Histopathological changes of the dural myeloid cells and lymphatic vessels in a mouse model of sepsis-associated encephalopathy.

As a common diffuse encephalopathy caused by sepsis, sepsis-associated encephalopathy (SAE) is closely associated with increased mortality, severe cognition dysfunction and increased cost of health care in patients of sepsis. Accumulating evidence suggests that the dura mater, the outermost meninges of the central nervous system (CNS), plays an important role in CNS immunity, especially with the discovery of meningeal lymphatic vessels (mLVs), as well as a plentiful array of resident or infiltrating immune cells harbored in the dura. Although these findings have significantly enhanced our understanding of the immune function of dura under both steady-state and pathological condition of CNS, whether and how the immune cells and mLVs within dura response to SAE still remains largely unexplored. Here, we established lipopolysaccharide (LPS) intraperitoneal injection-induced SAE model and examined the dural resident immune cells and mLVs. We analysed the histological change in dura by performing hematoxylin and eosin (H&E) and immunofluorescence staining. Results showed that systemic exposure to LPS induced neutrophils recruitment, exudation and gathering around the dural blood vessels. Moreover, resident macrophage altered its shape as well as location, and downregulated major histocompatibility (MHC) class II expression following LPS injection. We also found that LPS exposure induced dorsal meningeal lymphangiogenesis. Together, these findings collectively demonstrated that LPS-induced SAE can stimulate immune cells and mLVs within dura and provided more information about the immune response of the dura in sepsis.

Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database.

Background: Some studies had reported that patients with viral hepatitis are at increased risk of reduced bone mineral density and even osteoporosis. However, the interaction between reduced bone mineral density (BMD) and viral hepatitis remains inconclusive. Therefore, our study collected hepatitis test results and bone mineral density from respondents in the NHANES database. The aim of this study was to investigate whether there is an association between hepatitis and a decrease in bone mineral density. Methods: The respondents with both hepatitis- and BMD-related indicators from the NHANES database in the United States from 2005-2010, 2013-2014, to 2017-2020 were collected for this study. BMD were compared between respondents who were positive and negative for respondents related to hepatitis B and C. BMD was measured using dual-energy X-ray absorptiometry of the femur and lumbar spine. Finally, multiple regression analysis was performed between hepatitis B surface antigen (HBsAg) and hepatitis C RNA (HCV-RNA) and BMD in the respondents. Results: A total of 15,642 respondents were included in the hepatitis B surface antigen-related survey. Of these, 1,217 respondents were positive for hepatitis B surface antigen. A total of 5111 hepatitis C RNA-related responders were included. Hepatitis C RNA-positive had 268 respondents. According to the results of the multiple regression analysis, the femoral BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (-) respondents: -0.018 (-0.026, -0.009) (P < 0.01). Moreover, spinal BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (-) respondents: -0.020 (-0.030, -0.010) (P < 0.01). According to the results of multiple regression analysis for hepatitis C RNA, HCV-RNA (+) respondents had significantly lower BMD compared to HCV-RNA (-) respondents: -0.043 (-0.059, -0.026) (P < 0.01). Conclusion: During the analysis of respondents in the NHANES database in the United States, positive tests for hepatitis B surface antigen and hepatitis C RNA were found to be associated with a reduction in BMD. Positive serology for these hepatitis indicators may increase the risk of reduced BMD. Of course, this conclusion still needs to be further confirmed by more large clinical trials.

Overexpression of MicroRNA-155 aggravates pulpitis by targeting kinesin superfamily Proteins-5C based on illumina high-throughput sequencing.

