1.Construction of PD-L1hitol-DC derived from bone marrow of DA rats and identification of its immunological function
Zhiqi YANG ; Peibo HOU ; Lang WU ; Jing LIU ; Yang DING ; Minghao LI
Organ Transplantation 2025;16(1):83-90
Objective To construct programmed cell death protein-ligand 1(PD-LI)hi tolerogenic dendritic cell (tol-DC) derived from bone marrow of DA rats and identify its immunological function. Methods DA rat bone marrow cells were extracted, combined with recombinant mouse granulocyte macrophage colony-stimulating factor and recombinant mouse interleukin (IL)-4, and cultured for 6 days in vitro to induce the differentiation of bone marrow cells into immature dendritic cells (imDC). Lipopolysaccharide was used to stimulate cell maturation and cultured for 2 days to collect mature dendritic cells (mDC). PD-L1 lentiviral vector virus stock solution or equivalent dose lentiviral stock solution was added, and PD-L1hitol-DC and Lv-imDC were collected after culture for 2 days. The morphology of PD-L1hitol-DC was observed by inverted phase contrast microscope and transmission electron microscope. Real-time fluorescence quantitative reverse transcription polymerase chain reaction, Western blotting and flow cytometry were used to detect the expression level of specific markers on cell surface. CD8+T cells derived from Lewis rat spleen were co-cultured with imDC, mDC, Lv-imDC and PD-L1hitol-DC, respectively. The levels of inflammatory factors in the supernatant of each group were detected by enzyme-linked immunosorbent assay. The apoptosis of T cells and the differentiation of regulatory T cells (Treg) in each group were analyzed by flow cytometry. Results The morphology of PD-L1hitol-DC modified by PD-L1 gene was consistent with tol-DC characteristics, and the expression levels of CD80, CD86 and major histocompatibility complex (MHC) on the surface were low. After mixed culture with CD8+ T cells, the levels of IL-10 and transforming growth factor (TGF) -β1 in the supernatant of PD-L1hitol-DC group were higher, the levels of tumor necrosis factor (TNF) -α and IL-17A were lower, and the apoptosis of T cells and Treg differentiation were increased. Conclusions Overexpression of PD-L1 through lentiviral vectors may successfully induce the construction of bone-marrow derived PD-L1hitol-DC in DA rats, promote the secretion of anti-inflammatory factors and T cell apoptosis, induce the differentiation of Treg, and inhibit the immune response of allogeneic CD8+T cells, which provides experimental basis for the next organ transplantation immune tolerance study.
2.Pharmacokinetics of JS026 and JS026-JS016 for single intravenous administration in healthy volunteers
Yan TIAN ; Hui-Jing YE ; Jing-Jing WANG ; Nan-Yang LI ; Juan MA ; Xi TAN ; Fan WU ; Jie WANG ; Shu-Yan YU ; Xiao-Jie WU ; Jin-Jie HE ; Jing ZHANG ; Wen-Hong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2251-2255
Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.
3.Epidemiological characteristics of patients with severe fever with thrombocytopenia syndrome in Dongyang City
CHEN Kang ; WU Ailan ; MA Jingjing ; WU Zhenhua ; XU Yuechen ; ZHANG Jing ; JIN Xujing ; CAO Hui ; CHEN Shuang
Journal of Preventive Medicine 2024;36(1):47-50
Objective :
To investigate the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Dongyang City, Zhejiang Province from 2017 to 2022, so as to provide insights into SFTS prevention and control.
Methods:
Data pertaining to patients with SFTS in Dongyang City from 2017 to 2022 were collected from Notifiable Infectious Disease Reporting System of Chinese Disease Prevention and Control Information System. The epidemiological and clinical characteristics of patients with SFTS were descriptively analyzed, and the trends in incidence of SFTS was evaluated using annual percent change (APC).
Results:
A total of 32 SFTS cases were reported in Dongyang City from 2017 to 2022, with mean annual incidence of 0.63/105, and 8 cases died, with a fatality rate of 25.00%. The incidence of SFTS appeared a tendency towards a rise from 2017 to 2022 (APC=40.697%, P<0.05). The male to female ratio of SFTS cases was 0.78∶1, and farmer was the predominant occupation (31 cases, 96.88%). SFTS predominantly occurred among individuals at ages of 51 to 69 years (20 cases, 62.50%), and the incidence peaked during the period between March and May and between July and August (28 cases, 87.50%). SFTS cases were reported in 11 out of the 18 townships (streets) in Dongyang City, with the highest number found in Zuocun Township (8 cases, 28.13%), and had the lowest platelet count of (41.46±5.19)×109 platelets/L, with the lowest count of (3.00 to 67.00) ×109 platelets/L. All the SFTS cases had a history of mountain forest and farmland activities 2 weeks prior to onset of the disease, and 5 cases (15.63%) had a history of tick bites.
