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The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The genus Sylvirana includes 12 species widely distributed in South China and Southeast Asia. The phylogenetic relationships and species diversity for Sylvirana and allied genera remain unresolved and controversial due to insufficient data and incomplete taxon sampling. Using a combined dataset of mitochondrial genes (16S and COI) and 101 nuclear genes obtained through the amplicon sequence capture approach, we generated the most comprehensive phylogenetic analysis for the genus Sylvirana to date, inferring diversity, phylogenetic relationships, and historical biogeography with unprecedented levels of taxon and geographic sampling. Our results conservatively reveal six undescribed species, mostly distributed in peninsular Indochina. Phylogenetic analyses strongly support the non-monophyly of Sylvirana with respect to Pterorana. Additionally, phylogenetic results place Sylvirana guentheri and Pelophylax lateralis into genus Humerana, supporting the inclusion of Hylarana latouchii, Papurana milleti, and Hylarana attigua within Pterorana + Sylvirana. The long-disputed species of Hylarana bannanica (previously Sylvirana) cluster with genus Papurana. Because the results of multiple non-monophyletic genera create taxonomic confusion, we suggest relegating all genera to subgenus rank of Hylarana. Sylvirana is a junior synonym of the Pterorana. Biogeographically, we trace the origin of Pterorana to Southeast Asia during the early Miocene, with subsequent dispersal thereafter. Our study shows that climatic changes may have profoundly influenced the diversification of Pterorana during the Miocene., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Radical laparoscopic gastrectomy is an important treatment modality for gastric cancer. Surgery requires general anesthesia, and patients are susceptible to the effects of anesthetic drugs and carbon dioxide insufflation during the procedure, leading to inflammation or severe pain, which can affect patient outcome., Aim: To explore the efficacy of combining dexmedetomidine (DEX) with nalbuphine in patients underwent laparoscopic radical gastrectomy for gastric cancer., Methods: Patients scheduled to undergo laparoscopic radical gastrectomy were selected and randomly assigned to A or B group. In A group, patients received an intravenous injection of nalbuphine 0.2 mg/kg + DEX 0.4 μg/kg 10 min before the end of surgery; in B group, patients received only an intravenous injection of nalbuphine. The trends in hemodynamic parameter fluctuations, awakening quality during the recovery period, serum inflammatory markers, agitation scores, cough severity, incidence, and duration of postoperative delirium (POD) were compared., Results: The mean arterial pressure and heart rate in the A group were more stable ( P < 0.05). The A group had a lower average awakening time, extubation time, and agitation scores during recovery than the B group. Agitation control in the A group was more effective at different time points ( P < 0.05). Patients in the A group had lower serum interleukin (IL)-6, tumour necrosis factor alpha, and IL-10 levels at 1 h after surgery than the B group. The incidence of coughing and duration of POD were lower and shorter in the A group than in the B group. Adverse reactions caused by the two anesthesia methods were less frequent in the A group than in the B group ( P < 0.05)., Conclusion: The use of DEX and nalbuphine in patients undergoing laparoscopic radical gastrectomy for gastric cancer help reducing the inflammatory response, cough severity, and agitation and helps maintain hemodynamic stability., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The influence of native secondary succession associated with anthropogenic disturbance on the biodiversity of the forests in subtropical China remains uncertain. In particular, the evolutionary response of small understory shrubs, particularly pioneer species inhabiting continuously disturbed habitats, to topographic heterogeneity and climate change is poorly understood. This study aimed to address this knowledge gap by focusing on the Gaultheria crenulata group, a clade of small pioneer shrubs in subtropical China., Results: We examined the genetic structure and demographic history of all five species of the G. crenulata group with two maternally inherited chloroplast DNA (cpDNA) fragments and two biparentally inherited low-copy nuclear genes (LCG) over 89 natural populations. We found that the genetic differentiation of this group was influenced by the geomorphological boundary between different regions of China in association with Quaternary climatic events. Despite low overall genetic diversity, we observed an isolation-by-distance (IBD) pattern at a regional scale, rather than isolation-by-environment (IBE), which was attributed to ongoing human disturbance in the region., Conclusion: Our findings suggest that the genetic structure of the G. crenulata group reflects the interplay of geological topography, historical climates, and anthropogenic disturbance during the Pliocene-Pleistocene-Holocene periods in subtropical China. The observed IBD pattern, particularly prominent in western China, highlights the role of limited dispersal and gene flow, possibly influenced by physical barriers or decreased connectivity over geographic distance. Furthermore, the east-to-west trend of gene flow, potentially facilitated by the East Asian monsoon system, underscores the complex interplay of biotic and abiotic factors shaping the genetic dynamics of pioneer species in subtropical China's secondary forests. These findings can be used to assess the impact of environmental changes on the adaptation and persistence of biodiversity in subtropical forest ecosystems., (© 2024. The Author(s).)

