Objective To investigate the protective effect and mechanism of hyperoside(HYP)on paraquat(PQ)-induced acute lung injury in rats.Methods Rats were randomly divided into the control group,the PQ group,the low-dose hyperoside group(HYP-L group),the middle-dose hyperoside group(HYP-M group)and the high-dose hyperoside group(HYP-H group),with 12 rats in each group.After 7 days of corresponding treatment,the levels of interleukin(IL)-1β,IL-6 and macrophage inflammatory protein-2(MIP-2)in bronchoalveolar lavage fluid(BALF)of rats in each group,as well as the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in lung tissue were detected.The degree of lung injury and fibrosis of rats were evaluated by hematoxylin-eosin(HE)staining and Masson's trichrome staining.The expression levels of E-cadherin,α-smooth muscle actin(α-SMA),Vimentin,and protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),nuclear factor-κB(NF-κB)p65,p-NF-κB p65,transforming growth factor-β1(TGF-β1),Smad3 and p-Smad3 in lung tissue were detected by Western blot.Results Compared with the control group,the levels of IL-1β,IL-6 and MIP-2 in BALF of rats in the PQ group increased(P<0.05),the level of SOD in the lung tissue decreased,while the level of MDA increased(P<0.05),and the lung tissue showed obvious damage and fibrosis(P<0.05).Compared with the PQ group,the levels of IL-1β,IL-6 and MIP-2 in BALF of rats in the HYP-L group,the HYP-M group and the HYP-H group decreased(P<0.05),the levels of SOD in the lung tissue increased(P<0.05),while the levels of MDA decreased(P<0.05),and the lung tissue damages were alleviated,and the fibrosis score decreased(P<0.05).Compared with the control group,the expression level of E-cadherin in the lung tissue of rats in the PQ group decreased(P<0.05),the expression levels of α-SMA and Vimentin increased(P<0.05),the protein expression level of Nrf2 decreased(P<0.05),the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins increased(P<0.05).Compared with the PQ group,the expression levels of E-cadherin in the lung tissues of rats in the HYP-L group,the HYP-M group and the HYP-H group increased(P<0.05),the expression levels of α-SMA and Vimentin decreased(P<0.05),the protein expression levels of Nrf2 increased(P<0.05),the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins decreased(P<0.05).Conclusion Hyperoside effectively alleviates paraquat-induced acute lung injury in rats,and it may reduce lung oxidative stress,inflammation and fibrosis by regulating Nrf2,NF-κB and TGF-β1/Smad2/3 signal pathways.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Objective:To develop a task-oriented exercise(TOE)program suitable for hospitalized elderly frailty patients, and to evaluate its effects on patients' upper and lower limb mobility and activities of daily living.Methods:Using the convenience sampling method, 60 elderly frailty patients admitted to Beijing Hospital between August and December 2019 were selected and randomly divided into a TOE group and a conventional care group, with 30 in each group.In addition to conventional treatment and care, the TOE group performed task-oriented training(turning to fetch objects and multidirectional stepping), while the conventional care group performed aerobic training and resistance training.Both groups completed 10 training sessions.Baseline data of patients in both groups were assessed before intervention.Grip strength(as a measure of upper limb motor function), the motor component of the World Health Organization disability assessment schedule(WHODAS)2.0(as a measure of lower limb motor function), and the modified Barthel index(as measure of the ability to perform activities of daily living)were assessed after intervention.Results:Before intervention, the grip strength values of the TOE group and the conventional care group were(20.21±6.39)kg and(17.61±10.59)kg, and the scores of the motor component of WHODAS 2.0 were(16.07±6.64)and(20.23±1.18), respectively.After intervention, the grip strength value and the score of the motor component of WHODAS 2.0 of the TOE group were(22.13±5.97)kg and(12.86±5.17)kg, respectively, with statistically significant differences compared with those of the conventional care group, which were(19.05±9.16)kg for grip strength and(15.67±1.11)for the motor component of WHODAS 2.0( t=2.005, P=0.049; t=-18.210, P<0.001).The value of grip strength and the score of the motor component of WHODAS 2.0 were higher post-intervention than pre-intervention in the TOE group( t=5.005、-5.291, P<0.001 for both), but they showed no statistical differences in the conventional care group( t=0.247、1.614, P=0.806, 0.112).After intervention, the total modified Barthel index scores of the TOE and conventional care groups were (55.27±37.12)and(57.27±33.39), respectively, higher than the pre-intervention scores, which were(42.27±29.92)and(40.54±20.55), respectively(both P<0.05).There was no statistical difference in total Barthel score between the two groups after intervention( t=1.042, P=0.303). Conclusions:For hospitalized elderly frailty patients, the TOE program is simple, easy to implement, safe and effective, and can not only achieve the same purpose of improving the ability to perform activities of daily living as the conventional exercise program, but also improve the performance of upper and lower limb motor function more quickly.

