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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been infected rapidly and is generally susceptible to population. Moreover, it has become the most serious public health problem in the world. In the process of coronavirus disease 2019 (COVID-19) treatment, the traditional Chinese medicine (TCM) intervention has achieved positive efficacy and which is widely recognized. However, the COVID-19 epidemic is still very serious, especially due to the characteristics of asymptomatic infection such as concealment, limitations and subjective symptoms, which has increased the difficulty of prevention and control. In view of asymptomatic infection, isolation is the main management. There is little mention of specific treatment options in each version of COVID-19 treatment plan. Through systematic study of TCM theory, we explored the way of diagnosis and treatment of asymptomatic infections. Based on the theory of latent evil, clearing away latent pathogens to truncate the course of disease and reduce the incidence. Based on the theory of prevention of disease, strengthen the lung and stomach to protect the place from pathogen and prevent the transmission of disease evil. It is supplemented by accurate treatment according to individual, timing and local conditions, in order to provide reference for the treatment of asymptomatic infection.
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Objective:To evaluate the prognostic accuracy of the sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria in predicting the mortality in patients with infection or suspected infection by using network Meta-analysis.Methods:Five databases including Wanfang Data, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), PubMed, Web of Science were searched from February 23, 2016 to September 5, 2020 to identify the relevant literatures comparing the prognostic accuracy of two or more scores for mortality in patients with infection or suspected infection. The literatures screening, data extraction and the quality assessment of the included studies were all conducted independently by two reviewers. Stata 14.0 software was used to test the heterogeneity between the original studies of pairwise comparison of each of the three scoring systems. Ring inconsistency test was used to judge the consistency between direct comparison and indirect comparison. Then network Meta-analysis was performed and the results were ranked. The predictive ability of the three scoring systems was evaluated by surface under cumulative ranking curve (SUCRA). A "comparison-correction" funnel plot was drawn to assess whether there was publication bias in the included studies.Results:A total of 38 studies were enrolled, the overall quality was high. Network meta-analysis showed that SOFA had a great prognostic performance in predicting mortality for patients with infection or suspected infection, which was followed by qSOFA [mean difference ( MD) = 0.07, 95% confidence interval (95% CI) was 0.05-0.09] and SIRS scores ( MD = 0.16, 95% CI was 0.14-0.18), and the qSOFA score was better than SIRS score ( MD = 0.09, 95% CI was 0.07-0.11). In the order of predicting the death risk of patients with infection or suspected infection, SOFA score had higher predictive value, followed by qSOFA score, and SIRS score was the lowest, with SUCRA values of 1.0, 0.5 and 0, respectively. Funnel plot showed that all the studies were distributed on both sides of the midline, but the distribution was not symmetrical, suggesting that there was a high possibility of publication bias and small sample effect. Conclusions:SOFA score had the best prognostic performance in predicting mortality of patients with infection or suspected infection as compared with qSOFA score and SIRS score. However, the funnel plot showed that included literatures may exist small sample effects or publication bias. So the final results should be validated by more prospective studies with multicenters and large samples.
