[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

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.

Purpose To investigate the expression of POLR2M in colorectal cancer(CRC)and its effects on cell growth,apoptosis and invasion.Methods GEPIA2.0,TCGA and Kaplan-Meier Plotter databases were used to ana-lyze the differential expression of POLR2M in CRC tissues and normal adjacent tissues,and to evaluate its prognostic significance using the Log-rank test.Quantitative real-time PCR(qRT-PCR)was used to detect the expression of POLR2M in human colorectal cancer cell lines SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116,SW620 and human normal colorectal cell line FHC.DLD-1 and RKO cells were stably transfected with lentivirus,and the POLR2M groups were up-regulated into the control group(LV-NC)and experimental group(LV-POLR2M),and the transient transfec-tion of SW620 and SW480 cells with interfering fragments of SiRNA was used to down-regulate the POLR2M groups into the control group(Si-NC)and experimental group(Si-POLR2M),and the transfection efficiency of each group was verified.CCK-8,plate cloning,Transwell and scratch healing assays were used to detect cell proliferation,invasion and migration.Flow cytometry was used to detect the effects of POLR2M on cell cycle and apoptosis.Results GE-PIA2.0,TCGA and Kaplan-Meier Plotter database analysis showed that the expression of POLR2M in colorectal cancer was significantly higher than in normal adjacent tissues(P＜0.05),and the expression of POLR2M was closely associ-ated with the histological type of colorectal cancer and lymph node metastasis(P＜0.05),but not with the age,gen-der,tumor grade and vascular invasion of patients(P＞0.05).The prognosis of patients with POLR2M overexpression was poor(P＜0.05).The results of qRT-PCR showed that compared with FHC cells,the mRNA expression of POLR2M in SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116 and SW620 cell lines was increased(F=97.7,P＜0.05),and POLR2M stable overexpression and interference cell lines were successfully constructed.Compared with the LV-NC group,the viability,colony number,number of cells passing through the chamber and cell mobility of DLD-1 and RKO cells in the LV-POLR2M group were significantly increased(P＜0.05).Compared with the Si-NC group,the viability,colony number,number of cells passing through the chamber,and cell mobility of SW620 and SW480 cells in the Si-POLR2M group were significantly decreased(P＜0.05).Downregulation of POLR2M induced cell cycle arrest in G1 phase and promotes apoptosis(P＜0.05).Conclusion POLR2M may play a role as a pro-tumor gene in CRC,and its high expression can significantly promote the proliferation and invasion of CRC cells.

Aim To analyze the correlation between serum retinol-binding protein 4(RBP4),low density lipo-protein cholesterol to albumin ratio(LDLC/Alb),monocyte to high density lipoprotein ratio(MHR)and plaque stability in carotid atherosclerosis population and their predictive value for acute ischemic stroke(AIS).Methods A total of 197 patients with asymptomatic carotid atherosclerosis admitted to our hospital from September 2021 to January 2023 were selected for a prospective cohort study,and they were categorized into occurred group and non-occurred group according to whether AIS occurred within 12 months.Baseline information at time of visit,results of the cervical ultrasonography and serum RBP4,LDLC/Alb,MHR levels were compared between the two groups.Spearman/Pearson and receiver operating characteristic(ROC)curve were used to analyze the corr-elation of RBP4,LDLC/Alb and MHR with carotid atherosclerosis and plaque stability,and the value of predicting AIS in carotid atherosclerosis population.Hosmer-Lemeshow goodness of fit test was used to evaluate the calibration ability of serum RBP4,LDLC/Alb and MHR to jointly predict AIS in carotid atherosclerosis population.Results The carotid intima-media thickness(IMT)was higher in occurred group than that in non-occurred group.There were more soft plaques and mixed plaques in occurred group than in non-occurred group(P＜0.05).Serum levels of RBP4,LDLC/Alb and MHR were higher in occurred group than those in non-occurred group(P＜0.05).The correlation analysis showed that the levels of serum RBP4,LDLC/Alb and MHR were positively correla-ted with IMT(r=0.803,0.740,0.710)and plaque properties(r=0.736,0.685,0.703)(P＜0.001).ROC curve a-nalysis showed that the AUC of serum RBP4,LDLC/Alb and MHR in predicting AIS in carotid atherosclerosis population was 0.796,0.821 and 0.828,respectively,and the AUC of MHR was the largest;the AUC of the combination of serum RBP4,LDLC/Alb and MHR was 0.936,which was higher than that of MHR(Z=2.978,P＜0.05),the predictive sensi-tivity and specificity were 88.24％and 87.40％.Hosmer-Lemeshow goodness of fit test showed that there was no signifi-cant difference between serum RBP4,LDLC/Alb and MHR in predicting AIS and the actual observation value in carotid atherosclerosis population(P＞0.05),and the prediction model had good calibration ability.Conclusion Serum RBP4,LDLC/Alb,and MHR are positively correlated with carotid atherosclerosis and plaque stability,and can predict the occurrence of AIS.Combined detection of the three can be used as a method for early identification of potential high-risk populations for AIS,providing a new,quantifiable guidance scheme for the prevention and treatment of AIS in carotid ath-erosclerotic population.

