Objective:To observe any effect of bilateral high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on the swallowing of stroke survivors with dysphagia.Methods:Thirty-eight patients with post-stroke dysphagia were randomly divided into a cerebellar stimulation group of 20 and a sham group of 18. In addition to drug therapy and physical rehabilitation training, the cerebellar stimulation group received 500 pulses of rTMS of the cerebellum daily at 10Hz and 120% of the resting movement threshold lasting 1s at 9s intervals. The sham stimulation group was treated with sham rTMS (with the angle between the stimulation coil and the scalp at 90°). Twenty minutes later, both groups were given 30 minutes of routine swallowing training daily by the same speech therapist. The treatment was administered 5 times a week for 3 weeks. Before the treatment and afterward, both groups′ swallowing was evaluated y videofluoroscopic swallowing study (VFSS), using a functional dysphagia scale (FDS) and using the Rosenbek penetration aspiration scale (PAS). Oral transport time, swallowing response time, pharyngeal transport time, laryngeal vestibular closure time and upper esophageal sphincter opening duration were recorded, and the changes in swallowing function and swallowing time parameters before and after the treatment were compared between the two groups.Results:Before the stimulation there were no significant differences between the two groups. Afterward, the average PAS and FDS scores of both groups had improved significantly, but with significantly greater improvement in the cerebellar stimulation group than in the sham group. Average oral transit time and swallow response time had shortened significantly, but with significantly shorter time, on average, in the cerebellar stimulation group.Conclusion:Bilateral high-frequency rTMS of the cerebellum can improve the swallowing of persons with dysphagia, and shorten their oral transit time and swallow response time.

Objective:To explore the clinical characteristics and medical nutritional therapy of 6 patients with late-onset ornithine transcarbamylase (OTC) deficiency.Methods:The clinical features, biochemical data, gene variations and treatment outcomes of 6 children with late-onset OTC deficiency admitted to the Department of Clinical Nutrition, Children′s Hospital of Nanjing Medical University from January 2020 to April 2022 were retrospectively analyzed.The 6 patients were all intervened by a long-term medical nutrition management.Results:Liver dysfunction and hyperammonemia (172.1-348.0 μmol/L) were found in all the 6 children with late-onset OTC deficiency.Serum citrulline decreased in 3 patients (3.95-5.43 μmol/L). Three patients showed increased urine orotic acid (123.48-342.60 mmol/mol Cr). Urine uracil increased in 4 patients (106.77-1 207.26 mmol/mol Cr). Variations of the OTC gene [c.364G>C p. (E122Q), c.1028C>G p. (T343R), c.664-2(IVS6)A>C, c.635G>T p. (G212V), c.929_c.931delAAG p. (E310del), c.829C>T p. (R277W)] were identified in all patients.The 6 children were all managed by individualized medical nutrition program and followed up for a long time.During the follow-up period, 3 cases developed hypoproteinemia, acute metabolic crisis and growth retardation, 3 cases had normal growth and laboratory indicators, and 1 case received liver transplantation after 3 months of nutritional management. Conclusions:The clinical manifestations of OTC deficiency are non-specific.Blood amino acids, urine organic acids and genetic tests are important for the diagnosis.Long-term regular medical nutrition management is helpful to improve the prognosis and quality of life of children.

Objective:To observe any stimulatory effect of intermittent theta burst stimulation (iTBS) on the cerebral swallowing cortex and the cerebellar swallowing motor area and to explore the related mechanisms.Methods:Forty-four healthy right-handed subjects were divided at random into a dominant cerebellum group ( n=15), a non-dominant cerebellum group ( n=15) and a control group ( n=14). In the dominant cerebellum group, iTBS was administered to the cerebellum of the dominant hemisphere, and the other hemisphere was given sham stimulation. In the non-dominant cerebellum group, it was the opposite. The dominant cerebellum received the sham stimulation. In the control group both hemispheres received sham stimulation. Before and after the stimulation, single-pulse transcranial magnetic stimulation (TMS) was applied to the representative regions of suprahyoid muscles in bilateral brain and cerebellum to observe changes of the latency and amplitude of motor evoked potentials (MEPs). Results:After the intervention the MEP amplitude of the bilateral swallowing cortex and the stimulated cerebellum had increased in the non-dominant cerebellum group, with increased MEP amplitude only from the stimulated cerebellum of the dominant cerebellum group. Compared with the control group, the non-dominant cerebellum group showed the greatest improvement in MEP amplitude of the stimulated bilateral cerebral cortex and cerebellum. Improvement in the dominant cerebellum group was significantly smaller. However, there were no significant differences in MEP latency or the percentage change in MEP latency from baseline among the three groups.Conclusions:Applying iTBS to either the non-dominant or the dominant cerebellum excites the brain areas related to swallowing, but in different ways.

