Clinical characteristics and genetic analysis of childhood onset neurodegeneration associated with UBTF gene variation / 中华神经科杂志

Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.

Establishment and characterization of bone marrow mesenchymal stem cell lines stably synthesizing high-level dopamine / 生物工程学报

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.

Artificial intelligence in wearable electrocardiogram monitoring / 生物医学工程学杂志

Electrocardiogram (ECG) monitoring owns important clinical value in diagnosis, prevention and rehabilitation of cardiovascular disease (CVD). With the rapid development of Internet of Things (IoT), big data, cloud computing, artificial intelligence (AI) and other advanced technologies, wearable ECG is playing an increasingly important role. With the aging process of the population, it is more and more urgent to upgrade the diagnostic mode of CVD. Using AI technology to assist the clinical analysis of long-term ECGs, and thus to improve the ability of early detection and prediction of CVD has become an important direction. Intelligent wearable ECG monitoring needs the collaboration between edge and cloud computing. Meanwhile, the clarity of medical scene is conducive for the precise implementation of wearable ECG monitoring. This paper first summarized the progress of AI-related ECG studies and the current technical orientation. Then three cases were depicted to illustrate how the AI in wearable ECG cooperate with the clinic. Finally, we demonstrated the two core issues-the reliability and worth of AI-related ECG technology and prospected the future opportunities and challenges.

Phenotypic and genetic analysis of a boy with inv dup del(8p) / 中华医学遗传学杂志

OBJECTIVE@#To delineate the nature and origin of a chromosomal aberration detected in a boy with mental retardation.@*METHODS@#The proband and his parents were subjected to routine G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis.@*RESULTS@#The karyotype of the proband was determined as 46, XX, add(8)(p23). No karyotypic abnormality was detected in either of his parents. SNP-array has identified a 34.9 Mb duplication at 8p23.1q11.1 and a 6.78 Mb microdeletion at 8p23.1pter in the proband. No copy number variation was detected in either parent.@*CONCLUSION@#The child was diagnosed with 8p inverted duplication deletion syndrome, which might be induced by non-allelic homologous recombination between olfactory genes in the 8p23.1 region.

Kleefstra syndrome 1 and ring chromosome 9 in a case / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and molecular genetic characteristics of patient with Kleefstra syndrome 1.@*METHODS@#Clinical data, chromosomal karyotype and whole genome copy number variations (CNVs) of the patient were analyzed.@*RESULTS@#The patient was found to have a karyotype of 45,XX,-9[4]/46,XX,r(9)(p24q34)[56]. Whole-genome CNVs detection revealed that she has carried a heterozygous deletion of approximately 670 kb at 9q34.3, which encompassed the entire EHMT1 gene. The region is strongly associated with Kleefstra syndrome (1/9q telomere deletion). In addition, the patient also had heterozygous deletion of 9pter, which may predispose to formation of ring chromosome 9.@*CONCLUSION@#The child was diagnosed with Kleefstra syndrome type 1 in conjunct with ring chromosome 9.

A case of SBBYSS syndrome caused by KAT6B gene variant / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and molecular genetics features of a family affected with Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS).@*METHODS@#High-throughput sequencing was used to detect copy number variations (CNVs) and pathogenic variant within the whole exome of the affected child.@*RESULTS@#No pathogenic CNV was found in the child, while exome sequencing identified a heterozygous c.3367_c.3370delAGAA (p.Arg1123Argfs*6) frameshifting variant in the exon 16 of the KAT6B gene. The same variant was not found in either parent.@*CONCLUSION@#The c.3367_c.3370delAGAA (p.R1123Rfs*6) probably underlies the disease in the affected child. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.

Effects of moxibustion on immune function in children with cerebral palsy / 中国针灸

<p><b>OBJECTIVE</b>To compare the effects between moxibustion at Guanyuan (CV 4), Shenshu (BL 23), Zusanli (ST 36) and western medication on immune function in children with cerebral palsy.</p><p><b>METHODS</b>A total of 230 children with cerebral palsy were randomly divided into an observation group and a control group, 115 cases in each one. Patients in the observation group were treated with warm moxibustion at Guanyuan (CV 4), Shenshu (BL 23) and Zusanli (ST 36). Patients in the control group were treated with oral administration of pidotimod 10 mL every time. The treatment was given once a day, and 30 days were considered as one session for total 90 days. The changes of T-lymphoctyte subgroups, serum immunoglobulin and development quotient were compared 30 days, 60 days and 90 days into treatment respectively; also the occurrence rate.of disease was observed during 6-month and 12-month follow-up visit.</p><p><b>RESULTS</b>The T-lymphoctyte subgroups (CD3+, CD4+, CD4+/CD8+), serum immunoglobulin (IgG, IgA) and development quotient were significantly improved 30 days, 60 days and 90 days into treatment (P < 0.01, P < 0.05). Regarding the changes of CD3+, CD4+, CD4+/CD4+, IgG, IgA and development quotient, the control group was superior to the observation group 30 days into treatment (all P < 0.05), and the control group was similar to the observation group 60 days into treatment (all P > 0.05), and the observation group was superior to the control group 90 days into treatment (all P < 0.05). There was no significant difference of CD8+ and IgM before and after treatment in two groups (all P > 0.05). The rate of adverse events was 7.0% (8/115) in the observation group, which was lower than 23.5% (27/115) in the control group (P < 0.01); during 6-month and 12-month follow-up visit, the occurrence rate of disease in the observation group was lower than that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Moxibustion at Guanyuan (CV 4), Shenshu (BL 23) and Zusanli (ST 36) can improve immune function of children with cerebral palsy, which is superior to pidotimod.</p>

