1.Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.
Yunzhu LIN ; Xiang WANG ; Shi HE ; Zhongxin DUAN ; Yunchu ZHANG ; Xiaodong SUN ; Yuzhu HU ; Yuanyuan ZHANG ; Zhiyong QIAN ; Xiang GAO ; Zhirong ZHANG
Acta Pharmaceutica Sinica B 2024;14(2):854-868
Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
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.Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions (1): to improve the validity of real-world evidence
Zuoxiang LIU ; Zilin LONG ; Zhirong YANG ; Shuyuan SHI ; Xinran XU ; Houyu ZHAO ; Zuyao YANG ; Zhu FU ; Haibo SONG ; Tengfei LIN ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2024;45(2):286-293
Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.
4.Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions(2): to improve the extrapolation of efficacy
Zuoxiang LIU ; Zilin LONG ; Zhirong YANG ; Shuyuan SHI ; Xinran XU ; Houyu ZHAO ; Zuyao YANG ; Zhu FU ; Haibo SONG ; Tengfei LIN ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2024;45(4):579-584
Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.
5.Correlation between pen-holding posture, grip strength and myopia in school-aged children
Yuxiao WU ; Zhengyang TAO ; Zhirong XU ; Yu LIN ; Hongwei DENG ; Jun ZHAO
Chinese Journal of Experimental Ophthalmology 2024;42(9):827-833
Objective:To investigate the correlation between pen-holding posture, grip strength and myopia.Methods:A cross-sectional study was performed.A total of 496 school-aged children in grades 1-6, who underwent eye examinations at Shenzhen Eye Hospital from November 2021 to May 2022 were consecutively enrolled as subjects.The subjects' age, grade, sex, refractive error and age of school enrollment were recorded.Subjects' grip strength and pen-holding posture were obtained with an electronic grip strength meter and a tool pen, and subjects were divided into correct pen-holding posture group and incorrect pen-holding posture group according to their pen-holding posture.Propensity scores for sex, grade, age at school entry, and grip strength in the two groups were matched using the nearest neighbor matching method.Multifactorial binary logistic regression analysis was performed with binocular myopia, monocular myopia, and emmetropia as dependent variables and grip strength, grade, refractive error, and pen-holding posture as independent variables.The correlation between grip strength and spherical equivalent was examined by Spearman rank correlation analysis and partial correlation analysis.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shenzhen Eye Hospital (No.2022KYPJ032).Results:After matching propensity scores, there were 101 cases and 197 cases in the correct pen-holding posture group and incorrect pen-holding posture group, respectively.There was no statistical significance in sex, grade, age at enrollment, and grip strength between the two groups (all at P>0.05).Multinomial logistic regression results showed that using emmetropia as a reference, higher grade (4 versus 1∶7.601[1.307-44.206]; 5 versus 1∶4.392[1.039-18.562]), presence of anisometropia (21.366[5.750-79.397]) were relative risk factors for monocular myopia (all at P<0.05), and higher grade (3 versus 1∶4.389[1.783-10.800]); 4 versus 1∶15.398[3.267-72.574]; 5 versus 1∶7.447[2.232-24.851]; 6 versus 1∶6.462[2.116-19.734]) were relative risk factors for binocular myopia (all at P<0.05).Taking monocular myopia as a reference, higher grade (6 versus 1∶4.582[1.193-17.589]), presence of anisometropia (0.141[0.069-0.289]), and irregular pen-holding posture (2.608[1.340-5.075]) were associated factors for binocular myopia (all at P<0.05).According to partial correlation analysis, the spherical equivalent of the right eye of children with incorrect pen-holding posture was negatively correlated with the grip strength ( rs=-0.141, P=0.047). Conclusions:There is an association between pen-holding posture and myopia in school-aged children.Children with greater grip strength and incorrect pen-holding posture may have higher degrees of right eye refractive error.
