Objective:To investigate the clinical manifestations of medically refractory hereditary movement disorders in children and the efficacy of deep brain stimulation (DBS).Methods:A case series study.The clinical and follow-up data of 20 children with medically refractory hereditary movement disorders who underwent DBS treatment at the Neurology and Functional Neurosurgery Departments of Beijing Children′s Hospital, Capital Medical University, from July 2018 to April 2024, were retrospectively analyzed.The severity of movement disorder symptoms and surgical effects were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale Movement(BFMDRS-M) or the Unified Parkinson′s Disease Rating Scale Ⅲ(UPDRS Ⅲ).Results:There were 12 males and 8 females among the 20 children, with an onset age ranging from 4 months to 12 years and 5 months.Fourteen patients had hereditary dystonia, which is related to KMT2B in 11 patients, TOR1A in 2 patients and SGCE in 1 patient.Two patients had choreoathetosis, which is related to ADCY5-related familial movement disorders.Two patients had early-onset Parkinson′s disease, which is related to ATP6AP2 in 1 patient and VPS13C in 1 patient.Two patients had neurodevelopmental disorders with involuntary movements, which is related to GNAO1 in 1 patient, and the other patient was idiopathic.All the children were given oral Levodopa, Benzhexol, Baclofen, Tiapride Hydrochloride, Clonazepam alone or in combination.Three children showed obvious dyskinesia after Levodopa treatment.The symptoms of movement disorders in all children exhibited little to no improvement.Levetiracetam and Zonisamide had unstable effects in the treatment of myoclonia.DBS surgery was performed on all the patients aged from 3 to 16 years.Electrodes were successfully inserted into bilateral globus pallidus internus in 14 cases and bilateral subthalamic nuclei in 4 cases.The target was unknown in 2 cases.No surgery-related complications were observed.The patients were followed up for 3 months to 6 years, and the last follow-up age of the patients ranged from 5 years and 7 months to 22 years and 1 month.The rate of improvement in BFMDRS-M score was 37%-100% in 16 patients and >70% in 7 patients with hereditary dystonia.The rate of improvement in UPDRS Ⅲ score was 23% in 1 patient with VPS13C-related early-onset Parkinson′s disease. Conclusions:Childhood medically refractory hereditary movement disorders are a case series that exhibits significant phenotypic and genotypic heterogeneity.DBS surgery demonstrates significant efficacy for KMT2B-, TOR1A-, and SGCE-related hereditary movement disorders.

Objective:To investigate the clinical manifestations of medically refractory hereditary movement disorders in children and the efficacy of deep brain stimulation (DBS).Methods:A case series study.The clinical and follow-up data of 20 children with medically refractory hereditary movement disorders who underwent DBS treatment at the Neurology and Functional Neurosurgery Departments of Beijing Children′s Hospital, Capital Medical University, from July 2018 to April 2024, were retrospectively analyzed.The severity of movement disorder symptoms and surgical effects were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale Movement(BFMDRS-M) or the Unified Parkinson′s Disease Rating Scale Ⅲ(UPDRS Ⅲ).Results:There were 12 males and 8 females among the 20 children, with an onset age ranging from 4 months to 12 years and 5 months.Fourteen patients had hereditary dystonia, which is related to KMT2B in 11 patients, TOR1A in 2 patients and SGCE in 1 patient.Two patients had choreoathetosis, which is related to ADCY5-related familial movement disorders.Two patients had early-onset Parkinson′s disease, which is related to ATP6AP2 in 1 patient and VPS13C in 1 patient.Two patients had neurodevelopmental disorders with involuntary movements, which is related to GNAO1 in 1 patient, and the other patient was idiopathic.All the children were given oral Levodopa, Benzhexol, Baclofen, Tiapride Hydrochloride, Clonazepam alone or in combination.Three children showed obvious dyskinesia after Levodopa treatment.The symptoms of movement disorders in all children exhibited little to no improvement.Levetiracetam and Zonisamide had unstable effects in the treatment of myoclonia.DBS surgery was performed on all the patients aged from 3 to 16 years.Electrodes were successfully inserted into bilateral globus pallidus internus in 14 cases and bilateral subthalamic nuclei in 4 cases.The target was unknown in 2 cases.No surgery-related complications were observed.The patients were followed up for 3 months to 6 years, and the last follow-up age of the patients ranged from 5 years and 7 months to 22 years and 1 month.The rate of improvement in BFMDRS-M score was 37%-100% in 16 patients and >70% in 7 patients with hereditary dystonia.The rate of improvement in UPDRS Ⅲ score was 23% in 1 patient with VPS13C-related early-onset Parkinson′s disease. Conclusions:Childhood medically refractory hereditary movement disorders are a case series that exhibits significant phenotypic and genotypic heterogeneity.DBS surgery demonstrates significant efficacy for KMT2B-, TOR1A-, and SGCE-related hereditary movement disorders.

Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992％,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.

