ABSTRACT Taste is an important factor influencing the efficacy of oral formulations and patient compliance. Children have unique pathological and physiological characteristics and poor tolerance to adverse taste, which leads to inaccurate dosing and high risk of medication administration. Therefore, the establishment of an objective and scientific taste evaluation method is an important part of the research and development of drugs for children, which has important clinical significance and scientific value. This research group organized experts in the field of taste design and evaluation of pediatric drugs from five dimensions: instrumentation, research and development, clinical, review, and regulation, to clarify the current situation, discuss problems, and propose strategies for improvement, so as to provide reference for the development of suitable oral formulations for children.

In order to explore the treatment of Her-2 positive breast cancer patients who failed in multi-line treatments, we retrospectively analyzed the clinical data of a patient with refractory Her-2 positive breast cancer.The patient was initially diagnosed as Her-2 positive advanced breast cancer.After six line treatment in the outer hospital, the patient′s condition was basically in a progressive state.The breast tumor was broken and purulent, the lung metastasis increased, and the patient′s quality of life was poor.The patient was admitted to Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical University, after MDT discussion, we gave pyrrolotinib combined with capecitabine treatment, the chest wound healed gradually, the lung metastasis gradually reduced, and the quality of life was better.A retrospective analysis of this case showed that pyrrolidine combined with capecitabine may bring hope to Her-2 positive breast cancer patients who failed to receive multi-line therapies, especially those who failed to target therapy.

Objective:The hvKP phenotype strains were screened from the sensitive and multi-drug resistant Klebsiella pneumoniae, and the distribution and homology of their clinical infection characteristics were compared. Methods:A total of 158 Klebsiella pneumoniae strains isolated from clinical infection specimens in the Third Affiliated Hospital of Sun Yat-sen University from 2014 to 2018 were retrospectively collected. The string test (ST) was used to screen the hvKP infection, and a total of 65 were screened. The number of patients included 51 males and 14 females, with an average age of 56 years. The composition ratio of Klebsiellapneumoniae was analyzed for clinical infection related information. Matrix assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) was used to identify the hypervirulent Klebsiella pneumoniae and establish a new database, and bio-tree cluster analysis and principal component analysis were carried out for all strains that met the experimental conditions by using analysis software and the homology of protein level was obtained. Results:A total of 65 strains hvKP were screened, 62 of which were susceptible strains and 3 were multi-drug resistant strains. The main diseases of infected patients were diagnosed as hepatobiliary disease, encephalopathy and liver abscess. The basic diseases of the population were mainly diabetes and hypertension. Dendrogram cluster analysis divided hvKP into 3 groups at a distance of 550 from the horizontal line; principal component analysis found that some strains were closely related, and the Kc group with the largest proportion was mainly related to hepatobiliary diseases. Ka group was mainly related to infection after surgery.Conclusions:HvKP was highly invasive and the clinical manifestations of infection were diverse. The infected patients were mostly elderly patients with weakened immunity. The rapid homology analysis of MALDI-TOF MS mass spectrometry has important clinical significance for the rapid screening of hvKP infection.

Objective:To investigate the current status of multi-drug use in elderly inpatients with multiple chronic conditions in internal medicine and its correlation with nursing risk events, and to put forward targeted suggestions to help manage clinical multiple drug use in elderly patients.Methods:Using the convenient sampling method, a total of 2 254 elderly inpatients in Department of Internal Medicine in 4 Class Ⅲ Grade A general hospitals in Sichuan province were selected to conduct a questionnaire survey from March 2020 to January 2021, and their general conditions, multiple chronic conditions and multiple drug use were analyzed. Single factor and binary Logistic regression were used to analyze the current situation of multiple drug use in elderly patients with chronic disease and its influence on nursing risk events.Results:There were statistically significant differences in patients with different ages, weights, education levels, personal income, medical payment methods, whether they were weak or not, and whether patients with multiple chronic conditions took multiple drugs ( P<0.05) . Logistic regression analysis showed that education level and the number of chronic diseases were independent risk factors for multiple drug use ( P<0.05) . There were statistically significant differences in the total number of nursing risk events and the occurrence of pressure injuries, deep vein thrombosis and cardiac arrest in patients with multiple medications ( P<0.05) . In the same state of multimorbidity, the nursing risk events of patients with multiple drug use increased. In patients with the same multiple medications, the incidence of patient nursing risk events with an increase in the number of multimorbidities showed a downward trend. Conclusions:Elderly patients with a high education level, a large number of chronic diseases and aged 65-74 years old should pay special attention to whether they have multiple drug use behaviors. In the future, it is necessary to actively popularize the knowledge of rational drug use, actively prevent the occurrence of chronic diseases, strengthen the cooperation of drug management teams and comprehensively consider treatment options in multiple specialties, so as to fundamentally reduce multiple drug use.

