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 anti-hepatocellular carcinoma mechanism of Chloranthus fortunei(A.Gray)Solms-Laub.via network pharmacology,molecular docking techniques and in vitro experiments.Methods Chemical composition of Chloranthus fortunei(A.Gray)Solms-Laub.was searched by literature.Swiss Target Prediction was used to find corresponding targets.STRING was used to construct protein-protein interactions network(PPI).DAVID was used to enrich GO analysis and KEGG pathway.AutoDock Vina 1.1.2 and Pymol visualisation was used for docking and validation.Results Chloranthus fortunei(A.Gray)Solms-Laub.had 61 active components,685 targets,and 279 intersections with disease targets.The PPI showed that the main active components were Luteolin,Chloranthalactone C,Shizukanolide H,Esculetin,7-Hydroxycoumarin.The key targets were GAPDH,VEGFA,STAT3,JUN,HSP90AA1,AKT1,CTNNB1,CASP3,and ALB.Biological process(BP)involved protein phosphorylation,signal transduction,regulation of RNA polymerase II promoter transcription,cell proliferation,apoptosis.Cellular component(CC)involved cytoplasm,nucleus,cell membrane,cellular exosome.Molecular function(MF)involves protein binding,ATPase,threonine kinase,protein kinase activity.KEGG involved cancer pathway,metabolic pathway,PI3K-Akt signalling pathway,cancer proteoglycans,lipids and atherosclerosis,cytomegalovirus infection,microRNAs in cancer,human T-cell leukaemia virus type 1,Ras signalling pathway,MAPK signalling pathway.Molecular docking showed that silverweed lactone H had a strong affinity for each of the other target proteins,indicating that this component plays a key role.The results of RT-qPCR assay and WB assay showed that there were significant differences in gene and protein expression levels before and after drug administration.Conclusion The Chinese medicine in Chloranthus fortunei(A.Gray)Solms-Laub.can treat hepatocellular carcinoma through the MAPK pathway,and the main active ingredients have good docking effects with the core target proteins of the disease.

Objective:To investigate the clinical efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with CHOP in the treatment of preliminarily diagnosed peripheral T-cell lymphoma(PTCL)and to analyze the factors influencing its prognosis.Methods:Clinical data were collected from patients who were preliminarily diagnosed with PTCL,but had not received radiotherapy or chemotherapy at the Affiliated Hospital of Nantong University between April 2012 and August 2022.The patients were divided into two groups,based on the frontline treatment regimen:the chidamide+CHOP group(n=20)and the CHOP group(n=24).The differences in clinicopathological characteristics between the two groups were compared by chi-square test or Fisher's exact test.Survival curves were generated by Kaplan-Meier method,and univariate survival analysis was conducted by Log-Rank test.Subgroup analysis was performed to assess the survival outcomes of patients in the chidamide+CHOP group,and interaction tests were conducted to assess the factors that might influence the difference in survival prognosis between the two groups.Results:The baseline levels of the two groups were comparable in age,gender,and tumor stage,but there were more AITL patients(70.8%vs 15%)and fewer PTCL-NOS patients(16.7%vs 30%)in the chidamide+CHOP group.Efficacy analysis revealed that the median PFS was significantly longer in patients treated with chidamide+CHOP(7 months vs 3 months,P=0.032),and their median OS was also significantly longer(20 months vs 6 months,P=0.004).Univariate prognostic analysis revealed that PTCL patients with B symptoms had significantly poorer PFS(P=0.053)and OS(P=0.065)than PTCL patients without B symptoms;and patients with elevated baseline LDH levels had a worse OS(P=0.056).Further subgroup analysis of efficacy revealed that,among patients with normal baseline serum ferritin levels,those in the chidamide+CHOP group had significantly better PFS compared with those in the CHOP group(95%CI[1.14,43.58]).The interaction test between serum ferritin levels and treatment regimens demonstrated statistical significance(P=0.042).Conclusion:The combination of chidamide and CHOP has survival benefits for patients preliminarily diagnosed with PTCL,and baseline serum ferritin levels may serve as a potential predictor for combination therapy.

