Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma-an exploration of surrogate endpoint.

BACKGROUND: Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy. METHODS: Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation. RESULTS: PFS correlated moderately with OS in the retrospective cohort (Kendall's Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group. CONCLUSION: In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.

Trafficking protein TMED3 promotes esophageal squamous cell carcinoma.

BACKGROUND: The molecular mechanisms of esophageal squamous cell carcinoma (ESCC) remain poorly understood. Transmembrane emp24 trafficking protein 3 (TMED3) acts as an oncogene or tumor suppressor gene in different cancers. Our study was to explore the clinicopathological significance and functional roles of TMED3 in ESCC. METHODS: Immunohistochemistry, qPCR, and western blotting were used to analyze the expression of TMED3 in ESCC tissues and cells. Statistical analysis was performed to analyze the relationship between TMED3 expression and tumor characteristics in patients with ESCC. The role of TMED3 in vitro and in vivo was investigated by performing functional verification experiments and using a xenograft mouse model. Proteins that are functionally related to TMED3 were recognized by Affymetrix microarray and Ingenuity Pathway Analysis (IPA). Functional verification experiments were performed to analyze the role of FAM60A (a protein functionally related to TMED3) in vitro. RESULTS: We confirmed the overexpression of TMED3 was correlated with poor prognosis in ESCC patients. When TMED3 was knocked down, ESCC cell proliferation, migration, and invasion were inhibited whereas cell apoptosis was promoted in vitro, and tumorigenicity was inhibited in vivo. We further revealed significant changes in gene expression profile in TMED3 knockdown cells. Among these differentially expressed genes, FAM60A was overexpressed in ESCC tissues. Furthermore, knocking down FAM60A significantly weakened the proliferation ability of ESCC cells and reversed TMED3's tumorigenicity of ESCC cells. CONCLUSION: Our study revealed an oncogenic role of TMED3 in ESCC.

Role of CD4 + T and CD8 + T Lymphocytes-Mediated Cellular Immunity in Pathogenesis of Chronic Obstructive Pulmonary Disease.

This work was to explore the changes of T lymphocyte subsets in peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) (AECOPD) and the role of cellular immunity mediated in the disease process. Eighty-six patients with AECOPD who visited Qingdao Hiser Medical Center from June 2020 to December 2021 and 30 healthy people (controls) who underwent health examination in the same period were selected. The differences of pulmonary function (PF), arterial blood gas (ABG), blood routine inflammatory indexes, T lymphocyte and T lymphocyte subsets were compared between the two groups, and the correlation between T lymphocyte subsets and each index was analyzed. There were clear differences in PF, ABG, and PB inflammation indexes between AECOPD patients and the controls (P <0.05). Compared with the controls, the CD4 + and CD4 +/CD8 + ratio in PB of AECOPD group were obviously decreased, and the CD8 + level was clearly increased (P <0.05); Th1 of CD4 + cell subsets and Tc1 of CD8 + cell subsets were significantly increased, while Th2 of CD4 + cell subsets and Tc2 of CD8 + cell subsets were obviously decreased (P <0.05). However, CD4+ was significantly positively correlated with lung function indexes, and significantly negatively correlated with neutrophils/lymphocytes and high-sensitivity C-reactive protein (P <0.05) and significantly positively correlated with Hs-CRP (P <0.05). In summary, CD4+ and CD8+ T lymphocytes were involved in the occurrence and occurrence of AECOPD, the decrease of CD4+ and the increase of CD8+ may promote the deterioration of COPD.

Superhydrophobic polyurethane sponge based on sepiolite for efficient oil/water separation.

Massive oil leakage accidents and illegal discharge of oily wastewater have not just destroyed the sustainability of the ecological environment but caused permanent damage to marine ecosystems, which makes it urgent to handle it. In this paper, by means of sol-gel, micro-nan silica that grew from the surface of fibrous sepiolite was organically modified with 1 H, 1 H, 2 H, 2 H-perfluorodecyltriethoxysilane (PFDS). The superhydrophobic sepiolite/silica firmly attached to the surface of polyurethane sponge under the action of oily epoxy resin with strong adhesion. The sponge exhibited superhydrophobicity and excellent selective oil adsorption capacity (19.98-40 times of their own weight). More importantly, besides the effective separation of immiscible oil-water mixtures (the separation rate reached 98.72%), it could also efficiently separate oil with water and oil with salt solution emulsions. In addition, the sponges kept hydrophobic even after floating in extremely corrosive liquids for 20 h, showing a strong resistance to strong acidic as well as alkaline liquids. After 100 times of mechanical compression, the three-dimensional structure of sponge held still and the water contact angle was greater than 144°, demonstrating an excellent mechanical stability, which provided a reference for its practical application in oil-water separation.

Psychological Status and Influencing Factors of Hospital Medical Staff During the COVID-19 Outbreak.

BACKGROUND: The aim of this study was to analyze the psychological status of and its influencing factors in health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) outbreak so as to provide sufficient theory and scientific basis for the formulation and implementation of relevant policies and measures in improving the psychological status of HCWs. METHOD: During February 1 to February 20, 2020, 1,002 members of the HCWs from Xi'an and Wuhan completed a 12-item questionnaire regarding pressure about the COVID-19 influenza pandemic, along with the 12-item General Health Questionnaire (GHQ-12). The GHQ-12 scale was divided by three points. The positive group was scored more than 3. All data were analyzed by SPSS. RESULTS: More than half of the participants (61.1%) reported psychological distress. The HCWs have sufficient information about the COVID-19 symptoms, prognosis, treatment, infection route, and preventive measures (medians ranged from 6/9 to 8/9). Female, engaged in clinic work less than 7 years, married person, and working in Wuhan were risk factors affecting the psychological status of HCWs (P < 0.05). CONCLUSION: Psychological distress is common in HCWs during the COVID-19 outbreak. Hospitals and relevant departments should provide psychological support to HCWs, and strict infection control measures should be developed.

Concurrent chemoradiotherapy combined with enteral nutrition support: a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant fistulae.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) significantly increases the survival rate of esophageal squamous cell carcinoma (ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long-term survival. METHODS: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat-sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were retrospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening (NRS) before, during, and after treatment. Twenty-two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT. RESULTS: With a median follow-up of 18 months (range, 3-39 months), patients' 1-year overall survival (OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score (P = 0.003), increase in NRS score (P = 0.024), fistula closure (P = 0.011), and response to treatment (P < 0.001) were significantly associated with OS. Multivariate analysis showed that tumor response (P = 0.044) and increase in NRS score (P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients (20.0%), grade 3 neutropenia was observed in 11 patients (27.5%), and grade 3 cough was observed in 13 patients (32.5%); 2 patients (5.0%) died of massive bleeding during treatment. CONCLUSIONS: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T-category ESCC who undergo CCRT.