Clinical characteristics and genetic variant analysis of a child with Snijders Blok-Campeau syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS).@*METHODS@#A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members.@*RESULTS@#The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing.@*CONCLUSION@#The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.

Construction of quality evaluation index system for palliative care in ICU / 中国实用护理杂志

Objective:To construct a palliative care quality evaluation index system in ICU, and to provide guidance for implementing high-quality palliative care in ICU.Methods:The questionnaire was designed by literature review, qualitative interview and questionnaire survey, and 20 experts were inquired in two rounds by Delphi method from September to November 2020.Results:After two rounds of letter consultation, experts′ response rates were 80% and 100% respectively, experts′ authority coefficient was 0.873, and coordination coefficient of experts′ opinion were 0.198 and 0.176 respectively. The quality evaluation index system for palliative care in ICU included 6 first-level indicators, 22 second-level indicators and 95 third-level indicators.Conclution:The constructed evaluation system for palliative care is scientific and reliable,which can provide guidance for the implementation and development of ICU high-quality palliative care in China.

Biologics for targeting inflammatory cytokines and their clinical application / 生物工程学报

Inflammatory cytokines can mediate many biological processes and are tightly regulated by the body. Loss of control can trigger a range of diseases such as autoimmune inflammation and cancer. Therefore, a number of biological agents that can effectively regulate the biological effects of inflammatory cytokines such as recombinant anti-inflammatory cytokines, cytokine receptors and neutralizing antibodies have been extensively used in the treatment of related diseases caused by the imbalance of inflammatory cytokines. In recent years, in particular, a number of new innovative biological agents for blocking and regulating cytokine activities are emerging. In this article, we review the recent development and clinical use of the biologics targeting TNF-α, IL-1, IL-6 and IL-17, and point out their inherent limitations and clinical risks. Finally, based on the research findings of our own and other scholars, we suggest some approaches and methods for reducing their side-effects and clinical risk. We consider that using modern biotechnology to improve the tissue specificity to inflammatory site and tumor will be an important development direction of such biologics.

Preparation of monoclonal antibodies against human interleukin-35 and their application in a quantitative ELISA for interleukin-35 detection / 生物工程学报

To establish a quantitative ELISA for human interleukin-35 (IL-35) detection, we cloned cDNAs encoding the 2 subunits IL-27EBI3 and IL-12p35 of IL-35 by RT-PCR and transformed the cDNAs into Escherichia coli BL21 star (DE3) by recombinant DNA technology. IL-27EBI3 and IL-12p35 were expressed as recombinant proteins and used as immunogen to immunize Balb/c mice. Spleen cells from the positive serum mice were isolated and fused with SP-2/0 myeloma cells. We obtained the hybridoma cell lines stably secreting target antibodies by indirect ELISA screening of the cell supernatants with recombinant IL-27EBI3 and IL-12p35 as antigen and consecutive subcloning of the cells in the well with positive supernatant. Following further measurement of supernatant titers of the antibodies and identification of their antigen specificity, we obtained a hybridoma cell line 3B11 that stably secrets antibody against IL-27EBI3 and a hybridoma cell line 3A10 that secrets antibody against IL-12p35. Both monoclonal antibodies (mAbs) were identified as the subtype of IgG1. Finally, using the anti-IL-27EBI3 mAb from 3B11 as the capture antibody and the anti-IL-12p35 mAb from 3A10 as the secondary antibody, we established a quantitative double-antibodies sandwich ELISA for IL-35 detection with streptavidin-biotin amplification system. Results demonstrated that the quantitative assay had a detection range of 3.12-200 pg/mL, a detectability of 1.26 pg/mL, and a crossing-reactive rate of 0.1%. The intra-batch RSD and the inter-batch RSD of the quantitative assay were 5.1%-5.6% and 5.6%-7.2%, respectively, and the fortified recovery was 89%-103%. Therefore, the sandwich ELISA assay for IL-35 meets the qualification of quantitative analysis and laid a stable foundation for the development of quantitative ELISA kit for IL-35 detection.

