Objective:To observe any effect of early recumbent treadmill training on the balance and functional independence during hospitalization of children who have received hematopoietic stem cell transplantation (HSCT).Methods:This was a retrospective analysis of 106 children who had received HSCT. Sixty-nine of them were qualified for study. Of those, 32 had performed recumbent treadmill training and the other 37 had not. The children in both groups received routine clinical treatment and nursing care, and also health education advocating exercise and giving exercise programs before and after the transplantation. The daily exercise was conducted with the help of parents. It lasted 20 to 30 minutes each time, 4 or 5 times a week. The treadmill group additionally spent 30 minutes training on a recumbent treadmill 5 times a week for 6 weeks. Balance, functional independence and fatigue levels were quantified before and after the treatment using the Berg Balance Scale (BBS), the Functional Independence Measure for Children (WeeFIM) and the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale.Results:After the 6 weeks, significant improvement was observed in the experimental group′s average BBS score, motor function domain score, total WeeFIM score, general fatigue, and sleep/rest fatigue. All were then significantly better than the non-treadmill group′s results.Conclusion:Early recumbent treadmill training can promote the recovery of balance and functional independence of children after HSCT.

BACKGROUND:The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy,and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing.Therefore,this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology,thereby developing new ideas for the exploration of their mechanisms. OBJECTIVE:To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action. METHODS:Thirty-eight Sprague-Dawley rats were randomly divided into model group(n=14),treatment group(n=14)and sham-operated group(n=10).Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method.At 6 hours after modeling,neurological function was scored,and rats with a score of 2 were selected for subsequent experiments.The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage.Changes in body mass,24-hour food and water intake were recorded on days 2,7,14 and 30.The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30.After the swallowing test,the ischemic area of the brain in each group was measured by TTC staining.The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry.The mRNA and protein expression levels of BCL-2 and BAX in the insula,premotor cortex,cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham-operated group,the body mass,24-hour food intake and water intake were reduced,the swallow initiation response time was prolonged,and the number of swallows was reduced in the treatment and model groups at day 14 of gavage(P＜0.05).Compared with the model group,the body mass,24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage(P＜0.05),but were still lower than those in the sham-operated group.Compared with the model group,the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group,but the number of swallows was still significantly lower than that in the sham-operated group(P＜0.05).Cerebral ischemia area was reduced in the treatment group compared with the model group,and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group,but it was still significantly lower than that in the sham-operated group(P＜0.05).Compared with the model group,the expression of BCL-2 mRNA and protein in the insula,cingulate cortex and thalamus of rats in the treatment group were significantly increased,the expression of BAX mRNA and protein were significantly decreased,and the BCL-2/BAX ratio was significantly increased(P＜0.05).To conclude,the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time,as well as 24-hour food intake,body mass and other swallowing-related indexes in rats with post-stroke dysphagia.The mechanism of action may be achieved by improving the area of cerebral ischemia,inhibiting the apoptosis of neuronal cells in the insula,cingulate cortex and thalamus of rats,thus improving the regulation of the higher centers on the medulla oblongata swallowing center,and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius.

Objective To study the efficacy of speech training combined with Montessori education on speech problems in children after velopharyngeal insufficiency surgery.Methods A retrospective analysis of 63 cases of children who underwent velopharyngeal repair at Children's Hospital of Soochow University between January 2019 and December 2021 was conducted.Subjects were divided into three groups.A total of 21 patients who received family rehabilitation training after the operation were divided into control group A,42 patients who received regular hospital rehabilitation training after the operation were divided into group B and group C,of which 21 patients in group B received routine speech training,and 21 patients in group C received Montessori education and routine speech training.Nasal resonance status,assessment of dysarthric intelligibility,and cranially positioned lateral radi-ographs when pronouncing/i/sounds were evaluated individually before treatment and 6 months after treatment.The improvement of velopharyngeal function,nasal resonance status,and dysarthric articulation were evaluated.Results After the six-month intervention,the dysarthric speech intelligibility were significantly improved in three groups with improvement of 35.45％in group A,43.66％in group B,and 49.33％in group C,respectively(P＜0.05).The improvement rate of nasality reached 100％in the B and C group with nasality elimination rate of 70％in group B and 95.24％nasality elimination in group C,and the efficacy of the two groups was statistically signifi-cant(P＜0.05).During phonation of the/i/tone,velopharyngeal insufficiency was observed in seven patients in group B and in only one patient in group C,and the efficacy was statistically significant in both groups(P＜0.05).Conclusion Postoperative targeted speech training is necessary in patients with velopharyngeal insufficiency,and speech training combined with Montessori education can significantly improve the function of velopharyngeal clo-sure,thus achieving a good state of nasal resonance and correct articulation as early as possible.

