Hepatitis B virus X protein promotes podocyte pyroptosis in hepatitis B virus-associated glomerulonephritis by down-regulating microRNA -223 targeting NLRP3 inflammasome / 中华肝脏病杂志

Objective: To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx). Methods: HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA). Results: miRNA-223 was down-regulated in HBx overexpression group compared with the control group (P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression (P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury (P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion: HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.

Multi-functional osteoclasts in matrix-based tissue engineering bone / 中华创伤杂志(英文版)

The repair of bone defects, especially for the large segment of bone defects, has always been an urgent problem in orthopedic clinic and attracted researchers' attention. Nowadays, the application of tissue engineering bone in the repair of bone defects has become the research hotspot. With the rapid development of tissue engineering, the novel and functional scaffold materials for bone repair have emerged. In this review, we have summarized the multi-functional roles of osteoclasts in bone remodeling. The development of matrix-based tissue engineering bone has laid a theoretical foundation for further investigation about the novel bone regeneration materials which could perform high bioactivity. From the point of view on preserving pre-osteoclasts and targeting mature osteoclasts, this review introduced the novel matrix-based tissue engineering bone based on osteoclasts in the field of bone tissue engineering, which provides a potential direction for the development of novel scaffold materials for the treatment of bone defects.

acupuncture method for mild cognitive impairment: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of acupuncture method for mild cognitive impairment in the elderly.@*METHODS@#A total of 96 patients were randomly divided into an observation group, a control group and a waiting group, 32 cases in each group. The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Yintang (GV 29) and Sishencong (EX-HN 1), etc, while the patients in the control group were treated with nonpenetrating sham acupuncture at the same acupoints as the observation group. The treatment was given once every other day, three times a week for 8 weeks. The patients in the waiting group only received health guidance for 8 weeks. Montreal cognitive assessment scale (MoCA) and mini-mental state examination (MMSE) were used before and after 8-week treatment in all three groups. The observation group and the control group were followed up for 2 months and evaluated with MoCA and MMSE.@*RESULTS@#The MoCA scores in the observation group after treatment and during follow-up were higher than before treatment (0.05). The MoCA scores in the control group after treatment and during follow-up were higher than before treatment (0.05). The difference before and after treatment in the observation group was higher than the control group and waiting group (0.05). The MMSE scores after treatment and during follow-up were higher than before treatment in the control group (0.05). The difference before and after treatment the observation group and control group was not significant (>0.05), and those in the two groups were higher than the waiting group (<0.01). The difference between follow-up and before treatment in the observation group was higher than the control group (<0.01), and the difference between follow-up and after treatment was lower than the control group (<0.01).@*CONCLUSION@# acupuncture method could improve cognitive impairment in elderly patients with mild cognitive impairment.

An investigation of ketoacidosis in children with newly diagnosed type 1 diabetes / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the incidence of diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 224 children with newly diagnosed type 1 diabetes, and according to the presence or absence of DKA, these children were divided into DKA group and non-DKA group, with 112 children in each group. The DKA group was further divided into ≥5-year group (65 children) and <5-year group (47 children), and according to the blood gas parameters, this group was divided into mild group (26 children), moderate group (29 children), and severe group (57 children). The factors influencing the development of DKA were analyzed, as well as the clinical and laboratory features of DKA children with different ages.</p><p><b>RESULTS</b>The most common symptoms in these 224 children with type 1 diabetes were polydipsia (86.2%), polyuria (78.6%), and weight loss (57.1%). Compared with the non-DKA group, the DKA group had a significantly higher percentage of children who were aged <5 years, who had low family income, or whose parents had an educational level of senior high school or below. The DKA group had significantly higher levels of random blood glucose and HbA1C and significantly lower levels of pH, HCO3, and C-peptide than the non-DKA group (P<0.05). There was no significant difference in the percentage of children with severe DKA between the ≥5-year group and the <5-year group (P>0.05). Compared with the <5-year group, the ≥5-year group sufferred from symptoms for a significantly prolonged period, and had a significantly lower level of random blood glucose and significantly higher levels of HbA1C and C-peptide (P<0.05).</p><p><b>CONCLUSIONS</b>DKA has a high incidence rate in children with type 1 diabetes, and the development of DKA is associated with age, parents' educational level, and family income.</p>