OBJECTIVE： To study the effects of Atractylodes macrocephala ethanol extract （AM） on life span of Caenorhabditis elegans（called N 2 nematode for short ），and to investigate its mechanism based on transcription factor SKN- 1/ nuclear factor E 2 related factor 2（Nrf2）. METHODS ：N2 nematode were divided into blank control group ，positive control group （100 μ mol/L curcumin，similarly hereinafter ），AM low-dose ，medium-dose and high-dose groups （100，200，300 μ g/mL， similarly hereinafter ）. The effects of AM on the life span （by average survival time ）of N 2 nematode under normal condition and oxidant stress condition （40 mmol/L H 2O2）as well as its effects on reproductive capability （by the number of filial generation ）of N2 nematode under normal condition were investigated . 700 μmol/L H2O2 was used to establish neuroblastoma cells N 2a oxidant stress model. Effects of positive control ，low-dose，medium-dose and high-dose of AM on the survival rate of model cells were detected by MTT method. After human embryonic renalepithelial cells 293T were transfected with Nrf 2-ARE plasmid ， the effects of positive control and AM on luciferase activity of Nrf2-ARE were detected by luciferase reporter gene method at low，medium and high dose for 24 h and at medium dose for 12，18 and 24 h. RT-PCR was used to detect the effects ofpositive control ，low-dose，medium-dose and high-dose of AM on the mRNA expression of downstream genes NQO- 1 and HO- 1 of Nrf 2 in N 2a cells as well as mRN A expression of en@hactcm.edu.cn downstream genes GCS- 1，GST-7，GST-10，HSP-60，HSP- 16.2 and SOD- 3 of SKN- 1 in N 2 nematode. RESULTS ：Compared with blank control group ，average survival time of N 2 nematode under normal and oxidant stress condition was significantly prolonged in positive control group and AM groups ；the number of filial generation on the first day （except for AM high-dose group ），the number of filial generation on the second day （except for AM low-dose group ） and the total number of filial generation （except for AM low-dose group ） were increased significantly（P＜0.05 or P＜0.01）. The survival rate of N 2a cells in positive control group ，AM medium-dose and high-dose groups were significantly higher than that of model group （P＜0.05 or P＜0.01）. Compared with blank control group ，Nrf2-ARE luciferase relative activity of 293T cells in positive control group and AM groups as well as Nrf 2-ARE luciferase relative activity of 293T cells in AM medium-dose group after different time of treatment were increased significantly （P＜0.01），in dose-dependent and time-dependent trend. Compared with blank control group ，mRNA relative expression of HO- 1 and NQO- 1（except for positive control group ），GCS-1（except for AM low-dose group ），GST-7（except for positive control group and AM low-dose group ）， GST-10 and HSP- 60（except for AM low-dose group ），HSP-16.2（except for positive control group and AM low-dose group ）and SOD-3 （except for positive control group and AM low-dose group ） were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：AM can prolong the life span of N 2 nematode under normal and oxidant stress condition and improve the its reproductive capacity ，the mechanism of which may be associated with the activation of SKN- 1/Nrf2 signaling pathway.

