This study aimed to investigate the efficacy and safety of blinatumomab in adult patients with acute B-lymphoblastic leukemia (B-ALL) by conducting a retrospective analysis of the clinical data from 16 patients with B-ALL receiving blinatumomab at the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from June 2022 to April 2024. Among the 16 patients, 10 were classified as relapsed/refractory B-ALL and 6 were newly diagnosed Ph - B-ALL. Of the 10 patients with relapsed/refractory B-ALL, 8 achieved complete remission (CR) and minimal residual disease (MRD) negativity after one blinatumomab treatment cycle. In the 6 newly diagnosed patients, the bone marrow MRD was negative after one blinatumomab treatment cycle after initial induction chemotherapy followed by sequential blinatumomab treatment. Among them, four completed allogeneic hematopoietic stem cell transplantation and continuously maintained CR. This indicates that blinatumomab exhibits a high remission rate in both patients with relapsed/refractory and newly diagnosed B-ALL, thereby providing the possibility of bridging to transplantation and extending patient survival, with manageable adverse reactions.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Objective:To explore the association between sublingual microcirculatory perfusion vessel proportion (PPV), high mobility group protein B1 (HMGB1), and sepsis-induced coagulopathy (SIC), and to identify early predictive markers for clinical intervention.Methods:A total of 66 septic patients admitted to the Respiratory Intensive Care Unit (RICU) between November 2021 and May 2024 were enrolled. Based on SIC diagnosis within 24 hours of admission, patients were categorized into SIC ( n=36) and non-SIC ( n=30) groups. Clinical parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), sublingual PPV, and serum HMGB1 levels (measured at 0 h and 6 h), were analyzed. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to identify independent predictors. Results:Compared with the non-SIC group, the SIC group demonstrated significantly prolonged PT ( P<0.05) and APTT ( P<0.05), elevated 0 h lactate levels, and increased 6 h HMGB1. Spearman analysis revealed a positive correlation between 6 h PPV and platelet count ( P<0.05), while an inverse correlation was observed with 6 h PT ( P<0.05). Multivariate regression identified APTT, 6 h PPV, and 6 h HMGB1 as independent predictors of SIC. ROC analysis yielded AUC values of 0.732 for APTT, 0.802 for 6 h PPV, and 0.765 for 6 h HMGB1. The combination of 6 h PPV and HMGB1 further improved predictive accuracy (AUC=0.873). Conclusions:Prolonged APTT, decreased 6 h PPV, and elevated 6h HMGB1 are key indicators of SIC. Integrated assessment of these markers enhances early risk stratification in septic patients, facilitating timely clinical intervention.

Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.There-fore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural com-pounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehen-sive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objective:To construct and validate a competency-oriented entrustable professional activities (EPAs)-Competency-Milestones system for assessment of laparoscopic skills (ESALS).Methods:A research team composed of 15 members from five medical institutions was established. Taking the Staged Training and Assessment of Laparoscopic Skills program as the basis for EPAs, ESALS was constructed through scoping review and behavioral event interviews and the use of the Kawakita Jiro method. ESALS was applied to evaluate 49 trainees and 10 specialists (including 5 novices and 5 experts) on basic and advanced laparoscopic skills, respectively, in comparison with two other assessment tools—the Training and Assessment of Basic Laparoscopic Techniques (TABLT) and the Global Operative Assessment of Laparoscopic Skills (GOALS). Perform Mann Whitney U test using SPSS 23.0 software, and use Spearman coefficient for correlation analysis.Results:Through reviewing 13 literuature articles and interviewing 10 senior surgeons, the ESALS was developed, comprising 10 EPAs, 8 dimensions of competency characteristics, and 5 entrustable levels. In the basic skills evaluation, the ESALS score was significantly positively correlated with the TABLT score ( R=0.881, P<0.001). In the advanced skills evaluation, significant differences were observed between the novice and expert groups in all the ESALS competency scores (all P<0.05), while no difference was detected in the GOALS score of tissue handling ability. Conclusions:ESALS provides comprehensive evaluation, detailed standards, and precise feedback, with comparable efficacy to conventional tools. Future work should focus on expanding sample size to verify its generalizability and developing an electronic tool to enhance application efficiency.

Objective:To construct and validate a competency-oriented entrustable professional activities (EPAs)-Competency-Milestones system for assessment of laparoscopic skills (ESALS).Methods:A research team composed of 15 members from five medical institutions was established. Taking the Staged Training and Assessment of Laparoscopic Skills program as the basis for EPAs, ESALS was constructed through scoping review and behavioral event interviews and the use of the Kawakita Jiro method. ESALS was applied to evaluate 49 trainees and 10 specialists (including 5 novices and 5 experts) on basic and advanced laparoscopic skills, respectively, in comparison with two other assessment tools—the Training and Assessment of Basic Laparoscopic Techniques (TABLT) and the Global Operative Assessment of Laparoscopic Skills (GOALS). Perform Mann Whitney U test using SPSS 23.0 software, and use Spearman coefficient for correlation analysis.Results:Through reviewing 13 literuature articles and interviewing 10 senior surgeons, the ESALS was developed, comprising 10 EPAs, 8 dimensions of competency characteristics, and 5 entrustable levels. In the basic skills evaluation, the ESALS score was significantly positively correlated with the TABLT score ( R=0.881, P<0.001). In the advanced skills evaluation, significant differences were observed between the novice and expert groups in all the ESALS competency scores (all P<0.05), while no difference was detected in the GOALS score of tissue handling ability. Conclusions:ESALS provides comprehensive evaluation, detailed standards, and precise feedback, with comparable efficacy to conventional tools. Future work should focus on expanding sample size to verify its generalizability and developing an electronic tool to enhance application efficiency.

