1.Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway
Mengdi CUI ; Jiawei GAO ; Lvqun ZHU ; Guisheng CHEN ; Yiliang CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):101-108
ObjectiveTo investigate the promotional effect of astragaloside on the repair and healing of chronic non-healing wounds and its mechanism. MethodA total of 60 male SD rats were constructed with full-layer skin defect wounds on the back, and except for the control (Con) group, the rest were constructed with non-healing wounds, which were then randomly divided into the sham-operation (sham) group, the low-dose astragaloside group, the high-dose astragaloside group, the astragaloside + LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] group, and the astragaloside + EX527 [silencing regulatory protein 1 (SIRT1) inhibitor] group. The percentage of wound area in each group was observed on the 2nd, 4th, 6th, and 8th days after wound molding. Collagen type Ⅰ alpha 1 (COL1A1) and alpha smooth muscle actin (α-SMA) expressions in the wound tissue were detected by immunofluorescence. Hematoxylin and eosin (HE) staining was performed to determine the pathological structure of the wound. The mRNA expression of inflammatory factors in the wound was measured by real-time polymerase chain reaction (Real-time PCR), and the expression of proteins related to the SIRT1/ nuclear factor (NF)-κB and PI3K/protein kinase B (Akt) signaling pathways in the wound was tested by Western blot. ResultCompared with the sham group, the percentage of postoperative wound area of rats in both low-dose and high-dose astragaloside groups gradually decreased with time, and the efficacy of the high-dose astragaloside group was better. Compared with the Con group, the fluorescence intensity of COL1A1 in wound tissue of the sham group decreased, while the expression of α-SMA increased. The epithelial tissue was severely damaged, with an increase in the thickness, and a large number of inflammatory cells were seen in the infiltration. The mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase (iNOS) was elevated. The protein expression of NF-κB p65, p-PI3K/PI3K, and p-Akt/Akt was elevated, while SIRT1 expression was decreased (P<0.05). Compared with the sham group, the fluorescence intensity of COL1A1 and α-SMA increased after astragaloside treatment. The number of epithelial cells increased, and the thickness decreased. The inflammatory cells decreased, and the amount of collagen increased. The mRNA expression of TNF-α, IL-1β, IL-6, and iNOS was decreased, and the protein expression of NF-κB p65, p-PI3K/PI3K, and p-Akt/Akt was decreased. SIRT1 was elevated, and the effect was better in the high-dose astragaloside group (P<0.05). Compared with the high-dose astragaloside group, inhibition of the PI3K/Akt and SIRT1 pathways by LY294002 and EX527 prevented the therapeutic efficacy of astragaloside on chronic non-healing wounds. ConclusionThe topical application of astragaloside significantly promotes the healing of chronic non-healing wounds in rats, and the mechanism may be related to the activation of the PI3K/Akt pathway and the SIRT1/NF-κB pathway.
2.Risk factors for cage retropulsion following transforaminal lumbar interbody fusion
Jintao XI ; Qilin LU ; Yang WANG ; Xiaojuan WANG ; Peng LYU ; Long CHEN ; Zhen SHI ; Wei XIE ; Yiliang ZHU ; Xugui LI
Chinese Journal of Tissue Engineering Research 2024;28(9):1394-1398
BACKGROUND:Previous literature reported that the fusion cage moved more than 2 mm from its original position,which means that the fusion cage moved backward.At present,clinical observation has found that the factors leading to the displacement of the fusion cage are complex,and the relationship between these factors and the cage retropulsion is not clear. OBJECTIVE:To explore the risk factors related to cage retropulsion after lumbar interbody fusion. METHODS:Retrospective analysis was conducted in 200 patients who underwent transforaminal lumbar interbody fusion surgery with a polyetheretherketone interbody fusion from February 2020 to February 2022.According to the distance from the posterior edge of the vertebral fusion cage to the posterior edge of the vertebral body after the operation(the second day after the removal of the drainage tube)and 1,3,6 and 12 months after the operation,patients were divided into cage retropulsion group(≥2 mm)and cage non-retropulsion group(<2 mm).The factors that may affect cage retropulsion,such as age,gender,body mass index,bone mineral density,operation time,bleeding,endplate injury,preoperative and postoperative interbody height,cage implantation depth,cage size,and segmental anterior convexity angle,were analyzed by univariate and logistic regression analysis. RESULTS AND CONCLUSION:(1)Posterior displacement of the fusion cage occurred in 15 cases(15/200).The differences in basic information such as age and body mass index between the two groups were not statistically significant.(2)The results of the univariate analysis were that gap height difference,time to wear a brace,segmental anterior convexity angle difference,bone mineral density,and age were related to posterior migration of the cage.(3)The results of logistic regression analysis were that cage size,endplate injury condition,and depth of cage implantation were risk factors for cage retropulsion.(4)These findings suggest that cage retropulsion after lumbar interbody fusion is caused by multiple factors,including segmental anterior convexity angle difference,bone mineral density,cage size,endplate damage,time to wear a brace,and depth of cage implantation.
