Acta Academiae Medicinae Sinica

Objective To investigate the effect of α-asarone on the function and expression of P-glycoprotein(P-gp)in rat brain microvascular endothelial cells(rBMECs). Methods rBMECs were exposed to L-glutamate(100 μmol/L) for 30 mins to induce the overexpression of P-gp/multidrug resistance gene 1a(Mdr1a)on the cell membranes,which mimicked the overexpression of P-gp/Mdr1a in blood brain barrier(BBB) when drug-resistant epilepsy attacked.MTT assay was used to detect the safe range of α-asarone concentration.The model cells were intervened with different concentrations of α-asarone at 12.5,25.0,and 50.0 μg/μl for 24 hours.After the treatment of α-asarone,the expression and the function of P-gp/Mdr1 were measured by Western blotting,real-time PCR,and intracellular rhodamine 123 accumulation assays. Results The rBMECs,stimulated by glutamine,showed a high expression of P-gp(F=1.924,P=0.020)/Mdr1a(F=1.788,P=0.019) compared to the normal rBMECs.The treatment with 25.0(F=1.924,P=0.025;F=1.788,P=0.017) and 50.0 μg/μl(F=1.924,P=0.035;F=1.788,P=0.026) α-asarone significantly depressed the expression of P-gp/Mdr1a.The treatment with 25.0 and 50.0 μg/μl α-asarone significantly increased intracellular accumulation of Rhodamine 123 by 40% and 60% respectively. Conclusions α-asarone down-regulates the high expressions of P-gp and Mdr1a mRNA in rBMECs induced by L-glutamate.Moreover and increases intracellular accumulation of rhodamine-123.Thus,α-asarone may reverse drug resistance in P-gp-mediated drug-resistant epilepsy.

Objective To unravel the role of hematopoietic pre-B-cell leukemia transcription factor interacting protein(HPIP)in the proliferation,cell cycle,and apoptosis of pancreatic ductal adenocarcinoma(PDAC)cells. Methods The HPIP expression in PDAC tissue was determined by immunohistochemical staining.Knockdown of HPIP was accomplished in MIA PaCa-2 and BxPC-3 cell lines by transient transfection of HPIP siRNA and validated by Western blotting.Cell proliferation was assessed using the cell counting kit-8 assay and colony formation assay.Cell cycle and apoptosis were detected by flow cytometry.Western blotting was performed to detect the expression levels of cyclin D1,caspase 7,and cleaved caspase 7. Results HPIP was overexpressed in PDAC tissue compared with matched adjacent pancreatic tissue(Z=-2.060,P=0.039).Knockdown of HPIP inhibited the proliferation of MIA PaCa-2 and BxPC-3 cells(all P<0.05).Knockdown of HPIP significantly reduced the positive colonies formed by MIA PaCa-2 and BxPC-3 cells(t=4.706,P=0.009;t=9.514,P=0.000).Knockdown of HPIP decreased the proportion of S phase cells(t=7.642,P=0.001;t=2.714,P=0.051)and increased the proportion of G₀/G₁ phase cells(t=3.244,P=0.031;t=6.095,P=0.003)in MIA PaCa-2 and BxPC-3 cells.Meanwhile,knockdown of HPIP increased the proportions of late-phase MIA PaCa-2 and BxPC-3 cells(t=24.58,P=0.000;t=36.45,P=0.000)and the overall apoptosis rate(t=29.43,P=0.000;t=43.52,P=0.000).In MIA PaCa-2 and BxPC-3 cells,knockdown of HPIP decreased the expression level of cyclin D1(t=6.705,P=0.002;t=6.238,P=0.003)and increased the expression level of cleaved caspase 7(t=3.991,P=0.016;t=6.536,P=0.002). Conclusions HPIP is overexpressed in PDAC tissue.Knockdown of HPIP inhibits the proliferation and G₀/G₁ to S transition of PDAC cells.Meanwhile,knockdown of HPIP promotes the apoptosis of PDAC cells.Thus,HPIP may act as an oncogene in PDAC.