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value., Aim: To identify potential DNA methylation markers specific to ADE and CRC., Methods: Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape., Results: Comparing 22 CRC and 25 ADE samples, global methylation was higher in the former, but both showed similar methylation patterns regarding differentially methylated gene positions, chromatin signatures, and repeated elements. High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC. Combined with RNA-seq gene expression data, we identified 14 methylation-regulated differentially expressed genes, of which only AGTR1 and NECAB1 methylation had prognostic significance., Conclusion: Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC, suggesting prognostic biomarkers for CRC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study aimed to investigate whether brain anatomical structures and functional network connectivity are altered after chronic complete thoracic spinal cord injury (cctSCI) and to determine how these changes impact clinical outcomes. Structural and resting-state functional MRI was performed for 19 cctSCI patients (18 for final statistics) and 19 healthy controls. Voxel-based morphometry (VBM) was used to assess gray matter volume (GMV) with differences between cctSCI patients and controls. VBM results were used as seeds for whole-brain functional connectivity (FC) analysis. The relationship between brain changes and clinical variables was investigated. Compared with those of the control group, the left triangular inferior frontal gyrus, middle frontal gyrus, orbital inferior frontal gyrus, precuneus and parietal superior gyrus volumes of SCI patients decreased, while the left superior frontal gyrus and supplementary motor area volumes increased. Additionally, when the regions with increased GMV were used as seeds, the FC of the parahippocampus and thalamus increased. Subsequent partial correlation analysis showed a positive correlation between FC and total sensorimotor score based on the ASIA criteria (p = 0.001, r = 0.746). Overall, the structural and functional changes in the brain after cctSCI occurred in some visual and cognitive areas and sensory or motor control areas. These findings aid in improving our understanding of the underlying brain injury mechanisms and the subsequent structural and functional reorganization to reveal potential therapeutic targets and track treatment outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis. Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope. Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction. The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis, the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons, and the normal deep layers were collected from 20 adult cadavers. The penile fascia samples were stained with hematoxylin-eosin, Masson's trichrome, Sirius red, and Verhoeff's Van Gieson, and subjected to immunohistochemical examination and scanning electron microscopy. The penile shaft (mean ± standard deviation) was found to be significantly elongated after resecting the deep layer compared with that before resection (6.8 ± 1.9 cm vs 6.0 ± 1.6 cm, P < 0.001). An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8% (43/49) of buried penis samples, whereas no abnormal deep layer was observed in normal penises from cadavers (0/20, P < 0.001). Thus, the abnormal deep layer of dartos fascia plays an important role in the buried penis. Its resection is helpful for avoiding recurrence., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Sixteen patients with recurrent high-grade glioma who were treated by domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the Neurosurgery Department of Xuanwu Hospital of Capital Medical University from 1st January 2021 to 31st December 2021 were prospectively included, with 11 males and 5 females, and aged 27-74 (50±16) years. The duration of surgery, the rate of ablation after surgery, and perioperative complications were assessed. The patients were followed up every 3 months to assess survival and progression. A total of 5 WHO grade Ⅲ patients and 11 WHO grade Ⅳ patients were included. The operation time was 144 (109, 176) min, 28 targeted lesions were detected, and the ablation rate [ M ( Q 1 , Q 3 )] was 91.0% (87.4%, 93.3%). After surgery, 2 patients (2/16) had decreased limb muscle strength, and no perioperative death or other serious complications occurred. The median time to a complete response was 12 (5, 14) months in WHO Grade Ⅲ patients, and one died 12 months after surgery, while the median time to a complete response was 3 (1, 8) months in 11 WHO Grade Ⅳ patients, with a total of 8 deaths at the last follow-up. Therefore, domestic MRgLITT has certain efficacy and safety in the treatment of recurrent high-grade glioma, providing a new option for patients with recurrent glioma.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes., (© 2023 John Wiley & Sons Ltd.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Objectives: To integrate the glucose metabolism measured using [ 18 F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy., Methods: This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes., Results: The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38-161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02-50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13-101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90-73.80, p = 0.001) and 12.01 (95% CI 2.91-49.65, p = 0.001), respectively., Conclusion: Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery., Key Points: • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The rate and volume of lumbar spinal fusion (LSF) surgery performed for patients aged 75 years and older increased in recent years. The purposes of our study were to identify factors associated with postoperative dissatisfaction and evaluate the predictive value of comprehensive geriatric assessment (CGA) for dissatisfaction at 2 years after elective short-segment (one- or two- level) LSF in patients aged 75 and older., Methods: This was a retrospective study using a prospectively collected database of consecutive patients (aged 75 and older) who underwent elective short-segment transforaminal lumbar interbody fusion surgery for degenerative diseases from June 2018 to May 2020. Preoperative CGA consisting six domains was performed for each patient 1 day before the operative day. Univariate and multivariate analyses were performed to identify factors that predict for dissatisfaction with surgical treatment. The primary outcome was patient satisfaction with LSF surgery, as measured by the North American Spine Society (NASS) satisfaction scale. Secondary outcomes included postoperative complications, the length of stay, visual analog scale (VAS), and Oswestry Disability Index., Results: A total of 211 patients were available for a follow-up at 2 years and included in our final study cohort with a mean age of 80.0 years. A total of 175 patients (82.9%) were included in the satisfied group, and 36 patients (17.1%) were included in the not dissatisfied group. In the dissatisfied group, there was a higher incidence of postoperative complications (30.6% vs. 14.3%, p  = 0.024) and greater VAS scores for lower back (4.3 ± 1.9 vs. 1.3 ± 1.4, p  = 0.001) and leg (3.9 ± 2.1 vs. 0.9 ± 1.3, p  = 0.001). Multivariate regression analysis revealed that patients with greater CCI score [odd ratio (OR) 2.56, 95% CI, 1.12-5.76; p  = 0.030 for CCI 1 or 2 and OR 6.20, 95% CI, 1.20-28.69; p  = 0.024], and depression (OR 3.34, 95% CI, 1.26-9.20; p  = 0.016) were more likely to be dissatisfied compared with patients with the CCI score of 0 and without depression., Conclusions: Satisfaction after LSF in older patients (aged 75 and older) was similar to that of previously reported younger patients. Preoperative depression and higher CCI scores were independent risk factors for postoperative dissatisfaction two years after LSF surgery. These results help inform decision-making when considering LSF surgery for patients aged 75 and older., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Wang, Mu, Wang, Li, Kong, Cheng, Lu and Zhao.)

(1) Background: Accurate localization of the epileptogenic zone and understanding the related functional connectivity (FC) alterations are critical for the prediction of clinical prognosis in patients with temporal lobe epilepsy (TLE). We aim to localize the hypometabolic region in TLE patients, compare the differences in FC alterations based on hypometabolic region and structural lesion, respectively, and explore their relationships with clinical prognosis. (2) Methods: Thirty-two TLE patients and 26 controls were recruited. Patients underwent 18F-FDG PET/MR scan, surgical treatment, and a 2−3-year follow-up. Visual assessment and voxel-wise analyses were performed to identify hypometabolic regions. ROI-based FC analyses were performed. Relationships between clinical prognosis and FC values were performed by using Pearson correlation analyses and receiver operating characteristic (ROC) analysis. (3) Results: Hypometabolic regions in TLE patients were found in the ipsilateral hippocampus, parahippocampal gyrus, and temporal lobe (p < 0.001). Functional alterations based on hypometabolic regions showed a more extensive whole-brain FC reduction. FC values of these regions negatively correlated with epilepsy duration (p < 0.05), and the ROC curve of them showed significant accuracy in predicting postsurgical outcome. (4) Conclusions: In TLE patients, FC related with hypometabolic region obtained by PET/fMRI may provide value in the prediction of disease progression and seizure-free outcome.

Study Design: A retrospective study., Objective: To evaluate the different degeneration patterns of paraspinal muscles in degenerative lumbar diseases and their correlation with lumbar spine degeneration severity. The degeneration characteristics of different paraspinal muscles in degenerative lumbar diseases remain unclear., Methods: 78 patients diagnosed with single-level degenerative lumbar spondylolisthesis (DLS) and 76 patients with degenerative lumbar kyphosis (DLK) were included as DLS and DLK groups. Paraspinal muscle parameters of psoas major (PS), erector spinae (ES) and multifidus muscle (MF) were measured, including fatty infiltration (FI) and relative cross-sectional area (rCSA), namely the ratio of the paraspinal muscle CSA to the CSA of the vertebrae of the same segment. Sagittal parameters including lumbar lordosis (LL) and sagittal vertical axis (SVA) were measured. The paraspinal muscle parameters and ES/MF rCSA ratio were compared between the two groups. Paraspinal muscles parameters including rCSA and FI were also compared between each segments from L1 to L5 in both DLS and DLK groups. In order to determine the influence of sagittal spinal alignment on paraspinal muscle parameters, correlation analysis was conducted between the MF, ES, PS rCSA and FI and the LL in DLS and DLK group., Result: MF atrophy is more significant in DLS patients compared with DLK. Also, MF fatty infiltration in the lower lumbar spine of DLS patients was greater compared to DLK patients. DLK patients showed more significant atrophy of ES and heavier ES fatty infiltration. MF FI was significantly different between all adjacent segments in both DLS and DLK groups. In DLS group, ES FI was significantly different between L2/L3 to L3/L4 and L4/L5 to L5/S1, while in DLK group, the difference of ES FI between all adjacent segments was not significant, and ES FI was found negatively correlated with LL., Conclusions: Paraspinal muscles show different degeneration patterns in degenerative lumbar diseases. MF degeneration is segmental in both DLS and DLK patients, while ES degenerated diffusely in DLK patients and correlated with the severity of kyphosis. MF degeneration is more significant in the DLS group, while ES degeneration is more significant in DLK patients. MF is the stabilizer of the lumbar spine segments, while the ES tends to maintain the spinal sagittal balance., (© 2022. The Author(s).)