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Objective:To analyze the treatment-free remission (TFR) outcomes after discontinuation of tyrosine kinase inhibitor (TKI) in children with chronic myeloid leukemia (CML).Methods:In this retrospective cohort study, clinical data of 14 chronic phase CML children aged <18 years who had achieved stable deep molecular response (DMR) for ≥ 2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30, 2016 to January 30, 2022 were collected retrospectively. According to the different TFR outcomes after discontinuation of TKI, patients were divided into loss of major molecular response (MMR) group and without loss of MMR group, differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test. Results:Out of 14 children with TKI discontinuation, 7 were male and 7 were female. The age at diagnosis was 14.0 (4.8, 17.0) years, and the age at TKI discontinuation was 22.0 (12.5, 27.0) years. Among them, 8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation. The follow-up time was 37.0 (27.8, 47.5) months, and 7 cases lost MMR at the time of discontinuation of 3.0 (2.0, 11.0) months. Eight children gained TFR at 6 months, 7 children gained TFR at 12 and 24 months. Amongst the 6 children who received second-generation TKI prior to TKI discontinuation, 2 children lost MMR at 3 and 11 months and 4 children gained TFR, among the 8 children who discontinued imatinib, 5 children lost MMR at the time 3.0 (2.0, 9.0) months and 3 children gained TFR. The age at diagnosis and TKI discontinuation, the time from TKI treatment to the acquisition of DMR, the duration of TKI treatment before TKI discontinuation, the duration of DMR before TKI discontinuation, and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not lose the MMR and the 7 children in the group that lost the MMR (all P>0.05) . All the 7 children with confirmed loss of MMR immediately restarted TKI therapy, and all regained DMR after 2.0 (2.0, 11.0) months of therapy. None of the children had disease progression. After TKI discontinued, only 1 child had mild bone pain, which could be relieved by oral antipyretic analgesic drugs. Conclusions:Children with CML who have achieved a durable stable DMR for≥2 years on TKI therapy can discontinue the TKI and obtain TFR. Both the longer duration of TKI therapy, the longer duration of DMR and the use of second-generation TKI therapy before TKI discontinuation, may allow more children with CML who are expecting TKI discontinuation to have access to TFR.

Objective:To investigate the application of Galectin-9 and Pentraxin3 in cardiotoxicity assessment during anthracycline chemotherapy in breast cancer patients.Methods:A total of 143 breast cancer patients who received anthracycline chemotherapy in Department of Breast, Shanxi Provincial People’s Hospital from Oct. 2021 to Oct. 2023 were separated into cardiotoxic group ( n=47) and non-cardiotoxic group ( n=96) according to whether cardiotoxicity occurred. Clinical data of patients were collected and the risk factors of cardiotoxicity were analyzed by univariate and multivariate Logistic regression. The predictive efficacy of serum Galectin-9 and Pentraxin3 levels on cardiotoxicity was evaluated by receiver operating characteristic curve (ROC) . Results:There was no statistically significant difference in age, body mass index, total cholesterol, triglycerides, low density lipoprotein, high density lipoprotein, smoking history, drinking history, underlying disease (hypertension, diabetes, hyperlipidemia) , tumor stage, pathological type, tumor size, anthracycline type, or dose between the two groups ( t=1.07, 1.22, 0.96, 0.43, 1.07, 0.50; χ 2=0.12, 1.20, 0.14, 0.01, 0.47, 0.14, 3.32, 3.83, 1.91, 3.18, P > 0.05) ; The levels of troponin and B-type brain natriuretic peptide in cardiotoxicity group were higher than those in non-cardiotoxicity group ( t=13.48, 10.28, P < 0.05) , and serum Galectin-9 and Pentraxin3 levels were also higher ( t=22.53, 17.92, P < 0.05) . Multivariate Logistic regression analysis showed that high levels of troponin, B-type brain natriuretic peptide, Galectin-9 and Pentraxin3 were all influential factors in the occurrence of cardiotoxicity ( OR=2.221, 2.050, 1.925, 1.976, P < 0.05) . ROC curve analysis showed that the area under curve of serum Galectin-9 for predicting cardiotoxicity was 0.722, the predictive sensitivity was 68.09%, and the specificity was 77.08%; The area under the curve of miR-135 for predicting cardiotoxicity was 0.636, the predictive sensitivity was 44.68%, and the specificity was 82.29%. Conclusion:Serum Galectin-9 and Pentraxin3 have high expression levels in breast cancer patients treated with anthracyclines, which are influential factors for the occurrence of cardiotoxicity after chemotherapy, and have high predictive value for the occurrence of cardiotoxicity in patients.

