Incidence and risk factors of post-stroke seizures and epilepsy: systematic review and meta-analysis.

OBJECTIVE: Due to variability in reports, the aim of this meta-analysis was to evaluate the incidence and risk factors of post-stroke early seizures (ES) and post-stroke epilepsy (PSE). METHODS: The MEDLINE, EMBASE and Web of Science databases were searched for post-stroke ES/PSE articles published on any date up to November 2020. Post-stroke ES included seizures occurring within 7 days of stroke, and PSE included at least one unprovoked seizure. Using random effects models, the incidence and risk factors of post-stroke ES and PSE were evaluated. The study was retrospectively registered with INPLASY (INPLASY2023100008). RESULTS: Of 128 included studies in total, the incidence of post-stroke ES was 0.07 (95% confidence interval [CI] 0.05, 0.10) and PSE was 0.10 (95% CI 0.08, 0.13). The rates were higher in children than adults. Risk factors for post-stroke ES included hemorrhagic stroke (odds ratio [OR] 2.14, 95% CI 1.44, 3.18), severe strokes (OR 2.68, 95% CI 1.73, 4.14), cortical involvement (OR 3.09, 95% CI 2.11, 4.51) and hemorrhagic transformation (OR 2.70, 95% CI 1.58, 4.60). Risk factors for PSE included severe strokes (OR 4.92, 95% CI 3.43, 7.06), cortical involvement (OR 3.20, 95% CI 2.13, 4.81), anterior circulation infarcts (OR 3.28, 95% CI 1.34, 8.03), hemorrhagic transformation (OR 2.81, 95% CI 1.25, 6.30) and post-stroke ES (OR 7.24, 95% CI 3.73, 14.06). CONCLUSION: Understanding the risk factors of post-stroke ES/PSE may identify high-risk individuals who might benefit from prophylactic treatment.

Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops.

The Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.

Enhancement of acid-sensing ion channel activity by prostaglandin E2 in rat dorsal root ganglion neurons.

Prostaglandin E2 (PGE2) and proton are typical inflammatory mediators. They play a major role in pain processing and hypersensitivity through activating their cognate receptors expressed in terminals of nociceptive sensory neurons. However, it remains unclear whether there is an interaction between PGE2 receptors and proton-activated acid-sensing ion channels (ASICs). Herein, we show that PGE2 enhanced the functional activity of ASICs in rat dorsal root ganglion (DRG) neurons through EP1 and EP4 receptors. In the present study, PGE2 concentration-dependently increased ASIC currents in DRG neurons. It shifted the proton concentration-response curve upwards, without change in the apparent affinity of proton for ASICs. Moreover, PGE2 enhancement of ASIC currents was partially blocked by EP1 or EP4 receptor antagonist. PGE2 failed to enhance ASIC currents when simultaneous blockade of both EP1 and EP4 receptors. PGE2 enhancement was partially suppressed after inhibition of intracellular PKC or PKA signaling, and completely disappeared after concurrent blockade of both PKC and PKA signaling. PGE2 increased significantly the expression levels of p-PKCε and p-PKA in DRG cells. PGE2 also enhanced proton-evoked action potentials in rat DRG neurons. Finally, peripherally administration of PGE2 dose-dependently exacerbated acid-induced nocifensive behaviors in rats through EP1 and EP4 receptors. Our results indicate that PGE2 enhanced the electrophysiological activity of ASICs in DRG neurons and contributed to acidosis-evoked pain, which revealed a novel peripheral mechanism underlying PGE2 involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.

TGF-ß1 enhances the activity of acid-sensing ion channel in rat primary sensory neurons.

Transforming growth factor-ß1 (TGF-ß1) is an important member of multifunctional growth factor superfamily. It has been implicated in pain signaling, but little is known about the underlying mechanisms. Herein, we report that TGF-ß1 can exert a sustained enhancing effect on the functional activity of acid-sensing ion channels (ASICs) in rat dorsal root ganglia (DRG) neurons. Pre-application of TGF-ß1 increased the amplitude of proton-gated currents in a dose-dependent manner. Enhancement of ASIC currents lasted for more than 30 min although TGF-ß1 was treated once only. This sustained enhancement by TGF-ß1 could be blocked by extracellular treatment of selective TGF-ß receptor I antagonist SD-208, and abolished by blockade of intracellular several non-Smad-signaling pathways. TGF-ß1 also sustainedly enhanced proton-evoked spikes in rat DRG neurons. Moreover, peripheral pre-treatment with TGF-ß1 dose-dependently exacerbated nociceptive behaviors evoked by intraplantar injection of acetic acid through TGF-ß receptor I in rats. These results suggested that TGF-ß1 potentiated ASIC-mediated electrophysiological activity and nociceptive behaviors, which revealed a novel mechanism underlying TGF-ß1 implicated in peripheral pain signaling by sensitizing ASICs.

PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons.

Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibits the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application of PPAR-α agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted the concentration-response curve for proton downwards, with a decrease of 36.9 ± 2.3% in the maximal current response to proton. GW7647 inhibition of proton-gated currents can be blocked by GW6471, a selective PPAR-α antagonist. Moreover, PPAR-α activation decreased the number of acidosis-evoked action potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose-dependently relieved nociceptive responses to injection of acetic acid in rats. These results indicated that activation of peripheral PPAR-α acutely inhibited functional activity of ASICs in a non-genomic manner, which revealed a novel mechanism underlying rapid analgesia through peripheral PPAR-α.

Second generation of familial nonmedullary thyroid carcinoma: A meta-analysis on the clinicopathologic features and prognosis.

Whether the second generation of parent/offspring type familial nonmedullary thyroid carcinoma (FNMTC) is more aggressive and has worse prognosis than their first generation counterpart is controversial. To evaluate the clinicopathologic features and prognosis of the second generation via a comparison between the two groups, We searched three databases (PubMed, EMBASE and the Cochrane library) to review studies published before November 25, 2016. All original studies comparing the clinicopathologic features and prognosis in the first generation of parent/offspring type FNMTC with its second generation counterpart were included. The Q-test and I2 test were used to evaluate homogeneity and funnel plot with Egger's test was used to evaluate publication bias. 6 studies, including 424 subjects were included. There was significant difference between the first and second generation of parent/offspring type FNMTC in the age of onset (SMD = -1.20, 95% CI: -2.38, -0.03, p = 0.045), gender distribution (OR = 0.48, 95% CI: 0.25, 0.90, p = 0.022) and lymph node metastasis (OR = 1.84, 95%CI: 1.16, 2.92, p = 0.01), while no significant difference in other variables. Thus we conclude that the second generation of parent/offspring type FNMTC patients is in higher risk than their first generation counterpart. We believe continuous study is needed to confirm the result.

Evaluating the effectiveness of prophylactic central neck dissection with total thyroidectomy for cN0 papillary thyroid carcinoma: An updated meta-analysis.

BACKGROUND: The effectiveness of prophylactic central neck dissection (pCND) following total thyroidectomy (TT) in patients with clinical node-negative (cN0) papillary thyroid carcinoma (PTC) is still controversial. The aim of this meta-analysis is to evaluate the outcome of pCND and to provide quantitative evidence. METHOD: A detailed literature search of PubMed, EMBASE, ClinicalTrails.gov and Cochrane Library electronic databases for articles published up to October 2016 was carried out. This meta-analysis was performed by the random method (Mantel-Haenszel) model. Locoregional recurrence (LRR) and surgical complications were analyzed. RESULTS: Twenty-two studies comparing pCND + TT (combined) and TT alone in cN0 PTC patients were analyzed. A total of 6930 cases were enrolled, including 2381 cases in the combined group and 4009 cases in the TT-alone group. Compared with TT alone, patients in the combined group showed a significantly lower rate of overall LRR (OR = 0.66, 95% CI = 0.48-0.89) and central compartment recurrence (OR = 0.40, 95% CI = 0.22-0.73). There was no statistical difference in the rate of lateral compartment recurrence. However, the combined group showed a significantly higher rate of temporary and permanent hypoparathyroidism (OR = 2.28, 95% CI = 1.92-2.27/OR = 1.84, 95% CI = 1.15-2.95) and temporary recurrent laryngeal nerve injury (LNR) (OR = 1.53, 95% CI = 1.08-2.16). There was no statistical difference in the rate of permanent LNR, hematoma, hemorrhage or wound infection. CONCLUSIONS: This meta-analysis revealed that pCND with TT was a significantly efficient way to reduce the risk of LRR. However, pCND + TT increased the incidence rate of temporary and permanent hypoparathyroidism and temporary LNR.

Sensitization of ASIC3 by proteinase-activated receptor 2 signaling contributes to acidosis-induced nociception.

BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception. METHODS: Electrophysiological experiments were performed on both rat DRG neurons and Chinese hamster ovary (CHO) cells expressing ASIC3 and PAR2. Nociceptive behavior was induced by acetic acid in rats. RESULTS: PAR2-AP, PAR2-activating peptide, concentration-dependently increased the ASIC3 currents in CHO cells transfected with ASIC3 and PAR2. The proton concentration-response relationship was not changed, but that the maximal response increased 58.7 ± 3.8% after pretreatment of PAR2-AP. PAR2 mediated the potentiation of ASIC3 currents via an intracellular cascade. PAR2-AP potentiation of ASIC3 currents disappeared after inhibition of intracellular G protein, PLC, PKC, or PKA signaling. Moreover, PAR2 activation increased proton-evoked currents and spikes mediated by ASIC3 in rat dorsal root ganglion neurons. Finally, peripheral administration of PAR2-AP dose-dependently exacerbated acidosis-induced nocifensive behaviors in rats. CONCLUSIONS: These results indicated that PAR2 signaling sensitized ASIC3, which may contribute to acidosis-induced nociception. These represent a novel peripheral mechanism underlying PAR2 involvement in hyperalgesia by sensitizing ASIC3 in primary sensory neurons.

Preoperative ultrasound-guided carbon nanoparticles localization for metastatic lymph nodes in papillary thyroid carcinoma during reoperation: A retrospective cohort study.

Due to the damaged anatomical structure and a large amount of fibrous and scar tissues in the surgical field, reoperation of papillary thyroid carcinoma is difficult. This study introduces a new method of locating metastatic lymph nodes during reoperation and evaluates the effectiveness and safety of the preoperative ultrasound-guided carbon nanoparticles (CNs) localization. This retrospective cohort study enrolled 52 patients who were diagnosed with lymph node metastasis by histopathology and underwent reoperation from October 2015 to February 2016. The modified radical neck dissection or selective neck node dissection was performed. A total of 26 patients underwent preoperative ultrasound-guided CNs injection, and other 26 patients did not. Tolerance, the result of injection, the number of resected metastatic lymph nodes, and postoperative complications were recorded and analyzed. In CNs group, 102 suspicious nonpalpable lesions in 26 patients were injected with CNs, and 99 of the 102 lesions were successfully identified by surgeon in the reoperation. The positive rate of resected lymph nodes in total, in the central compartment, and in the lateral compartment were 31.6%, 31.2%, and 32.8%, respectively, which was significantly higher than that in the control group (P < 0.001, P < 0.001, and P = 0.041). In addition, the positive rates of levels III, IV, and V in the CNs group were 35.6%, 21.9%, and 30.5%, respectively, which was significantly higher than that in the control group (P < 0.001, P = 0.005, and P = 0.01). In additional, in the CNs group, the rate of temporary hypoparathyroidism was significantly lower compared with the control group (0% vs 26.9%, P = 0.021). Preoperative ultrasound-guided CNs injection is a safe and effective method for localization of the metastatic lymph nodes during reoperation.

An overview of published benzene exposure data by industry in China, 1960-2003.

This article presents an overview of occupational benzene exposures in China based on data published in Chinese medical journals. The data were derived from 384 reports of benzene poisoning or industrial hygiene surveys published in Chinese medical journals between 1960 and 2003. The following information was extracted whenever available: industry, occupation, task, date, benzene levels, sampling location, workplace descriptions and, for case reports, medical diagnosis. Each paper provided one or more sets of benzene data, each set representing a sampling location or job title with one to several measurements including, mainly, breathing zone area concentration measurements, and much less frequently personal monitoring. Two criteria based on data quality were applied to select suitable data for analyses. The selected exposure data were analyzed by industry and time period. Nine hundred five sets of benzene measurements from 72 industries were reported in the 384 papers selected for this review, and 621 sets (68.6%) presented average benzene concentrations, which covered 55 industries. The distribution of the reported average benzene exposures was skewed with a median of 51.5 mg/m3. The average benzene concentrations were below 100 mg/m3 for 406 (65%) of the 621 reported average concentrations. The medians of the reported averages in mg/m3 for the five industries with the highest exposures were: 124.8 for leather products, 98.7 for electronic devices, 75.4 for machinery, 50.4 for shoes, and 50.3 for office supplies and sports equipment manufacturing. These data describe the concentrations and changing patterns of occupational benzene exposure by industry and time period in China.