Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.

BACKGROUND: Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. METHODS/DESIGN: This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. DISCUSSION: The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. STUDY REGISTRATION: The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .

Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics.

Targeted therapies have revolutionized traditional cancer treatments by precisely targeting tumor cells, enhancing efficacy and safety. Despite this advancement, the proportion of cancer patients eligible for such therapies remains low due to the absence of suitable targets. Here, we investigate whether the translocation of the immunogenic cell death (ICD) marker calreticulin (CALR) from the endoplasmic reticulum (ER) to the cell surface following ICD induction can serve as a target for targeted therapies. To target CALR, a nanobody Nb215 identified from a naïve VHH phage library with high binding affinity to both human and mouse CALR was employed to engineer probiotic EcN 1917. Our results demonstrated that CALR nanobody-modified EcN-215 coupled with the photothermal dye indocyanine green (ICG) was able to exert NIR-II imaging-guide photothermal therapy (PTT). Moreover, PTT with EcN-215/ICG can reshape the tumor microenvironment by enhancing the infiltration of CD45+CD3+ T cells and CD11b+F4/80+ macrophages. Furthermore, the antitumor activity of CALR-targeted EcN-215/ICG is synergistically enhanced by blocking CD47-SIRPα axis. Collectively, our study provides a proof of concept for CALR-targeted therapy. Given that CALR translocation can be induced by various anticancer therapies across numerous tumor cell lines, CALR-targeted therapies hold promise as a novel approach for treating multiple types of cancers.

Application Value of Color Doppler Ultrasonography Combined with Thyroid Autoantibody Tests in Early Diagnosis of Thyroid Cancer.

Objective: To explore the application value of color Doppler ultrasonography combined with thyroid autoantibody tests in the early diagnosis of thyroid cancer. Methods: The medical data of 100 patients with thyroid nodules treated in our hospital from June 2019 to June 2021 were retrospectively analyzed; all patients received color Doppler ultrasonography and thyroid autoantibody tests before surgery and were divided into the benign lesion group (n = 45) and the malignant lesion group (n = 55) according to the postoperative pathological findings (the gold standard), so as to compare and analyze the application value of color Doppler ultrasonography, thyroid autoantibody tests, and their combination in the early diagnosis of thyroid cancer. Results: Compared with the pathological findings, the accuracy rate, sensitivity, specificity, positive predictive value, and negative predictive value of the combined diagnosis were significantly higher than those in the single diagnosis of color Doppler ultrasonography, TgAb test, TPOAb test, and TRAb test (P < 0.05), and by plotting the ROC curves to analyze the effect of these modalities in diagnosing early thyroid diseases, the results showed that the areas under the curve from large to small were combined diagnosis, color Doppler ultrasonography, TgAb test, TPOAb test, and TRAb test. Conclusion: Color Doppler ultrasonography has many advantages in the diagnosis of thyroid nodules, such as easy operation, painlessness, noninvasiveness, high efficiency, and repeatable detection, and the high-definition probe is able to show tiny lesions, echogenicity, blood flow signal, and other characteristics of foci. Combining color Doppler ultrasonography with testing thyroid autoantibodies such as TgAb, TPOAb, and TRAb can effectively improve the detection rate of early thyroid cancer, presenting significant reference value and meaning to clinical diagnosis and treatment of thyroid cancer.