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As people's living standards improve, the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B (NF-κB) in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors, so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer, and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine (TCM) treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad, it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation, oxidative stress, and energy metabolism, and it is involved in mediating inflammation, pancreatic β cell apoptosis, insulin signal transduction, and other physiological functions. Therefore, blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present, Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections, but the adverse reactions are obvious. TCM has been characterized by multi-target, extensive action, and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation, regulating qi and eliminating phlegm, clearing heat and detoxifying, and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper, the association between NF-κB signaling pathway and diabetes was summarized, and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed, so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.
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Objective:To explore the possible pharmacodynamic material basis and mechanism of Shaogan Fuzi Decoction in the treatment of rheumatoid arthritis through ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HRMS/MS) combined with network pharmacology and molecular docking method.Methods:The blood components of Shaogan Fuzi Decoction were analyzed by UPLC-HRMS/MS; the targets of blood components in Shaogan Fuzi Decoction were predicted by PubChem database and Swiss Target Prediction database; DrugBank database, Therapeutic Target Database (TTD) and GeneCards database were used to screen rheumatoid arthritis-related targets, and Venn map of common targets was obtained; the protein interaction network was constructed by STRING database, and the key targets and key components were screened; GO function enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID 6.8 database; the "blood component-target-pathway" network was constructed by Cytoscape 3.2.1 software; Autodock software was used to verify the molecular docking between the predicted key components and key targets in the network.Results:Totally 26 blood components of Shaogan Fuzi Decoction, 526 related targets, 478 related targets of rheumatoid arthritis, and 111 common targets were obtained; the key components such as tangeretin, kaempferol, glycyrrhetinic acid, liquiritigenin, quillaic acid and glabrolide were screened, which acted on key targets such as TNF, IL6, VEGFA, PTGS2, JUN and PPARG. They were mainly involved inflammatory response, steroid metabolic process, response to lipopolysaccharide, extracellular region, cytoplasm, RNA polymerase Ⅱ transcription factor activity, steroid bindingand other biological processes. It mainly regulated steroid hormone biosynthesis, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathway, rheumatoid arthritisand other signaling pathways. Molecular docking results showed that the key components had good binding activity with key targets.Conclusion:Shaogan Fuzi Decoction may act on TNF, IL6, VEGFA, PTGS2, JUN, PPARG and other targets through tangeretin, kaempferol, glycyrrhetinic acid and other blood components to regulate PI3K-Akt and other signaling pathways, inhibiting cell proliferation and promoting apoptosis, reducing inflammation, to treat rheumatoid arthritis.
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Objective To explore the clinical efficacy and safety of modified PPH combined with partial internal anal sphincterotomy in the treatment of circular mixed hemorrhoids.Methods Patients with annular mixed hemorrhoids were divided into two groups by a completely randomized controlled method.54 patients in the experimental group were treated with modified PPH combined with partial internal anal sphincterotomy,while 51 patients in the control group were treated with conventional PPH.The postoperative indicators,perioperative and long-term complication rates of the two groups were compared,and the clinical efficacy and safety were observed.Results The operation time in the experimental group was(48.35±4.37)minutes,which was higher than that in the control group(36.42 ±6.21)minutes(P<0.05).The incidence of postoperative anastomotic stenosis in the experimental group was 1.9%,lower than 15.6% in the control group(P<0.05).Anal pain,urinary retention,first defecation time,long-term anal distention,the experimental group was significantly better than the control group,the difference was statistically significant(P<0.05);The hospitalization time in the experimental group(4.8±0.62)days was not significantly different from that in the control group(5.1±0.54)days(P>0.05).The amount of intraoperative bleeding and anastomotic bleeding in the experimental group[(17.28±2.22)ml,3.7%]were not significantly different from those in the control group[(16.75± 2.13)ml,3.9%](P>0.05).Conclusion Compared with conventional PPH,the modified PPH combined with partial internal anal sphincterotomy slightly increases the operation time,but does not increase the risk of anastomotic bleeding,the incidence of rectal fistula,the amount of surgical bleeding,and the length of hospital stay.It can significantly improve postoperative anal pain,urinary retention,long-term distention symptoms,shorten the time of first defecation,ease the difficulty of defecation,and significantly reduce postoperative anastomotic stenosis,The long-term efficacy and safety are good.
