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 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.

Objectives:To investigate the clinical efficacy of staged percutaneous endoscopic posterior decom-pression for treating multi-segment thoracic ossification of ligamentum flavum(mTOLF).Methods:The clinical data of 16 patients with mTOLF who were treated with staged percutaneous endoscopic posterior decompres-sion at our hospital between June 2021 and June 2023 were retrospectively analyzed,including 9 males and 7 females,aged 46-67(55.4±6.8)years old.The preoperative imaging examinations of the patients indicated multi-segment ossification of ligamentum flavum,including double segments in 14 cases and triple segments in 2 cases.The responsible segments were as follows:upper thoracic spine(T1-T4)in 4 cases,middle thoracic spine(T5-T9)in 6 cases,and lower thoracic spine(T10-T12)in 24 cases.Staged percutaneous endoscopic posterior decompression was performed for mTOLF,targeting only one responsible segment in each surgery.The operative time,blood loss,hospitalization days,and complications were recorded.The Oswestry disability index(ODI)and the modified Japanese Orthopaedic Association(mJOA)11-point scale scores were recorded preoperatively,on 3d postoperatively,and at the final follow-up,and the mJOA improvement rate at the final follow-up was calculated.Statistical analysis was performed to evaluate the clinical efficacy.The spinal canal area and the anterior-posterior spinal canal diameter were measured on CT images preoperatively,on 3d post-operatively,and at the final follow-up to evaluate the improvement of imaging findings.Results:All the 16 patients successfully completed the surgery,and no cerebrospinal fluid leakage or permanent lower limb paral-ysis occurred except for one dural tear during operation.The operative time was 80-205min(150.2±36.1min),blood loss was 30-70mL(50.3±12.4mL),hospitalization days were 9-15d(10.8±1.8d)and the follow-up time ranged from 9-20(14.3±3.2)months.The mJOA scores and ODIs before surgery,on 3d after surgery,and at the final follow-up were 5.7±1.3,7.1±1.3,8.5±1.4,and(41.4±1.8)％,(17.8±1.6)％,(15.6±1.3)％,respectively,which were both significantly improved on 3d postoperatively and at final follow-up compared with those val-ues before operation(P＜0.05).The mJOA recovery rate was 28.6％-100％[(56.1±19.3)％],and according to the mJOA evaluation criteria,the outcomes were classified as excellent in 3 cases,good in 9 cases,fair in 4 cases,and poor in no case,with an excellent and good rate of 75.0％.The spinal canal area and anterior-posterior diameter before surgery,on 3d after surgery,and at the final follow-up were 76.7±12.5mm2,159.9±22.1mm2,157.7±21.6mm2,and 7.4±0.5mm,15.5±0.9mm,15.3±0.9mm,respectively.Both the spinal canal area and anterior-posterior diameter on 3d postoperatively and at the final follow-up significantly increased com-pared to preoperative values(P＜0.05).Conclusions:Staged percutaneous endoscopic posterior decompression for treating mTOLF is safe and effective,and yields satisfactory clinical outcomes.

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.