Objective To explore the mechanism of obstructive sleep apnea(OSA) by assessing the association between human TWIK-related acid-sensitive K ⁺ channel-1(TASK-1) gene and OSA. Methods A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region,China,from April to December 2016.Two single nucleotide polymorphisms(rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a Kompetitive Allele Specific PCR genotyping system. Results In patients with blood potassium <3.95 mmol/L,the distribution of rs1275988 alleles(G vs.A)(χ ²=4.474,P=0.034) and recessive model(GG+GA vs.AA)(χ ²=4.327,P=0.038) showed significant differences between severe and non-OSA groups.The distribution of rs2586886 alleles(G vs.A)(χ ²=6.345,P=0.012) and dominant model(AA+GA vs.GA)(χ ²=4.431,P=0.035) showed significant differences between severe and non-OSA groups.The Logistic regression analysis showed that the GG genotype was a risk factor for OSA patients with blood potassium <3.95 mmol/L(OR=7.854,95% CI:1.710-36.000,P=0.008;OR=8.849,95% CI:1.816-43.117,P=0.007). Conclusions Both the GG genotypes of rs1275988 and rs2586886 in the TASK-1 gene may be potential risk factors in severe OSA patients with blood potassium <3.95 mmol/L.Serum potassium>3.95 mmol/L in patients with TASK-1 GG genotype may be conducive to reducing the incidence of severe OSA.

Objective To explore the methods of screening and biological characteristics of lung cancer stem cells. Methods We selected the ABCG2 ⁺and ABCG2 ^-cells from SPC-A-1/adriamycin(ADM)cell line induced by ADM and analyzed the tumorigenicity of ABCG2 ⁺and ABCG2 ^-cells in vivo by flow cytometry and transplantation in nude mice. Results The average fluorescence intensity of SPC-A-1 cells was(1.001±0.014)×10 ²,which was significantly lower than that of SPC-A-1/ADM cells [(10.257±0.023) ×10 ² ](t=17.320,P=0.001);the difference was also statistically significant between the ABCG2/BCRP-FITC treatment group and the SPC-A-1 control group(t=5.269,P=0.021) and the SPC-A-1 control group(t=6.869, P=0.012) and between the SPC-A-1/ADM cell control group and the SPC-A-1/ADM cell homotype control group(t=8.112,P=0.015).The positive rate of SPC-A-1/ADM cells treated with ABCG2/BCRP-FITC was 9.8%,39.84 times higher than that of SPC-A-1 cells;it showed significant difference between the ABCG2/BCRP-FITC group and the SPC-A-1/ADM group(t=9.120,P=0.005) and the SPC-A-1/ADM group(t=8.257,P= 0.006).The positive rate of group B cells was 684 times that of group A cells,and the difference was statistically significant(t=11.235,P=0.001),and the fluorescence intensity of group B cells was strong.The average tumorigenic volume of the mice inoculated with SPC-A-1 cells,group A cells,and group B cells was(6.96±1.82),(6.70±2.55),and(9.17±2.41) mm ³,respectively.Among them,group B was the highest,but there was no significant difference among these three groups(F=2.362,P=0.086).The tumorigenic rate of group B cells was 75.00%,which was significantly higher than that of SPC-A-1 cells and group A cells(F=19.780,P=0.002). Conclusion ABCG2 cells from human lung adenocarcinoma SPC-A-1/ADM cell line can be isolated by ABCG2 antibody combined with immunomagnetic beads sorting method,and the tumor formation rate in nude mice can be observed to explore the identification and biological characterization of lung cancer stem cells.