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Objective: To explore the characteristics and rules of blood pressure changes in oceanauts during simulated operation of manipulator and troubleshooting tasks with different difficulty. Methods: In July 2020, 8 deep-sea manned submersible oceanauts, 6 males and 2 females, were selected as objects. In the 1∶1 model of Jiaolong deep-sea manned submersible, the oceanauts performed manipulator operation tasks and troubleshooting tasks with different difficulties, measured the continuous blood pressure of the oceanauts, filled in the NASA Task Load Index (NASA-TLX scale) after the completion of a single mission, and the changes of systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP) and mental workload were analyzed. Results: In a single task, the SBP, DBP and MAP of the oceanauts increased first and then decreased. The blood pressure values at the third minute were significantly lower than those at the first minute (P<0.01), and those at the fifth minute were significantly higher than those at the third minute (P<0.01). When performing the same task, compared with the quiet state, SBP, DBP and MAP increased when the oceanauts performed low difficulty, high difficulty, high difficulty+2-back manipulator operation task and troubleshooting task (P<0.05). When the task difficulty was the same, the SBP and MAP of oceanauts performing manipulator operation tasks were higher than those of oceanauts performing troubleshooting tasks (P<0.05). Compared with low difficulty tasks, the scores of NASA-TLX scale for oceanauts performing high difficulty manipulator operationtasks were significantly higher (P<0.05). Compared with the low difficulty task and high difficulty task, the scale score of the high difficulty+2-back troubleshooting task was significantly higher (P<0.05). When the task difficulty was the same, the scale scores of low difficulty and high difficulty manipulator operation tasks were significantly higher than those of troubleshooting tasks (P<0.05). SBP, DBP, MAP of No. 1, No. 3, No. 4, No. 5, and No. 7 oceanauts (all of whom had 6 years of diving) were positively correlated with NASA-TLX scale scores (r>0.8, P<0.05) . Conclusion: In the process of manned deep-sea diving, when the oceanauts perform manipulator operation tasks and troubleshooting tasks, with the increase of task difficulty, the mental load of oceanauts increases, and the blood pressure index increases significantly in a short time. At the same time, improving the proficiency of operation can reduce the variation range of blood pressure indexes. Blood pressure can be used as an effective reference to evaluate the difficulty of operation and guide scientific training.
الموضوعات
Female , Male , Humans , Blood Pressure , Diving , Workloadالملخص
Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.
الموضوعات
Humans , Vibrio parahaemolyticus/genetics , Diarrhea/epidemiology , Foodborne Diseases/epidemiology , Serogroup , Genomics , Dysentery , Vibrio Infections/epidemiology , Serotypingالملخص
ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 (CCK-8) assay was used to detect the effect of different concentration of rutin (3.125, 6.25, 12.5, 25, 50, 100, 200 μmol·L-1) on 3T3-L1 cell activity, and Western blot to examine the effect of rutin (12.5, 25, 50 μmol·L-1) on the expression of thermogenesis-associated proteins uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in adipocytes. After the optimal concentration of rutin was determined, the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining, and the expression of nuclear respiratory factor 1 (NRF1), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM), which were the landmark proteins of mitochondrial biosynthesis, was detected by Western blot. ResultCompared with the blank group, 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity (P<0.01). Compared with the blank group, at the concentration of 12.5, 25, 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins (UCP1, PRDM16, and PGC-1α) (P<0.01), which was determined as the optimal concentration. Compared with the blank group, 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells (P<0.01) and the expression of the markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM) (P<0.01). In addition, 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes (P<0.01). ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins (UCP1, PRDM16, and PGC-1α) and markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM), thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.