Clinical analysis of prenatal diagnosis and intervention for primary pleural effusion of 13 cases / 中华妇产科杂志

Objective To optimize the clinical managements of primary fetal hydrothorax(PFHT) fetus by comparing the perinatal survival rate of different prenatal treatments.Methods Totally 13 fetuses diagnosed with PFHT from July 2009 to December 2015 in the First Affiliated Hospital of Jinan University were collected and received prenatal expectant treatment, thoracocentesis (TC), and thoraco-amniotic shunting (TAS), respectively. The perinatal survival rate was compared among the three treatments. Results Among 13 fetuses of PFHT,pleural effusion was absorbed or remained stable in 2(2/13)cases,and progressed in 11(11/13) cases. Six cases received expectant treatment (2 cases had termination of pregnancy due to progressing effusion, 2 cases had term delivery, and 2 cases had intrauterine death); the perinatal survival rate was 2/6. Six cases received TC (2 cases had term delivery, 2 cases had preterm delivery,and 2 cases had termination of pregnancy due to progressing effusion),the perinatal survival rate was 4/6.One case received TC+TAS(term delivery),the perinatal survival rate was 1/1.The overall perinatal survival rate of prenatal intrauterine intervention was 5/7. Conclusions The clinical process of PFHT is changeable, and the pleural effusion will progress with gestational age. Intrauterine interventions could improve the perinatal survival rate.

A comparative study between narrow-band imaging(NBI) and iodine chromoscopy for early esopha-geal cancer and precancerous lesions / 中华消化内镜杂志

Objective To evaluate narrow?band imaging(NBI)for early esophageal cancer and pre?cancerous lesions. Methods A total of 170 patients ( 192 lesions) diagnosed as having superficial esophageal carcinoma and precancerous lesions by endoscopy were retrospectively analyzed. Clinical data of endoscopy, narrow?band imaging (NBI) and iodine chromoscopy were analyzed.Results The detection rates of early esophageal cancer were both 100?? 0% in NBI(13/ 13) and iodine staining (13/ 13), with no statisti?cally significant difference (P>0?? 05).The detection rate of high grade intraepithelial neoplasia in NBI and i?odine staining was 94?? 9% (94/ 99) and 100?? 0% (99/ 99) respectively with no statistically significant differ?ence (P>0?? 05); The detection rate of low grade intraepithelial neoplasia in iodine staining was 100?? 0%(80/ 80), significantly higher than that of NBI 78?? 8% (63/ 80) (P<0?? 01).Conclusion NBI and iodine staining endoscopy show better diagnostic value for early esophageal cancer and similar diagnostic value for high grade intraepithelial neoplasia in precancerous lesions. But for the low grade intraepithelial neoplasia, the diagnostic value of iodine staining endoscopy is better than that of NBI.

MiR-211 promotes invasion of hepatoma cells by targeting estrogen receptor alpha / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the regulatory functions and molecular mechanisms of miR211 in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Real-time reverse transcription-PCR was used to analyze the expression of miR-211 in 20 paired clinical specimens of HCC and adjacent noncancerous tissues.QGY7703 and HepG2 cells with stimulation or inhibition of miR-211 expression were used to evaluate the effects on malignant phenotypes with the transwell invasion assay. Candidate target genes of miR-211 were identified by bioinformatic screening and verified by the EGFP report assay, real-time PCR and western blotting. Moreover, the regulatory functions of miR-211 on the target genes were investigated by RNA interference and cell phenotype assays.</p><p><b>RESULTS</b>miR-211 was up-regulated in HCC tissue specimens (t =6.26, P < 0.01).HCC cells overexpressing miR-211 showed greater invasive capacity than cells with inhibited expression (QGY-7703:t =12.59, P < 0.01; HepG2: t =17.82, P < 0.01). Estrogen receptor a (ESR1) was identified and validated as a target gene of miR-211; knockdown of ESR 1 promoted HCC invasive capacity (QGY-7703:t =8.97, P < 0.01; HepG2:t =29.31, P < 0.01).</p><p><b>CONCLUSION</b>miR-211 promotes invasion of carcinoma cells by directly targeting ESR1.</p>

Expression and characterization of a bispecific antibody targeting TNF-α and ED-B containing fibronectin / 生物工程学报