Objective:To explore the application effect of Total Life Cycle Management(TLCM)in managing maintenance cost of ultrasound imaging equipment.Methods:Thirty ultrasound imaging equipment of the China-Japan Friendship Hospital from June 2021 to July 2023 were selected.From June 2021 to June 2022,a conventional maintenance mode was adopted to manage these equipment,and TLCM was implemented to manage them from July 2022 to July 2023.The qualified rate and failure frequency of the ultrasound imaging equipment,the satisfaction scores of medical staffs in using equipment,and the costs of operation and maintenance were compared between different management modes.Results:Under TLCM mode,the qualified rate was 93.33%,which was significantly higher than 73.33% under conventional maintenance mode,and the difference was significant(x2=4.320,P＜0.05). Under TLCM mode,the boot-up time of ultrasound imaging equipment was shorter than that under the conventional maintenance mode,and the difference was significant (t=7.146,P＜0.05). Under TLCM mode,the failure rate of long-term use of equipment was lower than that under conventional maintenance,and the difference was significant (x2=4.443,P＜0.05). The satisfaction scores of medical staffs for the performance,efficiency,and cleanliness of equipment under TLCM mode were higher than those under conventional maintenance mode,and the differences of them between two modes were significant (t=3.955,5.872,6.368,8.214,P＜0.05). Under TLCM mode,both maintenance costs and operational expenses were lower than those under conventional maintenance,and the differences of them between two modes were significant (t=41.353,16.743,P＜0.05). Conclusion:TLCM can effectively enhance operationally qualified rate of equipment,and reduce maintenance costs and failure rate of equipment in long-term use,and improves the satisfaction of medical staff.

Gout in modern medicine is often attributed to "Li Jie Disease （历节病）"， "Bai Hu Wind" （白虎风）， and "Bi （痹） Syndrome" categories in traditional Chinese medicine， mainly because its joint pain often presents as wandering attacks， and the clinical symptoms are similar to those caused by wind. However， the essence of gout is actually dietary disorders caused by internal injuries， so it should not be classified as Bi （痹） syndrome due to wind， cold， dampness. Focusing on the theory of "gout is not Bi syndrome" proposed by TONG Xiaolin， combining ancient and modern medical literature and modern clinical research， this article analyzes the underlying etiology of gout， which originates from dietary irregularities and accumulation of turbid toxins， as well as the disease mechanism of "toxicity hurts joints and accumulation of toxins impairs the kidneys"， in order to clarify the essential difference between gout and impediment syndrome. Using the theory of "state-targeted diagnosis and treatment"， gout is classified into two categories： dampness-heat and deficiency-cold， and the treatment strategy of lowering the turbid toxin， facilitating the joints， and preserving the kidneys was proposed in order to guide the clinical practice.

Objective Bibliometric analysis software VOSviewer and CiteSpace were applied to analyze literatures related to acupuncture for myocardial Ischemia/Reperfusion(I/R)injury published in Chinese and English,to explore the status quo,dynamic trend and hot spots in the field,in order to provide reference for future research.Methods Based on the literature on acupuncture and moxibustion for myocardial I/R injury published in CNKI and Web of Science Core Collection database,VOSviewer and CiteSpace software were used to analyze literature publication trends,authors,institutions,countries,journals,keywords and citations,and draw graphs and tables to show the development status of the field and analyze the future development direction.Results Both Chinese and English literatures on the treatment of myocardial I/R injury by acupuncture and moxibustion show an increasing trend,which is one of the academic hotspots with great potential at present.In terms of Chinese literature,Yan Jie is the scholar who has published the most papers,and Hunan University of Traditional Chinese Medicine is the representative of the high production institution.The journal of Acupuncture Research has published the most papers.In terms of English literature,lu sheng-feng is the representative scholar with a high number of publications,Nanjing University of Chinese Medicine is the institution with the largest number of publications,and Evidence-Based Complementary and Alternative Medicine is the journal with the largest number of publications.The authors in the field have weak interinstitutional cooperation and exchange,and their research is mainly from China,with little international collaboration and exchange.At present,acupuncture treatment of myocardial I/R injury covers three aspects:specific acupoints,molecular biological mechanisms and clinical studies,which mainly focus on seven hot spots.Conclusion The bibliometric visual analysis visually demonstrated the current status,hot spots and frontier trends of acupuncture in the treatment of myocardial I/R injury.In the future,it is necessary to strengthen international collaboration,promote exchanges and cooperation between scholars and institutions,and promote the publication of multi-center,large-sample and high-level clinical randomized controlled studies;At the same time,the effect mechanism was further discussed from the perspectives of new molecular biological mechanisms,new intervention measures and point selection,and clinical translational research was carried out.