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Objective To propose a drug pair extraction algorithm integrating co-occurrence and semantic information for prescription data.Methods The prescription data were transformed into matrix data,and the association information between drugs was calculated as the initial screening index.Then the word vector was constructed based on the prescription data,and the semantic similarity between drugs was calculated as the second screening index,so as to extract potential drug pairs.The algorithm of this paper and the classical Apriori algorithm were experimented on 1090 lung cancer outpatient prescriptions respectively,and the experimental extraction results were compared and analyzed,so as to verify the usability and effectiveness of this drug pair extraction algorithm.Results Compared with the Apriori algorithm,the present algorithm had better effect in extracting drug pairs,which could reasonably help to narrow down the range of options of potential drug pairs under the situation of large difference in drug frequencies,and successfully extracted 88 groups of drug pairs in medical cases under the range of recommended threshold settings.Conclusion The method of word frequency combined with semantic information for extracting potential drug pairs is feasible and effective,and can provide methodological reference for experience mining in clinical prescription medication.
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AIM To explore the effects of Shiquan Dabu Decoction on the synaptic function and cognitive impairment in a mouse model of Alzheimer's disease(AD).METHODS Sixty mice were randomly divided into the control group,the model group,the memantine group(5 mg/kg)and the high,medium and low dose Shiquan Dabu Decoction groups(6.24,3.12 and 1.56 g/kg),with 10 mice in each group.Except for those of the control group,the mice of other groups underwent their 70-day AD models induction by intraperitoneal injection of D-galactose and gavage feeding of AlCl3,followed by 42-day corresponding dosing of drugs by gavage on the 29th day.The mice had their spatial learning and associative memory detected by Morris water maze test and conditioned fear test;their morphological changes of hippocampal neurons observed by HE staining;their serum SOD activity,MDA level,and SOD,AChE activities and MDA,ACh,TNF-α and IL-1β levels in hippocampus detected by kits;and their PSD-95,Shank3,NR1,NR2A,NR2B,AMPK and p-AMPK protein expressions in hippocampus detected by Western blot.RESULTS Compared with the model group,the high-dose Shiquan Dabu Decoction group displayed improved spatial learning and memory ability and associative memory(P<0.05,P<0.01);reduced pathological damage of hippocampal neurons,decreased levels of oxidative stress and inflammation(P<0.05,P<0.01);enhanced cholinergic transmission(P<0.05,P<0.01),and increased protein expressions of PSD-95,Shank3,NR1,NR2A,NR2B,and p-AMPK in hippocampal tissue(P<0.05,P<0.01).CONCLUSION Shiquan Dabu Decoction can improve the cognitive impairment of in the mouse model of AD,and its mechanism may be related to AMPK activation and synaptic function restoration.
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As an emerging cancer treatment modality, immunotherapy has shown promising efficacy in a variety of solid tumors, but it has failed to achieve a breakthrough in the treatment of prostate cancer.This review aims to provide an overview of the current applications of immunotherapy for prostate cancer, including immune-checkpoint inhibitors, cancer vaccines and chimeric antigen receptor T-cell (CAR-T), briefly describe the mechanisms of various immunotherapy modalities, summarize the results of clinical trials, and discuss the challenges and prospects.
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Abstract@#Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.
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OBJECTIVE@#To investigate the effect of Akt2 inhibitor on macrophage polarization in the periapical tissue in a rat model of periapical inflammation.@*METHODS@#Rat models of periapical inflammation were established in 28 normal SD rats by opening the pulp cavity of the mandibular first molars, followed by injection of normal saline and Akt2 inhibitor into the left and right medullary cavities, respectively. Four rats without any treatment served as the healthy control group. At 7, 14, 21 and 28 days after modeling, 7 rat models and 1 control rat were randomly selected for observation of inflammatory infiltration in the periapical tissues by X-ray and HE staining. Immunohistochemistry was used to detect the expression and localization of Akt2, macrophages and the inflammatory mediators. RT-PCR was performed to detect the mRNA expressions of Akt2, CD86, CD163, inflammatory mediators, miR-155-5p and C/EBPβ to analyze the changes in macrophage polarization.@*RESULTS@#X-ray and HE staining showed that periapical inflammation was the most obvious at 21 days after modeling in the rats. Immunohistochemistry and RT-PCR showed that compared with those in the control rats, the expressions of Akt2, CD86, CD163, miR-155-5p, C/EBPβ, and IL-10 increased significantly in the rat models at 21 days (P < 0.05). Compared with saline treatment, treatment with the Akt2 inhibitor significantly decreased the expression levels of Akt2, CD86, miR-155-5p and IL-6 and the ratio of CD86+M1/CD163+M2 macrophages (P < 0.05) and increased the expression levels of CD163, C/EBPβ and IL-10 in the rat models (P < 0.05).@*CONCLUSION@#Inhibition of Akt2 can delay the progression of periapical inflammation in rats and promote M2 macrophage polarization in the periapical inflammatory microenvironment possibly by reducing miR-155-5p expression and activating the expression of C/EBPβ in the Akt signaling pathway.