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Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
الموضوعات
Mice , Animals , Adipose Tissue, Brown , Sirtuin 1/pharmacology , Diabetes Mellitus, Type 2/metabolism , AMP-Activated Protein Kinases/metabolism , Morus/metabolism , Flavonoids/metabolism , Prospective Studies , Signal Transduction , Adipose Tissue, White , Plant Leaves , Uncoupling Protein 1/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolismالملخص
ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus (T2DM) through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 (PI3K/Akt/PPARα/CPT-1) signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin (STZ). The model rats were randomly divided into a model group, a metformin (0.2 g·kg-1) group, and a Mori Folium water extract (4.0 g·kg-1) group according to blood glucose and body weight. In the 8-week administration, fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin (HE) staining and oil red O staining. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum were measured by biochemical methods. Western blot (WB) was used to quantitatively detect the protein expression of p-PI3K,PI3K,p-Akt,Akt,PPARα,and CPT-1 in the rat liver. ResultAfter 8-week administration, the blood glucose of rats was higher in the model group than that in the control group (P<0.01), and lower in the Mori Folium water extract group than that in the model group (P<0.01). The results of HE staining showed that the liver tissue structure of the control group was complete, and the hepatocytes were arranged radially around the central vein, while the hepatocyte injury in the model group was obvious. Compared with the model group, the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group, and no lipid droplets in the hepatocytes were observed, while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC, TG, LDL-C, AST, and ALT in the model group were significantly higher than those in control group (P<0.01). The levels of TC, TG, LDL-C, AST, and ALT in the Mori Folium water extract group were significantly lower than those in the model group (P<0.05,P<0.01). WB showed that the protein expression of p-PI3K/PI3K, p-Akt/Akt, PPARα, and CPT-1 in the model group were lower than those in the control group (P<0.01). Mori Folium water extract could increase the protein expression of p-PI3K/PI3K, p-Akt/Akt, PPARα, and CPT-1 (P<0.05 or P<0.01). ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.
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ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 (T2DM) rats, and the mechanism based on liver peroxidase proliferators activate receptors-α (PPAR-α) and carnitine palmityl transferase-1 (CPT-1) proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet (HFD) + streptozocin(STZ)method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose (300 mg·kg-1), medium dose (150 mg·kg-1), and low dose (75 mg·kg-1) of total flavonoids of mulberry leaves for 8 weeks, respectively, to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin (HE) staining. Biochemical method was used to detect the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) of blood lipid metabolism in rats. The messenger ribonucleic acid (mRNA) and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves, compared with the control group, the food intake, liver index, and fasting blood glucose of rats in the model group increased significantly (P<0.01). Compared with the model group, the food intake, fasting blood glucose, and liver index of rats in the administration groups decreased significantly (P<0.01). The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group, the levels of TC, TG, and LDL-C increased significantly (P<0.01), but the level of HDL-C decreased significantly (P<0.01) in the model group. Compared with the model group, the levels of TC, TG, and LDL-C decreased significantly (P<0.05, P<0.01), whereas the level of HDL-C increased significantly (P<0.01) in the administration groups. The results of Real-time PCR showed that compared with the control group, the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly (P<0.01). Compared with the model group, the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly (P<0.01). The results of Western blot showed that compared with the control group, the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly (P<0.01). Compared with the model group, the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly (P<0.05, P<0.01). ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.
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The incidence of diabetes has been on the rise as the result of lifestyle changes, especially the high-fat diet and reduced exercise. Thus, it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β (TGF-β) signaling pathways with diabetes complications and tumors, but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors, directly or indirectly leading to the apoptosis of islet β cells and insulin resistance (IR), and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase (AMPK), protooncogene (c-Myc), Ski-relatednovel protein N (SnoN), Smad ubiquitination regulatory factor 1 (Smurf1), miR-335-5p, and other signaling molecules. They participate in the occurrence and development of IR, apoptosis of islet β cells, insulin secretion disorder, fibrosis of adipocytes, and metabolic disorder of adipocytes, and inhibit the browning of white adipose tissue, playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine (TCM), the pathogenesis of diabetes is the deficiency of Qi and Yin, and the late stage is characterized by the syndrome of Qi deficiency, and Yang deficiency and blood stasis, which should be treated according to the principle of replenishing Qi and nourishing Yin, warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways, elucidating the roles of them in pathogenesis of diabetes, and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.