Objective To investigate the protective effect of salvianolic acid B(SAB)on the intestinal tract of rats after intestinal ischemia-reperfusion injury(IIRI). Methods Forty-eight healthy male SD rats were equally randomized into IIRI group,SAB+IIRI group,sham control group,and SAB+sham control group. The malonyldialdehyde(MDA)level and superoxide dismutase(SOD)activity in the ileum were measured in each group according to the kit instructions,the transcription levels of inflammatory factors in the ileum of rats were detected by real-time fluorescence quantitative RT-PCR,the secretion level of inflammatory factors was detected by ELISA,and the effects of intestinal ischemia-reperfusion on intestinal permeability and histological lesions were measured by histopathology. Results The MDA level in IIRI group was significantly higher than those in negative control group(P=0.005)and SAB+IIRI group(P=0.012). SOD activity of IIRI group was significantly lower than those of negative control group(P=0.006)and SAB+IIRI group(P=0.017). The optical densities of tumor necrosis factor-α(TNF-α)(P=0.003,P=0.009),interleukin(IL)-1β(P=0.026,P=0.005),IL-6(P=0.015,P=0.003),and nuclear factor kappa-B(NF-κB)(P=0.007,P=0.015)in IIRI group were significantly higher than those in sham control group and SAB+IIRI group. The TNF-α(P=0.002,P=0.006),IL-1β(P=0.002,P=0.006),IL-6(P=0.008,P=0.002),and NF-κB(P=0.026,P=0.005)levels in IIRI group were significantly higher than those in sham control group and SAB+IIRI group. The inulin level in IIRI group was significantly lower than that in negative control group(P=0.015)and significantly higher than that in SAB+IIRI group(P=0.011). The dextran level in IIRI group was significantly lower than those in sham control group(P=0.011)and SAB+IIRI group(P=0.012). The dextran gel level in IIRI group was significantly higher than those in sham control group(P=0.031)and SAB+IIRI group(P=0.020). SAB pretreatment remarkably improved the edema,necrosis,and villus stripping of the intestinal mucosa in the ileum of rats. The Chiu score was significantly higher in SAB+sham control group than in sham control group(P=0.001)and was significantly lower in SAB+IIRI group than in IIRI group(P=0.001). Conclusion SAB pretreatment can alleviate IIRI in rat models,and this protective effect may be achieved by alleviating oxidative stress and inflammation in the intestinal tract.

Objective To study the gene expression of cardiac mesenchymal cells in patients with type 2 diabetes mellitus (T2DM)based on a whole-genome high-throughput sequencing dataset,screen differentially expressed genes,analyze the genetics signature of cardiac mesenchymal cells in T2DM patients by bioinformatics analysis,and explore the environmental chemicals related to the key differentially expressed genes. Methods The dataset GSE106177 was obtained from Gene Expression Omnibus (GEO) database.The dataset was pre-processed and analyzed by Network Analyst,Cytoscape 3.7.1,String11.0,CTD,and HMDD for screening for differentially expressed genes,enrichment analysis,establishment of protein-protein interaction (PPI) networks,and screening for relevant environmental chemicals. Results The gene expression pattern of cardiac mesenchymal cells in T2DM patients was significantly different from that in the control group.There were 135 differentially expressed genes,of which 58 (42.96%) were up-regulated and 77 (57.04%) were down-regulated.The differentially expressed genes mainly participated in biological processes such as multicellular organism development,anatomical structure development,and system development and were mainly involved in hepatocellular carcinoma,Cushing’s syndrome,and cholesterol metabolism.PPI network showed that UBC was the core protein node.The microRNA-Gene interaction network showed that seven microRNAs,represented by hsa-mir-8485,interacted with the differentially expressed genes.Key T2DM related genes such as UBC,DNER,and CNTN1 interacted with bisphenol A. Conclusions The gene expression profile of cardiac mesenchymal cells markedly changes in T2DM patients,during which UBC may play an important biological role.Bisphenol A exposure may also affect the development and normal function of cardiac cells in T2DM patients.

