1.Effect of electroacupuncture on the expression of P53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis
Xiarong HUANG ; Lizhi HU ; Guanghua SUN ; Xinke PENG ; Ying LIAO ; Yuan LIAO ; Jing LIU ; Linwei YIN ; Peirui ZHONG ; Ting PENG ; Jun ZHOU ; Mengjian QU
Chinese Journal of Tissue Engineering Research 2024;28(8):1174-1179
BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.
2.Pulsed electromagnetic fields inhibit knee cartilage degeneration in aged rats
Linwei YIN ; Xiarong HUANG ; Guanghua SUN ; Jing LIU ; Peirui ZHONG ; Jinling WANG ; Jiaqian CHEN ; Xing WEN ; Shaoting GAN ; Wentao HU ; Mengmeng LI ; Jun ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(28):4522-4527
BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.
3.Genetic evolution of Penton base, Hexon and Fiber genes of human adenovirus 3 in a clustered fever outbreak in Kunming
Yanyan LIU ; Wenpeng GU ; Zhongwen DUAN ; Yu WANG ; Jiao GONG ; Qiyan CHA ; Linwei WU ; Min HOU
Chinese Journal of Microbiology and Immunology 2024;44(3):241-248
Objective:To perform adenovirus detection and genetic evolutionary analysis on specimens from a fever outbreak in Kunming city.Methods:Pharyngeal swabs from typical febrile patients were collected and tested for nucleic acids of 30 common respiratory pathogens using TaqMan Array Card technology. The full-length sequences of three important genes of adenovirus, Penton base, Hexon and Fiber, were amplified, sequenced and typed using Nanopore high-throughput sequencing. A phylogenetic tree was constructed. Molecular variations and genetic evolution of the three genes were analyzed.Results:Five specimens were collected and all of them tested positive for adenovirus and Haemophilus influenzae. The sequences of the full-length coding regions of the Penton base, Hexon and Fiber genes were obtained by Nanopore sequencing. The homology of the three gene sequences in the five specimens was 100.0%, 99.9%-100.0% and 100.0% in nucleotide sequences, and 100.0% in amino acid sequences. The three genes in the specimens had the highest homology with those of the reference strain of human adenovirus type 3 (HAdV3, accession number: AY599834) in nucleotide sequences, which was 98.6%, 98.7% and 98.9%, respectively. Results of the phylogenetic analysis of the three genes were basically consistent. These Kunming strains were clustered into an independent clade with the reference HAdV3 strain and had a distant relationship with the strains isolated in foreign countries and Taiwan, China in the early years. They were closely related to the domestic and foreign strains in recent years and highly homologous to the 2019 Japanese strain (accession: LC703523) and the Guangzhou strain (accession: MZ540961). Compared with the reference strain, these Kunming strains had five amino acid variations in Penton base, 10 in Hexon and 11 in Fiber. Conclusions:All of the adenovirus strains isolated in this outbreak belong to P3H3F3 type based on the full-length sequences of Penton base, Hexon and Fiber genes. They share high homology with the domestic and foreign HAdV3 strains, including the reference strain. Compared with the reference strain, several amino acid mutations are identified in these Kunming strains, and most of them are in the high variability region or functional regions. M7L in the Hexon protein is an unique amino acid mutation site of Kunming strains.
