Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Objective:This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD + R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods:The clinical data of 26 patients with FLT3-ITD + R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results:A total of 26 patients with FLT3-ITD + R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment ( P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion:The Gilt-based combination therapy is highly effective in treating FLT3-ITD + R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

Objective To analyze the status of influenza A and B virus infection in patients admitted to Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from 2022 to 2023,and to provide scientific basis for the adjustment of influenza prevention and control measures in this area.Methods The positive status of influenza A and B virus antigen and nucleic acid were analyzed to deter-mine the prevalence and dominant types of influenza in 2022-2023.The peak of influenza A virus infection in 2023 was analyzed by antigen detection and nucleic acid detection,and the positive rates of influenza A virus detection in patients with different genders and ages were compared.Results In 2022 and 2023,the majority of patients were infected with influenza A virus.There was no significant difference in the positive rate of in-fluenza A virus antigen and nucleic acid detection between male and female patients(P＞0.05).The positive rates of influenza A virus antigen and nucleic acid detection in patients of different ages were statistically sig-nificant(P＜0.05).Compared with other age range,the positive rate of influenza A virus antigen and nucleic acid detection was the highest in patients＞5-10 years old.From February to December 2023,the positive rate of influenza A virus nucleic acid detection(50.91％)was significantly higher than that of influenza A vi-rus antigen detection(28.73％),and the difference was statistically significant(P＜0.05).Conclusion There is no influenza virus infection peak in 2022,and there are two influenza A virus infection peaks in 2023.The positive rates of influenza A virus antigen and nucleic acid detection are different due to different detection methods.

Objective:To investigate the carrier rate and clinical characteristics of epigenetic modification gene mutations (EMMs) among patients with acute myeloid leukemia (AML).Methods:One hundred seventy two patients who were initially diagnosed with AML at the First People′s Hospital of Lianyungang from May 2011 to February 2021 were selected as the study subjects. Next-generation sequencing was carried out to detect variants of 42 myeloid genes among these patients. Clinical and molecular characteristics of patients with EMMs and the effect of demethylation drugs (HMAs) on their survival were analyzed.Results:Among the 172 AML patients, 71 (41.28%) were found to harbor the EMMs, and carrier rates were TET2 (14.53%, 25/172), DNMT3A (11.63%, 20/172), ASXL1 (9.30%, 16/172), IDH2 (9.30%, 16/172), IDH1 (8.14%, 14/172), EZH2 (0.58%, 1/172). Patients with EMMs (+ ) had lower peripheral hemoglobin compared with those with EMMs (-) (72 g/L vs. 88 g/L, Z=-1.985, P<0.05). The proportion of EMMs(+ ) among elderly AML patients was significantly higher than that of young AML patients [71.11% (32/45) vs. 30.70% (39/127), χ2 = 22.38, P < 0.001]. EMMs (+ ) were significantly correlated with NPM1 gene variants ( r=0.413, P < 0.001), while negatively correlated with CEPBA double variants ( r=-0.219, P<0.05). Compared with conventional chemotherapy regimens, HMAs-containing chemotherapy regimens have improved the median progression-free survival (PFS) and median overall survival (OS) among intermediate-risk AML patients with EMMs (+ ) (PFS: 11.5 months vs. 25.5 months, P<0.05; 12.5 months vs. 27 months, P<0.05). Similarly, Compared with conventional chemotherapy regimens, chemotherapy with HMAs had increased median PFS and median OS in elderly AML patients with EMMs(+ ) (4 months vs. 18.5 months, P<0.05; 7 months vs. 23.5 months, P<0.05). Conclusion:Patients with AML have a high rate of EMMs carriage, and HMAs-containing chemotherapy regimens can prolong the survival of elderly patients with AML with poor prognosis, which may provide a reference for individualized treatment.