Objective To investigate the application of Acute Gastrointestinal Injury(AGI) grading in evaluating gastrointestinal failure in patients with acute pancreatitis(AP). Methods In this retrospective observational study,patients presented with moderate severe AP and severe AP in our hospital from October 2013 to October 2016 were consecutively enrolled.Logistic regression analysis and receiver operating characteristic curve were used to explore and evaluate potential predictors of gastrointestinal failure. Results A total of 202 patients were included in this study,with 90 cases(44.6%) identified as gastrointestinal failure.Survival curve showed significantly increased risk of death in patients with gastrointestinal failure(P < 0.05).Logistic regression analysis showed age(OR=1.06,95%CI:1.03-1.09,P<0.001),complaint of stopping flatus and defecation(OR=7.02,95%CI:2.08-23.66,P=0.002),increased counts of white blood cells in peripheral blood(OR=1.09,95%CI:1.02-1.17,P=0.015),decreased level of serum albumin(OR=0.93,95%CI:0.86-1.00,P=0.048),and increased level of serum creatinine at admission(OR=1.02,95%CI:1.01-1.04,P=0.001) were the independent risk factors of gastrointestinal failure.The area under curves of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and Beside Index for Severity in Acute Pancreatitis (BISAP) scores in diagnosing gastrointestinal failure were 0.999 and 0.782,respectively. Conclusions Gastrointestinal failure can remarkably increase the risk of death in patients with AP.Both APACHE Ⅱ and BISAP scores at admission are useful in diagnosing gastrointestinal failure in patients with AP.

Objective To investigate the clinical values of nutritional status and chest CT phenotypes in the assessment of chronic obstructive pulmonary disease(COPD). Methods A total of 256 patients with stable COPD were enrolled from Peking Union Medical College Hospital and Civil Aviation General Hospital from June 2017 to June 2018.Demographic data,height,weight,smoking history,and number of exacerbations were collected.Pulmonary function tests and COPD assessment test(CAT)questionnaire-based survey were performed.The correlations of Goddard score with pulmonary function,CAT score,and number of exacerbations were analyzed.The clinical features of COPD patients with different body mass index(BMI)grades and CT phenotype were analyzed. Results The forced expiratory volume in one second as percentage of predicted value(FEV₁%pred)was significantly higher in normal body mass group(t=-2.701,P=0.0080),overweight group(t=-3.506,P=0.001),and obese group(t=-4.323,P=0.000)than in low body mass group and was significantly higher in obese group than in normal body mass group(t=-3.096,P=0.002).The forced vital capacity as percentage of predicted value(FVC%pred)of normal body mass group(t=-3.081,P=0.002)and overweight group(t=-2.766,P=0.006)were significantly higher than that of low body mass group.The forced expiratory volume in one second(FEV₁)/forced vital capacity(FVC)was significantly higher in overweight group than in normal body mass group(t=-3.702,P=0.001)and significantly higher in obese group than in low body mass group(t=-4.742,P=0.000),normal body mass group(t=-5.785,P=0.000),and overweight group(t=-2.984,P=0.003).In addition,the carbon monoxide diffusing capacity as percentage of predicted value(DLco%pred)was significantly higher in overweight group than in underweight(t=-3.042,P=0.003)and normal body mass groups(t=-3.128,P=0.002)and significantly higher in obese group than in underweight group(t=-4.742,P=0.000)and normal body mass group(t=-5.785,P=0.000).The Goddard scores of overweight(Z=4.535,P=0.000)and obese groups(Z=5.422,P=0.000)were significantly lower than that of normal body mass group.Partial correlation analysis showed that Goddard score was negatively correlated with FEV₁/FVC(r =-0.230,P = 0.022)and DLco%pred(r =-0.531,P = 0.000)and positively correlated with CAT score(r = 0.244,P = 0.021).BMI of phenotype E(t=3.467,P=0.001)and M(t=3.031,P=0.003),FEV₁/FVC of phenotype E(t=2.484,P=0.015)and M(t=2.969,P=0.004)as well as DLco%pred of phenotype E(t=4.928,P=0.000)and M(t=2.489,P=0.0163)were significantly lower than those of phenotype A.Patients with phenotype M had worse FEV₁%pred,FVC%pred,residual volume/total lung capacity and number of acute exacerbations than patients with phenotypes A and E,but the differences were not statistically significant(all P >0.05). Conclusions The nutritional status is closely related to lung function,severity of emphysema,and number of exacerbations in COPD patients.Chest CT phenotype is clinically valuable in the assessment of COPD.