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Rats , Animals , Proto-Oncogene Proteins c-akt/metabolism , MicroRNAs/genetics , Interleukin-10 , Rats, Sprague-Dawley , Macrophages/metabolism , Inflammation/metabolismABSTRACT
Objective:To explore the block-based charging method for centralized dispensing of neonatal drugs in pharmacy intravenous admixture service (PIVAS), analyze its effect on drug savings and inpatient drug cost, so as to provide the reference for the appropriate charging method of neonatal drugs.Methods:According to the balance quantity and amount of neonatal intravenous drugs that were centrally allocated by the PIVAS of our hospital, refer to the doctor′s orders, the dosage per dose as well as the number of patients per dose were analyzed, then the drug types and plans for block-based charging were formulated. Before and after the implementation of the plan, the monthly average drug balance quantity and amount, the average number of drug charges for the neonates, the average daily drug cost, and the adverse events of related drugs were used as the indicators to be investigated to clarify the implementation effect of the block-based charging mothod.Results:Fourteen medicines were charged by block-based, including 4 antibiotics, 2 ordinary infusion preparations, and 8 parenteral nutrition solution preparations. The monthly average drug balance quantity was reduced from 5 047±541 to 1 856±225, and the monthly average balance amount was reduced from 65 811±10 265 yuan to 20 659±6 002 yuan. The average drug dosage for children in the trial drug was significantly reduced with a decrease range of 39.2% to 90.1%. Both the inpatient daily drug cost of neonatus and the daily average antibacterial drug cost was decreased. During the centralized dispensing of neonatal drugs, no related adverse drug events occurred.Conclusions:The block-based charging method of centralized drug distribution can improve the utilization rate of drugs, reduce drug waste, reduce the cost of inpatient medicines the financial burden on children′s families, which is worthy of further promotion and implementation.
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Objective A knowledge graph construction pipeline of traditional Chinese medicine(TCM)diagnosis and treatment was designed and applied,aiming at the automatic construction of the"disease-symptom-pathogenesis-and medicine"knowledge graph based on the medical records of famous TCM physicians,to analyze,organize and present medical records efficiently.Methods Firstly,The entity extraction method of medical records combining Deep Learning and Regular Expression was designed to extract disease,symptom,pathogenesis,and TCM entities from unstructured medical records automatically;secondly,entity relationships were defined and the correlations between entities were calculated using HAN method,and then the"entity-relation-entity"triplets were built;the graph database Neo4j and Gephi were used for knowledge storage and visual display separately;Finally,the application was verified in the Medical records of lung cancer treated by the old famous TCM physicians.Results The precision,Recall and F1 of the knowledge extraction model for medical records entities extraction are 88.49%,90.02%and 89.25%,respectively,and each index is better than the comparison methods.A total of 1077 triples are extracted through entity correlation calculation,and the knowledge graph is successfully constructed.It can reflect the relationship between 'disease-symptom-pathogenesis-medicine' in the treatment of lung cancer by the famous specialists of TCM.Conclusion The method in this paper can effectively solve the extraction,organization and expression of clinical medical records of famous TCM physicians,and realize the automatic construction process from the text of medical records to the knowledge graph.Relevant research ideas and methods proposed in this paper could provide a reference for the construction of the diagnosis and treatment knowledge graph of famous TCM physicians based on medical records.
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Objective To investigate the pharmacodynamic effects of Poria triterpenes on tumor suppression in mice with ascites tumors,and to detect and identify the chemical components of Poria triterpenes using HPLC-LTQ-Orbitrap method,and to explore the potential mechanism of action of Poria triterpenes on tumor suppression in mice with ascites tumors based on both of them using non-labeled definitive proteomics techniques.Methods Poria triterpene parts were extracted by solvent method,and the main components were detected and identified by HPLC-LTQ-Orbitrap liquid mass spectrometer;mice were randomly divided into model group,Poria triterpene group and positive control group(mushroom polysaccharide group),after 21 days of continuous administration,to establish After continuous administration for 21 days,the H22 ascites tumor mouse model was established,and the effect of each drug group on the amount of ascites,spleen index,thymus index,liver index,serum TNF-Alpha and IL-2 in H22 ascites tumor mice was observed after one week of continued administration;then H22 cells were extracted from the ascites of mice,and the H22 cells in the model group and Poria triterpene group were detected by non-lable-free quantitative proteomics technique.The differentially expressed proteins(DEPs)were screened out by using GO,KEGG and other analyses.Results The abdominal water volume in the mouse Poria triterpene group was significantly lower than that in the model group(P<0.05);the thymus index in the mouse Poria triterpene group was significantly higher than that in the model group(P<0.05);the serum levels of TNF-Alpha in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01),and the serum levels of IL-2 in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01).Through the analysis of the chemical composition of Poria triterpene parts,a total of 19 triterpenoids were identified,with four main structural types.A total of 188 differentially expressed proteins were identified in the Poria triterpene group compared with the model group,of which 86 differentially expressed proteins were up-regulated and 102 differentially expressed proteins were down-regulated;GO database analysis showed that the differentially expressed proteins in the Poria triterpene group were mainly involved in the regulation of interleukin-1 production The KEGG database analysis showed that the differentially expressed proteins in the Poria triterpene group were involved in signaling pathways closely related to tumor,mainly MAPK,Apoptosis,mTOR,Wnt and p53 pathways,etc.The genes coding for the seven representative differential proteins were validated at the mRNA level by RT-qPCR.Conclusion The pharmacodynamic study found that Poria triterpenes had tumor suppressive effect on H22 ascites tumor mice,then by proteomics found Poria triterpenes group ascites H22 cell protein compared to the model group changed significantly,the study thus showed that Poria triterpenes for mice ascites tumor mechanism of tumor suppressive effect mainly involves apoptosis,inflammatory response and immune process.
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Androgen deprivation therapy is the basic therapy for the treatment of prostate cancer, however, most patients will progress to castration-resistant prostate cancer (CRPC) after therapy. Although abiraterone and enzalutamide are used for the first-line therapy for metastatic prostate cancer, drug resistance is still unavoidable. Gaining further insight into the role of androgen receptor would be critical to decipher the puzzle of therapy resistance. Current research on resistance mechanisms to androgen receptor inhibitors and treatment strategies after resistance were reviewed.
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Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.