Objective To investigate the anti-hepatocellular carcinoma mechanism of Chloranthus fortunei(A.Gray)Solms-Laub.via network pharmacology,molecular docking techniques and in vitro experiments.Methods Chemical composition of Chloranthus fortunei(A.Gray)Solms-Laub.was searched by literature.Swiss Target Prediction was used to find corresponding targets.STRING was used to construct protein-protein interactions network(PPI).DAVID was used to enrich GO analysis and KEGG pathway.AutoDock Vina 1.1.2 and Pymol visualisation was used for docking and validation.Results Chloranthus fortunei(A.Gray)Solms-Laub.had 61 active components,685 targets,and 279 intersections with disease targets.The PPI showed that the main active components were Luteolin,Chloranthalactone C,Shizukanolide H,Esculetin,7-Hydroxycoumarin.The key targets were GAPDH,VEGFA,STAT3,JUN,HSP90AA1,AKT1,CTNNB1,CASP3,and ALB.Biological process(BP)involved protein phosphorylation,signal transduction,regulation of RNA polymerase II promoter transcription,cell proliferation,apoptosis.Cellular component(CC)involved cytoplasm,nucleus,cell membrane,cellular exosome.Molecular function(MF)involves protein binding,ATPase,threonine kinase,protein kinase activity.KEGG involved cancer pathway,metabolic pathway,PI3K-Akt signalling pathway,cancer proteoglycans,lipids and atherosclerosis,cytomegalovirus infection,microRNAs in cancer,human T-cell leukaemia virus type 1,Ras signalling pathway,MAPK signalling pathway.Molecular docking showed that silverweed lactone H had a strong affinity for each of the other target proteins,indicating that this component plays a key role.The results of RT-qPCR assay and WB assay showed that there were significant differences in gene and protein expression levels before and after drug administration.Conclusion The Chinese medicine in Chloranthus fortunei(A.Gray)Solms-Laub.can treat hepatocellular carcinoma through the MAPK pathway,and the main active ingredients have good docking effects with the core target proteins of the disease.

Objective:To deepen the understanding of myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and to improve the levels of precise diagnosis and individualized treatment.Methods:The clinical data and next-generation sequencing molecular cloning results of two MDS/MPN-RS-T patients who were admitted to the First People's Hospital of Chuzhou in October 2017 and November 2019 were retrospectively analyzed, and the related literature was reviewed.Results:Case 1 was a 76-year-old female. The mutation loads from high to low were DNMT3A, JAK2 V617F and SF3B1. After administration of hydroxyurea, this patient acquired amelioration in anemia, and the platelet count improved. The clinical course was indolent. Case 2 was a 66-year-old male, who was initially diagnosed with essential thrombocythemia but failed to acquire response after hydroxyurea treatment. MDS/MP-RS-T was diagnosed after comprehensive examination. The mutation loads from high to low were SF3B1, ASXL1, JAK2 V617F and SRSF2. Pancytopenia occurred after disease progression, and the JAK2 V617F mutation finally turned negative. Administration of erythropoietin and lenalidomide failed to improve the condition, but low-dose decitabine treatment (10 mg/d, 3-5 d, once a month) improved the hematopoiesis.Conclusions:The co-mutation of JAK2 V617F and SF3B1 has a suggestive effect on the diagnosis of MDS/MPN-RS-T, and dynamic next-generation sequencing is helpful to elucidate the molecular nature of clinical heterogeneity of the disease. Low-dose decitabine has a certain curative effect on MDS/MPN-RS-T.

