1.CDH17-targeting CAR-NK cells synergize with CD47 blockade for potent suppression of gastrointestinal cancers.
Liuhai ZHENG ; Youbing DING ; Xiaolong XU ; Huifang WANG ; Guangwei SHI ; Yang LI ; Yuanqiao HE ; Yue GONG ; Xiaodong ZHANG ; Jinxi WEI ; Zhiyu DONG ; Jiexuan LI ; Shanchao ZHAO ; Rui HOU ; Wei ZHANG ; Jigang WANG ; Zhijie LI
Acta Pharmaceutica Sinica B 2025;15(5):2559-2574
Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.
2.Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province
Gaixiang XU ; Weimei JIN ; Baodong YE ; Songfu JIANG ; Chao HU ; Xin HUANG ; Bingshou XIE ; Huifang JIANG ; Lili CHEN ; Rongxin YAO ; Ying LU ; Linjie LI ; Jin ZHANG ; Guifang OUYANG ; Yongwei HONG ; Hongwei KONG ; Zhejun QIU ; Wenji LUO ; Binbin CHU ; Huiqi ZHANG ; Hui ZENG ; Xiujie ZHOU ; Pengfei SHI ; Ying XU ; Jie JIN ; Hongyan TONG
Chinese Journal of Hematology 2024;45(6):549-555
Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.
3.Influencing factors of visual acuity recovery in patients with high myopia af-ter posterior chamber phakic intraocular lens implantation
Huifang FENG ; Yadong LIU ; Beibei WANG ; Huijie ZHAO ; Luman SHI ; Xing WEI
Recent Advances in Ophthalmology 2024;44(9):723-727
Objective To explore the influencing factors of visual acuity recovery in patients with high myopia after posterior chamber phakic intraocular lens(ICL)implantation.Methods A prospective study was conducted on 210 pa-tients(420 eyes)with high myopia who underwent ICL implantation at the Second Affiliated Hospital of Zhengzhou Univer-sity from May 2021 to March 2023.The patients were divided into a good recovery group[best corrected visual acuity(BC-VA)recovery ≥0.3 D]and a poor recovery group(BCVA recovery<0.3 D)based on their visual acuity recovery status three months after surgery.The baseline data of patients in the two groups were compared,and the factors affecting visual acuity recovery were analyzed using Logistic regression.The receiver operating characteristic(ROC)curve was used to an-alyze the predictive value of the Logistic regression model for poor visual acuity recovery in patients with high myopia after ICL implantation.Results Three months after surgery,149 patients(298 eyes)were in the good recovery group,and 61 patients(122 eyes)were in the poor recovery group.There were no significant differences in gender,age,years of myopi-a,body mass index,and academic performance between the two groups(all P>0.05).The proportions of patients with corneal astigmatism<1.30 D(55.74%),corneal diopter<45 D(59.02%),Pittsburgh Sleep Quality Index(PSQI)<7 points(63.93%),and average central radius of curvature[(7.82±0.27)mm]in the poor recovery group were lower than those in the good recovery group[83.89%,81.88%,85.91%,and(7.90±0.24)mm,respectively].The central flat me-ridian curvature(k1)of the anterior corneal surface[(43.27±1.43)D],steep meridian curvature(k2)of the anterior corneal surface[(44.84±1.53)D],and arch height[(628.49±67.28)μm]in the poor recovery group were higher than those in the good recovery group[(42.73±1.42)D,(44.12±1.47)D],and[(417.56±80.14)pm],with significant differences(all P<0.05).Logistic regression analysis showed that corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score were independent influencing factors of poor visual acuity recovery after ICL implantation in pa-tients with high myopia(all P<0.05).ROC curve analysis showed that the area under the ROC curve for predicting poor visual acuity recovery after ICL implantation in patients with high myopia by Logistic regression model was 0.938(95%CI:0.896-0.966),the sensitivity was 83.61%,and the specificity was 91.95%(P<0.05).Conclusion The visual acuity recovery after ICL implantation in patients with high myopia is affected by corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score.The Logistic regression model based on these factors has high predictive value for visual acui-ty recovery after ICL implantation.
