Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

Objective:To explore the predictive value of systemic immune inflammation index (SII) for the risk of hospital death in critically ill patients.Methods:The basic information and clinical data of critically ill patients were extracted from the Medical Information Mart for Intensive Care database-Ⅳ (MIMIC-IV) database, including demographic data, vital signs, blood routine, Logistic organ dysfunction score (Lods), Oxford acute severity of illness score (Oasis), simplified acute physiology score (Saps-Ⅱ), acute physiology score Ⅲ (APS-Ⅲ), sequential organ failure score (SOFA) and outcome. The main outcome was hospital death, and the secondary outcomes were length of hospital stay, continuous renal replacement therapy (CRRT), invasive ventilation and 1-year mortality. Patients were divided into two groups according to in-hospital death, and the differences between the groups were compared. According to the SII tripartite for inter-group comparison, the patients were further divided into three groups for comparison, and Logistic regression model was used to analyze the odd ratio ( OR) of the three groups. Results:A total of 32 450 critically ill patients were included in the study, of which 3765 died in hospital, with a mortality rate of 11.6%. ① Compared with the survival group, the SII in the death group were significantly higher ( P < 0.05). ② The mortality for the SII tripartite grouping (<817; 817~2 151; >2 151) were 8.4%, 10.2% and 16.3%, respectively, and the differences between groups were statistically significant. ③ Further, Logistic regression model analysis showed that the risk of death increased gradually with the increase of groups (the first group was the reference group, OR of the second group was 1.38, 95% CI 1.24-1.54, and OR of the third group was 2.03, 95% CI 1.83-2.24 ( P < 0.05). Conclusions:SII has a certain value in predicting hospital death in critically ill patients. It is easy to obtain and can be used for risk stratification of critically ill patients.

Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.

Objective To explore the release and percutaneous penetration of cyclovirobuxine D patches at different concentrations in vitro. Methods The release curves of cyclovirobuxine D patch in vitro were fitted by ritger-peppas mathematical model, and the patch release mechanism was discussed according to the fitting parameters. At the same time, compared the percutaneous permeability characteristics of 0.25,0.5,1.0,2.0 mg.( cm2 )-1 of cyclovirobuxine D patch by using a modified Franz diffusion cell, with isolated rat skin serving as transdermal barrier. Results Ritger-Peppas model fitting equation for cyclovirobuxine D patch [1.00 mg.(cm2)-1]was: Mt/M=0.964 6 t1.621 6.And the percutaneous penetration curve was best fitted to Higuchi kinetics equation.The drug release rate from the patch matrix was greater than the rate of penetration through the skin, indicating the patch at the time through rat′s skin was a passive diffusion process, and transdermal process was rate-limited by skin. Conclusion Kinetics equation fitting is an effective method for analyzing drug release and permeation behavior of cyclovirobuxine D patch in vitro.

Objective In present study,we aimed to investigate the ictal and interictal electroencephalography (EEG) changes in patients with infantile convulsions with mild gastroenteritis,to understand the evolution of EEG and recurrence of convulsion by follow-up.Methods In this retrospective study,all patients with infantile convulsions with mild gastroenteritis visited our hospital from January 2005 to December 2009 were included,and were followed up for 3 to 7 years.All their clinical data were summarized and analyzed.Results Fist of all,we collected 128 interictal EEGs and 4 ictal (5 episodes) reports.Based on interictal EEGs,no discharge was observed in 63 subjects,and epileptic waves were discovered in other 65 patients.In most cases (48/65) epileptic waves were found to be located in the central area.For all 5 recorded ictal EEGs (2 were from same patient),epileptic waves were originated from different regions.Two months later,epileptic waves disappeared in 52/57 cases,but there were still discharge in 5 cases.Secondly,in the 103 cases who were successfully followed up,96 were seizure free,5 had recurrence during fever (3 cases) or gastroenteritis (2 cases),but remained seizure free for last 1.5 to 3.0 years.Overall,convulsion was recurred in 2 cases and finally diagnosed as epilepsy and then treated with antiepileptic drug,keeping seizure free for recent 1.5 to 2.5 years.Conclusion (1) Discharge can be found in nearly half of interictal EEGs in cases with infantile convulsion with mild gastrocnteritis,and most of them are located in central region.(2) All discharge come from local origin in ictal EEGs.(3) Seizure may recur in cases with infantile convulsion with mild gastroenteritis,especially in the presence of causative factors.Some children have risk of developing epilepsy.