This study aimed to investigate the efficacy and safety of blinatumomab in adult patients with acute B-lymphoblastic leukemia (B-ALL) by conducting a retrospective analysis of the clinical data from 16 patients with B-ALL receiving blinatumomab at the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from June 2022 to April 2024. Among the 16 patients, 10 were classified as relapsed/refractory B-ALL and 6 were newly diagnosed Ph - B-ALL. Of the 10 patients with relapsed/refractory B-ALL, 8 achieved complete remission (CR) and minimal residual disease (MRD) negativity after one blinatumomab treatment cycle. In the 6 newly diagnosed patients, the bone marrow MRD was negative after one blinatumomab treatment cycle after initial induction chemotherapy followed by sequential blinatumomab treatment. Among them, four completed allogeneic hematopoietic stem cell transplantation and continuously maintained CR. This indicates that blinatumomab exhibits a high remission rate in both patients with relapsed/refractory and newly diagnosed B-ALL, thereby providing the possibility of bridging to transplantation and extending patient survival, with manageable adverse reactions.

Objective To analyze the relationship between expression levels of long non-coding RNA(LncRNA)LINC00342 and microRNA-203a-3p(miR-203a-3p)in colorectal cancer tissue and the prognosis of patients within 5 years after surgery.Methods Samples of colorectal cancer tissue and paracancer tissue of 133 patients with colorectal cancer were collected.Expression levels of LncRNA LINC00342 and miR-203a-3p were detected by fluorescence quantitative PCR.Survival and death were recorded after 5 years of follow-up.The LncRNA LINC00342 and miR-203a-3p expressions and clinicopathological parameters in patients under different conditions were compared.The correlation between expressions of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue was analyzed,and their predictive value for the prognosis was also analyzed.Results The expression level of LncRNA LINC00342 was higher in colorectal cancer tissue than that in paracancer tissue,and the expression level of miR-203a-3p was lower in colorectal cancer tissue than that in paracancer tissue(P＜0.05).The expression levels of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue were negatively correlated(P＜0.05).The proportion of patients with low tumor differentiation,TNM stage Ⅲ and lymph node metastasis were higher in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group than those in the LncRNA LINC00342 low expression group and the miR-203a-3p high expression group,respectively(P＜0.05).The 5-year overall survival rate after operation was lower in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group(P＜0.05).The proportion of patients with low tumor differentiation,TNM stage Ⅲ,lymph node metastasis,and higher expression level of LncRNA LINC00342 were higher in colorectal cancer tissue of the death group than those in the survival group,and the expression level of miR-203a-3p was lower than that in the survival group(P＜0.05).Low tumor differentiation,TNM stage Ⅲ,lymph node metastasis,high expression of LncRNA LINC00342 and low expression of miR-203a-3p were independent risk factors for death within 5 years after colorectal cancer surgery(P＜0.05).The combined predictive value of LncRNA LINC00342 and miR-203a-3p for prognosis was greater than that of individual prediction.Conclusion LncRNA LINC00342 is higher expressed and miR-203a-3p is lower expressed in colorectal cancer tissue,and the combined detection of the two is expected to become a clinical evaluation indicator for predicting postoperative survival.

Objective:To prepare recombinant protein of group 36 allergen of Dermatophagoides farinae(Der f 36),to deter-mine its immunogenicity and bioinformatics analysis was performed.Methods:Nucleic acid sequence coding for Der f 36 was obtained and artificially synthesized,pET-28a(+)was inserted to construct pET-28a(+)-Der f 36 plasmid and transformed into BL21(DE3)receptor cells.After expressed and purified in BL21(DE3),recombinant allergen rDer f 36 was obtained,recombinant protein rDer f 36 was identified by SDS-PAGE and Western blot.Serum IgE binding rates of rDer f 36 was determined by IgE-ELISA.Cross-reactivity between rDer f 36 and rDer p 36 was detected by IgE-ELISA inhibition assay.HNEpC cells were cultured with rDer f 36 for 24 h and cytokines were detected.Bioinformatics softwares were used to analyze physicochemical properties and structures of Der f 36 and Der p 36.Results:Coding gene for Der f 36 was obtained with a total length of 690 bp,whose molecular weight was 25.6 kD;serum IgE binding rate of rDer f 36 was 42.1%by IgE-ELISA;IgE-ELISA inhibition assay showed that rDer p 36 had 40%(8/20)inhibition rate(>50%)for rDer f 36,with an average inhibition rate of 52.98%.Compared with control group,HNEpC cells cultured with rDer f 36 showed that IL-6,IL-8,IL-33,IL-25 and TSLP expressions had increased;bioinformatics analyses show that sequence consistency of Der f 36 and Der p 36 was 77.63%,with similar physicochemical properties.Secondary structure analysis showed that both of them contained α helix,β-turn and random coils,and content of random coils was the highest;structure of C2 domains was also highly overlapping(RMSD=0.046).Conclusion:Recombinant allergen rDer f 36 is successfully prepared with good immunogenicity,laying foundation for diagnosis and treatment of dust mite allergen single component.High similarity in physical and chemical properties,secondary structure,and tertiary structure between Der f 36 and Der p 36 determines their cross reactivity.