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 analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.

Objective:To analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.

【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.

AIM: To evaluate the safety and efficacy of ultrasonic cycloplasty(UCP)combined with anti-vascular endothelial growth factor(VEGF)+ panretinal photocoagulation(PRP)in the treatment of advanced neovascular glaucoma(NVG).METHODS: Retrospective study. A total of 45 patients(45 eyes)with advanced NVG who received surgery in our hospital from August 2020 to September 2022 were collected and divided into UCP+ anti-VEGF +PRP group(16 patients, 16 eyes), transscleral cyclophotocoagulation(TCP)+anti-VEGF+PRP group(20 patients, 20 eyes), UCP alone group(9 patients, 9 eyes). The intraocular pressure, pain scores, postoperative medication, effective rate, total success rate and the incidence of complications of the patients in the three groups were compared before surgery and at 1 d, 1 wk, 1 and 3 mo after surgery.RESULTS: There was no significant difference in preoperative intraocular pressure, pain scores and preoperative medication of patients in the three groups(all P>0.05). While there were statistical significance in the intraocular pressure and pain scores at 1 d, 1 wk, 1 and 3 mo after surgery(all P<0.01). The intraocular pressure of the UCP alone group(31.78±10.23 mmHg)was found to be higher than that of both the UCP+ anti-VEGF +PRP group(19.44±8.23 mmHg)and the TCP+ anti-VEGF +PRP group(20.80±10.27 mmHg)at 1 mo postoperatively(all P<0.017). The pain score of the TCP+ anti-VEGF +PRP group at 1 d and 1 wk postoperatively was higher than both the UCP+ anti-VEGF +PRP group and the UCP alone group(all P<0.017). The effective rates of UCP+ anti-VEGF +PRP group, TCP+ anti-VEGF +PRP group and UCP alone group were 81%(13/16), 75%(15/20)and 67%(6/9), respectively,(P=0.675), and the success rates were 69%(11/16), 50%(10/20), and 0(0/9), respectively(P=0.003). There was no significant difference in complications of patients in the three groups(P>0.05).CONCLUSION: UCP combined with anti-VEGF +PRP and TCP combined with anti-VEGF +PRP showed comparable efficacy in reducing intraocular pressure in advanced NVG. UCP combined with anti-VEGF+PRP was more effective in relieving pain and with no serious complications in advanced NVG. UCP alone can effectively control intraocular pressure and alleviate the pain of patients in the early postoperative period, but long-term control still requires anti-VEGF+PRP.

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 analyze the diversity and composition of the maternal gut microbiota and vaginal microbiota in late pregnancy,neonatal meconium microbiota and vernix caseosa microbiota,and analyze the similarities,differences and correlations.Methods·This is a prospective study.Maternal stool samples and vaginal swabs in late-pregnancy,and neonatal meconium samples were collected from 11 mother-infant pairs at Xinhua Hospital,Shanghai Jiao Tong University School of Medicine from August to November 2018;the vernix caseosa from three sites(forehead,axilla,and inguinal crease)and meconium samples were collected from 14 healthy newborns at International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine in December 2018.All births were vaginal deliveries.The 16S rRNA gene V3?V4 region sequencing was used.The diversity,composition and similarities/differences of the maternal gut microbiota,the vaginal microbiota,and the neonatal meconium microbiota from the 11 mother-infant pairs,as well as the neonatal vernix caseosa microbiota and the meconium microbiota from the 14 newborns were analyzed.Results·The number of operational taxonomic units(OTUs),ACE index,Chao1 index,and Shannon index of maternal gut microbiota were all higher than those of vaginal microbiota;the ACE indices and the Chao1 indices of the vernix caseosa microbiota at three sites were all higher than those of meconium microbiota(P<0.01).The β diversity varied among the maternal gut microbiota,vaginal microbiota,and neonatal meconium microbiota(P<0.01).The β diversity of neonatal vernix caseosa microbiota from three sites(forehead,axilla,and inguinal crease)was similar,but different from meconium microbiota(P<0.01).At the phylum level,the dominant bacteria were Firmicutes(52.76%)and Bacteroidetes(41.67%)in the maternal gut microbiota,Firmicutes(74.36%)and Actinobacteria(21.25%)in the maternal vaginal microbiota,and Firmicutes(84.22%)and Proteobacteria(8.80%)in the neonatal vernix caseosa microbiota.The dominant bacterium in the neonatal meconium was Proteobacteria in the two batches of samples(81.11%and 88.72%,respectively).At the genus level,the dominant bacteria were Bacteroides(35.42%)and Faecalibacterium(10.12%)in the maternal gut microbiota,Lactobacillus(69.10%)and Bifidobacterium(11.30%)in the vaginal microbiota,and Lactobacillus(79.81%)and Pseudomonas(3.23%)in the vernix caseosa microbiota.The dominant bacterium in the neonatal meconium was Escherichia in the two batches of samples(55.21%and 31.18%,respectively).Conclusion·The α diversity of maternal gut microbiota is higher than that of vaginal microbiota and neonatal meconium microbiota,and it is higher in neonatal vernix caseosa than that in meconium microbiota.The Firmicutes is the predominant phylum in the maternal late-pregnancy gut microbiota,vaginal microbiota,and neonatal vernix microbiota.Lactobacillus is the predominant genus in both maternal vaginal and neonatal vernix caseosa microbiota.Proteobacteria in phylum and Escherichia in genus are predominant in meconium microbiota.The microbiota composition is similar in vernix caseosa at different body sites,but there are differences between the vernix caseosa microbiota and meconium microbiota.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

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.