BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans ; Lung Neoplasms/metabolism* ; Interleukin-5/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Biomarkers ; Immunotherapy ; Disease Progression ; B7-H1 Antigen

Humans ; Acute Disease ; Pancreatitis/diagnosis* ; Follow-Up Studies ; Patient Discharge ; Disease Progression

OBJECTIVE: To explore the association between depressive symptoms and the risks of rapid decline in renal function and chronic kidney disease (CKD) in middle-aged and elderly with normal kidney function. METHODS: The residents aged 40- 75 years with eGFR≥60 mL·min^-1·1.73 m^-2 without proteinuria in Lanzhou region, who participated in the "REACTION" study carried out in 2011, were selected and followed up in 2014. A total of 4961 individuals with complete and qualified data from the two surveys were included in the subsequent analysis. Based on PHQ-9 questionnaire scores, the baseline population was divided into two groups with and without depressive symptoms. Cox proportional hazard analysis was used to compare the incidences of rapid renal function decline and CKD between the two groups and study the association of depressive symptoms with the risk of these renal conditions. RESULTS: PHQ-9 questionnaire scores were not found to correlate with baseline SCr, ALB, UACR or eGFR levels among the participarts (P>0.05). After a mean follow-up time of 3.4±0.6 years, 33.9% of the participants with depressive symptoms at baseline experienced a rapid decline in renal function and 3.6% progressed to CKD. During the follow-up, the incidence of rapid decline in renal function and the risk of developing CKD were not found to correlate with depressive symptoms in these participants (P>0.05) regardless of the type of the depressive syndromes. CONCLUSION Depressive symptoms are not associated with the risks of rapid renal function decline or progression to CKD in middle-aged and elderly with normal kidney function.
Aged ; Middle Aged ; Humans ; Cohort Studies ; Depression ; Glomerular Filtration Rate ; Disease Progression ; Renal Insufficiency, Chronic/epidemiology* ; Kidney/physiology* ; Risk Factors

Humans ; Diabetic Nephropathies/pathology* ; Kidney/pathology* ; Biopsy ; Diabetes Mellitus, Type 2/pathology* ; Retrospective Studies ; Glomerular Filtration Rate ; Disease Progression

BACKGROUND: Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC. METHODS: Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS. CONCLUSIONS ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.
Humans ; Female ; Breast Neoplasms/metabolism* ; Receptor, ErbB-2/metabolism* ; Progression-Free Survival ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease Progression ; Treatment Outcome

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.
Humans ; Idiopathic Pulmonary Fibrosis/diagnosis* ; Biomarkers ; Lung Diseases, Interstitial ; Lung ; Bronchoalveolar Lavage Fluid ; Disease Progression ; Prognosis

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14⁺⁺CD16^-), intermediated monocyte subsets (CD14⁺⁺CD16⁺) and non-classical monocyte subsets (CD14⁺CD16⁺⁺) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.
Humans ; Monocytes ; Lipopolysaccharide Receptors ; Hemorrhagic Fever with Renal Syndrome ; Receptors, IgG ; Disease Progression

A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.
Humans ; Male ; Alternative Splicing ; Cell Line, Tumor ; DEAD-box RNA Helicases/metabolism* ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Prostatic Neoplasms/pathology* ; Receptors, Androgen/metabolism* ; RNA Splicing Factors/metabolism*

OBJECTIVE: To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138⁺ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years. METHODS: 147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138⁺ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis. RESULTS: At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ²=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor. CONCLUSION The expression level of PAFAH1B3 mRNA in bone marrow CD138⁺ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.
Humans ; Disease Progression ; Hematopoietic Stem Cell Transplantation ; Multiple Myeloma/drug therapy* ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics*

Humans ; Bone Marrow ; Neoplasms ; Myelodysplastic Syndromes ; Disease Progression ; Tumor Microenvironment