The objective of this study was to identify the decussating dentato-rubro-thalamic tract (d-DRTT) and its afferent and efferent connections in healthy humans using diffusion spectrum imaging (DSI) techniques. In the present study, the trajectory and lateralization of the d-DRTT was explored using data from subjects in the Massachusetts General Hospital-Human Connectome Project adult diffusion dataset. The afferent and efferent networks that compose the cerebello-thalamo-cerebral pathways were also reconstructed. Correlation analysis was performed to identify interrelationships between subdivisions of the cerebello-dentato-rubro-thalamic and thalamo-cerebral connections. The d-DRTT was visualized bilaterally in 28 subjects. According to a normalized quantitative anisotropy and lateralization index evaluation, the left and right d-DRTT were relatively symmetric. Afferent regions were found mainly in the posterior cerebellum, especially the entire lobule VII (crus I, II and VIIb). Efferent fibers mainly are projected to the contralateral frontal cortex, including the motor and nonmotor regions. Correlations between cerebello-thalamic connections and thalamo-cerebral connections were positive, including the lobule VIIa (crus I and II) to the medial prefrontal cortex (MPFC) and the dorsolateral prefrontal cortex and lobules VI, VIIb, VIII, and IX, to the MPFC and motor and premotor areas. These results provide DSI-based tratographic evidence showing segregated and parallel cerebellar outputs to cerebral regions. The posterior cerebellum may play an important role in supporting and handling cognitive activities through d-DRTT. Future studies will allow for a more comprehensive understanding of cerebello-cerebral connections., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the clinical effect of biofeedback and electrical stimulation therapy (BFES) combined with Sabale capsules (SC) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS)., Methods: A total of 140 outpatients meeting CP/CPPS diagnostic and research criteria in the Second Affiliated Hospital of Xi'an Jiaotong University were randomly divided into groups A (blank control), B (BFES intervention), C (SC intervention) and D (BFES+SC intervention), 35 cases in each group. The patients in group A were left untreated, while those in groups B, C and D received BFES, SC and BFES+SC, respectively, all for 12 weeks. Then the patients were followed up at 30 days after treatment and the urinary flow rate and NIH-CPSI scores were obtained and compared with the baseline., Results: In comparison with the baseline, the total NIH-CPSI scores after intervention were significantly decreased in groups B, (［27.30 ± 2.44］ vs ［19.43 ± 2.33］), C (［26.77 ± 2.54］ vs ［19.40 ± 2.75］) and D (［27.67 ± 3.69］ vs ［15.57 ± 1.94］) (all P < 0.05), and so were the individual item scores in pain or discomfort (［12.50 ± 1.94］ vs ［9.40 ± 2.01］, ［11.93 ± 1.64］ vs ［9.23 ± 1.96］, and ［12.33 ± 2.20］ vs ［7.50 ± 1.55］), urination symptoms (［6.07 ± 1.57］ vs ［3.83 ± 1.05］, ［5.97 ± 1.33］ vs ［3.77 ± 1.14］, and ［6.20 ± 1.88］ vs ［2.87 ± 0.94］), quality of life (QOL) (［8.73 ± 1.62］ vs ［6.20 ± 1.42］, ［8.87 ± 1.25］ vs ［6.40 ± 1.59］, and ［9.13 ± 1.70］ vs ［5.20 ± 1.40］) (all P < 0.05), while the maximum urinary flow rate (Qmax) was remarkably increased (［15.72 ± 2.38］ vs ［19.73 ± 2.85］, ［16.20 ± 2.44］ vs ［19.46 ± 2.48］, and ［15.83 ± 2.52］ vs ［22.49 ± 2.76］) (all P < 0.05), and so was the average urinary flow rate (Qavg) (［9. 282 ± 1.52］ vs ［11.27 ± 1.95］, ［8.97 ± 1.25］ vs ［11.16 ± 1.74］, and ［9.20 ± 1.36］ vs ［13.50 ± 2.30］) (all P < 0.05). The decrease in NIH-CPSI total and item scores and increase in Qmax and Qavg after treatment were more significant in group D than in B and C (P < 0.05), but showed no statistically significant difference between groups B and C (P > 0.05). Nor was any significant change observed in the above parameters in group A after treatment ( P > 0.05)., Conclusions: Biofeedback and electrical stimulation therapy combined with Sabale capsules can alleviate urination dysfunction, pelvic floor tension myalgia and other symptoms and significantly improve the QOL of CP/CPPS patients.

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Epilepsy is a common neurological disease that seriously affects the health of the human population. The treatment of epilepsy has always been an important direction in the field of neurosurgery. New epilepsy theories and surgical treatment techniques contribute new direction of epilepsy surgical treatment in the future. This article aims to review the therapeutic advances in the treatment of epilepsy, including project of the brain networks, epileptic networks, the construction of epilepsy brain networks, and to explore the new branch of epilepsy surgery (brain-networks oriented epilepsy surgery), thereby providing a new precision treatment method for epileptic patients.

Objective: To investigate the safety and efficacy of stereotactic-EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) with three-dimensional lesioning in the treatment of drug-resistant insular epilepsy. Methods: Seven patients with drug-resistant insular epilepsy who underwent SEEG-guided RF-TC with three-dimensional ablation at the Department of Neurosurgery of Xuanwu Hospital, Capital Medical University from February 2017 to June 2019 were retrospectively enrolled. Presurgical evaluation including semiology, EEG and imaging results suggested that the epileptogenic zone was located in the insular lobe. All patients underwent SEEG recording and three-dimensional RF-TC. Postoperative follow-up was conducted by outpatient visits or telephone, the clinical efficacy was evaluated based on Engel classification and the relevant complications were documented. Results: Seven patients were followed up at 18 months after surgery. Among them, 4 were seizure free (Engel ⅠA), 2 had nondisabling simple partial seizures (Engel ⅠB) and 1 achieved 75% decrease (Engel ⅢA) in seizure frequency. Postoperative complications occurred in 3 patients which included decreased sensation in the right lower extremity, decreased strength in the right upper extremity, glossolalia, decline in memory and comprehension. No permanent neurological dysfunction was detected. Conclusion: SEEG-guided RF-TC with three-dimensional lesioning is minimally invasive, safe and effective in the treatment of drug-resistant insular epilepsy and can serve as a complementary method for resection surgery.

