Objective In this study,Knoevenagel derivatives of curcumin were synthesized,and their oil-water partition coefficient were determined.Our aim is to provide an experimental basis for further development of curcumin derivatives.Methods Two Knoevenagel derivatives of curcumin,including 4-(thiophen-2-ylidene)curcumin(3a)and 4-(pyridine-4-ylidene)curcumin(3b),were obtained by using the methylene group of curcumin as the modification site and purified by column chromatography.The structures of these derivatives were confirmed by nuclear magnetic resonance spectroscopy(NMR),infrared(IR)and high-resolution liquid mass spectrometry(HRLC-MS).The oil-water partition coefficient of the derivatives in n-octanol aqueous solution was determined by quantitative analysis using HPLC.Results Knoevenagel derivatives of curcumin were successfully synthesis.The oil-water partition coefficients(lgPap)of curcumin derivatives 3a and 3b are 0.96 and 0.82,respectively.Compared with the oil-water partition coefficient of curcumin(lgPap=3.85),it suggested that curcumin derivatives showed better water solubility than curcumin.Conclusion Compared to the curcumin prototype,Knoevenagel derivatives of curcumin increased water solubility and improved bioavailability.Thus,it may provide experimental basis for introducing heteroarylene moiety of the methylene position of curcumin to enhance pharmacological activity.

Objective:To explore the genetic etiology of a child with Cowden syndrome 1 (CS1).Methods:A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c. 781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The c. 781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree featuring non-simplex blepharocheilodontic syndrome. METHODS: Whole exome sequencing was carried out to detect genetic variant and copy number variations (CNVs) in the pedigree. Suspected variants were verified by Sanger sequencing and qPCR. RESULTS: The fetus and its elder brother, father and grandfather were found to harbor a heterozygous c.83delG (p.A29Rfs*55) variant of the CTNND1 gene, which was unreported previously. In addition, its elder brother was also found to be a double heterozygote for a c.235delC (p.L79Cfs*3) variant of GJB2 gene and a c.538C>T (p.R180X) variant of GJB3 gene, which were respectively inherited from his mother and father. CNVs analysis revealed a de novo heterozygotic deletion (1.46 Mb) at 17q12 in the mother, which was confirmed by qPCR. Based on American College of Medical Genetics and Genomics guidelines, the c.83delG variant, the c.235delC variant and the 17q12 microdeletion were predicted as pathogenic, while the c.538C>T variant was of uncertain significance. CONCLUSION The c.83delG (p.A29Rfs*55) variant of the CTNND1 gene probably underlay the pathogenesis of non-simplex blepharocheilodontic syndrome in this pedigree. The double heterozygous variants of c.235delC (p.L79Cfs*3) of GJB2 gene and c.538C>T (p.R180X) of GJB3 gene probably underlay the hearing loss in the elder brother. The bilateral renal cysts in the mother may be attributed to the 17q12 microdeletion. Above results have provided guidance for genetic counseling and prenatal diagnosis for this pedigree.
Male ; Pregnancy ; Female ; Humans ; Aged ; Pedigree ; Mutation ; DNA Copy Number Variations ; East Asian People ; China

Objective:Numerous miRNAs have been found to be abnormally expressed in hepatocellular carcinoma(HCC).However,clinical significance of miR-5010-3p in HCC is not elucidated.This study aims to explore the prognostic value and role of miR-5010-3p in HCC.Methods:The differential gene expression analysis of miR-5010-3p in HCC was performed based on the Cancer Genome Atlas(TCGA)database.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of miR-5010-3p expression level for HCC prognosis.The Kaplan-Meier,Cox univariate,and Cox multivariate analysis were used to predict its role in the prognosis of HCC.The downstream target genes were predicted.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed to predict the potential functional pathways they may participate in.Finally,methyl thiazolyl tetrazolium(MTT)assay and 5-ethyl-2'-deoxyuridine(EDU)incorporation experiment were carried out to prove its effect on proliferation.Results:The expression of miR-5010-3p was associated with histological grade(P=0.019),vascular invasion degree(P=0.049),TP53 level(P=0.004),and alpha fetoprotein(AFP)level(P=0.012).A moderate ability to distinguish between tumor and paracancerous tissues of miR-5010-3p in HCC was perceived by ROC curve(AUC:0.712,95%CI 0.649 to 0.776).High expression of miR-5010-3p was associated with shorter overall survival(OS)(P=0.003).The results of functional enrichment analysis showed that miR-5010-3p was related to the tumorigenesis process.In vitro experiments verified that miR-5010-3p promoted the proliferation of hepatocellular carcinoma cells.Conclusion:MiR-5010-3p promotes the proliferation of liver cancer cells,and its high expression is associated with poor prognosis,which may be a potential prognostic marker.

