Association between gut microbiota dysbiosis and poor functional outcomes in acute ischemic stroke patients with COVID-19 infection.

Acute ischemic stroke (AIS) patients with active COVID-19 infection often have more severe symptoms and worse recovery. COVID-19 infection can cause gut microbiota dysbiosis, which is also a risk factor for poor outcomes in AIS patients. However, the association between gut microbiota and functional outcomes among AIS patients with COVID-19 infection has not been fully clarified yet. In this study, we performed 16S rRNA gene sequencing to characterize the gut microbial community among AIS patients with acute COVID-19 infection, AIS patients with post-acute COVID-19 infection, and AIS patients without COVID-19 infection. We found that AIS patients with acute COVID-19 experienced poorer recovery and significant gut dysbiosis, characterized by higher levels of Enterobacteriaceae and lower levels of Ruminococcaceae and Lachnospiraceae. Furthermore, a shorter time window (less than 28 days) between COVID-19 infection and stroke was identified as a risk factor for poor functional outcomes in AIS patients with COVID-19, and the enrichment of Enterobacteriaceae was indicated as a mediator in the relationship between infection time window and poor stroke outcomes. Our findings highlight the importance of early intervention after COVID-19 infection, especially by regulating the gut microbiota, which plays a role in the prognosis of AIS patients with COVID-19 infection.IMPORTANCEThe gut microbiota plays an important role in the association between respiratory system and cerebrovascular system through the gut-lung axis and gut-brain axis. However, the specific connection between gut bacteria and the functional outcomes of acute ischemic stroke (AIS) patients with COVID-19 is not fully understood yet. In our study, we observed a significant decrease in bacterial diversity and shifts in the abundance of key bacterial families in AIS patients with acute COVID-19 infection. Furthermore, we identified that the time window was a critical influence factor for stroke outcomes, and the enrichment of Enterobacteriaceae acted as a mediator in the relationship between the infection time window and poor stroke outcomes. Our research provides a new perspective on the complex interplay among AIS, COVID-19 infection, and gut microbiota dysbiosis. Moreover, recognizing Enterobacteriaceae as a potential mediator of poor stroke prognosis offers a novel avenue for future exploration and therapeutic interventions.

[Effect of nasal swell body on nasal airflow and Artemisia pollen deposition].

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.

Dopamine D2 receptor on CD4+ T cells is protective against inflammatory responses and signs in a mouse model of rheumatoid arthritis.

BACKGROUND: Dopamine is a neurotransmitter and has been found to regulate lymphocytes by acting on dopamine receptors (DRs). CD4+ T cells express all the five subtypes of DRs, D1R to D5R. Although CD4+ T cells have been involved in pathogenesis of rheumatoid arthritis (RA), roles of DRs expressed on these cells in RA are poorly understood. This study determined whether D2R expressed on CD4+ T cells regulates inflammatory responses and signs in collagen type II (CII)-induced arthritis (CIA), a mouse model of RA. METHODS: DBA/1 mice and C57BL/6 mice with global D1r or D2r deficiency (D1r-/- or D2r-/-) or CD4+ T cell-specific D2r deletion (D2rfl/fl/CD4Cre) were used to prepare CIA model by intradermal injection of CII. D2R agonist sumanirole was intraperitoneally administered in CIA mice. CD4+ T cells obtained from CIA mice were exposed to sumanirole or/and D2R antagonist L-741,626 in vitro. Arthritic symptoms were assessed by clinical arthritis scores. Flow cytometric assay measured frequencies of CD4+ T cell subsets (Th1, Th2, Th17 and Treg cells). Expression of specific transcription factors for the CD4+ T cell subsets was tested by Western blot. Cytokine production was estimated by quantitative PCR and ELISA. RESULTS: CIA mice manifested a bias of CD4+ T cells towards Th1 and Th17 cells. D2r-/- CIA mice showed a stronger bias towards Th1 and Th17 phenotypes than CIA mice, while D1r-/- CIA mice did not show the changes. CD4+ T cell-specific D2r deletion exacerbated both the polarization towards Th1 and Th17 cells and the symptoms of arthritis. Sumanirole administration in CIA mice ameliorated the bias of CD4+ T cells towards Th1 and Th17 phenotypes as well as arthritic symptoms. Sumanirole treatment of in vitro CD4+ T cells obtained from CIA mice promoted the shift to Treg cells, and the effect of sumanirole was blocked by L-741,626. CONCLUSIONS: D2R expressed on CD4+ T cells is protective against imbalance between pro-inflammatory and anti-inflammatory T cells and arthritic symptoms in CIA.