Objective To observe the effect of tiopronin combined with glutathione on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT),blood fat and laminin (LN) in patients with non-alcoholic fatty liver. Methods A total of 84 non-alcoholic fatty liver patients admitted to our hospital from March 2018 to September 2019 were selected and randomly divided into control group and observation group, with 42 cases in each group. The control group was treated with tiopronin, and the observation group was treated with glutathione and tiopronin. The levels of ALT, AST, GGT and blood fat were recorded and compared before and after treatment. Results After treatment, the levels of ALT, AST and GGT in the two groups were significantly lower than before treatment (P<0.05). After treatment, the levels of ALT, AST, and GGT in the observation group were different from those in the control group, which was statistically significant (P<0.05). Before treatment, there was no difference in serum TC, TG, and LDL levels between the two groups, which was not statistically significant (P>0.05). The above-mentioned serum levels of the observation group after treatment were lower than those in the control group, and there was a difference, which was statistically significant (P<0.05); the levels of PCⅢ, PCⅣ, and LN in the treatment group after treatment were significantly lower than those of the control group. The difference was statistically significant (P<0.05). Conclusion The application of tiopronin combined with glutathione in the treatment of non-alcoholic fatty liver can promote the recovery of liver function and reduce the concentrations of TC, TG and LDL, which is worthy of clinical promotion.

【Objective】 To develop an assay to determine β-lactam antibiotics using microcolumn gels and to study the β-lactam antibiotics present in the blood of patients and their clinical significances. 【Methods】 446 patients with a history of taking β-lactam antibiotics from January 2019 to June 2019 were randomly selected from Trauma Emergency Center, Department of Arthrosis, Department of Spine and Department of Bone Oncology of our hospital, and 4 mL(per capita) venous blood was collected. Irregular antibody screening, anti-globulin detection and drug antibody determination were performed by microcolumn gel method. The data of gender, age, disease, blood transfusion history and medication were collected. The test results and clinical data were retrospective analyzed. 【Results】 The yielding rate of antibody was 0.45%(2/446) in patients with a history of taking β -lactam antibiotics. 16.38%(73/446) of the samples were positive in direct antiglobulin test, and 64.38%(47/73) of them did not agglutinate with RBCs treated with drugs. The yielding rate of specific antibodies against drug was 4.93%(22/446), and the titer ranged from 2 to 128(8). 1 case of auto-IgM antibody, 1 case of blood group related antibody and 2 cases of non-specific protein adsorption were detected. The yielding rate of drug antibody in patients with blood transfusion history reached to 12.10 %(22/124), so it was also high in patients with bone tumor. 【Conclusion】 Direct antiglobulin assay is helpful for the detection of β-lactam antibodies. The negative results of antibody screening cannot completely exclude the presence of drug antibodies. The yielding rate of drug antibody can be greatly improved by specific drug antibody detection, and it was higher in transfused patients relative to non-transfused one.

Objective To study the relationship between serum betatrophin and early growth of macrosomia.Method Full-term macrosomia born in the Maternity and Children's Branch of Ruian People's Hospital of Zhejiang Province from January to June 2018 followed up to 6 months and their mother were enrolled in the prospective case-control study as the fetal macrosomia group.The full-term infants appropriate for gestational age,who met all the above requirements were randomly enrolled in the AGA group in a 1∶1 ratio.Enzyme linked immunosorbent assay (ELISA) was used to detect the level of blood betatrophin at birth and 6 months respectively,and the relationship between serum betatrophin level and the growth and development of infants was analyzed.Result A total of 4 823 live births were delivered during the study period,308 of them were full-term macrosomia,the incidence was 6.4％.30 cases were included in the macrosomia group and the AGA group,respectively.The level of blood betatrophin at birth and 6 months in the macrosomia group were higher than that in the AGA Group [(1 088.3 ± 67.8) ng/L vs.(929.5 ± 81.0) ng/L,(1 057.1 ± 114.2) ng/L vs.(976.4 ±76.6) ng/L],and the differences were statistically significant (P ＜ 0.01).The incidence of overweight was 26.7％ (8/30) in the macrosomia group and 6.7％ (2/30) in AGA group at 6 months of age,the difference was statistically significant (P ＜ 0.05).The level of blood betatrophin in overweight infants was statistically significantly higher than that in non-overweight infants (P ＜ 0.001).There was a positive correlation (P ＜ 0.001) between the level of blood betatrophin at the age of 6 months and the weight,body length,Z-score of weight/body length,triglyceride level at birth and the age of 6 months,and the level of umbilical blood betatrophin.But it was not correlated to gender,feeding pattern,other components of blood lipid,blood glucose and insulin in the cord blood and mother's blood,and the level of blood betatrophin in mother's blood (P ＞ 0.05).Conclusion The betatrophin is involved in the regulation of infant growth and development,which is associated with the occurrence of overweight.