Objective: To investigate the safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the treatment of drug-resistant epilepsy. Methods: Patients with drug-resistant epilepsy treated with a domestic MRgLITT system in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University from October 2020 to April 2021 were prospectively enrolled. The damage volume ratio was assessed immediately after surgery, and perioperative complications were recorded and followed up. The clinical safety and short-term efficacy were evaluated using the Engel classification. Results: A total of 22 patients were included, including 12 males and 10 females, aged from 3 to 45 years old [(24±13) years]. There were 5 cases of medial temporal lobe epilepsy (MTLE), 3 cases of hypothalamic hamartoma (HH), 7 cases of focal cortical dysplasia (FCD), and 7 cases of other types, respectively. The mean operation time and blood loss was (173±49) min and (3.7±1.6) ml. The postoperative length of hospital stay was (5.5±1.8) days, and the average damage volume ratio was 92.6%. Among them, only 2 patients (FCD of the parietal lobe) showed transient contralateral limb weakness, without any serious complications such as symptomatic intracranial hemorrhage and cerebral infarction. The follow-up time was 14 to 168 days. There were 13 Engel class Ⅰ cases (59.1%), 2 Engel class Ⅱ cases (9.1%), 2 Engel class Ⅲ cases (9.1%) and 5 Engel class Ⅳ cases (22.7%), respectively. Short-term incident-free rates were MTLE 5/5and FCD4/7, respectively. Conclusion: Domestic MRgLITT system is stable, reliable and safe in the treatment of drug-refractory epilepsy, and has better short-term efficacy in MTLE and FCD patients.

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases., (© 2021. The Author(s).)

Introduction: In this report, we aim to describe the design for the randomised controlled trial of Stereotactic electroencephalogram (EEG)-guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE., Methods and Analysis: STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is the cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes., Discussion: SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual field protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide higher levels of clinical evidence for the treatment of mTLE., Trial Registration: ClinicalTrials.gov NCT03941613 . Registered on May 8, 2019. The STARTS protocol has been registered on the US National Institutes of Health. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.

In China, stroke is a major cause of mortality, and long-term physical and cognitive impairment. To meet this challenge, the Ministry of Health China Stroke Prevention Project Committee (CSPPC) was established in April 2011. This committee actively promotes stroke prevention and control in China. With government financial support of 838.4 million CNY, 8.352 million people from 536 screening points in 31 provinces have received stroke screening and follow-up over the last seven years (2012-2018). In 2016, the CSPPC issued a plan to establish stroke centers. To shorten the pre-hospital period, the CSPPC established a stroke center network, stroke map, and stroke "Green Channel" to create three 1-h gold rescue circles, abbreviated as "1-1-1" (onset to call time <1 h; pre-hospital transfer time < 1 h, and door-to-needle time < 1 h). From 2017 to 2018, the median door-to-needle time dropped by 4.0% (95% confidence interval (CI), 1.4-9.4) from 50 min to 48 min, and the median onset-to-needle time dropped by 2.8% (95% CI, 0.4-5.2) from 180 min to 175 min. As of 31 December 2018, the CSPPC has established 380 stroke centers in mainland China. From 1 November 2018, the CSPPC has monitored the quality of stroke care in stroke center hospitals through the China Stroke Data Center Data Reporting Platform. The CSPPC Stroke program has led to a significant improvement in stroke care. This program needs to be further promoted nationwide.

Background: Conflicts in regarding the lateralization of the seizure onset for mesial temporal lobe epilepsy (MTLE) are frequently encountered during presurgical evaluation. As a more elaborate, quantified protocol, indices of diffusion spectrum imaging (DSI) might be sensitive to evaluate the seizure involvement. However, the accuracy was less revealed. Herein, we determined the lateralizing value of the DSI indices among MTLE patients., Methods: Eleven MTLE patients were enrolled together with 11 matched health contrasts. All the participants underwent a DSI scan and with reconstruction of the diffusion scalar, including quantitative anisotropy (QA), isotropic (ISO), and track density imaging (TDI) values. Statistics of these indices were applied to identify the differences between the healthy and ipsilateral sides, and those between the patients and the controls, with special attention to areas of the crura of fornix (FORX), the parahippocampal radiation of the cingulum (PHCR), the hippocampus (HP), parahippocampus (PHC), amygdala (AM) and entorhinal cortex (EC)., Results: Regarding lateralization, TDI of the FORX and the PHCR reached an AUC value of 0.95 and 0.93, respectively (P<0.05), and QA, ISO, TDI of the PHCR, as well as TDI of the FORX were statistically significant amongst the laterals of the patients (P<0.05). Also, the QA of the PHCR were statistically different in the patients' ipsilateral side relative to the contrasts (P<0.017). The diffusion level on different grey matter structures were significantly decreased including HP, AM and EC in GQI space (P<0.017)., Conclusions: The quantitative diffusion scalars of the DSI, especially TDI of the FORX and the PHCR, are sensitive indices to define the ipsilateral side for MTLE patients. For preliminary exploration, the use of quantitative DSI scalars may help to improve the seizure outcome by increasing the accuracy of localization and lateralization for MTLE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5719). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Purpose: There are few studies on the glucose metabolic characteristics of the extra-hypothalamic cortex in the hypothalamic hamartomas (HH). A comprehensive understanding of pathogenic progression of the disease is required from the perspective of cortical metabolism; therefore, we aimed to characterize metabolic characteristics of extra-hypothalamic in HH patients. Methods: We investigated the metabolic characteristics of 16 HH patients, all of whom underwent epilepsy evaluation at Xuan Wu Hospital between 2017 and 2019. The lateralization and cortical distribution pattern of hypometabolism was assessed and related to HH mass neuroanatomy on magnetic resonance imaging (MRI) as well as scalp-electroencephalogram (scalp-EEG) abnormalities. Furthermore, asymmetry measurements of region of interest (ROI) in the temporal cortex (hippocampal formation, amygdala, and lateral temporal neocortex) were quantitatively assessed based on the normalized average positron emission tomography (PET) voxel values. The surgery prognosis was assessed using the International League Against Epilepsy (ILAE) classification system. Results: The lateralization of hypometabolism in global visual ratings was consistent with the HH mass lateralization seen on MRI. Cortical hypometabolism showed three patterns depending whether the HH mass involved mammillary bodies, middle hypothalamus nucleus, or both. The three patterns were hypometabolism of the mesial temporal cortex with symptom of mesial temporal epilepsy (3/16, pattern I), lateral temporal, and extratemporal (frontal or parietal) cortex with symptom of neocortex temporal or frontal epilepsy (5/16, pattern II), and mesial and lateral temporal cortex and extratemporal (frontal or parietal) cortex with varied symptoms (8/16, pattern III), respectively. A significant difference in PET voxel values was found between bilateral hippocampal formation ( P = 0.001) and lateral temporal neocortex in the third group ( P = 0.005). We suggest that the hypometabolic characteristics of the extra-hypothalamic cortex in HH patients have three patterns. The final cortical hypometabolic pattern depends on the neuroanatomic location of the HH mass and was consistent with the main involved cortex of the interictal and ictal discharges. The third hypometabolic pattern with the most extensive cortical hypometabolism has a poorer prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Wei, Meng, An, Fan, Wang, Wang, Ren, Shan and Zhao.)