Clinical features of patients with cerebral venous sinus thrombosis at plateau areas.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is believed to be associated with high-altitude exposure and has worse clinical prognosis in plateau areas than in plain areas, although this needs to be further verified. This retrospective study aims to compare the clinical differences of patients with CVST in plateau and plain areas and further ascertain the role of high-altitude exposure in the etiology of aggravating predisposition toward CVST. METHODS: Twenty-four symptomatic CVST patients occurring at plateau areas (altitude ≥ 4000 m), in corresponding with 24 CVST patients occurring at plain areas (altitude ≤ 1000 m), were recruited according to the inclusion and exclusion criteria from June 2020 to December 2021. The collected data and compared parameters include clinical features, neuroimaging findings, hematology profile, lipid profile, and coagulation profile within 24 h of hospital admission, as well as the treatment method and final outcome. RESULTS: There were no obvious differences of demographic characteristics, including gender, age, height, and weight between patients with CVST in plateau and plain areas, as well as medical history, neuroimaging findings, treatment protocols, and clinical outcome (all p > .05). Compared to patients with CVST at plain areas, time before hospital admission was longer and heartbeat was slower in patients with CVST at plateau areas (all p < .05). More importantly, elevated red blood cells counts, hemoglobin level, and altered coagulation function were found in patients with CVST at plateau areas (all p < .05). CONCLUSION: CVST patients in plateau areas presented with altered clinical characteristics, altered coagulation function, and aggravated predisposition toward venous thromboembolism compared with CVST patients in plain areas. Future prospective studies will be needed to further elucidate the influences of a high altitude on the pathogenesis of CVST.

Activation of ß2-adrenergic Receptor Alleviates Collagen-induced Arthritis by Ameliorating Th17/Treg Imbalance.

Background: Recent research in our laboratory shows that CD4+ T cells express the ß2 adrenergic receptor (ß2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via ß2-AR signaling. However, the immunoregulatory effect of ß2-AR and its related mechanisms on rheumatoid arthritis is unknown. Objective: To explore the effects of ß2-AR in collagen-induced arthritis (CIA) on the imbalance of T helper (Th) 17/ regulatory T (Treg) cells. Methods: In DBA1/J mice, collagen type II was injected intradermally at the tail base to prepare the CIA model. The specific ß2-AR agonist, terbutaline (TBL), was administered intraperitoneally beginning on day 31 and continuing until day 47 after primary vaccination, twice a day. Magnetic beads were used to sort CD3+ T cells subsets from spleen tissues. Results: In vivo, ß2-AR agonist TBL alleviated arthritis symptoms in the CIA mice including histopathology of the ankle joints, four limbs' arthritis score, the thickness of ankle joints, and rear paws. After TBL treatment, in the ankle joints, the levels of proinflammatory factors (IL-17/22) notably decreased and the levels of immunosuppressive factors (IL-10/TGF-ß) significantly increased. In vitro, ROR-γt protein expression, Th17 cell number, mRNA expression and the releasing of IL-17/22 from CD3+ T cells reduced following TBL administration. Moreover, TBL enhanced the anti-inflammatory responses of Treg cells. Conclusion: These results suggest that ß2-AR activation exerts anti-inflammatory effects through the amelioration of Th17/Treg imbalance in the CIA disease.

Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/- mice with spontaneously diabetic Ins2Akita (Akita) mice. Blood glucose levels and body weights were monitored from 2-32 weeks of age. When mice were 32 weeks of age, behavioral tests were performed, including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory. IL-17A levels in the serum, cerebrospinal fluid, and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction. Moreover, proteins related to cognitive dysfunction (amyloid precursor protein, ß-amyloid cleavage enzyme 1, p-tau, and tau), apoptosis (caspase-3 and -9), inflammation (inducible nitric oxide synthase and cyclooxygenase 2), and occludin were detected by western blot assays. Pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1ß, and interferon-γ in serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays. Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining. Compared with that in wild-type mice, mice with diabetic encephalopathy had higher IL-17A levels in the serum, cerebrospinal fluid, and hippocampus; downregulation of occludin expression; lower cognitive ability; greater loss of hippocampal neurons; increased microglial activation; and higher expression of inflammatory factors in the serum and hippocampus. IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy. These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy. Furthermore, IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects. These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.

The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas.

Objective: Traumatic brain injury (TBI) is a leading cause of death and disability, which tends to have a worse clinical recovery if it occurs in plateau areas than in plain areas. To explore the underlying cause of this outcome preliminarily, this retrospective study was conducted to compare the clinical differences of patients with TBI in plateau and plain areas. Methods: In this study, 32 patients with TBI in plateau areas (altitude ≥ 4,000 m) and 32 in plain areas (altitude ≤ 1,000 m) were recruited according to the inclusion and exclusion criteria from June 2020 to December 2021. The collected data and compared parameters include clinical features, head CT presentations and Marshall classifications, hematology profile, lipid profile, coagulation profile, and multiorgan (cardiac, liver, renal) function within 24 h of hospital admission, as well as the treatment method and final outcome. Results: There were no obvious differences in demographic characteristics, including gender, age, height, and weight, between patients with TBI in plateau and plain areas (all P > 0.05). Compared to patients with TBI in plain areas, the time before hospital admission was longer, heartbeat was slower, systolic blood pressure (SBP) was lower, and hospital stays were longer in patients with TBI in plateau areas (all P < 0.05). More importantly, elevated red blood cells (RBCs) count and hemoglobin (HGB) level, enhanced coagulation function, and higher rates of multiorgan (cardiac, liver, and renal) injury were found in patients with TBI in plateau areas (all P < 0.05). Conclusion: Patients with TBI in plateau areas presented with altered clinical characteristics, enhanced coagulation function, and aggravated predisposition toward multiorgan (cardiac, liver, and renal) injury, compared to patients with TBI in plain areas. Future prospective studies are needed to further elucidate the influences of high altitude on the disease course of TBI.

LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway.

Background: LIM domain only protein1(LMO1), a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the clinical significance and potential mechanism of LMO1 in human gliomas remain to be determined. Methods: In this study, expression level data and clinical information were obtained via three databases. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. In vitro and in vivo assays were used to explore the function of LMO1 in human glioma. Gene set enrichment analysis (GSEA), RNA-seq and western blot were used to explore the potential molecular mechanisms. A prognostic model was built for predicting the overall survival(OS) of human glioma patients. Results: High LMO1 expression was associated with a high tumor grade and a poor prognosis in patients. High levels of LMO1 mRNA were correlated with poor prognosis in patients with isocitrate dehydrogenase (IDH)-wild-type (wt) and 1p/19q non-codeletion gliomas. Gene silencing of LMO1 significantly inhibited tumor growth, invasion and migration in vitro. In contrast, LMO1 over-expression promoted tumor growth, invasion and migration. Mechanically, LMO1 may positively regulate the level of NGFR mRNA and protein. NGFR mediated the regulation between LMO1 and NF-kB activation. Consistently, the nude mice study further confirmed that knockdown of LMO1 blocked tumor growth via NGFR-NF-kB axis. Finally, The nomogram based on the LMO1 signature for overall survival (OS) prediction in human glioma patients exhibited good performance in the individual mortality risk. Conclusion: This study provides new insights and evidences that high level expression of LMO1 is significantly correlated with progression and prognosis in human gliomas. LMO1 played a critical role in tumorigenesis and progression. The present study first investigated the LMO1-NGFR-NF-kB axis regulate cell growth and invasion in human glioma cells, whereby targeting this pathway may be a therapeutic target for glioma.

