1.Summary of evidence for non-pharmacological management of delirium in PICU patients
Lingling ZUO ; Shan HE ; Zelan ZUO ; Min LIAO
Chinese Pediatric Emergency Medicine 2023;30(5):327-333
Objective:To search and summarize the evidence for the non-pharmacological management of delirium of critically ill patients in PICU, and to provide evidence-based guidance for clinical practice.Methods:According to the "6S" evidence pyramid model, we searched computerized decision support system, websites of guidelines, and databases, and obtained the guidelines, clinical decisions, systematic reviews, and evidence summaries.After screening the articles, two researchers independently appraise articles using validated tools, and finally formed the evidence summary of delirium non-pharmacological management of critically ill patients in PICU.Results:Totally six articles were included for the evidence synthesis, including three guidelines, two systematic reviews, and one expert advice.Twenty pieces of evidence including four aspects were summarized, namely delirium screening, risk prediction, non-pharmacological prevention and management strategies, health care provider education and departmental standardization.Conclusion:The evidence summarized in this study can provide a reference to health care professionals.When we apply this evidence in the clinical setting, we should adapt it accordingly to the specific clinical setting to improve the effectiveness of the evidence.
2.Quantitative proteomics analysis of parthenogenetically induced pluripotent stem cells.
Zhe HU ; Lei WANG ; Zhensheng XIE ; Xinlei ZHANG ; Du FENG ; Fang WANG ; Bingfeng ZUO ; Lingling WANG ; Zhong LIU ; Zhisheng CHEN ; Fuquan YANG ; Lin LIU
Protein & Cell 2011;2(8):631-646
Parthenogenetic embryonic stem (pES) cells isolated from parthenogenetic activation of oocytes and embryos, also called parthenogenetically induced pluripotent stem cells, exhibit pluripotency evidenced by both in vitro and in vivo differentiation potential. Differential proteomic analysis was performed using differential in-gel electrophoresis and isotope-coded affinity tag-based quantitative proteomics to investigate the molecular mechanisms underlying the developmental pluripotency of pES cells and to compare the protein expression of pES cells generated from either the in vivo-matured ovulated (IVO) oocytes or from the in vitro-matured (IVM) oocytes with that of fertilized embryonic stem (fES) cells derived from fertilized embryos. A total of 76 proteins were upregulated and 16 proteins were downregulated in the IVM pES cells, whereas 91 proteins were upregulated and 9 were downregulated in the IVO pES cells based on a minimal 1.5-fold change as the cutoff value. No distinct pathways were found in the differentially expressed proteins except for those involved in metabolism and physiological processes. Notably, no differences were found in the protein expression of imprinted genes between the pES and fES cells, suggesting that genomic imprinting can be corrected in the pES cells at least at the early passages. The germline competent IVM pES cells may be applicable for germ cell renewal in aging ovaries if oocytes are retrieved at a younger age.
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Electrophoresis, Gel, Two-Dimensional
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Parthenogenesis
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physiology
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Pluripotent Stem Cells
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metabolism
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3.Effect of Tangbikang Granules on PI3K Pathway in Type 2 Diabetic Mellitus Rats with Non-alcoholic Fatty Liver Disease
Yaqi ZHANG ; Lingling QIN ; Chengfei ZHANG ; Qiue ZHANG ; Huizhong BAI ; Gang LIU ; Xinwei ZUO ; Yi ZHAO ; Tonghua LIU ; Xiaohong MU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):71-80
ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules(TBK) on type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats, which were then respectively treated (ig) with low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK for 12 weeks. Fasting blood glucose (FBG) and body mass were recorded every 4 weeks during the treatment. One week before sampling, the feed intake of rats was detected, and after 12 h night fasting, oral glucose tolerance test (OGTT) was performed. The area under the curve (AUC) was used to evaluate glucose tolerance, and the homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes: Fasting serum insulin (FINS), serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and nonesterified fatty acids (NEFA). The liver was weighed to calculate the liver index, and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The protein levels of insulin receptor substrate (IRS), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group (P<0.01), and the feed intake the administration groups was lower than that in the model group (P<0.05, P<0.01). At the 8th and 12th week, the body mass in the model group was lower than that in the normal group (P<0.01). Compared with the model group, TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group (P<0.01). The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group, and AUC in the administration groups was significantly different from that in the model group (P<0.01). The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group (P<0.01), and they were lower in the TBK groups than in the model group (P<0.01). Serum levels of TG, TC, HDL-C, NEFA (P<0.05, P<0.01), and LDL-C were higher in the model group than in the normal group. Serum levels of TG, TC, LDL-C, and NEFA in the TBK groups were lower than those in the model group, and the levels of TG, LDL-C, and NEFA in TBK groups were concentration-dependent (lowest levels in high-dose TBK group). Compared with the model group, high-dose TBK significantly increased the level of HDL-C (P<0.05). Liver index of the model group was higher than that in the normal group (P<0.01). The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver, the model group had unclear structure of liver lobule, enlarged cells of different sizes, and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury, particularly the high dose. For the PAS staining, compared with the normal group, the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein, p-IRS1/IRS1, and p-Akt/Akt in the model group were lower than those in the normal group (P<0.01), and they were higher in the high-dose TBK group than in the model group (P<0.01). ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.