4.Investigation of coordinated development between blood banks and apheresis plasma collection banks
Qun LIU ; Dunzhu GONGJUE ; Qian ZHANG ; Hui YE ; Hua SHEN ; Mingming QIAO ; Linwei LI ; Xingzhe ZHANG ; Xiangwen CHEN ; Liliang CHEN ; Yang LIU ; Yunlong ZHUANG
Chinese Journal of Blood Transfusion 2024;37(8):927-932
Objective To explore the factors that affect the coordinated development of blood banks and apheresis plas-ma collection banks(hereinafter referred to as plasma banks),and explore feasible measures for the coordinated develop-ment of blood banks and plasma banks.Methods The blood information management system and blood source information management system were used to retrieve related data of blood and plasma donation from 9 cities in Shandong province from 2017 to 2021.The number of blood donors and plasma donors and the intersection of them were analyzed.The data analysis was performed using chi-square test,and a questionnaire survey was conducted to investigate the policies and information status,as well as expectations for coordinated development for blood and plasma donation.Results From 2017 to 2021,the total number of blood donors in 9 cities was higher than that of plasma donors,both have been increasing year by year,and the increase in plasma donors was significantly higher than that of blood donors(131.78%vs 23.90%,P<0.05).The inter-section proportion of blood and plasma donors had increased from 0.45%in 2017 to 1.04%in 2021,with an increase of 131.11%.Among the administrative regions where the participating blood and plasma banks located,94.2%have not re-leased relevant policy to promote the coordinated development of blood and plasma donation.The majority(63%)expected blood banks and plasma banks to be set at a distance more than 50 km apart.The top four functional requirements for the in-terconnection between blood banks and plasma banks management information system were blood test results(94.61%),ID number(87.54%),blood and plasma donation records(85.51%)and health consultation/examination results(82.15%).The top four elements of coordinated development between blood and plasma banks were policy support(96.25%),informa-tion networking(92.36%),top-level design(87.44%)and cultural construction(86.58%).Conclusion The number of donors who donate both blood(mainly whole blood)and plasma has been increasing year by year,which deserves our close attention.To achieve the coordinated development of blood donation and plasma donation,policy support is the most crucial and fundamental means.Establishment of a standard system and the share of blood and plasma donation information is neces-sary for blood informatization construction.It was critical to promote the coordinated development of blood and plasma dona-tion and ensure blood safety with improving legislation,formulating policies for coordinated development,strengthening top-level design,standardizing the publicity of blood and plasma donation and establishing the idea that blood and plasma dona-tion are equally honorable.
5.Effect of mandibular third molar tooth germ extraction on mandibular development: a retrospective study
Linwei ZHENG ; Rui SUN ; Yangruoxuan LIU ; Lizhuo LIN ; Jihong ZHAO
Chinese Journal of Stomatology 2024;59(8):798-803
Objective:To investigate the effect of extraction of mandibular third molar (M3) tooth germ on the development of the mandible in orthodontic patients, with a view to providing a reference for clinical M3 tooth germ extraction.Methods:One hundred and twenty-nine Angel class Ⅰ malocclusion patients aged 10-16 years who attended the Department of Orthodontics Division 1, School & Hospital of Stomatology, Wuhan University from 1 January 2013 to 30 December 2021 and fulfilled the criteria for nativity were included. Those who had their M3 extracted in the Department of Oral and Maxillofacial Surgery were included in the study group, with a total of 66 cases; and those who did not have their M3 extracted were included in the control group, with a total of 63 cases. The average annual growth was calculated by tracing point measurements on cephalometric films before and after orthodontic treatment according to the Jarabak and McNamara methods, with measurements of the mandibular ramus height (Ar-Go′), mandibular body length (Go′-Me), and overall mandibular length (Co-Gn) values, respectively. The average annual growth of Ar-Go′, Go′-Me, and Co-Gn were compared between the two groups for the overall sample of patients, patients of the same sex (male/female), patients of the same age group (>10 and ≤12 years old, >12 and ≤14 years old, >14 and ≤16 years old), and patients of the same cervical vertebral maturation stage (stages Ⅱ, Ⅲ, and Ⅳ), respectively, to see if there was any difference in the average annual growth of Ar-Go′, Go′-Me, and Co-Gn.Results:There was no statistically significant difference in the average annual growth of Ar-Go′, Go′-Me, and Co-Gn between the study group [0.88 (0.40, 1.80), 0.67 (0.15, 1.18), and 0.86 (0.40, 1.90) mm, respectively] and the control group [1.08 (0.45, 1.60), 0.53 (0.25, 1.13), and 1.20 (0.46, 2.28) mm, respectively] ( P>0.05). In addition, there was no significant difference in the average annual growth in the Ar-Go′, Go′-Me, and Co-Gn between the groups for patients of the same sex group, patients of the same age group, and patients of the same cervical vertebral maturation stage group( P>0.05). Conclusions:Extraction of the mandibular third molar tooth germ has no significant effect on the development of the mandible in Angle class Ⅰ malocclusion patients.