Background: Recent studies have shown the challenges involved in detecting small conflicting vessels (1.0-1.5 mm) on contrast-enhanced (CE) T1 images during stereoelectroencephalography (SEEG) planning. Improving the resolution of non-invasive approaches to identify these vessels is possible and important. We present a superior sagittal sinus mapping-based CE-magnetic resonance venography (CE-MRV) protocol calibrated by craniotomies., Method: Seven patients with epileptic symptoms who received craniotomy were enrolled. CE-MRV was acquired with a bolus mapping of the superior sagittal sinus. Together with the T1 image, 3D veins and the brain surface were visualized. The resolution of the CE-MRV was quantified by measuring the diameter of superficial drainages after exposure of the brain surface during craniotomy., Results: A total of 37 superficial drainages were exposed in the bone windows. CE-MRV visualized all these drainages. On average, one superficial drainage could be found in every 13.2 mm diameter of the bone window. The boundary resolution of the CE-MRV was 0.58-0.8 mm in vessel diameter, while drainages larger than 0.8 mm were visualized consistently., Conclusions: The resolution of the CE-MRV in the present study met the requirement for detection of small conflicting vessels during SEEG planning. The visualized venous landmarks could be used for visual guidance to the surgical zone. As a non-invasive approach, CE-MRV is practical to use in the clinical setting.

Objective: To investigate the relationship between microRNA-34b/c single nucleotide polymorphism (SNP) rs4938723 and the risk of male infertility., Methods: This case-control study included 553 males aged 19－40 (29.42 ± 5.09) years with idiopathic infertility, 153 with azoospermia and 400 with oligoasthenospermia, and another 332 normal fertile men aged 19－40 (28.5 4 ± 4.63) years as controls. We collected the clinical data and peripheral blood samples from the subjects, genotyped microRNA-34b/c rs4938723 by Sequenom MassARRAY, and analyzed the relationship between the genotypes of microRNA-34b/c rs4938723 and the risk of male infertility using the logistic regression model., Results: Statistically significant differences were observed between the infertility patients and normal controls in sperm concentration (［18.71 ± 15.19］ vs ［79.91 ± 43.96］ × 10⁶/ml, P < 0.01), the percentage of progressively motile sperm (［13.27 ± 24.52］% vs ［42.82 ± 8.86］%, P < 0.01) and the level of follicle stimulating hormone (［16.09 ± 17.37］ vs ［12.20 ± 4.73］ IU/L, P < 0.01). Compared with the TT genotype, the TC and CC genotypes showed no correlation with male infertility, nor did the genetic locus in the subgroup analysis., Conclusions: No correlation was found between microRNA-34b/c SNP rs4938723 and male infertility, which, however, needs to be further verified by larger-sized samples.

Objective: To investigate the mutation of the DPY19L2 gene in patients with globozoospermia., Methods: We collected the clinical data and peripheral blood from 2 patients with globozoospermia and screened for mutation of the DPY19L2 gene by PCR amplification and DNA sequencing technology., Results: The sperm from the 2 globozoospermia patients were round morphologically under the light microscope, with deeply stained nuclei but no acrosome. Electron microscopy showed the sperm with a large round head but no acrosomal structure, the nuclei enveloped by a single layer of membrane and the cytoplasm dispersed. PCR amplification revealed homozygous deletion of Exon 5, Exon6 and Exon15 in the DPY19L2 gene in both the patients., Conclusions: This study proved that the homozygous mutation of DPY19L2 could lead to globozoospermia, which has an important significance for researches on the molecular mechanisms and gene diagnosis of the disease as well as for clinicians in genetic counseling and treatment.

Objective: To investigate the diagnostic value of miRNA let-7a, high mobility group A2 (HMGA2) expression and serum miRNA let-7a level in pancreatic cancer., Methods: From January 2014 to January 2019, 60 patients with pancreatic cancer were collected for fresh pancreatic ductal adenocarcinoma tissue and normal pancreatic tissue adjacent to the cancer after the operation. Serum samples before and after operation were also collected, while 60 healthy people were enrolled as the control group. The expression of miRNA let-7a (qRT-PCR) and HMGA2 (qRT-PCR and Western blot) in cancer and adjacent normal tissues were measured. The serum level of miRNA let-7a was detected by qRT-PCR. The relationship between miRNA let-7a and HMGA2 expression and the clinicopathological features of pancreatic cancer was analyzed. The diagnostic value of serum miRNA let-7a pre-operation in patients with pancreatic cancer was also analyzed with ROC curve., Results: Compared with normal tissues adjacent to the cancer, the expression level of miRNA let-7a in pancreatic cancer tissues decreased ( t =20.291, P <0.01), and the expression of HMGA 2 mRNA increased ( t =46.681, P <0.01). The expression of HMGA2 protein in cancer tissues was higher than that in normal tissues adjacent to the cancer ( t =22.973, P <0.01). The serum level of miRNA let-7a in pancreatic cancer patients was significantly lower than that in healthy controls ( t =24.854, P <0.01). The relative level of serum miRNA let-7a at 1 week after surgery was significantly lower than that before surgery in pancreatic cancer patients ( t =6.885, P <0.01). There was a positive correlation between cancer tissue and serum miRNA let-7a expression 1 week after surgery ( r =0.411, P =0.000). The relative expression levels of miRNA let-7a and HMGA2 in pancreatic cancer tissues were significantly different in different TNM stages and lymph node metastasis ( P <0.05). The area under curve of pre-operation serum miRNA let-7a for the diagnosis of pancreatic cancer was 0.823 ( 95% confidence interval: 0.665-0.917); when the optimal cut-off value of miRNA let-7a was 0.614, the sensitivity was 82.3%, the specificity was 74.1%., Conclusion: The expression of HMGA2 may be involved in the invasion and metastasis of pancreatic cancer. The level of serum miRNA let-7a may provide a reference for the diagnosis and postoperative monitoring of pancreatic cancer., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Background: Introducing multiple different stereoelectroencephalography electrodes in a three-dimensional (3D) network to create a 3D-lesioning field or stereo-crossed radiofrequency thermocoagulation (scRF-TC) might create larger lesioning size; however, this has not been quantified to date. This study aimed to quantify the configurations essential for scRF-TC., Methods: By using polyacrylamide gel (PAG), we investigated the effect of electrode conformation (angled/parallel/multiple edges) and electrode distance of creating an electrode network. Volume, time, and temperature were analyzed quantitatively with magnetic resonance imaging, video analysis, and machine learning. A network of electrodes to the pathological left area 47 was created in a patient; the seizure outcome and coverage range were further observed., Results: After the compatibility test between the PAG and brain tissue, the sufficient distance of contacts (from different electrodes) for confluent lesioning was 7 mm with the PAG. Connection to the lesioning field could be achieved even with a different arrangement of electrodes. One contact could achieve at least six connections with different peripheral contacts. Coagulation with a network of electrodes can create more significant lesioning sizes, 1.81-2.12 times those of the classic approaches. The confluent lesioning field created by scRF-TC had a volume of 38.7 cm 3 ; the low metabolic area was adequately covered. The representative patient was free of seizures throughout the 12-month follow up., Conclusion: Lesioning with electrodes in a network manner is practical for adequate 3D coverage. A secondary craniotomy could be potentially prevented by combining both monitoring and a large volume of lesions., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time., Methods: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients)., Results: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively., Conclusion: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