Objective To analyze the risk factors for postoperative recurrence of chronic suppurative otitis media(CSOM) and explore the intervention measures to prevent postoperative recurrence of CSOM. Methods A total of 1066 patients with CSOM who underwent concurrent surgical treatment and achieved clinical cure in our hospital from January 2012 to December 2018 were enrolled.The clinical data and laboratory findings were reviewed by using an electronic medical record system and the patients were followed up for 1 year.The patients were divided into the non-recurrent group and the recurrent group.Chi-square test and multivariate logistic regression were used to compare the factors may contribute to the postoperative recurrence. Results The recurrence rate of CSOM was 6.38%.Multi-drug-resistant(MDR) infection before surgery(χ ²=16.338,P=0.000),aged ≥60 years(χ ²=5.182,P=0.023),frequency of occurrence ≥3 times/year(χ ²=4.388,P=0.036),duration of active period>7 d(χ ²=4.729,P=0.030),repeated upper respiratory tract infection>3 times/year(χ ²=11.913,P=0.001),accompanied by chronic sinusitis(χ ²=11.077,P=0.001),blood glucose>6.11 mmol/L(χ ²=15.327,P=0.000),postoperative serum procalcitonin(PCT)>0.5 μg/L(χ ²=8.337,P=0.004) were the risk factors for postoperative recurrence.The use of snorkel was a protective factor for postoperative recurrence(χ ²=5.308,P=0.021).Multivariate analysis showed that MDR infection(OR=3.373,95%CI:1.825-6.234,P=0.000),repeated upper respiratory tract infection>3 times/year(OR=2.727,95%CI:1.479-5.030,P=0.001),accompanied by chronic sinusitis(OR=2.980,95%CI:1.654-5.369,P=0.000),blood glucose>6.11 mmol/L(OR=3.219,95%CI:1.741-5.953,P=0.000),and postoperative serum PCT>0.5 μg/L(OR=2.085,95%CI:1.106-3.931,P=0.023) were independent risk factors for postoperative recurrence in CSOM patients. Conclusions Effective prevention and control of MDR infection,control of blood sugar,prevention of upper respiratory tract infection,and lowering the recurrence of chronic sinusitis are the main measures to reduce postoperative recurrence of CSOM.Monitoring of the infection marker PCT can help to achieve early intervention.

