Objective To establish the population pharmacokinetics(PPK)model of Lamotrigine(LTG)in children with epilepsy in China for promoting individualized dosage regimen. Methods The sparse data of LTG serum concentrations from 60 pediatric patients with epilepsy were collected. One hundred and fourteen serum concentration points were divided into LTG+valproic acid (VPA) group(n=56),LTG+enzymatic inducer(E1)group(n=26),LTG+EI+VPA group(n=16)and single LTG group(n=16).The serum drug concentrations were the clinical routinely tested steadv state concentrations.The LTG PPK parameters were calculated using the non-parametric expectation maximization(NPEM) Program of USC*PACK software,and then a PPK model was established. Based on this model,LTG serum concentrations were predicted with Bayesian fitting program of USC*PACK software.Mean prediction error(MPE)and mean squared prediction error(MSPE) were calculated to evaluate the accuracy and precision of the concentration prediction and to valid the PPK model.Results The greatest likelihood was-192.87.Optimum PPK parameters were:Ka=(1.97 1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05±0.05)h~(-1).The linear regression function Y_(OBS)=-0.09+1.05 Y_(PRED)(R~2=0.98,P<0.001),and determination of coefficient was 0.98.MPE was-0.16 g/mL,and MSPE was 0.28(μg/mL)~2.Conclusion A PPK model of LTG in children with epilepsy in China can be successfully established using the USC*PACK software, based on which LTG serum concentrations can be predicted accurately with a Bayesian approach.

Objective To identify clinical predictive factors in intractable childhood epilepsy,to provide some evidence for its early diagnosis.Methods Six hundred and twenty-four children with newly diagnosed epilepsy were retrospectively identified in Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical School(1993-2009).The epileptic children were divided into a drug-responsive epilepsy group (n =584) and an intractable epilepsy group (n =40).Clinical data of patients were retrospectively analyzed,including the gender,age,pathogen,inducement,number of pre-treatment seizures,seizure type,seizure type change,seizure duration,family history,previous history,physical examination,brain CT and initial electroencephalogram(EEG) findings.Single factor analysis and Logistic regression analysis were made in 2 groups.Results Strong univariate associations suggested that some factors could increase the risks of intractable epilepsy:symptomatic or cryptogenic epilepsy,mental retardation,type of infantile spasm,positive neurological examination and large absolute number of pre-treatment seizures,and changes in seizure types in the course of the disease.With multiple Logistic regression,independent predictors of intractability were symptomatic or cryptogenic etiology(OR =3.61),large absolute number of pre-treatment seizures and changes in seizure types in the course of the disease(OR =4.76).Conclusions It's necessary to be wary of intractable epilepsy and to adjust therapy accordingly when seizures were uncontrollable and accompanied by one or more conditions such as symptomatic or cryptogenic epilepsy,large absolute number of pre-treatment seizures,changes in seizure types in the course of the disease.

Objective To determine the content of aconitine-type alkaloids in Bitongxiao Ointment,and to control the limits of aconitine-type alkaloids in the ointment.Methods Acid-dye colorimetry was employed and methodology was examined for linear range,average recovery,precision,exclusivity and stability.Results The method has a good precision and stability.The linear range of aconitine-type alkaloids was in 0.111 9～0.714 mg(r=0.999 3),and the average recovery was 97.4 %.Conclusion The method is accurate,reliable,simple,can be used to determine the content of aconitine-type alkaloids in Bitongxiao Ointment.

Objective To explore clinical classification and strategies for irreducible femur intertrochateric fractures.Methods A retrospective study was conducted of the 96 patients with irreducible intertrochanteric fracture who had been treated from January 2012 through December 2014 at our department.They were 47 men and 49 women,aged from 48 to 97 years (average,78.5 years).We classified the fractures according to location of fracture line and mechanism of fracture displacement into 5 types:13 cases of type Ⅰ (sagittal irreducible fracture),7 cases of type Ⅱ] (coronal irreducible fracture),72 cases of type Ⅲll (sagittal plus coronal irreducible fracture),zero of type Ⅳ (irreducible fracture involving the lesser trochanter),and 4 cases of type Ⅴ (irreducible fracture involving the greater trochanter).All the patients were managed using different techniques for closed reduction and fixation with proximal femoral nails antirotation Ⅱ.Results Of this series,limited open reduction was eventually conducted in 7.The operation time averaged 40 min;the amount of intraoperative blood loss averaged 200 mL.Fracture reduction was rated as grade Ⅰ in 78 cases and as grade Ⅱ in 18.The follow-up time averaged 16.6 months (from 12 to 24 months).All the fractures got united after an average of 5.8 months (from 3 to 9 months).The function of the affected hip was rated at the final follow-up using Harris scoring system as excellent in 79 cases and as good in 17,with an excellent to good rate of 100％.Refracture happened in one patient due to striking injury,urinary infection occurred in 2 patients and no wound infection was observed.Conclusion According to the classification and reduction strategy proposed by us,satisfactory reduction and fracture fixation can be achieved in management of irreducible intertrochanteric fractures.

