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 investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Patients with Alzheimer′s disease (AD) often exhibit both cognitive and depressive symptoms, suggesting a strong connection between the two, potentially indicating shared pathological factors. This article reviews the common pathological factors underlying cognitive and depressive symptoms in AD, focusing on aspects such as genetic factors, neurodegeneration, hypothalamic pituitary adrenal axis (HPA) dysfunction, neurotrophic factor deficiency, enhanced neuroinflammation, gut microbiota imbalance, and neurotransmitter systems imbalance. Further research on these common pathological factors is of great significance for future AD treatment.

Patients with Alzheimer′s disease (AD) often exhibit both cognitive and depressive symptoms, suggesting a strong connection between the two, potentially indicating shared pathological factors. This article reviews the common pathological factors underlying cognitive and depressive symptoms in AD, focusing on aspects such as genetic factors, neurodegeneration, hypothalamic pituitary adrenal axis (HPA) dysfunction, neurotrophic factor deficiency, enhanced neuroinflammation, gut microbiota imbalance, and neurotransmitter systems imbalance. Further research on these common pathological factors is of great significance for future AD treatment.

【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.

Objective To establish transgenic mice model with over expression of neuritin in bone mar-row,for the further study on the function of neuritin protein in the treatment of peripheral neuropathy. Methods Two pairs of transgenic mice(loxp-stop-loxp-neuritin and lyz-Cre/+)were fed and propagated,the DNA from the mice tails extracted and the genotype of transgenic mice identified by PCR. The wild type mice with B6 were as-signed as the controls,and the immunofluorescence was used to detect the accuracy of the neuritinloxp/+ _lyz -Cre/+. Results The two trensgenetic homozygous mice had the ability to reproduce,and the hybrid offsprings were neuritinloxp/+_lyz-Cre/+,neuritinloxp/-_lyz-Cre/+,neuritinloxp/+_lyz-Cre/-,neuritinloxp/-_lyz-Cre/-. The re-sults were met with the Mendel′s law. The results of immunofluorescence showed that the expression of neuritin of neuritinloxp/+_lyz-Cre/+ mice in bone marrow was significantly higher than the wild type mice(P < 0.05). Con-clusion The PCR method is of high reliability for identification of sub pus genotype and the female neuritinloxp/+mice mating with the male lyz-Cre/+ ones is an effective way for obtaining the neuritinloxp/+_lyz-Cre/+ mice.

Objective To study and compare the efficacy of surgery and conservative treatments for patients with critical(30 to 50 ml) spontaneous deep supratentorial intracerebral hemorrhage. Methods The clinical data of 420 patients diagnosed as spontaneous deep supratentorial intracerebral hemorrhage in Affiliated Hospital of Yan'an and Central Hospital of Baoji from August 2011 to September 2016 in this study were retrospectively analyzed. All patients were divided into surgery group(210 cases) and conservative group(210 cases) according to the difference of treatment methods. Large trauma craniotomy was used by the operation group, external ventricular drainage as the standby in necessary. The treatment of conservative group mainly included reduction of intracranial pressure, blood pressure management, prevention of complications and other individualized treatment. The primary outcome was neurological functional status of patients at 6 months of discharging, and the secondary outcomes included the mortality at 1 month and 6 months of discharging, and complications. Continuous data were presented as (x)± s and were compared using the t test, while categorical data were presented as number and percentage and were compared using the χ2 test. Results No obvious difference on mRS score and NIHSS score occurred between two groups(All P>0.05). Stratified analysis, patients with midline shift >5 mm and with intraventricular hemorrhage were more likely to have a favorable outcome from surgery compared with conservative group(18.2％ vs.8.1％, X =4.099, P=0.043; 17.3％ vs.5.0％, χ2 =4.836, P=0.028). The mortality at 1 month days and 6 months in surgery group were significantly lower than that in conservative group(19.0％ vs.31.0％, X2 =7.937, P=0.005; 23.8％ vs.36.7％, X2=8.228, P=0.004). Meanwhile, the incidence of pulmonary infection and with long-term pipe in surgery group were significantly higher than those in conservative group(31.9％ vs.15.7％, X2 =15. 173, P=0.000; 28.6％ rs.19.5％ =4.706, P=0.030). Conclusion Surgery can reduce the 1 month and 6 months mortality in patients with spontaneous deep supratentorial hemorrhage and improve the functional outcomes in patients with large midline shift or with intraventricular hemorrhage compared with conservative treatment.