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Objective To investigate the effects of inhibiting NgR on retinal ganglion cells density and synaptophysin expression of diabetic rat.Methods Thirty-two SD male rats were randomly divided into normal control group,diabetic group,siNgR group and scNgR group,8 rats in each group.Normal control group was given no any treatment.Diabetes model was induced by intraperitoneal injection of 50 mg · kg-1 streptozotocin in diabetic group,siNgR group and scNgR group,and the blood giucose more than 16.7 mmol · L-1 at 72 hours was set as the successfully model.The rats of siNgR group were intravitreally administrated with anti-NgR nucleotide and the rats of scNgR group intravitreally administrated with negative nucleotide.Eight weeks later,HE staining was conducted to detect density of retinal ganglion cell (RGC),immunofluorescence was used to evaluate the expression and distribution of synaptophysin (a marker of synaptic number).Relative expression of NgR and synaptophysin in retina were analyzed by Western blot.Results RGC density in normal control group,diabetes group,siNgR group and scNgR group were (624.33 ± 3.51) mm-2,(420.00 ± 2.65) mm-2,(621.67 ± 1.53) mm-2,(416.67 ± 2.52) mm-2,respectively.There was significant difference among four groups (F =5985.37,P ＜ 0.01).Compared with normal control group,RGC density in diabetes group and scNgR group were obviously decreased (all P ＜0.01),but siNgR group had no obviously change (P ＞ 0.05).The synaptophysin mainly expressed in the inner and outer network layer.Compared with normal control group,the positive expression of synaptophysin in diabetes group and scNgR group were decreased,but siNgR group had no obviously change.The relative expression of NgR in normal control group,diabetes group,siNgR group and scNgR group were (11.26 ±0.02) ％,(19.38 ± 0.10) ％,(11.17 ± 0.02) ％,(19.47 ± 0.31) ％,respectively.There was significant difference among four groups (F =2466.09,P ＜ 0.01).Compared with normal control group,the relative expression of NgR in diabetes group and scNgR group were obviously decreased (all P ＜ 0.01),but siNgR group had no obviously change (P ＞0.05).The relative expression of synaptophysin in normal control group,diabetes group,siNgR group and scNgR group were (35.76 ± 0.15) ％,(25.47 ± 0.36) ％,(35.28 ± 0.12) ％,(25.03 ± 0.75) ％,respectively.There was significant difference among four groups (F =583.70,P ＜ 0.01).Compared with the normal control group,the expression of synaptophysin in diabetic group and scNgR group were decreased increased (all P ＜ 0.01),while there was no significant difference in siNgR group (P ＞ 0.05).Conclusion Inhibiting the expression of NgR in the retina of diabetic rats can help to restore the number of synapses and protect the damaged RGC.
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Objective To investigate the effects of nerve growth factor (NGF) on retinal synaptic plasticity of diabetic mellitus rat and its underlying mechanisms.Methods A total of 24 clean SD male rats were randomly divided into three groups (n =8),and they were control group,diabetic group and treatment group.In the latter two groups,a model of diabetic rats was induced by streptozotocin,and then the rats of treatment group were injected intraperitoneally 800 U · kg-1 NGF once a day after the model was induced successfully.Both control group and diabetic group were given the same amount of normal saline.Twelve weeks later,MDA content and SOD activity were detected;meanwhile,the expression of retinal synaptophysin was detected by immunofluorescence,and the expressions of retina synaptophysin and Caspase-3 were detected by Western blot.Results The difference of MDA content in the three groups was statistically significant (F =85.46,P ＜ 0.01);and the content of MDA in the diabetic group was significantly higher than that in the control group (P ＜0.01),while its content in the treatment group was significantly lower than that in the diabetic group (P ＜0.01).The difference of SOD activity in the three groups was statistically significant (F =17.76,P ＜0.01);and the SOD activity in the diabetic group was significantly lower than that in the control group (P ＜0.01),while its activity in the treatment group was significantly higher than that in the diabetic group (P ＜0.01).The difference of immunofluorescence intensity of synaptophysin in the three groups was statistically significant (F =395.42,P ＜ 0.01);immunofluorescence intensity of synaptophysin in the diabetic group was attenuated compared with the control group (P ＜0.01),while the intensity in the treatment group was enhanced compared with the diabetic group(P ＜0.01).The difference of the relative expression of synaptophysin in the three groups was statistically significant (F =17.27,P ＜ 0.01);and the expression of synaptophysin in the diabetic group was significantly downregulated compared with the control group (P ＜ 0.01),while its expression in the treatment group was upregulated compared with the diabetic group (P ＜ 0.01).The difference of relative expression of Caspase 3 protein in the three groups was statistically significant (F=217.13,P ＜0.01);and the expression level of Caspase 3 in the diabetic group was significantly higher than that in the control group (P ＜0.01),while its level in the treatment group was significantly lower than that in the diabetic group (P ＜ 0.01).Conclusion NGF can help to inhibit the apoptosis of retinal cell,restore the number of retina synapse by reducing the oxidative stress in diabetic retina,which suggests that NGF may be involved in the changes of synaptic plasticity in diabetic retina via oxidative stress pathway.