Objective:To explore whether CD5 + CD19 + B cells has the function of secreteing interleukin-10 (IL-10) in vitro, and to further investigate its possible effects and mechanisms on CD8 + cells in the process of hepatitis B virus (HBV) infection. Methods:From July 2017 to June 2018, at Wuxi Second People′s Hospital Affiliated to Nanjing Medical University, 23 patients with chronic hepatitis B (chronic hepatitis B group), 18 patients with liver cirrhosis (liver cirrhosis group) and 19 healthy individuals in the same period as healthy controls (healthy control group) were enrolled. Peripheral blood mononuclear cell (PBMC) were isolated and cultured. CD5 + CD19 + B cells were isolated. The cells were analyzed by flow cytometry. The ratio of high CD5 + CD19 + B cells content (>6 % of lymphocytes), the secretion of IL-10 by CD5 + CD19 + B and the ratio of high IL-10 + cells content (>4 % of lymphocytes) of three groups were compared. The effects and possible mechanisms of CD5 + CD19 + B cells on the secreting of interferon-γ (IFN-γ) by CD8 + cells were analyzed. Liver biopsy and immunohistochemistry examination were conducted in 18 patients (13 patients with chronic hepatitis B and 5 patients with liver cirrhosis) and the expression of CD5 + CD19 + B cells in human liver tissues was analyzed. Chi square test and Fisher exact probability test were used for statistical analysis. Results:The ratio of high CD5 + CD19 + B cells content of liver cirrhosis group was higher than that of healthy control group (8/18 vs. 2/19) and the difference was statistically significant (Fisher exact probability test, P=0.029). The precentage of CD5 + CD19 + B cells in healthy control group ( n=10), chronic hepatitis B group ( n=23) and liver cirrhosis group ( n=18) accounted for 81.6%, 82.3% and 70.1%of IL-10 + cells, respectively, and the number of patients with high IL-10 + cells precentage was 2, 7 and 2, respectively. There were no statistically significant differences among three groups (all P>0.05). After stimulated with lipopolysaccharide and cultured for 48 hours, the precentage of CD8 + IFN-γ + cells in lymphocytes of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10) were compared, and the differences were not statistically significant (all P>0.05). After CD5 + CD19 + B cells were eliminated, the precentage of CD8 + IFN-γ + cells in lymphocytes increased in 5, 4 and 4 patients of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10). After adding IL-10 receptor blocker, the precentage of CD8 + IFN-γ + cells in lymphocytes in PBMC increased compared with that before the addition of IL-10 receptor blocker (7.23% vs. 6.87%). The results of immunohistochemistry examination of liver biopsy indicated that CD4 + and CD8 + cells were strong expressed in portal area of liver tissue of patients, while CD5 + and CD19 + were less expressed. Conclusions:CD5 + CD19 + B cells do not show obvious quantitative and functional differences in the process of chronic HBV infection, however the ability of CD8 + cells to secrete IFN-γ, which may be achieved by secreting IL-10 rather than by direct contact between cells.

Objective To investigate the prevalence and correlation factors of cardiovascular damage in patients with diabetic nephropathy (DN) and non-diabetic nephropathy (NDN).Methods A total of 278 chronic kidney disease (CKD) patients admitted to the First Affiliated Hospital of Jinan University from January 2014 to May 2016 were enrolled,including 78 case of DN and 200 case of NDN.Patients had cardiac and carotid ultrasonography test by colour doppler ultrasonography,and their clinical and biochemical data were collected.Multiple linear regression analysis and multivariable logistic regression analysis were applied to study the correlation factors of cardiovascular damage in CKD patients.Results Mean age was 48.22 years in the 278-patient cohort,which included 178(64.03％) men.Compared with NDN group,DN patients had higher left atrial dimension,interventricular septal thickness,left ventricular end-diastolic dimension,left ventricular posterior wall thickness,left ventricular mass index (LVMI),carotid intima-media thickness (cIMT) and carotid plaques ratio.Their estimated glomerular filtration rate (eGFR) and the ratio between the peak speed of the early filling wave and that of the atrial contraction wave (E/A ratio) were however lower (all P ＜ 0.05).Prevalence of left ventricular hypertrophy (LVH),left ventricular relaxant function reduction and cIMT thickening in DN group were 67.95％,70.27％ and 57.14％,higher than those in NDN group (40.00％,42.31％ and 17.39％,respectively) (all P＜ 0.05).Along with the progress of CKD,LVMI and LVH proportion in patients with DN and NDN increased gradually.LVMI and LVH proportion in DN patients in CKD 1-2 phase and CKD 3-4 phase were higher than those in NDN patients (all P ＜ 0.05).In all CKD phases,cIMT and cIMT thickening proportion in DN group were higher than those in NDN group (all P ＜ 0.05).Just in CKD 1-2 phase,DN group had lower E/A ratio and higher proportion of left ventricular relaxant function reduction than NDN group (all P ＜ 0.05).After multiple linear regression analysis,gender,BMI,hemoglobin,eGFR and DN were related with LVMI;age,serum calcium and DN were related with E/A ratio;age and DN were related with cIMT (all P ＜ 0.05).In multivariate logistic regression,DN,hemoglobin and eGFR decrease were independently associated with LVH;age and BMI were independently associated with reduction of left ventricular relaxant function;age and DN were independently associated with cIMT thickening in all CKD patients (all P ＜ 0.05).Conclusions DN patients have more severe cardiovascular damage than NDN patients,and DN may be associated with LVMI,E/A ratio,cIMT,LVH and cIMT thickening in all CKD patients.