3.Strontium ranelate-loaded sodium alginate/collagen hydrogel promotes bone defect repair in osteoarthritis
Kunyang SU ; Bineng CHEN ; Yiliang CHEN ; Shaofeng JIN
Chinese Journal of Tissue Engineering Research 2024;28(10):1568-1574
BACKGROUND:Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis,and treatment based on this pathological feature will be a promising improvement for osteoarthritis. OBJECTIVE:To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis. METHODS:(1)In vitro experiment:Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system,and the in vitro slow release performance of the system was characterized.Strontium ranelate-loaded sodium alginate/collagen hydrogel(experimental group)and alginate sodium/collagen hydrogel(control group)were co-cultured with bone marrow mesenchymal stem cells,respectively,and cultured cells were used as a blank control group to detect cell proliferative activity.After chondroblast-induced differentiation,saffron O staining,Alcian blue staining and RT-qPCR were performed respectively.The two hydrogels were co-cultured with osteoblasts,and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR.(2)In vivo experiment:A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy.After 1 week,the rats were divided into three groups by the random number table method:The blank group did not receive any treatment.The control group was injected with sodium alginate/collagen hydrogel in the knee,and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel,with 6 rats in each group.After 6 weeks,the samples were subjected to Micro-CT scanning,hematoxylin-eosin staining,saffron O-solid green staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)In vitro experiment:Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release of strontium ranelate.At 21 days,the cumulative release reached(60.89±0.58)%.Bone marrow mesenchymal stem cell staining showed that both hydrogels had good cytocompatibility.The results of the CCK-8 assay demonstrated that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote the proliferation of bone marrow mesenchymal stem cells.The results of Safranin O staining,Alcian blue staining,immunofluorescence staining and RT-qPCR exhibited that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote chondrogenic differentiation of bone marrow mesenchymal stem cells.Immunofluorescence staining and RT-qPCR revealed that strontium ranelate-loaded sodium alginate/collagen hydrogel could decrease bone resorptivity by increasing the ratio of osteophosphorin/nuclear factor κB receptor activator ligand.(2)In vivo experiment:Micro-CT scan verified that compared with the blank group and control group,the subchondral bone volume fraction and bone mineral density of the knee of rats were increased in the experimental group(P<0.05,P<0.01).Histological staining displayed that compared with the blank group and control group,the knee cartilage injury was significantly reduced;the expression of type II collagen was promoted,and the expression of matrix metalloproteinase 2 protein was inhibited in the experimental group(P<0.05,P<0.01).(3)These results confirm that the strontium ranelate-loaded sodium alginate/collagen hydrogel can promote the repair of cartilage defects in osteoarthritis and reconstruct the complex interface between cartilage and subchondral bone.