6.Analysis of doctor′s diagnosis and treatment behavior before and after the implementation of diagnosis-intervention packet based on propensity score matching: taking chronic diseases as an example
Lu LI ; Lizhong LIANG ; Yanwei LIN ; Zhirong ZENG
Chinese Journal of Hospital Administration 2023;39(3):195-200
Objective:To analyze the effect of the implementation of diagnosis-intervention packet (DIP) on the doctors′ diagnosis and treatment behavior of chronic diseases, so as to provide reference for further improving medical insurance payment related policies.Methods:The first page information of chronic disease patients admitted to hospitals with diabetes, hypertension and coronary atherosclerotic heart disease as the main conditions in 103 hospitals at all levels and township health centers in a city from 2016 to 2020 was collected, and the patients were divided into non-DIP group and DIP group according to the implementation time of DIP. After 1∶1 propensity score matching to balance the general conditions of the 2 groups, the diagnosis and treatment behaviors were analyzed from two dimensions: diagnostic behavior and treatment behavior. The grade A rate of medical record writing, admission and discharge diagnosis coincidence rate, and the average length of stay were used to evaluate the diagnostic behavior; the proportion of drugs and the degree of change in the cost structure were used as the evaluation indicators of treatment behavior.Results:After matching, 41 050 patients were included in both the non-DIP group and the DIP group.From the perspective of diagnostic behavior, the grade A rate of medical record writing in the non-DIP group and the DIP group was 99.40% and 99.83%, the coincidence rate of admission and discharge diagnosis was 58.42% and 61.79%, the average hospital stay was 8.03 days and 7.04 days respectively, and the difference between the groups was significant ( P<0.05). From the view of treatment behavior, the proportion of drugs decreased from 33.00% in the non-DIP group to 27.59% in the DIP group, with a significant difference ( P<0.05); the drug cost represented by Western medicine changed negatively, while the diagnostic cost showed a positive change. Conclusions:DIP has played a certain role in regulating doctors′ diagnosis and treatment behavior for chronic diseases. Among them, doctors have significantly improved their diagnostic behavior for chronic diseases, and the proportion of drugs in treatment behavior has been well controlled.
7.Analysis on the risk of refracture after osteoporotic vertebral fracture with changes in blood calcium and bone metabolism
Hong PAN ; Hong CHEN ; Zongyang LIN ; Zhirong LIU ; Shuchen DING
Chinese Journal of Endocrine Surgery 2022;16(1):108-112
Objective:To study the risk of refracture after osteoporotic vertebral fracture with changes in blood calcium and bone metabolism.Methods:260 patients with osteoporotic vertebral fracture treated in our hospital from Feb. 2018 to Feb. 2020 were selected for study. All patients were treated with kyphoplasty. The clinical curative effect, blood calcium, PINP, and β-CTX level changes were observed, postoperative recurrence was followed up. Clinical data of fracture patients were collected, risk factors of osteoporotic vertebral fractures in patients with postoperative recurrence of fracture were analyzed, receiver-operating characteristic curve was drawn to analyze the predictive value of blood calcium, PINP, andβ-CTX in postoperative recurrence of osteoporotic vertebral fracture.Results:The total clinical response rate was 95.77% (249/260) after treatment. After treatment, serum calcium, PINP, and β-CTX decreased with time, and the difference was significant ( P<0.05) . All patients were followed up for 6 months. There were 81 cases (31.15%) suffering postoperative fracture and 179 cases (68.85%) without fracture. According to univariate analysis, there were no statistically significant differences in age, sex, BMI, history of trauma, underlying disease, site of surgical vertebral body, segment of surgical vertebral body, correction angle of sagittal kyphosis, or amount of bone cement injection between the two groups ( P>0.05) . Long-term history of glucocorticoid use, preoperative fractured vertebra number, surgical vertebra number, blood calcium, PINP, β-CTX, fracture compression rate, vertebra height recovery rate, reinforced vertebra number, and bone cement leakage were correlated with postoperative recurrence of fracture in patients with osteoporotic vertebral fracture ( P<0.05) . Multivariate Logistic analysis showed that long-term history of glucocorticoid use, preoperative number of fractured vertebrae, surgical vertebra number, fracture compression rate, vertebral height recovery rate, enhanced vertebral body number, bone cement leakage, blood calcium, PINP, and β-CTX were all independent risk factors for postoperative recurrence of osteoporotic vertebral fracture ( P<0.05) . ROC curve results showed that AUC, 95%CI and truncation value were 0.820, 0.770-0.871 and 2.12mmol/L vs 0.915, 0.873-0.957 and 45.51 ng/mL vs 0.973, 0.957-0.988, and 463.29 for serum calcium, PINP, and β-CTX respectively in predicting the recurrence of osteoporotic vertebral fracture. Conclusion:Kyphoplasty has a significant effect on osteoporotic vertebral fracture, and it can effectively improve the serum calcium, PINP, and β-CTX, which have a certain monitoring value for postoperative recurrence of fracture.
