OBJECTIVE: To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family. METHODS: Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009). RESULTS: CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent. CONCLUSION This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Duplication/genetics* ; Male ; Pedigree ; DiGeorge Syndrome/diagnosis* ; Adult ; Chromosomes, Human, Pair 22/genetics* ; Abnormalities, Multiple

Objective To investigate the effects of Forskolin on the activation of nucleotide－binding oligome-rization domain like receptor family,pyrin domain－containing 3(NLRP－3)inflammasome and the secretion of inter-leukin－1β(IL－1β)in activated human THP－1 macrophages,which can provide evidence for clinical treatment of inflammatory diseases in children.Methods Human monocyte cell line THP－1 cells were induced to differentiate into macrophages by Phorbol－12－myristate－13－acetate(PMA),and Forskolin(10,50,100 μmol/L)stimulated activa-ted macrophages by nigericin.The mRNA of the inflammasome markers NLRP－3,IL－1β and Caspase－1 were detec-ted by real－time quantitative polymerase chain reaction(qPCR)method.The protein of NLRP －3,pro －IL －1β, pro－Caspase－1 and Caspase－1 were detected by Western blot.The secretion of inflammatory cytokines IL－1β was detected by enzyme－linked immuno－sorbent assay(ELISA).Results Nigericin activated the cells and the mRNA expression of NLRP－3,IL－1β and Caspase－1 increased by 7.59 times(P＜0.001),579.10 times(P＜0.001)and 3. 59 times (P ＜0. 001 ),compared to non － activated cells;Forskolin had no effect on the mRNA expression of NLRP－3,Caspase－1 and IL－1β on activated THP－1 macrophages(P＞0.05).Western blot showed that Forskolin also had no effect on the protein expression of pro－Caspase－1 and pro－IL－1β in activated THP－1 macrophages (P＞0. 05),but the expression of NLRP －3 and Caspase －1 decreased significantly (P ＜0.001). The results of ELISA showed that the IL －1β secretion increased from basal 584. 0 nmol/L to activated 2 695. 6 nmol/L (t ＝16.031 1,P＜0. 001)on THP －1 macrophages by nigericin,but Forskolin(10,50,100 μmol/L)reduced it to 1 858. 4 nmol/L(t＝5.365 5,P ＜0. 001),1 467.9 nmol/L(t ＝8.047 5,P ＜0.001)and 1 246.7 nmol/L(t ＝10.199 0,P＜0.001)on the activated THP－1 macrophages.Conclusions Forskolin can not affect the expression of pro－cytokines at the gene transcription and protein translation levels in activated THP－1 cells,but inhibit the secre-tion of inflammatory cytokines IL－1β,so as to inhibit inflammatory response,which can be used to treat pediatric in-flammatory diseases caused by IL－1β.

Objective: To observe the intestinal viral shedding time in patients with hand, food and mouth disease (HFMD) induced by coxsackievirus A6 (CA6). Method: Throat swab specimens and stool specimens of HFMD children were collected from those admitted to Hangzhou Children′s Hospital between May and October 2015, while fluorescence quantitative PCR was used to detect the viral load.Eeighteen cases of HFMD children were followed up, who were confirmed as CA6 infection via laboratory tests.Stool specimen was collected every 4-7 days, and fluorescence PCR was used for virus nucleic acid detection until the stool viral nucleic acids of infected children turned to be negative.The intestinal virus shedding time of CA6-infected HFMD was compared with the intestinal virus shedding time of 65 children with enterovirus 71 (EV71) infection and 44 children with coxsackievirus A16 (CA16) infection of the previous studies (from May to September 2012). Result: The median stool viral load was 25×10⁵ copies/ml (55×10⁴ copies/mL, 9×10⁶ copies/ml) in CA6-infected children.The numbers of stool virus nucleic acid turning negative were 0 case, 4 cases, 9 cases, 3 cases and 2 cases in 18 children at 1st, 2nd, 3rd, 4th, 5th weeks. At 5th week, the stool virus nucleic acid of children in CA6 group all turned to be negative.The positive rates of stool virus nucleic acid in EV71 group and CA16 group at the 5th week, however, were 31% and 27% respectively.There were statistically significant differences in distribution of positive rate of stool virus nucleic acid between CA6 infected children with EV71 and CA16 infected children (χ²=13.894, 10.698, P<0.05). Conclusion The longest intestinal virus shedding time for CA6-infected HFMD children was 5 weeks, which is obviously shorter than that of EV71- infected children and CA16-infected children.

Medical device going home is an inevitable trend, however, using these devices has potential safety risks. Through introducing the home use electronic medical device products and related medical device standards, this paper provides recommendations on construction of standard system for home use electronic medical devices, to improve the advancement of existing medical device standard system and guide future medical standardization work, to fully utilize standars's guiding and security role in the scientific and technological innovation, industrial development.

