1.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
2.Evaluation of asymptomatic ocular surface disorders in hospitalized patients with primary pterygium before surgery
Chengfang ZHU ; Zhirong LIN ; Xie FANG ; Xianwen XIAO ; Zhiwen XIE ; Shunrong LUO ; Bin LIU ; Xumin SHANG ; Nuo DONG ; Huping WU
International Eye Science 2024;24(1):131-135
AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.
3.Comprehensive evaluation of salt-alkali tolerance of rice germplasms at germination and seedling stages and analysis of salt-tolerant genes.
Pingyong SUN ; Wuhan ZHANG ; Fu SHU ; Qiang HE ; Li ZHANG ; Zhuhong YANG ; Zhirong PENG ; Yun XIE ; Huafeng DENG
Chinese Journal of Biotechnology 2022;38(1):252-263
Cultivating salt-alkali tolerant rice varieties is one of the important ways to meet the increasing food demand of growing global population. In this study, twenty-one rice germplasms with different salt-alkali tolerance were treated with six salt-alkali concentrations at germination and seedling stages. The germination potential, germination rate, shoot length, root length, root number, fresh weight of shoot and seedlings were measured. The average value of salt damage rate was used to evaluate the salt-alkali tolerance. As the salt-alkali concentration increases, the inhibition on seed germination and growth became more obvious. Upon treatment with 1% NaCl plus 0.25% NaHCO3, the salt damage rate of germination rate has the largest variation, ranging from 0% to 89.80%. The salt damage rate of each trait shows a similar trend at all concentrations. Four germplasm resources with strong salt-alkali tolerance (Dajiugu, Nippobare, Mowanggu and 02428) and 7 sensitive germplasms were screened. The salt-tolerant gene sequence of 4 salt-alkali tolerant varieties and 3 sensitive germplasms were analyzed. OSHAL3 and OsRR22 were identical among the 7 germplasms, but SKC1 and DST showed clear variations between the salt-alkali tolerant and sensitive germplasms. Besides the salt-alkali tolerant germplasm resources, this study can also serve as a reference for mining of genes involved in salt-alkali tolerance and breeding of salt-alkali tolerant rice varieties.
Alkalies
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Germination
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Oryza/genetics*
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Plant Breeding
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Seedlings/genetics*
4.The study on the inflammatory factors of the G6PD-deficiency children with bacterial infection
Wugui MO ; Yupeng TANG ; Rong WEI ; Youjun XIE ; Weizhen HUANG ; Jun FU ; Gongzhi LU ; Zhirong MO ; Ying WANG ; Botao NING
Chinese Journal of Emergency Medicine 2020;29(6):793-798
Objective:To investigate the clinical significance of inflammatory factors in bacterial infection children with glucose-6-phosphate dehydrogenase (G6PD) deficiency in PICU.Methods:A prospective cohort study was carried out from June 2014 to December 2017. 77 bacterial infection children with pediatric critical illness score less than 80 who were admitted to the PICU, were recruit in the study.The patient diagnosed as other basic diseases,with history of high-dose glucocorticoid use, discharged or died within 24 hours were excluded.The recruited patients were divided into G6PD deficiency group (observation group with 36 cases) and non-G6PD deficiency group (control group with 41 cases) according to the presence or absence of G6PD deficiency.Blood samples were taken at admission, 12 hand 24 h after hospitalization to detect the concentrations of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) andC-reactive protein (CRP). T test, χ2 test and Fisher exact test were used to analyze the changes of the above inflammatory factors, complications, prognosis, PICU stay time and hospitalization costs. Results:The levels of inflammatory factors in the observation group were significantly higher than those in the control group at admission, 12 and 24 hours after hospitalization, the differences were statistically significant (all P< 0.05). There was no statistically significant difference in thechangerate of inflammatory factors between the two groups during treatment; The PICU stay time of observation group was longer [(7.98 ± 6.55) vs (5.01 ± 6.21)] and the hospitalization cost (yuan) was higher [(36 634.09 ± 11 876.67) vs (31 571.42 ± 10 245.80)], P<0.05; Compared to the control group, the incidence ofsevere sepsis, septic shock, MODS increased significantly, and the curative rate decreasedsignificantly in observation group( P<0.05). Conclusions:G6PD-deficient children with bacterial infections had serious inflammatory reactions with poor prognosis and higher hospitalization costs and were susceptible to the occurrence of severe sepsis, septic shock and MODS.
