1.In Vitro and in Vivo Evaluation of Scutellarin-phospholipid Complex Nanoemulsion and Analysis of Its Activity in Ameliorating LPS-induced Vascular Endothelial Injury
Tian LUO ; Zhiyong HE ; Xiangjun MAO ; Xue LIU ; Jinggang HE ; Yuan ZHI ; Xiangchun SHEN ; Qianli XU ; Ling TAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):159-168
		                        		
		                        			
		                        			ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion(SCU-PC-NE), such as release, cell uptake and tissue distribution, and to investigate its effect on ameliorating lipopolysaccharide(LPS)-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC, ethyl oleate, Kolliphor HS15, 1,2-propylene glycol(50, 400, 514.3, 85.7 mg), respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope, the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis, thiazolyl blue(MTT) colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells(HUVECs), the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe, the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS(1 mg·L-1) and HUVECs, the effect of SCU-PC-NE on the levels of interleukin(IL)-1β and IL-6 were determined by enzyme-linked immunosorbent assay(ELISA), 18 Kunming male mice were randomly divided into blank group, model group, blank preparation group(equivalent to high dose group), SCU group and SCU-PC-NE low and high dose groups(5, 10 mg·kg-1), 3 mice in each group, and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h, equal volume of normal saline was given to the blank group and the model group, and the drug was administered for 4 consecutive times. Except for the blank group, the endothelial inflammatory injury was induced by intraperitoneal injection of LPS(10 mg·kg-1) at 12 h before the last administration in each group. Hematoxylin-eosin(HE) staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light, mostly spherical with rounded appearance and relatively uniform particle size distribution, with the average particle size of 35.31 nm, Zeta potential of 7.23 mV, and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group(P<0.01). Compared with normal mice, the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen, kidney, brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS(P<0.05, P<0.01), especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group(P<0.05, P<0.01), and compare with the model group, all administration groups significantly down-regulated IL-1β level, with the strongest effect in the SCU-PC-NE high-dose group(P<0.01), and all administration groups significantly down-regulated IL-6 level, with the strongest effect in the SCU-PC-NE low-dose group(P<0.05). Compare with the blank group, the results of HE staining showed that the endothelial cells were damaged, the elastic fibers were broken and arranged loosely in the model group, although similar vascular injury could be observed in the blank preparation group, SCU group and SCU-PC-NE low-dose group, the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE, which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS, suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU. 
		                        		
		                        		
		                        		
		                        	
2.Predictive Value of Lymphocyte Count Changes on Checkpoint-inhibitor-related Pneumonitis in Patients with Non-small Cell Lung Cancer
Zhiyong WANG ; Yingsong ZHANG ; Yuewen LI ; Ling FU ; Li ZHUANG
Cancer Research on Prevention and Treatment 2023;50(8):772-776
		                        		
		                        			
		                        			Objective To investigate the correlation of peripheral blood lymphocyte, T-cell, Th-cell, and Ts-cell counts with the development of checkpoint-inhibitor-related pneumonitis in NSCLC. Methods The clinical data of 85 patients with NSCLC treated with immune checkpoint inhibitors (ICIs) were retrospectively analyzed.Paired 
		                        		
		                        	
3.Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study
Ruihua BA ; Lixia TANG ; Wei SHEN ; Lian WANG ; Zhi ZHENG ; Xinzhu LIN ; Fan WU ; Qianxin TIAN ; Qiliang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Yumei WANG ; Bizhen SHI ; Ling LIU ; Jinghui ZHANG ; Yanmei CHANG ; Xiaomei TONG ; Yan ZHU ; Rong ZHANG ; Xiuzhen YE ; Jingjing ZOU ; Huaiyu LI ; Baoyin ZHAO ; Yinping QIU ; Shuhua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wenli ZHOU ; Hui WU ; Zhiyong LIU ; Dongmei CHEN ; Jinzhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chunyan YANG ; Ping XU ; Yayu ZHANG ; Sile HU ; Hua MEI ; Zuming YANG ; Zongtai FENG ; Sannan WANG ; Eryan MENG ; Lihong SHANG ; Falin XU ; Shaoping OU ; Rong JU
Chinese Pediatric Emergency Medicine 2022;29(6):433-439
		                        		
		                        			
		                        			Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.
		                        		