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Objective To explore effects of ginsenosides Rg1 on the expression of poly(ADP-ribose) polymerase-1 (PARP-1) and tumor necrosis factor receptor (TNFR) 1 in cortex cells after focal cerebral ischemia in rats. Methods Ninety healthy rats were randomly divided into sham-operative group, focal cerebral ischemia group, ginsenoside Rg 1groups (low, medium and high concentrations) and drug control group. Rats were intraperitoneally injected saline 45 mg/kg, saline 45 mg/kg+ginsenosides Rg1 10, 20 and 40 mg/kg, nimodipine 1 mg/kg 5 d before surgery, respectively. Focal cerebral isch?emia model was made by middle cerebral artery occluding in rats. The neurological deficit score and TTC staining were used to verify the success of the rat model. The expressions of PARP-1 and TNFR1 were evaluated by immunohistochemical meth?od and Western blot technique. Results There were obvious symptoms of neurological deficit and large pale infarct area in focal cerebral ischemia group compared with those of sham-operative group. There were higher percentages of neurological deficit score and infarct area in ginsenosides Rg1 groups and positive control group than those of sham-operative group, but which were lower than those of ischemia group (P<0.05). There were no significant differences between ginsenosides Rg1 groups and positive control group. The positive cells of PARP-1 and TNFR1 were higher in ginsenosides Rg1 low-dose group than those of sham-operative group and positive control group, while ones of medium and high-dose Rg1 group were higher than those of sham-operative group, and were lower than those of ischemia group (P<0.05). Compared with sham-op?erative group, PARP-1 and TNFR1 expression strips were significantly enhanced in ischemia group. Expression strips were higher in ginsenosides Rg1 low-dose group than those of sham-operative group. Expression strips were higher in ginsen?osides Rg1 medium-dose group than those of sham-operative group, but which were lower than those of ischemia group, and ones of high-dose group were lower than ischemia group (P<0.05). Conclusion Ginsenoside Rg1 shows protective effects on focal ischemia injury, which may be related with down-regulation of the expression of PARP-1 and TNFR1.
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Objective to investigate the effect of berberine on the expression of AQP4 and neuronal injury after focal cerebral ischemia in diabetic rats. Methods Male SD rats were randomly divided into four groups:control(sham surgery),middle cerebral artery occlusion and reperfusion (MCAO/R),MCAO/R treated with vehicle(DMSO),MCAO/R treated with berberine. the transient focal ischemia/reperfusion was induced by in-troducing silicone-coated monofilament nylon suture from the right external carotid artery into the origin of the middle cerebral artery,which was re-moved after 60 min. In group treated with berberine,the rats were injected with berberine before and after suffered from cerebral ischemia. Similarly, in group vehicle,the animals received DMSO vehicle at the same time. the score of neurological behavior was evaluated 24 h after reperfusion. Mean-while,the rats were sacrificed for Nissl staining. to estimate cerebral edema,the wet-dry ratio was measured. the expression of AQP4 in the border of the infarct region in different groups was observed by Western blot. Results Compared with the model group,berberine improved neurological deficits(P < 0.05). Berberine treatment inhibited the neuronal deformation shown by Nissl staining(P < 0.05). Berberine significantly decreased the wet-dry ratio and reduced the expression of AQP4(P < 0.05). Conclusion these results suggested that berberine could induce neuroprotection against ischemic injury by inhibiting the expression of AQP4 in diabetic rats.