Objective To assess the efficacy and safety of two different protocols of ketogenic diet (KD)-eating on demand or eating at regular intervals for refractory epilepsy in children.Methods Sixty children with refractory epilepsy were randomly divided into eating on demand group (n =30) and eating at regular intervals group (n =30) by random number table method.After taking the whole amount of KD,the capillary blood ketone and glucose level and urine ketone were monitored every 6 hours in 72 continuous hours.Seizure frequency and onset time were recorded.Antiepileptic efficacy and diet tolerability of the two groups were evaluated on 4 weeks,12 weeks,24 weeks and 48 weeks after initiating the diet.Adverse effects were monitored.Results After treatment of 4 weeks,the complete seizure remission rates of eating on demand group and eating at regular intervals group were 33.3％ (10/30) and 30.0％ (9/30) respectively,which suggested a comparable efficacy for two groups (P ＞ 0.05).The day when KD started to work was averaged (6.18 ± 2.42) d and (8.63 ± 2.63) d respectively.The group of eating on demand showed a faster onset of action (P ＜0.05).After treatment of 12 weeks,24 weeks and 48 weeks,complete seizure remission rates of eating on demand group were 30.0％ (9/30),34.8％ (8/23) and 36.8％ (7/19) respectively;the eating at regular intervals group were 33.3％ (10/30),30.4％ (7/23) and 44.4％ (8/18) respectively.The two groups had no significant difference (P ＞ 0.05).One year later,the treatment retention rates of the two groups were 63.3 ％ (19/30) and 60.0％ (18/30) respectively.There was no significant difference (P ＞ 0.05).The adverse effects mainly including transient gastrointestinal symptoms and metabolic disturbances were mostly tolerable and curable.Conclusion The two different protocols of KD-eating on demand and eating at regular intervals are both effective and well-tolerated for refractory epilepsy in children.While protocol of eating on demand is more easier to achieve ketotic state and the effect is more quickly,so it can be more easily received by children.Therefore in clinical practice,we can choose flexible eating time according to children's eating habits,which can improve the therapeutic compliance.

ObjectiveThis clinical study is aimed to investigate whether levetiracetam (LEV) can improve electrocorticogram (EEG) in epileptic children epilepsy patients with better clinical manifestation but abnormal EEG findings.MethodsTotally 39 children from our neurological clinic with partial or complex partial epilepsy seizure were included in present study and assigned equally into three groups receiving different treatment:control group,sodium valproate (VPA) group,and LEV group.Their clinical symptoms had been controlled for over one year by carbamazepine ( CBZ),but EEG results showed clearly abnormal.Epileptiform discharges were observed in routine EEG exams half a month before recruiting.After recruiting,they continued to receive CBZ alone (control group) or co-treated with VPA ( VPA group) or LEV (LEVgroup),respectively.Six months later,EEG was taken again and results were analyzed.ResultsImprovement rate were 9.1％ ( control group),23.1％ ( VPA group),and 66.7％ (LEV group),respectively;Overall statistical difference was reached among three groups ( P＜0.01 ) and between control group and LEV group( P＜0.012 5 ),but no statistical difference between control group and VPA group was reached ( P＞0.0125).ConclusionCo-treatment of LEV in child epilepsy patients receiving CBZ can significantly decrease abnormal EEG discharge frequency during interictal period.

Objective To explore the common pathogen of infantile convulsions associated with mild gastroenteritis, and to study the differences between the seizures caused by the two kinds of virus.Methods RT-PCR was used to detect Rotavirus (RV) and Norwalkvirus (NoV) in stool and cerebrospinal fluid of 30 cases with infantile convulsions associated with mild gastroenteritis. The differences between the frequency of seizures caused by two kinds of virus were analyzed by statistical methods (two-sample t-test).Results 17/30 (56. 7%) were RV-positive in stool and 3/17 (17. 7%) in cerebrospinal fluid; 6/30 (25.0%) were NoV-positive in stool and 1/6 (16. 7%) in cerebrospinal fluid. The seizure frequency with NoV infection was (4. 33 ± 1.75) times, and RV infection patients was (2. 53 ± 1.12) times (P ＜ 0. 01).The seizure frequency of CSF virus-positive children was (4. 75 ± 1.71) times compared to (2. 63 ± 1.21)times in virus-negative children (P ＜ 0.01). Conclusion The common pathogens causing infantile convulsions associated with mild gastroenteritis were RV and NoV. The degree of NoV infection affecting the central nervous system may be greater than RV. The presence of the virus in cerebrospinal fluid may lead to higher incidence of seizures,but their exact roles related to the occurrence of seizures remain to be further studied.

Objective To analyse the value of video-EEG (VEEG) in the infantile spasms (IS)children treated with adrenocorticotrophic hormone (ACTH). Methods The clinical data of 65 children with IS in our hospital from Jan 2005 to Dec 2009 were collected and the characteristics of VEEG were analyzed before and after treated with ACTH. Results All the 65 cases appeared hypsarrhythmia in the interphase before treated with ACTH. Cluster spasms and the characteristics of VEEG were recorded. After treated with ACTH,40 of 65 cases (61.5%) with epileptic seizure were controlled,in whom 27 cases (67.5% ,27/40)with hypsarrhythmia disappeared or improved obviously. The other 25 of 65 cases (38.5%) with epileptic seizure were uncontrolled,in whom only 5 cases (20. 0% ,5/25) with hypsarrhythmia disappeared. The rate of hypsarrhythmia disappeared or improved was significantly different between the epileptic seizure controlled and uncontrolled children (x2 = 13. 888, P ＜ 0. 000). Conclusion VEEG is not only important to make a definite diagnosis for IS,but also can provide an evidence in evaluating the effect of ACTH in IS children.