5.Dynamic changes of inflammatory factors and prognosis in acute infection children with glucose-6-phosphate dehydrogenase deficiency
Wugui MO ; Yupeng TANG ; Rong WEI ; Youjun XIE ; Weizhen HUANG ; Jun FU ; Gongzhi LU ; Zhirong MO ; Jie ZHENG
Chinese Pediatric Emergency Medicine 2020;27(6):469-472
Objective:To explore the serum levels of inflammatory cytokines and prognosis in severe acute infection children with glucose-6-phosphate dehydrogenase(G6PD) deficiency.Methods:A total number of 160 children with severe acute infections admitted to PICU of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from June 2014 to December 2017 were selected as subjects in this study, including 80 children with G6PD deficiency(observation group) and 80 children without G6PD deficiency(control group). The changes of TNF-α, IL-6, IL-10 and CRP were dynamically monitored at 0-hour, 12-hour and 24-hour after admision, and the occurrences of sepsis, multiple organ dysfunction syndrome(MODS) were prospectively analyzed.Results:The levels of serum cytokines and CRP in the observation group were significantly higher than those in the control group at admission[TNF-α: (65.57±19.09) pg/ml vs.(46.53±20.34) pg/ml; IL-6: (98.90±29.02) pg/ml vs.(89.89±25.54) pg/ml; IL-10: (87.66±21.84) pg/ml vs.(76.34±19.01) pg/ml; CRP: (60.18±22.24) mg/L vs.(41.43±19.51) mg/L, respectively], and the differences between two groups were statistically significant( P<0.05). The levels of cytokines and CRP in the observation group were higher than those in the control group at 12 h and 24 h after treatment( P<0.01). Compared with the control group, the incidences of sepsis(82.50% vs 67.50%) and MODS(73.75% vs 58.75%) in the observation group increased, and the recovery rate(81.25% vs 92.50%) decreased, with statistical significance between two groups( P<0.05). Conclusion:Children with G6PD deficiency need to be paid more attention to inflammation, sepsis, MODS and the difficulty of treatment when they are infected.The potential mechanism may be related to oxidative stress.
6.Effects of recombinant human epidermal growth factor on epithelial recovery and tear film stability after enhanced transepithelial corneal crosslinking
Zhirong LIN ; Huping WU ; Shunrong LUO ; Zhiwen XIE ; Xie FANG ; Xianwen XIAO ; Lei YAN ; Nuo DONG ; Xumin SHANG ; Zhaosheng LIU
Chinese Journal of Experimental Ophthalmology 2020;38(12):1052-1059
Objective:To investigate the impact of recombinant human epidermal growth factor (rh-EGF) on the epithelial recovery and the tear film stability after trans-epithelial corneal collagen crosslinking in patients with progressive keratoconus.Methods:A randomized controlled clinical trail was designed.Consecutive 66 patients (37 males and 29 females) with an average age of (21.27±3.80) years old diagnosed with primary progressive keratoconus and hospitalized in Xiamen Eye Center Affiliated to Xiamen University from October, 2016 to January, 2017 were enrolled and treated with unilateral enhanced transepithelial corneal crosslinking surgery by iontophoresis, and the patients were randomly divided into control group and experimental group according to random number table method, with 33 patients 33 eyes in each group.The eyes in the control group were treated with carboxy-methylcellulose sodium lubricant eye drops and the eyes in the experimental group were treated with rh-EGF eye drops.The ocular surface disease index (OSDI) questionare, slit lamp examination, Schirmer Ⅰ test, corneal fluorescein sodium staining scoring, non-contact tonometry, uncorrected visual acuity, best corrected visual acuity, bulbar conjunctival congestion scoring, lacrimal sevretion test, non-invasive break-up time of tear film (NIBUT), as well as tear meniscus height analysis were performed before surgery, and on day 1, day 3, day 5, day 7, day 14 and day 28 after surgery.