Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective:To construct an evaluation indicator system for the health management effects in high-risk stroke population.Methods:From March to May 2020, based on health ecology theory, social cognitive theory and knowledge, attitude/belief, practice theory, the first draft of the evaluation index system for health management effects of high-risk stroke groups was drawn up by literature review and group discussion. Through two rounds of Delphi expert consultation, the evaluation index system of health management effects of high-risk stroke groups was established, and the weight of each index was determined by analytic hierarchy process (AHP). A total of 22 experts were invited to participate in expert consultation. Twenty-two questionnaires were sent out in the first round, and 20 questionnaires were recovered, of which 20 were valid (90.9%). In the second round of correspondence, 20 questionnaires were sent out and 19 questionnaires were recovered, of which 19 were valid (95.0%).Results:The authority coefficients of the two rounds of expert consultation (Cr) was 0.933 and 0.937, respectively. The Kendall coordination coefficients W of importance in the second round was significantly higher than that in the first round (0.299 vs 0.172) ( P<0.001). The mean of importance score (Mj) of each index was 4.10-5.00, coefficient of variation (CV) was 0-0.235, and full mark ratio (Kj) was 0.26-1.00. Finally, an evaluation index system of the health management effects for high-risk stroke population was constructed, which included 3 first-level indicators (individual characteristics, behavior style, environmental support), 12 second-level indicators and 58 third-level indicators. Conclusions:The evaluation index system of the health management effects for high-risk stroke population is established in this study, which provides scientific quantitative indicators and evaluation tools. The enthusiasm, authority and coordination of consultation experts are strong, which indicates that the indicator system is feasible.

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

ObjectiveTo explore the effective components， targets， and mechanism of Houttuynia cordata against lung cancer by means of systems pharmacology and further to provide a reference for the further development and clinical application of this medicinal. MethodChemical components of H. cordata were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the active components were screened based on oral bioavailability （OB） and drug-likeness （DL）. Then the potential targets were predicted， followed by enrichment analysis. Finally， sodium houttuyfonate （SH） was selected for verifying the anti-tumor mechanism. Cell counting kit-8 （CCK-8） assay was used to evaluate the effect of SH on the in vitro proliferation of two lung cancer cell lines： A549 and LLC， and the regulation of tumor-related proteins by SH was verified by Western blot. ResultA total of 7 active compounds and 352 targets of the active components were screened out. According to the enrichment analysis of targets， H. cordata had potential therapeutic effects on cancer. SH had inhibitory effect on both A549 and LLC. Western blot results showed that G₁/S-specific Cyclin D₁， E₁ and cyclin-dependent kinase （CDK）2， CDK4 all tended to be down-regulated， and Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） also changed significantly. ConclusionH. cordata has the potential anti-tumor effects by arresting the tumor cells in the G₁ phase through the JAK2/STAT3 pathway.

Objective:To explore a new method of ultrasound-guided positioning of the tip of neonatal peri-pherally inserted central catheter (PICC).Methods:Clinical data of 174 newborn infants hospitalized in the Neonatal Intensive Care Unit (NICU) of Beijing Chaoyang District Maternal and Child Healthcare Hospital from January 2019 to April 2021 receiving PICC catheter intubated under the guidance of ultrasound for positioning the tip were retrospectively analyzed to explore the accuracy, reliability and feasibility of the improved ultrasound-guided positioning technique.Before lower extremity catheterization, ultrasound was performed to monitor the vascular pattern and catheterization of PICC was conducted under the guidance of ultrasound.Results:(1) Among 174 infants intubated with ultrasound-guided positioning of the PICC tip, 172(98.9%) of them had the ideal position, and 2(1.1%) did not achieve the ideal position, but achieved the ideal position after ultrasound-guided correction.(2) Lower extremity venous catheterization was successfully performed at 100.0% after ultrasound-guided monitoring of blood vessels.The time-consuming of lower extremity venous catheterization was significantly shorter than that of the previous method [(31.50±2.58) min vs.(56.10 ±5.30 min)]( t=46.84, P<0.001). The total success rate of catheterization and catheterization of lower limb vein increased by 7.0% and 17.5%, respectively.(3) Only 1 (0.57%) case reported the complication of catheter tip thrombosis, the complication rate of which decreased from the previous 79.00% to 2.70%(2/112 cases). Conclusions:The improved ultrasound-guided positioning of the PICC tip is convenient, simple, faster and accurate, which enhances the success rate and is worthy to be applied in clinical practice.