6.Predictive value of Naples prognostic score on long-term outcome in patients with intrahepatic cholangiocarcinoma
Hang JIANG ; Xing CHEN ; Jia WU ; Fang HAN ; Chao HU ; Linwei XU ; Jiangshu LIU ; Yuhua ZHANG
Chinese Journal of General Surgery 2024;39(8):609-614
Objective:To investigate the predictive value of Naples prognostic score (NPS) in assessing the overall survival of intrahepatic cholangiocarcinoma (ICC) patients after receiving hepatectomy treatment.Methods:Clinicopathological characteristics and follow-up data of 164 ICC patients who underwent curative hepatectomy at Zhejiang Cancer Hospital from Jan 2010 to Aug 2022 were retrospectively collected. NPS was calculated basing on preoperative serum albumin concentration, total cholesterol concentration, the neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio. The relationship between NPS and overall survival was analyzed, and the efficacy of NPS in predicting long-term survival was compared to TNM staging system and other independent risk factors.Results:Multivariate analysis identified the NPS [Score 1 versus 0: 1.864 (1.011-3.437), P=0.046; Score 2 versus 0: 3.013 (1.465-6.199), P=0.003] as an independent risk factor for overall survival. The area under curve (AUC) of the rece中iver operating characteristic (ROC) curve for predicting 5-year OS based on NPS is 0.75, which is higher than TNM staging (0.59) and other independent risk factors (CA19-9:0.71, lymph node metastasis: 0.66, tumor size: 0.62, microvascular invasion: 0.56). Conclusion:NPS as an independent predictor of overall survival for ICC patients, is more accurate than TNM staging system and other clinicopathological factors.
7.Predictive value of Pcv-aCO 2 on left ventricular ejection fraction in myocardial infarction
Chao YANG ; Jie LIN ; Chunjin LIN ; Guojian XIANG ; Linwei LIU ; Tingting SHI ; Yonghong ZHENG
Chinese Journal of Emergency Medicine 2023;32(5):667-673
Objective:To investigate the relationship between central venous-arterial blood carbon dioxide partial pressure difference (Pcv-aCO 2) and left ventricular ejection fraction(LVEF) in acute myocardial infarction. Methods:Clinical data of patients with acute myocardial infarction admitted to the Intensive Care Unit of Fujian Provincial Hospital from November 2019 to October 2021 were retrospectively analyzed. LVEF was measured by bedside echocardiogram. The patients were divided into the normal LVEF group (LVEF ≥ 52%) and decreased LVEF group (LVEF < 52%) according to LVEF. The differences in general information and hemodynamic parameters between the two groups were compared. The normality of the above data was tested by the Jarque-Bera test. Correlation analysis of hemodynamic indices with LVEF was performed. Binary logistic regression was used to analyze the risk factors associated with the decrease in LVEF. The feasibility of diagnosing LVEF decline with Pcv-aCO 2 was assessed using receiver operating characteristic (ROC) curve. Results:Seventy-two patients with acute myocardial infarction were included for analysis, including 25 patients in the normal LVEF group and 47 patients in the decreased LVEF group. Pcv-aCO 2 was significantly higher in the decreased LVEF group than that in the normal LVEF group [(7.13±1.19) mmHg vs. (5.41±1.23) mmHg, P<0.01]. There was a negative correlation between LVEF and Pcv-aCO 2 ( rs= -0.740, P<0.01). The area under the ROC curve for Pcv-aCO 2 was 0.849 (95% CI: 0.758-0.939, P<0.01). The binary logistic regression analysis showed that Pcv-aCO 2 was an independent risk factor for decreased LVEF ( OR=2.251, 95% CI: 1.326-3.820). Conclusions:To a certain extent, the increase of Pcv-aCO 2 can predict the decrease of LVEF in acute myocardial infarction.
8.All-stage targeted therapy for the brain metastasis from triple-negative breast cancer.
Zimiao LUO ; Sunyi WU ; Jianfen ZHOU ; Weixia XU ; Qianzhu XU ; Linwei LU ; Cao XIE ; Yu LIU ; Weiyue LU
Acta Pharmaceutica Sinica B 2023;13(1):359-371
Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.