Objective To evaluate the relationship of volumetric changes and endoleaks after endovascular aneurysm repair(EVAR)for abdominal aortic aneurysms(AAAs). Methods We retrospectively evaluated the clinical and imaging data of 54 patients who had underwent EVAR within 1 month after their aneurysms were detected.All patients received abdominal and pelvic enhanced computed tomography(CTA)for two follow-up visits in Peking Union Medical College Hospital from July 2014 to February 2019.Three-dimensional volumes and maximum diameters on axial CT of the aortic aneurysms were calculated by dedicated semi-automated 3D segmentation software before surgery(V₀ and D₀),in the 4 ^th postoperative month(V₁and D₁),and in the 12 ^th postoperative month(V₂and D₂),respectively.The presence or absence of endoleak for each patient with the V₁/V₀,V₂/V₀,and V₂/V₁ were calculated to assess the significance of volume changes with respect to endoleaks and the correlation between volume changes and maximum diameter changes on axial CT images. Results Of the 54 patients,endoleaks were found in 11 patients at the first follow-up visit(4 months after surgery),among whom 8 patients were arranged a second follow-up visit(12 months after surgery),during which endoleaks were found in 5 patients.Fifteen of 43 non-leaked patients underwent a second CTA examination,which revealed endoleak in one case.Patients who did exhibit endoleaks[n =11,V₁/V₀=1.086(1.033,1.116)]showed significant increases in aneurysm volume when compared with those who did not exhbit endoleaks[n =43,V₁/V₀=1.019(0.970,1.065)]at the first follow-up visit(Z=-2.695,P=0.007),although no significant difference was found with regard to volume changes between endoleaks(n=6,V₂/V₀=1.1±0.2,V₂/V₁=1.0±0.1)and non-endoleaks(n=17,V₂/V₀=1.0±0.1,V₂/V₁=1.0±0.1)at the second follow-up visit(t=0.725,P=0.476)as well as between these two follow-up visits(t=-0.021,P=0.984).V₀ and D₀ were moderately correlated with V₁ and D₁,respectively(r=0.5,P<0.001)and strongly correlated with V₂ and D₂,respectively(r=0.8,P<0.001).V₁ and D₁ were strongly correlated with V₂ and D₂,respectively(r=0.8,P<0.001). Conclusions The changes of aneurysm volume cannot reliably reflect the occurrence of endoleaks.The change of maximum axial diameter of aneurysm has certain correlation with the changes of aneurysm volume.

Objective To explore the value of trans-rectal shear wave elastic mode combined with elastic modulus in the diagnosis of prostate cancer and establish a new method for the evaluation of prostate with trans-rectal shear wave elastography(SWE). Methods The typical findings of trans-rectal ultrasound(US)and SWE in 79 patients with prostate cancer(n=41)and benign prostatic hyperplasia(BPH)(n=38)confirmed by surgery or US-guided biopsy were analyzed retrospectively.Their diagnostic value were evaluated with the pathological results as the golden standards. Results Three or more malignant features detected by conventional trans-rectal US(χ ²=42.5,P<0.001)and asymmetrical SWE mode(χ ²=54.2,P<0.001)showed statistically significant difference in prostate cancer and BPH groups.The elastic modulus of Emean and Emax in the prostate cancer group were(92.8±21.5)and(114.2±29.8)kPa,which were significantly higher than those in the BPH group [(56.7±14.0)(t=-8.8,P<0.001)and(68.4±17.2)kPa(t=-8.3,P<0.001)].The receiver-operating characteristic(ROC)curve with Logistic regression showed that the elastic model combined elastic modulus had the largest area under ROC curve and the highest diagnosis efficiency of prostate cancer,with the cutoff value of 0.45.The diagnosis sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of the combination were 95.1%,89.5%,90.7%,94.4%,and 92.4%,respectively. Conclusion Combination of SWE mode and elastic modulus is more valuable than elastic modulus alone in the diagnosis of prostate cancer.

Objective To investigate the value of contrast-enhanced ultrasound(CEUS)quantitative parameters in the diagnosis of thyroid benign and malignant nodules. Methods The CEUS features of 85 histopathologically confirmed thyroid nodules were quantitatively analyzed using five parameters including rising time(RT),time to peak(TTP),area under the curve(AUC),maximum intensity(Imax),and mean transit time(mTT).The dynamic vascular pattern(DVP)curves were also drawn. Results The Imax(Z=-7.08,P=0.01)and AUC(Z=-2.03,P=0.04)of thyroid malignant nodules were significantly smaller than those of thyroid tissue,and the Imax(Z=-1.35,P=0.02)and AUC(Z=-0.21,P=0.02)of thyroid benign nodules were significantly larger than those of thyroid tissue.There were significant differences between thyroid benign and malignant nodules in Imax(Z=-4.16,P=0.00),AUC(Z=-3.01,P=0.01),and DVP curve types(P=0.00).RT(Z=-0.28,P=0.62),TTP(Z=-0.10,P=0.89),and mTT(Z=-0.79,P=0.05)were not significantly different between thyroid benign and malignant nodules. Conclusion The quantitative parameters of CEUS,especially Imax and AUC parameters,are valuable in the diagnosis of benign and malignant thyroid nodules.