4.Proximal femoral nail antirotation Asian version for treating femoral intertrochanteric fractures:comparison of the protruding degree of intramedullary nails in Asian population
Anquan WANG ; Hao CHEN ; Xingyi HUA ; Xiaolin LU ; Jian ZHOU ; Yiliang CUI ; Guangyu LI ; Zongsheng YIN
Chinese Journal of Tissue Engineering Research 2024;28(12):1901-1906
BACKGROUND:Due to the mismatch between the design of the proximal femoral nail antirotation Asian version(PFNA-Ⅱ)and Asian population,extrusion of the proximal femoral intertrochanteric nail may occur in the treatment of femoral intertrochanteric fractures.The influence of the protruding length on the curative effect of the operation needs to be further discussed. OBJECTIVE:To quantitatively measure the protruding length of the proximal trochanter of the femur with intramedullary nail after PFNA-Ⅱ,and to analyze the effect of protruding length on the efficacy of PFNA-Ⅱ in the treatment of femoral intertrochanteric fractures. METHODS:Totally 68 patients with femoral intertrochanteric fractures treated with PFNA-Ⅱ internal fixation in the First Affiliated Hospital of Anhui Medical University were selected.The extramedullary process of the proximal trochanter of the femur was quantitatively measured on the anterior and posterior X-ray films of the hip joint within 6 months after operation.According to the existence of extrusion of the proximal trochanter intramedullary nail,the patients were divided into protruding group and non-protruding group.The data of sex,height,fracture type,length and diameter of the intramedullary nail,the position of screw blade in the femoral neck and protruding length of proximal greater trochanter were collected.The postoperative curative effect was judged by visual analog scale pain score and hip joint Harris score at 6 months after operation.The influence of protruding proximal trochanter of the PFNA-Ⅱ intramedullary nail on the operative effect was observed. RESULTS AND CONCLUSION:(1)There were significant differences in sexual characteristics between the protruding group and the non-protruding group(P=0.001).(2)According to AO/OTA classification,there were no significant differences in fracture type between the protruding group and the non-protruding group(P=0.289).(3)There was no significant difference in the length and diameter of the intramedullary nail between the two groups(P=0.067,P=1.000).(4)There was no significant correlation between the height of all patients and the length of the intramedullary nail(P=0.510),but there was a significant correlation between height and protruding length(P=0.034).There was no significant correlation between screw blade position and protruding length(P=0.968).(5)Six months after operation,there was no significant difference in the hip Harris score(P=0.373),but the visual analog scale pain score was significantly higher in the protruding group than that in the non-protruding group(P=0.000).(6)The results suggest that nail extrusion often occurs in the proximal greater trochanter when PFNA-Ⅱ is used in the treatment of intertrochanteric fractures in Asians.When the nail extended into the proximal soft tissue of the greater trochanter,patients complained of proximal greater trochanteric pain and the visual analog scale score of proximal greater trochanter pain in the patient was significantly higher than that in the non-protruding group.To be more suitable for the Asian population,we suggest that the PFNA-Ⅱ should be improved to further shorten the proximal nail end to obtain better clinical results of femoral intertrochanteric fracture fixation.
5.Generation and characterization of humanized monoclonal antibody against human IFNAR1
Jiwan QIU ; Yong KONG ; Wei CHEN ; Lei XU ; Chunjie CAO ; Tao CHEN ; Yiliang WU
Journal of China Pharmaceutical University 2024;55(3):404-411
Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus(SLE).Monoclonal antibody shows therapeutic potential by blocking the signaling pathway.This study used recombinant human subunit 1 of the type I interferon receptor(IFNAR1)protein to immunize New Zealand white rabbits,and applied B cell cloning technology to screen and obtain rabbit parental antibodies.After humanization modification,QX006N was obtained.In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L,and neutralize the type I interferon signaling pathway and this pathway mediated biological effects.This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.
6.Analysis of the epidemic characteristics and disease burden of hospitalized children with viral myocarditis in China from 2016 to 2021
Luci HUANG ; Wei SHAO ; Lingyun GUO ; Yiliang FU ; Fei LI ; Hui XU ; Guoshuang FENG ; Lu GAO ; Zhengde XIE ; Yue YUAN ; Gang LIU ; Xiangpeng CHEN
Chinese Journal of Experimental and Clinical Virology 2024;38(4):432-438
Objective:This study aimed to provide basic data for the prevention, diagnosis and treatment of pediatric viral myocarditis (VMC) in China through analyzing the epidemic characteristics and disease burden of pediatric inpatients with VMC from 2016 to 2021.Methods:We performed a descriptive statistical analysis to the age, genders, seasons, regions and hospitalization cost and days of pediatric VMC inpatients and the death. All of the information was obtained from 27 Children′s hospitals or Maternal and Child Health hospitals of 23 provinces of China from 2016 to 2021.Results:A total of 7 647 599 cases including 1 646 VMC inpatients were admitted into our study. The annual numbers of hospitalizations were 173, 227, 313, 301, 295 and 337, with the hospitalized constituent ratios being 14.9/100 000, 17.9/100 000, 23.0/100 000, 20.5/100 000, 26.5/100 000 and 26.4/100 000 from 2016 to 2021. In recent 6 years, the proportion of VMC hospitalizations had increased yearly ( P<0.001), and had associated with the onset age ( P<0.001). Aged 12-≤18 years owned the highest hospitalized constituent ratio. The Northeast of China owned the largest number of VMC inpatients, and the East second to it. Among the 1 646 VMC children, there were 68 deaths, with the hospitalized case fatality rate of 4.13%. There were no significant differences between genders, age, seasons, years and fatality rate of VMC inpatients. For the diseases burden, the median of hospitalization days of all VMC inpatients was 10 days (IQR 6, 21), and the median of hospitalization cost was 1 1 842.3 RMB (IQR 6 969.22, 19 714.78). The median of hospitalization days of deceased VMC children was only 1 day (IQR 1, 3), the median cost could be 8 874.03 RMB (IQR 5 277.94, 5 6 151.59). Conclusions:In this study, we found that proportion of hospitalization of VMC children increased year by year, adolescence might be a risk factor of VMC. The fatality of VMC inpatients could be up to 4.13%, and the death led to a huge economic burden of society, family and individuals.