Objective:To study the pathological changes of the spleen in patients with COVID-19 and to analyze the relationship between the weakened immune system and splenic lesions.Methods:Postmortem needle autopsies from the spleen were carried out on 10 patients who died from COVID-19 in Wuhan. Routine hematoxylin and eosin (HE) staining was used to observe the pathological changes. The changes of lymphocytes were studied further with immunohistochemistry.RT-PCR was used to detect 2019-nCoV RNA in the spleen. In addition,the Epstein-Barr virus (EBV) was detected by in situ hybridization, and coronavirus particles were detected by transmission electron microscopy in 2 cases.Results:There were 7 males and 3 females, with an average age of 68.3 years.Of the 10 cases, 4 had cancer history and another 4 had other underlying diseases respectively.Cough, fever, malaise and dyspnea were the main clinical symptoms.The time from onset to death was 15-45 days.Ten cases patients had normal or slight increase in peripheral blood leukocyte count in the early stage of the disease, 6 cases had significant increase before death. Five patients′ peripheral blood lymphocyte count decreased in the early stage of the disease, and 10 patients′ peripheral blood lymphocyte count decreased significantly before the disease progressed or died. Seven cases were treated with corticosteroid (methylprednisolone ≤40?mg/d, not more than 5 days). Histopathological examination showed that the cell composition of the spleen decreased, white pulp atrophied at different levels, meanwhile lymphoid follicles decreased or absent;in addition, the ratio of red pulp to white pulp increased with varying degrees. In 7 cases, more neutrophil infiltration was found, and in 5 cases, scattered plasma cell infiltration was found. Macrophage proliferation and hemophagocytic phenomena in a few cells were found in a case. Meanwhile, necrosis and lymphocyte apoptosis were detected in 2 cases, small artery thrombosis and spleen infarction in 1 case, and fungal infection in 1 case. The results of immunohistochemistry showed that the T and B lymphocyte components of the spleen in all cases decreased in varying degrees. CD20 + B cells were found to accumulate in the lymphoid sheath around the splenic artery in 8 cases. However, CD20 and CD21 immunostaining in 2 cases showed that the number of white pulp was almost normal, and splenic nodules were atrophic. CD3 +, CD4 + and CD8 +T cells were decreased. In 9 cases,CD68 + macrophages were no significant changes in the distribution and quantity. While more CD68 + cells were found in the medullary sinuses of 1 case (related to fungal infection). Few CD56 + cells were found. EBV was negative by in situ hybridization. RT-PCR was used to detect the nucleic acid of 2019-nCoV. One of 10 cases was positive, 39 years old,who was the youngest patient in this group, and the other 9 cases were negative. Coronavirus particles were found in the cytoplasm of macrophage under electron microscope in 2 cases. Conclusions:The death of COVID-19 occurs mainly in the elderly, and some cases have no underlying diseases. Spleen may be one of the organs directly attacked by the virus in some patients who died from COVID-19. T and B lymphocyte in the spleen decrease in varying degrees, lymphoid follicles are atrophied, decreased or absent, and the number of NK cells do not change significantly. And the pathological changes of the spleen are not related to the use of low dose corticosteroid, which may be related to the direct attack of virus and the attack of immune system on its own tissues.

Objective To investigate the nutritional risk of hospitalized infants with severe pneumonia and its relationship with clinical outcome. Methods Totally 113 infants with severe pneumonia admitted to pediatric intensive care unit (PICU)were enrolled in the study. Nutritional risks were screened by STRONGkids, and the nutritional were assessment with WHO Anthro. Clinical outcomes were recorded and analyzed, including mechanical ventilation, length of PICU stay, total hospital expenses, prognosis, and biochemical test index. Results A total of 44 infants (38.9％) had high nutritional risk, 49 (43.4％) had medium nutritional risk, 20 (17.7％) had low nutritional risk when they admitted to PICU. A total of 59 (52.2％) infants were malnourished when they admitted to PICU. There was a significant correlation between the degree of malnutrition and nutritional risk (r =0.574, P<0.01).The incidence of high nutritional risk was significantly higher in 28d～1year-old group than in 1～3 year-old group (χ2=20.46, P<0.01). Nearly 42.5％(48/113) of the children had congenital disease and had higher incidence of high nutritional risk (χ2=11.375, P=0.003) and higher incidence of malnutrition (χ2=10.083, P=0.001) than those without congenital disease. The rate of mechanical ventilation (P=0.028), the duration of mechanical ventilation (P<0.01), total hospital expenses (P=0.002) and the incidence of poor prognosis(P=0.014) were significantly higher in high nutritional risk group than the low nutritional risk group. The retinol binding protein in the high nutrition risk group was significantly lower than the low nutrition risk group (χ2=6.333, P=0.021). Conclusions High nutritional risk and malnutrition are common in infants with severe pneumonia. Malnutrition and nutritional risk are increased in patients less than 1 year old or suffering from congenital disease. Patients with high nutritional risk are more likely to have worse clinical outcomes. STRONGkids is a valid tool for nutritional risk screening in hospitalized children, and early nutrition support is recommended.

