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*

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.

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

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.

With the number of cases of coronavirus disease-2019 (COVID-19) increasing rapidly, the World Health Organization (WHO) has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting, and self-isolate in the community. This may pose a potential virus transmission risk. We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients. This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort. Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9, 13, 17, and 21 d after admission. The nomogram was validated in the validation cohort and evaluated by concordance index (C-index), area under the curve (AUC), and calibration curve. A higher absolute lymphocyte count (
Aged ; Aged, 80 and over ; Antibodies, Viral/blood* ; Area Under Curve ; COVID-19/virology* ; Female ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Nomograms ; Proportional Hazards Models ; Retrospective Studies ; Viral Load ; Virus Shedding

Objective:To investigate the clinical efficacy of P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) as a first-line regimen for the treatment of primary extranasal nasal-type NK/T cell lymphoma (NKTCL).Methods:The clinical manifestations, treatment response and prognosis of 7 patients with primary extranasal nasal-type NKTCL who underwent P-GEMOX chemotherapy as a first-line therapy in Shenzhen People's Hospital from September 2015 to October 2018 were retrospectively analyzed.Results:The median age of 7 patients with primary extranasal nasal-type NKTCL was 41 years old (27-74 years old), which was more commonly found in males (6 cases); the primary and invading extranasal sites included ileocecal, lymph nodes, skin, testis, adrenal gland, central nervous system, etc. The P-GEMOX regimen was used as a first-line therapy, although some patients had a short-term effect, all patients eventually progressed rapidly and died. The overall survival time was 2 weeks to 21 months.Conclusion:The short-term efficacy of P-GEMOX as a first-line therapy for the treatment of primary extranasal nasal-type NKTCL is acceptable, but the long-term efficacy is poor.

Inflammatory bowel disease is chronic intestinal inflammatory disease with unknown etiology, which may be associated with environmental , genetic and immune factors.The personalized or accurate diagnosis and treatment are a new development trend for IBD clinical management .The detection of biomarkers is very important in the diagnosis , treatment and clinical management of IBD .In addition to the traditional biomarkers , the emerging new markers based on genetics , epigenetics , microbial and metabolomics have also shown better future applications in several areas , such as the applications of biomarkers in diagnosis and differential diagnosis of IBD .The determination of disease activity , severity and complications.The selection for treatments in IBD and prediction of therapeutic effects .These biomarkers will also contribute to personalized clinical management of IBD .

To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM.Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015. The expressions of miR-221/222 in serum and in sorted CD138 positive plasma cells were detected by qRT-PCR, and the relative expression of miR-221/222 (Δct) was compared between the groups. Serum levels of miR-221 before and after treatment were compared in both remission group (=22) and refractory group (=13) in MM patients, and its correlation with serum level of β-MG was assessed using Pearson's correlation analysis.Serum levels of miR-221/222 in MGUS and MM groups were significantly higher than those in control group (all<0.01), while miR-221/222 levels in plasma cells were significantly lower in MGUS and MM groups than those in the control group (<0.05 or<0.01). No significant difference in miR-221/222 levels in serum and plasma cells was observed between MGUS group and MM group (all>0.05). There was no correlation between miR-221/222 levels in serum and plasma cells (=0.024 and -0.127, all>0.05), but miR-221 levels were correlated with miR-222 levels in both serum and plasma cells (=0.534 and 0.552, all<0.01). Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUCs) of serum miR-221/222, plasma cell miR-221/222 in diagnosis of MGUS/MM were 0.968, 0.976, 0.801 and 0.727, respectively. There was no significant difference in serum level of miR-221 among MM patients with different paraprotein isotypes (>0.05), but serum level of miR-221 in patients with relapsed MM was higher than that in patients with newly diagnosed MM (<0.01). Compared with the patients with MGUS or MM stageⅠ and Ⅱ, patients with MM stage Ⅲ were of higher serum levels of miR-221 (<0.01). Serum level of miR-221 decreased after chemotherapy in the remission group (=51.5,<0.01), but such decrease was not observed in the refractory group (=67.5,>0.05). Serum level of β-MG was positively correlated with serum level of miR-221 (=0.524,<0.01).miR-221/222 in serum and plasma cells may be biomarkers for early diagnosis of MGUS, and are helpful for diagnosis and efficacy evaluation of MM.
Biomarkers ; analysis ; blood ; Bone Marrow ; chemistry ; Disease Progression ; Humans ; MicroRNAs ; analysis ; blood ; Monoclonal Gammopathy of Undetermined Significance ; genetics ; physiopathology ; Multiple Myeloma ; chemistry ; genetics ; physiopathology ; Myeloma Proteins ; analysis ; Paraproteinemias ; genetics ; physiopathology ; Prognosis ; Recurrence

Since 2015, US government announced the Precision Medicine Initiative, the concept of“precision medicine” is spreading rapidly, which has seemingly become the mainstream of future medicine.Laboratory medicine based on personalized information brought by the development of precision medicine will be an entirely new area, however its complexity is far beyond the current knowledge and laboratory medical scientists are encouraged to be actively involved in this emerging field.Opportunities and challenges may coexist, which mainly include: screening and evaluation of circulating biomarkers, selection and standardization of appropriate molecular diagnostic techniques, acquisition of high quality biological specimens and establishment of sample library, and comprehensive interpretation of the results in order to achieve and improve individualized precise prevention, diagnosis, and treatment for specific diseases and patients.