Reinvestigating Tumor-Ventricle Relationship of Craniopharyngiomas With Predominantly Ventricular Involvement: An Endoscopic Endonasal Series Based on Histopathological Assessment.

OBJECTIVE: Craniopharyngiomas (CPs) predominantly involving the third ventricle were commonly termed "intraventricular" lesions. The aim of this study was to clarify the anatomical relationship between the tumor and the third ventricle by both surgical and histological investigation. METHODS: A retrospective review of primarily resected CPs by endoscopic endonasal surgery was performed. CPs with predominantly ventricular involvement were selected for study inclusion by preoperative imaging. The surgical procedure of each case was reviewed. The wholly removed tumor specimens were histologically analyzed, in all cases, to investigate the tumor-third ventricle relationship using hematoxylin and eosin, immunochemical, and immunofluorescence staining. RESULTS: Twenty-six primary CPs predominantly involving the third ventricle were selected from our series of 223 CPs treated by endoscopic endonasal surgery between January 2017 and March 2021. Gross-total resection was achieved in 24 (92.3%) of 26 patients, with achievement of near-total resection in the remaining patients. A circumferential layer of stretched third ventricle floor was identified surrounding the tumor capsule, which could be peeled off easily from the ventricle floor remnants at most areas of the plane of tumor attachment. Some portions of the tumor capsule tightly adhered to the third ventricle floor were removed together with the floor. A breach of various size was observed at the third ventricle floor after tumor removal in most cases, the floor remaining intact in only two cases (7.7%). Histological examination on marked portions of tumor capsule showed that the pia mater was frequently detected at most of the tumor-brain interface, except at the antero-frontal border of tumor contacting with the third ventricle floor. At this point, a layer of gliosis with various thickness was observed between the tumor and the neural tissue of the third ventricle floor. CONCLUSION: CPs with predominantly ventricular involvement should be considered as lesions with an extraventricular, epi-pia topography rather than "intraventricular" or "subpial" topography. Accurate understanding of the relationship between the third ventricle and such tumors would predict the circumferential cleavage plane of dissection, and remind neurosurgeons of performing dissection along the safe surgical plane to achieve total tumoral resection with minimizing hypothalamic damage.

[Effects of α1-adrenoreceptor on Treg cell function in collagen-induced arthritis].

Objective: An animal model of collagen-induced arthritis (CIA) was used to investigate the effects of norepinephrine (NE) and α1-adrenoreceptor (α1-AR) on Treg cells in CIA. Methods: Thirty-two male DBA/1 mice were randomly divided into control group and CIA model group. CIA was prepared by intradermal injection of collagen type II (CII, 100 µl) at the tail base of DBA/1 mice. On the 41th day following primary immunization, co-expression of CD4+T and α1-AR in mouse spleens was observed. Protein expressions of α1-AR in the ankle joints and the spleens of mice were measured by Western blot analysis. The CD4+ T cells were isolated from the mouse spleen tissues in CIA mice and treated with NE or α1-AR agonist phenylephrine. Percentage of Treg cells in mouse CD4+ T cells of CIA mice was determined by flow cytometry. Expressions of α1-AR, transforming growth factor-ß (TGF-ß) and IL-10 in CD4+T cells of CIA mice were assessed by Western blot. Results: Co-expression of CD4 and α1-AR was observed in spleens of both intact and CIA mice. Compared with intace mice, α1-AR expressions in the ankle joints and spleens were down-regulated in CIA mice. NE increased the function of Treg cells in CD4+ T cells of CIA mice compared with that of nothing-treated CD4+T cells of CIA mice. Moreover, the α1-AR agonist phenylephrine increased the Treg cell function in CD4+ T cells of CIA mice relative to that of nothing-treated CD4+T cells of CIA mice. Conclusion: Activating α1-AR on CD4+T cells of CIA mice enhances Treg cell function,facilitating a shift of CD4+T cells toward Treg polarization.