Objective To identify the possible factors that may influence the success and the complications of ultrasound-guided out-of-plane radial arterial cannulation. Methods Multivariate Logistic regression analysis was used to analyze the clinical data of 131 patients undergoing elective surgery and ultrasound-guided out-of-plane radial artery cannulation,dynamic needle tip positioning(DNTP) technique or angular distance(AD) technique and to find out the factors associated with the one-attempt success rate,overall success rate,posterior arterial wall perforation,and local hematoma. Results The depth of the anterior arterial wall≥3 mm was the factor associated with posterior arterial wall perforation(OR=0.314,95%CI:0.143-0.691,P=0.004) and local hematoma(OR=0.250,95%CI:0.107-0.585,P=0.001).The use of DNTP method was significantly associated with posterior arterial wall perforation(OR=0.303,95%CI:0.138-0.667,P=0.003). Conclusions During ultrasound-guided out-of-plane radial cannulation,puncture at the arterial anterior wall sites with a depth of≥3 mm can reduce the incidence of posterior arterial wall perforation and local hematoma.Compared with AD,DNTP can lower the incidence of posterior arterial wall perforation.

Objective To evaluate the value of oxycodone hydrochloride for postoperative pain management in patients undergoing patient-controlled intravenous analgesia(PCIA). Methods The medical records on postoperative pain management in our department from January 1 to June 30,2018,were retrospectively analyzed.Totally 136 patients were assigned into oxycodone,sufentanil,or morphine groups according to the opioid used in the PCIA.Patients were assessed for postoperative pain severity(scored with NRS)and adverse reactions 24,36,and 48 hours after surgery.The area under curve(AUC)was calculated. Results The score of pain at exercise was significantly lower in the oxycodone group(2.2±2.4)than in the sufentanil group(3.4±2.1)(t=0.305,P=0.0126)or the morphine group(3.4±1.7)(t=0.104,P=0.0277)36 hours after surgery.AUC at rest was significantly lower in the oxycodone and morphine groups than in the sufentanil group(29.00,27.00,and 40.01,respectively);in contrast,AUC at exercise was significantly lower in the oxycodone group(63.17)than in the sufentanil and morphine groups(82.00 and 80.93,respectively).The consumption of opioids was significantly higher in the sufentanil group[(37.2±16.1),(46.1±24.3),(64.4±33.4)mg]than in the oxycodone group[(20.4±14.8)(t=3.571,P=0.001),(24.2±16.1)(t=4.63,P<0.0001),(34.4±25.1)mg(t=6.409,P<0.0001)]or the morphine group[(16.6±11.7)(t=4.233,P<0.0001),(20.5±14.1)(t=5.250,P<0.0001),(28.8±19.0)mg(t=7.354,P<0.0001)]24,36,48 hours after surgery.The oxycodone group experienced less vomiting(χ ²=11.360,P=0.003)and early termination of PCIA(χ ²=7.914,P=0.019)compared with the other two groups. Conclusions Oxycodone can be used for postoperative PCIA.It can alleviate a variety of postoperative pain,with superior analgesic efficiency and safety to sufentanil and morphine.

