Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

【Objective】 To investigate the effects of lamellar surgical techniques with urethral plate to strengthen the tissue of glans penis to widen the two flanks of glans penis on the basis of Duckett method in the treatment of congenital hypospadias with small glans penis deformity. 【Methods】 A total of 22 patients admitted to our hospital during Jun.2017 and Oct.2020 were involved. Urethral plate was used to replace the glans penis tissue to widen the two flanks of glans penis based on Duckett method. Lamellar surgical techniques were adopted to fully dissociate the two flanks of glans penis and urethral plate for urethroplasty. 【Results】 Of the 22 operations, 19 were successful,with a success rate of 86.3%. The success rate of penile head urethroplasty reached 96.1%. 【Conclusion】 Widening the glans penis by using the urethral plate based on Duckett method combined with lamellar surgical techniques can improve the success rate of glans penis urethroplasty.

Taking case discussion of clinical treatment options of primary liver cancer during clinical internship as an example, the course design of basic elements of case-based learning (CBL) was discussed. The purpose of clinical practice is to cultivate the clinical thinking ability of "selecting the best one from multiple treatment options", which is suitable for taking CBL teaching method. The design of CBL course includes 8 elements: teaching object, purpose, objectives, course content, implementation plan, key points for assessment, course evaluation and reference materials. The core points of the design of CBL course are that: ①The teaching objectives include knowledge, ability and professionalism; ②The course content should includes the training of decision-making organizations and clinical thinking ability of selecting the best one from multiple treatment options; ③The general CBL teaching procedure can be adopted in the implementation of the scheme that focuses on the decision-making issues defined in each decision-making step. The teaching practice of CBL on primary liver cancer cases discussion shows the basic design of CBL course is universal, which is helpful for teachers to design and implement CBL course on clinical treatment options.

Objective: Balb/c mice infected with respiratory syncytial virus(RSV) were used to investigate the metabolic changes in cecal luminal content. Methods: A total of 13 female Balb/c mice were randomly divided into Case group(n=7) and control(Ctrl) group(n=6). Animals in Case group were infected with RSV by using intranasal method, while mice in Ctrl group were treated with DMEM medium. Mice were anesthetized with intraperitoneal administration of 10% chloral hydrate and the cecal luminal contents were harvested under sterile conditions. Metabolite concentrations were measured by UPLC-QTOF/MS system. Univariate and multivariate statistical analysis were used to identify differential metabolites between Case and Ctrl groups. Results: The overall base peak chromatogram between Case and Ctrl groups had a clear disparity, and PCA and OPLS-DA analysis showed obviously discrepancy based overall metabolomic profile. L-serine, 2-ketobutyric acid, Oleic acid and Chenodeoxycholic acid glycine conjugate were enriched in Case group, whereas L-methionine, L-tyrosine and Nicotinic acid were depleted. Pathway analysis showed lysine degradation, Cysteine and methionine metabolism were enriched. Conclusion Lung injury induced by RSV infection may cause the endogenous metabolism disorder of cecal contents.

Stargardt disease (STGD) is one of the most prevalent inherited macular dystrophy, and most often occurs in child or adolescence. Irreversible vision loss is observed in almost all cases. Type 1 (STGD1) is one of the most common type. It is an autosomal recessive condition, caused by mutations in the Abca4 gene. In recent years, encouraging progress has been made in the treatment of STGD1. C20-D3-retinyl acetate (ALK- 001), fenretinide and ICR-14967 (A1120) as visual cycle modulators, StarGen as gene supplementation therapies, and the stem cell transplantation of human embryonic stem cell-derived retinal pigment epithelium cells are the most promising therapies. With the development of studies and clinical trials, the clinical application of various treatments of STGD1 are expected in the near feature, which are expected to save the vision of most patients.

Objective:To summarize the experiences in the construction of Clinical Research Unite (CRU) at a hospital level, provide reference for CRU construction in the Chinese hospitals.Methods:The CRU construction should take clinical research project management as working priority, strengthen clinical research team building, improve process management, as well as improve project performance and output.Results:During the CRU construction period, the number and level of clinical research projects have been improved in various disciplines. The sample database and disease specific data have been accumulated. The CRU mode helps the high-quality development of clinical researches in hospital.Conclusions:The way our hospital take in the construction of CRU was a good example, and it may truly improve the quality and capacity of clinical researches.