To enhance the specificity of anti-TNF-α single chain Fv antibody (TNF-scFv) to inflamed site, we constructed a bispecific antibody BsDb that targets TNF-α and ED-B-containing fibronectin (B-FN) by covalently linking TNF-scFv and the anti-ED-B scFv L19 at the gene level via a flexible peptide linker deriving from human serum albumin. BsDb was successfully secreted from Pichia pastoris as functional protein, identified by immunoblotting, and purified to homogeneity with affinity chromatography. BsDb retained the immunoreactivity of its original antibodies TNF-scFv and L19, and showed a marked gain in antigen-binding affinity and in TNF-α-neutralizing ability, when compared to TNF-scFv and L19 that were produced in Escherichia coli. In the adjuvant-induced arthritis (AIA) mice model, BsDb showed selective accumulation and retention in the inflamed paws but rapid clearance from blood, resulting in high arthritic paw to blood ratios. These data indicate that BsDb is endowed with high specificity to inflamed site and low toxicity to normal tissues and holds great potential for in vivo application for the targeted therapy of RA and other chronic inflammatory diseases.

Decompression of acute left-sided obstruction of colorectum / 中华消化内镜杂志

Objective To evaluate the effectiveness and safety of a transanal drainage tube(TDT) for decompression of acute left-sided obstruction of colorectum.Methods Fifty-seven patients with acute left-sided colorectal obstruction were enrolled in this study from January 2010 to December 2014.The obstruction location, property, success rate of insertion, one-procedure rate and complication rate were analyzed.Results There were 53 cases of primary colorectal cancer,among which lesions were located in the transverse colon in 1 case, in descending colon in 10, in sigmoid colon in 24,and in rectum in 18.There were 4other cases, one sigmoid colonic metastases of pulmonary cancer, 1 adhesive colonic obstruction after ovary surgery, 1 cervical cancer involved with rectum with stricture and obstruction, and 1 descending colonic obstruction caused by Crohn's Disease.TDT was successfully inserted in 55 cases(96.5％) without complications,in which 43 cases of primary colorectal cancer finally underwent surgery.TDT indwelled from 0 to 22days, for an average of (8.7± 4.4)d.Hartmann operation was performed in 9 patients,6 of which underwent sufficient lymphnode dissection.Among the 43 patients, one-stage operation was performed in 34 (79.1％),of which 30 cases underwent sufficient lymph node dissection, without stoma leakage.And the rest of 13 cases refused surgery because of poor prognosis and financial problems.One patient with Crohn's Disease refused surgery after TDT insertion and was discharged after palliation of distention.Conclusion TDT is safe and effective in decompressing acute left-sided benign obstruction with high success rate and low expenditure, and can achieve preoperative colonic lavage in one-stage operation for acute left-sided colorectal malignant obstruction.

Construction and functional analysis of a bispecific antibody that targets TNF-α and ED-B / 药学学报

In order to enhance the specificity of TNF-α monoclonal antibody to inflamed site, a bispecific antibody BsDb that targets TNF-α and the extra-domain B (ED-B) of fibronectin (FN) was constructed by covalently linking the anti-TNF-α single chain Fv antibody (TNF-scFv) and the anti-ED-B scFv L19 via a flexible peptide linker deriving from human serum albumin (HSA). ED-B is an antigen specifically expressed at the inflamed site. BsDb is expressed in E. coli, identified by immunoblot, and purified with affinity chromatography. This was followed by further examination of its bioactivities and pharmacokinetics. We demonstrated that BsDb retained the immunoreactivity of its original antibodies as it could simultaneously bind to TNF-α and ED-B and neutralize the biological action of TNF-α. In the collagen-induced arthritis mice model, BsDb selectively accumulate in the inflamed joint with a maximal uptake of (12.2 ± 1.50)% ID/g in a single inflamed paw and retain in the inflamed paw for at least 72 h. In contrast, BsDb showed a short serum half-life of (0.50 ± 0.05) h and a rapid clearance from normal tissues. The findings reported herein indicate that BsDb has good specificity to the inflamed site and low toxicity to normal tissues. BsDb is therefore likely to have greater clinical applications in the treatment of rheumatoid arthritis and other autoimmune diseases. This laid a stable basis for its preclinical study.