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Objective:To investigate the regulatory mechanism of Bushen Zhuyun prescription(BSZYP) on endoplasmic reticulum stress (ERS) in rats with luteal phase defect (LPD) induced by mifepristone. Method:Fifty SD rats were randomly divided into a blank group, a model group, a positive control group (dydrogesterone,0.02 g·kg<sup>-1</sup>), and low-(0.08 g·kg<sup>-1</sup>)and high-dose (0.24 g·kg<sup>-1</sup>) BSZYP groups. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR) were used to detect the mRNA and protein expression levels of immunoglobulin binding protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP). The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum progesterone (P) and estradiol (E<sub>2</sub>) levels. Result:Compared with the blank group, the model group showed the elevated protein expression of BIP, PERK, and CHOP (<italic>P</italic><0.01) and the dwindled mRNA expression of PERK and CHOP (<italic>P</italic><0.05), while no significant difference was observed in the protein expression of IRE-1 and ATF6, mRNA expression of IRE-1, BIP, and ATF6, and serum E<sub>2</sub> and P levels. Compared with the model group, the positive control group displayed diminished protein expression of CHOP (<italic>P</italic><0.01), while no significant difference was observed in the protein expression of PERK, IRE-1, BIP, and ATF6, mRNA expression of PERK, IRE-1, BIP, ATF6, and CHOP, and serum levels of E<sub>2</sub> and P. The protein expression of CHOP decreased (<italic>P</italic><0.01) and the mRNA expression of CHOP increased (<italic>P</italic><0.05) in the low-dose BSZYP group, while no significant difference was observed in the mRNA and protein expression of PERK, IRE-1, BIP, and ATF6, and serum E<sub>2</sub> and P levels. In the high-dose BSZYP group, the protein expression of PERK, BIP, and CHOP was down-regulated (<italic>P</italic><0.01), and the mRNA expression of CHOP was up-regulated (<italic>P</italic><0.01), while no significant difference was observed in the protein expression of IRE-1 and ATF6, mRNA expression of PERK, IRE-1, BIP, and ATF6, and serum E<sub>2</sub> and P levels. Conclusion:BSZYP can treat LPD by relieving ERS.
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Novel coronavirus (2019-nCoV) is the pathogen of COVID-19. Some severe cases may suffer from respiratory failure or even death, which poses a great challenge to global public health. 2019-nCoV proteins not only participate in virus proliferation, but also play an important role in antagonizing host innate immune response, especially interferon response. In this paper, 2019-nCoV proteins involved in regulating host interferon response and the complex interaction between 2019-nCoV and interferons were summarized, aiming to provide a theoretical reference for the prevention and control of COVID-19.
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Insect samples found on human corpses can provide the information important to estimating the minimum postmortem interval (PMImin). A female cadaver, found in a deserted factory in Chongqing of China, was confirmed as a homicide case after the forensic investigation and autopsy. Determining the time of death was difficult due to the inconsistent degree of decomposition in different parts of the decedent. The insect specimens found on the cadaver were identified to be Chrysomya rufifacies (C. rufifacies, Macquart) by morphology and mitochondrial DNA sequence analysis. The PMImin was estimated to be 452 h, based on the developmental rate of C. rufifacies. The PMImin was estimated suc-cessfully to be almost precise, which provided an important entomological evidence for case investiga-tion and suspect prosecution. In so doing, this highlights the usefulness of entomological evidence of specific species in the geographic area for PMI accurate estimation, especially in the case of advanceddecomposed corpses.