5-HT 4 R, 5-HT 6 R, and 5-HT 7A R are three constitutively active G s -coupled 5-HT receptors that have key roles in brain development, learning, memory, cognition, and other physiological processes in the central nervous system. In addition to G s signaling cascade mediated by these three 5-HT receptors, the ERK1/2 signaling which is dependent on cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activation downstream of G s signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three G s -coupled 5-HT receptors in AD293 cells. We found that the phosphorylation and activation of ERK1/2 are ligand-induced, in contrast to the constitutively active G s signaling. This indicates that G s signaling alone is not sufficient for ERK1/2 activation in these three 5-HT receptors. In addition to G s , we found that β-arrestin and Fyn are essential for the activation of ERK1/2. Together, these results put forth a novel mechanism for ERK1/2 activation involving the cooperative action of G s , β-arrestin, and Fyn.

Objective: To investigate the association between the 5T site polymorphism of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the risk of congenital bilateral absence of the vas deferens (CBAVD)., Methods: This case-control study included 40 male patients with isolated CBAVD in the experimental group and 104 healthy men as controls. We used the Sanger sequencing method to encode the CFTR gene intron 9 (TG) m-n(T) and type the haplotypes, followed by a review and meta-analysis of the data obtained from the experiment and relevant literature from the PubMed, Web of science, Medline, CNKI and an exploration of the correlation between 5T mutation and the risk of CBAVD., Results: Sanger sequencing revealed 6 genotypes in the CBAVD patients, including TG11-5T, TG12-5T, TG13-5T, TG11-7T, TG12-7T and TG11-9T, and 7 in the healthy controls, which were TG11-5T, TG12-5T, TG10-7T, TG11-7T, TG12-7T, TG13-7T and TG11-9T. Compared with the controls, the CBAVD patients showed obviously increased rates of the TG12-5T haplotype (4.81% ［10/208］ vs 16.25% ［13/80］) and the TG13-5T haplotype (0% vs 7.5% ［6/80］), but no significant difference in the TG11-5T haplotype (1.92% ［4/208］ vs 2.50% ［2/80］). There was a statistically significant difference between the experimental and control groups in the TG12&#95;13-5T haplotype (OR = 7.40, 95% CI: 4.83－11.34, P < 0.01). The TG12&#95;13-5T haplotype was found to be highly correlated with CBAVD., Conclusions: The haplotype of TG12&#95;13-5T increases the risk of CBAVD in men, which has provided a theoretical basis for male reproduction.

Objective: In the detection of seizure onset zones, arterial spin labeling (ASL) can overcome the limitations of positron emission tomography (PET) with 18 F-fluorodeoxyglucose ( 18 F-FDG), which is invasive, expensive, and radioactive. PET/magnetic resonance (MR) systems have been introduced that allow simultaneous performance of ASL and PET, but comparisons of these techniques with stereoelectroencephalography (SEEG) and comparisons among the treatment outcomes of these techniques are still lacking. Here, we investigate the effectiveness of ASL compared with that of SEEG and their outcomes in localizing mesial temporal lobe epilepsy (MTLE) and assess the correlation between simultaneously acquired PET and ASL., Methods: Between October 2016 and August 2017, we retrospectively studied 12 patients diagnosed with pure unilateral MTLE. We extracted and quantitatively computed values for ASL and PET in the bilateral hippocampus. SEEG findings and outcome were considered the gold standard of lateralization. Finally, the bilateral asymmetry index (AI) was calculated to assess the correlation between PET and ASL., Results: Our results showed that hypoperfusion in the hippocampus detected using ASL matched the SEEG-defined epileptogenic zone in this series of patients. The mean normalized voxel value of ASL in the contralateral hippocampus was 0.97 ± 0.19, while in the ipsilateral hippocampus, it was 0.84 ± 0.14. Meanwhile, significantly decreased perfusion and metabolism were observed in these patients (Wilcoxon, p  < 0.05), with a significant positive correlation between the AI values derived from PET and ASL (Pearson's correlation, r  = 0.74, p  < 0.05)., Significance: In our SEEG- and outcome-defined patients with MTLE, ASL could provide significant information during presurgical evaluation, with the hypoperfusion detected with ASL reliably lateralizing MTLE. This non-invasive technique may be used as an alternative diagnostic tool for MTLE lateralization.

