Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective To investigate the evaluation of the nursing staff of the tertiary hospitals in Shenzhen City on the status quo of the nursing clinical support system,and to analyze its influencing factors so as to provide reference and basis for perfecting the nursing clinical support system.Methods The nursing staffs in 16 hospitals of 8 districts of Shenzhen City from December 2022 to January 2023 were selected as the survey subjects,and the general data questionnaire and the nursing clinical support system questionnaire were used for conducting the survey.Results A total of 572 questionnaires were collected,and 520 questionnaires were valid,with an effective recovery rate of 90.9％.The scores of each dimension in the nursing clinical sup-port system scale were(1.87±0.81)points for equipment and appliance support,(1.07±0.62)points for aux-iliary staff support,(1.91±0.80)points for the logistics departments support,(0.88±0.67)points for the auxiliary departments support.The results of univariate analysis showed that there were statistical differences in the equipment and appliance support scores among the nurses with different ages,different professional ti-tles and different education levels(P＜0.01);the scores of 4 dimensions had statistical differences among the nursing staffs with different departments(P＜0.01).All factors had statistically significant differences in the dimension of auxiliary department support(P＜0.05).Conclusion The popularity degree of nursing clinical support system in tertiary hospitals in Shenzhen City is high,and equipment and appliance show the character-istics of advancement and diversity.The hospital managers should strengthen the force of nursing clinical sup-port system and reduce the nursing staff to engage in non-nursing work.

Objective To detect the expression changes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)during the development of deep vein thrombosis in mice,and to explore the application value of them in thrombus age estimation.Methods The mice in the experimental group were subjected to ligation of inferior vena cava.The mice were sacrificed by excessive anesthesia at 1 d,3 d,5 d,7 d,10 d,14 d and 21 d after ligation,respectively.The inferior vena cava segment with thrombosis was extracted below the ligation point.The mice in the control group were not ligated,and the inferior vena cava segment at the same position as the experimental group was extracted.The ex-pression changes of IL-10 and TGF-β1 were detected by immunohistochemistry(IHC),Western blot-ting and real-time qPCR.Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis.Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group.The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation,respectively.The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group,and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group.The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation,respectively.The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group,and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes,and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

OBJECTIVE To investigate whether Moslae herba oil has penetration enhancing effect on the active components of Evodia rutaecarpa and its ability to promote transdermal absorption.METHODS In vitro transdermal experiments were performed u-sing the diffusion pool and the isolated skin of rats.Using various components of Evodia rutaecarpa as indicators,HPLC was deter-mined to calculate the umulative penetration amount of each component.Changes in the skin and cuticle layers were observed by HE staining,immunohistochemical staining,and ATR-FTIR.GC-MS was used to measure Moslae herba oil components after administration.RESULTS Moslae herba oil showed the penetration-enhancing effect on various components in Evodia rutaecarpa.Compared with the postive drug nitrogenone,the cumulative penetration amounts of hyperoside,evodiamine and rutae-carpine were greater.In addition,the sesquiterpene composition and thymol in the Moslae herba oil were more likely to be stored in the skin,which could disturb the lipid structure of the cuticle layer and promote the penetration of drugs.CONCLUSION The results provide reference for the selection of transdermal absorption agent.

Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P＜0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

AIM: To investigate the characteristics of changes in corneal epithelial thickness at the early postoperative stage of femtosecond assisted laser in situ keratomileusis(FS-LASIK)and its related influencing factors.METHOD: Retrospective study. A total of 120 patients(240 eyes)of myopia undergoing FS-LASIK from May 2021 to June 2022 were selected. The corneal epithelium thickness in the central area, inner ring area, and outer ring area of patients before and at 1d, 1wk, 1 and 3mo after operation was recorded. The relationship between the variation of corneal epithelium thickness and spherical equivalent, optical zone diameter, depth of cut and cutting ratio was analyzed by Pearson correlation.RESULTS: There was no statistical significance in corneal epithelial thickness in the central area, inner ring area and outer ring area at 1d after FS-LASIK compared with that before operation(P>0.05). At 1wk, 1 and 3mo after surgery, the corneal epithelial thickness in the central area, inner ring area and outer ring area increased compared with that before surgery, and the corneal epithelial thickness in the central area and inner ring area at 1 and 3mo after surgery was greater than that in the outer ring area(all P<0.05). The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thicker than that of low and moderate myopia patients before operation. The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thinner than that of low and moderate myopia patients at 1wk after operation(P<0.05). At 1 and 3mo after operation, the corneal epithelial thickness in the central, inner and outer ring areas of patients with high myopia was greater than that of patients with low and moderate myopia, and the changes of corneal epithelial thickness in the central, inner and outer ring areas were greater than those of patients with low and moderate myopia(P<0.05). The results of Pearson correlation showed that the changes in corneal epithelial thickness in the central and inner ring area were positively correlated with the corneal curvature, depth of cut and cutting ratio at 3mo after surgery, and they were in negative correlation with the age, spherical equivalent and optical zone diameter(P<0.05).CONCLUSION: The corneal epithelial thickness of patients thickened after the FS-LASIK operation, and it was correlated with age, corneal curvature, preoperative depth of cut, cutting ratio, spherical equivalent and the optic zone diameter.

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L

Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.
Humans ; Animals ; Serotonin ; Insular Cortex ; Pruritus/chemically induced* ; Cerebral Cortex/physiology* ; Neurons

Objective Current data are insufficient for comparisons of effectiveness between percutaneous coronary intervention(PCI)and coronary artery bypass grafting(CABG)among patients with coronary artery disease(CAD)and left ventricular dysfunction.Methods A total of 905 CAD patients with reduced left ventricular ejection fraction(LVEF≤35％)in single center of China who underwent either PCI or CABG were enrolled in a real-world cohort study.Clinical outcomes included short-and long-term all-cause mortality,rates of heart failure(HF)hospitalization and repeat revascularization.Propensity score matching was used to balance the 2 cohorts.Results PCI was associated with lower 30-day mortality rate(HR 0.29,95％CI 0.09-0.88,P=0.029).At a mean follow-up of 4.5 years,PCI and CABG had similar all-cause death(HR 1.00,95％CI 0.67-1.50,P=0.990)and HF hospitalization(HR 0.81,95％CI 0.40-1.64,P=0.561),but PCI had higher risk of repeat revascularization(HR 14.46,95％CI 3.43-60.98,P＜0.001).PCI was associated with more significant LVEF improvement than CABG(P=0.031 for interaction).Conclusions CAD patients with reduced LVEF who underwent PCI had lower short-term mortality rate and more LVEF improvement but higher risk of repeat revascularization during follow-up than patients who underwent CABG.PCI showed comparable long-term survival and HF hospitalization risk.