Conclusions
The incidence of SFTS appeared a tendency towards a rise in Dongyang City from 2017 to 2022, and SFTS was highly prevalent in spring and summer, with high incidence among farmers. Intensified health education of SFTS is recommended among residents in high-incidence areas.
4.A case of sudden hearing loss combined with familial hyperlipidemia.
Hui ZHONG ; Xiaonan WU ; Jing GUAN ; Dayong WANG ; Qiuju WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(1):70-72
Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.
Humans
;
Audiometry, Pure-Tone
;
Deafness/complications*
;
Hearing Loss, Sensorineural/diagnosis*
;
Hearing Loss, Sudden/diagnosis*
;
Hyperlipidemias/complications*
;
Lipids
5.Epidemiological characteristics and diagnosis of imported Plasmodium malariae and Plasmodium ovale malaria cases in five provinces of China from 2014 to 2021
Wen LIN ; Duoquan WANG ; Lingcong SUN ; Tao ZHANG ; Hui YAN ; Wei RUAN ; Ying LIU ; Dongni WU ; Shizhu LI ; Jing XIA ; Hong ZHU
Chinese Journal of Schistosomiasis Control 2024;36(4):407-411
Objective To investigate the epidemiological characteristics and diagnosis of imported Plasmodium malariae and P. ovale malaria cases in Anhui Province, Hubei Province, Zhejiang Province, Guangxi Zhuang Autonomous Region and Henan Province from 2014 to 2021, so as to provide insights into malaria control in these five provinces. Methods All data pertaining to malaria cases reported in five provinces of China were captured from Chinese Disease Control and Prevention Information System from 2014 to 2021, and the epidemiological characteristics of imported P. malariae and P. ovale malaria cases were analysed using a descriptive epidemiological method. The duration from onset of malaria to initial diagnosis, duration from initial diagnosis to definitive diagnosis, institutions of initial and definitive diagnoses, and proportion of correct malaria diagnosis at initial diagnosis were statistically analyzed. Results A total of 1 223 imported P. malariae and P. ovale malaria cases were reported in Anhui Province, Hubei Province, Zhejiang Province, Henan Province and Guangxi Zhuang Autonomous Region from 2014 to 2021, there were 158 P. malariae malaria cases (12.92%) and 1 065 P. ovale malaria cases (87.08%). Totally 98.53% (1 205/1 223) of the imported malaria cases were from Africa, with Angola (18.99%, 30/158), Nigeria (11.39%,18/158), Cameroon (10.76%, 17/158), Ghana (10.13%, 16/158) and the Democratic Republic of the Congo (10.13%,16/158) as predominant countries where P. malariae malaria cases were from, and Ghana (23.19%, 247/1 065), Cameroon (14.74%, 157/1 065), Nigeria (9.39%, 100/1 065) and Angola (6.95%, 74/1 065) as predominant countries where P. ovale malaria cases were from. There were significant differences in the duration from onset of malaria to initial diagnosis (χ2 = 27.673, P = 0.000) and duration from initial diagnosis to definitive diagnosis of P. malariae and P. ovale malaria cases (χ2 = 29.808, P = 0.000), and the proportions of correct initial diagnosis of P. malariae and P. ovale malaria cases were 38.61% (61/158) and 56.53% (602/1 065). There were 74.69% (118/158) of P. malariae malaria cases with definitive diagnosis in county-, city-, and province-level medical institutions, and 79.25% (844/1 065) of P. ovale malaria cases with definitive diagnosis in county- and city-level medical institutions and county-level centers for disease control and prevention. Conclusions The imported P. malariae and P. ovale malaria cases in Anhui Province, Hubei Province, Zhejiang Province, Henan Province and Guangxi Zhuang Autonomous Region from 2014 to 2021 were mainly returned from Africa and the proportion of correct diagnosis of P. malariae and P. ovale malaria was low at initial diagnosis. Persistent improvements in the diagnostic capability of malaria are required in medical institutions.