Expression of miRNA-21 in colonic mucosa and peripheral blood CD4+ T cells of 49 patients with active inflammatory bowel disease / 中华消化杂志

Objective To investigate the role and significance of miRNA-21 in the pathogenesis and development of inflammatory bowel disease (IBD).Methods The expressions of microRNA-21 (miRNA-21) in colonic mucosa and peripheral blood CD4+T cells were analyzed by fluorescence quantitative polymerase chain reaction (PCR) in 26 patients with active Crohn's disease (CD), 23 patients with active ulcerative colitis (UC) and 19 healthy controls.The relative expression amount of miRNA-21 in colonic mucosal and peripheral blood CD4+ T cells in 11 patients with CD was compared before and after infliximab (IFX) treatment, and its correlation with tumor necrosis factor (TNF)-α was analyzed.t-test was performed for comparison between groups.The correlation between miRNA-21 expression in peripheral blood CD4+ T cells and serum TNF-α was analyzed by Spearman correlation analysis.Results The expression of miRNA-21 in colonic mucosa of CD patients and UC patients was 4.720 ± 0.397 and 4.993±-0.415, respectively, which were both higher than that of healthy control group (1.101±-0.284),and the differences were statistically significant (t =7.657 and 8.356, both P＜0.01).The expression of miRNA-21 in peripheral blood CD4+ T cells of CD patients and UC patients was 3.254 ± 0.323 and 3.450±0.311, which were both higher than that of healthy control group (0.891 ±0.220), and the differences were statistically significant (t=6.007 and 7.098, both P＜0.01).After 12 weeks of IFX treatment, simple endoscopic score for Crohn's disease (SES-CD) of CD patients was 8.019 ± 0.349,which was lower than that before treatment (21.502 ± 1.185), and the difference was statistically significant (t=10.910, P＜0.01).The serum TNF-α level was 61.570±6.252, which was lower than that before treatment (173.500 ± 12.670), and the difference was statistically significant (t=7.926, P＜0.01).The results of correlation analysis indicated that serum TNF-α level was positively correlated with miRNA-21 expression in peripheral blood CD4+ T cells (r =0.780 4, P ＜ 0.01).Conclusions The increasing of miRNA-21 expression in IBD was closely correlated with the serum TNF-α level and severity of inflammation.miRNA-21 might be a new target for IBD treatment.

Awareness rate of knowledge,attitude and behavior about disinfection and sterilization among clinical health care workers / 中国感染控制杂志

Objective To investigate the awareness of knowledge,attitude and behavior about disinfection and sterilization among clinical health care workers (HCWs).Methods 200 clinical HCWs were investigated randomly by using questionnaires.Results The average awareness rates of knowledge,attitude and behavior about disinfec-tion and sterilization among HCWs were 71 .49%,63.79%,and 86.45% respectively.The awareness rates of knowledge about the expiration dates of sterilized articles,classification of infectious diseases,and biological moni-toring were 49.43%,42.53%,and 23.56%,respectively;HCWs’attitude towards disinfection and sterilization:awareness rate of whether they paid attention to the new technology in specialty of central sterile supply was the lowest (26.44%);86.45% of HCWs thought they could master the aseptic operation technique,correct applica-tion method for sterile apparatus and related items,but easily ignored to check the integrity of aseptic packages and indicators before operation (67.24%).Conclusion The knowledge,attitude and behavior about disinfection and sterilization among HCWs still need to be improved,training on knowledge about disinfection and sterilization among HCWs should be strengthened.

PROTECTIVE EFFECT OF ASTRAGALUS MEMBRANCE ON MICE OF ACUTE TOXOPLASMOSIS / 中国血吸虫病防治杂志

Objective To study the protective effect of Astragalus membrance on mice infected with tachyzoites of Toxoplasma gondii. Methods ICR mice were infected intraperitoneally with 10 5, 10 3, 10 2 tachyzoites of virulent RH strain of Toxoplasma gondii, and the mice were orally treated with Astragalus membrance 0 075 g/d per mouse or Azithromycin [150 mg/(d?kg)] each day starting from day 1 post-infection for 10 days. The survival rate and period were investigated. The parasite loads of livers and lungs of the mice infected with 10 2 tachyzoites were determined by fluorescence PCR methods at 4 day-post-infection (dpi) and 8 dpi. Results When infected with 10 5, 10 3 tachyzoites, treated with Astragalus membrance, the average survived days of the mice were 5 57 days and 6 23 days, and treated with azithromycin were 6 96 days and 8 12 days respectively. The azithromycin group but not the astragli group survived significantly longer than the control(P

Effect of ERK1/2 on ischemic preconditioning in diabetic rat hearts / 中国病理生理杂志

AIM: To test the effect of ERK1/2 on ischemic preconditioning (IPC) in diabetic rat hearts. METHODS: The diabetic rat model was made with alloxan. After eight weeks, 24 rats were divided into 4 groups: non-diabetic IPC rats (group A); non-diabetic non-IPC rats (group B); diabetic IPC rats (group C); diabetic non-IPC rats (group D). ECGⅡ lead, left ventricular development pressure (LVDP), and first derivative of LVDP ~(?dp/dt_~max ) were recorded. Myocardial phosphorylation of extracellular signal regulated kinases1/2 (ERK1/2) was detected by Western-blotting. RESULTS: (1) The ventricular arrythmia score was significantly lower in group A than that in group C (P