Journal of Translational Internal Medicine最新文献

Circular RNAs (circRNAs) are a class of single-stranded RNAs with covalently closed structures. Owing to their not having 3' or 5' ends, circRNAs are highly durable and insusceptible to exonuclease-mediated degradation. Moreover, some circRNAs with certain structures are translatable, making them novel vaccines. Vaccines are efficient tools for immunotherapy, such as for the prevention of infectious diseases and cancer treatment. The immune system is activated during immunotherapy to fight against abnormal allies or invaders. CircRNA vaccines represent a potential new avenue in the vaccine era. Recently, several circRNA vaccines have been synthesized and tested in vitro and in vivo. Our review briefly introduces the current understanding of the biology and function of translatable circRNAs, molecular biology, synthetic methods, delivery of circRNA, and current circRNA vaccines. We also discussed the challenges and future directions in the field by summarizing the developments in circRNA vaccines in the past few years.

Background: Diabetic retinopathy (DR) is a risk factor for diabetic kidney disease (DKD). Whether the duration, especially the short-term duration, of DR is associated with the development and progression of DKD remains unclear.

Materials and methods: A retrospective study and two-sample Mendelian randomization (MR) analysis were conducted. Kidney disease was defined by the urinary albumin-to-creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR). DR was diagnosed by an expert ophthalmologist by using a digital fundus camera. Binary and ordinal logistic regression analyses were performed. A restricted cubic spline was utilized to detect nonlinear associations. Summary statistics for DR- and DKD-associated single-nuclear polymorphisms (SNPs) were extracted from the FinnGen and the UK Biobank consortia.

Results: A total of 2674 patients with type 2 diabetes mellitus (T2DM) and type 2 diabetic kidney disease (T2DKD) were included. The prevalence and mean duration of DR increased with elevation of ACR and decline in eGFR. Renal function was significantly reduced in patients with DR in the fifth year of life. Binary and ordinal logistic regression showed that each 1-year increase in DR duration was associated with a 19% risk increase in the development of DKD, 16% in the elevation of ACR, and 21% in the decline of renal function. MR estimates indicated that DR was causally associated with DKD development, with an odds ratio of 2.89.

Conclusions: DR and the duration of DR were independent risk factors for the development and progression of DKD. The short-term duration of DR may be associated with DKD development. DR had a statistically significant effect on DKD.

Objective: QL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein, is a romiplostim (Nplate^®) biosimilar used to treat primary immune thrombocytopenia (ITP). This phase III study aimed to assess the efficacy and safety of QL0911 in adult patients with chronic primary ITP over a 24-week treatment period.

Methods: We conducted a double-blind, placebo-controlled, phase III study in patients diagnosed with primary ITP for at least 12 months who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who relapsed after splenectomy at 44 sites in China. Patients were randomly allocated (2:1 ratio) to QL0911 or placebo injection subcutaneously once weekly at an initial dose of 1 μg/kg for 24 weeks. The doses were adjusted to maintain the target platelet counts from 50 × 109/L to 200 × 109/L. Patients and investigators were blinded to the assignment. The primary endpoints were the proportion of patients who achieved a durable platelet response at week 24 (platelet count, ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. The study was registered at ClinicalTrials.gov (NCT05621330).

Results: Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911,144; placebo,72). A durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% CI: 53.3-69.8; P < 0.0001) than in the placebo group (0%). The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE:0.26) week with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no), concomitant ITP treatment (yes/no), and baseline platelet count (≤ 10 × 109/L, > 10 × 109/L, ≤ 20 × 109/L, > 20 × 109/L, and < 30 × 109/L). The incidence of TEAEs was comparable between the QL0911 and the placebo groups (91.7% and 88.9%, respectively). The most common adverse events overall were ecchymosis (28.5% for QL0911 vs. 37.5% for placebo), upper respiratory tract infections respiratory tract infections (31.9% for QL0911 vs. 27.8% for placebo), and gingival bleeding (17.4% for QL0911 vs. 26.4% for placebo).

Conclusion: QL0911 was well-tolerated and increased and maintained platelet counts in adults with ITP. QL0911, a biosimilar to romiplostim (Nplate®), may be a novel treatment option for patients with ITP who have failed or relapsed from first-line treatment in China. Ongoing studies will provide further data on long-term efficacy and safety in such patient populations.

Background and objectives: An increased risk of cardiovascular and metabolic diseases (CVMDs) among patients with cancer suggests a potential link between CVMD and cancer. The impact of CVMD on the survival time of patients with esophageal and gastric cancer remains unknown. We aimed to determine the incidence of CVMD and its impact on the longterm outcomes in esophageal and gastric cancer patients.

Methods: A total of 2074 cancer patients were enrolled from January 1, 2007 to December 31, 2017 in two hospitals, including 1205 cases of esophageal cancer and 869 cases of gastric cancer, who were followed up for a median of 79.8 and 79.3 months, respectively. Survival time was analyzed using the Kaplan-Meier method before and after propensity score matching.

Results: The incidence of CVMD in patients with esophageal and gastric cancer was 34.1% (411/1205) and 34.3% (298/869), respectively. The effects of hypertension, diabetes, and stroke on the long-term survival of esophageal and gastric cancer patients were not significant (all P > 0.05). The survival time was significantly longer in esophageal cancer patients without ischemic heart disease than in patients with ischemic heart disease, both before matching (36.5 vs. 29.1 months, P = 0.027) and after matching (37.4 vs. 27.9 months, P = 0.011). The survival time in gastric cancer patients without ischemic heart disease was significantly longer than in patients with ischemic heart disease, both before (28.4 vs.17.5 months, P = 0.032) and after matching (29.5 vs.17.5 months, P = 0.02).