4.Cognition of Colorectal Cancer-related Knowledge and Influencing Factors of Patients with Middle- and Advanced-stage Colorectal Cancer in Inner Mongolia
Jingru GAO ; Jiaxin LI ; Youlin QIAO ; Xi ZHANG ; Shaokai ZHANG ; Huifang XU ; Yunqi HUA ; Jinqi HAO ; Ying FU ; Zhengyang SHI ; Yanqin YU ; Jihai SHI
Cancer Research on Prevention and Treatment 2023;50(6):603-608
Objective To investigate the cognition of colorectal cancer-related knowledge and influencing factors of patients with middle- and advanced-stage colorectal cancer in ethnic minority areas of Inner Mongolia. Methods According to the national population and the prevalence of colorectal cancer, 277 patients with colorectal cancer were selected by stratified and random sampling in Inner Mongolia. The patients were surveyed in Baotou, Chifeng, Bayannaoer, and other hospitals. The questionnaire included patients' basic information, cognition of colorectal cancer risk factors and screening knowledge, screening information,
5.Research progress in quality research and evaluation of human mesenchymal stem cells
Yue SHI ; Yan LI ; Huifang JIN ; Xinrui ZHAO
International Journal of Biomedical Engineering 2023;46(3):275-280
As adult stem cells, human mesenchymal stem cells (hMSCs) have the potential for self-replication, renewal, and multidirection differentiation. Their unique biological function determines their wide clinical indications. Researchers can define the quality attributes of hMSCs according to clinical expectations. The quality study of hMSCs should consider microbiological safety, biological safety, cell biological properties, and biological effectiveness. Quality evaluation is a common physical, chemical, and biological evaluation method for hMSCs. Traditional product safety evaluation strategies cannot fully adapt to current technology and product usage characteristics. Researchers have developed new, effective evaluation methods based on current technology. In terms of product efficacy evaluation strategies, an efficacy evaluation system has been gradually established and standardized according to the intended clinical use and based on quality studies, which can enable researchers to evaluate hMSCs products more comprehensively at different stages and processes. In this paper, the progress of quality research and evaluation of human mesenchymal stem cells was reviewed to provide a reference for the utilization of stem cells in the field of regenerative medicine.
6.Predictive analysis of the number of hospitalized patients with acute pancreatitis based on time series model
Xinyi ZENG ; Xiao PAN ; Huan XU ; Han ZHANG ; Huifang XIA ; Xiaomin SHI ; Lei SHI ; Yan PENG ; Xiaowei TANG
Chinese Journal of Pancreatology 2023;23(4):251-256
Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.
7. Effects of geniposide metabolites genipin on induced HK-2 cells injury and NLRP3 pathway
Mingzhu SHI ; Tianxiang YE ; Yixuan LIU ; Huifang LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(5):481-488
AIM: To study the toxicity of genipin-a kind of geniposide metabolites induced human tubular epithelial cells HK-2 and its effect on NLRP3 pathway. METHODS: The dose of GP on HK-2 cells were preliminarily determined by CCK8 method, the apoptosis or necrosis rate of HK-2 cells was detected by Hoechst 33342 / PI, the level of LDH release and reactive oxygen species was detected by Kits, and mitochondrial membrane potential and intracellular calcium ion concentration were detected by high content imaging. Real-time PCR detected mRNA levels of kindey injury factor-1, osteopontin, NLRP3, Caspase-1, interleukin 1β, and interleukin 18. RESULTS: Compared with the 0 μg / mL group, GP>50 μg/mL significantly reduced cell viability (P< 0.05, P<0.01), and the IC50 value was 110.50 μg/mL. Set the control group, the low, medium and high dose groups of GP (50, 100, 200 μg/mL); Compared with the control group, the cell density decreased in the medium and high dose groups of GP, and the PI positivity, LDH release, ROS, Ca
8.Effects of a health management model based on reflexive reconstruction strategy in patients with acute pancreatitis
Yanru YIN ; Huifang LI ; Weiwei SHI
Chinese Journal of Modern Nursing 2023;29(33):4607-4611
Objective:To explore the effect of a health management model constructed based on reflexive reconstruction strategy in patients with acute pancreatitis.Methods:Totally 150 patients with acute pancreatitis admitted to Jincheng No.2 People's Hospital from January 2020 to January 2022 were selected by convenience sampling. They were divided into observation and control groups, each containing 75 individuals, using a random number table. Patients in the observation group were managed using a health management model under the reflexive reconstruction strategy, while patients in the control group followed a conventional health management model.Results:Six months post-intervention, the total score of health behavior capacity and the scores of its four dimensions, as well as the score indicating the level of health knowledge mastery in the observation group, were significantly higher than those in the control group ( P<0.01). Furthermore, the recurrence rate of acute pancreatitis in the observation group was 5.3% (4/75), which was lower than 16.0% (12/75) observed in the control group, demonstrating a statistically significant difference (χ 2=4.478, P=0.034) . Conclusions:The health management model developed based on the reflexive reconstruction strategy can enhance the health behavior capacity and the level of health knowledge mastery in patients with acute pancreatitis and reduce the recurrence rate of acute pancreatitis. It can serve as a reference for the continuous improvement of clinical health care management programs.