Cilia are protruding cell structures on the cell surface and are found in almost every type of cell.According to the different structures and quantity of tubulins,cilia can be divided into two categories:motor cilia and sensory cilia.Sensory cilia are also called non-motor cilia and primary cilia,due to the composition and number of tubulins.They are closely related to the development of internal organs and many human physiological activities.Recent studies have demonstrated that cilia are involved in regulating the formation of left and right symmetry of the heart structure,and eventually the heart develops into the left-right asymmetry structures.Since congenital heart diseases(CHD)are characterized by abnormalities in the spatial structure of the heart chamber and outflow tract,cilia may play an important role in the pathogenesis of CHD.Cilia,mainly through ciliary transduction signal pathways,regulate both the formation of left and right asymmetrical structures and the polarity and the migration of cells.Therefore,a clear understanding of the regulation mechanism of ciliary signaling pathway on heart development can provide new therapeutic targets and new ideas for the clinical treatment of CHD and may offer new target genes for prenatal screening of CHD.This article summarizes recent advances in the role of cilia in heart development and CHD pathogenesis and its mechanisms.

Heart failure(HF)is the terminal stage of cardiovascular diseases and has long been one of the most deadly condition due to its high morbidity and mortality.Since the currently available treatment options cannot meet the clinical needs,new therapeutic strategies for HF should be actively explored.Epigenetics does not involve the changes of genetic sequences but focuses on the stable inheritance of genes in different individuals.It is affected by the interaction between genes and environments,which may result in DNA methylation,histone modification,and other changes.This article summarizes the recent research advances in epigenetics in HF.

G protein-gated inward rectifier potassium(GIRK)channels are widely distributed in the central nervous system and play important roles in maintaining the resting membrane potential of neurons,adjusting neuronal excitability,and regulating the release of neurotransmitter.Studies have shown that addictive behavior is closely related to the expression and activity of the GIRK channels in the brain reward system and the GIRK channels may be a potential target for addiction treatment.This article summarizes the recent research advances in GIRK channels in terms of structure,intracranial tissue distribution,and especially substance addiction.

Tumors are highly complex systems. Understanding the compositions and functions of the tumor immune microenvironment is a prerequisite for effective tumor immunotherapy. Single-cell RNA sequencing can detect the transcriptome of a cell at the resolution of single-cell level,describe its functional status,and thus deepen the understanding of the composition and function of different cell clusters in tumor immune microenvironment. This article reviews the application of single-cell RNA sequencing in research on tumor immune microenvironment.

Patients with uremia can suffer from decreased renal function and endocrine and metabolism disorders,which can lead to the accumulation of toxins in the body.Accumulation of uremic toxins is a major cause of cognitive dysfunction in uremic patients.This article summarizes some of the cognitive dysfunction-related uremic toxins and their possible mechanisms.

As an important branch of artificial intelligence,the emerging medical artificial intelligence(MAI)is facing many ethical issues.MAI may offer the optimal diagnosis and treatment for patients but may also bring adverse effects on society and human beings.This article discusses the ethical problems caused by MAI and elucidates its development in a direction that meets ethical principles and requirements.

Based on our experience in treating one patients with non-small cell lung cancer complicated with hyperthyroidism,the following considerations in immunotherapy and pharmaceutical care are proposed:role of iodine contrast and contrast agent selection in patients with hyperthyroidism;selection of hemostatic agents and assessment of thrombosis risk in patients with hemoptysis caused by tumor invasion of bronchus;influence of glucocorticoid use on the treatment with programmed cell death-1(PD-1)inhibitor and the role of PD-1 inhibitors in patients with a history of hyperthyroidism;education methods for patients refuse to receive opioids.The participation of clinical pharmacists in the Multiple Disciplinary Team and the multi-dimensional pharmaceutical monitoring for patients can improve the safety and rationality of medications.

Pituitary metastasis is a rare intracranial malignant tumor originated from other malignant tumors at other parts of the body.Pituitary metastases are typically hypervascular,while hypovascular pituitary metastasis is rare.Radiologically,hypovascular pituitary metastasis is difficult to be distinguished from pituitary adenoma.This article reports one case of pathologically confirmed hypovascular pituitary metastasis,with the main diagnostic clues including history of malignant tumor,presence of normal pituitary in the intrasellar region,and isointensity on T1 and T2 sequence.