Objective:To evaluate the effect of intestinal carbapenem-resistant Enterobacteriaceae (CRE) active screening combined with enhanced intervention in the prevention and control of nosocomial infection in patients admitted to the hematological ward.Methods:Patients who were admitted to the Department of Hematology in a tertiary-care general hospital from March 1, 2017 to December 31, 2019 and underwent chemotherapy or immunosuppressive therapy comprised the intervention group. They were screened for intestinal CRE at least thrice. From December 1, 2016 to February 28, 2017, patients who underwent chemotherapy or immunosuppressive therapy without active intestinal CRE screening in the Department of Hematology formed the control group. Both the patient groups were monitored for CRE infection in real time. The χ2 test was used to compare the changes in the CRE infection rate and mortality in high-risk patients before and after the active screening. Results:During the intervention period, the CRE colonization rate of patients was 16.46% (66/401) ; in terms of disease distribution, the colonization rate of acute leukemia was the highest 23.03% (26/113) . Of the 66 colonized patients, 27 (40.9%) patients were identified as positive for CRE at the first screening, 15 (22.7%) were identified at the time of the second screening, and the remaining 24 (36.4%) were identified at the third or subsequent screening; Carbapenem-resistant Klebsiella pneumoniae (CRPK) strains were dominant among the pathogens, accounting for 54.55% (36/66) . During the active screening period, the CRE infection rate (2.49%) and mortality rate (50.00%) of high-risk patients were significantly lower than those of the controls (11.30% and 69.23%, respectively) . The pathogens of 10 CRE infection patients during the intervention period were exactly the same as the previous active screening pathogens, and the coincidence rate was 100%.Conclusion:The CRE colonization rate was the highest in patients with acute leukemia who were admitted in the hematology wards. CRPK is the main pathogen of CRE colonization, infection, and death. Increasing the frequency of screening can significantly raise the positive rate of screening, Active screening can effectively reduce the incidence and subsequent mortality of CRE in high-risk patients admitted in the hematological wards. High coincidence rate between CRE screening positive pathogens and subsequent CRE infection pathogens. Intestinal CRE screening can serve as an indicator of CRE bloodstream infection in patients with hematological diseases as well as provide information for antibiotics therapy.

Objective To explore the protective effect and mechanism of the dihydromyricetin (DHM) on cognitive dysfunction in Alzheimer’s disease (AD) rat model. Methods The AD model of rats was established by injecting Aβ1-42 oligomolymer into the hippocampus. According to the random number table,30 successfully constructed AD model rats were divided into AD group,AD+DHM1 group and AD+DHM2 group,with 10 in each group. And the rats in the three groups were intraperitoneally injected with nor-mal saline,100 mg/kg DHM and 200 mg/kg DHM for 21 days,respectively. Another 10 rats with body mass matching were taken as the control group. Morris water maze was used to evaluate the spatial learning and memory ability of rats in each group,the expression of inflammatory cytokines were detected by Elisa,and the expressions of AMPK and SIRT1 proteins were detected by Western blot. Results Compared with the con-trol group,the escape incubation period of rats in AD group was prolonged,and the difference was statistically significant (day 5 :(10. 36±2. 80)s,(22. 40±2. 98)s;t=-18. 63,P<0. 05). Compared with AD group,the escape latency of rats in AD+DHM1 group and AD+DHM2 group were shortened (day 5:AD+DHM1 group (15. 68±3. 06) s,AD+DHM2 group (18. 85±3. 22) s; t=10. 65,4. 13,both P<0. 05). Compared with AD group,rats in AD+DHM1 group and AD+DHM2 group had more crossing times ((1. 87± 0. 76),( 2. 75± 0. 63) and (3. 78±0. 71);t=-6. 86,-9. 83,both P<0. 05),and the target quadrant residence time were ex-tended ((17. 08±1. 99) s,(16. 33±4. 33) s,(22. 59±4. 21) s;t= 28. 5,8. 63,both P<0. 05). Compared with the control group,the levels of IL-1β,IL-6 and TNF-α in the serum and hippocampus of the AD group were significantly increased (serum: t=4. 98, 7. 87, 5. 43, all P<0. 05; hippocampus: t=11. 13, 30. 50, 23. 38,all P<0. 05). Compared with the AD group,the levels of IL-1β,IL-6 and TNF-α in the serum and hippocampus of the AD+DHM1 group and the AD+DHM2 group were significantly decreased,the difference was statistically significant ( serum: AD+DHM1 group t=-4. 13,-10. 70,-9. 22, AD+DHM2 group t=-1. 75,-3. 63,-18. 75,all P<0. 05;hippocampus:AD+DHM1 group t=-69. 13,-15. 13,-6. 50,AD+DHM2 group t=-10. 25,-39. 00,-8. 00,all P<0. 05). Compared with the control group,the expression of p-AMPK/AMPK protein and SIRT1 protein in the AD group were decreased. The expression of the two pro-teins in the AD+DHM1 group and the AD+DHM2 group were increased,comparing with those of AD group, and the difference was statistically significant(all P<0. 05). Conclusion DHM exerts protective role in AD model rats,which may be related to the activation of AMPK/SIRT1 pathway and the inhibition of inflammato-ry response.