		                        		
		                        		
		                        	
4.Urinary retinol binding protein and β 2-microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients
Simin LI ; Yan'ai WANG ; Wei LIU ; Zhiyong WU ; Ling CHEN ; Xiaoling CAI ; Rui ZHANG ; Wenjia YANG ; Yan LIU ; Yumin MA ; Siqian GONG ; Simin ZHANG ; Qian REN ; Xueyao HAN ; Linong JI
Chinese Journal of Internal Medicine 2021;60(5):438-445
		                        		
		                        			
		                        			Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.
		                        		
		                        		
		                        		
		                        	
5.Comparison of effects of different anesthetic methods on prognosis in patients with stage Ⅲ breast cancer
Mohan LI ; Lijian PEI ; Chen SUN ; Ling LAN ; Yuelun ZHANG ; Zhiyong ZHANG ; Gang TAN ; Yuguang HUANG
Chinese Journal of Anesthesiology 2021;41(3):300-305
		                        		
		                        			
		                        			Objective:To compare the effects of different anesthetic methods on the prognosis in the patients with stage Ⅲ breast cancer.Methods:Based on a multicenter randomized controlled trial (NCT00418457), 274 patients with untreated stage Ⅲ breast cancer, aged 18-85 yr, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, were enrolled in the study and assigned to thoracic paravertebral block (TPVB) combined with total intravenous anesthesia group (TPVB+ TIVA group, n=141) and general anesthesia group (GA group, n=133) by computer-generated randomization stratified by study site.The primary outcome parameter of this study was postoperative recurrence rate.The secondary outcome parameters were the degree of postoperative acute pain (assessed using visual analogue scale score), the incidence of postoperative nausea and vomiting (PONV), postoperative hospital stay time, and the incidence of persistent pain after breast cancer surgery (PPBCS) at 6 and 12 months after surgery (assessed using the modified Brief Pain Inventory). Results:Compared with group GA, no significant change was found in the postoperative recurrence rate ( HR=0.711, 95% confidence interval (CI) 0.418-1.210, P=0.209), the degree of postoperative acute pain and the incidence of PONV were decreased (mean difference ( MD) of visual analogue scale score -0.890, 95% CI -1.344--0.436, P<0.001; OR=0.236, 95% CI 0.083-0.674, P=0.007), and no significant change was found in postoperative hospital stay time and the incidence of PPBCS ( HR=1.000, 95% CI 0.778-1.286, P=1.000; OR=2.100, 95% CI 0.599-7.362, P=0.246) in group TPVB+ TIVA. Conclusion:Compared with general anesthesia alone, TPVB combined with total intravenous anesthesia can provide lower degree of postoperative acute pain and lower incidence of PONV, and exert no effects on postoperative recurrence, postoperative hospital stay time and PPBCS in patients with stage Ⅲ breast cancer.
		                        		
		                        		
		                        		
		                        	
6.Myofascial self-release law
Zhiyong HOU ; Xingui WANG ; Yingchao YIN ; Ruipeng ZHANG ; Ling WANG ; Chen FENG ; Xin XING ; Jialiang GUO ; Lin JIN ; Junfei GUO ; Ze GAO ; Yingze ZHANG
Chinese Journal of Trauma 2019;35(1):83-86
		                        		
		                        			
		                        			Osteofascial compartment syndrome (OFCS) is clinically common and is well known to orthopedic surgeons.Clinicians attach great importance to OFCS because of its severe clinical consequences,and decompression of fascial compartment is often performed in emergency treatment.This article reviews the literature on the threshold of fascial compartment decompression proposed by many scholars in the past and discusses the problems in the clinical diagnosis of acute compartment syndrome,especially the inconsistent pressure thresholds as the indication for emergency decompression surgery.By observing calf fractures patients with tension blister,we found that the pressure of fascia decreased sharply upon the appearance of blisters.Meanwhile,the swelling gradually subsided as well as the clinical manifestations of pain and parasthsia.In view of the uncertainty of various thresholds of fascial decompression and self-decompression,the concepts of myofascial self-release law and muscle-swelling syndrome were first proposed.The author believes that when intracompartmental pressure rises to a point,some unknown mechanisms of fascia can achieve self-decompression.Therefore,no compartment syndrome will take place.We also emphasize that the ' muscle-swelling syndrome'should be strictly distinguished from the soft tissue necrosis caused by crush syndrome and acute limb vascular injury,so as to provide more precise treatment.We believe that without external restrictions such as casts,splints and compression bandages,the muscle-swelling syndrome can achieve self decompression by releasing the pressure in the compartment through tension blisters,and there is no need for fasciotomy.
		                        		