6.Clinical Study on Therapy of Soothing Liver and Strengthening Spleen in the Treatment of Active Thyroid-Associated Ophthalmopathy Complicated with Dry Eye
Jing BAI ; Wei WANG ; Ren-Tang HUANG ; Wen-Jun WU ; Mei-Zheng WANG ; Ze-Hui CHEN ; Yi-Bing CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):917-922
Objective To investigate the efficacy of the therapy of soothing liver and strengthening spleen(shortened as Shugan Jianpi therapy)in the treatment of active thyroid-associated ophthalmopathy(TAO)complicated with dry eye,and to provide a reference basis for clinical treatment.Methods A total of 108 patients with active TAO complicated with dry eye of liver depression and qi stagnation type were randomly divided into observation group and control group,54 patients in each group.Both groups were given conventional treatment for intervention of Graves'disease,and additionally the control group was given hormone shock therapy by intravenous injection of Methylprednisolone Sodium Succinate,and the observation group was treated with Chinese medicine prescription for soothing liver and strengthening spleen orally and intravenous injection of Methylprednisolone Sodium Succinate.The treatment period lasted for 12 weeks,and then the patients were followed up till to the 6th month.The changes of clinical activity score(CAS),proptosis,ocular surface disease index(OSDI),corneal fluorescein staining(FL),Schirmer I test(SIT)and tear film break-up time(BUT)in the two groups were observed before and after the treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate in the observation group was 94.44%(51/54)and that in the control group was 74.07%(40/54),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the CAS,OSDI score and proptosis of the patients in the two groups were all lower than those before treatment(P<0.01),and the reduction in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the indicators of tear secretion function such as SIT,FL score and BUT of patients in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group,the differences being all statistically significant(P<0.01).Conclusion Shugan Jianpi therapy exerts certain clinical efficacy in treating patients with active TAO complicated with dry eye of liver depression and qi stagnation type,which can effectively relieve the proptosis,prolong the tear film break-up time,promote the secretion of tears and the repair of corneal epithelium,improve the visual function,and enhance the quality of life of the patients.
7.Research hotspots and prospects of integrating traditional Chinese medicine culture into ideological and political education from 2013 to 2022
Shan HUI ; Yonggang WU ; Yifan HU ; Jing OUYANG
Chinese Medical Ethics 2024;37(3):359-365
By analyzing information such as the number of publications,authors,institutions and keywords in the literature on the integration of traditional Chinese medicine(TCM)culture into ideological and political education in the past 10 years,it was found that the overall number of publications showed an increasing trend. As the main research fronts,TCM colleges and universities had not yet formed teams in cooperation with other universities. The research hotspots were relatively concentrated,but the research horizons were not broad enough. It is suggested that in the future,policy should be taken as the guide to build a cross-regional interdisciplinary cooperation system,horizontally and vertically extend research subjects,innovate and construct diversified teaching models,continue to deeply explore and organically integrate ideological and political education elements,continuously improve the evaluation system of educational functions,and further enhance the timeliness of integrating traditional Chinese medicine culture into ideological and political education. So as to make greater contributions to cultivating talents in the new era and promoting the inheritance and innovation of TCM culture.
8.Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report
Shuo LI ; Xi YAO ; Hui-Xue JIA ; Wei-Guang LI ; Xun HUANG ; Shu-Mei SUN ; Xi CHENG ; Qing-Lan MENG ; Xiang ZHANG ; Jing-Ping ZHANG ; Ya-Wei XING ; Qing-Qing JIANG ; Lian-Xuan WU ; Bing-Li ZHANG ; Xiao-Jing LIU ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(3):323-329
Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24%of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66%,85.96%,80.77%,and 74.19%,respectively.51.22%MCH institutions adopted information surveillance system on HAI cases.94.31%MCH institutions carried out surveillance on hand hygiene compliance.Over 90%MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54%MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90%MCH insti-tutions established three-level pre-examination triage systems.86.18%set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50%.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.