Objective:To explore the correlation of early urinary continence(UC)after laparoscopic radical prostatectomy(LRP)with relevant preoperative MRI parameters of the urinary tract structure and provide some theoretical evidence for screening the high-risk population with postoperative urinary incontinence.Methods:This study included 49 PCa patients aged 50-78 years trea-ted by LRP in Beijing Tongren Hospital from January 2015 to February 2021,and all followed up for 12 months.We collected the com-plete baseline data on the patients,the clinical data possibly related to early postoperative UC,the MRI anatomical parameters associat-ed with UC,and the data on the recovery of early postoperative UC.We recorded the number of urinary pads used,submitted the data obtained to SPSS 23.0 statistical analysis,and identified the possible relevant factors by univariate correlation analysis,followed by R40.3 or SPSS 23.0 multivariate logistic regression analysis of the included factors and the results of UC.Results:MRI images mani-fested that the prostate anteroposterior diameter averaged(4.0±1.11)cm,the transverse diameter(4.6±0.83)cm,the cephalo-caudal diameter 2.4-6.4 cm,the membranous urethral length(MUL)(13.16±3.52)mm,and the thickness of the urethral rhab-dosphincter(URS)1.08-4.37 mm.Multivariate analysis showed that age was significantly correlated with the recovery of UC at 1 month after LRP(P=0.035,OR=0.16),and so was the URS thickness at 3 months(P=0.011,OR=0.02),9 months(P=0.014,OR=0.039)and 12 months(P=0.014,OR=0.039).Urinary incontinence with the URS thickness ≤1.6 mm at 12 months after operation was found of a high severity(P=0.010,OR[95％CI]=0.858-6.240).The MUL was positively correla-ted with the recovery of UC at 9 months(P=0.024,OR=0.508)and 12 months(P=0.024,OR=0.508)postoperatively.Correlation analysis revealed that the prostate volume,prostate diameter and other factors included in this study were not significantly correlated to postoperative UC.Conclusion:The thickness of the URS is positively correlated with the recovery of early UC,the thinner the URS,the severer the UC,and so is MUL.Age is an independent risk factor for the recovery of UC at 1 month after LRP.These findings need to be further verified by more prospective studies with long-term follow-ups.

Objective:To identify the key genes involved in the development and progression of prostate cancer(PCa)and those associated with the prognosis of the malignancy.Methods:We obtained the single-cell sequencing data on 4 cases of PCa from the GSE156632 database.Using R language and the Seurat package,we performed cell clustering and annotation,selected the subpop-ulations of epithelial cells for differential analysis after quality control and cell type identification,and conducted enrichment analysis of the identified differential genes using the Hiplot website.Then we downloaded the single nucleotide polymorphism(SNP)loci corre-sponding to the expression quantitative trait loci(eQTL)of these genes from the UK Biobank(UKB)database,and the clinical data and corresponding gene expression data on PCa patients from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),followed by univariate COX regression analysis of the impact of the genes on the prognosis of the patients after Mendelian ran-domization.Results:A total of 1 566 genes were identified and subjected to enrichment analysis,which indicated that the differenti-al genes might be enriched in the Ras,apoptosis and oxidative phosphorylation signaling pathways.Subsequent Mendelian randomiza-tion revealed 74 potential causal genes among the 1 566 genes,and univariate COX regression analysis of the 74 genes identified 4 pos-sibly related genes FAM3B,JUNB,TMEM59,and KRT5.Comparison of the results of Mendelian randomization and univariate COX regression showed that KRT5 might be the most important gene influencing PCa.Conclusion:FAM3B,JUNB,TMEM59 and KRT5 may play a role in the progression of PCa,and KRT5 may potentially serve as a prognostic predictor and therapeutic target for the malig-nancy.