		                        		
		                        		
		                        	
7.Clinical significance of apolipoprotein F in prognosis of patients with hepatocellular carcinoma
Boxuan ZHOU ; Zhicheng YAO ; Zhiyong XIONG ; Ruixi LI ; Tianxing DAI ; Mingxing XU ; Weiming FAN ; Zheng ZHOU ; Hao LIANG ; Meihai DENG ; Yunbiao LING
Chinese Journal of Hepatic Surgery(Electronic Edition) 2018;7(1):73-76
		                        		
		                        			
		                        			Objective To investigate the expression of apolipoprotein (Apo) F in hepatocellular carcinoma (HCC) and its application value in the prognosis of patients with HCC. Methods 50 HCC samples were procured from patients undergoing surgical resection in the Third Affiliated Hospital of Sun Yat-sen University between September 2015 and September 2016, and all the samples were confirmed by postoperative pathological examination. The informed consents of all patients were obtained and the local ethical committee approval was received. There were 37 males and 13 females, aged from 31-67 with a median age of 53 years old. The expression of ApoF mRNA in HCC tissues was detected by RT-PCR. The expression profile was analyzed by using data from the Gene Expression Omnibus (GEO). The expression of ApoF between two groups were compared by t test. Correlation analysis of clinical related parameter was conducted by Chi-square test, and survival prognosis was analyzed by Kaplan-Meier test and Log rank test. Results The average relative expression of ApoF mRNA in HCC tissues was 0.15±0.07, significantly lower than 0.55±0.09 in the adjacent tissues (t=-6.26, P<0.05). GEO online analysis showed that expression of ApoF was significantly correlated with the status of liver cirrhosis, and most HCC patients with liver cirrhosis presented low expression of ApoF (χ2=4.626, P<0.05). The 5-year disease-free survival was respectively 55.9% and 32.0% in ApoF high expression group and low expression group, where significant difference was observed (χ2=3.939, P<0.05). Conclusions Low expression of ApoF exists in HCC tissues, and it is related to the liver cirrhosis status of patients. Patients with low ApoF expression present poorer prognosis. ApoF plays a role in inhibiting the cancer.
		                        		
		                        		
		                        		
		                        	
8.Preparation and Characterization of Aspirin Phospholipid Complex
Zhiyong HE ; Chaohua WU ; Junli YAN ; Haizhi LI ; Xiangchun SHEN ; Ling TAO
China Pharmacy 2017;28(25):3562-3565
		                        		
		                        			
		                        			OBJECTIVE:To prepare aspirin phospholipid complex (ASP-PC) and conduct the characterization. METHODS:Using the combination rate of ASP and PC as index,single factor test was used to screen the preparation method of ASP-PC,PC type,solvent type,reaction time,reaction temperature,solvent volume and drug-lipid ratio. The verification test was conducted. UV spectrophotometry,Thermogravimetric analysis,X-ray diffraction and Fourier transform infrared spectroscopy were used for the characterization of ASP-PC. RESULTS:Magnetic stirring-condensing reflux method was adopted,drug-soybean phospholipids ratio was 1:3 (mol/mol),solvent was tetrahydrofuran,reacting for 3 h under 58 ℃. The average combination rate of prepared ASP-PC was 83.52%(RSD=1.16%,n=3). Compared with ASP,physical mixture of ASP and PC,UV spectrum showed that ASP-PC had no new absorption peak. Thermogravimetric analysis,X-ray diffraction and Fourier transform infrared spectroscopy showed the ASP and PC in ASP-PC were interacted;and ASP-PC changed little in quality within 0-300 ℃. CONCLUSIONS:ASP-PC can be successfully prepared,in which,ASP and PC were combined successfully;while there are still trace amounts of ASP in the form of crystals.
		                        		
