BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective To explore the predictive value of early changes in platelet counts in the prognosis of severe pneumonia in aged patients.Methods This retrospective study included elderly patients with severe pneumonia,who were ≥65 years old and whose length of ICU stay ≥72 hours,admitted to the intensive care unit(ICU)of NO.2 People's Hospital of Changzhou from January 2014 to January 2017.They were divided into a survival group and a death group according to the 28-day outcome.General information and serum platelet levels at 0,24,36,and 72 hours after admission were collected.Receiver operating characteristic curve (ROC)was plotted according to platelet counts,changes in platelet counts and rates of change in platelet counts to evaluate their predictive value for 28-day prognosis.Kaplan-Meier survival curve was used to analyze the 28-day cumulative survival rate between different groups of patients,who were further divided according to platelet counts at 0 and 72 hours after admission to ICU,changes in platelet counts and rates of change in platelet counts at 72 hours after admission.Results (1)One hundred elderly patients with severe pneumonia were enrolled,among whom 41 cases were in the death group,thus with a mortality of 41.0％.The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ),sequential organ failure assessment (SOFA),C-reactive protein (CRP),and procalcitonin(PCT)in the death group were significantly higher than those in the survival group.2)Serum platelet levels showed a downward trend in both the death group and the survival group.The level of serum platelets at 72 hours after admission to ICU in the death group was significantly lower than that in the survival group(80.00 × 109/L vs.171.00 × 109/L,Z=5.786,P＜0.05);changes in platelet counts and rates of change in platelet counts in the death group were significantly higher than those in the survival group,especially at 72 hours after admission to ICU(/△PLT72:-79.00 × 109/L vs.-38.00 × 109/L,Z =4.938,P ＜0.05;△PLT 72％:43.6％ vs.-17.7％,Z=6.816,P＜0.05).(3)ROC curve analysis showed that platelet levels,changes in platelet counts,and rates of change in platelet counts could predict 28-day mortality in aged patients with severe pneumonia.The largest area under ROC curve was 0.902 when plotted with the rate of platelet counts at 72 hours after admission to ICU.Using the cut-off value of-36.14％ in the rate of change at 72 hours after admission to evaluate the predictive value in 28 day mortality,the sensitivity and specificity were 89.8％ and 75.6％,respectively.(4)Kaplan-Meier survival analysis showed that the 28 day survival rate was significantly higher and the length of survival was significantly greater when platelet counts at 0 and 72 hours after admission to ICU were higher than the cut-off value,and this also occurred in changes in platelet count and rates of change at 72 hours after admission to ICU.Conclusions Continuous decline in serum p[atelet levels indicates poor prognosis.When combined with platelet counts,changes in platelet counts and rates of change in platelet counts at 72 hours after admission to ICU,it may play an important role in assessing the prognosis of aged patients with severe pneumonia.

G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility.
Animals ; Computational Biology ; Crystallography, X-Ray ; Gene Expression ; Humans ; Plasmids ; genetics ; metabolism ; Protein Domains ; Receptors, Adrenergic, beta-1 ; Receptors, G-Protein-Coupled ; classification ; genetics ; metabolism ; Receptors, Odorant ; metabolism ; Receptors, Purinergic P1 ; genetics ; metabolism ; Sf9 Cells ; Spodoptera

Objective To establish the molecular weight distribution of Ganlong capsule by HPSEC the content of the peptide determined by Lowry and Methods The superdex peptide 10/300 GL (10 mm ×300 mm) column was used.The pH=6.0 and phosphate buffer of 0.05 mol/L was used as the mobile phase, containing 0.1 mol/L NaCl.The flow rate was set at 0.7 mL/min;The column temperature was 25℃;The detection wavelength was 214 nm.Results The content of the peptide ranged from 0.08 mg to 0.4 mg ( r =0.9996 ) .The RSDs of measurement precision of molecular weight and content were 0.08% and 0%(n=6), respectively.The RSDs of the repeatability were 1.3% and 1.1%(n=6);The regression equation of standard material was logMr =5.1455 -0.0871tR, r =0.9983,the relative molecular weight ranged from 2.68 ×102 Da ~5.73 ×103 Da(r =0.9983). Conclusion on The method is simple and rapid for determining the peptide content and the molecular weight distribution of Ganlong capsule.It can be used quality control method for Ganlong capsule.