Objectives:To investigate the clinical efficacy of staged percutaneous endoscopic posterior decom-pression for treating multi-segment thoracic ossification of ligamentum flavum(mTOLF).Methods:The clinical data of 16 patients with mTOLF who were treated with staged percutaneous endoscopic posterior decompres-sion at our hospital between June 2021 and June 2023 were retrospectively analyzed,including 9 males and 7 females,aged 46-67(55.4±6.8)years old.The preoperative imaging examinations of the patients indicated multi-segment ossification of ligamentum flavum,including double segments in 14 cases and triple segments in 2 cases.The responsible segments were as follows:upper thoracic spine(T1-T4)in 4 cases,middle thoracic spine(T5-T9)in 6 cases,and lower thoracic spine(T10-T12)in 24 cases.Staged percutaneous endoscopic posterior decompression was performed for mTOLF,targeting only one responsible segment in each surgery.The operative time,blood loss,hospitalization days,and complications were recorded.The Oswestry disability index(ODI)and the modified Japanese Orthopaedic Association(mJOA)11-point scale scores were recorded preoperatively,on 3d postoperatively,and at the final follow-up,and the mJOA improvement rate at the final follow-up was calculated.Statistical analysis was performed to evaluate the clinical efficacy.The spinal canal area and the anterior-posterior spinal canal diameter were measured on CT images preoperatively,on 3d post-operatively,and at the final follow-up to evaluate the improvement of imaging findings.Results:All the 16 patients successfully completed the surgery,and no cerebrospinal fluid leakage or permanent lower limb paral-ysis occurred except for one dural tear during operation.The operative time was 80-205min(150.2±36.1min),blood loss was 30-70mL(50.3±12.4mL),hospitalization days were 9-15d(10.8±1.8d)and the follow-up time ranged from 9-20(14.3±3.2)months.The mJOA scores and ODIs before surgery,on 3d after surgery,and at the final follow-up were 5.7±1.3,7.1±1.3,8.5±1.4,and(41.4±1.8)％,(17.8±1.6)％,(15.6±1.3)％,respectively,which were both significantly improved on 3d postoperatively and at final follow-up compared with those val-ues before operation(P＜0.05).The mJOA recovery rate was 28.6％-100％[(56.1±19.3)％],and according to the mJOA evaluation criteria,the outcomes were classified as excellent in 3 cases,good in 9 cases,fair in 4 cases,and poor in no case,with an excellent and good rate of 75.0％.The spinal canal area and anterior-posterior diameter before surgery,on 3d after surgery,and at the final follow-up were 76.7±12.5mm2,159.9±22.1mm2,157.7±21.6mm2,and 7.4±0.5mm,15.5±0.9mm,15.3±0.9mm,respectively.Both the spinal canal area and anterior-posterior diameter on 3d postoperatively and at the final follow-up significantly increased com-pared to preoperative values(P＜0.05).Conclusions:Staged percutaneous endoscopic posterior decompression for treating mTOLF is safe and effective,and yields satisfactory clinical outcomes.

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.

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.

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.

Objective:To investigate the effect of myopia on retinal vascular geometry in young subjects.Methods:A retrospective cross-sectional study. From June 2018 to December 2018, 235 participants (235 eyes) who took part in routine physical examination in Huadong Sanatorium were included. There were 94 males and 141 females; age was (34.89±6.15) years old; equivalent spherical refraction (SE) was (-3.78±3.25) D. 59 (25.11%, 59/235) were divided into high myopia group (SE≤-6.0 D), along with 131 (55.74%, 131/235) low to moderate myopia group (-0.5 D> SE>-6.0 D), and 45 (19.15%, 45/235) emmetropia group (0.5 D≥SE≥-0.5 D). Retinal vascular geometric measurements, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), fractal dimension arteriole (FDa), fractal dimension venule (FDv), curvature tortuosity arteriole (CTORTa), curvature tortuosity venule, branch angle arteriole (BAa), branch angle venule, branch coefficient arteriole and branching coefficient venule, were extracted by using a validated computer program. One-way analysis of variance and analysis of covariance were performed to compare the measurements across the high myopia, low to moderate myopia, and emmetropia groups. Linear regression analysis was used to explore the relationship between SE and retinal vascular geometric parameters.Results:The differences in CRAE ( F=65.11), CRVE ( F=61.52), FDa (F=14.26), FDv ( F=8.31), CTORTa ( F=5.07) and BAa (F=6.51) among eys of high myopia group, low to moderate myopia group and emmetropia group remained significant ( P<0.05) after adjusting for age, glycosylated hemoglobin, mean arterial pressure, body mass index, and intraocular pressure. CRAE and CRVE were linearly correlated with the SE ( P<0.05). FDa, FDv, cTORTa and BAa decreased with the decrease of SE in high myopia ( P<0.05). Conclusions:Myopia is associated with the change of the retinal vascular geometric characteristics. With the deepening of myopia, the change of retinal vascular geometric characteristics gradually worsens.