8.Application effect of timing theory in educational intervention for mothers of premature infants
Zhirong HUANG ; Mei LIN ; Zhengzhong LI ; Nini MA ; Dongmei XU ; Yujuan LI
Chinese Journal of Practical Nursing 2022;38(19):1458-1464
Objective:To explore the effect of educational intervention based on timing theory on mothers of premature infants.Methods:Using the convenience sampling method, 80 mothers of premature infants hospitalized in the Neonatology Department of Affiliated Hospital of Youjiang Medical University for Nationalities from May 2019 to October 2020 were included in this study. According to the time of admission, they were divided into the control group (42 cases) and the observation group (38 cases). The mothers in the control group were given routine educational guidance during the hospitalization of premature infants, while the mothers in the observation group were given comprehensive educational intervention based on timing theory on the basis of the control group. The mothers′ caring ability during the transition period, breastfeeding self-efficacy and breastfeeding rate at a month after discharge, and mother′s coping ability at 3 months after discharge were compared between the two groups.Results:There were 35 cases in each group completed the study. The observation group scored (100.86 ± 6.22) on the maternal care ability of premature infants in transition period, and the control group scored (89.51 ± 4.17), the difference between the two groups was statistically significant ( t=-8.97, P<0.05). The breastfeeding self-efficacy score of the observation group a month after discharge from hospital was (47.83 ± 2.54) points, which was higher than (41.20 ± 1.97) points of the control group, and the difference was statistically significant ( t=-12.21, P<0.05). The breastfeeding rate a month after discharge in the observation group was 62.9% (22/35), which was higher than 37.1% (13/35) in the control group, and the difference was statistically significant ( χ2=4.63, P<0.05). The maternal coping ability scores of the premature infants in the observation group and control group 3 months after discharge were (119.29 ± 6.03) and (113.66 ± 6.59) points respectively, and the difference between the two groups was statistically significant ( t=-3.73, P<0.05). Conclusions:The educational intervention based on timing theory can help mothers of premature infants master the nursing knowledge and skills, strengthen the mother′s transitional care ability and post-discharge coping ability, improve the breastfeeding self-efficacy and breastfeeding rate of premature infants, promote and development the growth of premature infants, worthy of clinical application.
9.Research progress on fear of dementia
Xiang LONG ; Zhirong JIANG ; Min QING ; Chunhui CHEN ; Lin LONG
Sichuan Mental Health 2022;35(5):483-488
The purpose of this article is to review the research progress on fear of dementia, and to provide references for clinical treatment and nursing care. Fear of dementia is a widespread problem for adults, and adults with high degrees of fear were more likely to develop adverse psychological consequences, including aggravation of anxiety and depression, decreased inclination toward health-promoting behaviours, avoidance of medical treatment, and suicidal ideation. At present, domestic and foreign studies have mainly focused on the current situation and influencing factors of fear of dementia. Therefore, this article gives a review on the fear of dementia in terms of its concept, incidence, impact, influencing factors, assessment tools and intervention measures, with a view to provide a reference for the subsequent studies.
10.Diagnosis and clinical characteristics analysis in elderly patients with severe pneumonia caused by Chlamydia psittaci
Haiwen ZENG ; Zhirong DING ; Yijuan ZHENG ; Rongfu LI ; Yazheng CHEN ; Xuejuan WANG ; Tianlai LIN
Chinese Journal of Geriatrics 2021;40(12):1526-1531
Objective:To investigate the diagnosis and clinical characteristics of five elderly patients with Chlamydia psittaci-caused severe pneumonia.Methods:Through retrospective analysis, diagnosis and treatment process and clinical characteristics of five elderly inpatients with severe pneumonia caused by Chlamydia psittaci were summarized in the Department of Critical Care Medicine, Quanzhou First Hospital East Street Branch Area, affiliated to Fujian Medical University between January to June 2021.Results:Five patients with severe pneumonia caused by Chlamydia psittaci were aged from 64 to 74 years, with various underlying diseases such as coronary heart disease, chronic heart failure, chronic obstructive pulmonary disease, etc.All patients had an established history of poultry exposure.These cases had high fever, cough, spitting, and dyspnea as the main clinical manifestations.Some of them also had systemic symptoms or weakness of the limbs as the prodromal symptoms.The disease progressed rapidly, with severe respiratory failure, acute kidney injury, and shock appearing soon, accompanied by different degrees of muscle injury, and damage to the heart, liver, blood coagulation, and immune systems at the same time.Laboratory examination showed that levels of inflammatory indicators were increased: at 3, 5, 7 d after admission, the level of C reactive protein was 214.6(153.9-256.3)mg/L, 199.2(115.8-333.8)mg/L, 151.0(11.19-173.7)mg/L, respectively; and interleukin 6 level was 1 241.0(912.1-6822.0)ng/L, 779.1(451.2-7122.0)ng/L, 631.2(7.0-4 321.0)ng/L, respectively.And monitoring results of nutritional index indicated a high metabolic state.The imaging examinations showed that consolidation and ground-glass shadows spreaded to both lungs, may accompany the miliary and nodular shadows, and may also involve pleural which caused pleural effusion.After the clinical use of metagenomic next-generation sequencing(mNGS), mNGS has been confirmed as an important method for the diagnosis of Chlamydia psittaci infection.The disease course and prognosis were related to the severity of the disease, advanced age, underlying diseases, and timely diagnosis and effective treatment.Conclusions:The progression of Chlamydia psittaci pneumonia to severe disease may be related to advanced age, more basic diseases such as chronic cardiopulmonary disease, smoking, and timely diagnosis and treatment.Generally, laboratory and imaging examinations have no diagnostic specificity, but mNGS is of great significance for early diagnosis, transition to target treatment and improvement of prognosis.

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