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Objective To observe the impact of modified Liangge powder (MLP) on platelet activation markers and the release of proinflammatory cytokine in mice by stimulation of lipopolysaccharide (LPS). Methods 112 male mice were randomly divided into control group, model group and MLP low, middle and high dose treatment groups. The sepsis model was reproduced by injection of LPS 10 mg/kg into a mouse tail vein. In the control group, normal saline 10 mg/kg was injected into the tail vein of mouse. The MLP low, middle, and high dose groups received 0.94, 1.89, 2.84 g/mL MLP 0.02 mL/g by gavage respectively for 3 days, while the control group and model group received equal amount of normal saline by gavage for 3 days. After modeling for 24 hours and 72 hours, 8 mice in each of the three different dose MLP groups and model group were killed and their blood was taken. In the control group, after modeling for 24 hours, 8 mice were killed and their blood was taken. Platelet (PLT) was counted by blood cell analyzer, plasma interleukin-10 (IL-10), high mobility group protein B1 (HMGB1) and platelet factor 4 (PF4) were detected by enzyme-linked immunosorbent assay (ELISA). In each group after modeling for 72 hours, another 8 mice were taken, and laser scanning confocal microscopy was used to measure the platelet cytosolic Ca2+ concentration. Results Compared with the control group, the level of PLT at 24 hours(×109/L: 347.70±115.10 vs. 1 013.10±136.60) was decreased, and the levels of IL-10 (μg/L: 356.86±34.72 vs. 39.50±23.45), HMGB1 (mg/L: 16.24±4.49 vs. 10.75±1.91), PF4 (μg/L: 5.43±0.61 vs. 1.33±0.40) and Ca2+ (nmoL/L: 8.60±0.52 vs. 1.05±0.33) were elevated in model group. Compared with the model group, the levels of PLT in the MLP high, middle and low dose groups were all significantly elevated; the increase in PLT in middle dose group after modeling for 72 hours was the most remarkable (×109/L:952.13±104.02 vs. 771.50±129.30, P < 0.05); the levels of IL-10, HMGB1, PF4, Ca2+ in MLP low, middle, high dose groups were significantly decreased. The most obvious degree of decrease in level of the following indexes were as follows:IL-10 in MLP high dose group at 72 hours after modeling (μg/L:110.17±29.12 vs. 441.50±30.72), HMGB1 in MLP high dose group after modeling for 24 hours (mg/L: 10.33±3.52 vs. 16.24±4.49), PF4 in MLP middle dose group after modeling for 24 hours (μg/L:2.08±0.92 vs. 5.43±0.61) and Ca2+ in MLP high dose group (nmoL/L:2.97±0.96 vs. 8.60±0.52, all P<0.05). Conclusion MLP may possibly down-regulate the inflammatory cytokines release induced by LPS to inhibit the activation of platelet Ca2+, in turn prevent the activation of platelet and improve thrombocytopenia caused by LPS.
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BACKGROUND:Streptozotocin-induced diabetic ophthalmopathy is commonly used in animal models, but the pathological changes are local that mainly emphasize on the retina. Little evidence is found about the animal models of the pathology of diabetic ophthalmopathy. OBJECTIVE:To investigate the long-term stability of type 2 diabetic melitus rat models induced by streptozotocin combined with high-fat feeding and to observe the characteristics of eye disease. METHODS: Rats were randomly divided into control group and diabetes group. Control group was given normal feeding, while diabetes group was given intraperitoneal injection of streptozotocin combined with high-fat feeding to establish diabetic models. RESULTS AND CONCLUSION:Compared with the control group, at 1 month after modeling, the fasting blood glucose levels increased, and the insulin sensitivity index decreased in the diabetic group (P < 0.05). Evans blue staining results showed that, at 3 months after modeling, retinal cel lesions exacerbated in the diabetic group; at 5 months after modeling, retinal blood vessels traveled in circuity and disorderly, accompanied by the leakage in the diabetic group, Evans blue content in the retina increased as the time after modeling went by (P < 0.05). Under transmission electron microscopy, at 5 months after modeling, the eye lenses in the diabetes group were flocculent pieces, which were the typical characteristics of cataract. Experimental findings indicate that the rat model of type 2 diabetic melitus induced by streptozotocin combined with high-fat feeding has a long-term stability, and its eye changes are consistent with the characteristics of diabetic ophthalmopathy. Therefore, it is an ideal animal model for diabetic ophthalmopathy.
