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 impact of recent rhythmic interventions on the depth of sedation during anesthesia induction in patients undergoing general anesthesia with remazolam toluene sulfonate.Methods Patients aged 18～65 years who underwent elective surgery under general anesthesia were selected and divided into a day group(7:00～19:00)and a night group(19:00～7:00 the following day)based on the start time of anesthesia induction.Each group comprised 70 patients,further subdivided into five equal dose groups of remazolam toluene sulfonate at 0.11,0.13,0.16,0.18,and 0.22 mg/kg,with 14 patients in each subgroup.The Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score and Bispectral Index(BIS)value were recorded 3 minutes post-administration,and the correlation coefficient between these two parameters was calculated.The induction dose and unit body weight dose of remazolam toluene sulfonate were documented when the MOAA/S score was≤1.Addition-ally,the induction dose of remazolam for both day and night groups as well as for patients of different genders was recorded.The half effective dose(ED50),95％effective dose(ED95),and 95％confidence interval(CI)for both the day and night groups were also calculated.Results When MOAA/S≤1,the induced dose of remazolam in the night group(12.34±3.51)mg was significantly lower than that in the day group(13.98±4.21)mg.Additionally,the dose per unit body weight of remazolam in the night group(0.20±0.049)mg/kg was also significantly lower than that in the day group(0.22±0.056)mg/kg.Statistically significant differences were observed in the ED50 and ED95 values of remazolam between the day and night groups(P<0.05).The correlation coefficient between BIS and MOAA/S was 0.902(95％CI:0.876～0.925)in the day group and 0.905(95％CI:0.879～0.929)in the night group,indicating a strong correlation between MOAA/S and BIS in both groups.However,there was no significant difference in the correlation coefficients between the two groups(P>0.05).The correlation coefficients between BIS and MOAA/S were 0.763(95％CI:0.726～0.799)in the daytime group and 0.777(95％CI:0.739～0.808)in the nighttime group.In a separate analysis,the correlation coefficients were 0.768(95％CI:0.723～0.804)for the day-time group and 0.771(95％CI:0.723～0.811)for the nighttime group.A strong correlation was observed between MOAA/S and BIS in both male and female patients during both day and night,with no significant difference in corre-lation coefficients between groups(P>0.05).However,BIS values were significantly lower in the nighttime group compared to the daytime group(P<0.05).Additionally,male patients required a higher total induced dose of rem-azolam than female patients during both day and night,with this difference being statistically significant(P<0.05).Furthermore,female patients exhibited a significant decrease in BIS values at night(P<0.05).Conclusions Recent studies have shown that circadian rhythm significantly influences anesthesia-induced sedation in patients undergoing general anesthesia with remazolam toluenesulfonate.Specifically,the sedation effect is more pronounced in nighttime procedures,and there is a notable gender difference,with female patients exhibiting better sedation outcomes during nighttime surgeries.

Objective To investigate the impact of recent rhythmic interventions on the depth of sedation during anesthesia induction in patients undergoing general anesthesia with remazolam toluene sulfonate.Methods Patients aged 18～65 years who underwent elective surgery under general anesthesia were selected and divided into a day group(7:00～19:00)and a night group(19:00～7:00 the following day)based on the start time of anesthesia induction.Each group comprised 70 patients,further subdivided into five equal dose groups of remazolam toluene sulfonate at 0.11,0.13,0.16,0.18,and 0.22 mg/kg,with 14 patients in each subgroup.The Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score and Bispectral Index(BIS)value were recorded 3 minutes post-administration,and the correlation coefficient between these two parameters was calculated.The induction dose and unit body weight dose of remazolam toluene sulfonate were documented when the MOAA/S score was≤1.Addition-ally,the induction dose of remazolam for both day and night groups as well as for patients of different genders was recorded.The half effective dose(ED50),95％effective dose(ED95),and 95％confidence interval(CI)for both the day and night groups were also calculated.Results When MOAA/S≤1,the induced dose of remazolam in the night group(12.34±3.51)mg was significantly lower than that in the day group(13.98±4.21)mg.Additionally,the dose per unit body weight of remazolam in the night group(0.20±0.049)mg/kg was also significantly lower than that in the day group(0.22±0.056)mg/kg.Statistically significant differences were observed in the ED50 and ED95 values of remazolam between the day and night groups(P<0.05).The correlation coefficient between BIS and MOAA/S was 0.902(95％CI:0.876～0.925)in the day group and 0.905(95％CI:0.879～0.929)in the night group,indicating a strong correlation between MOAA/S and BIS in both groups.However,there was no significant difference in the correlation coefficients between the two groups(P>0.05).The correlation coefficients between BIS and MOAA/S were 0.763(95％CI:0.726～0.799)in the daytime group and 0.777(95％CI:0.739～0.808)in the nighttime group.In a separate analysis,the correlation coefficients were 0.768(95％CI:0.723～0.804)for the day-time group and 0.771(95％CI:0.723～0.811)for the nighttime group.A strong correlation was observed between MOAA/S and BIS in both male and female patients during both day and night,with no significant difference in corre-lation coefficients between groups(P>0.05).However,BIS values were significantly lower in the nighttime group compared to the daytime group(P<0.05).Additionally,male patients required a higher total induced dose of rem-azolam than female patients during both day and night,with this difference being statistically significant(P<0.05).Furthermore,female patients exhibited a significant decrease in BIS values at night(P<0.05).Conclusions Recent studies have shown that circadian rhythm significantly influences anesthesia-induced sedation in patients undergoing general anesthesia with remazolam toluenesulfonate.Specifically,the sedation effect is more pronounced in nighttime procedures,and there is a notable gender difference,with female patients exhibiting better sedation outcomes during nighttime surgeries.

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 intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.