Objective To explore and analyse the signals of adverse events of esketamine,and to provide references for rational clinical use of the drug.Methods The adverse event reports of esketamine from the first quarter of 2019 to the fourth quarter of 2023 in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database were collected.The reporting odds ratio(ROR)method and information component(IC)method in the disproportionality analysis and random forest(RF)algorithm,K-nearest neighbor algorithm and extreme gradient boosting(XGBoost)algorithm in machine learning algorithms were used for signal mining of target medicines respectively.The accuracy of machine learning signal detection results was assessed by the area under the curve(AUC).Results A total of 5 247 adverse event records with esketamine as the primary suspect drug were obtained.Using the traditional detection measures of dis-proportionality,138 positive signal results were detected,6 new adverse events including anticholinergic syndrome,urinary incontinence,double vision,pyelonephritis,spontaneous pneumothorax,biliary obstruction,were not included in the FDA drug inserts,and it was found that the drug may be more likely to cause cardiovascular problems.The results of the machine learning training showed that XGBoost algorithm and RF algorithm performed moderately well,with AUC means of 0.928 and 0.921,respectively.A total of 4 new potential adverse drug event signals,diplopia,deterioration of general physical health,suicidal ideation and withdrawal syndrome were detected by XGBoost algorithm and RF algorithm.Conclusion Esketamine is accompanied by some unknown risks while obtaining significant efficacy and adverse events not mentioned in the specification may occur in clinical practice.Healthcare professionals should be fully alert to the relevant adverse events when applying them in clinical treatment and take timely measures to ensure the safety of the treatment.

Objective:To observe the effect of rich environmental rehabilitation training on the physical system and ner-vous system development of newboms with hypoxic-ischemic encephalopathy(HIE). Method:Sixty-one HIE newboms were divided into the observation group(n=31)and the control group(n=30).The control group was given the routine clinical treatment and care,and the observation group was supplemented with enriched environmental rehabilitation training on the basis of the control group for 3 weeks.The body length and weight,and the head circumference of the two groups were measured to assess the physical development at admis-sion and 3 weeks after the intervention,and the neonatal behavioral neurological assessment(NBNA)and test of in-fant motor performance(TIMP)were used to evaluate the neurological development and motor function. Result:After the intervention,the changes of body length and weight changes in the observed group were bet-ter than the control group(P＜0.05),no significant difference in head circumference(P＞0.05),and the NB-NA score and TIMP score were higher than those of the control group(P＜0.05). Conclusion:The application of rich environmental rehabilitation training can promote the rapid development of physique and nervous system of the newboms with HIE and improve the motor function.

Objective:To determine the analytical performance of a candidate reference measurement procedure for 17α-hydroxyprogesterone in human serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Methods:The serum spiked with a deuterium-labeled internal standard was extracted from serum from individual undergoing physical examination by liquid-liquid extraction with n-hexane/ethyl acetate (3∶2, v/v), separated by C18 reversed-phase chromatography and detected by positive electrospray ionization mass spectrometry. According to the Clinical and Laboratory Standards Institute (CLSI) C62-A documents, the analytical performance including linearity, limit of detection,limit of quantitation,relative matrix effect,precision and trueness,carry-over and specificity was evaluated.Results:The linear range of 17α-hydroxyprogesterone by LC-MS/MS was 0.21-119.67 μg/L. The limit of detection and limit of quantitation were 5.218 ng/L and 0.116 μg/L. The relative matrix effects were -0.02%, -0.40% and -0.90% for sera and solution mixtures in 3 different ratios (50∶50, 80:20 and 20∶80). The coefficients of variation ( CVs) of intra-assay were 1.73%-2.11%, 0.98%-1.71%, 0.47%-0.87% at 0.164 μg/L, 14.81 μg/L, 81.63 μg/L and the CVs of inter-assay were 1.82%, 1.03%, 0.80% at above three concentrations. The average recovery rates of 3 levels (0.5, 20 and 100 μg/L) were 100.4%, 101.7%, 102.8%, respectively. The measured values of GBW09829 of National Institute of Metrology were within the specified uncertainty range. Conclusion:The candidate reference measurement procedure for 17α-hydroxyprogesterone in human by LC-MS/MS is established with good accuracy and precision, which can be clinically used for measurement traceability.

Objective: The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision. Methods: Two time points, the summer and winter solstice, which are the longest and shortest days of the year, respectively, were selected. Male Sprague-Dawley rats that underwent a sham operation without pineal excision were included as a control group. The concentrations of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) were determined by radioimmunoassays and enzyme-linked immunosorbent assays, respectively. Results: In the winter, the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group (P < .01). A difference was also noted in GABA levels be-tween the normal group and the sham operation group (P<.05). The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter (P < .01), while the GABA levels in the sham operation group exhibited a significant difference, with elevation during the summer and reduction during the winter (P<.01). In the operation group, GABA showed the same trend (P<.01). Conclusion: The seasonal rhythm of neurotransmitter secretion by the hippocampus (5-HT and GABA) consisted of elevation during the summer and reduction during the winter. During the winter, the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus, and it exhibited seasonal selectivity with regard to the regulation of 5-HT.

Objective: To establish a reference measurement procedure for the determination of human serum homocysteine by isotope dilution high performance liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS), and to apply it to establish sample target values for external quality assessment (EQA) in clinical laboratories. Methods: The reference method of Hcyquantification in our laboratory was establishedaccording to the method recommended by the Joint Committee for Traceability in Laboratory Medicine (JCTLM). The precision, trueness, specificity, residue and matrix effect of the method were evaluated. The reference method was applied to establish Hcy target values for samples of the second EQA in Shanghai of 2018. Results: The method detects 12.5μmol/L and 37.4μmol/L samples in three batches in three days, and the CV between batches is 1.03% and 2.10%, respectively. The measured values of Standard reference material (SRM) 1955 of National Institute of Standards and Technology (NIST) were within the specified uncertainty range. No matrix effect and carryover were observed. The second EQA data in 2018 showed that the average value of domestic reagent group was lower than that of reference method, and that of imported reagent group was higher than that of reference method. Conclusion Thereference measurement procedure of ID-LC/MS/MS was successfully established to determine the human serum homocysteine. It is expected to play a role in tracing the quantities of Hcy in clinical laboratories.

Objective To establish an isotope dilution liquid chromatography tandem mass spectrometry method (ID-LC-MS) for quantification of serum apolipoprotein E and phenotyping. Methods Method establishment. Samples underwent denaturing, alkylation and trypsin digestion with addition of internal standards as isotope labelling arginine. SB-C18 column was used for the liquid chromatographic separation and mass spectrometry positive ion mode and multiple reaction monitoring were employed for quantification and phenotyping. Precision, accuracy and linearity were investigated for method evaluation. 40 serum samples from Shanghai Dongfang Hospital during Oct. to Dec., 2018 were used for method comparison between ID-LC-MS and immunoassay. Deming regression and Bland-Altman were used for method comparison analysis and SPSS 24 for linearity. Results Target peptides reached their releasing maximum within 4 hours and SE did at 3 hours. 3 phenotyping of ApoE were observed, such as E3/E3, E2/E3 and E3 / E4. The imprecision of IQC was 5.2 ％ . The relative bias for low and high levels of accuracy-based samples was 7.6 ％ and 3.6 ％, respectively. Deming regression showed the intercept with 95 ％ confidence interval (CI) was 6.44-11.44 (P<0.05 and the 95％ confidence interval for the slopewas 0.77-0.89 (P<0.05). The coefficient was r=0.97. The mean difference was - 2.95 mg / L with 95 ％ CI-4.26--1.65 mg/L. The linearity covered from 16.9 to 58.5 mg/L. Conclusion ID-LC-MS can be used to quantify serum apolipoprotein E and simultaneously detect its phenotyping.

Objective Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China,so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking.This study aimed to analyze the direct,indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China.Methods The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study.All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases.The direct expenditure included direct medical cost and direct non-medical cost.The indirect expenditure,including work loss of patients and caregivers,were calculated by using human capital method for urban and rural populations in 12 areas.The intangible expenditure were reflected by willing to pay and stochastic tournament.The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis.Results A total of 27 hospitals in 12 areas were included in the survey.A total of 4 718 cases were surveyed,the overall response rate was 77.7％.The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case,in which the highest proportion (61.2％)was medicine fees [10 365.10 yuan (RMB)].The average direct expenditure and indirect expenditure were consistent with the severity of illness,which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively,with the ratio of 3.85:1.The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)].It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures.Among the average indirect expenditure,the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)],The total direct and indirect expenditure was highest for liver transplantation,followed by severe hepatitis,hepatocellular carcinoma and decompensated cirrhosis,acute hepatitis B,compensated cirrhosis and chronic hepatitis B.The influencing factors for both direct and indirect expenditure were high hospital level,severity of hepatitis B,living in urban area,antiviral therapy,long hospitalization and monthly income of family.For average 3.74 outpatient visits and 1.51 hospitalization,the average annual direct,indirect and intangible expenditure for HB-related diseases were 30 135.30,6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)],accounting for 37.3％,7.7％ and 55.0％,respectively.Of the annual direct medical expenditure [28 402.80 yuan (RMB)],which were much higher than non-medical expenditure [1 732.50 yuan (RMB)],hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)].The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB),respectively.Of the annual intangible expenditure,the highest was that for/primary hepatocellular carcinoma,followed by cirrhosis,chronic hepatitis B,severe hepatitis B,liver transplantation and acute hepatitis B.Conclusions A heavy economic burden has been caused by HB-related diseases in China,and patients are more likely to rely on medical service rather than non-medical service.It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits.The influence of HB related diseases on mental health of the people can be reflected by an economics term,intangible expenditure.