Objective:To observe the effect of medium-length intravenous catheter infusion on the intima and hemodynamics of the implanted blood vessel, in order to early detect the asymptomatic ultrasound imaging manifestations of indwelling blood vessel injury in patients, and observe the occurrence of catheter-related complications.Methods:Totally 105 patients who had medium-length venous catheters inserted through the upper arm in Huangshi Central Hospital from July to December 2021 were selected by random sampling. A self-control study was adopted. According to the time of data collection, they were divided into pre-catheterization group and the post-extubation group. Color Doppler ultrasonography was used to observe the image morphology, blood flow velocity, and blood flow of the vein intima at the outlet of the catheter tip before catheterization and after extubation, and to monitor the incidence of catheter-related complications. Among the 105 patients, 5 cases dropped out, and the effective sample size was 100 cases.Results:Among the 100 patients, before catheterization and after extubation, the vascular intima at the indwelling catheter tip showed no damages such as roughness and thickening; there was no statistically significant difference in venous blood flow velocity and the blood flow at the catheter tip before and after catheter extraction ( P>0.05) . There were 5 cases (4.76%, 5/105) of catheter-related complications. Conclusions:Medium-length intravenous catheter infusion of hyperosmolar parenteral nutrition solution does not significantly affect the morphology and hemodynamics of the intima of the implanted vessel, the implanted vessel is not damaged, and no serious complications such as catheter-related thrombosis and bloodstream infection occur, which achieve relatively safe clinical outcomes.

Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.

Objective:To investigate the correlation between the muscle mass loss and severe postoperative pulmonary complications(PPC)in elderly patients with non-small cell lung cancer(NSCLC).Methods:Elderly patients with NSCLC undergoing lobectomy at the Lung Cancer Institute and the Department of Thoracic Surgery of Guangdong Provincial People's Hospital were recruited from Feb.2019 to Dec.2019.Data of the body composition, lung function, respiratory muscle strength test, cardiopulmonary exercise test were collected before operation.All patients were grouped into two groups: with versus without severe PPC at 30 d after operation.The differences of the above parameters were compared between the two groups.A multiple logistic regression analysis was used to analyze the risk factors for severe PPC.Results:In this study, 120 elderly NSCLC patients undergoing lobectomy were recruited, All evaluations were completed in 113 patients(aged 68.13±7.01 years)in whom, 21(18.58%, 21/113)patients had serious PPC.Compared with patients without PPC, patients with severe PPC had a lower appendicular skeletal muscle mass index(ASMI)(5.67±0.90 kg/m 2vs.7.71±1.40 kg/m 2, t=3.900, P=0.001), a lower forced expiratory volume in 1 second(FEV 1)(1.85±0.40 L vs.2.12±0.57 L, t=2.412, P=0.027), a lower maximal mid-expiratory flow(MMF)(1.40±0.69 L/s vs.2.11±1.09 L/s, t=2.502, P=0.021), a lower maximum inspiratory pressure(Pimax)(55.13±32.52 cmH 2O vs.64.71±20.60, t=0.778, P=0.047, 1 cmH 2O=0.098 kPa), a lower maximal oxygen consumption(Vo 2max)(1.14±0.41 L/min vs.1.40±0.34 L/min, t=0.779, P=0.046), a lower peak O 2 consumption(Vo 2max@kg)(20.00±1.91 L·min -1·kg -1vs.22.33±2.37 L·min -1·kg -1, t=0.813, P=0.041). Multiple logistic regression analysis showed that in addition to FEV 1( OR=2.824, 95% CI: 1.127-5.158, P=0.001)and Vo 2max@kg( OR=3.149, 95%CI: 1.829-6.592, P<0.001), ASMI was also an independent risk factor for serious PPC( OR=1.919, 95% CI: 1.604-3.466, P=0.006), in which the best cut-off value was 6.295 kg/m 2, the sensitivity and specificity were 0.816 and 0.818 respectively, and the area under the receiver operating characteristic(ROC)curve(AUC)was 0.887(95% CI: 0.793-0.981, P<0.0001). Conclusions:Muscle mass loss can increase the risk for the occurrence of severe PPC within 30 days after lobectomy in elderly patients with NSCLC.

The metabolic stability test of drugs is a key step in drug discovery and achieving low clearance is frequently the goal in the design of drug. Increased drug metabolism stability can reduce drug dosage, enhance drug exposure and prolong drug half-life. Accurately assessing the metabolic stability parameters of low clearance drugs and predicting human pharmacokinetics has become a challenge. Traditional tools in vitro including microsomes and suspended primary hepatocytes are limited by incubation time, which is not long enough to make sufficient metabolic conversion. Determination of intrinsic clearance or metabolic pathways and mechanisms of drug are implicated. Novel models tend to further mimic the in vivo environment in order to prolong lifetime of hepatocytes and achieve sufficient metabolic turnover of drugs for monitoring. In vitro-in vivo correlation of intrinsic clearance of methodologies has evaluated to support the reliability in predicting human pharmacokinetics. Application of these methodologies greatly decreases the forthputting of experimental animals and the release of expensive clinical trials during the acquisition of pharmacokinetic parameters. In this review, we summarized the principles, advantages and disadvantages of the novel in vitro methodologies for metabolic stability dealing with low-turnover drugs, including hepatocyte relay method, plated human hepatocytes, coculture system and microfluidic devices. Future prospect is proposed for in vitro metabolic models and it provides reference and optimization in metabolic stability for early lead compounds.