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BACKGROUND:Breviscapine treatment of cerebral infarction has curative effects, few side effects, stable long-term efficacy and few side effects, which can improve the micro-environment of damaged central nervous system after cerebral infarction. OBJECTIVE:To investigate the effects of breviscapine injection combined with bone marrow mesenchymal stem cel transplantation on neurological recovery and growth-associated protein 43 expression in rats after cerebral infarction. METHODS:Sixty Sprague-Dawley rats undergoing middle cerebral artery occlusion were randomized into cerebral infarction group, cel transplantation group and combined group. At 6 hours after modeling, 1 mL PBS, 1 mL bone marrow mesenchymal stem cel suspension (2.5×106), and 1 mL bone marrow mesenchymal stem cel suspension (2.5×106)+75 mg/kg breviscapine injection were respectively injected via the tail vein in the three groups, once a day, continuously for 5 days. RESULTS AND CONCLUSION:At 2 weeks after transplantation, BrdU-positive bone marrow mesenchymal stem cels were mainly gathered in the peri-infarction region, and the number of positive cels was higher in the combined group than the other two groups (P < 0.01). At 1, 2, 3 weeks after transplantation, the neurological deficit scores were significantly lower in the combined group than the other two groups (P < 0.05). At 2 weeks after transplantation, the combined group had smaler infarct size, milder edema, and higher expression of growth-associated protein 43 as compared with the other two groups (P < 0.05). Under light microscope, glial cels proliferated dramaticaly and brain edema significantly reduced in the combined group. These findings indicate that breviscapine injection combined with bone marrow mesenchymal stem cel transplantation can significantly reduce infarct size and brain edema, promote neurological recovery and increase the expression of growth-associated protein 43 in rats with cerebral infarction.
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Objective To investigate the effect of Nogo receptor on the apoptosis of retinal ganglion cell (RGC) in di-abetic rats, and the potential mechanism thereof. Methods Thirty diabetic model rats were induced by intraperitoneal ad-ministration of streptozotocin. Model rats were randomly divided into control group, diabetes mellitus (DM) group, siNgR group and siRNA control group (n=10 for each group). Diabetic rats in siNgR group were intravitreally administrated with No-go receptor antisense nucleotide. Diabetic rats in siRNA control group were intravitreally administrated with negative nucleo-tide. One month after diabetes onset, colocalization of Nogo receptor and Brn3a (marker of RGC) was observed by immunohis-tochemistry. The apoptosis of RGC was detected by TUNEL staining. The level of retinal malondialdehyde (MDA) was ob-served with kit, and the expressions of Nogo receptor and caspase-3 were detected with Western blot assay. Results It was found that the Nogo receptor was highly expressed in RGC. The levels of retinal MDA were (3.68±0.47), (8.07±1.24), (7.54± 1.53) and (5.12 ± 0.62) μmol/g protein for control group, DM group, siRNA control group and siNgR group. The apoptotic rates of RGC were (5.1 ± 0.2)%, (49.3 ± 2.7)%, (45.6 ± 1.8)%and (12.4 ± 0.6)%respectively. The expressions of Nogo receptor were (0.18 ± 0.07)%, (0.45 ± 0.12)%, (0.40 ± 0.09)%and (0.16 ± 0.09)%. The expressions of caspase-3 were (0.16 ± 0.05)%, (0.40±0.18)%, (0.42±0.12)%and (0.17±0.08)%. Compared with control group, there was significant increase in apoptosis of RGC, significantly up-regulated expressions in Nogo receptor and caspase-3, and significantly increased level of MDA in DM group and siRNA control group(P<0.05). Compared with DM group, there were decreased apoptotic rate of RGC, de-creased expressions of Nogo receptor and caspase-3, and decreased level of retinal MDA in siNgR group (P<0.05). Conclu-sion The increased level of Nogo receptor induces oxidative stress and up-regulation of caspase-3 in diabetic retina, play-ing an important role in the apoptosis of RGC.
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Objective To explore protective effects and potential underlying mechanisms of panax notoginseng (PTS) on retinal ganglion cell (RGC) in diabetic rats. Methods SD rats were randomly divided into control group, diabetic group and treatment group. The diabetic model rats were induced by intraperitoneal injection of streptozotocin. Rats were giv-en PTS 50 mg·kg-1·d-1 in treatment group. One month later, the coexistence of nogo receptor and Brn3a (special marker of RGC) was observed by immunofluorescence staining double-labeled method. The expression of Nogo receptor was detected by Western blot assay. The level of malondialdehyde (MDA) in retina was measured with detection kit. HE-staining was in-troduced to reveal the number of retinal RGC. Results A large number of Brn3a and Nogo receptors were co-existed in the retina. The Nogo receptor was exclusively expressed in RGC, which was up regulated in diabetic group compared with that of control group. The level of retinal MDA was increased and the number of RGC decreased in diabetic group than that of con-trol group (P＜0.001). Compared with diabetic group, there were decreased retina Nogo receptor, decreased level of MDA and increased number of RGC in treatment group (P＜0.001). Conclusion PTS attenuates diabetes-induced loss of RGC, which may ascribe for down-regulation of retina Nogo receptor and decreased oxidative stress.
