Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective Readout segmentation of long variable echo-trains diffusion weighted imaging(RESOLVE DWI)was used to analyze the difference of apparent diffusion coefficient(ADC)value in deep cerebral nucleus and its correlation with clinical characteristics in patients with Parkinson's disease(PD).Methods Clinical data of 60 patients with PD were retrospectively analyzed as PD group,and were divided in-to the tremor group(n=30)and the bradykinesia group(n=30)according to symptom type,middle-aged(≤65 years old)group(n=23)and elderly(＞65 years old)group(n=37)according to age,and 60 healthy vol-unteers were selected as the control group during the same period.ADC values were measured on the ADC map of RESOLVE DWI sequence,and the ADC values of bilateral putamen,pallidus,substantia nigra,rubra,and dentate nucleus were analyzed and their correlation with UPDRS-Ⅲ score and H&Y grading.Results Compared with the control group,the ADC values of both putamen,globus pallidus,globus pallidus,red nucleus,right substantia nigra and right dentate nucleus were increased in the PD group,the ADC values of both putamen,globus pallidus,red nucleus and right substantia nigra in the tremor group were increased,and the ADC values of right putamen,globus pallidus and bilateral red nucleus in the bradykinesia group were increased(P＜0.05).Compared with the bradykinesia group,the values of ADC in the tremor group were similar.Compared with the middle-aged group,the ADC values of right putamen,bilateral globus pallidus,left substantia nigra and left red nucleus were higher in the elderly group(P＜0.05).In the PD group,the ADC values of the right putamen,globus pallidus,and dentate nucleus were positively correlated with H&Y grade and UPDRS-Ⅲscore,and the ADC value of the left putamen was positively correlated with H&Y grade.Conclusion RE-SOLVE DWI can be used to evaluate the differences in deep gray matter nuclei in PD patients,and its ADC value may be used to evaluate and predict the severity of nuclear mass damage and motor symptoms in PD pa-tients.

In recent years， data mining algorithms have been widely employed in scientific research within the field of traditional Chinese medicine （TCM）. The data mining algorithms are used to effectively handle and analyze the complex data in TCM formulas， providing a rational explanation for the mechanism of action. This method has proven particularly useful in uncovering patterns of compatibility and frequent combinations of herbs in TCM， thereby enhancing the reliability and accuracy of clinical diagnosis， target screening， and the study of new drugs. This paper reviews and analyzes 147 papers on TCM formula research that utilize data mining algorithms. The results indicate that data mining algorithms play a unique advantage in six sub- areas， including the study on the mechanism of action in TCM formula， the dose-efficacy of TCM formulas， the identification of core drugs pairs/groups， mining the relationships among “formulas-drug-symptom”， the discovery of new formulas， and mining the compatibility law. Notably， association rules and clustering algorithms are the most representative.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative method for various hematological diseases. With the optimization of transplantation technology, the clinical application of allo-HSCT is more and more mature. Post-transplant liver injury is one of the common postoperative complications, which seriously affects the quality of life and long-term survival of patients. The causes of liver injury after allo-HSCT can be divided into non-infectious and infectious factors, which show similar clinical manifestations and different treatment principles. Timely diagnosis of post-transplant liver injury and the identification of the disease cause will be beneficial for early prevention or targeted treatment, thereby improving patients' prognosis. This review focuses on the etiology, clinical features, and treatment options of liver injury after allo-HSCT, aiming to deepen the understanding of hematologists on liver injury after allo-HSCT.

Flow cytometry (FCM) is a technique that can perform the multiparametric analysis of single cell. Recently, FCM has become an important tool to assist the management of chronic diseases. The clinical application of FCM has expanded from blood diseases such as leukemia and lymphoma to other chronic diseases such as solid tumors and chronic obstructive lung. Besides, FCM plays an important role in improving the efficacy of early diagnosis, monitoring on the immune status of patients, understanding of the disease progression, and assessment of prognosis of patients. Henceforth, more assistance could be provided by FCM to optimize the management of chronic diseases with the continuous innovation.

