Inherited protein C deficiency in pregnancy: a case report / 中华围产医学杂志

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

Scutellarin alleviates lipopolysaccharide-induced renal injury via mediating cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 expression to inhibit nuclear factor-κB signaling pathway / 中华危重病急救医学

Objective:To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI).Methods:① In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). ② In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 μmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. Results:① The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. ② The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2 -ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT) : 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2 -ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2 -ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1β mRNA (2 -ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2 -ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2 -ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. Conclusions:Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Naringenin protects ischemia-reperfusion-induced acute kidney injury by nuclear factor κB / 中华肾脏病杂志

Objective:To explore the effect and involved mechanism of naringenin on acute kidney injury (AKI) induced by ischemia-reperfusion (IR).Methods:The IR-AKI rat model was constructed using the classic bilateral renal pedicle clamping method, then renal function and pathological change were assessed, as well as inflammation-associated genes were detected by quantitative real-time PCR. The hub genes were selected through differential gene analysis and protein-protein interaction network analysis, and their transcription factors were predicted, which constructed a protein library together. The proteins binding to naringenin were selected by reverse molecular docking analysis and further their binding patterns were predicted to explore the mechanism of naringenin. Finally, the results of bioinformatics were verified by experimental methods.Results:Compared with the AKI group, the kidney pathology of the rats in the naringenin pretreatment group was significantly improved, and the renal tubular injury score was reduced ( P<0.01); meanwhile the serum creatinine level and the mRNA expression of the kidney injury molecule 1 (KIM-1) were significantly decreased (both P<0.05). Compared to sham group, IR-AKI increased the level of nuclear factor κB (NF-κB), tumor necrosis factor-α and interleukin-1β (all P<0.05), which reversed by naringenin indicated that naringenin inhibited inflammation in IR-AKI. Differential gene analysis was performed on the GSE98622 data set, and 359 differential genes were obtained. In reverse molecular docking, the proteins with smallest binding energy including NFKBIA, BCL3, NFKB2 and RELA were considered to be related to the preventive effect of naringenin, which were mainly enriched in NF-κB-related inflammation pathways. Domain functional analysis of NF-κB-related genes showed that naringenin could stably bind to its key domain. According to quantitative real-time PCR results, naringenin increased BCL3 level after AKI ( P<0.05), and further decreased the expression level of RELA and NFKB2 (both P<0.05). Conclusion:Naringenin protects IR-AKI by alleviating inflammation, and its mechanism is related to increasing BCL3 and thereby inhibiting the NF-κB pathway.

Study on GLIS3 mutations in children with congenital hypothyroidism / 中华实用儿科临床杂志

Objective To investigate the features and characteristics of GLIS3 gene mutation in patients with congenital hypothyroidism(CH),and to establish the theoretical basis for gene diagnosis and prenatal diagnosis of CH.Methods Genomic DNA was extracted from peripheral blood leukocytes of 50 patients with CH who were collected from February 2007 to November 2016 in Shandong Province.The exon 2 to 11 of GLIS3 were amplified with 11 pairs of sequence specific primers designed by Primer 5.0.Polymerase chain reaction and the first generation of sequencing method(Sanger sequencing) were used to detect the mutation.Comparison of the sequencing results with the GLIS3 reference sequence (National Center for Biotechnology Information Reference Sequence:NC_000009.12) helped to screen gene mutations.Results The 50 CH patients included 22 boys and 28 girls,and the sex ratio was 1.0 ∶ 1.3.The mean age was (2.5 ± 0.5) years.Six cases (12％) had thyroid gland hypoplasia,23 cases (46％) had thyroid gland agenesis and 21 cases(42％) with ectopic thyroid gland.C2507A missense mutation was found in exon 10 of GLIS3 in a thyroid gland agenesis case,which might result in proline to glutamine substitution at codon 836.One mutant (rs780019691,c.C289T) was detected which was nonsense mutation (Arg→Stop) in another thyroid gland agenesis child.Conclusions The mutation rate of GLIS3 gene is very low in CH children of Shandong province.Further studies are needed to investigate the relationship between GLIS3 genotypes and clinical phenotypes.

Clinical use of recombinant human growth hormone in aged patients with postoperative fatigue syndrome / 肠外与肠内营养

Objectives: The aim of this study was to define whether growth hormone therapy would reduce the course of postoperative fatigue (POF) in aged patients (60～80 years old) with nutritional support. Methods: Forty aged patients who underwent partial gastrectomy or other operations were randomized into two groups. All patients were treated with the same nutritional support formula.A group of patients was treated with rhGH for 7 day from the third day after operation, and control group treated with placebo.The score of POF, nitrogen balance, transferrin level and body weight were monitored. Results: Score of POF in rhGH group on day 7 and 14 after operation was lower than that in control group(P0.05). Conclusions: Aged patients with rhGH after major operation can recover more rapidly from POF.