7.Study based on the impact of the timeliness of the first elective operation start time on the operating room costs
Zhihao TAN ; Yiliang CAI ; Jinhuan FENG ; Qin LI ; Xiaozhen XU ; Shishen XU ; Yanfu HUANG ; Jiachen CHEN
Modern Hospital 2024;24(9):1407-1410
Objective To analyze the timeliness of the start time of the first elective operation in a hospital and observe its impact on the operating room cost.Methods Make statistics and analysis on the opening of the first operation in a hospital,record the on-time opening rate of the first operation,analyze the reasons for the delay in the opening time of the first operation,formulate corresponding intervention measures and set up a"management team to improve the efficiency of operating room use".The on-time rate of the first operation,operation,cost control and the satisfaction of surgeons and patients were compared before and after the operation.Results The overall punctuality rate of the first operation was 53.74%,among which the colorectal sur-gery department had the highest punctuality rate of 63.16%,while the minimally invasive surgery department had the lowest punctuality rate of 45.45%.The main reasons for the delay of first operation(35.29%),failed anesthesia(30.88%),and the termination of the operation(17.65%);compared with before implementation,higher overtime time of nurses,shorter opening time and expected time,decreased interval between operation(P<0.05),lower frequency of centralized delivery and unnecessa-ry consumables cost within 1 month after implementation(P<0.05),and higher satisfaction of patients and physicians after im-plementation(P<0.05).Conclusion By improving the first elective operation on time,can effectively reduce the cost of the operating room,shorten the nurse overtime time,at the same time improve the satisfaction of doctors and patients,and improve the management efficiency of the operating room,the first operation on time improved,interval time and unnecessary consumables costs are significantly reduced,optimize the use efficiency of the operating room resources.
8.Epidemic characteristics of soil borne nematode disease in Sihong County, Suqian City in 2022
Shuhui TIAN ; Xiaojun CHEN ; Qian XU ; Xiuhua ZHU ; Jiangshan MENG ; Zijiao WANG ; Yiliang WANG ; Guizhi SHE ; Chengzhong ZANG
Chinese Journal of Endemiology 2024;43(7):549-553
Objective:To study the infection and epidemiological characteristics of soil borne nematode disease in Sihong County, Suqian City, and to provide scientific basis for further development of prevention and control measures.Methods:In 2022, according to geographic location, Sihong County was divided into east and west areas. Jieji Town, Shiji Township, and Linhuai Town were selected from the east area, and Tianganghu Township, Meihua Town from the west area. One administrative village was selected as a survey point in each township. Using cluster sampling method, 450 permanent residents aged 3 years old and older in the village were selected as the respondents for questionnaire survey and fecal sample collection. The infection status of hookworms, roundworms, whipworms and pinworms in fecal samples were examined, transparent tape anal swab method for detecting pinworm eggs in children, and influencing factors were analyzed.Results:A total of 2 264 survey subjects were included, 18 cases of soil borne nematodes were detected as positive, with an overall positive rate of 0.80%. Among them, 15 cases were positive for hookworms, 1 case was positive for whipworms, and 2 cases were positive for pinworms, with detection rates of 0.66%, 0.04%, and 0.09%, respectively. No ascaris lumbricoides were detected. Transparent tape anal swab method was used to examine 142 children, and the positivity rate of 1.41% (2/142). By township, the detection rate of soil borne nematodes was the highest in Jieji Town, at 2.41% (11/457); the others were Meihua Town, Tianganghu Township, Shiji Township, and Linhuai Town, with detection rates of 0.89% (4/451),0.66% (3/454), 0 (0/451) and 0 (0/451), respectively. There was a statistically significant difference between different townships (χ 2 = 19.21, P < 0.001). Among the 18 positive cases of soil borne nematode, 7 were males and 11 were females, with detection rates of 0.66% (7/1 063) and 0.92% (11/1 201), respectively, the difference was not statistically