Dopamine receptor D2 on CD4+ T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4+ T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5. However, roles of DRs particularly DRD2 expressed on CD4+ T cells in PD remain elucidated. Global Drd1- or Drd2-knockout (Drd1-/- or Drd2-/-) mice or CD4+ T cell-specific Drd2-knockout (Drd2fl/fl/CD4Cre) mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD with the different mutants. On the 7th day following MPTP injection, mice were assessed for dopaminergic neurodegeneration, locomotor impairments, microglial activation, as well as CD4+ T-cell differentiation and function. Furthermore, in vitro CD4+ T cells were exposed to DRD2 agonist and antagonist and then differentiation and function of the cells were determined. MPTP induced dopaminergic neuronal loss in the nigrostriatal system, motor coordinative and behavioral impairments, microglial activation, and CD4+ T-cell polarization to pro-inflammatory T-helper (Th)1 and Th17 phenotypes. Importantly, either Drd2-/- or Drd2fl/fl/CD4Cre mice manifested more severe dopaminergic neurodegeneration, motor deficits, microglial activation, and CD4+ T-cell bias towards Th1 and Th17 phenotypes in response to MPTP, but Drd1-/- did not further alter MPTP intoxication. DRD2 agonist sumanirole inhibited shift of CD4+ T cells obtained from MPTP-intoxicated mice to Th1 and Th17 phenotypes and DRD2 antagonist L-741,626 reversed sumanirole effects. These findings suggest that DRD2 expressed on CD4+ T cells is protective against neuroinflammation and neurodegeneration in PD. Thus, developing a therapeutic strategy of stimulating DRD2 may be promising for mitigation of PD.

Bioleaching and Electrochemical Behavior of Chalcopyrite by a Mixed Culture at Low Temperature.

Low-temperature biohydrometallurgy is implicated in metal recovery in alpine mining areas, but bioleaching using microbial consortia at temperatures <10°C was scarcely discussed. To this end, a mixed culture was used for chalcopyrite bioleaching at 6°C. The mixed culture resulted in a higher copper leaching rate than the pure culture of Acidithiobacillus ferrivorans strain YL15. High-throughput sequencing technology showed that Acidithiobacillus spp. and Sulfobacillus spp. were the mixed culture's major lineages. Cyclic voltammograms, potentiodynamic polarization and electrochemical impedance spectroscopy unveiled that the mixed culture enhanced the dissolution reactions, decreased the corrosion potential and increased the corrosion current, and lowered the charge transfer resistance and passivation layer impedance of the chalcopyrite electrode compared with the pure culture. This study revealed the mechanisms via which the mixed culture promoted the chalcopyrite bioleaching.

Spliceosome-regulated RSRP1-dependent NF-κB activation promotes the glioblastoma mesenchymal phenotype.

BACKGROUND: The glioblastoma (GBM) mesenchymal (MES) phenotype, induced by NF-κB activation, is characterized by aggressive tumor progression and poor clinical outcomes. Our previous analysis indicated that MES GBM has a unique alternative splicing (AS) pattern; however, the underlying mechanism remains obscure. We aimed to reveal how splicing regulation contributes to MES phenotype promotion in GBM. METHODS: We screened novel candidate splicing factors that participate in NF-κB activation and MES phenotype promotion in GBM. In vitro and in vivo assays were used to explore the function of RSRP1 in MES GBM. RESULTS: Here, we identified that arginine/serine-rich protein 1 (RSRP1) promotes the MES phenotype by facilitating GBM cell invasion and apoptosis resistance. Proteomic, transcriptomic, and functional analyses confirmed that RSRP1 regulates AS in MES GBM through mediating spliceosome assembly. One RSRP1-regulated AS event resulted in skipping PARP6 exon 18 to form truncated, oncogenic PARP6-s. This isoform was unable to effectively suppress NF-κB. Cotreatment of cultured GBM cells and GBM tumor-bearing mice with spliceosome and NF-κB inhibitors exerted a synergistic effect on MES GBM growth. CONCLUSION: We identified a novel mechanism through which RSRP1-dependent splicing promotes the GBM MES phenotype. Targeting AS via RSRP1-related spliceosomal factors might constitute a promising treatment for GBM.

Endoscopic endonasal versus transcranial surgery for primary resection of craniopharyngiomas based on a new QST classification system: a comparative series of 315 patients.

