Monocyte HLA-DR level on admission predicting in-hospital mortality rate in exertional heatstroke: A 12-year retrospective study.

BACKGROUND: Exertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocyte human leukocyte-DR antigen (mHLA-DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro-inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA-DR in EHS. The present study tried to explore the prognostic value of mHLA-DR levels in EHS patients. METHODS: This was a single-center retrospective study. Clinical data of EHS patients admitted to the intensive care unit of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. RESULTS: Seventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA-DR in the nonsurvivors (41.8% [38.1-68.1]%) were significantly lower than those in the survivors (83.1% [67.6-89.4]%, p < 0.001). Multivariate logistic regression indicated that mHLA-DR (odds ratio [OR] = 0.939; 95% confidence interval [CI]: 0.892-0.988; p = 0.016) and Glasgow coma scale (GCS) scores (OR = 0.726; 95% CI: 0.591-0.892; p = 0.002) were independent risk factors related with in-hospital mortality rate in EHS. A nomogram incorporated mHLA-DR with GCS demonstrated excellent discrimination and calibration abilities. Compared to the traditional scoring systems, the prediction model incorporated mHLA-DR with GCS had the highest area under the curve (0.947, 95% CI: [0.865-0.986]) and Youden index (0.8333), with sensitivity of 100% and specificity of 83.33%, and a greater clinical net benefit. CONCLUSION: Patients with EHS were at a risk of early experiencing decreased mHLA-DR early. A nomogram based on mHLA-DR with GCS was developed to facilitate early identification and timely treatment of individuals with potentially poor prognosis.

A nomogram based on lymphocyte percentage for predicting hospital mortality in exertional heatstroke patients: a 13-year retrospective study.

BACKGROUND: Exertional heatstroke (EHS) is a life-threatening disease without ideal prognostic markers for predicting hospital mortality. METHODS: This is a single-center retrospective study. Clinical data from EHS patients admitted to the Intensive Care Unit (ICU) of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. Univariate and multivariate logistic regression were used to identify the factors for mortality. The prediction model was developed with the prognostic markers, and a nomogram was established. RESULTS: The study ultimately enrolled 156 patients, and 15 (9.6%) of patients died before discharge. The lymphocyte count (Lym) and percentage (Lym%) were significantly lower in non-survivors (P<0.05). The univariate and multivariate logistic regression analyses indicated that Lym% at the third day of admission (Lym% D3) (OR=0.609, 95%CI: 0.454-0.816) and hematocrit (HCT) (OR=0.908, 95%CI: 0.834-0.988) were independent protective factors for hospital mortality. A nomogram incorporating Lym% D3 with HCT was developed and demonstrated good discrimination and calibration ability. The comparison between the prediction model and scoring systems revealed that the prediction model had the largest area under the curve (AUC) (0.948, 95%CI: 0.900-0.977), with 100.00% sensitivity and 83.69% specificity, and a greater clinical net benefit. CONCLUSION: Severe EHS patients had a higher risk of experiencing prolonged lymphopenia. A nomogram based on Lym% D3 and HCT was developed to facilitate early identification and timely treatment of patients with potentially unfavorable prognoses.

Ferroptosis and mitochondrial dysfunction in acute central nervous system injury.

Acute central nervous system injuries (ACNSI), encompassing traumatic brain injury (TBI), non-traumatic brain injury like stroke and encephalomeningitis, as well as spinal cord injuries, are linked to significant rates of disability and mortality globally. Nevertheless, effective and feasible treatment plans are still to be formulated. There are primary and secondary injuries occurred after ACNSI. Most ACNSIs exhibit comparable secondary injuries, which offer numerous potential therapeutic targets for enhancing clinical outcomes. Ferroptosis, a newly discovered form of cell death, is characterized as a lipid peroxidation process that is dependent on iron and oxidative conditions, which is also indispensable to mitochondria. Ferroptosis play a vital role in many neuropathological pathways, and ACNSIs may induce mitochondrial dysfunction, thereby indicating the essentiality of the mitochondrial connection to ferroptosis in ACNSIs. Nevertheless, there remains a lack of clarity regarding the involvement of mitochondria in the occurrence of ferroptosis as a secondary injuries of ACNSIs. In recent studies, anti-ferroptosis agents such as the ferroptosis inhibitor Ferrostain-1 and iron chelation therapy have shown potential in ameliorating the deleterious effects of ferroptosis in cases of traumatic ACNSI. The importance of this evidence is extremely significant in relation to the research and control of ACNSIs. Therefore, our review aims to provide researchers focusing on enhancing the therapeutic outcomes of ACNSIs with valuable insights by summarizing the physiopathological mechanisms of ACNSIs and exploring the correlation between ferroptosis, mitochondrial dysfunction, and ACNSIs.

Targeted inhibition of HDAC8 increases the doxorubicin sensitivity of neuroblastoma cells via up regulation of miR-137.