The application of procalcitonin in the diagnosis of bacterial infection of the immunosuppression individuals / 国际儿科学杂志

Serum procalcitonin(PCT) is considered to be the most sensitive and high specificity index.In recent years,it is gradually found that C-reactive protein sensitivity is much higher than PCT in the diagnosis of bacterial infection of those patients with immune system diseases and application of immune inhibitors.Therefore,this paper summarizes whether the PCT is still of higher sensitivity and specificity in the diagnosis of bacterial infection of the immunosuppression individual or not.

Progress in renal tubulointerstitial fibrosis / 国际儿科学杂志

Renal tubulointerstitial fibrosis is the final common pathway in end-stage renal disease.Whereas molecular mechanisms underlying fibrogenesis are still not completely understood.To know the latest pathogenesis and treatment methods is of important significance to prevent disease progression and save life.

Effects of total glucosides of peony on expression of inflammatory cytokines and phosphorylated MAPK signal molecules in hippocampus induced by fibrillar Aβ42 / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effects of hippocampal Abeta42 deposition on the expression of inflammatory cytokines and phosphorylated MAPK signal molecules as well as the intervention of AD by total glucosides of paeony (TGP).</p><p><b>METHOD</b>12 week-old female SD rats were stereotactic injected one-time with a fibrillar Abeta42 positioning hippocampus to replicate AD pathology model and interfered with TGP. The expression of inflammatory cytokines and phosphorylated MAPK pathway signaling molecules were observed by immunohistochemistry (SABC), and SABC images were analyzed by image analysis software.</p><p><b>RESULT</b>Compared with the control group, the IL-1beta, IL-6 and p-p38, p-JNK, p-MEK3/6 positive stained areas of AD pathology model group increased and their staining intensity decreased (the protein expression quantity inversely proportional to the staining intensity), while the IL-1beta, IL-6 and p-p38, p-JNK, p-MEK3/6 positive stained areas of the treatment groups decreased and their staining intensity increased compared with AD pathology model group.</p><p><b>CONCLUSION</b>Abeta42 deposition in hippocampus can induce the brain inflammation and the over-expression of IL-1beta, IL-6 and p-p38, p-JNK, p-MEK3/6. Inhibiting the over-expression of inflammatory cytokines and phosphorylated MAPK signaling molecules may be a major antagonistic mechanism of TGP against AD.</p>

Effect of Zhibo Dihuang Pill on Leptin-induced Idiopathic Central Precocious Puberty in Mice / 广州中医药大学学报

Objective To observe the effect of Zhibo Dihuang Pill(ZDP) on leptin-induced idiopathic central precocious puberty(ICPP) in mice.Methods Eighteen BALB/c female mice aged 18 months were randomized into 6 groups: normal group,model group,high-and low-dose ZDP groups(at the dose of 101.4 and 50.7 g?kg-1?d-1 respectively),and megestrol acetate(3.9 mg?kg-1?d-1)group and gonadotropin releasing hormone analogues(GnRH-A) group(at the first dose of 1573.5 ?g/kg,the second and the third dose of 1180 ?g/kg,once every other day).Except the normal group,the mice in other groups received intraperitoneal injection of leptin 20mg/kg to establish ICPP model.After treatment,the vaginal opening,body weight,uterus weight and ovaries weight as well as the serum levels of luteinizing hormone(LH),estrogen(E2) were detected.Meanwhile,the uterus index and ovaries index were also examined.Results High-dose ZDP had an inhibition on the advance of vaginal opening induced by leptin after modeling for 4~6 days(P0.05).Conclusion The therapeutic effect of ZDP for ICPP is probably related with the inhibition of the advance of hypothalamic-pituitary-gonad axis activation.

Studies on the prolactin receptors on the membrane of rat liver cells / 中国病理生理杂志

Binding sites or receptors for prolactin were identified in crude membrane fractions prepared from female lactating Sprague-Dawley rat using receptor radioassay. The results further indicated that the membrane of rat liver cells are rich in prolactin receptors, and the Scatchard analysis of the binding of ~(125)I-oPRL to receptors revealed that female rat liver cells contained two classes of prolactin receptors (Kd_1=3.20?10~(-10) M, Kd_2=1.26?10~(-8)M) with high specificity.