Objective To explore the effect of human leukocyte antigen B* genotype and age on serum homocysteine (Hcy) levels in children with seizures or epilepsy. Methods Fifteen children with seizures or epilepsy in whom HLA-B*15:02 genotype was detected during October 2015 to June 2016 were included. The plasma Hcy concentration in children with different genotypes was compared. The association of Hcy concentration and age was performed by linear-regression analysis. Results The mean concentration of Hcy was 8.38±4.23 μmol/L in children not carrying HLA-B*15:02 gene, which was obviously higher than that in children carrying HLA-B*15:02 gene 13.03±0.97 μmol/L (P<0.05). The Hcy concentration increased with the age (r2 =0.29, P<0.05). Conclusions Elder children with seizures or epilepsy carrying HLA-B*15:02 gene tend to have higher Hcy concentration and increased potential risk of disease. HLA-B*15:02 gene type and age can predict the changes of Hcy concentration in children with convulsions.

Anti-N-methyl-D-aspartate receptor encephalitis is severe diffuse encephalitis caused by cerebrospinal fluid(CSF)antibodies against the GluN1 subunit of the NMDAR.Pediatric NMDAR encephalitis is mainly characterized by neurological symptoms such as dyskinesia, ataxia and epilepsy.Auxiliary examinations of the patients show positive CSF IgG antibodies, EEG slow waves and metabolic changes in FDG-PET/CT.But there is lacking of clinical biomarkers for early diagnosis of children with atypical symptoms and negative antibody.Immunotherapy is effective for most children and early treatment can improve prognosis remarkably.At the same time, antipsychotic drugs and antiepileptic drugs can treat children with psycho behavioral symptoms and seizures.However, some patients are refractory to conventional therapies and have neurological sequela even after the application of multiple immunosuppressants.Therefore, more further studies are needed to clarify the pathogenesis and find biomarkers for early diagnosis of pediatric patients.This article reviews the pathogenesis, clinical characteristics, diagnosis and treatments of the disease.

Objective To analyze the relationship between cognitive and psychiatric symptoms and serum folate,homocysteine(Hcy)and vitamin B12 in patients with Alzheimer's disease(AD).Methods Fifty-eight patients with AD who were treated in Hangzhou Seventh People's Hospital from March 2019 to April 2022 were retrospectively selected.According to the score of neuropsychiatric inventory questionnaire(NPI-Q),they were divided into observation group A(NPI-Q<14 points,36 cases)and observation group B(NPI-Q≥14 points,22 cases).Fifty-eight elderly persons who underwent physical examination during the same period were included in control group.The general data,serum folate,Hcy,vitamin B12 levels,mini-mental state examination(MMSE)score,NPI-Q score,clinical dementia rating(CDR)score were compared among the three groups.Results There was statistical significance in age comparison among the three groups(P<0.05),that is control group0.05).There were significant differences in MMSE,NPI-Q,CDR scores and serum folate,Hcy and vitamin B12 levels among the three groups(P<0.05).After controlling for variables,MMSE score was positively correlated with folate and negatively correlated with Hcy;NPI-Q score was negatively correlated with folate and vitamin B12,and positively correlated with Hcy;CDR score was negatively correlated with folate and vitamin B12,and positively correlated with Hcy(P<0.05).Serum Hcy levels in AD patients with emotional symptoms or psychiatric symptoms or impaired frontal lobe function were significantly higher than those in asymptomatic AD patients(P<0.05).Conclusion Detection of serum folate,Hcy,vitamin B12 levels is beneficial to the diagnosis of AD patients.