		                        		
		                        		
		                        	
9.Amplitude of low frequency fluctuations abnormalities in liver cirrhosis patients before and after liv-er transplantation:a resting-state fMRI study
Hongying HAN ; Wusheng LIN ; Ling LI ; Guihua CHEN ; Zhiyong ZHONG
Chinese Journal of Behavioral Medicine and Brain Science 2017;26(12):1101-1105
		                        		
		                        			
		                        			Objective To investigate regional activity abnormalities of patients with liver cirrhosis before and after liver transplantation using resting-state fMRI and amplitude of low frequency fluctuations (ALFF)method.Methods Totally 11 patients preparing to accept liver transplantation were adopted into liver cirrhosis group and 11 healthy volunteers in the health examination were adopted into the control group. The liver cirrhosis group was investigated at a week before operation and repeatedly a month after liver trans-plantation.Healthy volunteers were investigated at the same time.MR imaging data were obtained from a Phil-ips Achieva 1.5-T MR imager.The imaging data were mainly preprocessed with a MATLAB toolbox called DPARSF.REST software was used to calculate the ALFF value of each subject.A second-level random-effect two-sample t-test was performed on the individual ALFF.Significant differences were set at the standard of a corrected cluster level of P<0.05,and software Xjview 8.1 was adopted to express the outcome.Results (1)Compared with control group,decreased ALFF were found in bilateral middle occipital gyrus(MOG) (MNI:x=36,y=-72,z=9),bilateral precuneus/cuneus(PCu/Cu)/posterior cingulated(PCC)(MNI:x=15,y=-66,z=24),left inferior parietal lobule(LIPL)(MNI:x=-39,y=-54,z=42),and bilateral para-central lobule/cingulate gyrus(MNI:x=3,y=-36,z=45)of cirrhosis patients,no increased ALFF were found.(2)Compared with cirrhosis patients,no increased or decreased ALFF were found in postoperative group.After relaxing standards of statistics,increased ALFF were found in left inferior parietal lobule(IPL) (MNI:x=-39,y=-51,z=42),cingulate gyrus(MNI:x=3,y=-33,z=42),and right middle frontal gyrus (MNI:x=35,y=57,z=0)of postoperative group,no decreased ALFF were found.(3)Compared with control group,decreased ALFF were found in bilateral precuneus/posterior cingulated(PCC),and left middle occipi-tal gyrus(MOG)of postoperative group,no increased ALFF were found.Conclusions Significant decreased ALFF is found in visual cortex(PCu),DMN((PCu/Cu/PCC),and LIPL of cirrrhosis patients,and those ab-normalities reflect the weakness of local neurons spontaneous low-frequency.Compared with beforeoperative group,ALFF of LIPL,in cingulate gyrus,and right middle frontal gyrus have a tendency of rising.One month after liver transplantation,decreased ALFF is found in BA7 and BA 31,suggesting that the spontaneous low-frequency of local neurons haven't recoverd to normal level.
		                        		
		                        		
		                        		
		                        	
10.Pharmacokinetic and Bioavailability Study of Aspirin Phospholipid Complex Self-microemulsion in Rats in vivo
Yini XU ; Yi WANG ; Junli YAN ; Zhiyong HE ; Xue ZHOU ; Xiangchun SHEN ; Ling TAO
China Pharmacy 2017;28(31):4373-4376
		                        		
		                        			
		                        			OBJECTIVE:To study the pharmacokinetics behaviors and the bioavailability of aspirin phospholipid complex self-microemulsion in rats in vivo. METHODS:12 SD rats were randomly divided into aspirin suspension group(10 mg/kg)and as-pirin phospholipid complex self-microemulsion group (10 mg/kg),6 in each group. Rats were intragastrically administrated,and blood sample 0.6 mL was taken from jugular vein before administration and after 0.083,0.25,0.5,0.75,1.0,2.0,3.0,4.0,6.0, 8.0,12.0 h of administration. HPLC was used to determine the concentration of salicylic acid in rats'plasma. DAS 2.0 pharmacoki-netic software was adopted to calculate the pharmacokinetic parameters and relative bioavailability. RESULTS:The pharmacokinetic processes of both aspirin suspension and aspirin phospholipid complex self-microemulsion were in line with one-compartment mod-el. The salicylic acid of cmax of rats in aspirin suspension group and aspirin phospholipid complex self-microemulsion group were (1.904 ± 0.208),(6.457 ± 1.091) μg/mL;AUC0-12 h were (12.860 ± 1.327),(47.270 ± 12.860) μg/(h·mL);tmax were (2.167 ± 0.983),(0.917±0.540)h,respectively. Compared with aspirin suspension,salicylic acid of cmax and AUC0-12 h of aspirin phospholip-id complex self-microemulsion in rats in vivo were significantly increased (P<0.01),while tmax was significantly decreased (P<0.05);the relative bioavailability was 367.57%. CONCLUSIONS:Making aspirin into phospholipid complex self-microemulsion can improve the gastrointestinal absorption,with high relative bioavailability.
		                        		
		                        		
		                        		
		                        	
            
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