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@#In recent years, tumor immunotherapy has become a new hot spot in the field of cancer treatment. Besides the great success of immunological checkpoint inhibitors and cellular immunotherapy, small molecule immunotherapy has also attracted more and more attention. As a key signal transduction molecule involved in the innate immune response, stimulator of interferon genes plays an important role in defending against viral and intracellular bacterial infections, mediating type I IFN production and regulating the production of spontaneous anti-tumor immune responses in vivo. This paper briefly introduces the biological mechanism of STING signaling pathway and reviews the research progress of STING agonists based on the structural classification, so as to provide some reference for the design and discovery of STING agonist drugs.
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@#The core protein allosteric modulator targets the core protein and inhibits hepatitis B virus(HBV)replication by regulating the formation of covalently closed circular DNA(cccDNA), which is expected to completely cure hepatitis B and overcome the drug resistance of nucleoside drugs. This paper reviews the replication process of HBV, the function of core proteins, the mechanism, classification and research progress of core protein allosteric modulators, lists 12 drugs, and summarizes their mechanisms, categories, chemical structures, safety, anti-HBV effects, combined drug use, etc. In addition, the advantages and problems of core protein allosteric modulators are discussed to provide references for the development of new anti-HBV drugs.
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Objective To investigate the abuse tendency of disabled elderly caregivers and analyze its causes.Methods With the convenience sampling method,The main caregivers of 300 disabled elderly people were investigated by the general questionnaire, Activities Daily Living Scale (ADLs) and Caregiver Abuse Screen (CASE) in Guangzhou. Results The degree of disability of the elderly was moderate to severe degree.The average score of the elderly caregiver′s propensity for abuse tendency was(3.3 ± 2.3).178 (59.4 %, 178/300) of the elderly caregivers have abuse tendency (the average score was more than 3). Conclusion Caregivers′ abuse tendency against the elderly is high. The situation of the elderly is not optimistic.
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To explore the practical characteristic of Innovation and Creative Thinking course inte-grated with challenge based learning (CBL), Flanders Interaction Analysis System was used to analyze the class interaction of Solution Identifying and Implementation Context. It was shown that the class was con-ducted in open free and safe environment. Students were the center and involved in the class highly. Inno-vation and Creative Thinking course was helpful to nurturing the ability to innovate and create among nurs-ing students. The practical characteristic of this course will provide new ways to improve the innovativeness and creative thinking, which also will support the promotion of CBL in Chinese mainland.
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Objective To evaluate the prognostic value of combing pre-procedural red cell distribution width(RDW)with serum uric acid(SUA)levels in patients with acute coronary syndrome(ACS)undergoing percutaneous coronary intervention(PCI).Meth-ods A total of 1 52 consecutive patients with ACS who underwent successful PCI within 12 hours after onset of symptom were en-rolled.RDW and SUA were determined within 12 hours before PCI.The patients were divided into 3 groups according to the cut-off values showed by receiver operating characteristic(ROC)curve:73 cases in group I,RDW14.5% and SUA>402 μmol/L.The pre-procedural RDW and SUA status associated with 30 days any cause mortality and major adverse combined cardiac events including revascularization,non-fatal recurrent myocardial infarction,secondary heart failure,rehos-pitalization and death were analyzed.Results Pre-procedural RDW and SUA level predicted 30 days cardiac mortality,RDW and SUA level correlated linearly(r=0.336,P =0.001).30 days major adverse combined cardiac events and any cause mortality were significantly different among the three groups(P =0.031,P =0.012).Conclusion Pre-procedural RDW≥ 14.5% and SUA≥402μmol/L indicates poor prognosis in ACS patients underwent successful PCI.Therefore the combination of RDW and SUA measure-ment should be taken into consideration for risk stratification to decide about the management strategies in ACS patients.
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ObjectiveTo explore feasibility study of the Montreal cognitive assessment (MoCA) in detecting subcortcial vascular cognitive impairment-no dementia(VaCIND-S).MethodsSeventy-five Chinese Han were assessed by the MoCA and MMSE.40 met criteria for VaCIND -S and 35 were considered cognitively normal.ROC curve analyses were performed to determine optimal sensitivity and specificity.ResultsNo differences were found between groups on age,gender,education degrees.According to their MoCA scores,cognitive impairments including memory,visuospatial,executive function,attention,language,and orientation sub-scores in VaCIND-S ( (0.43 ± 1.01),(2.21 ± 1.19),(2.11 ± 1.13),(4.66 ± 1.48),(4.42 ±1.31),(4.86 ± 1.12)) significantly decreased compared with those in controls( (2.93 ± 1.36),(3.29 ± 1.06),(3.53 ±0.93),(5.94 ±0.24),(5.44 ± 0.71 ),(5.80 ± 0.48 ) ) (P ＜ 0.05 ).The MMSE scale was insensitive to cognitive impairment as compared with MoCA scale.Using cut-off score of 23.5,the MoCA exhibited excellent sensitivity (0.971 ) and specificity (0.789).ConclusionMoCA is a more sensitive instrument than the MMSE for the detection of VaCIND-S and warrants further investigation regarding its applicability in large and varying ethnic population.
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P-glycoprotein (P-gp) is an ATP-dependent multidrug efflux pump that acts as a major obstacle for oral drug delivery and cancer therapy. Recent reports have provided evidence that excipients often used in pharmaceutical formulations, such as Pluronic and TPGS, also have inhibitory effects on P-glycoprotein. Because inhibition of efflux transporters by polymeric inhibitors may dramatically increase the bioavailability of P-gp substrates with negligible side effects, identification of the mechanism and their structure activity relationship is therefore of significant importance for pharmaceutical development. Other than competitive inhibition for traditional inhibitors, polymeric inhibitors may modify P-gp function through alterations on membrane fluidity, inhibition of P-gp ATPase, depletion of intracellular ATP and down-regulating of P-gp expression. In the present review, the inhibition mechanism of potential polymeric inhibitors and their structure activity relationship will be discussed along with a brief introduction to the established methodologies.
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Objective To investigate the clincal characteristics of central hyponatremia.Methods The clinical data of 34 patients with central hyponatremia were analysed retrospectively.Results 34 patients with different cerebral diseases appeared dysphoria,sleepiness,aggravating disturbances of consciousness,vomiting,limb seizures and dehydration basis on primary diseases during the hospitalization.The laboratory examinations showed that the level of blood natrium was 260 mmol/d in all the cases,and the central venous pressures in 5 cases were lower than 6 cm H2O among 8 cases.The 19 cases were diagnosed as central hyponatremia——syndrome of inappropriate ADH secretion(SIADH);7 cases were diagnosed as central hyponatremia——cerebral salt wasting syndrome(CSWS).The other 8 cases were diagnosed as SIADH firstly,but final diagnosis were corrected as CSWS according to the symptoms increasing after dehydration therapy.The 19 case of SIADH received the therapy of limiting water and diuresis,and 15 cases of CSWS received the therapy of hydration and supplementing sodium.The several days after the treatment,the levels of the blood natrium and the urinary natrium were backed to the normal values in all the patients and the condition was improved exapet 3 cases remained coma.Conclusions Hyponatremia,hypernatruria and changes of consciousness are the clinical charateritics of central hyponatremia.The treatment principle in SIADH is limiting water,and in CSWS is hydration and supplementing sodium.