1.Arrhythmias and electrocardiographic characteristics in cancer patients treated with immune checkpoint inhibitors
Xuhong GENG ; Nan ZHANG ; Wenhua SONG ; Siyao CHENG ; Yi ZHENG ; Xiaotong MA ; Li WANG ; Xuan LI ; Tong LIU
Chinese Journal of Cardiology 2024;52(6):690-697
Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.
2.Comparison of clinical characteristics between first-episode and recurrent acute hypertrigly-ceridemic pancreatitis: a national multicenter clinical research
Shuai LI ; Jing ZHOU ; Guixian LUO ; Hongwei ZHANG ; Siyao LIU ; Weijie YAO ; Donghuang HONG ; Kaixiu QIN ; Lanting WANG ; Rong WEI ; Yizhen XU ; Longxiang CAO ; Zhihui TONG ; Yuxiu LIU ; Weiqin LI ; Lu KE
Chinese Journal of Digestive Surgery 2024;23(5):703-711
Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.
3.Discovery of a potent PROTAC degrader for RNA demethylase FTO as antileukemic therapy.
Lu LIU ; Yuanlai QIU ; Yuying SUO ; Siyao TONG ; Yiqing WANG ; Xi ZHANG ; Liang CHEN ; Yue HUANG ; Huchen ZHOU ; Hu ZHOU ; Ze DONG ; Cai-Guang YANG
Acta Pharmaceutica Sinica B 2024;14(12):5382-5392
The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of N 6-methyladenosine (m6A); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown. Herein, we designed the first FTO-targeting proteolysis targeting chimera (PROTAC) degrader QP73 using our FTO inhibitor Dac85-which potently inhibits FTO demethylation in AML cell lines-as a warhead. Notably, QP73 significantly induced FTO degradation in a time-, dose-, and ubiquitin-proteasome system-dependent manner and had superior antiproliferative activities to the FTO inhibitor Dac85 in various AML cell lines. Moreover, QP73 treatment significantly increased m6A modification on mRNA, promoted myeloid differentiation, and induced apoptosis of AML cells. Quantitative proteomics analysis showed that QP73 induced complete FTO degradation, upregulating RARA and ASB2 abundance and downregulating CEBPA, MYC, PFKP, and LDHB levels in AML cells. Lastly, QP73 exhibited antileukemic activity by increasing m6A modification and decreasing FTO levels in xenograft AML tumors. This proof-of-concept study shows that FTO-targeting PROTAC degraders can regulate the FTO signaling pathway and have potential antileukemia applications.
4.User experience of Nursing-Online Practice Promotion Application
Siyao WANG ; Ruting GU ; Yan ZHANG ; Qianqian LI ; Jingyuan WANG ; Tong SUN ; Kai CHEN ; Lili WEI
Chinese Journal of Modern Nursing 2022;28(9):1246-1251
Objective:To understand the user experience of Nursing-Online Practice Promotion Application ("N-OPP" APP) .Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 537 nursing students who had practiced in the Affiliated Hospital of Qingdao University from August to November 2020 and had used "N-OPP" APP were selected as the research objects. The general data questionnaire and the "N-OPP" APP user experience evaluation questionnaire were used for the investigation. A total of 537 questionnaires were distributed in this study and 529 valid questionnaires were recovered, with an effective recovery rate of 98.51%.Results:The total average score of the "N-OPP" APP user experience evaluation questionnaire items of 529 nursing students was (3.89±0.47) , and the average scores of items of operation performance, service performance, user experience and risk were respectively (3.87±0.65) , (4.04±0.60) , (3.90±0.70) and (3.42±0.62) . There were statistically significant differences in the use experience and operation performance dimensions of nursing students from different educational backgrounds, contact time of mobile learning APP, use time and use frequency of "N-OPP" APP ( P<0.05) . The service performance dimension items of nursing students with different educational background and frequency of "N-OPP" APP were compared, and the differences were statistically significant ( P<0.01) . The risk dimension items of nursing students with different "N-OPP" APP use frequencies were compared, and the difference was statistically significant ( P<0.01) . Conclusions:The development of "N-OPP" APP can solve some problems in the traditional teaching and training of clinical nursing skills, help nursing students to consolidate their nursing skills and obtain high recognition from nursing students, which can be used as an auxiliary tool for teaching and training of clinical nursing skills.
5.Construction of newly recruited nurses' core competence indicator system based on the concept of safety and quality improvement
Zhen LI ; Xia ZHAO ; Bingdu TONG ; Xinwei PAN ; Meng ZHANG ; Siyao WANG ; Xiaopeng HUO
Chinese Journal of Modern Nursing 2022;28(10):1281-1286
Objective:To construct the core competence indicator system of newly recruited nurses based on the concept of safety and quality improvement, so as to provide a reference for the construction of the training system of the core competence and the formulation of evaluation standards of newly recruited nurses.Methods:Through literature retrieval and analysis, a framework of core competency indicator system of newly recruited nurses guided by the concept of safety and quality improvement was initially constructed. From November 2020 to March 2021, 15 nursing education and nursing practice experts across the country were consulted for 3 rounds through the Delphi expert consultation, and the expert opinions were collected to finally determine the indicator system.Results:Among 3 rounds of expert consultation, the response rates of the questionnaires were all 100%, and the expert authority coefficient was 0.90, and the Kendall coordination coefficient of the three-level indicators was from 0.14 to 0.20 ( P<0.05) . The finalized core competence indicator system of newly recruited nurses included 7 first-level indicators (professional knowledge and ability, patient-centered nursing, cooperative communication, quality promotion, safety, nursing information ability, professional development) , 18 second-level indicators and 103 third-level indicators. Conclusions:The indicators of the core competence indicator system of newly recruited nurses are good, which can provide a reference for optimizing the training courses for newly recruited nurses and improving the evaluation standards.
6.Is axillary reverse mapping in patients with breast cancer oncologically safe?
Miao LIU ; Siyao LIU ; Nan WANG ; Peng LIU ; Lin CHENG ; Fuzhong TONG ; Hongjun LIU ; Shu WANG
Chinese Journal of General Surgery 2019;34(6):475-478
Objective To evaluate the oncological safety of axillary reverse mapping in patients with breast cancer.Methods Patients with sentinel lymph node biopsy(SLNB) or axillary lymphnode dissection (ALND) between Oct 2015 and Feb 2016 were enrolled in this study prospectively.Axillary reverse mapping (ARM) procedure was done using a radioisotope before the surgery.All the ARM nodes were identified and sent separately for histologic analysis.Results 78 patients underwent 78 axillary operations.Of 53 patients with SLNB,33 (62.3%)had ARM nodes identified.22 (41.5%)had the crossover of the ARM nodes with the SLNs,and one (4.5%) had positive ARM node.Of 36 patients with ALND,33 (91.7%) had ARM nodes identified.9(25%)had positive ARM nodes.Positive ARM node status was significantly associated with advanced axillary disease(P =0.036).Conclusion Preserving ARM nodes in SLNB is oncologically safe to reduce upper extremity lymphedema.

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