Histone deacetylases (HDACs) have been suggested to be potential therapeutic targets for cancer treatment. Recent studies revealed that HDAC8 expression was associated with poor prognostic markers and poor overall survival rate of neuroblastoma (NB). Our present study revealed that among the four members of class I HDACs, HDAC8 is significantly over expressed in NB cells as compared with the normal fibroblast 3T3 cells or primary normal human astrocytes (NHA) cells. Targeted inhibition of HDAC8 by its specific siRNA (si-HDAC8) can inhibit the in vitro growth of NB cells. Furthermore, si-HDAC8 significantly increases the sensitivity of NB cells to doxorubicin (Dox). Silencing of HDAC8 can increase the expression of miR-137, which has been suggested to mediate the Dox sensitivity of NB cells. Knockdown of miR-137 can attenuate si-HDAC8 enhanced Dox sensitivity. Further, si-HDAC8 can also inhibit the expression of multi-drug resistance gene 1 (MDR1). While knockdown of miR-137 can attenuate si-HDAC8 induced down regulation of MDR1. Collectively, our data revealed that targeted inhibition of HDAC8 can suppress the growth of NB cells and increase Dox sensitivity via up regulation of miR-137 and suppression of MDR1. Therefor, combination of HDAC8 inhibitor will be helpful to elevate the treatment outcome of NB patients.

Mutation of isocitrate dehydrogenase 1 induces glioma cell proliferation via nuclear factor-κB activation in a hypoxia-inducible factor 1-α dependent manner.

Recently, mutations of the isocitrate dehydrogenase (IDH) 1 gene, which specifically occur in the majority of low-grade and secondary high-grade gliomas, have drawn particular attention of neuro-oncologists. Mutations of the IDH1 gene have been proposed to have significant roles in the tumorigenesis, progression and prognosis of gliomas. However, the molecular mechanism of the role of IDH1 mutants in gliomagenesis remains to be elucidated. The present study, showed that forced expression of an IDH1 mutant, of which the 132th amino acid residue arginine is substituted by histidine (IDH1R132H), promoted cell proliferation in cultured cells, while wild-type IDH1 overexpression had no effect on cell proliferation. Consistent with previous studies, it was also observed that expression of hypoxia-inducible factor 1-α (HIF1-α) was upregulated in IDH1R132H expressing cells with the induction of vascular endothelial growth factor (VEGF) expression. However, knockdown of VEGF via small RNA interference had no significant influence on the cell proliferation induced by overexpression of IDH1R132H, implying that another signaling pathway may be involved. Next, forced expression of IDH1R132H was found to activate nuclear factor-κB (NF-κB), since the inhibitory IκB protein (IκBα) was highly phosphorylated and the NF-κB p65 subunit was translocated into the nucleus. Notably, knockdown of HIF1-α significantly blocked NF-κB activation, which was induced by the overexpression of IDH1 mutants. In addition, expression of IDH1 mutants markedly induced the NF-κB target gene expression, including cyclin D1 and E and c-myc, which were involved in the regulation of cell proliferation. In conclusion, it was demonstrated that the IDH1 mutant activated NF-κB in a HIF1-α­dependent manner and was involved in the regulation of cell proliferation.

Endovascular treatment of ruptured distal posterior inferior cerebellar artery aneurysms: report of 11 cases.

OBJECTIVE: To investigate the clinical characteristics and endovascular treatment of ruptured distal posterior inferior cerebellar artery (PICA) aneurysms. METHODS: 11 consecutive patients (7 women, 4 men, mean age of 49.2 years) with ruptured distal PICA aneurysms were studied retrospectively. All had onset of acute intraventricular or cerebellar haemorrhage, and subarachnoid hemorrhage (SAH). Hunt-Hess (HH) grades were H-H I in 1 patient, H-H II in 5 patients, H-H 111 in 4 patients and H-H IV in 1 patient on admission. RESULTS: All patients were treated by endovascular treatment, seven cases got endosaccular coiling and four cases got parent artery occlusion at the same time. All the patients were followed up one to four years. Recurrences occurred in 1 patient two years post-treatment, and were successfully retreated by endosaccular coiling and parent artery occlusion. The occluded PICA was recanalized one year post-treatment but without any growth of the aneurysm in one case. One year post-treatment, 2 patients had a modified Rankin Scale (mRS) score of 0, 8 patients had a mRS score of 1 and 1 patient had a mRS score of 2. CONCLUSIONS: Coiling of ruptured distal PICA aneury, with or without parent vessel occlusion, was feasible, relatively safe and effective in preventing early/medium-term rebleeding. A strict angiographic follow-up, however, was necessary to detect recurrence.

14-3-3ß regulates the proliferation of glioma cells through the GSK3ß/ß-catenin signaling pathway.