9.A successful liver transplantation from an 81-year-old donor and literature review
Jia YU ; Weizhong LIU ; Linwei WU
Chinese Journal of Organ Transplantation 2021;42(8):480-484
Objective:To explore how to optimize selection, acquisition, and matching for the use of an aged donor liver.Methods:A case of 81-year-old senior donor liver transplantation performed at our institution is reported, the donor was an 81-year-old female who was brain-dead and the recipient was a 21-year-old male who underwent liver transplantation because of chronic hepatitis B complicated with hepatocellular carcinoma. Combined with the literature, the preliminary experience of age-related marginal donor liver in clinical liver transplantation was discussed.Results:The recipient recovered smoothly. Aspartate aminotransferase(AST)and glutamate-pyruvate transaminase(ALT)were 1131 U/L and 846 U/L on the first postoperative day, and decreased gradually to normal until 2 weeks later.Total bilirubin(TBIL)56.4umol/L on the first day and decreased to 22.1umol/L on the third day after operation, however, it began to rise on postoperative day 5 to a maximum of 66.0 umol/L, which decreased to normal about 2 months after surgery. During the follow-up, AST, ALT, TBIL and other indexes were normal, and AFP decreased progressively.Conclusions:Using of elderly liver donors may achieve satisfactory results, asifthe elderly donors been evaluatedcarefullyandthe low-risk recipients been selected.
10.Triptolide increases the radiosensitivity of lung cancer cells by inhibiting DNA repair and inducing apoptosis
Rongqin DAI ; Haibo WANG ; Weiqing LIU ; Linwei LI ; Wei WANG
Chinese Journal of Oncology 2021;43(12):1235-1240
Objective:To investigate the effect of triptolide on radiosensitivity of lung cancer cells and its mechanism.Methods:The lung cancer cells H1299, A549, H157 and H838 were cultured. The strongest radio resistance cell line, H1299 was selected by cell clone formation experiment and for the subsequent experiments. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect the effect of different concentrations of triptolide on the proliferation of H1299 cells. The optimal concentration of triptolide was 50nmol/L, and the optimal treatment time was 48 hours. The H1299 cells were divided into the control group, triptolide group (50 nmol/L), 4 Gy group and triptolide+ 4 Gy group. Flow cytometry was used to detect the apoptosis rate of H1299 cell. Western Blot was used to detect the proteins expression levels of p-Chk2, p-ATM, p-p53, Bcl-2, Bax and cleaved-Caspase 3.Results:The apoptotic rate and protein levels of Bax, cleaved-Caspase 3, p-Chk2, p-ATM and p-p53 in the 4 Gy group were (12.38±1.34)%, 0.42±0.04, 0.38±0.04, 0.98±0.11, 0.73±0.08, 0.95±0.09, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03, 0.32±0.03, 0.21±0.02, 0.25±0.03 in the control group ( P<0.05). However, the protein level of Bcl-2 was (0.52±0.05), lower than (0.93±0.09) of the control group ( P<0.05). The survival fraction (0.462) and protein level of Bcl-2 (0.44±0.04) in the triptolide group were lower than those of the control group (0.702 and 0.93±0.09, P<0.05). The apoptotic rate and the protein levels of Bax and cleaved-Caspase 3 in the triptolide group were (9.27±1.08)%, 0.45±0.05, 0.41±0.04, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03 in the control group ( P<0.05), and the sensitization ratio in the triptolide group was 1.579. The apoptosis rate, Bax and cleaved Caspase 3 protein expression levels in triptolide + 4 Gy group were (26.53±2.19)%, 0.91±0.09 and 0.79±0.08, respectively, higher than (12.38±1.34)%, 0.42±0.04 and 0.38±0.04 in 4 Gy group ( P<0.05). The expression level of Bcl-2 protein was (0.21±0.02), lower than (0.52±0.05) in 4 Gy group ( P<0.05). Conclusion:Triptolide increases the radiosensitivity of radiation-induced lung cancer cells by inhibiting DNA repair and inducing apoptosis.

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