Objective To investigate the efficacy of lateral decubitus intramedullary nailing for treatment of subtrochanteric fractures of the femur.Methods From January 2012 to December 2015,23 patients with simple femoral subtrochanteric fracture were treated at Department of Orthopedic Trauma,Changhai Hospital.They were 15 males and 8 females,aged from 19 to 77 years (average,48.3 years).According to the Seinsheimer classification,there were 6 cases of type ⅡB,8 cases of type ⅡC,6 cases of type Ⅲ A,and 3 cases of type ⅢB.Their injuries were caused by traffic accident in 10 cases,falling from a height in 5 cases,and sprain in 8 cases.All patients were treated by closed reduction and anterograde intrarnedullary nailing at lateral decubitus.Their operative time,bleeding volume,fluoroscopic frequency,fracture healing time,functional recovery and complications were recorded and analyzed.Results Their operative time ranged from 55 to 80 min,averaging 65.7 min;their bleeding volumes ranged from 240 to 420 mL,averaging 304.3 mL;their fluoroscopic frequency ranged from 30 to 60 times,averaging 42.7 times.This cohort was followed up for 12 to 28 months (average,17.9 months).Their fracture healing time ranged from 4 to 10 months,averaging 5.5 months.Nonunion occurred in one patient but was cured by secondary operation.The HSS evaluation at the final follow-ups showed 17 excellent cases and 6 good ones,yielding an excellent to good rate of 100％.All the wounds healed by the first intention.No infection,deep vein thrombosis or implant failure was observed.Conclusion As lateral decubitus intramedullary nailing can achieve satisfactory clinical efficacy for subtrochanteric fractures of the femur,the body position of lateral decubitus may be a good alternative.

Objective:To revise the 2017 classification of irreducible intertrochanteric fractures and summarize reduction techniques of 2021 classification.Methods:A retrospective analysis was conducted of the 17 patients with irreducible intertrochanteric fracture who had been treated at Department of Orthopaedic Surgery, The Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine from January 2015 to December 2019. They were 7 males and 10 females, with an age of (73.2 ± 16.1) years. On the basis of 2017 classification, the irreducible intertrochanteric fractures were classified into 2 types in the present 2021 classification. Type Ⅰ were interlocking fractures which were further classified into 3 subtypes: type ⅠA were sagittal interlocking ones (7 cases), type ⅠB greater trochanter interlocking ones (one case) and type ⅠC lesser trochanter interlocking ones (one case). Type Ⅱ were separating fractures which were further classified into 4 subtypes: type ⅡA were sagittal separating ones (4 cases), type ⅡB coronal separating ones (one case), type ⅡC rotational separating ones(one case) and type ⅡD complete separating ones (2 cases). All patients were treated by closed reduction and intramedullary nailing with different reduction strategies corresponding to their fracture types (application of ejector rods, clamps or prying techniques, etc.). A total of 132 patients with reducible femoral intertrochanteric fracture who had been admitted during the same period were selected as the control group. The fracture reduction time, intraoperative blood loss and Harris hip score at the last follow-up were compared between the 2 groups.Results:The 2 groups were comparable because there was no significant difference in their preoperative general data ( P>0.05). Type ⅠA accounted for the highest proportion of irreducible intertrochanteric fractures [41.3% (7/17)], followed by type ⅡA [23.6% (4/17)]. The fracture reduction time [(44.6 ± 6.7) min] in the irreducible group was significantly longer than that in the control group [(39.2 ± 9.6) min] ( P<0.05). There was no significant difference in intraoperative blood loss or Harris hip score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Compared with the "2017 classification" , the "2021 classification" is more concise and easy to remember, and can directly prompt the corresponding proper fracture reduction techniques. The patients with irreducible intertrochanteric fracture using proper reduction techniques can obtain functional recovery similar to that in the patients with reducible intertrochanteric fracture after reduction and fixation.

Objective : To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition (MMT) of peritoneal mesothelial cells (HMrSV5) , and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3 (STAT3) on rat peritoneal fibrosis (PF) model . Methods : The animals were divided into three groups : the sham group , the model group , and the STAT3 inhibitor group . A miniature per- itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate . After 10 weeks , HE staining was used to evaluate the histology of the peritoneum , and the level of transforming growth factor-β1 (TGF-β1) in the peritoneum was measured by immuno- histochemistry . HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot. High glucose was used to stimulate HMrSV5 after successful transfection with si - STAT3 and Western blot was used to measure the protein level of STAT3 , p-STAT3 , and the key enzymes of glycol- ysis 6-phosphofructo-2-kinase/fructose-2 , 6-biphosphatase 3 (PFKFB3) and lactate dehydrogenase A (LDHA) . Results : HE staining showed that administration of STAT3 inhibitor ( BP-1-102) could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats . The expression of TGF-β1 in the rats perito- neum of the model group was significantly higher than that in the sham group , and the level of TGF-β1 was marked- ly lower in the STAT3 inhibitor group compared to the model group (P < 0. 05) . Compared to the control group , high glucose induced the up-regulation of α-smooth muscle actin ( α-SMA) , the down-regulation of E-cadherin and STAT3 activation in HMrSV5 (P < 0. 05) . Mesothelial cells treated with high glucose also exhibited high expres- sion of the key enzymes of glycolysis ( PFKFB3 , LDHA) ( P < 0. 05) , and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose ( P < 0. 05) . Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT , and targeting STAT3 alleviates peritoneal fibrosis and an- giogenesis during peritoneal dialysis treatment in rats .