Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavior.Methods Sixty 6～8-week-old SPF-grade ICR male mice were divided into two groups.5-Aza-CdR was administered to one group of mice via lateral ventricular injection,while the control group was injected with bovine serum albumin.Notch1 and HES1 mRNA and protein expression levels were detected by Real-time PCR and Western blot 24 hours after injection;5-bromo-2'-deoxyuridine-positive cells were observed by laser confocal microscopy,and Notch1 expression in hippocampal dentate gyrus was viewed with laser confocal microscopy.Notch1 methylation changes were detected by ethylation-specific PCR,and learning and memory behaviors of mice were assessed by passive avoidance tests and shuttle avoidance assays.Results Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity,promoted neuronal regeneration in the DG region,decreased methylation levels in the Notch1 promoter region,and enhanced the ability of mice to perform active avoidance behavior.Conclusions The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch 1 pathway.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

ObjectiveFrom the perspective of energy metabolism， the mechanism of Osteoking （OK） in the treatment of myofascial pain syndrome （MPS） was revealed through systems biology prediction combined with holistic animal experimental validation methods. MethodFirstly， the key targets of MPS and their related molecular mechanisms were predicted by the systems biology method， and the core network targets were screened. Then， the network-predicted targets were verified by animal experiments. Specifically， 60 SD rats were randomly divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg^-1）， and positive celecoxib group （21 mg·kg^-1）. The MPS model was established by beating combined with a centrifugal exercise method for eight weeks. Except for two days after modeling， the intervention of OK or celecoxib was performed. After the completion of the model， the drug was administered for two weeks. The histopathological changes of trigger point muscle tissue were observed by hematoxylin-eosin staining. The content/activity of Na-K-ATP enzyme （Na⁺-K⁺-ATPase）， Ca²⁺ pump （Ca²⁺ATPase）， Ca²⁺， lactate dehydrogenase （LDH）， glutathione （GSH）， malondialal （MDA）， superoxide dismutase （SOD）， cyclic adenosine phosphate （cAMP）， and protein kinase A （PKA） in serum and/or trigger point muscle tissue in MPS rats was detected by enzyme-linked immunosorbent assay. Protein expression levels of PKA and the peroxisome proliferator-activated receptor γ coactivator 1α （PGC1α） in MPS rats were detected by immunohistochemistry. The protein expression levels of PKA， PGC1α， and mitochondrial transcription factor A （TFAM） in MPS rats were detected by Western blot. ResultThe network prediction results suggest that OK acts on the key target of energy metabolism related to the occurrence and development of MPS and may participate in the activation of the cAMP/PKA/PGC1α signaling pathway. The experimental validation results show that compared with the normal group， contracture nodules and disordered arrangement of muscle fibers appear in the trigger point muscle tissue of MPS rats. Na⁺-K⁺-ATPase， Ca²⁺ATPase， SOD activity， Ca²⁺， and GSH contents in serum and/or trigger point muscle tissue are significantly decreased （P<0.01）. Both LDH activity and MDA contents are significantly increased （P<0.01）， and the protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly decreased （P<0.01）. Compared with the model group， OK improves the histopathological morphology of trigger point muscle fibers in MPS rats， and after the intervention of OK， Na⁺-K⁺-ATPase， Ca²⁺ATPase， SOD activity， Ca²⁺， and GSH contents in serum and/or trigger point muscle tissue in MPS rats are significantly increased （P<0.05， P<0.01）. LDH activity and MDA contents are significantly reduced （P<0.05， P<0.01）. The protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly increased （P<0.05， P<0.01）. ConclusionThe mechanism of OK's intervention in MPS rats may be related to its effective activation of the cAMP/PKA/PGC1α signaling pathway， thus promoting mitochondrial energy metabolism and trigger point muscle fiber damage repair in muscle cells.

Objective:To investigate the influence of trimethylamine N-oxide(TMAO)on the development of early neurological deterioration(END)in diabetic patients with acute ischemic stroke.Methods:In this cross-sectional study, 108 type 2 diabetes patients with acute ischemic stroke treated at the Department of Neurology in the Affiliated Wuxi People’s Hospital of Nanjing Medical University between October 2019 and November 2020 were consecutively recruited.END was defined as an increase in the National Institutes of Health Stroke Scale(NIHSS)≥ 2 points and exclusion of intracranial hemorrhage or bleeding transformation in cranial imaging evaluation within 5 days of initial deterioration of neurological dysfunction.The patients were divided into 2 groups, an END(n=36)group and a non-END group(n=72). Fasting plasma TMAO was measured using isotope dilution liquid chromatography coupled to tandem mass spectrometry.Results:Of the 108 patients, 36(33.3%)were diagnosed with END, and their plasma TMAO levels were significantly higher compared with patients without END( Z=-3.500, P<0.001). For prediction of END, the area under the ROC curve for plasma TMAO levels was 0.707(95% CI: 0.603-0.811, P<0.001). The frequencies of END in subjects grouped via tertiles of TMAO were 22.2%, 19.4% and 58.3%, respectively, with significant differences between the 3 groups( χ2=14.979, P=0.001). Univariate analysis showed that elevated TMAO( OR=1.160, 95% CI: 1.050-1.282, P=0.004)was associated with END.A multivariate logistic regression model further confirmed the association between TMAO and END( OR=1.145, 95% CI: 1.033-1.269, P=0.010). Conclusions:Increased plasma TMAO levels are associated with END in diabetic patients with acute ischemic stroke.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Biotin-thiamine-responsive basal ganglia disease is a rare treatable autosomal recessive neurometabolic disorder caused by mutations in SLC19A3 gene, encoding a transporter of thiamine across the plasma membrane. In the present study, a 29-year-old male patient with epilepsy as the first symptom, accompanied by hypokinesia, extraocular muscle paralysis and delayed dystonia was reported. The brain magnetic resonance imaging revealed abnormal symmetrical signals of bilateral caudate nucleus and lenticular nucleus. The patient was diagnosed as biotin-thiamine-responsive basal ganglia disease by gene detection. After treatment with biotin and thiamine, the symptoms were relieved and the brain lesions subsided.