Objective:The hvKP phenotype strains were screened from the sensitive and multi-drug resistant Klebsiella pneumoniae, and the distribution and homology of their clinical infection characteristics were compared. Methods:A total of 158 Klebsiella pneumoniae strains isolated from clinical infection specimens in the Third Affiliated Hospital of Sun Yat-sen University from 2014 to 2018 were retrospectively collected. The string test (ST) was used to screen the hvKP infection, and a total of 65 were screened. The number of patients included 51 males and 14 females, with an average age of 56 years. The composition ratio of Klebsiellapneumoniae was analyzed for clinical infection related information. Matrix assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) was used to identify the hypervirulent Klebsiella pneumoniae and establish a new database, and bio-tree cluster analysis and principal component analysis were carried out for all strains that met the experimental conditions by using analysis software and the homology of protein level was obtained. Results:A total of 65 strains hvKP were screened, 62 of which were susceptible strains and 3 were multi-drug resistant strains. The main diseases of infected patients were diagnosed as hepatobiliary disease, encephalopathy and liver abscess. The basic diseases of the population were mainly diabetes and hypertension. Dendrogram cluster analysis divided hvKP into 3 groups at a distance of 550 from the horizontal line; principal component analysis found that some strains were closely related, and the Kc group with the largest proportion was mainly related to hepatobiliary diseases. Ka group was mainly related to infection after surgery.Conclusions:HvKP was highly invasive and the clinical manifestations of infection were diverse. The infected patients were mostly elderly patients with weakened immunity. The rapid homology analysis of MALDI-TOF MS mass spectrometry has important clinical significance for the rapid screening of hvKP infection.

Objective:To explore the correlation of serum neurogenic exosome MicroRNA-211-5p(miR-211-5p)levels and brain derived neurotrophic factor(BDNF)levels with cognitive impairment in patients with Parkinson's disease and their diagnostic value.Methods:A total of 80 patients with Parkinson's disease(PD)admitted to the Second Hospital of Jiaxing City from January 2017 to April 2018 were enrolled.According to the Montreal cognitive assessment scale, patients were divided into the cognitive impairment group(n=36)and the non-cognitive impairment group(n=44). Meanwhile, 30 healthy people who took health check-ups during the same period were selected as the control group.Exosomes were extracted from peripheral blood of subjects by using the ExoQuick kit, and the neurogenic exosomes were separated by an L1 cell adhesion molecule(L1CAM)biotinylated antibody.BDNF levels in the exosomes were measured with an enzyme-linked immunosorbent assay(ELISA), and the expression level of miR-211-5p in the exosome was determined by real-time fluorescence quantitative PCR(RT-QPCR).Results:There was a correlation between BDNF and miR-211-5p( r=-0.805, P<0.001)in serum neurogenic exosomes( r=-0.805, P<0.001). BDNF was correlated with miR-211-5p in both the PD and control groups( r=-0.785 and-0.867, P=0.002 and 0.001). The miR-211-5p level was higher and the BDNF level was lower in the PD group than in the control group(0.30±0.08 vs. 0.17±0.04, 0.55±0.06 mg/L vs. 0.75±0.06 mg/L, t=7.125 and 6.368, P=0.000 and 0.000). The BDNF level was lower(0.45±0.07 mg/L vs.0.63±0.07 6.368 and 0.75±0.08 mg/L, t=8.999 and 7.608, P=0.000 and 0.000)and the MiR-211-5p level was higher(0.36±0.07 vs. 0.24±0.05 and 0.17±0.04, t=10.923 and 7.520, P=0.000 and 0.000)in the cognitive impairment group than in the non-cognitive impairment and control groups.The receiver-operating characteristics(ROC)curve showed that the area under the curve of miR-211-5p as a measure for cognitive impairment in Parkinson's disease was 0.860(95% CI: 0.770-0.950)with a threshold of 0.32.The area under the curve of BDNF as a measure for cognitive impairment in Parkinson's disease was 0.891(95% CI: 0.822-0.961)with a threshold of 0.67.BDNF seemed to be the target gene of miR-211-5p, since the latter could inhibit BDNF expression by reducing BDNF mRNA levels. Conclusions:Human serum neurogenic exosome miR-211-5p is highly expressed in PD patients with cognitive impairment and has the potential to be used as one of diagnostic parameters for cognitive impairment in PD patients.The high expression of serum neurogenic exosome miR-211-5p may be related to the inhibition of BDNF by reducing its mRNA levels.