significant (χ 2 = 0.47, P = 0.491). The age distribution showed the highest detection rate in the 40 - < 60 age group, at 1.42% (9/634), with statistically significant differences between different age groups (χ 2 = 6.41, P = 0.033). The occupational distribution showed the highest detection rate in farmers, at 1.46% (9/617), with statistically significant differences between different professions (χ 2 = 8.00, P = 0.034). The differences in total soil borne nematode and hookworm detection rates were statistically significant among different methods of treating human and animal feces (χ 2 = 11.01, 9.02, P = 0.003, 0.011). Conclusions:The main species of soil borne nematode infections in Sihong County, Suqian City are hookworms, with fewer infections of whipworms and pinworms, and no roundworm infections observed. There are regional differences in detection rate. In the future, it is necessary to strengthen health education for key populations, enhance health knowledge publicity, and effectively intervene to change unhealthy production and lifestyle, further reducing the infection of soil borne nematodes in Suqian City.
9.Research progress of boron-containing drugs
Fenghua DU ; Zhengchuan DONG ; Leyuan CHEN ; Wenbin HOU ; Yiliang LI
Journal of China Pharmaceutical University 2023;54(2):159-171
In recent years, the research on boron-containing drugs, especially boric acid drugs, has been increasing gradually.Boron-containing drugs, which have been a new area of research for pharmaceutical chemists in the development of new drugs, play an increasingly important anti-inflammatory, antibacterial, and anti-tumor role.At present, five boron-containing drugs have been approved, many are under clinical trials, and more are under investigation around the world, which has greatly expanded the application of boron in the research of new drugs.This paper introduces the characteristics of boron, and reviews the indications of representative boron-containing drugs in various research stages, their binding mechanisms with targets, and their progress after entering clinical trials, aiming to provide reference for further research on boron-containing drugs.
10.Analysis of the epidemic characteristics and disease burden of herpangina in hospitalized children in China from 2016 to 2020
Yiliang FU ; Hui XU ; Qi LI ; Guoshuang FENG ; Xiangpeng CHEN ; Zhengde XIE
Chinese Journal of Experimental and Clinical Virology 2023;37(1):7-12
Objective:To analyze the prevalence and burden of herpangina(HA)in Chinese children from 2016 to 2020, which provides basic data reference for the diagnosis, treatment and prevention and control of HA in China.Methods:The homepage information of hospitalized children with HA were collected from 27 children′s hospitals and maternal and child health hospitals in 23 provinces of China from 2016 to 2020 and the epidemiology, severity and disease burden of HA were descriptively and statistically analyzed.Results:A total of 24, 099 hospitalized children with HA were reported from 27 children′s hospitals and maternal and child health hospitals in 2016-2020. In all that the hospitalized children, the male-to-female ratio was 1.46∶1 and 23, 432 children (97.23%) were ≤ 6 years old. HA onset lasted from April to September and its peak was in June or July every year except 2020. The largest number of hospitalized children with HA were found in East China (8, 520/23, 849; 35.72%). During study years, the proportion of hospitalized children with HA among all admissions in 27 investigated hospitals was 0.42% (24, 099/5, 790, 910). In terms of regions, the highest proportion was in Northeast China 0.69% (1, 720/249, 244). A total of 1, 510 (6.27%) children were severe cases and the male-to-female ratio was about 1.35∶1; 1, 326 (87.81%) children were ≤ 3 years old and the highest proportion of severe cases was in 28 days to ≤ 1 years old children (7.47%, 784/10, 494). The median of expenses for hospitalized children with HA was 3, 570.41 RMB (IQR 2, 698.03-4, 747.30), and the median hospital stay was 5 days (IQR 4-6).Conclusions:HA onset in China was predominantly in summer and at the age of ≤ 6 years. Meanwhile, owing to a large number of hospitalized children with HA and the high expenditures they generated, HA caused a considerable disease burden.

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