OBJECTIVE: An assessment of the transcranial approach (TCA) and the endoscopic endonasal approach (EEA) for craniopharyngiomas (CPs) according to tumor types has not been reported. The aim of this study was to evaluate both surgical approaches for different types of CPs. METHODS: A retrospective review of primary resected CPs was performed. A QST classification system based on tumor origin was used to classify tumors into 3 types as follows: infrasellar/subdiaphragmatic CPs (Q-CPs), subarachnoidal CPs (S-CPs), and pars tuberalis CPs (T-CPs). Within each tumor type, patients were further arranged into two groups: those treated via the TCA and those treated via the EEA. Patient and tumor characteristics, surgical outcomes, and postoperative complications were obtained. All variables were statistically analyzed between surgical groups for each tumor type. RESULTS: A total of 315 patients were included in this series, of whom 87 were identified with Q-CPs (49 treated via TCA and 38 via EEA); 56 with S-CPs (36 treated via TCA and 20 via EEA); and 172 with T-CPs (105 treated via TCA and 67 via EEA). Patient and tumor characteristics were equivalent between both surgical groups in each tumor type. The overall gross-total resection rate (90.5% TCA vs 91.2% EEA, p = 0.85) and recurrence rate (8.9% TCA vs 6.4% EEA, p = 0.35) were similar between surgical groups. The EEA group had a greater chance of visual improvement (61.6% vs 35.8%, p = 0.01) and a decreased risk of visual deterioration (1.6% vs 11.0%, p < 0.001). Of the patients with T-CPs, postoperative hypothalamic status was better in the TCA group than in the EEA group (p = 0.016). Postoperative CSF leaks and nasal complication rates occurred more frequently in the EEA group (12.0% vs 0.5%, and 9.6% vs 0.5%; both p < 0.001). For Q-CPs, EEA was associated with an increased gross-total resection rate (97.4% vs 85.7%, p = 0.017), decreased recurrence rate (2.6% vs 12.2%, p = 0.001), and lower new hypopituitarism rate (28.9% vs 57.1%, p = 0.008). The recurrence-free survival in patients with Q-CPs was also significantly different between surgical groups (log-rank test, p = 0.037). The EEA required longer surgical time for T-CPs (p = 0.01). CONCLUSIONS: CPs could be effectively treated by radical surgery with favorable results. Both TCA and EEA have their advantages and limitations when used to manage different types of tumors. Individualized surgical strategies based on tumor growth patterns are mandatory to achieve optimal outcomes.

Intervention of Tyrosine Hydroxylase Expression Alters Joint Inflammation and Th17/Treg Imbalance in Collagen-Induced Arthritis.

BACKGROUND/AIMS: Neuroendocrine dysregulation has been associated with rheumatoid arthritis (RA). Tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of neuroendocrine hormones such as epinephrine, is also expressed in T lymphocytes and regulates balance between helper T (Th) 17 cells and regulatory T (Treg) cells. Herein, we aimed to show that TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in collagen-induced arthritis (CIA), an animal model of RA, and these effects may be implemented by the mechanism of epinephrine action on α1-adrenoreceptor (α1-AR) in T cells. METHODS: CIA was prepared by intradermal injection of collagen type II in tail base of DBA1/J mice. On the 33rd day post-immunization, lentiviral vectors encoding TH or TH shRNA were injected into ankle joints of CIA mice. Limb inflammation of the mice was assessed beginning from day 21 until day 69 post-immunization by measurement of limb swelling, erythema and rigidity. Th17 and Treg differentiation and function in ankle joints were assessed on day 69 post-immunization by test of the expression of Th17 transcriptional factor ROR-γt and the levels of proinflammatory cytokines interleukin (IL)-17 and IL-22 as well as the expression of Treg transcriptional factor Foxp3 and the levels of antiinflammatory cytokines transforming growth factor (TGF)-ß1 and IL-10. T cells were obtained from the spleen of mice that had been immunized with collagen type II 41 day earlier and treated with epinephrine or α1-AR agonist phenylephrine in vitro. Flow cytometry was used to analyze the percentages of CD25-IL-17+ cells and CD25+Foxp3+ cells in CD4+ T cells. RESULTS: TH gene overexpression in ankle joints of CIA mice reduced limb inflammation and Th17-related transcription factor expression and inflammatory cytokine production but increased Treg-related antiinflammatory cytokine production in the joints. In contrast, TH gene silence in ankle joints of CIA mice enhanced limb inflammation and Th17 cell activity but decreased Treg cell function in the joints. Epinephrine upregulated α1-AR expression in T cells derived from CIA mice. Both epinephrine and phenylephrine reduced CIA-induced Th17 transcription factor expression and inflammatory cytokine production but enhanced Treg antiinflammatory cytokine production in vitro. CONCLUSION: Upregulating TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in CIA at least partially by enhancing epinephrine action on α1-AR in T cells.