9.Pharmacodynamic Substances in Promoting Osteogenic Differentiation of Epimedii Folium and Epimedii Wushanensis Folium Based on Chemical Fingerprint-cell Metabolomics Correlation Analysis
Yunfen HUANG ; Linchao ZHAO ; Songnan WU ; Fangzhu XU ; Hui GAO ; Xuelian CHEN ; Zimin YUAN ; Jing WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):155-163
ObjectiveTo determine the pharmacodynamic substance basis of Epimedii Folium(EF) and Epimedii Wushanensis Folium(EWF) in promoting osteogenic differentiation, and to establish a method to analyze the material basis of Chinese materia medica based on the correlation between chemical fingerprint and cellular metabolomics. MethodThe chemical fingerprints of 15 batches of EF with 4 species and 3 batches of EWF were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS), and partial least squares-discriminant analysis(PLS-DA) was used to analyze the peak areas of chemical fingerprints of samples. The effects of different samples on proliferative activity of MC3T3-E1 osteoblast precursors, as well as the activity of alkaline phosphatase(ALP) in osteoblasts were detected by cell counting kit-8(CCK-8) and enzyme-linked immunosorbent assay(ELISA). At the same time, UPLC-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to analyze the effects of different samples on the metabolomics of MC3T3-E1 cells, then metabolic peak table of osteogenic differentiation cells was constructed, and pharmacodynamic index mean Y0 was introduced into the peak table. PLS was used to calculate mean Y0 of each group, and the mean Y0 was added to the peak table of chemical fingerprint to construct the correlation between chemical fingerprint and cell metabolome, the pharmacodynamic components of EF and EWF that promote bone differentiation were screened according to variable importance in the projection(VIP) value>1. The pharmacodynamic effects of EF and EWF were evaluated according to the mean Y0 of each group. ResultThe chemical fingerprints of EF with different origins and EWF were completely separated. Compared with the blank group, the activity of MC3T3-E1 cells in EF and EWF groups was significantly increased, the activity of ALP in the Epimedium brevicornu(Gansu province), E. koreanum and E. pubescens groups was significantly increased(P<0.05). The results of cell metabolomics showed that the blank group and the model group had an obvious trend of separation. EF with different origins and EWF had different distance from the model group, indicating that EF with different origins and EWF had different effect on promoting osteogenic differentiation. Chemical fingerprint-cell metabolomics integration analysis screened 9 components closely related to the efficacy of EF and EWF, including diphylloside B, epimedin C, icariin, baohuoside Ⅰ, yinyanghuo B, β-anhydroicaritin, magnoflorine, cryptochlorogenic acid and quercetin. E. koreanum had the strongest effect on promoting osteogenic differentiation. ConclusionThis study determined that the material basis of EF and EWF promoting osteogenic differentiation were mostly flavonoids, alkaloids and organic acids, which provided ideas and methods for the screening of pharmacodynamic components and the prediction of therapeutic effect of Chinese materia medica.
10.Optimization of 18F-FDG PET/CT semi-quantitative diagnostic model for children with autoimmune encephalitis with epilepsy and negative MRI
Ziyuan LI ; Jing WU ; Shuqi WU ; Mingming CAO ; Suyun CHEN ; Ling LI ; Hui WANG ; Yafu YIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(4):213-219
Objective:To investigate the value of 18F-FDG PET/CT imaging in the diagnosis of suspected autoimmune encephalitis (AE) in children with epilepsy and negative MRI. Methods:From May 2019 to August 2022, 94 suspected AE children (49 males, 45 females; age 1-15 years) with epilepsy and negative MRI who underwent brain 18F-FDG PET/CT imaging at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. All patients were divided into AE and non-AE groups based on clinical final diagnosis. The effectiveness of visual diagnosis was evaluated. The cortical lesion extent score (S), and SUV max, SUV mean and minimum of SUV (SUV min) of cortical lesions (L), basal ganglia (B) and thalamus (T) were measured and SUV ratios (SUVR) of L/B or L/T were obtained. Independent-sample t test or Mann-Whitney U test was used to analyze data. Binary logistic regression analysis was used to screen the diagnostic factors of AE, and a diagnostic model was established. The diagnostic efficiency was evaluated by ROC curve analysis and Delong test. Results:There were 53 cases in AE group and 41 cases in non-AE group. Based on visual analysis, the sensitivity, specificity and accuracy of 18F-FDG PET/CT for AE were 100%(53/53), 43.9%(18/41) and 75.5%(71/94), respectively. Differences of LSUV max, LSUV mean, LSUV min, L/BSUVR max, L/BSUVR mean, L/BSUVR min, L/TSUVR max, L/TSUVR mean, L/TSUVR min and S between AE and non-AE groups were statistically significant ( z=-6.74, t values: from -8.51 to -3.97, all P<0.001). ROC curve analysis showed that the AUC of L/BSUVR max was the highest (0.914) among visual analysis and semi-quantitative parameters. Logistic regression analysis showed that S (odds ratio ( OR)=11.40, 95% CI: 2.18-59.52, P=0.004), L/BSUVR max( OR=13.19, 95% CI: 2.11-82.51, P=0.006) and L/TSUVR max( OR=9.66, 95% CI: 1.57-59.55, P=0.015) were independent diagnostic factors for AE. Regression model was established: P=1/(1+ e - x), x=2.433×S+ 2.580×L/BSUVR max+ 2.267×L/TSUVR max-3.802. The AUC of this model was 0.948, with the sensitivity, specificity and accuracy of 98.1%(52/53), 90.2%(37/41) and 94.7%(89/94), respectively. The diagnostic efficacy of the optimized scoring system was consistent with the pre-optimization model, and were both superior to L/BSUVR max(both z=2.01, both P=0.040). Conclusion:The diagnostic model and scoring system based on the semi-quantitative analysis of 18F-FDG PET/CT have better diagnostic efficacy for AE and are superior to semi-quantitative parameters alone.


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