ophthalmic artery occurred in 3 patients after placement of a covered stent, with 1 patient suffering an irreversible vision decrease. None of the other patients who underwent the treatment have experienced an aggravation of their symptoms since the treatment; During the imaging follow-up, 1 case of recurrence and 1 case of endoleak occurred in this case series.Conclusions: TICAs are associated with significant morbidity and mortality, and endovascular treatment has emerged as a valuable option, which may be promising to improve the clinical outcomes due to their advantages of preserving the parent artery if occlusion of the side branch artery can be avoided.

Background To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique. Methods Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively. Results A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE. Conclusions EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.

The present study aimed to investigate the effects of the overexpression of sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2a) on endoplasmic reticulum (ER) stress (ERS)‑associated inflammation in neonatal rat cardiomyocytes (NRCMs) induced by tunicamycin (TM) or hypoxia/reoxygenation (H/R). The optimal multiplicity of infection (MOI) was 2 pfu/cell. Neonatal Sprague‑Dawley rat cardiomyocytes cultured in vitro were infected with adenoviral vectors carrying SERCA2a or enhanced green fluorescent protein genes, the latter used as a control. At 48 h following gene transfer, the NRCMs were treated with TM (10 µg/ml) or subjected to H/R to induce ERS. The results of electrophoretic mobility shift assay (EMSA) revealed that overexpression of SERCA2a attenuated the upregulation of nuclear factor (NF)‑κB and activator protein‑1 (AP‑1) DNA‑binding activities induced by TM or H/R. Western blot analysis and semi‑quantitative RT‑PCR revealed that the overexpression of SERCA2a attenuated the activation of the inositol‑requiring 1α (IRE1α) signaling pathway and ERS‑associated apoptosis induced by TM. The overexpression of SERCA2a also decreased the level of phospho‑p65 (Ser536) in the nucleus, as assessed by western blot analysis. However, the overexpression of SERCA2a induced the further nuclear translocation of NF‑κB p65 and higher levels of tumor necrosis factor (TNF)‑α transcripts in the NRCMs, indicating the occurrence of the ER overload response (EOR). Therefore, the overexpression of SERCA2a has a 'double‑edged sword' effect on ERS‑associated inflammation. On the one hand, it attenuates ERS and the activation of the IRE1α signaling pathway induced by TM, resulting in the attenuation of the upregulation of NF‑κB and AP‑1 DNA‑binding activities in the nucleus, and on the other hand, it induces EOR, leading to the further nuclear translocation of NF‑κB and the transcription of TNF‑α. The preceding EOR may precondition the NRCMs against subsequent ERS induced by TM. Further studies using adult rat cardiomyocytes are required to prevent the interference of EOR. The findings of the present study may enhance the current understanding of the role of SERCA2a in cardiomyocytes.

Background The objective of this study was to establish a risk assessment model for lower extremity deep venous thrombosis in critically ill patients and compared with Caprini, Padua and Wells risk assessment model to evaluate its efficacy. Methods We conducted a pooled analysis of prospective cohort studies. The outcomes of interest were lower extremity deep vein thrombosis group and Non-lower extremity deep vein thrombosis group were determined by univariate analysis, and SPSS was used to establish the back propagation artificial neural network prediction model. ROC curve was used to evaluate the predictive effectiveness of the model. Medcalc15.2 was used to compare the predictive capabilities of different models. Results 600 cases of intensive care unit patients were selected in this study. The prevalence of lower extremity venous thromboembolism after ICU admission was 12.5%. The results of univariate analysis that showed 16 statistically significant difference influencing factors. The ROC curve area of BP-ANN risk assessment model was 0.828, showing good predictive efficacy. In addition to the ROC curve area of BP-ANN risk assessment model was higher than Caprini, Padua and Wells model. Conclusion BP-ANN risk assessment model can play an auxiliary role in predicting the occurrence of lower extremity venous thromboembolism in critically ill patients. This model can provide a reference for medical staff to take preventive management measures.

BackgroundCerebral fat embolism (CFE) syndrome at high altitude was rare complicated with paroxysmal sympathetic hyperactivity (PSH) syndrome and septic shock. It is a challenge to differential diagnosis and treatment at high altitude.Case presentationThis case presents a CFE with PSH and septic shock of a 23-year-old man occurred at high altitude of 3800 m above sea level, transferred by airplane successfully and cured in the department of neurosurgery, Xi’an Tangdu Hospital.ConclusionsIt is key that CFE with PSH can be rapid diagnosed and treatment bundles of septic shock should be initiated as soon as possible. Early neurological rehabilitation played an important role for good outcome.

PurposeDiffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival.MethodsWe retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort.ResultsThe median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030).ConclusionLow preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.