Background: The use of magnetic resonance imaging (MRI)-guided ablation methods, such as laser interstitial thermal therapy and MRI-guided radiofrequency thermocoagulation (RF-TC), poses a risk of mistreatment in patients with nonepileptic hypothalamic hamartoma (HH). Using stereoelectroencephalography (SEEG)-guided RF-TC could solve this problem; however, there are no reports on the efficacy of this technique. Thus, we examined the safety and efficacy of this method., Methods: This retrospective study was conducted in 9 consecutive patients with HH treated between August 2015 and July 2017. All patients underwent a single round of SEEG-guided RF-TC treatment after comprehensive assessment. Outcomes were assessed using Engel's classification system. Spearman's correlation and receiver operating characteristic curves were analyzed to identify potential factors predictive of seizure outcome after an average follow-up duration of 18.78 months., Results: A total of 20 SEEG electrodes were implanted in 9 patients with HH, and 73 lesions were created within the tumors. No obvious symptoms were observed during coagulation. Five patients (55.56%) achieved Engel's class I recovery, and the other 4 (44.44%) achieved Engel's class II recovery; weight gain was observed in 1 patient. Correlation analysis revealed a trend of better seizure outcomes for larger-sized tumors., Conclusions: The SEEG signal can guide ablation of HH. SEEG-guided RF-TC is a safe procedure that shows promising efficacy. Special attention to the tumor attachment and multiple rounds of RF-TC might help improve seizure-free rates in the future., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Various V 2 O 5 three-dimensional nanostructures are synthesized using a facile template-free hydrothermal method and evaluated for use as supercapacitor electrode materials. As a result, the yolk-shell structure assembled from ultrathin nanosheets shows the best electrochemical performance, with a specific capacitance of 704.17 F g -1 at 1.0 A g -1 and a high capacity retention of 89% over 4000 cycles at 3.0 A g -1 . In addition, a continuous three-dimensional porous coralline-shaped carbon is synthesized from osmanthus and has a large Brunauer-Emmett-Teller surface area of 2840.88 m 2 g -1 . Then, an asymmetric supercapacitor is developed using the as-prepared yolk-shell V 2 O 5 as a positive electrode and the osmanthus derived coralline-shaped carbon as a negative electrode. This exhibits an energy density of 29.49 W h kg -1 at a power density of 800 W kg -1 with a good cycling performance that retains 90.6% of its initial capacity after 2000 cycles at 3.0 A g -1 . Furthermore, two cells in series can easily brightly light up a light-emitting diode (3 V), further demonstrating the great potential of the prepared materials for high-performance supercapacitor devices.

Aims: To study three atypical glioneuronal tumours (GNTs), in order to shed light on the clinical and pathological features of this diverse tumour group., Methods and Results: Clinical and neuropathological data for each case were retrospectively reviewed. Case 1 involved a 17-year-old boy with left leg movement difficulty. A mass lesion in the basal ganglia was detected radiologically; histopathological features included neurocytic/perivascular rosettes and a pilocytic astrocytoma component. Case 2 involved a 33-year-old man with intractable epilepsy. His left parietal lobe contained a cyst-like mass, resembling dysembryoplastic neuroepithelial tumour and rosette-forming glioneuronal tumour of the fourth ventricle microscopically. Case 3 involved a 21-year-old woman with a mass lesion in the mesencephalic tegmentum extending to the third and fourth ventricles and the suprasellar region. The lesion contained perivascular/neurocytic rosettes and an oligodendroglioma-like component. None of the tumours expressed an isocitrate dehydrogenase I mutation of the R132H type or contained a 1p/19q deletion, a BRAF(V600E) mutation, or KIAA1549-BRAF fusion., Conclusions: We describe three GNTs with atypical histopathology and locations. Additional cases and molecular studies are needed to better understand the biological nature of GNTs and to refine their classification system., (© 2015 John Wiley & Sons Ltd.)

Background: The aim of this study is to explore the treatment and outcome of epileptogenic temporal lobe cavernous malformations (CMs)., Methods: We analyzed retrospectively the profiles of 52 patients diagnosed as temporal lobe CMs associated with epilepsy. Among the 52 cases, 11 underwent a direct resection of CM along with the adjacent zone of hemosiderin rim without electrocorticogram (ECoG) monitoring while the other 41 cases had operations under the guidance of ECoG. Forty-six patients were treated by lesionectomy + hemosiderin rim while the other six were treated by lesionectomy + hemosiderin rim along with extended epileptogenic zone resection. The locations of lesions, the duration of illness, the manifestation, the excision ranges and the outcomes of postoperative follow-up were analyzed, respectively., Results: All of the 52 patients were treated by microsurgery. There was no neurological deficit through the long-term follow-up. Outcomes of seizure control are as follows: 42 patients (80.8%) belong to Engel Class I, 5 patients (9.6%) belong to Engel Class II, 3 patients (5.8%) belong to Engel Class III and 2 patients (3.8%) belong to Engel Class IV., Conclusion: Patients with epilepsy caused by temporal CMs should be treated as early as possible. Resection of the lesion and the surrounding hemosiderin zone is necessary. Moreover, an extended excision of epileptogenic cortex or cerebral lobes is needed to achieve a better prognosis if the ECoG indicates the existence of an extra epilepsy onset origin outside the lesion itself.

This study investigated the effect of restricting nasal breathing during a series of 20-m shuttle runs. Ten male participants (mean age = 21.7 ± 2.4 years, height = 1.80 ± 0.62 m, mass = 79.2 ± 10.4 kg, sum of 4 skinfolds = 54.5 ± 7.8 mm) were required to either (a) dive on the ground and complete a rolling sequence (condition = GRD) or (b) complete the shuttles while staying on their feet and tagging the line with 1 foot, at the end of each 20-m segment (condition = STD). The shuttle runs were completed with and without a nose clip (no clip = nc; with a clip = clip) under 4 different trial conditions in a randomized order (GRDnc; GRDclip; STDnc; and STDclip), requiring the participants to return on 4 separate occasions separated by 5-7 days. Heart rate was recorded throughout each trial, and the rate of perceived exertion (RPE) was measured at the completion of each shuttle sequence. Pretrial and posttrial lactate and respiratory function measures were also recorded. The general linear model with repeated measures analysis indicated that there was a significant effect for Roll (GRD > STD) (p ≤ 0.05) but not for Clip (p > 0.05) on total time to completion in the trials. There was no significant interaction of the conditions (Roll × Clip) for RPE (p > 0.05). Similarly, there was no significant effect for blood lactate measured 3 minutes post the last shuttle for Roll (p > 0.05) and Clip (p > 0.05). There was a significant main effect on the HR across all 6 time points (i.e., pre, intervals 1-4 and 10 minutes post) (p ≤ 0.05) and for Roll (GRD > STD) (p ≤ 0.05), but not for Clip (p > 0.05). No significant effect of Roll or Clip was found for any of the recorded ventilation measures (p > 0.05). On the basis of these findings, the use of restricted nasal breathing, while performing a high-intensity shuttle sequence as a method of increasing the acute training effect on athletes, is questionable, so strength and conditioning coaches should carefully consider their rationale for using such a training strategy.