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center Affiliated to Xiamen University (No.2016-ME-003).Results:On day 7 after surgery, the OSDI values were increased in both groups than the preoperative value, while the value in the experimental group was significantly lower than that in the control group ( P<0.05). There were statistically significant differences in the overall corneal epithelial staining score values between the two groups at different time points ( Fgroup=16.701, P<0.01; Ftime=454.418, P<0.01). The corneal epithelial staining score in the experimental group on day 3 and day 5 after surgery were significantly lower than those in the control group (1.79±0.65 vs. 2.70±0.68; 0.91±0.46 vs. 1.55±0.51) (both at P<0.01). The conjunctival congestion score in the experimental group was significantly lower than that of the control group on day 3 and day 5 after surgery (both at P<0.05). There were statistically significant differences in the overall NIBUT values between the two groups at different time points ( Fgroup=13.084, P<0.01; Ftime=34.383, P<0.01). The NIBUT values were significantly decreased rapidly on day 7, day 14 and day 28 after surgery in both groups (all at P<0.01), but gradually recovered.The NIBUT of the experimental group on day 7 and day 14 after surgery were significantly higher than those of the control group ([8.18±2.26]seconds vs. [5.93±2.33]seconds; [9.49±1.95]seconds vs. [7.52±2.27]seconds) (both at P<0.01). No statistical differences were found in the tonometry value, visual acuity, value of Schirmer I test as well as tear meniscus height at any time point before or after surgery between the two groups (all at P>0.05). Conclusions:Recombinant human epidermal growth factor has positive effects in the patients received enhanced transepithelial corneal crosslinking surgery, presenting with promotion of epithelial healing, relief of post-operative discomfort, and the recovery of tear film stability.
7.Quantitative analysis of setup errors in lung SBRT with R 624-SCF immobilization equipment
Jun ZHANG ; Xiaotian HUANG ; Conghua XIE ; Yunfeng ZHOU ; Zhirong BAO ; Dajiang WANG ; Cheng CHEN ; Hui LIU
Chinese Journal of Radiation Oncology 2018;27(4):396-400
Objective KV-CBCT was utilized to evaluate the setup errors in lung SBRT with R624-SCF immobilization equipment,quantitatively analyze the percentage of all types of errors in the cumulative errors and unravel the main sources of setup errors.Methods The CBCT data weekly and QA data monthly from 32 patients diagnosed with lung neoplasms were collected to quantitatively analyze the setup errors.The cumulative errors were calculated by statistical model.The proportion and source of each type of setup error was analyzed.Results All 32 patients received a total of 420 times of CBCT.The setup errors of immobilization equipment in the lateral,supine-inferior,anterior-posterior directions were (0.03±0.72) mm,(0.73± 1.16) mm and (0.21±0.95) mm,respectively.The errors of tumor motion in three directions were (0.71±2.61) mm,(-0.80±2.60) mm and (0.075± 1.77) mm,respectively.According to the calculation formula proposed by Vance Keeling,the proportion of the cumulative error was 54.55%,9.21% for immobilization equipment,12.97% for tumor motion,2.55% for couch sagging,5.70% for Gantry radiation isocenter,4.73% for Collimator radiation isocenter,4.61% for couch radiation isocenter and 5.70% for Xray field isocenter,respectively.Conclusions The main factors of setup errors during SBRT treatment for lung cancer are setup random,tumor motion,immobilization equipment,couch sagging and machine isocenter.During radiotherapy,targeted control of tumor motion is of significance for minimizing the cumulative errors.