We previously demonstrated that 14-3-3ß is overexpressed in astrocytomas; however, the underlying mechanisms are poorly understood. Based on the reported multiple functions of 14-3-3ß, we hypothesized that it interacts with glycogen synthase kinase 3 ß (GSK3ß), which regulates ß-catenin-mediated oncogene expression and contributes to tumorigenesis and astrocytoma progression. To test these hypotheses, we used 14-3-3ß overexpression vectors and small interfering RNA (siRNA) transfection in the human normal astrocyte cell line SVGp12 and the glioma cell line U87, respectively. The results showed that overexpression of 14-3-3ß promoted the proliferation of SVGp12 cells, while knockdown of 14-3-3ß inhibited the proliferation of U87 cells as analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) assays. In Flag-tagged 14-3-3ß-overexpressing cells, GSK3ß was co-immunoprecipitated with 14-3-3ß using a Flag antibody. Knockdown of ß-catenin by siRNA blocked cell proliferation induced by overexpression of 14-3-3ß. Furthermore, overexpression of 14-3-3ß suppressed the phosphorylation of ß-catenin leading to its accumulation and nuclear translocation as revealed by western blot analysis. In addition, ß-catenin nuclear translocation induced by overexpression of 14-3-3ß activated the transcription of oncogenes including c-myc and cyclin D1. Collectively, these results revealed that 14-3-3ß regulates the proliferation of astrocytes and glioma cells through the GSK3ß/ß-catenin signaling pathway. The delineated mechanism of 14-3-3ß may be responsible for the tumorigenesis and progression of human astrocytomas. Thus, new therapeutic strategies or drugs aimed at 14-3-3ß may have potential for the treatment of human astrocytomas.

[Predisposing factors for postoperative epilepsy in patients with gliomas].

OBJECTIVE: To explore the predisposing factors for postoperative epilepsy in patients with gliomas. METHODS: A total of 258 glioma patients with complete clinical data receiving cranial surgeries were analyzed retrospectively. With gender, age, predominant symptoms, positive signs, history of preoperative epilepsy, time of epilepsy onset, tumor location, surgical approaches, cortical injury, arterial and venous injury, scope of tumor resection, postoperative edema, tumor pathology, tumor recurrence, number of operation, radiation therapy as the independent variables, the occurrence of postoperative epilepsy was analyzed as the dependent variable using logistic regression to identify the risk factors for postoperative epilepsy. RESULTS: History of preoperative epilepsy, surgical approaches, postoperative edema, tumor pathology and tumor recurrence were identified as the risk factors for postoperative epilepsy in glioma patients. CONCLUSIONS: Postoperative epilepsy severely affected the quality of life of glioma patients, and rigorous treatment targeting the risk factors may decrease the occurrence of postoperative epilepsy.

[Establishment of rat hypophyseal compression model and changes in its postoperative biological characteristics].

OBJECTIVE: To establish a rat model of hypophyseal compression and observe and analyze the changes in its biological characteristics after operation. METHODS: The rats were subjected to compression of the pituitary gland by stuffing the autologous muscular tissue into the hypophyseal fossa. The postoperative mortality of the rats was recorded and the volume of the hypophyeseal fossa, body weight, daily food intake, water intake, urine volume and urine specific gravity were measured. RESULTS: Rat models of the hypophyseal compression model were successfully established by this procedure, which resulted in an increase of the volume of hypophyseal fossa by 35%. Rapid body weight loss occurred within 5 weeks after the operation (by as much as 31% on day 10). The rats exhibited recovery of appetite after 2 weeks, but their food intake was still less than that in the control group. Manifestations of central diabetes insipidus occurred gradually, which were especially obvious at 2 weeks and persisted afterwards, and at this time point, significant increment of urine volume (55.4-/+15.9 vs 18.5-/+5.8 ml) and lowered urine gravity (1.011-/+0.004 vs 1.036-/+0.006) were observed. CONCLUSION: Rat models of hypophyseal compression can be established successfully by the described procedure, and the compression results in alteration of the rats' metabolic behaviors, which may differ from the effects of hypophysectomy and damage of pituitary stalk.

[Changes and effects of group II metabotropic glutamate receptors in the cerebral cortex of rats after diffuse brain injuries coupled with hypopiesia secondary brain insults].

OBJECTIVE: To study the changes and effects of group II metabotropic glutamate receptors (mGluR) after diffuse brain injuries (DBI) coupled with hypopiesia secondary brain insults (SBI). METHODS: Male SD rats were randomized into four groups: normal control, sham-operated, DBI alone and DBI coupled with SBI group. The SBI model was made on the basis of Marmarou's model. The mRNAs of the mGluRs were detected at 1, 3, 6, 12, 24, 48 and 72 hours after injuries by in-situ hybridization, and the positive neurons were counted. RESULTS: Statistical analysis showed no significance between normal control group and sham-operated group, DBI group in mGluR 2, 3 mRNA (all P>0.05). The number of mGluR 2, 3 positive neurons decreased at 12 hours after injury and the peak occurred at 48 hours after injury in the injured cerebral cortex in DBI alone group (both P<0.05). However, in DBI with SBI group, there was a significant decrease of the number of mGluR2, 3 positive neurons at 6 hours after injury and the peak happened at 24 hours after injury (both P<0.05). CONCLUSION: mGluR2, 3, factors with the function of protecting brain, might play an important role in the path physiology of DBI and SBI.