Objective To study effect of three time intervals heat preservation nursing on the core temperature of patients with ureteral calculi.Methods A total of 60 patients who receive holmium laser lithotripsy for kidney and ureteral calculi were divided into two groups.Experimental group received three time intervals heat preservation nursing care while control group received routine temperature preservation nursing care.Core temperature was recorded after induction, 30 min and 60 min after surgery and completion of surgery.Time to be awake, time of removing urine tube, length of hospital stay and shiver score were recorded.Results There was no significant difference in core temperature after 60 min of surgery and completion of surgery(P＜0.01).Time to be awake, time of removing urine tube, length to hospital stay in the experimental group were better than the control group(P＜0.01).Conclusion Multimode of three-process temperature preservation nursing can keep patients'stable temperature, and decrease the incidence of shiver, reduce length to stay and time to be awake, decrease occurrence of complication.

Objective To study effect of three time intervals heat preservation nursing on the core temperature of patients with ureteral calculi.Methods A total of 60 patients who receive holmium laser lithotripsy for kidney and ureteral calculi were divided into two groups.Experimental group received three time intervals heat preservation nursing care while control group received routine temperature preservation nursing care.Core temperature was recorded after induction, 30 min and 60 min after surgery and completion of surgery.Time to be awake, time of removing urine tube, length of hospital stay and shiver score were recorded.Results There was no significant difference in core temperature after 60 min of surgery and completion of surgery(P＜0.01).Time to be awake, time of removing urine tube, length to hospital stay in the experimental group were better than the control group(P＜0.01).Conclusion Multimode of three-process temperature preservation nursing can keep patients'stable temperature, and decrease the incidence of shiver, reduce length to stay and time to be awake, decrease occurrence of complication.

Objective To explore the relationship between reversed dipper blood pressure (BP) pattern with target organ damage in Chinese chronic kidney disease (CKD) patients. Methods A total of 1 116 CKD patients from the Third hospital of Sun Yat?sen university were enrolled from May 2010 to April 2014, all of whom carried ambulatory blood pressure monitoring (ABPM), and clinical data and ultrasonography were collected. Results Total of 23.39% CKD patients were reversed dipper BP pattern, 46.95% patients were non?dipper BP pattern, and dipper BP pattern was only 27.15%. Compared with dipper and non?dipper BP pattern group, patients with reversed dipper BP pattern had higher left ventricular mass index (LVMI), lower estimated glomerular filtration rate (eGFR) and severely damaged left ventricular diastolic function (all P<0.0083). After multiple linear regression analysis, reversed dipper BP pattern was an independent predictor for determining eGFR and LVMI. Age, lower hemoglobin and combination of diabetes were independently associated with reversed dipper BP pattern. Conclusion Reversed dipper BP pattern is common in Chinese CKD patients, which is closely related to renal damage and cardiovascular injuries.