The First Hospital of Jiaxing

Background: The diagnostic value of AFP CA19-9 and CEA as biomarkers in gastric carcinoma remains uncertain. This research explores their role in forecasting patient survival and disease progression. Methods: A total of 630 early-stage gastric cancer patients who underwent gastrectomy between January 2018 and June 2024 were analysed. Pathological evaluations were conducted, and serum concentrations of CEA, CA19-9, and AFP were measured. Statistical methods were employed to evaluate the relationship between these markers, tumour characteristics, and their impact on prognosis. Results: The mean age of patients was 59 years. The 1-year and 5-year survival rates were 98.3% and 91.4%, respectively. The positivity rates for CEA, CA19-9, and AFP were 5.1%, 6.2%, and 2.3%, respectively, resulting in an overall detection rate of 12.4%. The mean serum concentration of CEA was 4.8 ng/mL, the median concentration of CA19-9 was 45.2 U/mL, and the concentration range of AFP was from 3.5 ng/mL to 12.7 ng/mL. Elevated levels of CEA and CA19-9 were associated with metastasis of lymph nodes and higher tumour stages, while AFP showed no meaningful association with disease characteristics. Multivariate analysis identified age over 65, lymph node metastasis, and high CEA levels as independent risk factors for poorer outcomes in gastric cancer. Conclusions: Although CEA, CA19-9, and AFP individually show low detection rates in gastric cancer, their combined use improves diagnostic accuracy. Elevated CA19-9 is associated with lymph node metastasis, and high CEA independently indicates a poorer prognosis. Additional research is necessary to clarify the clinical utility of these biomarkers in early detection and prognostic evaluation.

Immunotherapy has been effective in many cancer types but has failed in multiple clinical trials in prostate cancers, with the underlying mechanisms remaining largely unclear. Here, we demonstrate that androgen receptor pathway inhibitor (ARPI) plus irradiation (IR) triggered robust anticancer immunity in prostate cancers in both patients and mice. We show that androgen-activated AR suppressed innate immune signaling by inducing inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) gene repression through HDAC2 interaction with an IKBKE enhancer RNA (IKBKE eRNA, or IKBKE-e). ARPI treatment caused IKBKE derepression and enhanced an IR-induced innate immune response via action of RIG-I and MDA5 dsRNA sensors. IKBKE-e ablation largely enhanced innate immunity in prostate cancer cells in culture and anticancer immunity in mice. Our results revealed AR, HDAC2, and IKBKE eRNA as critical intrinsic immune suppressors in prostate cancer cells, suggesting that rejuvenating inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε) signaling by targeting IKBKE-e is an actionable strategy to elicit synthetic anticancer immunity in immunologically "cold" cancers such as prostate cancer.

