G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Objective To evaluate the CT features of small lung invasive adenocarcinoma with air?containing space and its relationship with pathological types, and to explore the pathological basis of air?containing space. Methods CT and pathological data of fifty patients with surgically proven lung invasive adenocarcinoma with air?containing space in our hospital from January 2012 to December 2017 were retrospectively reviewed. CT image analysis included image features of tumor and air?containing space. Pathological analysis included pathological subtype, differentiation degree. CT features of tumor and air?containing space were compared with regard to pathological types using chi?square test or Fisher exact text. Analysis of variance was used to compare quantitative data satisfying normal distribution, while those data not satisfying normal distribution were compared with Kruskal?Wallis test. In addition, Spearman correlation was used to analyze the correlation between nodule density and pathological types. Results (1) CT features of tumors: Tumors were predominantly located in peripheral lungs (46/50). Most of the tumors were subsolid nodules (37/50). Tumor?lung interface was generally clear (46/50). Tumors are often accompanied by malignant signs such as lobulation (37/50), spicule sign (27/50), air bronchogram sign (43/50), and pleural indentation (36/50). The mean diameter of nodules ranged from 7.50 mm to 18.12 mm, with an average of (12.91±2.85)mm. The nodule density ranged from-657.00 to 73.00 HU with an average of (-213.88±206.16) HU. (2) CT features of air?containing space:Air?containing spaces were commonly solitary (37/50) and were found to be mainly in an eccentric distribution (29/37). The maximum diameter of air?containing space ranged from 1.00 to 16.00mm, and the average diameter was (4.23±3.14)mm. Air?containing spaces less than 5mm were found in 35 cases (70%), and air?containing spaces more than 5mm were found in 15 cases. (3) Comparison of CT features and corresponding pathological types: Nodule density, number of air?containing space, and type of nodule density in different pathological types were statistically different (P<0.05). There was a correlation between nodule density and pathological subtypes (r=0.371, P=0.008). Differences of nodule density, short?dimension of nodule, type of nodule density, spicule sign, pleural indentation among different tumor differentiation degrees were significant (P<0.05). The degree of tumor differentiation was negatively correlated with nodule density (r=-0.451, P=0.001). Conclusion The detection rate of air?containing space in lung invasive adenocarcinomas is 12.7%. Most small lung invasive adenocarcinomas with air?containing space are presented as peripheral subsolid nodule, and there is a certain correlation between their CT features and pathological types. The pathological basis of air?containing space was supposed to be dilated distal bronchiole induced by check?valve mechanism and destruction of alveolar structure by tumor.

Objective: To evaluate the CT features of small lung invasive adenocarcinoma with air-containing space and its relationship with pathological types, and to explore the pathological basis of air-containing space. Methods: CT and pathological data of fifty patients with surgically proven lung invasive adenocarcinoma with air-containing space in our hospital from January 2012 to December 2017 were retrospectively reviewed. CT image analysis included image features of tumor and air-containing space. Pathological analysis included pathological subtype, differentiation degree. CT features of tumor and air-containing space were compared with regard to pathological types using chi-square test or Fisher exact text. Analysis of variance was used to compare quantitative data satisfying normal distribution, while those data not satisfying normal distribution were compared with Kruskal-Wallis test. In addition, Spearman correlation was used to analyze the correlation between nodule density and pathological types. Results: (1) CT features of tumors: Tumors were predominantly located in peripheral lungs (46/50). Most of the tumors were subsolid nodules (37/50). Tumor-lung interface was generally clear (46/50). Tumors are often accompanied by malignant signs such as lobulation (37/50), spicule sign (27/50), air bronchogram sign (43/50), and pleural indentation (36/50). The mean diameter of nodules ranged from 7.50 mm to 18.12 mm, with an average of (12.91±2.85)mm. The nodule density ranged from-657.00 to 73.00 HU with an average of (-213.88±206.16) HU. (2) CT features of air-containing space: Air-containing spaces were commonly solitary (37/50) and were found to be mainly in an eccentric distribution (29/37). The maximum diameter of air-containing space ranged from 1.00 to 16.00mm, and the average diameter was (4.23±3.14)mm. Air-containing spaces less than 5mm were found in 35 cases (70%), and air-containing spaces more than 5mm were found in 15 cases. (3) Comparison of CT features and corresponding pathological types: Nodule density, number of air-containing space, and type of nodule density in different pathological types were statistically different (P<0.05). There was a correlation between nodule density and pathological subtypes (r=0.371, P=0.008). Differences of nodule density, short-dimension of nodule, type of nodule density, spicule sign, pleural indentation among different tumor differentiation degrees were significant (P<0.05). The degree of tumor differentiation was negatively correlated with nodule density (r=-0.451, P=0.001). Conclusion The detection rate of air-containing space in lung invasive adenocarcinomas is 12.7%. Most small lung invasive adenocarcinomas with air-containing space are presented as peripheral subsolid nodule, and there is a certain correlation between their CT features and pathological types. The pathological basis of air-containing space was supposed to be dilated distal bronchiole induced by check-valve mechanism and destruction of alveolar structure by tumor.

