ABSTRACT
Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.
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OBJECTIVE：To compare the efficacy and safety of vancomycin given by continuous infusion vs. intermittent infusion，and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from PubMed ，the Cochrane Library，Embase，Wanfang database ，CNKI and VIP databases ，ranomized controlled trials （RCT）and cohort studies about vancomycin given by continuous infusion （trial group ）vs. intermittent infusion （control group ）were collected during the inception to Apr. 2020. After literature screening and data extraction ，the qualities of RCTs were evaluated by using bias risk evaluation tool recommended by Cochrane system evaluator manual 6.0. The qualities of cohort studies were evaluated by NOS ；Rev Man 5.3 software was used to perform Meta-analysis and publication bias analysis. RESULTS ：A total of 20 studies were included （3 RCTs and 17 cohort studies ），involving 2 380 patients in total. Results of Meta-analysis showed that ，target concentration attainment rate [RR ＝1.24，95％CI（1.12，1.38），P＜0.000 1] and attainment rate of target clinical efficacy [RR ＝1.20，95％CI（1.04，1.38）， P＝0.01] of trial group was significantly higher than those of control group. The incidence of nephrotoxicity [RR ＝0.56，95％CI （0.45，0.70），P＜0.000 01] was significantly lower than control group. There was no statistical significance in the therapeutic efficiency [RR ＝1.02，95％CI（0.95，1.10），P＝0.53]，drug treatment duration [MD ＝－0.50，95％CI（－1.40，0.39），P＝0.27] or mortality [RR ＝1.03，95％CI（0.78，1.35），P＝0.83] between 2 groups. The results of publication bias showed that the probability of publication bias was high when the incidence of nephrotoxicity was used as the index. CONCLUSIONS ：Vancomycin continuous infusion can improve the attainment rate of target concentration and target clinical efficacy ，reduce the incidence of nephrotoxicity ， but can not improve the treatment efficiency. Due to the inconsistent results of publication bias analysis ，the above conclusion needs to be interpreted carefully.
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OBJECTIVE:To optimize the extraction technology of total polyphenol and total flavonoid in Gardenia jasminoi-des. METHODS:Plackett-burman(PB)design was used to select the ethanol volume fraction,liquid-solid ratio,particle size,ex-traction time and extraction temperature to determine the key factor affecting the extraction of total polyphenol and total flavonoids in G. jasminoides. Then central composite design (CCD) was combined with response surface method to optimize the extraction technology,and verification test was conducted. RESULTS:The optimal extraction conditions of total polyphenol were 40% etha-nol,particle size of 0.20 mm,extraction temperature of 60 ℃,liquid-solid ratio of 20,and extraction time of 20 min;the optimal extraction conditions of total flavonoids were 40% ethanol,particle size of 0.20 mm,extraction temperature of 30 ℃,liquid-solid ratio of 20,and extraction time of 20 min. In verification test,the contents of total polyphenol and total flavonoids in G. jasminoi-des were 1.70%(RSD=1.43%,n=3),3.23%(RSD=3.72%,n=3),with relative error of 1.80%,8.75% with predicted val-ues,respectively. CONCLUSIONS:The response surface method based on PB and CCD is simple,reasonable and feasible to opti-mize the extraction technology of total polyphenol and total flavonoids in G. jasminoides. The method can provide reference for its industrial extraction.
ABSTRACT
OBJECTIVE:To optimize the extraction technology of total polyphenol and total flavonoid in Gardenia jasminoi-des. METHODS:Plackett-burman(PB)design was used to select the ethanol volume fraction,liquid-solid ratio,particle size,ex-traction time and extraction temperature to determine the key factor affecting the extraction of total polyphenol and total flavonoids in G. jasminoides. Then central composite design (CCD) was combined with response surface method to optimize the extraction technology,and verification test was conducted. RESULTS:The optimal extraction conditions of total polyphenol were 40% etha-nol,particle size of 0.20 mm,extraction temperature of 60 ℃,liquid-solid ratio of 20,and extraction time of 20 min;the optimal extraction conditions of total flavonoids were 40% ethanol,particle size of 0.20 mm,extraction temperature of 30 ℃,liquid-solid ratio of 20,and extraction time of 20 min. In verification test,the contents of total polyphenol and total flavonoids in G. jasminoi-des were 1.70%(RSD=1.43%,n=3),3.23%(RSD=3.72%,n=3),with relative error of 1.80%,8.75% with predicted val-ues,respectively. CONCLUSIONS:The response surface method based on PB and CCD is simple,reasonable and feasible to opti-mize the extraction technology of total polyphenol and total flavonoids in G. jasminoides. The method can provide reference for its industrial extraction.
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Objective To investigate the anti-inflammatory and analgesic activities of different extracts from X. mongolicum compared with that of X. sibiricum. Methods Seventy male Kunming mices were randomly divided into seven groups:control group,aspirin group,the ethanol extracts of X. sibiricum group and X. mongolicum group,the extracts from X. mongolicum with ether,ethyl acetate,and n-butyl alcohol group(n=10 each). The mice were administrated with 500 mg·kg-1 ( p. o. ) of different extracts. The hot-plate tests and the xylene-induced ear edema in mice were performed to observe the analgesic and anti-inflammatory activities,respectively. Results In the hot-plate tests,the pain threshold from the extracts of X. sibiricum and the different extracts from X. mongolicum at 60,120,180 min were prolonged,and there was no statistically significant differences(P>0. 05) between the ethanol extracts from X. sibiricum and X. mongolicum. The best analgesic activity was the ether and butyl alcohol extracts from X. mongolicum. Meanwile,the ear edema from the extracts of X. sibiricum and the different extracts of X. mongolicum were inhibited significantly(P0. 05). The ether and butyl alcohol extracts from of X. mongolicum showed the best anti-inflammatory effect. Conclusion X. mongolicum exhibites significant anti-inflammatory and analgesic activities comparable to that of X. sibiricum. The best anti-inflammation and analgesic activities were from ether and butyl alcohol extracts from X. mongolicum.
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Objective To explore the clinical effect of reconstruction of coracoclavicular and acromioclavicular ligaments with multi - bundle - polystyrene - suture for treatment of Ⅲ degree acromioclavicular dislocation. Methods 30 patients with Ⅲ degree acromio-clavicular dislocation were randomly divided into two groups. Multi - bundle - polystyrene - suture was used to reconstruct coracoclavicular and acromioclavicular ligaments in treatment group; Cross - Kirschner and tension bands or clavicular hook plates were used to reconstruct coracoclavicular ligaments in control group. Then the clinical effects of the two methods were analyzed and assessed clinically. Results The clinical effects of treated group was significantly better than those of the control group on the volume of blood loss, surgical time and shoulder function. Conclusion It is a simple, minimally invasive, inexpensive and effective method. We need not to remove the internal fixation to reconstruct coracoclavicular and acromioclavicular ligaments with multi - bundle - polystyrene - suture for treatment of Ⅲ degree acromioclavicular dislocation.