Objective: To explore the protective effect and mechanism of the dihydromyricetin (DHM) on cognitive dysfunction in Alzheimer’s disease (AD) rat model. Methods: The AD model of rats was established by injecting Aβ1-42 oligomolymer into the hippocampus. According to the random number table, 30 successfully constructed AD model rats were divided into AD group, AD+ DHM1 group and AD+ DHM2 group, with 10 in each group.And the rats in the three groups were intraperitoneally injected with normal saline, 100 mg/kg DHM and 200 mg/kg DHM for 21 days, respectively.Another 10 rats with body mass matching were taken as the control group.Morris water maze was used to evaluate the spatial learning and memory ability of rats in each group, the expression of inflammatory cytokines were detected by Elisa, and the expressions of AMPK and SIRT1 proteins were detected by Western blot. Results: Compared with the control group, the escape incubation period of rats in AD group was prolonged, and the difference was statistically significant (day 5 : (10.36±2.80)s, (22.40±2.98)s; t=-18.63, P<0.05). Compared with AD group, the escape latency of rats in AD+ DHM1 group and AD+ DHM2 group were shortened (day 5: AD+ DHM1 group (15.68±3.06) s, AD+ DHM2 group (18.85±3.22) s; t=10.65, 4.13, both P<0.05). Compared with AD group, rats in AD+ DHM1 group and AD+ DHM2 group had more crossing times ((1.87±0.76), (2.75±0.63) and (3.78±0.71); t=-6.86, -9.83, both P<0.05), and the target quadrant residence time were extended ((17.08±1.99) s, (16.33±4.33) s, (22.59±4.21) s; t= 28.5, 8.63, both P<0.05). Compared with the control group, the levels of IL-1β, IL-6 and TNF-α in the serum and hippocampus of the AD group were significantly increased (serum: t=4.98, 7.87, 5.43, all P<0.05; hippocampus: t=11.13, 30.50, 23.38, all P<0.05). Compared with the AD group, the levels of IL-1β, IL-6 and TNF-α in the serum and hippocampus of the AD+ DHM1 group and the AD+ DHM2 group were significantly decreased, the difference was statistically significant(serum: AD+ DHM1 group t=-4.13, -10.70, -9.22, AD+ DHM2 group t=-1.75, -3.63, -18.75, all P<0.05; hippocampus: AD+ DHM1 group t=-69.13, -15.13, -6.50, AD+ DHM2 group t=-10.25, -39.00, -8.00, all P<0.05). Compared with the control group, the expression of p-AMPK/AMPK protein and SIRT1 protein in the AD group were decreased.The expression of the two proteins in the AD+ DHM1 group and the AD+ DHM2 group were increased, comparing with those of AD group, and the difference was statistically significant(all P<0.05). Conclusion DHM exerts protective role in AD model rats, which may be related to the activation of AMPK/SIRT1 pathway and the inhibition of inflammatory response.

Objective To investigate the distribution of diarrhea pathogens in infants without rotavirus-detection in Hangzhou. Methods 605 stool samples of children with rotavirus-negative diarrhea were collected from Hangzhou First People's Hospital of Zhejiang University, Children's Hospital of Zhejiang University and Hangzhou Children's Hospital from March 2017 to June 2018. The routine test results were analyzed retrospectively and Bristol score was used for the characteristics of stool samples. DNA and/or RNA were extracted from fecal samples with DNA and RNA extraction kit. The extracted DNA and RNA-reversed cDNA were used as templates. 7 common pathogens DNA and/or RNA were amplified by polymerase chain reaction (PCR). The amplified products were detected by agarose gel electrophoresis. The positive rates of pathogens were analyzed by chi-square test. Results Among 605 children, 375 were male (28±11) months and 230 were female (29±10) months. Bristol score of stool samples was mainly in type 6 (496, 82％), followed by type 7 (85, 14％) and type 5 (24, 4％). Among 605 results 97 cases were occult blood positive (positive rate 16％) and 170 cases were white blood cell positive (positive rate 28％).452 of 605 stool samples were positive for pathogen target genes. The positive rate was 74.7％. 319 cases detected single pathogen gene fragments. 127 cases detected two pathogen genes and 6 cases detected three pathogen gene fragments. The positive rate of Clostridium difficile toxin B (48.9％, 296/605)was the highest than the others, followed by Salmonella (20.0％, 121/605) and Norovirus (10.9％, 66/605). The positive rate of Clostridium difficile toxin A was 1.0％ (6/605). The positive rates of pathogens in male and female children were 86.7％(325 / 375) and 86.5％ (199 / 230) respectively, with (χ2 =0.002, P=0.959). Conclusions Salmonella and Norovirus were the main pathogens in children with diarrhea who were negative for rotavirus detection in Hangzhou. The high positive rate of Clostridium difficile toxin B may be related to the colonization of Clostridium difficile in the gastrointestinal tract of infants rather than the pathogen of diarrhea because of the low positive rate of Clostridium difficile toxin A. There was no gender difference in the detection rate of diarrhea pathogens.