Objective To investigate the clinical application of different puncture positions in percutaneous nephrolithotomy (PCNL).Methods From February 2015 to March 2017,102 patients with kidney urinary calculi in our hospital were enrolled in the study.According to the selected puncture position,they were divided into prone position (group A,32 cases),lateral decubitus position (group B,37 cases) and half stone oblique supine position (group C,33 cases).The mean arterial pressure (MAP),heart rate (HR) and blood oxygen saturation (SpO2) were observed before placement of 5 min (T0),after placement of 5 min (T1),30 min (T2),and postoperative 5 min (T3),and the time of established passage,the time of operation and the amount of bleeding during operation and so on.Results The MAP in group B and group C at T1 was significantly higher than that in group A (P ＜ 0.05);The HR in Group B and group C at T2 and T3 were significantly lower than those in group A (P ＜ 0.05);The SpO2 in Group B and group C at T1 and T2 were significantly higher than those in group A (P ＜ 0.05);There was no significant difference in the time of establishment passage,the rate of primary clearing stone and the hospital stay in the groups (P ＞0.05);The operation time and intraoperative blood loss in group C were (120.07 ± 20.19) min and (90.01 ±30.11)ml,significantly less than those in group B and group A (P ＜0.05);The operation time and intraoperative blood loss in group B were (140.17 ±20.48) min and (110.04 ±29.82) ml,significantly less than that in group A [(170.02 ± 21.02) min,(164.02 ± 30.12) ml] (P ＜ 0.05);The postural comfort of group C was better than that of group A and group B (P ＜ 0.05);There was no significant difference in the incidence of postoperative complications in the three groups (P ＞ 0.05).Conclusions Half stone oblique supine position in the PCNL application has good effect,which is conducive to improving the patient's tolerance to surgery,shorten the operation time,and it is worth popularizing.

Vegetable oil is one of the most potential alternatives of petroleum and has become a hot issue in recent years. This review focuses on the influence of vegetable oil structure on platform compounds and polymers properties, and further systematically introduces their developments and the latest progress. Meanwhile, we also summarized the main confronting problems and the future development directions in the research of oil-based platform compounds and polymers. The review provides useful information for readers to fully understand biochemical engineering of vegetable oils and their prospects.

The aim of this study was to develop a formulation to improve the oral absorption of baicalin (BA) by combining a phospholipid complex (PC) and self-emulsifying microemulsion drug delivery system (SMEDDS), termed BA-PC-SMEDDS. BA-PC was prepared by a solvent evaporation method and evaluated by complexation percentage (CP). The physicochemical properties of BA-PC were determined. The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model. The improved bioavailability of BA in BA-PC-SMEDDS was confirmed in an in vivo rat model. The CP of BA-PC reached 100% when the molar ratio of drug to phospholipid (PP) was ≥1:1. The solubility of BA-PC increased in both water and octanol, and the log P o/w of BA-PC was increased significantly. BA-PC-SMEDDS could be dispersed more evenly in water, compared to BA and BA-PC. Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA-PC was lower than that of free BA, while improved significantly in BA-PC-SMEDDS. The relative bioavailability of BA-PC(1:2)-SMEDDS was 220.37%. The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.

Objective To explore the chiaical value of cerebral perfusion reduction after subarachnoid hemorrhage(SAH)by multi spiral CT perfusion in rabbits.Methods 32 male Japanese big-ear rabbits of clean level were randomly divided into 2 groups:Group A(n =8),the normal group,were to obtain normal MS-CTP values of rabbit cerebrums;Group B(n =24),the SAH group was made into two-hemorrhage animal models,checked on seven day by multi spiral CT perfusion.The source data was transmitted to the post-processing workstation ADW 4.2.Perfusion parameters maps(CBF)of both sides of frontal,parietal and basal ganglia were got by computing.Each rabbit was killed immediately after scanning,and the spider blood was observed.Results The average CBF value of the two groups:The difference was not statistically significant at the frontal(t =1.740,P =0.092)and parietal(t =1.868,P =0.072); The average values of CBF were significantly decreased at the basal ganglia(t =2.481,P =0.019).Group B showed the distribution of blood clot in the basal cistern,but there was no blood clot at the frontal and parietal.Conclusion The monitor perfusion changes of rabbit brain after SAH could be detected by MS-CTP,and the lower of regional cerebral perfusion had a relationship with the distribution with the blood clot,and it could instruct the early diagnosis of cerebral perfusion,and the clinical benefit to early intervention treatment.