Correction to: A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma.

In the original publication, there are errors in Fig. 3D and Fig. 5C and are corrected as follows.

Psychoneuroimmunology goes East: Development of the PNIRSChina affiliate and its expansion into PNIRSAsia-Pacific.

The Psychoneuroimmunology Research Society (PNIRS) created an official Chinese regional affiliate in 2012, designated PNIRSChina. Now, just eight years later, the program has been so successful in advancing the science of psychoneuroimmunology that it has expanded to the whole of Asia-Oceania. In 2017, PNIRSChina became PNIRSAsia-Pacific. Between 2012 and 2019, this outreach affiliate of PNIRS organized seven symposia at major scientific meetings in China as well as nine others in Taiwan, Japan, South Korea, Australia and New Zealand. This paper summarizes the remarkable growth of PNIRSAsia-Pacific. Here, regional experts who have been instrumental in organizing these PNIRSAsia-Pacific symposia briefly review and share their views about the past, present and future state of psychoneuroimmunology research in China, Taiwan, Australia and Japan. The newest initiative of PNIRSAsia-Pacific is connecting Asia-Pacific laboratories with those in Western countries through a simple web-based registration system. These efforts not only contribute to the efforts of PNIRS to serve a truly global scientific society but also to answer the imperative call of increasing diversity in our science.

TGF-ß1 Provides Neuroprotection via Inhibition of Microglial Activation in 3-Acetylpyridine-Induced Cerebellar Ataxia Model Rats.

Cerebellar ataxias (CAs) consist of a heterogeneous group of neurodegenerative diseases hallmarked by motor deficits and deterioration of the cerebellum and its associated circuitries. Neuroinflammatory responses are present in CA brain, but how neuroinflammation may contribute to CA pathogenesis remain unresolved. Here, we investigate whether transforming growth factor (TGF)-ß1, which possesses anti-inflammatory and neuroprotective properties, can ameliorate the microglia-mediated neuroinflammation and thereby alleviate neurodegeneration in CA. In the current study, we administered TGF-ß1 via the intracerebroventricle (ICV) in CA model rats, by intraperitoneal injection of 3-acetylpyridine (3-AP), to reveal the neuroprotective role of TGF-ß1. The TGF-ß1 administration after 3-AP injection ameliorated motor impairments and reduced the calbindin-positive neuron loss and apoptosis in the brain stem and cerebellum. Meanwhile, 3-AP induced microglial activation and inflammatory responses in vivo, which were determined by morphological alteration and an increase in expression of CD11b, enhancement of percentage of CD40 + and CD86 + microglial cells, upregulation of pro-inflammatory mediators, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, and a downregulation of neurotrophic factor, insulin-like growth factor (IGF)-1 in the brain stem and cerebellum. TGF-ß1 treatment significantly prevented all the changes caused by 3-AP. In addition, in vitro experiments, TGF-ß1 directly attenuated 3-AP-induced microglial activation and inflammatory responses in primary cultures. Purkinje cell exposure to supernatants of primary microglia that had been treated with TGF-ß1 reduced neuronal loss and apoptosis induced by 3-AP-treated microglial supernatants. Furthermore, the protective effect was similar to those treated with TNF-α-neutralizing antibody. These findings suggest that TGF-ß1 protects against neurodegeneration in 3-AP-induced CA rats via inhibiting microglial activation and at least partly TNF-α release.