Conclusion: The survival time of esophageal and gastric cancer patients with ischemic heart disease was significantly reduced compared to that of esophageal and gastric cancer patients without ischemic heart disease.

Background: Primary biliary cholangitis (PBC) has been long associated with impairment of various aspects of health-related quality of life (HRQoL) with substantial differences among populations. This study evaluated for the first-time the HRQoL in Greek PBC patients in conjunction with clinical and laboratory parameters of patients.

Methods: We analyzed prospectively collected data regarding the HRQoL by using the PBC-40 and SF-36 questionnaires in 374 Greek PBC patients and 131 age- and sex-matched non-PBC controls.

Results: The PBC-40 questionnaire is a reliable tool for HRQoL assessment in Greek PBC patients (Cronbach's α > 0.7 for all domains). Implementation of PBC-40 and SF-36 demonstrated significant impairment of HRQoL in Greek PBC patients compared to controls (P < 0.001 for all comparisons). Emotional dysfunction, social impairment, and fatigue (100%, 80.5% and 78%, respectively) were amongst those with the highest, while cognitive dysfunction (32%) with the least impact on quality of life. Fatigue was associated with female sex (P = 0.02), longer disease duration (P = 0.01), presence of cirrhosis (P = 0.02) and positivity for PBC-specific ANA (P < 0.05), while social dysfunction with increased age (P < 0.001), longer disease duration (P < 0.001) and presence of cirrhosis (P = 0.004). Living in urban areas was linked to impaired social function (P = 0.04), cognition (P = 0.02), fatigue (P = 0.04) and increased total PBC-40 score (P = 0.01).

Conclusions: Implementation of PBC-40 and SF-36 revealed impaired HRQoL in Greek PBC patients with fatigue, social and emotional dysfunction exerting the highest impact. However, total, and individual PBC-40 scores were lower than that reported in studies from Northern/Central Europe and Canada. Deranged HRQoL was associated with severity of liver disease and presence of PBC-specific ANA.

Chronic stress refers to continuous emotional changes and psychological pressure that individuals experience when they are unable to adjust and stabilize the internal environment over an extended period. It can increase the pressure on endocrine mediators and cytokines in the circulation, as well as tissues throughout the hypothalamic-pituitary-adrenaline (HPA) axis and sympathetic nervous system (SNS); thus, evolving the internal environment of the tumor. This review assesses several key issues, involving psychosocial factors, and integrates clinical, cellular, and molecular studies-as well as the latest research progress-to provide a mechanistic understanding regarding breast oncopsychology. We propose that chronic stress contributes to large individual diferences in the prognosis of breast cancer survivors because they change the basic physiological processes of the endocrine and immune systems, which in turn regulate tumor growth. The study of psychological and physiological reactions of breast cancer patients suggests a new idea for psychological intervention and clinical treatment for breast cancer patients.

Background and objectives: Asthma is a chronic inflammatory airway disease and brings heavy economic and spiritual burdens to patients' families and the society. Airway smooth muscle cells (ASMCs) afect the development of asthma by secreting cytokines, growth factors, and prostates. The stress-inducing protein, Sestrin2, plays a vital role in antioxidant defense. The aim of this study is to investigate the role of Sestrin2 in asthma and its corresponding molecular mechanism.

Materials and methods: Airway remodeling was induced by construction of asthma rat model. Primary ASMCs were isolated through combining tissue block adherence and enzymatic digestion and identified by immunofluorescence staining. Gene expression was measured by quantitative real-time PCR (qPCR) and western blot (WB) experiments. Cell viability, proliferation, migration, and calcium flow of ASMCs were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-deoxyuridine (EdU), Transwell, and Fluo-3AM, respectively. The binding of miR-182 and Sestrin2 3'-untranslated region (3'-UTR) was measured by luciferase reporter system and RNA-binding protein immunoprecipitation (RIP) analysis.

Results: Sestrin2 expression was upregulated in asthma rat model and cell model. Overexpression of Sestrin2 enhanced the growth, migration, and calcium flow, and inversely, repression of Sestrin2 was reduced in ASMCs from the asthma group. MiR-182, one of the microRNAs (miRNAs) that possesses the potential to regulate Sestrin2, was downregulated in ASMCs from the asthma group. Further experiments revealed that Sestrin2 was inhibited by miR-182 and that overexpression of Sestrin2 reversed the miR-182-induced inhibition of the cellular progression of ASMCs from the asthma group. This study further investigated the downstream signaling pathway of Sestrin2 and found that increased expression of Sestrin2 activated 5'-adenosine monophosphate-activated protein kinase (AMPK), leading to the inactivation of mammalian target of rapamycin (mTOR) and thus promoting the growth, migration, and calcium flow of ASMCs from the asthma group.

Conclusion: This study investigated the role of Sestrin2 for the first time and further dissected the regulatory factor of Sestrin2, ultimately elucidating the downstream signaling pathway of Sestrin2 in asthma, providing a novel pathway, and improving the understanding of the development and progression of asthma.