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.

Objective To study the effect of intestinal bacteria on motor ability of amyotrophic lateral sclerosis (ALS) mice models and its mechanism. Methods Twenty wild type C57BL/6J mice (WT group) and 20 SOD1-G93A transgenic ALS mice (ALS group) were selected as the research subjects. (1) Ten mice in both WT group and ALS group were selected, respectively; 5 mice in each group were fed in SPF environment, and the remaining 5 mice were fed in aseptic environment; they were defined as WT+SPF group, WT+aseptic group, ALS+SPF group and ALS+aseptic group. (2) Ten mice in WT group and ALS group were fed in sterile environment; 5 mice in each group were transplanted with fecal bacteria, and the remaining 5 mice were not interfered; they were defined as WT+transplantation group, WT+non-transplantation group, ALS+transplantation group and ALS+non transplantation group. The grip strength of mice was measured by grip force meter, the motor coordination ability of mice was tested by roller treadmill and rotating rod test, the number of motor neurons in the anterior horn of spinal cord was measured by Nissl staining, the expression of microglia activation marker ionic calcium junction protein (IBA-1) in spinal cord tissues was detected by immunohistochemical staining, and the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in spinal cord tissues were detected by Western blotting; the β-N-methylamino-L-alanine (BMAA) expression was detected by high performance liquid chromatography-tandem mass spectrometry. Results (1) The grip strength, drop latency and drop time of ALS+aseptic mice were significantly higher than those of ALS+SPF mice, the number of Nissl-stained positive cells was significantly larger than that of ALS+SPF mice, the number of IBA-1 positive cells was significantly smaller than that of ALS+SPF mice, the levels of TNF-α and IL-6 protein expressions and BMAA concentration were statistically lower than those of ALS+SPF mice (P<0.05). (2) The grip strength, drop latency and drop time of ALS+transplantion mice were significantly lower than those of ALS+non-transplantation mice, the number of Nissl-stained positive cells was significantly smaller than that of ALS+non-transplantation mice, the number of IBA-1 positive cells was significantly larger than that of ALS+non-transplantation mice, the TNF-α and IL-6 protein expressions and BMAA concentration were significantly higher than those of ALS+non-transplantation mice (P<0.05). Conclusion Imbalance of intestinal bacteria homeostasis can decrease the motor ability of ALS mice, which is related to the activation of microglia.