Background and Aims: Despite previous reports implying a role of β2-microglobulin (β2M) in the development of prostate cancer (PCa), the correlation of serum β2M with the clinicopathological features, therapy efficacy and prognosis of patients with PCa have not been fully clarified. The present study aims to investigate the serum levels of β2M in patients with PCa and explore the potential use of β2M as a tumor marker for diagnosis, treatment and prognosis of PCa., Methods: Serum β2M levels in 120 patients with PCa, 50 patients with benign prostate hyperplasia (BPH) and 85 healthy age-matched controls were measured by enzyme immunoassay. The correlation of serum β2M with the clinicopathological features, therapy efficacy and the prognosis of PCa were subsequently assessed., Results: Our results showed that: (i) PCa patients had significantly higher levels of β2M compared to those of patients with BPH or those of healthy controls. (ii) Serum β2M were markedly elevated in patients with high stage or grade PCa as compared to patients with low stage or grade PCa. (iii) We measured significantly higher levels of β2M in patients with metastasis as compared to patients lacking metastasis. (iv) During follow-up, serum β2M showed a marked decrease after successful therapy and a significant further increase in recurrent disease., Conclusions: Our results demonstrate that serum β2M is correlated closely with the clinical stage, Gleason grade, PSA, distant metastasis and therapy efficacy in patients with PCa. Serum β2M may be a useful biomarker for clinical diagnosis, follow-up and prognosis of PCa., (Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the prognostic factors influencing overall survival (OS) in patients with spontaneous rupture of hepatocellular carcinoma (HCC-SR)., Methods: The medical records of 44 patients with HCC-SR treated in our department from January 1, 2005 to April 1 2011 were retrospectively reviewed. The clinical and prognostic data of 19 HCC-SR patients who received curative hepatectomy were compared with data of 137 HCC patients with no SR who were managed by curative hepatectomy during the same period. Type of HCC-SR was defined according to previously established criteria. The clinicopathological data were evaluated for possible associations with OS of HCC-SR by univariate analysis with the Kaplan-Meier method followed by multivariate analysis with the Cox proportional hazard model., Results: While some clinical features differed between the HCC-SR patients and non-HCC-SR patients, the postoperative prognosis was comparable between the two groups: (1) The 1-, 2-, 3- and 5-year postoperative cumulative recurrence rates were 78.9% (15/19), 89.5% (17/19), 94.7% (18/19) and 94.7% (18/19) in the HCC-SR group but 43.1% (59/137), 54.0% (74/137), 59.1% (81/137) and 66.4% (91/137) in the non-HCC-SR group respectively, and the differences reached statistical significance (P = 0.006, 0.003, 0.002, and 0.014); (2) The 1-, 2-, 3- and 5-year postoperative disease-free survival rates were 10.5% (2/19), 5.3% (1/19), 5.3% (1/19) and 5.3% (1/19) in the HCC-SR group but 40.1% (55/137), 21.2% (29/137), 12.4% (17/137) and 4.4% (6/137) in the non-HCC-SR group respectively, and only the 1-year disease-free survival rate was significantly different (P = 0.032); (3) The 1-, 2-, 3- and 5-year postoperative OS rates were 42.1% (8/19), 10.5% (2/19), 5.3% (1/19) and 5.3% (1/19) in the HCC-SR group but 59.1% (81/137), 32.8% (45/137), 19.0% (26/137) and 6.6% (9/137) in the non-HCC-SR group, and none of the differences reached statistical significance (P = 1.972, 0.061, 0.200, 1.000). Multivariate analysis identified that severity of concomitant liver cirrhosis, levels of alpha fetoprotein (AFP), choice of treatment modality, and type of HCC-SR acted as factors influencing OS., Conclusions: Patients with HCC-SR receiving curative hepatectomy have higher postoperative recurrence rates than their non-HCC-SR counterparts, but the two groups have similar postoperative OS rates. OS is influenced by severity of concomitant liver cirrhosis, level of AFP, choice of treatment modality, and type of HCC-SR.

The infection and degree of cucumber aphis pests was studied by analyzing chlorophyllfluorescence spectrum in greenhouse. Based on the configuration of the spectrum, characteristic points were established, in which the intensity of waveband F632 was the first characteristic point between healthy and aphis pests leaves. The second characteristic point was K which was the change rate of spectral curve from waveband F512 to F632. The early warning could be executed on plants depending on these two points. The models of the infection and degrees of aphis pests were established for different wavebands by the least square support vector machine classification method (LSSVMR) radial basis function(RBF). The accuracy rate of classification and prediction of the models was compared by different peaks and valleys value in wavebands. The results indicated that the prediction accuracy of the model established by waveband F632 was the most perfect (96.34%).

The present paper is based on chlorophyll fluorescence spectrum analysis. The wavelength 685 nm was determined as the primary characteristic point for the analysis of healthy or disease and insect damaged leaf by spectrum configuration. Dimensionality reduction of the spectrum was achieved by combining simple intercorrelation bands selection and principal component analysis (PCA). The principal component factor was reduced from 10 to 5 while the spectrum information was kept reaching 99.999%. By comparing and analysing three modeling methods, namely the partial least square regression (PLSR), BP neural network (BP) and least square support vector machine regression (LSSVMR), regarding correlation coefficient of true value and predicted value as evaluation criterion, eventually, LSSVMR was confirmed as the appropriate method for modeling of greenhouse cucumber disease and insect damage chlorophyll fluorescence spectrum analysis.

Objective: To observe the effect of acupuncture of "Zusanli" (ST 36) on immune function in progressively exhausted swimming rats so as to reveal its mechanism underlying improvement of strenuous exercise., Methods: Thirty-two SD rats were randomly allocated into control group, strenuous exercise (model) group, acupuncture-Xuehai (SP 10) group, Acupuncture-Zusanli (ST 36) group (n = 8/group). The rats were forced to have a swimming in a water tank for 15-90 min in the first 8 days (once daily), then, a progressively exhausted load swimming 1 - 3 times everyday from day 9 to 13. Bilateral SP 10 and ST 36 were punctured with filiform needles and stimulated with uniform reinforcing and reducing manipulation, once daily, after termination of the swimming and for 13 days. Serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) contents were assayed by using enzyme linked immunosorbent assay. The rat's body weight and the spleen weight were weighted by using an electronic balance for calculating the spleen index (spleen weight /body weight x 100%) after killing the rat under deep anesthesia., Results: Compared with the model group, the time of swimming-induced exhaustion appearing at the first time from day 9 to day 13 in the SP 10 and ST 36 groups was apparently lengthened (P < 0.01). No significant difference was found between SP 10 and ST 36 groups in the time of swimming-induced exhaustion appearing at the first time of the forced swimming. Compared with the control group, the spleen index, serum IFN-gamma contents and IFN-gamma/IL-4 in the model group were decreased significantly (P < 0.01, P < 0.05). In comparison with the model group, the serum IL-4 contents in the SP 10 and ST 36 groups were decreased markedly (P < 0.05, P < 0.01), and serum IFN-gamma content and IFN-gamma/IL-4 in the ST 36 group were increased significantly (P < 0.05, P < 0.01). The IFN-gamma level was significantly higher in the ST 36 group than in the SP 10 group (P < 0.05). No significant differences were found between SP 10 and ST 36 groups in the spleen index, IL-4 and IFN-gamma/IL-4 (P > 0.05)., Conclusion: Acupuncture at "Zusanli" (ST 36) can lengthen the time of forced swimming-induced exhaustion, and upregulate serum IFN-gamma content and IFN-gamma/IL-4 in exhausted swimming rats, which may contribute to its effect in correcting Th1/Th2 imbalance after strenuous exercise. The effect of acupuncture of ST 36 is superior to that of acupuncture of SP 10.