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BACKGROUND:Wnt signaling pathway is the key to regulation of cell proliferation and differentiation.The evidence suggests that this pathway participates in the neural precursor cell proliferation,differentiation and determination of the regulation of cell fate.At present,the Wnt signaling pathway effects on the mesenchymal stem cells(MSCs)differentiated into neuron-like cells have not been reported.OBJECTIVE:To seek Wnt signal molecule that promotes the differentiation of MSCs into neuron-like cells.METHODS:MSCs were isolated from the femur of Sprague Dawley rats in vitro using the density gradient centrifugation,and then cultured.Following passage,cell surface markers CD29,CD44,CD34 and CD45 were measured using morphology and flow cytometry.These cells were selected and evaluated.Using neurotrophic factor and basic fibroblast growth factor combined with Wnt3a and Wnt5a induction scheme,effects of Wnt3a and Wnt5a during the differentiation of MSCs into neuron-like cells were compared utilizing immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR).Simple culture of basic fibroblast growth factor served as controls.RESULTS AND CONCLUSION:Following culture and passage of MSCs,cells adhered to the wall,showing even spindle shape.Flow cytometry showed great expression of CD29 and CD44 and low expression of CD34 and CD45.Following Wnt3a induction,cells were positive for nestin,neuron specific enolase,but no significantly expressed glial fibrillary acidic protein.Following induction,cell viability was good.In the Wnt5a induction and control groups,weakly positive expression of nestin was found,but neuron specific enolase and glial fibrillary acidic protein were negative.RT-PCR results demonstrated that nestin expression was detected in the Wnt3a induction group before and after induction.Significant amplified bands for neuron specific enolase were detected at day 5 following induction,and became more significant at day 10.Weak bands for glial fibrillary acidic protein were visible at day 10 following induction.These indicated that Wnt3a can promote the differentiation of MSCs into neuron-like cells in vitro.
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BACKGROUND:In vitro experiment has shown that the survival time of conventional chemical induction-induced neuron-like cells differentiated from bone marrow mesenchymal stem cells(BMSCs)was short,which limited its further application.With regard to the possibility of extension of iodine-induced neuron-like cells,the survival time has not yet been professionally reported.OBJECTIVE:To research the effects of the micro-element iodine on the survival time of neuron-like cells differentiated by BMSCs.METHODS:Rat mesenchymal stem cells at passage 3 were obtained under sterile condition,and divided into groups A-F.In group A,iodine ion was not added.In groups B-F,iodine ion at mass concentrations of 2,55,90,125 and 2 500 mg/L was added respectively.An additional blank control group was established,and simultaneously the cells were induced into neuron-like cells with dimethyl sulphoxide(DMSO).Cells following induction were subjected to immunohistochemistry.Survival time of neuron-like cells was observed under different mass concentrations of iodine ion.RESULTS AND CONCLUSION:When mass concentrations of iodine ion were between 55-125 mg/L,the survival time of neuron-like cells prolonged to about 5 days and structures of induced cells were intact.From then on,the number of dead cells was gradually increased till approximately one week,all neuron-like cells died.When mass concentrations of iodine ion were 2 mg/L and 2 500 mg/L,cell survival time was from 12-36 hours.No significant difference was determined compared with group A.Till 2 or 3 days,all neuron-like cells died.Above-described results indicated that an appropriated concentration of iodine iron added in the common chemical induction may be benefit for the survival time of the neuron-like cells differentiated by BMSCs,but the effect may be negligible for the survival time of neuron-like cells induced when the added concentration of iodine iron is too low or too high.