Objective To analyze the incidence and risk factors of postoperative pulmonary complications(PPCs)in elderly patients undergoing video-assisted thoracoscopic surgery(VATS).Methods Elderly patients aged≥65 years who underwent VATS in Peking Union Medical College Hospital from January 2013 to December 2017,were reviewed retrospectively and divided into non-PPCs group and PPCs group.General information,past medi-cal history,and postoperative complications were recorded in a uniform case report form.The clinical factors with statistical significance in univariate analysis and important clinical significance according to experience were ana-lyzed with Logistic regression to evaluate the independent risk factors for PPCs.Results A total of 900 patients were included,and 48(5.3%)of them suffered PPCs.Multivariate logistic regression showed that pre-operative smoking history,history of stroke,chronic obstructive pulmonary disease(COPD)and pulmonary lobectomy were independent risk factors for PPCs in elderly patients after VATS.Conclusions Elderly patient is a high-risk group for PPCs after VATS.The risk factors include smoking history,stroke,COPD and scope of surgery.Therefore,perioperative management needs to optimize,and monitoring should be strengthened for these high-risk patients.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

Objective:To analyze the evolution of predominant Norovirus strain GⅡ.4 Sydney[P31] from 2017 to 2020 in China.Methods:Universal primers and next-generation sequencing technology were applied to establish Norovirus genogroup Ⅱ genome amplification method . Phylogenetic and key sites were analyzed on GⅡ.4 Sydney[P31] strains.Results:Among the 8 GⅡ.4 Sydney[P31] strains, 6 were successfully amplified and the genome sequences were obtained using the preliminarily established GⅡ genome amplification method . Phylogenetic analysis showed that the 6 strains obtained in this study from 2017-2020 strains grouped with the 2015-2019 GⅡ.4 Sydney[P31] reference strains in one cluster, and the Chinese strain GZ20133135 in 2013 and the 2012-2014 GⅡ.4 Sydney[P31] reference strains grouped into another one. A mutation Asp372Asn was found adjacent to the HBGA binding site Ⅱ. Epitope analysis showed that strains after 2017 have developed several aa mutations in A epitopes (297, 372, and 373), B epitopes (333), E epitopes (414), and H epitopes (309, 310), wherein the 2020 strains 20HN261 and 20HN253 have new changes in the A epitope (368) and G epitope (355) compared with the previous strains.Conclusions:The key mutation sites of the Chinese predominant Norovirus strain GⅡ.4 Sydney[P31] have been determined, which provides a scientific basis for tracking the emergence of new strains, and provides basic data for the development of vaccines against epidemic strains in China.

Objective:This study aims to investigate the efficacy and safety of chimeric antigen receptor (CAR) T-cell bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of recurrent and refractory acute B-lymphocytic leukemia (R/R B-ALL) .Methods:A total of 50 R/R B-ALL patients who underwent CAR T-scell therapy to bridge allo-HSCT in the First Affiliated Hospital of Soochow University from January 2017 to May 2019 were retrospectively analyzed. The overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR) , and transplant-related mortality (TRM) of patients with different bone marrow minimal residual disease (MRD) levels were analyzed before and after CAR T-cell infusion and before allo-HSCT.Results:The response rate of CAR T-cell therapy and the incidence rate of severe cytokine release syndrome were 92% and 28% , respectively. During 55 infusions, no treatment-related deaths occurred in any of the patients. The median time of CAR T-cell infusion to allo-HSCT was 54 (26-232) days, the median follow-up time after CAR T-cell infusion was 637 (117-1097) days, and the 1-year OS and EFS rates were (80.0±5.7) % and (60.0±6.9) % . The 1-year CIR and TRM after allo-HSCT were (28.0±0.4) % and (8.0±0.2) % . After CAR T-cell infusion and before allo-HSCT, patients with bone marrow MRD<0.01% had a significantly longer EFS [ (70.0±7.2) % vs (20.0±12.6) % , P<0.001; (66.7±7.5) % vs (36.4±14.5) % , P=0.008]and lower CIR [ (25.0±0.5) % vs (70.0±2.6) % , P<0.001; (23.08±0.47) % vs (45.45±2.60) % , P=0.038]. Conclusion:CAR T-cell therapy bridging allo-HSCT is safe and effective for recurrent and refractory B-ALL.