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Objective: To study the mechanism of Shaoyao Gancao Decoction in the treatment of rheumatoid arthritis (RA) based on network pharmacology. Methods: The active components of Shaoyao Gancao Decoction were obtained from traditional Chinese medicine systems pharmacology (TCMSP) database, and human target proteins corresponding to active components were searched in Swiss Target Prediction and TCMSP database. The targets of RA were collected through Therapeutic Target Database and Drugbank database. The key targets of Shaoyao Gancao Decoction to treat RA were screened by building the Venn diagram. And the key protein interaction (PPI) network model was constructed by STRING database. The gene ontology (GO) and pathway enrichment analysis were performed by DAVID database. All of the correlative results were visualized by Cytoscape 3.7.2, and the network feature analysis was made by Network Analyzer. Results: A total of 102 compounds were obtained from Shaoyao Gancao Decoction, with 310 corresponding targets, and 68 common targets of Shaoyao Gancao Decoction-RA were obtained. Herb-compound-target-pathway network showed that kaempferol, quercetin, formononetin, naringenin, isorhamnetin were the key compounds of Shaoyao Gancao Decoction in the treatment of RA, and PTGS2, NOS2, MAPK14, PPARG, IL-6, TNF, and IL-1β were the key targets. GO entries included 28 biological process entries, two cellular component entries, and 13 molecular function entries. There were 40 pathways involving TNF signaling pathway, osteoclast differentiation, T cell receptor signaling pathway, MAPK signaling pathway, steroid hormone biosynthesis and toll-like receptor signaling pathway. Conclusion: The results of this study verify the multi-component, multi-target and multi-pathway regulation characteristics of Shaoyao Gancao Decoction, preliminarily predict material basis and mechanism of Shaoyao Gancao Decoction in the treatment of RA, which provides reference for further research.
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OBJECTIVE:To study the effects of augmented renal clearance (ARC)on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS :Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg,q12 h×3 doses,maintenance dose of 6-10 mg/kg,qd,and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ,clinical efficacy ,Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS :A total of 56 patients were included and divided into ARC group (18 cases)and normal renal function group (38 cases). ARC group had younger age (P<0.001)and lower serum albumin level (P=0.025)than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group (P=0.034;P=0.035). The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage (P=0.003;P<0.001). The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8% and 76.2%,which were lower than those of the normal renal function group ,but there was no statistical difference (P=0.195;P=0.223). There was no liver function damage ,hemocytopenia and allergic reaction in both groups ,but in the normal renal function group ,the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS :ARC patients are younger ,most of them have hypoproteinemia,and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ,it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.
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Objective:To estimate the predictive performance of the population pharmacokinetics software JPKD-vancomycin on predicting the vancomycin steady-state trough concentration, and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with vancomycin and received therapeutic drug monitoring (TDM) admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to December 2018 were enrolled. All patients were designed an empirical vancomycin regimen (initial regimen) according to vancomycin medication guidelines. Steady-state trough concentrations of vancomycin were determined at 48 hours after the first dose and 0.5 hour before the next dose. Dosage regimen was adjusted when steady-state trough concentration was not in 10-20 mg/L (adjustment regimen), and then the steady-state trough concentration was determined again 48 hours after adjustment. First, the JPKD-vancomycin software was used to calculate the initial regimen and predict the steady-state trough concentration according to the results calculated by classic pharmacokinetic software Vancomycin Calculator. Second, the JPKD-vancomycin software was used to adjust the vancomycin dosage regime and predict the steady-state trough concentration of adjustment regimen. The weight residual (WRES) between the predicted steady-state trough concentration (C pre) and the measured steady-state trough concentration (C real) was used to evaluate the ability of the JPKD-vancomycin software for predicting the vancomycin steady-state trough concentration. The TDM results of initial regimen were divided