Objective:To analyze the respiratory muscle functioning of stroke survivors and explore factors influencing it so as to provide references for clinical rehabilitation intervention.Methods:A total of 139 stroke survivors were randomly divided into a respiratory muscle dysfunction group and a control group based on the actual strength of their inspiratory muscles divided by the predicted strength. Beyond typical clinical data, information was collected about the subjects′ exercise habits. Balance ability was evaluated using the Fugl-Meyer assessment scale (FMA) and the simplified Berg Balance Scale (BBS). Multivariate logistic regression was used to analyze the factors influencing respiratory muscle dysfunction.Results:Among the 139 patients, 81 (58.27%) had respiratory muscle dysfunction. Univariate analysis showed that patients with stroke in the brainstem and dysphagia and those with poor FMA and BBS scores were at significantly greater risk of respiratory muscle dysfunction. Logistic regression analysis showed that dysphagia, FMA and BBS scores were factors independently predicting respiratory muscle dysfunction among stroke survivors, with dysphagia as a risk factor, and high FMA and BBS scores as protective factors.Conclusion:Some stroke survivors may have respiratory muscle dysfunction, and dysphagia is a risk factor, while the high FMA and BBS scores are protective.

Sterol C24-methyltransferase (SMT) plays multiple important roles in plant growth and development. SMT1, which belongs to the family of transferases and transforms cycloartenol into 24-methylene cycloartenol, is involved in the biosynthesis of 24-methyl sterols. Here, we report the cloning and characterization of a cDNA encoding a sterol C24-methyltransferase from().(GenBank access number KU885950) is a 1530 bp cDNA with a 1041 bp open reading frame predicted to encode a 346-amino acid, 38.62 kDa protein. The polypeptide encoded by thecDNA was expressed and purified as a recombinant protein from() and showed SMT activity. The expression ofwas highly up-regulated incell suspension cultures treated with methyl jasmonate (MeJA). Tissue expression pattern analysis showed higher expression in the phellem layer compared to the other four organs (leaf, stem, xylem and phloem), which is about ten times that of the lowest expression in leaf. The results are meaningful for the study of sterol biosynthesis ofand will further lay the foundations for the research in regulating both the content of other main compounds and growth and development of

The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) is the last step key enzyme of the methylerythritol phosphate (MEP) pathway, synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate, which is important for regulation of isoprenoid biosynthesis. Here the full-length cDNA of, designated(GenBank Accession No. KJ933412.1), was isolated fromfor the first time. TwHDR has an open reading frame (ORF) of 1386 bp encoding 461 amino acids. TwHDR exhibits high homology with HDRs of other plants, with an N-terminal conserved domain and three conserved cysteine residues.cDNA was cloned into an expression vector and transformed into anmutant. Since loss-of-functionmutant is lethal, the result showed that transformation ofcDNA rescued themutant. This complementation assay suggests that thecDNA encodes a functional HDR enzyme. The expression ofwas induced by methyl-jasmonate (MJ) insuspension cells. The expression ofreached the highest level after 1 h of MJ treatment. These results indicate that we have identified a functional TwHDR enzyme, which may play a pivotal role in the biosynthesis of diterpenoid triptolide in.

Objective To evaluate the sensitivity and specificity of different HbA1C cutoff points for diabetes diagnosis in high risk outpatients in Harbin.Methods A total of 2 122 high risk outpatients(male 1 032 and female 1 090)for diabetes screening in the Fourth affiliated Hospital of Harbin Medical University from April 2013 to February 2015 were included in this study, with the average age of(49.26±13.00)year. Oral glucose tolerance tests(OGTT)were conducted and HbA1C levels were examined in these patients. The sensitivity and specificity of different HbA1C cutoff points were calculated and a receiver operator characteristic(ROC)curve was then built.Results The average level of HbA1C in these subjects was(6.45±1.72)%. The prevalence of diabetes was 41.85%. The area under ROC curve(AUC)was 0.89 with the optimal cutoff point of HbA1C 6.0% and 0.68 for the highest Yonden index. The sensitivity and specificity of HbA1C 6.0% were 84.01% and 83.67% respectively. The sensitivity and specificity of HbA1C 6.5% were 62.84% and 95.92%, respectively. The AUC of HbA1C≥6.5% was 0.732. Conclusion HbA1C works well as the diagnostic standard for diabetes in high risk outpatients of Harbin city. The cutoff point of HbA1C 6.0% is suitable for screening diabetes in high risk population, and HbA1C 6.5% is appropriate for diabetes diagnosis, with high sensitivity and specificity.