Flow cytometry (FCM) is an interdisciplinary cell analysis technology that integrates optics, fluid dynamics, electronics, and computer science. While FCM is widely utilized in diagnosing and monitoring hematologic malignancies, its application in nonhematopoietic neoplasms (NHN) remains in its nascent stages. However, recent advancements in science and technology have led to the emergence of innovative FCM technologies, such as mass spectrometry flow cytometry (CyTOF) and spectral flow cytometry (SFC), offering promising avenues for their clinical application aiming to assist the clinical diagnosis of NHN patients. This review summarizes the features of fundamentals of traditional FCM, CyTOF, and SFC technologies, along with their applications and future prospective in NHN diagnosis and treatment, aiming to offer updated insights for the continued expansion and utilization of FCM technology in clinical laboratory settings.

Objective:To explore the efficacy and adverse reactions of bcl-2 inhibitor venetoclax (VEN) combined with hypomethylating agents (HMA) in treatment of adult myeloid neoplasms.Methods:A retrospective case series study was conducted. The clinical data of 43 patients with myeloid neoplasms treated by VEN combined with HMA in Shenzhen People's Hospital between December 2018 and December 2022 were collected. The general data, short-term efficacy, survival and adverse reactions of patients were summarized.Results:A total of 43 patients were enrolled in the study, of which 24 cases (55.8%) were male with the mean age [ M ( Q1, Q3)] of 64 years (55 years, 69 years). All 43 patients included 28 cases (65.1%) of acute myeloid leukemia (AML), 14 cases (32.6%) of high-risk myelodysplastic syndrome (HR-MDS) and 1 case (2.3%) of chronic myelomonocytic leukemia. The overall response rate (ORR) was 83.7%(36/43); the rate of complete remission (CR) / incomplete blood count recovery (CRi) or marrow complete remission (mCR) rate was 72.1% (31/43); and the negative rate of minimal residual disease (MRD) of patients achieving CR/CRi or mCR was 45.2% (14/31). The ORR of AML and HR-MDS patients was 89.3% (25/28), 71.4% (10/14), respectively; the CR/CRi or mCR rate of AML and HR-MDS patients was 75.0% (21/28) and 64.3% (9/14), respectively. The negative rate of MRD of patients achieving CR/CRi or mCR was 47.6% (10/21), 44.4% (4/9); there were no statistically significant differences in ORR, CR/CRi or mCR rates and the MRD negative rates among patients achieving CR/CRi or mCR (all P > 0.05). The median follow-up time was 30.0 months (range: 1.0-41.0 months). The median progress-free survival (PFS) and the overall survival (OS) time of all groups was 8.0 months, 15.0 months, respectively. The median PFS time was 8.5 months and 7.0 months, respectively in AML and HR-MDS patients, and the difference in PFS was statistically significant ( P = 0.154); the median OS time was 24.0 months and 10.0 months, respectively in AML and HR-MDS patients, and the difference in OS was statistically significant ( P = 0.020). The median OS was not reached in 12 patients who bridged to allogeneic hematopoietic stem cell transplantation and the median OS time was 15.0 months in 13 patients who did not undergo the transplantation; and the difference in OS between the transplantation group and non-transplantation group was statistically significant ( P = 0.008). Grade 3-4 myelosuppression occurred in 97.7% patients (42/43) in all groups and grade 3-4 agranulocytosis combined with fever occurred in 48.8% patients (21/43). In all groups, 6 patients (14.0%) developed grade 3-4 infection during treatment, and 3 HR-MDS patients of them died due to severe infection during treatment. All the non-hematological adverse reactions were grade 1-2. Conclusions:VEN+HMA regimen shows good therapeutic effects in myeloid neoplasms patients, with rapid deep remission. The prolonged survival time can be achieved in some patients who successfully bridged to allogeneic hematopoietic stem cell transplantation. The survival benefit in AML patients may be better than that in HR-MDS patients. Most myeloid neoplasms patients still suffer the different degrees of bone marrow suppression during treatment with VEN+HMA.