Importance:ICP-332 is a tyrosine kinase 2 inhibitor currently under investigation for the treatment of atopic dermatitis (AD). Objective:To evaluate the safety and efficacy of ICP-332 for moderate to severe AD. Design, Setting, and Participants:This double-blind, placebo-controlled, phase 2 randomized clinical trial was conducted between February 6 and November 7, 2023, across 19 centers in China. Individuals aged 18 to 75 years who had diagnosis of AD for 1 year or longer and a history of contraindication or inadequate response to topical therapies were included. Intervention:Participants were randomized 1:1:1 to receive ICP-332 at 80 mg or 120 mg, or placebo orally once daily for 4 weeks. Study participants and personnel were blinded to group assignment. Main Outcomes and Measures:The primary outcome was safety. The key efficacy outcome was the percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4. Other outcomes included percentages of patients achieving EASI-75 (a ≥75% improvement in EASI) and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or more points improvement. Results:This study included 75 patients (mean [SD] age, 37.3 [18.0] years in the ICP-332 groups and 44.5 [17.4] years in the placebo group; 21 women [28%] and 54 men [72%]). Among the 74 patients included in the safety set, 17 of 25 (68%) in the placebo group, 19 of 25 (76%) in the 80-mg ICP-332 group, and 18 of 24 (75%) in the 120-mg ICP-332 group experienced treatment-emergent adverse events, with all events being mild or moderate. The most common adverse event was decreased blood fibrinogen (1 of 25 [4%] in the placebo group, 6 of 25 [44%] in the 80-mg ICP-332 group, and 5 of 24 [21%] in the 120-mg ICP-332 group). Percentage reductions in EASI at week 4 were -78.2% (95% CI, -89.8% to -66.6%) in the 80-mg ICP-332 group, -72.5% (95% CI, -84.3% to -60.7%) in the 120-mg ICP-332 group, and -16.7% (95% CI, -28.7% to -4.6%) for those receiving placebo. Mean differences vs placebo for percentage reductions from baseline at week 4 in EASI were -61.6% (95% CI, -78.4% to -44.7%; P < .001) and -55.8% (95% CI, -72.8% to -38.9%; P < .001) for 80-mg ICP-332 and 120-mg ICP-332, respectively. There was a statistically significant higher EASI-75 response rate with both ICP-332 doses (64.0% for each; difference vs placebo, 56.0%; 95% CI, 34.4%-77.6%; P < .001) than with placebo and a greater percentage of Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and improvement of 2 or more points at week 4 in the 80-mg ICP-332 group vs placebo (36.0%; difference vs placebo, 32.0%; 95% CI, 11.7%-52.3%; P = .005). Conclusions and Relevance:In this phase 2 randomized clinical trial, ICP-332 demonstrated a favorable safety profile and encouraging efficacy, supporting further development for AD. Trial Registration:ClinicalTrials.gov Identifier: NCT05702268.

Herpesviruses are widely distributed in the lower respiratory tract, yet no study has comprehensively characterized their clinical features and prognostic impact in severe pneumonia. In this multicenter, retrospective study, we included severe pneumonia patients who underwent bronchoalveolar lavage fluid (BALF) metagenomic testing in intensive care units across 17 medical centers from January 2019 to June 2023. Based on metagenomic results, patients were categorized into herpesvirus-negative, HSV-1, EBV, CMV, HHV-6B, and HHV-7 groups. Propensity score matching and multivariable Cox regression were used to compare mortality between herpesvirus-positive and -negative patients. Interaction analyses were conducted to assess the impact of co-detection of different herpesviruses. Besides, main findings were validated using data from a prospective multicenter cohort. Among 1,737 enrolled patients, the 28-day mortality rate was 41.3

Suraxavir marboxil (GP681) is an antiviral drug inhibiting the polymerase acidic protein (PA) of RNA polymerase, of influenza. It has shown therapeutic activity against influenza A and B virus infections in preclinical studies. In this multicenter randomized, double-blind, placebo-controlled, phase 3 trial, we aimed to investigate the efficacy and safety of single-dose suraxavir marboxil (40-mg oral dose) in otherwise healthy outpatients aged 5–65 years with uncomplicated influenza unaccompanied by severe issues. From 28 July 2022 to 31 October 2023, 591 outpatients aged 5–65 years with uncomplicated influenza underwent randomization in 46 research centers in China and were randomly assigned in a 2:1 ratio to receive suraxavir marboxil (40 mg) or placebo within 2 days of symptom onset. The primary outcome was time to alleviation of influenza symptoms (TTAS) (from the start of treatment until body temperature returned to 37.2 °C or less and all seven influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) resolved for at least 21.5 h) within 15 days by treatment. The secondary endpoints included virological indicators, system and respiratory symptoms, PA variant mutation and adverse events. The median TTAS was significantly shorter in the group that received suraxavir marboxil compared to the placebo group (42.0 h versus 63.0 h, P = 0.002). Suraxavir marboxil was associated with more rapid decrease in viral load from baseline than placebo by 1 day after administration, with a mean change of −2.2 ± 1.3 compared to −1.3 ± 1.7 log10 copies per ml (P < 0.001) in the placebo group. Adverse events were reported in 28.4 NCT05474755 . Suraxavir marboxil, an antiviral drug designed to inhibit the polymerase acidic protein of influenza, alleviates symptoms in individuals with influenza faster than placebo in a phase 3 trial conducted in China.