Objective To investigate the nutritional status and the clinical outcome of the critically ill chil-dren,and to provide scientific evidence for further clinical nutrition management. Methods Nutritional risk screening was performed on 1183 critically ill children hospitalized at the Intensive Care Unit (ICU),Children′s Hospital of Nanjing Medical University from October 2016 to October 2017 by using the Screening Tool for Risk on Nutritional Sta-tus and Growth (STRONGkids),the ICU including of Pediatric Intensive Care Unit (PICU),Surgical Intensive Care Unit (SICU)and Coronary Care Unit (CCU). Median age of the children was (2. 6 ± 2. 4)years (29 d - 12. 9 years). Nutritional status was estimated,and scores of anthropometric parameters such as weight - for - age Z - score (WAZ)(< 5 years)or body mass index - for - age Z - score (BAZ)(≥5 years)were calculated. The data on inci-dence of infectious complications,duration of ICU stay and mechanical ventilation,the total hospital expenses and in -hospital mortality were recorded. Results Of the 1183 cases,134 children(11. 3％)had low nutritional risk,746 children(63. 1％)had moderate nutritional risk and 303 children(25. 6％)high nutritional risk. The prevalence of se-vere malnutrition,moderate malnutrition and mild malnutrition was 8. 1％ (96 / 1183 cases),8. 2％ (97 / 1183 ca-ses),and 12. 8％ (151 / 1183 cases)respectively. The severe malnutrition group had a higher incidence of high nutri-tional risk than other groups [74. 0％(71 / 96 cases)vs. 67. 0％(65 / 97 cases),40. 4％(61/ 151 cases),12. 6％(106/839 cases)],and the differe-nce was statistically significant (P < 0. 001). The incidence of high nutritional risk in the CCU was higher than that than that in the PICU and SICU,and the difference was statistically significant [36. 5％(96 /263 cases),23. 8％(125 / 524 cases)and 20. 7％(82 / 396 cases)respectively,P < 0. 01]. And the incidence of high nutritional risk was higher in infants[37. 6％(198 / 527 cases)]than those in the other age groups[18. 4％(52 / 282 cases),12. 0％(21 / 175 cases),16. 0％(32 / 199 cases)],and the difference was statistically significant (χ2 = 68. 90, P < 0. 0001). Children with a high nutritional risk had increased incidence of infectious complications [8. 6％(26 / 303 cases)vs. 4. 7％ (35 / 746 cases),3. 7％ (5 / 134 cases)],incidence of mechanical ventilation [66. 0％ (200 / 303 cases)vs. 41. 4％(309 / 746 cases),38. 8％(52 / 134 cases)]and total hospital expenses (￥ 52500 vs. ￥ 39700 and￥ 48700 RMB)compared with those with the moderate or the low nutritional risk,and the differences were statistically significant(all P < 0. 05). There were 16 deaths and 8 deaths (2. 7％)in the high nutrition risk group,which was sig-nificantly higher than those in the moderate nutrition risk group [8 cases (1. 1％)]and the low nutrition risk group [0 case(0)](χ2 = 7. 60,P = 0. 02). Conclusions Moderate or high nutritional risk is seen in the critically ill chil-dren,especially in infants and the children with congenital heart disease. Nutritional risk score is correlated with clinical outcomes. Nutritional risk screening and standard nutritional support are recommended so as to improve clinical treat-ment outcomes.