8.Susceptibility of Acinetobacter baumannii isolates to eight antimicrobial agents tested by different methods
Hainan WEN ; Shoujun XIE ; Jianhong ZHAO ; Qian SUN ; Honglian WEI ; Dongyan SHI ; Zhirong LI ; Li XU ; Haifeng WEN
Chinese Journal of Infection and Chemotherapy 2017;17(6):680-684
Objective The purpose of this study was to analyze the susceptibility profile of Acinetobacter baumannii to antimicrobial agents,and validate the results of different antimicrobial susceptibility testing methods,for improving the quality of antibiotic resistance monitoring data.Methods The susceptibility data of Hebei Provincial Antimicrobial Resistant Investigation Net were analyzed retrospectively and 126 strains ofA.baumannii were collected.The susceptibility ofA.baumannii to piperacillintazobactam,amikacin,gentamicin,ciprofloxacin,levofloxacin,ceftazidime,imipenem,and meropenem was tested by E-test,KirbyBauer method and VITEK system.Results The susceptibility results of the 126 A.baumannii strains showed that the susceptibility to piperacillin-tazobactam,amikacin,gentamicin,levofloxacin and ceftazidime was significantly different between the three methods (P<0.05).The categorical agreement,major error,minor error,and very major error of Kirby-Bauer method were within acceptable range.There were evident difference in classification consistency for piperacillin-tazobactam,amikacin,levofloxacin between Kirby-Bauer method and VITEK (P<0.05).Conclusions Different antimicrobial susceptibility testing methods may lead to different results of resistance monitoring data.Bias may be generated in antibiotic resistance surveillance if different methods are used.The susceptibility results of piperacillin-tazobactam,amikacin,levofloxacin derived from VITEK system should be validated by Kirby-Bauer or E-test method.
9.Trend and characteristics of fall in elderly adults based on data from national injury surveillance sentinel hospitals in Anhui province, 2006-2014
Xiuya XING ; Wei XU ; Yeji CHEN ; Zhirong LIU ; Shangchun JIA ; Jianrong XIE ; Qingsheng WU
Chinese Journal of Epidemiology 2016;37(5):702-707
Objective To understand the incidence pattern of fall among older adults in Anhui province during 2006-2014,and provide scientific basis for intervention strategies and decision-making.Methods The incidence data of fall in elderly adults from 6 sentinel hospitals in 2 national injury surveillance areas in Anhui province between 2006 and 2014 were collected for this descriptive epidemiological analysis of the overall incidence trend,demographic characteristics,case distribution and clinical characteristics of fall cases in the elderly.Results The fall case number,the proportions of fall cases to injury cases and to overall fall cases in the elderly all increased from 2006 to 2014.The fall was the first cause of the elderly injury during the past 9 years.The sex ratio was 0.74 and the cases in males decreased with age.In both males and females,the cases in retirees and the jobless accounted for the highest proportions.The annual incidence peak was during August to October,and two daily incidence peaks were during 9 am-ll am and 16 pm-18 pm.The elderly falls mainly occurred at home (62.07%),and more females were affected than males (70.27% vs.50.97%).Leisure activity and homework related falls accounted for 49.18% and 28.67% respectively,and more housework related falls occurred in females than in males.Contusion/abrasion was the first injury caused by fall in males (42.63%) and fracture was the first injury caused by fall in females (47.27%).Head was the first injury site in males (38.04%) and leg was the first injury site in females (29.29%).Most injuries caused by fall were mild (55.12%) and moderate (41.84%) in severity,but the proportions of moderate and severe cases increased gradually with age.Conclusion Fall in the elderly has become a public health problem.It is necessary to take targeted prevention and control measures according to the gender and age distributions of the fall in the elderly.
10.Development of knowledge resources database for health dissemination and education in hospitals and its application
Zulin CHEN ; Changjun XIE ; Zhirong XU ; Hong ZOU ; Bing SHI ; Jun YIN
Chinese Journal of Medical Library and Information Science 2015;(9):50-52
Information resources of health education , disease knowledge and drug knowledge extracted by seconda-ry development fromhospital electronic librarywere disseminated on the Website , WIFI and WeChat platforms of People's Armed Police for the self-learning of users according to the demand of health dissemination and education in hospitals and health education at grass-roots level, in order to improve the efficiency and service of health edu-cation, solve the lack of resources and talents for health education, and to enhance the health service support ability for People's Armed Police.

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