Objective To investigate the effects of α-linolenic acid (ALA) on acute inflammation and neurological functional recovery of mice with traumatic brain injury (TBI). Methods The C57BL6/N mice were divided into high ALA dietary group (20 pregnant and 88 new-born mice) and low ALA dietary group (20 pregnant and 84 new-born mice) in this study. The contents of polyunsaturated fatty acids in the brain of the two groups were detected by gas chromatography. Mouse TBI model was established by control cortical impact method. The expression levels of inflammatory cytokines and cellular markers of the two groups were detected by reverse transcription-quantitative polymerase chain reaction and enzyme linked immunosorbent assay or Western Blotting at 0, 4, 24 and 96 h after TBI, respectively. The neurological functions were analyzed by the rotarod, beam walk test and fear conditioning experiment. Results The content of brain docosahexoenoic acid (DHA) was significantly higher in the high ALA dietary group than in the low ALA dietary group (15.48±1.20% vs 9.98±1.10%, P<0.05). The expression levels of TNF-α, IL-1β , IL-6 and CCL12 were lower in high ALA groups than in low ALA group after TBI (P<0.05). The motor function recovery 24 h after TBI was faster in the high ALA dietary group than in the lower ALA diet group. The cognitive function 24 h after TBI was better in the high ALA dietary group than in the low ALA group. Conclusion Increasing DHA levels in the brain can reduce acute inflammation and improve neurological function recovery after TBI.

Objective To study the relationship between intrauterine infection and early neonatal sepsis.Method From October 2015 to September 2016,the clinical data of pregnant mothers and their newborns in Shenzhen Longhua District Central Hospital were collected,and data of Shenzhen People's Hospital from January 2016 to June 2016 were collected.100 pairs of pregnant mothers and their newborns with confirmed or suspected intrauterine infection were selected as the observation group,and another 100 pairs without intrauterine infection during the same period as the control group.The ratio of term infants vs.premature infants was 1∶ 1.The complete blood count (CBC),CD64,procalcitonin (PCT) and C-reactive protein (CRP) were measured in peripheral blood of all mothers on the day of delivery.The CBC,CD64,CRP,PCT,blood culture of both umbilical venous blood and peripheral blood in neonates were examined and the pathological examination of placenta was performed.Result The positive rate of placental pathology and umbilical cord blood culture in observation group were significantly higher than that in the control and the positive rate in preterms was higher than the terms in observation group (P ＜ 0.05).No significant differences existed between term and premature newborns on the positive rate of peripheral blood culture (P ＞ 0.05).The positive rate of blood culture from umbilical cord blood was higher than peripheral blood in observation group (P ＜ 0.05),but no significant difference in control group (P ＞ 0.05).The incidence of septicemia in term and premature newborns in observation group was significantly higher than the control group (P＜ 0.05).The CD64,PCT in mother's peripheral blood and umbilical cord blood,and CRP in mother's blood were all higher than the control group,the differences were statistically significant (P ＜ 0.05),but CRP in umbilical cord blood in both group were similar (P ＞ 0.05).The area under ROC curve of CD64 and PCT in mother's peripheral blood,CD64 and PCT in umbilical cord blood to diagnose early-onset septicemia in newborns was 0.755,0.793,0.852 and 0.811,respectively.Conclusion The risk of neonatal infections is significantly increased because of intrauterine infection.Combination of peripheral and umbilical blood cultures can increase the accuracy of sepsis diagnosis.Both CD64 and PCT in umbilical cord blood and maternal blood can be used as indicators of intrauterine infection with a predictive value in the diagnosis of early-onset neonatal sepsis.

OBJECTIVE:To optimize the formulation of Budesonide sustained-release tablet. METHODS:Using the cumula-tive releases in 2,4,8 h as investigation indexes,central composite design-response surface method was used to optimize the amount of hydroxypropylcellulose L(HPC-L),amount of soybean phosphatides,and filler(fixed total 200 mg)lactose- micro-crystalline cellulose mass ratio in the formulation of Budesonide sustained-release tablet,and the verification test was conducted. The release behaviors of prepared sustained-release tablet and original preparation in pH 7.2,7.0,6.8 phosphate buffer were com-pared. RESULTS:The optimal formulation was as follow as budesonide of 9 mg,HPC-L of 46.49 mg,soybean phosphatides of 9.23 mg,filler lactose-microcrystalline cellulose mass ratio of 1:2.9;the cumulative releases in 2,4,8 h were 21.9%,50.1%, 99.5%,the relative errors with predicted values (22.0%,50.0%,98.5%) were 0.45%,0.20%,1.02%(n=3),respectively. Compared with cumulative release of original preparation,the f2 was higher than 50. CONCLUSIONS:Budesonide sustained-re-lease tablet is successfully prepared,which shows similar release behavior to original preparations.