Objective:To evaluate the effect of oral cryotherapy in patients with hematopoietic stem cell transplantation (HSCT) .Methods:Randomized controlled trials on the effect of oral cryotherapy in HSCT patients were retrieved in Cochrane Library, PubMed, Embase, Web of Science, Scopus, China Biology Medicine disc, CNKI, WanFang Data and VIP. The retrieval time limit was from the establishment of the database to August 31, 2022. Two researchers conducted article screening, data extraction and evaluation of article quality, and used RevMan 5.3 software for meta-analysis.Results:A total of 9 articles were included, including 639 HSCT patients. Meta-analysis showed that oral cold therapy could reduce the incidence of severe oral mucositis (OM) (grade 3 to 4) [ OR=0.34, 95% CI (0.18, 0.66), P=0.001]and the use of total parenteral nutrition [ OR=0.34, 95% CI (0.13, 0.88), P=0.03]in patients with HSCT, and reduce the incidence of OM [ OR=0.09, 95% CI (0.04, 0.19), P<0.001], OM severity score [ MD=-0.71, 95% CI (-0.78, -0.64), P<0.001]and use of intravenous painkillers [ OR=0.12, 95% CI (0.04, 0.40), P=0.000 4]in patients with autologous HSCT. The relationship between oral cryotherapy and OM incidence of allogeneic HSCT patients [ OR=1.23, 95% CI (0.57, 2.68), P=0.60], OM severity score [ MD=-0.15, 95% CI (-0.57, 0.27), P=0.48], and the length of hospital stay of autologous HSCT patients [ MD=-0.67, 95% CI (-2.10, 0.76), P=0.36]was not clear. Conclusions:Oral cryotherapy can reduce the incidence of OM in patients with autologous HSCT, the use of intravenous painkillers and total parenteral nutrition, but the effect and safety of oral cryotherapy in patients with allogenic HSCT need to be further verified, which needs to be verified by a large number of high-quality, multi-center, large-sample randomized controlled trials.

Objective:To explore the effect of action research method in optimizing follow-up of patients undergoing knee arthroplasty, so as to provide reference for improving follow-up efficiency and success rate and promoting patients ' rehabilitation. Methods:From August 2019 to August 2021, 282 patients undergoing knee arthroplasty in Second Ward of Orthopedics of Peking Union Medical College Hospital were selected as the study subjects by convenience sampling method. Set patients who underwent routine follow-up from August to September 2019 as the baseline group. Three stages of follow-up mode optimization were conducted in clinical practice, evaluating the average follow-up duration, success rate of follow-up, and range of motion of patients undergoing knee arthroplasty.Results:The average follow-up duration of first, second and third stage follow-up procedures had no statistically differences ( P>0.05) , while the follow-up success rate gradually increased ( P<0.05) . The range of motion of patients undergoing knee arthroplasty in the second and third stage of the follow-up was better than those in the first stage and baseline, and the differences were statistically significant ( P<0.05) . Conclusions:The application of action research method can optimize the follow-up mode of patients undergoing knee arthroplasty, and improve the follow-up efficiency and quality.

Objective:To analyze common respiratory pathogens epidemiology in hospitalized children with lower respiratory tract infection (LRTI) in a single center in Shanghai, and to provide the basic data support for clinical diagnosis and treatment of children with LRTI in Shanghai.Methods:Children with LRTI in Children′s Hospital of Fudan University were enrolled from January 1, 2015 to December 31, 2019, and respiratory samples were collected and tested by direct immunofluorescence assay and real time polymerase chain reaction. The epidemiological characteristics of different respiratory pathogens were analyzed. Chi-square test was used for statistical analysis.Results:A total of 18 716 children were included, the total detection rate of respiratory pathogens was 36.96% (6 918/18 716), and the most frequent detected pathogen was Mycoplasma pneumoniae (MP) (15.31%(2 866/18 716)), followed by respiratory syncytial virus (RSV) (10.40%(1 946/18 716)) and parainfluenza virus Ⅲ (PIV-Ⅲ) (4.65%(871/18 716)). The detection rate of pathogens in female was significantly higher than that in male (38.48%(2 936/7 630) vs 35.92%(3 982/11 086), χ2=12.72, P<0.001). RSV and influenza virus A (Flu-A) infections peaked in winter. The detection rates of influenza virus B (Flu-B) and human metapneumovirus (MPV) were higher in winter and spring. PIV-Ⅲ infection peaked in spring and summer. The peak of PIV-Ⅱ infection occurred in summer and autumn. The infections of adenovirus (ADV), MP, Chlamydia trachomatis (CT) and PIV-Ⅰ were prevalent throughout the year without significant seasonality. The detection rate of RSV declined with age, while the detection rate of MP increased with age. The co-infection rate was 1.65%(309/18 716), and the predominant co-infection type was MP and RSV (0.37%(70/18 716)). Conclusions:A variety of pathogens lead to children′s LRTI in Shanghai from 2015 to 2019, with the common infection of MP, RSV and PIV-Ⅲ. Different pathogens showed different epidemiological characteristics in age and season distributions.

Objective:To investigate the efficiency, safety and complication of 0.7 mg dexamethasone sustained release agent (Ozurdex ?) vitreous cavity implantation for macular edema secondary to vitrectomy. Methods:A total of 15 patients (16 eyes) were included in this retrospective case series study. There were 7 males (8 eyes) and 8 females (8 eyes). Age ranged from 47 to 72 years old with an average age of (60.2±8.6)years. Among them, 8 cases were diabetic retinopathy (6 cases combined cataract surgery). 4 cases were silicone oil removal after retinal detachment surgery (all combined cataract surgery). 2 cases were epi-macular membrane (all combined with cataract surgery) and 1 case was vitreous hemorrhage (combined with cataract surgery). Ozurdex ? was implanted for macular edema after vitrectomy. The number of implantation was from 1 to 3 times (mean 1.67 times). The follow-up time was from 3 to 12 months, with an average of (7.33±3.50)months. Results:The best corrected visual acuity (BCVA) was improved in 10 cases (11 eyes), unchanged in 4 cases and decreased in 1 case within 3 months after Ozurdex ? implantation in the 15 cases (16 eyes). The macular edema was significantly improved in all cases. The central macular thickness (CMT) measured by optical coherence tomography (OCT) was from 350 to 1 370 γm before surgery with average thickness (621.60±235.48)γm, and the CMT postoperative was 118 to 556 γm with average thickness (269.87±118.14)γm, with statistically significant difference ( P<0.001). Cataract was not progressive after Ozurdex ? implantation. Macular edema was recurrent in 7 cases after first implantation and stable for additional 1-2 injections. Intraocular pressure elevation occurred in 3 cases 1 to 2 months after implantation with the highest intraocular pressure of 36 mmHg, which were controlled by local anti-glaucoma eye drops. Drugs entered into the anterior chamber in 2 cases and was taken out in 1 case. Conclusions:The efficiency of Ozurdex ? vitreous cavity implantation is definite and the complications are controllable, so it is a safe and effective method to treat macular edema after vitrectomy.

Objective:To investigate the epidemiological characteristics of classic human astrovirus (HAstV) among children under five years old with acute diarrhea, and to understand the role of HAstV in children acute diarrhea.Methods:A total of 1 010 fecal specimens were collected in 1 010 outpatients under five years old with acute diarrhea admitted to Children′s Hospital of Fudan University, Shanghai from January 2012 to December 2016. Reverse transcription polymerase chain reaction (PCR) or PCR was used for screening classic HAstV, group A rotavirus, norovirus and adenovirus. Genotypes of classic HAstV were determined by nucleotide sequencing and phylogenetic tree analysis.Results:The overall positive rate of classic HAstV was 2.7%(27/1 010). The detection rates of classic HAstV from 2012 to 2016 were 6.9%(10/144), 3.5%(5/144), 2.1%(3/144), 1.5%(4/265) and 1.6%(5/313), respectively. Almost 96.3%(26/27) of children infected with HAstV were 0 to 36 months of age. The prevalence of classic HAstV infections displayed a typical autumn/winter seasonality except in 2016. All the positive classic HAstV strains were genotyped as HAstV-1 with two lineages of HAstV-1a and HAstV-1b. Among them, the lineage of HAstV-1a was the predominant subtype (63.0%, 17/27). There were 77.8%(21/27) of the children with acute diarrhea only infected with classic HAstV, whereas for the remaining cases a variety of other enteric viruses were detected (three cases co-infected with HAstV and group A rotavirus, two cases co-infected with HAstV and adenovirus, and one case co-infected with HAstV, group A rotavirus and adenovirus).Conclusions:Children infected with HAstV are mainly less than 36 months of age. Although the genotype of classic HAstV detected in this study is single, but the lineages are in a state of dynamic change. Long-time and continuous monitor for the epidemiology of classic HAstV is needed to avoid outbreak of diarrhea in children.

Overall progress of the Healthy China initiative highlights the importance of medical humanities in the connotation construction of health services, hence making standardized construction and effective governance of medical social workers a focus of the current healthcare reform. This study summarized the practices of medical social workers engaged in the cabin hospital in Wuchang district, Wuhan city, Hubei province during the outbreak of COVID-19. Their efforts aimed at reducing the stress faced by front-line medical workers, and assisting the patients to achieve body-mind balance for better treatment outcomes." Online+ offline" and" in-cabin+ out-of-cabin" service teams were organized to assist these medical staff, provide social support, and integrate resources. The study analyzed the problems and challenges in the process of practice, and provided a reference for further improving the management of public health emergency services.