Objective:To investigate the cause of the allograft IgA nephropathy (IgAN) recurrence or de novo, and the risk factors for the graft-survival in allograft IgAN. Methods:Patients from the First Affiliated Hospital of Zhejiang University Medical College who were diagnosed as a transplanted kidney IgAN by allo-renal biopsy during November 2012 to December 2018 were selected. According to the increased levels of serum creatinine and the descent rate of estimated glomerular filtration rate (eGFR) on the last follow up, the patients were divided into the graft-function stable group (increased Scr<20 μmol/L, eGFR descent rate<10%), the graft-function inadequacy progressive group (Scr increased but less than doubling increase, 30%

Objective To explore the clinical characteristics of tertiary hyperparathyroidism (THPT) after renal transplantation .Methods The levels of bone mineral density (BMD) , serum calcium , phosphates , alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH ) were retrospectively analyzed in 36 RTx recipients with persistent hypercalcemia and stable kidney function (eGFR 76 .71 ± 17 .44) ml/min/1 .73 m2 .Results Among them ,serum total calcium level increased (2 .97 ± 0 .20 ) mmol/L for 6 to 170 months ,blood phosphorus decreased (0 .59 ± 0 .19 ) mmol/L , serum alkaline phosphatase (ALP) increased to (295 .73 ± 194 .22)U/L and T-score of BMD decreased (T - 2 .78 ± 0 .84 in lumbar vertebrae and T - 2 .09 ± 0 .66 in hip joint) .And 11 /36 (30 .6％ ) cases had a complication of extraosseous calcification .Parathyroid hyperplasia was detected in 17 /36 cases (47 .2％ ) .iPTH was significantly higher at pre-operation and 1 week post-operation than that in control group (n= 45) (859 .50 ± 495 .44 vs 345 .56 ± 216 .55 pg/ml) , P = 0 .001 ,(759 .25 ± 907 .07 vs 197 .45 ± 249 .31 pg/ml) , P= 0 .001 .The value of iPTH at the last follow-up (198 .26 ± 155 .22) pg/ml was still higher than normal reference value (15 .0 - 65 .0 pg/ml) . Multivariate stepwise regression analysis showed the last iPTH was correlated with preoperative iPTH ,serum calcium and postoperative serum phosphor ,ALP and 25OHD3 (P= 0 .024 , P= 0 .002 , P = 0 .001 , P = 0 .037 , P = 0 .026 ) .Conclusions Renal recipients had a higher levels iPTH with persistent hypercalcemia , hypophosphatemia , osteoporosis and extraosseous calcification showing the features of tertiary hyperparathyroidism .

Objective To evaluate the influence of preset adaptive statistical iterative reconstruction-V (ASIR-V) techniques on image quality and radiation dose reduction of abdominal CT in phantom,and to investigate the optimal ASIR-V level.Methods Abdominal anthropomorphic phantom was scanned using Revolution CT,when noise index (NI) were set as 6,8,10,12 and 14,respectively.Then 0-100％ ASIR-V and conventional scan was performed and 55 sets of images were obtained.CT value,noise,subjective score and radiation dose were recorded,and the optimal ASIR-V was obtained.Subjective scores of images in each group were compared using rank sum test,and CT value,noise and radiation dose were compared with one way ANOVA and paired t test.Results The image subjective score unchanged when NI was 6,8 or 10,slightly increased when NI was 12 and 14 with 0-40％ ASIR-V,and decreased above 50％ ASIR-V at all NI.When NI was 6,8 or 10,more than 70％ ASIR-V image subjective score fell below 3 points.When NI was 12 or 14 group,more than 60％ ASIR V subjective score fell below 3 points.The image quality score of conventional scan had no difference with 40％ ASIR-V when NI was 6,8 or 10,respectively (P=0.626,0.915,0.514),and inferior to 40％ ASIR-V when NI was 12 or 14 (P=0.041,0.036),while in all NI group,image quality score of conventional scan was superior to 60％ ASIR-V (P=0.021,0.012,0.015,0.014,0.007).CT values and image noises had no significant differences in different parts in all NI groups (all P＞0.05).CT dose index volume (CTDIvol) continuing decreased with ASIR-V.Compared with that of conventional scan,at 40％,50％ and 60％ ASIR-V,CTDIvol reduced by 49.82％,62.51％ and 71.63％,respectively.Conclusion Preset ASIR-V can reduce radiation dose obviously while maintaining the overall image quality,and 40％-60％ ASIR-V can be recommended for abdominal CT in clinical application.