OBJECTIVETo investigate the effect of curcumin on oligomer formation and mitochondrial ATP-sensitive potassium channels (mitoKATP) induced by overexpression or mutation of α-synuclein.

METHODSRecombinant plasmids α-synuclein-pEGFP-A53T and α-synuclein-pEGFP-WT were transfected into PC12 cells by lipofectamin method, and intervened by application of curcumin (20 μmol/L) and 5-hydroxydecanoate (5-HD). Oligomer formation in the cultured cells was identified by Western blotting and Dot blotting. Cytotoxicity and apoptosis of the PC12 cells were measured by lactate dehydrogenase (LDH) and JC-1 assays. mitoKATP were identified by Western blotting and whole cell patch clamp.

RESULTSCurcumin has significantly reduced the oligomer formation induced by overexpression or mutation of α-synuclein in the cultured cells. LDH has decreased by 36.3% and 23.5%, and red/green fluorescence ratio of JC-1 was increased respectively by 48.46% and 50.33% after application of curcumin (P<0.05). Protein expression of Kir6.2 has decreased and mitoKATP channel current has significantly increased (P<0.05).

CONCLUSIONCurcumin can inhibit α-synuclein gene overexpression or mutation induced α-synuclein oligomers formation. It may block apoptosis induced by wild-type overexpression or mutation of α-synuclein. By stabilizing mitochondrial membrane potential. Opening of mitoKATP channel may have been the initiating protective mechanism of apoptosis induced by wild-type overexpression or mutation of α-synuclein. Curcumin may antagonize above cytotoxicity through further opening the mitoKATP channel.

Animals ; Apoptosis ; drug effects ; Cell Line ; Curcumin ; pharmacology ; Humans ; KATP Channels ; chemistry ; genetics ; metabolism ; Mitochondria ; drug effects ; genetics ; metabolism ; Mutation ; drug effects ; PC12 Cells ; Parkinson Disease ; drug therapy ; genetics ; metabolism ; physiopathology ; Rats ; alpha-Synuclein ; genetics

Objective To investigate the effect of nuclear-transcription factor-κB signal transduction pathway on differentiation of rat marrow mesenchymal stem cells (MSCs) into neurons.Methods The MSCs were purified at least four generations in vitro.And then,the MSCs were assigned into three groups:non-serum control group (group A),fasudil treatment group (group B) and fasudil and lipopolysaccharide treatment group (group C).Cells in group A were added serum-free DMEM,those in group B were added induced liquid (DMEM 900 μL+fetal bovine serum 100 μL that contains final concentration of 200 μmol/L of fasudil),and those in group C were added induced liquid (DMEM 900 μL+fetal bovine serum 100 μL that contains final concentration of 200 μmol/1 of fasudil and final concentration of 1000 μg/L of lipopolysaccharide).All the MSCs were induced into neurons for 6 h.The morphology of MSCs was observed under inverted fluorescence microscope.The expressions of neuronspecific enolase (NSE),microtubule-associated protein (MAP)-2,cyclin D1 and glial fibrillary acidic protein (GFAP) in neurons were detected by immunocytochemical method.The mRNA expressions ofcyclin D1 and MA P-2 in neurons were detected by real time-PCR.The protein expressions ofcyclin D1 and MAP-2 were detected by Western blotting.Results (1) The MSCs of group A kept flat and the neurites were scarce;the MSCs of group B and C could differentiate into neurons,and the speed of MSCs of group B differentiating into neurons was faster than that in group C;there was typical neural network in group B and the neural network in group C was scarcer than group B.(2) As compared with those in group A,higher expression levels of NSE and MAP-2,and lower cyclin D1 expression level in group B and group C were noted (P＜0.05);the expression percentage of GFAP was lower than 1％ in both three groups.(3) As compared with group A,group B and group C had significantly lower cyclin D1 protein and mRNA expressions and significantly higher MAP-2 protein and mRNA expressions (P＜0.05).Conclusion The NF-κB signal transduction pathway,by regulating the expression of cyclin D1,participates in the neuronal differentiation of rat marrow mesenchymal stem cells induced by fasudil.

genes related to pancreatic cancer was mainly associated with biological process,cellular location,molecular function,which suggested the development of pancreatic cancer was caused by multiple genes.

Objective To observe the effect of consciousness-restoring obstruction-clearing needing technique combined with swallowing function training on pseudobulbar paralysis after stroke.Methods 80 stroke patients with pseudobulbar paralysis were randomly divided into the trial group and control group with 40 cases in each group.The patients of the trial group were treated with consciousness-restoring obstruction-clearing needing technique combined with swallowing function training and routine medicine,those of the control group were treated only with routine medicine.Results After treatment,the whole effective rate of the trial group was 92.5%,that of the control group was 60.0%,there was a significant difference between two groups(P<0.05).Conclusion The therapeutic effect of consciousness-restoring obstruction-clearing needing technique combined with swallowing function training and routine medicine on pscudobulbar paralysis after stroke is superior to simply routine medicine.