Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping.

BACKGROUND: Cortical spreading depression (CSD) is an electrophysiological event underlying migraine aura. Traditional CSD models are invasive and often cause injuries. The aim of the study was to establish a minimally invasive optogenetic CSD model and identify the active networks after CSD using whole-brain activity mapping. METHODS: CSD was induced in mice by light illumination, and their periorbital thresholds and behaviours in the open field, elevated plus-maze and light-aversion were recorded. Using c-fos, we mapped the brain activity after CSD. The whole brain was imaged, reconstructed and analyzed using the Volumetric Imaging with Synchronized on-the-fly-scan and Readout technique. To ensure the accuracy of the results, the immunofluorescence staining method was used to verify the imaging results. RESULTS: The optogenetic CSD model showed significantly decreased periorbital thresholds, increased facial grooming and freezing behaviours and prominent light-aversion behaviours. Brain activity mapping revealed that the somatosensory, primary sensory, olfactory, basal ganglia and default mode networks were activated. However, the thalamus and trigeminal nucleus caudalis were not activated. CONCLUSIONS: Optogenetic CSD model could mimic the behaviours of headache and photophobia. Moreover, the optogenetic CSD could activate multiple sensory cortical regions without the thalamus or trigeminal nucleus caudalis to induce cortical pain.

Effects on neuromodulation, acupuncture, and aerobic exercises on migraine and tension-type headache outcomes: A systematic review and meta-analysis.

BACKGROUND: Headache disorders are common diseases that cause a social burden. This systematic review and meta-analysis aimed to evaluate the effects of various non-pharmacological treatments to address or prevent acute headaches, including neuromodulation, acupuncture, and aerobic exercises in patients with episodic migraine and tension-type headache (TTH). METHODS: We performed a systematic search of the electronic databases PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, WANFANG MEDICINE ONLINE, and Chinese Medical Journal database using Stata/SE 14.0 to obtain weighted mean differences (WMDs). The outcomes included monthly headache days, headache intensity, headache duration, days per month of acute medication use, and the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Of 872 identified articles, 27 were included in the meta-analysis. Neuromodulation was associated with reduced headache days (WMD: -1.274, 95% CI [-1.914, -0.634], P < .001), duration (WMD: -2.2, 95% CI [-3.32, -0.107], P < .001) and medication consumption (WMD: -1.808, 95% CI [-2.546, -1.071], P < .001) in cases of migraine. Acupuncture was associated with the alleviation of headache days (WMD: -0.677, 95% CI [-0.932, -0.422], P < .001) and intensity (WMD: -0.893, 95% CI [-1.573, -0.212], P = .01) in cases of migraine and acute medication use (WMD: -3.29, 95% CI [-4.86, -1.72], P < .001) in cases of TTH. Aerobic exercise was associated with reduced headache duration (WMD: -5.1, 95% CI [-8.97, -1.22], P = .01) in cases of TTH. The risk of bias for included articles was moderate. CONCLUSIONS: There is low- and moderate-quality evidence that neuromodulation, acupuncture, and aerobic exercises are associated with attenuated headache symptoms in patients with episodic migraine or TTH. However, high-quality studies are needed to draw more detailed conclusions.

The determinants of collateral circulation status in patients with chronic cerebral arterial circle occlusion: A STROBE Study.

The condition of collateral pathways is an important predictor of stroke prognoses; however the major determinants of collaterals are still unknown. The purpose of this study is to identify potentially determinants for collateral circulation status in patients with chronic occlusion of cerebral arterial circle. All patients with chronic occlusion of either unilateral internal carotid artery or middle cerebral artery M1 or M2 segment, diagnosed by digital subtraction angiography at the neurology department of the First Medical Centre of Chinese PLA General Hospital from January 2015 to December 2017, were retrospectively collected in our sample. After screening according to inclusion and exclusion criteria, the patients' relevant clinical data were collected and analyzed. Collateral circulations were assessed by 2 independent raters using the American society of interventional and therapeutic neuroradiology/society of interventional radiology flow-grading system. Baseline characteristics (n = 163): our sample consists of 116 (71.2%) male and 47 (28.8%) female patients with an average age of 57.5 ± 11.9 years. Cerebral collateral flow was poor in 59 (36.2%) patients. Our univariate analyses showed that poor collateral circulation was associated with lower high-density lipoproteins cholesterol (HDL), elevated homocysteine levels, aging and hyperlipidemia. A multivariate analysis identified HDL, homocysteine levels and ageing as major predictors for collateral circulation status. In the subgroup analysis, the HDL contributed to collateral angiogenesis internal carotid artery occlusion group. In the middle cerebral artery occlusion group, the homocysteine and ageing were related to the poor collateral status. Low HDL, high levels of homocysteine and ageing are identified as possible risk factors for a poor collateral vessel blood flow in patients with chronic anterior circulation occlusion.

Generation of induced pluripotent stem cell line (FMCPGHi001-A) from a 25-year-old Chinese Han healthy male donor.

Peripheral blood mononuclear cells (PBMC) were donated by a healthy 25-year-old Han Chinese man and reprogrammed with human transcription factors (Oct4, Sox2, Klf4, and c-Myc) using CytoTune™-iPS 2.0 Sendai Reprogramming Kit. The pluripotency was confirmed by pluripotency markers. The iPSC lines could be differentiated into three germ layers and be used as a control in drug development and studies on pathological mechanisms.

Prognostic Value of the Pretreatment Lung Immune Prognostic Index in Advanced Small Cell Lung Cancer Patients Treated With First-Line PD-1/PD-L1 Inhibitors Plus Chemotherapy.

BACKGROUND: Lung immune prognostic index (LIPI) refers to a biomarker combining derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). Its prognostic effect on advanced small cell lung cancer (SCLC) patients receiving programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors plus chemotherapy as first-line treatment remains unclear. Our research investigated the relationship between pretreatment LIPI and the prognosis of patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy. METHODS: Advanced SCLC patients receiving PD-1/PD-L1 inhibitors plus chemotherapy as first-line treatment from Jan 2015 to Oct 2020 were included. Based on the values of dNLR and LDH, the study population was divided into two groups: LIPI good and LIPI intermediate/poor. The Kaplan-Meier method was used to compute the median survival time and the log-rank test was used to compare the two groups. Univariate and multivariate analyses were used to examine the correlation between the pretreatment LIPI and clinical outcomes. RESULTS: One hundred patients were included in this study, of which, 64% were LIPI good (dNLR < 4.0 and LDH < 283 U/L), 11% were LIPI poor (dNLR ≥ 4.0 and LDH ≥ 283 U/L), and the remaining 25% were LIPI intermediate. The LIPI good group had better progression-free survival (PFS) (median: 8.4 vs 4.7 months, p = 0.02) and overall survival (OS) (median: 23.8 vs 13.3 months, p = 0.0006) than the LIPI intermediate/poor group. Multivariate analysis showed that pretreatment LIPI intermediate/poor was an independent risk factor for OS (HR: 2.34; 95%CI, 1.13, 4.86; p = 0.02). Subgroup analysis showed that pretreatment LIPI good was associated with better PFS and OS in males, extensive disease (ED), PD-1 inhibitor treatment, smokers, and liver metastasis (p < 0.05). CONCLUSIONS: Pretreatment LIPI could serve as a prognostic biomarker for advanced SCLC patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy.