Effects of Qishen Dihuang Granules on Intestinal Microbiota in Experimental Autoimmune Myasthenia Gravis Model Rats.

Objective: Effects of Qishen Dihuang (QSDH) granules on intestinal flora of an experimental autoimmune myasthenia gravis (EAMG) model rat were investigated (CNBI:PRJNA910532). Methods: Thirty-six female Lewis rats were assigned to Control, EAMG, QSDH-low-dose, QSDH-medium-dose, QSDH-high-dose, and Prednisone groups using the random number table method (6 rats/group). A rat EAMG model was established by injecting Rα97-116 peptide antigen. Each day for 30 days, gavages were administered to rats in the Chinese medicine group (QSDH granules in different concentrations), Prednisone group (prednisone), and Control and Model groups (0.5% CMC). After 30-day gavages, rat fecal samples were collected and the microbial community composition and diversity differences between intestinal microbiota of EAMG and QSDH granule-treated groups were analyzed using 16S amplicon sequencing to explore the effect underlying QSDH granules alleviation of EAMG. Results: The clinical symptoms of rats in each treatment group improved significantly after the intervention treatment with QSDH granules. Comparison of the relative abundance of microorganisms in the gut flora of different groups with that of the EAMG group rats revealed: significantly lower phylum-level Bacteroidetes abundance and significantly greater Actinobacteria abundance in the QSDH-high-dose group and a significantly greater Firmicutes/Bacteroidetes ratio in the QSDH-medium-dose group; significantly increased family-level QSDH-high-dose group abundances of Lachnospiraceae and Trichospiraceae (Firmicutes), significantly increased QSDH-medium-dose group Lactobacillaceae abundance, and significantly increased QSDH-low-dose group Bacteroidaceae abundance; genus-level, QSDH-high-dose group Prevotella and Coprococcus abundances were significantly increased and Turicibacter and Lactobacillus abundances were significantly decreased, while QSDH-medium-dose group Akkermansia and Lactobacillus abundances were significantly increased. Greater overall community richness, diversity, and genetic diversity were observed in QSDH granules-treated groups, but differences were insignificant (P > .05). The most significant inter-group genus-level community marker differences involved Prevotella, Ruminococcus, Coprococcus, and Turicibacter. Conclusion: QSDH granules may regulate EAMG rat intestinal flora by decreasing relative abundances of Turicibacter and Clostridium and increasing relative abundances of Bifidobacterium, Lachnospiraceae, and Prevotella.

An Indoor Fire Detection Method Based on Multi-Sensor Fusion and a Lightweight Convolutional Neural Network.

Indoor fires pose significant threats in terms of casualties and economic losses globally. Thus, it is vital to accurately detect indoor fires at an early stage. To improve the accuracy of indoor fire detection for the resource-constrained embedded platform, an indoor fire detection method based on multi-sensor fusion and a lightweight convolutional neural network (CNN) is proposed. Firstly, the Savitzky-Golay (SG) filter is used to clean the three types of heterogeneous sensor data, then the cleaned sensor data are transformed by means of the Gramian Angular Field (GAF) method into matrices, which are finally integrated into a three-dimensional matrix. This preprocessing stage will preserve temporal dependency and enlarge the characteristics of time-series data. Therefore, we could reduce the number of blocks, channels and layers in the network, leading to a lightweight CNN for indoor fire detection. Furthermore, we use the Fire Dynamic Simulator (FDS) to simulate data for the training stage, enhancing the robustness of the network. The fire detection performance of the proposed method is verified through an experiment. It was found that the proposed method achieved an impressive accuracy of 99.1%, while the number of CNN parameters and the amount of computation is still small, which is more suitable for the resource-constrained embedded platform of an indoor fire detection system.

Credibility Assessment Method of Sensor Data Based on Multi-Source Heterogeneous Information Fusion.

The credibility of sensor data is essential for security monitoring. High-credibility data are the precondition for utilizing data and data analysis, but the existing data credibility evaluation methods rarely consider the spatio-temporal relationship between data sources, which usually leads to low accuracy and low flexibility. In order to solve this problem, a new credibility evaluation method is proposed in this article, which includes two factors: the spatio-temporal relationship between data sources and the temporal correlation between time series data. First, the spatio-temporal relationship was used to obtain the credibility of data sources. Then, the combined credibility of data was calculated based on the autoregressive integrated moving average (ARIMA) model and back propagation (BP) neural network. Finally, the comprehensive data reliability for evaluating data quality can be acquired based on the credibility of data sources and combined data credibility. The experimental results show the effectiveness of the proposed method.

Expression of Aldehyde Dehydrogenase 1A1 (ALDH1A1) as a Prognostic Biomarker in Colorectal Cancer Using Immunohistochemistry.

BACKGROUND The expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is increased in several human tumors, including colorectal carcinoma (CRC). The aim of this study was to compare the expression ALDH1A1 in CRC tumor tissue compared with non-tumor adjacent tissue (NAT), using immunohistochemistry (IHC), and to determine whether the expression of the ALDH1A1 protein was associated with prognostic factors in CRC. MATERIAL AND METHODS Formalin-fixed paraffin-embedded (FFPE) tissue from 424 patients diagnosed with CRC, and 196 matched NATs were used to prepare tissue microarrays (TMAs). IHC was performed using an immunoperoxidase method with a primary polyclonal rabbit anti-ALDH1A1 antibody. The IHC scores by light microscopy were the staining intensity (scored from 0-3) multiplied by the percentage area of positive immunostaining within the visual field (scored from 0-4). Associations between tumor expression levels of ALDH1A1 and patient clinicopathological characteristics, including tumor grade, size, and TNM stage at surgery were analyzed. RESULTS ALDH1A1 protein expression was significantly increased in CRC tissues compared with matched NATs. In patients with CRC, increased expression of the ALDH1A1 protein was significantly associated with the presence of lymph node metastasis: 64.28% in N0 cases; 75.49% in N1 cases; and 82.14% in N2 cases, (P=0.002). Univariate and multivariate analysis showed that ALDH1A1 expression was an independent prognostic marker for CRC (P<0.001). CONCLUSIONS Using IHC, the expression of the ALDH1A1 protein in CRC tissues was significantly associated with the presence of lymph node metastases and might be a potential prognostic marker in patients with CRC.

HIPEC with CRS versus cytoreductive surgery (CRS) for the gastric cancer metastasis to peritoneum.

BACKGROUND: Peritoneal metastases (PM) have a poor prognosis in gastric cancer (GC). Cytoreductive surgery (CRS) gives favorable outcomes, but the influence of hyperthermic intraperitoneal chemotherapy (HIPEC) remains contentious. We designed to distinguish results between CRS versus HIPEC-CRS in patients with peritoneal metastases from gastric cancer. MATERIALS AND METHODS: PubMed, Scopus, Embase and Cochrane library accessed to collect data and language is restricted to English. RevMan 5.4 was used to perform statistical analysis. The outcomes for categorical variables are mentioned in the risk ratio. RESULTS: Ten trials involving 1367 patients in which 707 were CRS-HIPEC, while 660 CRS. We got significant results in 3rd year survival (P < 0.05), while 1st and 5th years are not statistically significant P > 0.05. CONCLUSION: To compare with CRS, CRS-HIPEC has improved survival rate in deprived of further morbidity or mortality.

Robot-assisted surgery versus laparoscopic surgery of ureteropelvic junction obstruction in children: a systematic review and meta-analysis.

The clinical effectiveness and safety of robot-assisted laparoscopic pyeloplasty (RP) compared with laparoscopic pyeloplasty (LP) have not been clearly established in ureteropelvic junction obstruction (UPJO) children and require review. We searched in the Cochrane, MEDLINE, EMBASE, Web of Science, and CNKI database on 30 June 2022. This systematic review and meta-analysis were performed in RevMan 5.4 based on studies comparing RP versus LP in children with UPJO and subgroup analysis in children < 2 years of age has been performed. The Newcastle-Ottawa Scale was used to evaluate the studies. We included one RCT, and eighteen cohort studies, a total involving 3370 children. Compared with LP, RP showed higher surgical success rates (OR 2.57, 95%CI (1.24, 5.32), P < 0.05), lower postoperative complication rates (OR 0.61, 95%CI (0.38, 0.99), P < 0.05), shorter hospital stay (MD - 1.04, 95% CI (- 1.6, - 0.47), P < 0.05) as well as operative time (MD - 22.11, 95%CI (- 35.91, - 8.31), P < 0.05). No significant differences were detected for intraoperative complication rates or conversion to open surgery rates. RP is an alternative to UPJO with higher success rates, and less postoperative complications. Evidence on the effectiveness and safety of RP compared with LP for UPJO children is of low certainty. More quality evidence in the form of randomized controlled trials is needed to obtain more reliable analysis results.

Toxoplasma gondii excretory/secretory proteins promotes osteogenic differentiation of bone marrow mesenchymal stem cells via aerobic glycolysis mediated by Wnt/ß­catenin signaling pathway.

Toxoplasma gondii excretory/secretory proteins (TgESPs) are a group of proteins secreted by the parasite and have an important role in the interaction between the host and Toxoplasma gondii (T. gondii). They can participate in various biological processes in different cells and regulate cellular energy metabolism. However, the effect of TgESPs on energy metabolism and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) has remained elusive. In the present study, TgESPs were extracted from the T. gondii RH strain and used to treat BMSCs to observe the effect of TgESPs on energy metabolism and osteogenic differentiation of BMSCs and to explore the molecular mechanisms involved. The osteogenic differentiation and energy metabolism of BMSCs were evaluated using Alizarin Red S staining, qRT-PCR, western blot, immunofluorescence and Seahorse extracellular flux assays. The results indicated that TgESPs activated the Wnt/ß­catenin signaling pathway to enhance glycolysis and lactate production in BMSCs, and promoted cell mineralization and expression of osteogenic markers. In conclusion, the present study uncovered the potential mechanism by which TgESPs regulate BMSCs, which will provide a theoretical reference for the study of the function of TgESPs in the future.

Investigation of the Underlying Mechanism of Huangqi-Dangshen for Myasthenia Gravis Treatment via Molecular Docking and Network Pharmacology.

The herbal pairing of Huangqi and Dangshen (HD) is traditional Chinese herbal medicine and has been widely used in China, especially to treat myasthenia gravis (MG). However, the mechanism of HD on MG is unclear. Aim of the Study. This study aims to investigate HD's possible role in MG treatment. Materials and Methods. The TCMSP database was used to identify the active chemicals and their targets. The GeneCards, DisGeNET, and OMIM databases were used to search for MG-related targets. The STRING database was employed in order to identify the common PPI network targets. We next utilised Cytoscape 3.8.2 for target identification and the DAVID database for gene ontology (GO) function analysis as well as Encyclopaedia of Genomes (KEGG) pathway enrichment analysis on the selected targets. The AutoDock Vina software was used to test the affinity of essential components with the hub gene before concluding that the primary targets were corrected through molecular docking. Results. 41 active compounds were screened from HD, and the number of putative-identified target genes screened from HD was 112. There were 21 target genes that overlapped with the targets of MG, which were postulated to be potential treatment targets. Through further analysis, the results showed that the active compounds from HD (such as 7-methoxy-2-methylisoflavone, quercetin, luteolin, Kaempferol, and isorhamnetin) may achieve the purpose of treating MG by acting on some core targets and related pathways (such as EGFR, FOS, ESR2, MYC, ESR1, CASP3, and IL-6). Molecular docking findings demonstrated that these active molecules have a near-perfect ability to attach to the primary targets. Conclusion. Through network pharmacology, the findings in this study provide light on the coordinated action of several HD formula components, targets, and pathways. It provided a theoretical basis for further study of HD pharmacological action.

Aloin promotes osteogenesis of bone-marrow-derived mesenchymal stem cells via the ERK1/2-dependent Runx2 signaling pathway.

Osteoporosis is characterized by low bone mass and the degeneration of bone structure, conditions which increase the risk of fracture. Aloin has been shown to affect bone metabolism, but its role in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The aim of our study was to determine whether aloin promotes the proliferation and osteogenic differentiation of BMSCs and, if so, whether it acts via activation of the ERK1/2-Runx2 signaling pathway. We found that the different concentrations of aloin tested had no obvious cytotoxic effects on the viability of BMSCs. Under osteogenic induction conditions, aloin increased cellular alkaline phosphatase activity, promoted BMSC mineralization, and increased osteogenic-related gene expression. In addition, treating the BMSCs with the signal transduction inhibitor PD98059 (ERK1/2) effectively attenuated Runx2 activation in these cells and also suppressed osteoblastic differentiation. Overall, our study demonstrates that aloin promotes osteogenic differentiation of BMSCs through activation of the ERK1/2-Runx2 signaling pathway.

Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is an inflammatory disease of the joints that causes progressive disability in the elderly. Reactive oxygen species (ROS) play an important role in OA development; they may activate the NLRP3 inflammasome, thereby inducing the secretion of proinflammatory IL-1ß and IL-18, leading to the aggravation of the downstream inflammatory response. Nrf2 is a key transcription factor that regulates the expression of antioxidant enzymes that protect against oxidative stress and tissue damage. We aimed to explore the underlying mechanism of OA development by investigating NLRP3, ASC, Nrf2, and HO-1 expression in synovia and their regulatory networks in OA. METHODS: Human total knee replacement samples were subjected to histology and micro-CT analysis to determine the pathological changes in the cartilage and subchondral bone and to assess the expression of inflammation-related markers in the synovial tissue by immunohistochemistry (IHC), qRT-PCR, and Western blot. To investigate these pathological changes in an OA animal model, adult Sprague-Dawley rats were subjected to anterior cruciate ligament transection and medial meniscectomy. Articular cartilage and subchondral bone changes and synovial tissue were also determined by the same methods used for the human samples. Finally, SW982 cells were stimulated with lipopolysaccharide (LPS) as an in vitro inflammatory cell model. The correlation between NLRP3 and Nrf2 expression was confirmed by knocking down NLRP3 or Nrf2. RESULTS: Cartilage destruction and subchondral bone sclerosis were found in the OA patients and OA model rats. Significantly increased expression levels of NLRP3, ASC, Nrf2, and HO-1 were found in the synovial tissue from OA patients. NLRP3, ASC, Nrf2, and HO-1 expression in the synovium was also upregulated in the OA group compared with the sham group. Furthermore, the NLRP3, Nrf2, HO-1, IL-1ß, and IL-18 expression in LPS-treated SW982 cells was increased in a dose-dependent manner. As expected, the expression of NLRP3 was upregulated, and the expression of IL-1ß and IL-18 was downregulated after Nrf2 silencing. However, knocking down NLRP3 did not affect the expression of Nrf2. CONCLUSIONS: ROS-induced oxidative stress may be the main cause of NLRP3 inflammasome activation and subsequent release of downstream factors during OA development. Nrf2/HO-1 signaling could be a key pathway for the activation of the NLRP3 inflammasome, which may contribute to the progression of OA. Herein, we discovered a novel role of Nrf2/HO-1 signaling in the production of NLRP3, which may facilitate the prevention and treatment of OA.

Biomineralization improves mechanical and osteogenic properties of multilayer-modified PLGA porous scaffolds.

Poly-(lactide-co-glycolide acid) (PLGA) has been widely investigated as scaffold material for bone tissue engineering owing to its biosafety, biodegradability, and biocompatibility. However, the bioinert surface of PLGA may fail in regulating cellular behavior and directing osteointegration between the scaffold and the host tissue. In this article, oxidized chondroitin sulfate (oCS) and type I collagen (Col I) were assembled onto PLGA surface via layer by layer technique (LbL) as an adhesive coating for the attachment of inorganic minerals. The multilayer-modified PLGA scaffold was mineralized in vitro to ensure the deposition of nanohydroxyapatite (nHAP). It was found that nHAP crystals were more uniformly and firmly attached on the multilayer-modified PLGA as compared with the pure PLGA scaffold, which remarkably improved PLGA surface and mechanical properties. Additionally, in vitro biocompatibility of PLGA scaffold, in terms of bone mesenchymal stem cells (BMSCs) attachment, spreading and proliferation was greatly enhanced by nHAP coating and multilayer deposition. Furthermore, the fabricated composite scaffold also shows the ability to promote the osteogenic differentiation of BMSCs through the up-regulation of osteogenic marker genes. Thus, this novel biomimetic composite scaffold might achieve a desirable therapeutic result for bone tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2714-2725, 2018.

[Effects of leptin and insulin on leptin receptors mRNA expression in human hepatocellular HepG2 cells].

OBJECTIVE: To study the leptin receptor isoforms regulation by leptin and insulin. METHODS: Human hepatocellular carcinoma cells of the line HepG2 were cultured in DMEM containing 10% FBS in six-well plate and were incubated for 24 hours in serum-free medium containing 0, 10(-9), 10(-8), 10(-7), and 10(-6) mol/L of human leptin or insulin. Using the semi-quantitative RT-PCR technique, the mRNA expressions of long (OB-Rb) and short (OB-Ra: OB-R219.3) leptin receptor isoforms were measured. RESULTS: OB-Rb and OB-R219.3 mRNAs were expressed in this cell line. Leptin of the concentrations of 10(-7) approximately 10(-6) mol/L significantly inhibited the OB-Rb mRNA expression, with the maximum decrease (by 43%) at the concentration of 10(-6) mol/L. Similarly the mRNA expression of OB-R219.3 was also markedly reduced in cells treated with leptin of the concentrations of 10(-8) approximately 10(-6) (mol/L), with the maximum inhibition (by 49%) at the concentrations of 10(-6) mol/L. Insulin showed no effect on OB-Rb and OB-R219.3 mRNAs expression in HepG2 cell. CONCLUSION: In HepG2 cells, leptin down-regulates the expressions of OB-Rb and OB-R219.3 mRNAs, and insulin has no effect on OB-Rb and OB-R219.3 mRNAs, which contributes at least partly to an understanding of the mechanism of leptin resistance in vivo and suggests that leptin-induced receptor down-regulation may be relevant to leptin resistance at sites of peripheral action.