Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.

ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg^-1·d^-1）， and indometacin group （10 mg·kg^-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Rheumatoid arthritis(RA)is a common systemic autoimmune disease.Chronic synovial inflammation,angiogene-sis,pannus formation,joint destruction of cartilage and bone are important pathological characteristics in RA.Semaphorins(Sema)is a kind of secreted and membrane-bound glycoprotein with nerve guiding effect.Recent studies have shown that Sema family members play an important role in the various pathological stages of RA.Therefore,this paper reviews and discusses the latest research progress on the involvement of Sema family members in different pathological links of RA,which can help to find new feasible targets for RA and provide new research ideas for the pathogenesis of RA.

Objective To explore the efficacy and safety of endoscopic retrograde appendicitis therapy (ERAT) for pediatric acute appendicitis. Methods Thirty-five pediatric patients with acute simple appendicitis admitted between June 2021 and November 2023 were selected as study subjects. Relevant perioperative data including clinical manifestations, diagnostic and therapeutic processes, as well as treatment and follow-up outcomes were collected. Results All 35 patients successfully underwent ERAT with an operation time ranging from 24 to 75 min. Intubation of the appendiceal lumen was successful in all patients, with pus flushed out or stones removed. After contrast administration and flushing, 16 patients were found to have pus only in the appendiceal lumen with no appendicoliths, while 19 patients had both pus and visible appendicoliths with diameters ranging from 2 to 5 mm. Of 19 patients, 17 appendicoliths were loose and 2 were well-formed. Abdominal pain symptoms were alleviated within a short period, with the average VAS score decreasing from 6.6 preoperatively to 1.7 at 3 hours postoperatively and to 0.2 at 24 hours postoperatively. There was a statistically significant difference in Visual Analogue Scale(VAS) scores before and after surgery (P < 0.05). During follow-up ranging from 3 to 11 months postoperatively, appendicitis recurred in one patient one week after ERAT, while no surgery-related complications occurred in the other patients during follow-up. Conclusion ERAT is a safe and effective endoscopic treatment for pediatric acute appendicitis, with advantages including reduced trauma and shorter recovery time. It is particularly suitable for pediatric patients with acute simple appendicitis complicated by appendicoliths, appendiceal lumen stenosis, or intra-appendiceal abscesses.

Objective To investigate ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (F_ST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm² in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm², the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm² in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm², the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.

Objective:To evaluate the accuracy of an ultrasound-guided robot-assisted system for percutaneous facet joint puncture in an animal experiment by registration of ultrasound images and two-dimensional X-ray fluorescence images.Methods:Six specimens of fresh adult sheep lumbar spine were prepared and soaked in gelatin solution. The specimens contained a total of 48 facet joints with 24 ones respectively on the left and right sides. Half of the joints were assigned by the random number table method into a robot-assisted group which were subjected to percutaneous facet joint puncture assisted by the ultrasound-guided robot-assisted system while the contralateral ones into a freehand group which were subjected to percutaneous facet joint puncture by freehand. In the robot-assisted group, the left facet joints were 3 L 1, 3 L 2, 3 L 3 and 3 L 4 ones while the right facet joints were 2 L 1, 3 L 2, 5 L 3 and 2 L 4 ones. In this self-control animal experiment, both the robot-assisted punctures and the freehand punctures were carried out in the same specimen. The puncture success rate, puncture needle adjustment, positioning deviation, orientation deviation and operation time were recorded. Results:The positioning deviation and orientation deviation in the robot-assisted group [(2.21 ± 1.12) mm and 1.51° ± 0.47°] were significantly lower than those in the freehand group [(3.26 ± 1.44) mm and 2.24° ± 0.89°] ( P < 0.05). All the articular facet joint punctures were successfully accomplished for the first time in the robot-assisted group while those required multiple adjustments in the freehand group. In the robot-assisted group, the total operation time [(463.84 ± 34.93) s] was significantly longer than that in the freehand group [(298.40 ± 27.48) s], but the puncture time [(37.97 ± 6.87) s] was significantly shorter than that in the freehand group [(261.61 ± 33.15) s] ( P < 0.05). Conclusion:The ultrasound-guided robot-assisted system for percutaneous facet joint puncture can lead to accurate puncture with limited needle adjustments.

【Objective】 To explore the surgical characteristics and clinical efficacy of percutaneous endoscopic visualization trephine for thoracic spinal stenosis. 【Methods】 We made a retrospective analysis of 37 patients with single-segment thoracic spinal stenosis treated with percutaneous endoscopic visualization trephine from January 2019 to June 2020. Among them， there were 14 males and 23 females； their age ranged from 31 to 82 years old， with an average of （57.6±11.8） years old. Their posture， length of hospital stay， length of operation and blood loss were recorded. The visual analogue scale （VAS）， Oswestry disability index （ODI） and the modified Japanese Orthopaedic Association （JOA） score were used to evaluate the preoperative and final conditions of patients and calculate the improvement rate. 【Results】 The operation was successfully completed in all the patients， and no patients developed epidural hematoma， incision infection or postoperative paralysis. Among the 37 patients， 24 ones with ossification of ligamentum flavum （OLF） were in the prone position， and 13 patients had lateral surgery. Among them， thoracic disc herniation （TDH） occurred in 3 cases， OPLL in 5 cases and OLF+OPLL in 5 cases. The hospital stay was （7.2±1.6） days， the operation time was （96.5±20.0） min， and the blood loss was （41.9±10.8） mL. VAS score decreased from （7.0±0.9） to （1.9±0.8）； ODI improved from （41.7±2.1） to （16.1±1.7）； and JOA score increased from （5.8±1.4） to （8.6±1.4）. The preoperative and postoperative differences were statistically significant （P<0.05）. 【Conclusion】 Percutaneous endoscopic visualization of thoracic spinal stenosis is treated by choosing different positions according to the type of compression. The spinal canal is fully decompressed. The surgical method is safe and minimally invasive， and the postoperative effect is satisfactory.

Background: The systemic immune inflammation index (SII) is a reproducible biomarker of inflammatory process. Aims: To explore the predictive value of SII for severe acute pancreatitis (SAP). Methods: A total of 406 patients with acute pancreatitis (AP) from Jan. 2013 to Dec. 2020 at Affiliated Hospital of Yangzhou University were collected, and were divided into SAP group and non SAP group. ROC curve was drawn to evaluate the value of SII, NLR, PLR, CAR for predicting SAP. Results: Compared with non‑SAP group, SII, NLR, PLR, CAR were significantly increased in SAP group (P<0.05). When the best cut‑off value was 1 705.83, AUC of SII for predicting SAP was 0.754, the sensitivity was 75.47%, and the specificity was 69.12%. AUC of SII for predicting SAP was higher than that of PLR, CAR (Z=2.647, P=0.007; Z= 2.616, P=0.008), while no significant difference was found between SII and NLR (P>0.05). And no significant difference in AUC was found between PLR and CAR (P>0.05). Conclusions: SII is a good new hematological index that can be used to predict the severity of AP, its predictive ability is similar to NLR, better than PLR and CAR.