4.Molecular Mechanism of Tangbikang Granules Against Diabetic Peripheral Neuropathy: Based on Network Pharmacology and Experimental Verification
Yaqi ZHANG ; Lingling QIN ; Huizhong BAI ; Chengfei ZHANG ; Qiue ZHANG ; Xinwei ZUO ; Shengyuan JIANG ; Yi ZHAO ; Tonghua LIU ; Xiaohong MU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):81-90
ObjectiveTo explore the mechanism of Tangbikang granules (TBK) against diabetic peripheral neuropathy (DPN) based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME, the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN, which were uploaded to Metascape for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin (STZ, ip) were employed to induce diabetes in rats, and then the model rats were respectively treated with low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK for 12 weeks. Sensory nerve conduction velocity (SNCV) was evaluated. After hematoxylin and eosin (HE) staining, the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase (AMPK) pathway-related targets in rat sciatic nerve, and Western blot to measure the protein expression of AMPK and phosphorylated (p)-AMPK in rat sciatic nerve. ResultThe main active components of TBK, such as quercetin, kaempferol, β-sitosterol, leech pteridine A, stigmasterol, and baicalein were screened out, mainly acting on interleukin-6 (IL-6), tumor necrosis factor (TNF), protein kinase B (Akt), JUN, and HSP90AA1 and signaling pathways such as AMPK, nuclear factor-κB (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6, TNF, JUN, and HSP90AA1. As for the animal experiment, compared with the normal group, model group had low SNCV of sciatic nerve (P<0.01), disordered and loose myelinated nerve fibers with axonotmesis and demyelinization, low mRNA expression of AMPKα, AMPKβ, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Sirtuin 3 (SirT3), mitochondrial transcription factor A (TFAM), and low p-AMPK/AMPK ratio in sciatic nerve (P<0.05, P<0.01). Compared with the model group, TBK of the three doses raised the SNCV (P<0.01), restored nerve morphology and nerve compactness, and increased the mRNA expression of AMPKα, AMPKβ, PGC-1α, SirT3, and TFAM (P<0.05, P<0.01). The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group (P<0.01), while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling, which lays a basis for further study of TBK in the treatment of DPN.
5.Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats
Huizhong BAI ; Lingling QIN ; Yaqi ZHANG ; Chengfei ZHANG ; Qiue ZHANG ; Xinwei ZUO ; Gang LIU ; Yu ZHAO ; Yi ZHAO ; Tonghua LIU ; Xiaohong MU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):91-98
ObjectiveTo explore the effect of Tangbikang granules (TBK) on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor (NF)-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin (STZ, ip) at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group, low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK groups, and lipoic acid group (0.026 8 g·kg-1) according to body weight and blood glucose level, and a normal group was designed. After modeling, administration began and lasted 12 weeks. The body mass, blood glucose level, and thermal withdrawal latency (TWL) of the rats were detected before treatment and at the 4th, 8th, and 12th week of administration. At the 12th week, the sciatic nerve was collected for hematoxylin-eosin (HE) and Luxol fast blue (LFB) staining, and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in sciatic nerve were measured by enzyme-linked immunosorbent assay (ELISA), and the levels of AMPK, phosphorylated (p)-AMPK, and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point (P<0.01). The levels of IL-1β, TNF-α, and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group (P<0.01), and the p-AMPK/AMPK ratio was smaller than that in the normal group (P<0.01). Compared with the model group, TBK of the three doses lowered the TWL (P<0.05, P<0.01) and the levels of IL-1β, TNF-α, and NF-κB protein in sciatic nerve of rats (P<0.05, P<0.01), and high-dose and medium-dose TBK raised p-AMPK/AMPK (P<0.05, P<0.01). The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB, thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.