9.Knowledge, Attitude and Practice about Human Papillomavirus and HPV Vaccine in Chinese Mainland: A Meta-analysis
Zhengyang SHI ; Jinqi HAO ; Jihai SHI ; Zheng SU ; Shujun LIU ; Xi ZHANG ; Huifang XU ; Jingru GAO ; Ying FU ; Youlin QIAO ; Yanqin YU
Cancer Research on Prevention and Treatment 2022;49(5):464-471
Objective To understand and evaluate the knowledge, attitude and practice of female human papillomavirus and HPV vaccine in Chinese mainland. Methods We searched the relevant studies about the knowledge, attitude and behavior factors of HPV infection and HPV vaccine published in PubMed, MEDLINE, CNKI and Wanfang databases about Chinese mainland women from January 1, 1995 to January 31, 2021.Two researchers independently screened the literatures, extracted data and the literatures with quality score≥5 points.Chi square test was used to evaluate its heterogeneity.Begg' s test was used to evaluate publication bias. Results A total of 33 literatures were included, with a total number of 46013 people.The results showed that the total awareness rate of HPV in the population was 65.9%, the lowest rates were 16.0%, 41.2% and 14.4% in Northeast, rural areas and middle school students, respectively; while the highest rates of HPV were 77.4%, 56.3% and 71.0% in Central China, cities and towns and college students, respectively.The main source of HPV knowledge was the network/WeChat official account number (38.9%), and the lowest was family/friend (4.5%).The population's awareness rate of HPV vaccine related knowledge was 41.4%, the highest rates were 51.8% and 69.7% in East China and medical staff, respectively, while the lowest were 23.6% and 12.7% in Southwest and middle school students. Conclusion In order to achieve the total elimination of cervical cancer in China by 2030 as soon as possible, people should strengthen their awareness of HPV and HPV vaccine related knowledge.
10.The influence of duration of intra-abdominal hypertension on the prognosis of critically ill patients
Jianshe SHI ; Jialong ZHENG ; Jiahai CHEN ; Yeqing AI ; Huifang LIU ; Bingquan GUO ; Zhiqiang PAN ; Qiulian CHEN ; Mingzhi CHEN ; Yong YE ; Rongkai LIN ; Chenghua ZHANG ; Yijie CHEN
Chinese Journal of Emergency Medicine 2022;31(4):544-550
Background:In the clinical setting, the effect of intra-abdominal hypertension on the human body is dependent on time, but its role is not yet clear.Objective:To investigate the effect of the duration of intra-abdominal hypertension (IAH) on the prognosis of critically ill patients.Methods:This prospective cohort study enrolled 256 IAH patients who were admitted to the Surgical ICU of 10 Grade A hospitals in Fujian Province from January 2018 to December 2020. The duration of IAH (DIAH) was obtained after monitoring IAP, and ICU length of stay, duration of mechanical ventilation, duration of continuous renal replacement therapy (CRRT) and average daily energy intake from enteral nutrition during ICU stay were observed and recorded. The correlation was analyzed by Spearman rank correlation. The patients were divided into the survival group and the death group according to their survival state at 60 days after enrollment. Thereafter, clinical characteristics between the two groups were compared. Multivariable logistic regression was used to study and validate the relationship between DIAH and 60-day mortality. The receiver operating characteristics (ROC) curve was established to evaluate the predictive abilities of DIAH on the mortality risk.Results:In critically ill patients, DIAH was positively correlated with duration of mechanical ventilation ( r=0.679, P<0.001), duration of CRRT ( r=0.541, P<0.001) and ICU length of stay ( r=0.794, P<0.001), respectively. In addition, there was a negative correlation between DIAH and average daily energy intake from enteral nutrition ( r=-0.669, P<0.001). After multivariable adjustment, DIAH was an independent risk factor for 60-day mortality in critically patients with IAH ( OR=1.05, 95% CI: 1.01-1.12; P = 0.012), and exhibited a linearity change trend relationship with mortality risk. The ROC curve analysis of DIAH showed that the area under ROC curve (AUC) was 0.825 (95% CI: 0.763~0.886, P<0.01). When the cut-off value was 16.5 days, the sensitivity was 78.4% and the specificity was 75.4%. Conclusions:DIAH is an important risk factor for prognosis in critically ill patients. Early identification and rapid intervention for the etiology of IAH should be performed to shorten DIAH.

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