into accurate prediction group (WRES < 30%) and the inaccurate prediction group (WRES ≥ 30%) according to the WRES value. Patient and disease characteristics including gender, age, weight, height, the length of hospital stay, comorbidities, vasoactive agent, mechanical ventilation, smoking history, postoperative, obstetric patients, trauma, laboratory indicators, vancomycin therapy and TDM results were collected from electronic medical records. Univariate and multivariate Logistic regression analysis was used to screen the related factors that influence the predictive performance of JPKD-vancomycin software, and the receiver operating characteristic (ROC) curve was drawn to evaluate its predictive value. Results:A total of 310 patients were enrolled, and 467 steady-state trough concentrations of vancomycin were collected, including 310 concentrations of initial regimen and 157 concentrations of adjustment regimen. Compared with the initial regimen, the WRES of adjusted regimen was significantly reduced [14.84 (6.05, 22.89)% vs. 20.41 (11.06, 45.76)%, P < 0.01], and the proportion of WRES < 30% increased significantly [82.80% (130/157) vs. 63.87% (198/310), P < 0.01]. These results indicated that JPKD-vancomycin software had a better accuracy prediction for steady-state trough concentration of the adjusted regimen than the initial regimen. There were 198 concentrations in the accurate prediction group and 112 in the inaccurate prediction group. Univariate Logistic regression analysis showed that women [odds ratio ( OR) = 0.466, 95% confidence interval (95% CI) was 0.290-0.746, P = 0.002], low body weight ( OR = 0.974, 95% CI was 0.953-0.996, P = 0.022), short height ( OR = 0.963, 95% CI was 0.935-0.992, P = 0.014), low vancomycin clearance (CL Van; OR < 0.001, 95% CI was 0.000-0.231, P = 0.023) and postoperative patients ( OR = 1.695, 95% CI was 1.063-2.702, P = 0.027) were related factors affecting the predictive performance of JPKD-vancomycin software. Multivariate Logistic regression analysis indicated that women ( OR = 0.449, 95% CI was 0.205-0.986, P = 0.046), low CL Van ( OR < 0.001, 95% CI was 0.000-0.081, P = 0.015) and postoperative patients ( OR = 2.493, 95% CI was 1.455-4.272, P = 0.001) were independent risk factors for inaccurate prediction of JPKD-vancomycin software. The ROC analysis indicated that the area under ROC curve (AUC) of the CL Van for evaluating the accuracy of JPKD-vancomycin software in predicting vancomycin steady-state trough concentration was 0.571, the sensitivity was 56.3%, and the specificity was 57.1%. The predictive performance of JPKD-vancomycin software was decreased when CL Van was lower than 0.065 L·h -1·kg -1. Conclusions:JPKD-vancomycin software had a better predictive performance for the vancomycin steady-state trough concentrations of adjustment regimen than initial regimen. JPKD-vancomycin software had a poor predictive performance when the patient was female, having low CL Van, and was postoperative. The predictive performance of JPKD-vancomycin software was decreased when CL Van was lower than 0.065 L·h -1·kg -1.
الموضوعات
Humans , Female , Adult , Carbamazepine/adverse effects , Stevens-Johnson Syndrome/etiology , Subcutaneous Absorption/drug effects , Anticonvulsants/adverse effects , Arm , Biopsy , Carbamazepine/administration & dosage , Stevens-Johnson Syndrome/surgery , Subcutaneous Tissue/surgery , Subcutaneous Tissue/pathology , Anticonvulsants/administration & dosageالملخص
Aim To investigate the effect of ginseng polysaccharides(WGP) on renal fibrosis in mice with diabetic nephropathy(DN) and its possible mecha-nism. Methods Diabetic mice were induced by intra-venous injection with 120 mg·kg-1streptozotocin (STZ) and were randomly divided into the following four groups with 10 mice per group: model group, low-, medium-, high-dose(25,50,100 mg·kg-1) of WGP groups. Other 10 normal mice were treated as normal control group. The mice were administered o-rally for 12 weeks. After that,the levels of fasting blood-glucose(FBG),microalbuminuria(mAlb),serum creatinine(Scr) and blood urea nitrogen(BUN) were detected. The expression of collagen fibers and the ex-pression of α-SMA protein in renal cortex were detec-ted using Masson staining and immunohistochemical staining. The cAMP content in renal cortex was detec-ted by radioimmunoassay. The protein expressions re-lated to extracellular matrix composition and PKA/CREB in renal cortex were detected by Western blot.Results WGP could obviously reduce the contents of FBG,mAlb,Scr and BUN in DN mice,meanwhile de-creasing the expressions of α-SMA,LN and FN protein by inhibiting the activation of cAMP/PKA/CREB sig-nal pathway,which led to the alleviation of degree of glomerular sclerosis and interstitial fibrosis in kidney. Conclusion WGP has inhibitory effect on renal fibro-sis in DN mice model,which might be related with the suppression of cAMP/ PKA /CREB signaling pathway.