Objective To investigate the effects of dl-3-n-butylphthalide ( NBP) on angiogenesis of human umbilical vein endothelial cells ( HUVEC) in vitro under ischemia/hypoxia and the correlation with vascular endothelial growth factor/vascular endothelial growth factor receptor 2 ( VEGF/VEGFR2 )-Notch1/Dll4 signaling pathway .Methods The control group , ischemia/hypoxia group , and ischemia/hypoxia +NBP group ( high dose group and low dose group ) were set up after HUVEC subculture . The cell concentration was adjusted to be 1 ×105/ml, and each group was randomly added 1 ml (1 ×105 cells in each group).Both of the ischemia/hypoxia group and the ischemia/hypoxia +NBP group were cultured under the condition of ischemia and hypoxia .The NBP concentrations of the high and low dose groups were 20 μmol/L and 5 μmol/L respectively.The cell viability of each group was detected by cell counting kit-8, and cell scratch test was used to detect the migration ability of the cells in each group .The cell formation ability of each group was examined by in vitro angiogenesis assay.Western blotting was used to detect the expressions of receptor proteins VEGFR2, Notch1 and Dll4,and mRNA expressions of VEGF, VEGFR2, Notch1 and Dll4 were detected by real-time quantitative PCR.Results NBP increased the survival rates of HUVEC under ischemia/hypoxia condition.In the low dose group, the survival rates of HUVEC at 6, 12, 24, 48 h were 78.6％ ±3.0％, 59.6％ ±5.3％, 44.6％ ±4.2％, 38.2％ ±4.3％, respectively, significantly higher than that in the ischemia/hypoxia group (75.2％±5.8％, 53.2％±4.8％, 36.2％± 7.8％, 22.5％±4.1％;t=4.513, 6.231, 9.322, 9.674; P=0.021, 0.018, 0.026, 0.015).In the high dose group, the survival rates of HUVEC at 6, 12, 24, 48 h were 88.6％±6.3％, 67.5％±5.4％, 53.3％±4.2％, 46.3％±3.9％, respectively , also significantly higher than that in the ischemia/hypoxia group (t=8.123, 11.211, 12.312, 14.154;P=0.001, 0.002, 0.001, 0.001).The mobility of the low dose group was 52.3％+4.2％, with statistically significant difference compared with that in the ischemia /hypoxia group ( 18.5％ ±3.2％) and the control group ( 22.3％ ±4.1％; t=18.324, 15.183; P=0.000, 0.000).The mobility of the high dose group was 87.5％±5.2％, also with statistically significant difference compared with that in the ischemia/hypoxia group and the control group ( t=22.142, 19.341;P=0.000, 0.000).NBP increased the protein and mRNA expression of VEGF , VEGFR2, Notch1 and Dll4.The relative expression of VEGFR2, Notch1 and Dll4 in the low dose group was 1.12 ±0.17, 0.35 ± 0.07 and 0.42 ±0.08, respectively, with statistically significant difference compared with that in the ischemia/hypoxia group (0.82 ±0.05, 0.30 ±0.03, 0.32 ±0.04;t=6.120, 2.123, 4.112;P=0.000, 0.020, 0.003).The relative expression of VEGFR2, Notch1 and Dll4 in the high dose group was 1.30 ± 0.15, 0.41 ±0.10 and 0.48 ±0.11, respectively, also with statistically significant difference compared with that in the ischemia/hypoxia group ( t=8.122, 3.851, 5.130; P=0.000, 0.000, 0.001 ) .The mRNA expressions of VEGF , VEGFR2, Notch1 and Dll4 in the low dose group were 0.43 ±0.08, 0.41 ± 0.05, 0.38 ±0.03 and 0.36 ±0.04, respectively, with statistically significant difference compared with that in the ischemia/hypoxia group (0.28 ±0.03, 0.34 ±0.04, 0.27 ±0.03, 0.19 ±0.04;t=3.122, 3.825, 4.311, 5.211; P=0.000, 0.006, 0.001, 0.000).And the mRNA expressions of VEGF, VEGFR2, Notch1 and Dll4 in the high dose group were 0.58 ±0.05, 0.50 ±0.06, 0.41 ±0.05, 0.52 ±0.06, respectively, also with statistically significant difference compared with that in the ischemia /hypoxia group (t=4.225, 4.872, 5.311, 8.220;P=0.000, 0.000, 0.000, 0.000).Conclusions NBP can promote HUVEC to form blood vessels under ischemia/hypoxia condition , the mechanism of which may be related to the activation of VEGF/VEGFR2-Notch1/Dll4 signaling pathway .It may be one of the mechanisms that NBP improves cerebral microcirculation in acute ischemic stroke .

Objective To observe imaging features of uterus duplication combined with mesonephric duct dysplasia related abnormalities.Methods Imaging data of 17 female with uterus duplication and renal dysplasia were retrospectively analyzed.Seven patients underwent CT and 10 patients underwent MR scanning.Results The basic abnormalities in 17 patients were uterus duplication combined with unilateral renal-ureter dysplasia with/without other associated malformation which were further classified as follows:①7 patients presented as basic abnormalities without other associated malformations,include 5 (CT diagnosed 1,MR diagnosed 4) with uterus duplex and unilateral renal-ureter agenesis,2 (CT 1,MR 1) with uterus bifidus and unilateral renal-ureter dysplasia;②2 patients (CT 1,MR 1) presented as basic abnormalities accompanied with ectopic ureter orifice,uterus duplex and unilateral renal dysplasia with ectopic ureter orifice opening in vagina;③5 patients (CT 3,MR 2) of Herlyn-Werner-Wunderlich syndrome presented as uterus duplication,oblique vagina septum as well as unilateral renal-ureter dysplasia,which shown as uterus duplex,oblique vaginal septum with hematocolpos,also unilateral renal-ureter agenesis;④2 patients presented as basic abnormalities accompanied with mesonephric residual cyst,CT showed one with uterus duplex and unilateral renal-ureter agenesis with ipsilateral mesonephric residual cyst,MRI showed as the other one with Herlyn-Werner-Wunderlich syndrome combined with mesonephric residual cyst opening in vagina;⑤MRI showed 1 patient with basic abnormalities and a nephrogenic adenoma,which demonstrated as uterus duplex combined with left renal-ureter agenesis,and a tumor on the left wall of bladder accompanied with endometriosis.Conclusion Further classification into 5 types from simple to complex based on uterus duplication combined with unilateral renal-ureter dysplasia with/without other associated malformations is helpful to the diagnosis and treatment of these abnormalities.