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 preventive effect of multidisciplinary collaborative evidence-based nursing on dysphagia in patients with orotracheal intubation in intensive care unit(ICU)after extubation.Methods A retrospective analysis was performed on 200 patients with orotracheal intubation in ICU who were admitted to Dongguan Traditional Chinese Medicine Hospital between January and December 2023.Of them,96 patients who were admitted to our hospital between January and May 2023 received routine nursing(routine group),104 patients who were admitted to our hospital between June and December 2023 received multidisciplinary collaborative evidence-based nursing(evidence-based group).The incidence of dysphagia after extubation,water swallowing test result,swallowing function measured with M.D.Anderson dysphagia inventory(MDADI),psychological state assessed by connor-davidson resilience scale(CD-RISC),quality of life assessed by swallowing quality-of-life questionnaire(SWAL-QOL),and the incidence of dysphagia complications(aspiration,aspiration pneumonia,and malnutrition)were compared between the two groups.Results The incidence of dysphagia after extubation and the water swallowing test class in the evidence-based group were lower than those in the routine group(both P<0.05).The total score of MDADI and CD-RISC scores in the evidence-based group were significantly higher than those in the routine group(P<0.05),while the SWAL-QOL scores were lower(P<0.05).The incidence of complications in the evidence-based group was significantly lower than that in the routine group(P<0.05).Conclusion Multidisciplinary collaborative evidence-based nursing can effectively reduce the incidence of dysphagia in patients with orotracheal intubation in ICU after extubation,improve swallowing function,psychological state and quality of life,and reduce the incidence of complications.

Objective To compare the safety and efficacy of flow diverter with adjunctive spring coils(FAC)and simple flow diverter(FD)in the treatment of large or giant intracranial aneurysms.Methods The clinical data of 48 patients with large or giant intracranial aneurysm(55 intracranial aneurysms in total),who were treated at the First Affiliated Hospital of Zhengzhou University of China from January 2018 to September 2023,were retrospectively analyzed.According to the treatment method,the patients were divided into pure FD group and FAC group.The aneurysm occlusion rate and the incidence of procedure-related complications were compared between the two groups.Univariate and multivariate logistic regression analyses were used to identify risk factors for procedure-related complications.Results A total of 55 intracranial aneurysms detected in the 48 patients were included in this study.The median maximum diameter of aneurysms was 20.25 mm(16.45,24.62 mm).Among them,12 aneurysms were treated with FD alone,and 43 aneurysms were treated with FAC.The median follow-up time was 6.63 months(5.88,8.07 months).Compared with pure FD group,in FAC group the occlusion rate of aneurysms was significantly higher(86.1％vs.50.0％,P=0.023),while there was no statistically significant difference in the incidence of procedure-related complications between the two groups(18.18％vs.16.67％,P=1.000).Multivariate logistic regression analysis showed that the use of more than one stent(OR=6.63,95％CI=1.10-39.88,P=0.039)and the difference between the distal parent artery diameter and the stent diameter(Dd)(OR=7.00,95％CI=1.4-35.7,P=0.019)were the independent risk factors for procedure-related complications.The area under the receiver operating characteristic curve(AUC)of the receiver operating characteristic curve(ROC)for distal parent artery Dd was 0.854(95％CI=0.746-0.963).Conclusion For the treatment of large or giant intracranial aneurysms,FAC is clinically safe and effective.The mid-term follow-up aneurysm occlusion rate of FAC is higher than that of simple FD treatment.The use of more than one stent and the distal parent artery Dd are the independent risk factors for procedure-related complications in the treatment of large or giant intracranial aneurysms with FD.

【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.

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.

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 create a novel chitosan antibacterial hemostatic sponge(NCAHS)and to evaluate its material and biological properties.Methods Chitosan,a polysaccharide,was used as the sponge substrate and different proportions of sodium tripolyphosphate(STPP),glycerol,and phenol sulfonyl ethylamine were added to prepare the sponges through the freeze-drying method.The whole-blood coagulation index(BCI)was used as the screening criterion to determine the optimal concentrations of chitosan and the other additives and the hemostatic sponges were prepared accordingly.Zein/calcium carbonate(Zein/CaCO3)composite microspheres loaded with ciprofloxacin hydrochloride were prepared and added to the hemostatic sponges to obtain NCAHS.Scanning electron microscope was used to observe the microscopic morphology and porosity of the NCAHS.The water absorption rate,in vitro antibacterial susceptibility rate against Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli),in vitro coagulation performance,and hemocompatibility of NCAHS were examined.The coagulation performance of NCAHS was evaluated by using rabbit liver injury and rabbit auricular artery hemorrhageear models and commercial hemostatic sponge(CHS)was used as a control.The in vivo biocompatibility,including such aspects as cytotoxicity,skin irritation in animals,and acute in vivo toxicity,of the NCAHS extracts was examined by using as a reference the national standards for biological evaluation of medical devices.Results The NCAHS prepared with 1.5%chitosan(W/V),0.01%STPP(W/V),0%glycerol(V/V),0.15%phenol-sulfonyl-ethylamine(V/V),Zein and CaCO3 at the mixing ratio of 5∶1(W/W),Zein at the final mass concentration of 2.5 g/L,and ethanol at the final concentration of 17.5%(V/V)were fine and homogeneous,possessing a honeycomb-like porous structure with a pore size of about 200 μm.The NCAHS thus prepared had the lowest BCI value.The water absorption([2362.16±201.15]%vs.[1102.56±91.79]%)and in vitro coagulation performance(31.338%vs.1.591%)of NCAHS were significantly better than those of CHS(P<0.01).Tests with the in vivo auricular artery hemorrhage model([36.00±13.42]s vs.[80.00±17.32]s)and rabbit liver bleeding model([30.00±0]s vs.[70.00±17.32]s)showed that the hemostasis time of NCAHS was significantly shorter than that of CHS(P<0.01).NCAHS had significant inhibitory ability against S.aureus and E.coli.In addition,NCAHS showed good in vitro and in vivo biocompatibility.Conclusion NCAHS is a composite sponge that shows excellent antimicrobial properties,hemostatic effect,and biocompatibility.Therefore,its extensive application in clinical settings is warranted.

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.