Objective:This study aimed to investigate the predictive value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory on future major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (SCAD) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted on SCAD patients admitted to the Department of Cardiology at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, from January 2013 to December 2021. A total of 828 subjects were enrolled, comprising 592 males and 236 females, with an average age of (66.44±11.71) years. SCAD patients post-percutaneous coronary intervention (PCI) were stratified into three NT-proBNP trajectory groups: T1 Low-Low (219 cases), T2 Medium-Low (363 cases), and T3 High-High (246 cases). The median follow-up time was 2.1 years, and the maximum follow-up time was 9 years. The primary clinical endpoint event was MACE. The NT-proBNP concentration in patients′ serum was measured using enzyme-linked fluorescent assay, and different trajectory groups were determined using latent class trajectory modeling. The association between NT-proBNP trajectory and occurrence of MACE in SCAD patients was evaluated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression models.Results:A total of 67 (8.1%) major adverse cardiovascular events occurred, including 43 cases (5.2%) of all-cause mortality, 13 cases (1.6%) of heart failure death, 9 cases (1.1%) of non-fatal myocardial infarction, and 15 cases (1.8%) of non-fatal stroke. Kaplan-Meier survival curve analysis showed significant differences in survival rates among T1, T2, and T3 groups of SCAD patients for MACE, all-cause mortality, and heart failure death (all P<0.001). In the multivariable Cox regression analysis, the risk of MACE occurrence for patients in the T2 group and T3 group was 1.708 times (95% CI 0.72-4.05) and 3.842 times (95% CI 1.625-9.081) compared to the T1 group, respectively. Moreover, a statistically significant linear trend was observed for the risk of MACE occurrence across trajectory groups ( P<0.001). Conclusions:NT-proBNP trajectory groups after PCI in SCAD patients are strongly associated with the risk of MACE occurrence and can serve as an independent predictor for MACE. Dynamic monitoring of NT-proBNP during follow-up to obtain longitudinal trajectories helps identify high-risk SCAD patients and implement timely effective intervention measures.

Objective:To explore the influence of substance abuse history on anxiety and depression of male prisoners during their imprisonment, and its relationship with violent behavior.Methods:A questionnaire survey was conducted among 1 455 prisoners from October to November 2019.Self-administered personal substance abuse history questionnaires were used to collect the information on substance abuse (alcohol, tobacco, and drug use). The generalized anxiety scale (GAD-7) and patient health questionnaire (PHQ-9) were used to investigate anxiety and depression.All subjects were divided into substance abuse group ( n=871) and non substance abuse group ( n=584) according to whether they had a history of substance abuse or not.SPSS 21.0 software was used for statistical analysis.The statistical methods were t-test, chi square test and Logistic regression analysis. Results:(1)The scores of GAD-7 ((4.95±5.88) vs (3.35±5.33), t=-5.407, P<0.01) and PHQ-9 ((6.69±6.50) vs (4.48±5.73), t=-6.821, P<0.01) scales in the substance abuse group were higher than those in the no-substance abuse group.(2)Somatic disease( β=0.700, OR=2.014, 95% CI=1.599-2.538, P<0.05), history of alcohol abuse( β=0.434, OR=1.543, 95% CI=1.176-2.025, P<0.05), history of tobacco abuse( β=0.387, OR=1.473, 95% CI=1.154-1.880, P<0.05), age ≤ 45( β=0.372, OR=1.450, 95% CI=1.118-1.881, P<0.05) were the risk factors of anxiety among prisoners.Somatic disease( β=0.686, OR=1.986, 95% CI=1.581-2.496, P<0.05), history of tobacco abuse( β=0.488, OR=1.629, 95% CI=1.286-2.063, P<0.05), age ≤ 45( β=0.484, OR=1.622, 95% CI=1.260-2.089, P<0.05), history of alcohol abuse( β=0.344, OR=1.410, 95% CI=1.073-1.854, P<0.05) were the risk factors of depression among prisoners.(3) Years of education ≤ 9 years( β=0.900, OR=2.459, 95% CI=1.855-3.261, P<0.05), age ≤ 45( β=0.788, OR=2.199, 95% CI=1.690~2.860, P<0.05), unmarried( β=0.683, OR=1.980, 95% CI=1.421-2.759, P<0.05), history of alcohol abuse( β=0.308, OR=1.361, 95% CI=1.053-1.758, P<0.05), history of drug abuse( β=0.557, OR=1.745, 95% CI=1.055-2.885, P<0.05) were risk factors for violent behavior of prisoners. Conclusion:The history of substance abuse may be a risk factor for anxiety and depression of prisoners during their imprisonment.Alcohol and drug abuse are both factors influencing the occurrence of violent behavior.

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.
Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/adverse effects* ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; Apoptosis