AIM: To investigate the regulatory role of miR-155 and Kinesin Superfamily Proteins-5C (KIF-5C) in the progression of pulpitis based on bioinformatic analysis. METHODOLOGY: Normal pulp tissues and pulpitis pulp tissues were collected and subjected to high-throughput sequencing and the differentially expressed miRNAs were determined. An in vitro and in vivo pulpitis model was established. HE, IHC staining and histological evaluation were used to verify the inflammatory state of human and mouse pulp tissues. The mRNA expression of IL-1ß and TGF-ß1 were determined by RT-qPCR and protein expression of IL-1α, IL-4, IL-8, IL-13, IFN-γ, IL-6, IL-10 and MCP-1 were determined by protein chip. The target genes of miR-155 were predicted by miRanda database and verified by Dual-luciferase reporter assay, RT-qPCR and western blotting. MiR-155 lentivirus were used to upregulate or downregulate miR-155 and the siRNA of KIF-5C was used to downregulate KIF-5C. The expression of miR-155 or KIF-5C was determined by RT-qPCR. All statistics were analysed using GraphPad prism 8.2. RESULTS: The high-throughput sequencing results showed that 6 miRNAs (miR-155, miR-21, miR-142, miR-223, miR-486, miR-675) were significantly upregulated in diseased human pulp tissues, and miR-155 was significantly elevated among the six miRNAs. RT-qPCR results demonstrated that miR-155 expression was upregulated in human pulpitic tissue, mice pulpitic tissue and LPS-HDPCs. IL-1ß was increased while TGF-ß1 was decreased in lenti-miR-155 transfected LPS-HDPCs. Analysis of protein chip results indicated that lenti-miR-155 transfected LPS-HDPCs produced higher levels of IL-8, IL-6, MCP-1. The opposite results were obtained when miR-155 was inhibited. Through miRanda database screen and Dual-luciferase reporter assay, the target gene (KIF-5C) of miR-155 was identified. In lenti-miR-155 transfected LPS-HDPCs, the expression of KIF-5C was downregulated. However, when shRNA-miR-155 was transfected to LPS-HDPCs, the opposite result was obtained. Silent RNA was used to knock down KIF-5C, the results showed that when both KIF-5C and miR-155 were knocked down simultaneously, the downregulated expression of inflammatory factors observed in LPS-HDPCs following miR-155 knockdown was rescued. CONCLUSION: MiR-155 plays an important role in promoting pulpitis through targeting KIF-5C and may serve as a potential therapeutic target.

[Progress in possible effects of BCG vaccine on the prevention of SARS-CoV-2 infection: An update].

The research and development of the coronavirus disease 2019 (COVID-19) vaccine is being carried out globally. Although vaccine research and development technology has made great progress, the possibility of obtaining a safe and effective vaccine that can control the global epidemic in a short period of time is still low due to the antibody-dependent enhancement effect (ADE) of the vaccine and the mutation of the virus. In the absence of specific treatment for COVID-19, finding other alternative protection schemes has become another treatment idea. Epidemiological studies have found that, in this COVID-19 epidemic, countries with long-term Bacillus Calmette-Guerin (BCG) vaccination policies have relatively less cases and lower mortality rates than countries without relevant policies. This phenomenon may be related to the "training immunity" effect of BCG. In order to further clarify the preventive and protective effects of BCG vaccine on SARS-CoV-2 infection, a number of clinical trials are underway.

[Clinical evaluation of modified free gingival transplantation technique].

PURPOSE: To evaluate the clinical effect of modified free gingival graft technique of the peri-implant. METHODS: There were 42 mandibular posterior area implant sites in 36 patients. The width of the keratinized gingiva at the midpoint of buccal gingival margin was less than 2 mm after implantation. Two months before restoration, modified free gingival graft technique was used, i.e. the donor site was treated with individualized palatal protective plate and the recipient site was treated with individualized graft pressure plate. The survival of the graft after operation was observed. The width of buccal keratinized gingiva was measured immediately, 2, 6, 12 months after operation. Visual analogue scale (VAS) was used to record postoperative pain of the patient 1, 3, 6 days after operation. SPSS 25.0 software package was used for t test and one-way variance analysis. RESULTS: All 42 implant sites survived. The average width of buccal keratinized gingiva of the preoperative implants was (0.39±0.41) mm and (4.17±0.43) mm 12 months, postoperatively; the average increase was (3.78±0.21) mm compared with preoperative measurement. The average shrinkage was (1.12±0.12) mm. CONCLUSIONS: Modified free gingival graft technique can effectively increase the width of buccal keratinized gingiva of the implants, with minimal shrinkage of the graft 1 year after operation without significant pain after operation.