As the number of patients suffering from cardiovascular diseases and peripheral vascular diseases rises, the constraints of autologous transplantation remain unavoidable. As a result, artificial vascular grafts must be developed. Adhesion of proteins, platelets and bacteria on implants can result in stenosis, thrombus formation, and postoperative infection, which can be fatal for an implantation. Polyurethane, as a commonly used biomaterial, has been modified in various ways to deal with the adhesions of proteins, platelets, and bacteria and to stimulate endothelium adhesion. In this review, we briefly summarize the mechanisms behind adhesions, overview the current strategies of surface modifications of polyurethane biomaterials used in vascular grafts, and highlight the challenges that need to be addressed in future studies, aiming to gain a more profound understanding of how to develop artificial polyurethane vascular grafts with an enhanced implantation success rate and reduced side effect.
Humans ; Polyurethanes ; Biocompatible Materials ; Blood Vessel Prosthesis/adverse effects* ; Cardiovascular Diseases

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

[Abstract] Objective To investigate the branching pattern of the ureteric bud and the number of the nephron induced by each ureteric bud tip, through the three-dimensional tracing of the ureteric tree, combined with the morphological analysis and measurement of the ureteric tree. Methods The kidneys were obtained from three mice at various developing time points and prepared for paraffin and epoxy sections. Then the microscopic images were digitized and aligned from these sections. Based on the computer-assisted tracing and visualization of ureteric tree, the number of branches and the nephron induced by each ureteric bud tip were obtained by counting. In addition, paraffin sections were stained with HE staining for morphological observation of nephrogenic zone and ureteric bud, while in order to reflect the density of the ureteric bud tips at nephrogenic zone, the distance between two neighboring ureteric bud tips was measured aided with the Claudin-7 immunohistochemical staining. Results The ureteric bud branching tree revealed that the initial bifid iterative branching formed the framework of renal medulla, the branching became complicated and dense in cortex and nephrogenic zone, while the distance between ureteric bud tips were also decreasing. The number of the nephron induced by each ureteric bud tip increased from one (E14. 5) to two (E17. 5), and occasionally to three. Conclusion Threedimeasional Visualization of ureteric bud branching tree reveals regional complication, suggesting molecules in different regions drive different branching patterns; While the density of the ureteric bud tips at nephrogenic zone increases corresponding to decreasing of thickness of the nephrogenic zone, and the disappearance of the ureteric bud tips after birth is also consistent with the gradual consumption of nephron progenitor cells.

OBJECTIVE: To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice. METHODS: Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice. RESULTS: After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05). CONCLUSION Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.
Mice ; Female ; Animals ; Genistein ; Lymphoma ; Cyclophosphamide ; Thrombophilia ; Inflammation ; Lectins, C-Type

Objective To compare and analyze the disease burden caused by drinking in China in 1990 and 2019. Methods The global disease burden database 2019 was used to analyze the attribution score (PAF), mortality, disability adjusted life year (DALY) and other indicators attributed to drinking in China in 1990 and 2019. The disease burden caused by alcohol consumption was compared between China and the world as well as different social demographic index (SDI) regions. Results From 1990 to 2019, the PAF attributed to drinking increased by 12.85%. The number of deaths attributed to drinking increased to 514 700, and the mortality increased to 36.18/100 000, while the DALY attributed to drinking increased to 17.2651 million person-years, and the DALY rate increased by 5.16%. The disease burden attributed to drinking was higher in men than that in women, and the attributable mortality and DALY rate in the elderly over 70 years old were higher than those in the young. From 1990 to 2019, the attributable disease burden of esophageal cancer was the highest in China, followed by colorectal cancer. Compared with the world and different SDI regions, China had the lowest standardized DALY rate attributed to drinking. Conclusion Drinking is one of the important risk factors for related diseases and cancers in China, and effective intervention measures should be taken for key populations.