Objective To investigate the value of permeability surface (PS) in predicting hemorrhagic transformation (HT) in acute ischernic stroke (AIS) using CT peffusion (CTP).Methods The study included 31 consecutive patients who presented symptoms suggestive of an AIS for 3-9 h. All patients underwent CT examination (noncontrast CT,CTP).HT was determined by follow-up CT images.According to presence of HT,the AIS was divided into HT group (PSHT,11 patients) and non-HT group(PSNo-HT,20 patients).PS,cerebral blood flow (CBF),cerebral blood volume (CBV) and mean transit time (MTT) on both sides of brains were measured.The relative PS(rPS),relative CBF (rCBF),relative CBV(rCBV) and relative MTT(rMTT) were obtained by calculating the ratio of the values of bilateral regions.The rPS between PSHT and PSNo-HT was compared with an exact Wilcoxon signed-rank test. The rCBF,rCBV,rMTT and the PS of the ischemic side between PSHr and PSNo-HT were compared with independent-sample t test.Meanwhile,Spearman rank correlation analysis was conducted to analyze the relationship between the CTP parameters and HT.ResultsThe PS value of ischemic side was (1.61±0.77) ml · min - 1 · 100 g-1 for the PSHT group,and the value was (0.91 ± 0.49) ml · min - 1 · 100 g- 1 for the PSNo-HT group.For the PSHT group,rPS,rCBF,rCBV,rMTT were 2.76 ±0.78,0.32 ±0.18,0.66 ±0.31,2.67 ±0.71,and for the PSNo-HT group,rPS,rCBF,rCBV,rMTT were 1.35 ±0.19,0.50±0.21,0.91 ±0.28,2.62 ± 1.31.Compared with PSNo-HT,PSHT had higher rPS and PS value,and there were significant statistical differences (U =0.000,t =3.070,P ＜0.01).But rCBF and rCBV values were lower in the PSHT group compared to the PSNo-HT group,and there were significant statistical differences (trCsF =2.343,trCBV =2.210,P ＜ 0.05).There was no significant statistical difference in rMTT between the two groups(t =0.118,P ＞ 0.05).Significant positive correlations were detected between the rPS and PS with HT(r=0.496,0.821,P ＜0.01).ConclusionsThe value of rPS is helpful in predicting HT in AIS.And it can be used as a predictor in determining clinical personalized treatment and thus reduce the incidence of adverse events.

Objective To investigate the risk factors for persistent hemodynamic depression after carotid angioplasty and stenting(CAS). Methods Sixty-one patients with CAS were included. By univariate Logistic regression analysis,the influencing factors for persistent hemodynamic depression were analyzed,by stepwise Logistic regression analysis and adjustment for age and gender factors,the independent risk factors for persistent hemodynamic depression were analyzed. Results In 61 patients,25 cases had hypotension,25 cases had bradycardia,all for 41.0% incidence. According to the patients intraoperative and postoperative blood pressure,heart rate conditions,the duration of hemodynamic depression,the cases were divided into persistent hemodynamic depression group (20 cases) and no-persistent hemodynamic depression group(41 cases). Univariate Logistic regression analysis indicated that persistent hemodynamic depression influencing factors were the symptomatic stenosis, severe stenosis, using balloon dilatation, implantation of laser-carving stent(P<0.05). With adjustment for age and gender factors, stepwise Logistic regression analysis showed that using balloon dilatation, implantation of laser-carving stent were the independent risk factors for persistent hemodynamic depression (OR = 5.046,95%CI 1.342-18.977,P = 0.017;OR = 4.142,95%CI 1.151-14.902, P= 0.030),symptomatic stenosis was the independent protective factor for persistent hemodynamic depression (OR = 0.264,95% CI 0.073-0.964,P= 0.044). Conclusions Persistent hemodynamic depression after CAS is a common complication.CAS patients with using balloon dilatation, implantation of laser-carving stent are more susceptible to persistent hemodynamic depression, while symptomatic stenosis is its protective factor.

Objective To observe the onset of vascular smooth muscle cell (VSMC) senescence induced by tert-butyl hydroperoxide (t-BHP) and the intervention effect of dehydroepiandrosterone (DHEA). Methods The VSMCs were divided into four groups: blank control group, t-BHP group (incubated with 80 μmol/L t-BHP for 72 h), 10 nmol/L DHEA intervention group (pretreated with 10 nmol/L DHEA 30 min before t-BHP) and 100 nmol/L DHEA intervention group (pretreated with 100nmol/L DHEA 30 min before t-BHP). Two ageing markers of ageing associated β-galactosidase activity and cell proliferation activity were adopted as main indexes. β-galactosidase activity was measured with immunocytochemical method and cell proliferation activity was measured with flowcytometry. Results After continuous treatment with 80 mmol/L t-BHP for 72 h, the ratios of G0/G1 phase cells and SA-β-galactosidase staining positive cells increased as compared with blank controlgroup [(89.4±3.4)% vs. (49.5±5.5)%, (3.5±1.2)% vs. (75.3±4.3)%], which indicated that VSMCs senescence were successfully induced by t-BHP. While the above changes were smaller in 100 nmol/L DHEA intervention group than in t-BHP group. Conclusions With ageing,accumulation of damage produced by reactive oxygen species may be an important mechanism causing the onset of VSMCs senescence. DHEA may be able to retard the progression of VSMCs senescence through antioxidant effect.