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OBJECTIVE@#To investigate the effects of simulated 100 m Trimix conventional diving on tissue inflammatory cytokines in rabbits.@*METHODS@#Eight New Zealand rabbits were performed a simulated 100 m Trimix conventional diving program which was established according to the Haldane theory. The expression levels of interferon-gamma(IFN-), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), myeloperoxidase(MPO) and matrix metallo proteinase-9 (MMP-9) in rabbits lung and brain tissues were detected by Elisa after diving decompression. The tissue wet/dry ratio was calculated. The serum levels of superoxide dismutase (SOD),glutathione(GSH), catalase(CAT), malondiadehyde(MDA) and lipid peroxide(LPO) were detected by Elisa method in rabbits before and after diving.@*RESULTS@#The expressions of IFN-, TNF-α, IL-6, IL-8, MPO and MMP-9 in simulated diving group rabbits were significantly increased compared with the intact group(<0.05, <0.01); the simulated diving rabbits tissues wet/dry ratio had no significant changes compared with the intact group. After diving, the activities of SOD and GSH were decreased significantly (<0.01), while the contents of CAT, MDA and LPO were increased significantly (<0.01).@*CONCLUSIONS@#The simulated 100 m Trimix conventional diving had significant impact on oxidative stress and inflammatory reaction in rabbits, the results of wet/dry ratio showed that the diving rabbits had no tissue edema after decompression.
الموضوعات
Animals , Rabbits , Catalase , Diving , Physiology , Glutathione , Helium , Inflammation , Interleukin-6 , Interleukin-8 , Malondialdehyde , Matrix Metalloproteinase 9 , Nitrogen , Oxidative Stress , Oxygen , Peroxidase , Superoxide Dismutase , Tumor Necrosis Factor-alphaالملخص
Objective: To investigate the dynamic electrocardiogram (ECG) changes of head-up tilt test in patients with suspected vasovagal syncope. Methods: A total of 502 outpatients of our hospital with suspicious vasovagal syncope from 2015-08 to 2016-12 were enrolled. All patients received head-up tilt test with synchronization of 12 lead ECG. Based on head-up tilt test result, the patients were divided into 2 groups: Positive group,n=244 and Negative group,n=258. The P wave duration, corrective QT (QTc) duration and P wave axis in ECG were compared between 2 groups. Results: Compared with Negative group, Positive group had the longer P wave duration (95.65±38.50) ms vs (88.61±17.09) ms,P<0.05; P wave axis was right shifted before syncope (69.87±18.18)° vs (66.82±16.51)° , while left shifted during syncope (62.87±25.39)° vs (68.47±15.30)° and after syncope (56.87±22.45)° vs (68.49±16.35)°, allP<0.05; the shorter QTc duration before syncope (418.69±92.35) ms vs (435.76±59.29) ms,P<0.05. Conclusion: The patients with vasovagal syncope had some speciifc ECG features during head-up tilt test including P wave duration, P wave axis and QTc duration, those may play certain forewarning function for vasovagal syncope onset.