Objective: To explore the correlation between allogeneic red blood cell (RBC) transfusion and healthcare-associated infections (HAIs) in patients undergoing coronary artery bypass grafting (CABG) during the perioperative period. Methods: A single-center retrospective cohort of 1,170 patients undergoing isolated CABG was analyzed. Multivariable logistic regression and restricted cubic splines (RCS) were employed to explore the nonlinear association between perioperative RBC transfusion (from intraoperative period to 72 hours postoperatively) and HAIs. Results: Among the 1,170 CABG patients, 109 patients (9.2%) received RBC transfusion during the operation or within 3 days after the operation. The risk of HAIs in those who received ≥4 units of RBCs during and within 3 days after the operation was 6.89 times higher than that in the non-transfusion group (95% CI: 3.65-17.20). Furthermore, there was a nonlinear threshold effect between the blood transfusion volume and postoperative HAIs (inflection point: 7.8 units). When the transfusion volume was ≤7.8 units, the risk of HAIs increased by 61% for each additional unit transfused (OR=1.61, 95% CI: 1.21-2.15). Beyond this threshold, no statistically significant association was observed (P=0.289). Conclusion: Perioperative RBC transfusion in CABG patients is associated with an increased incidence of HAIs. The perioperative blood transfusion volume has a curvilinear relationship with the risk of postoperative HAIs. When the blood transfusion volume is ≤7.8 units, the blood transfusion volume has a dose-dependent relationship with postoperative infection, with higher blood transfusion volumes correlating with greater postoperative infection risk. When the blood transfusion volume is >7.8 units, the relationship between the two is not statistically significant. The preventive effect of reducing RBC transfusion on HAIs requires further validation in the future.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Background and purpose:Esophageal carcinoma(ESCA)is one of the malignant tumors with high mortality rate,and the underlying mechanism of its development is largely unknown.CDC20 plays an important role in tumorigenesis,and its dysregulated expression is closely related to tumor occurrence and development.The expression of CDC20 is increased in a variety of tumors,and knocking down CDC20 can inhibit tumor cell proliferation.NLRP3 is the main component of the inflammasome,and inflammasome is also closely related to tumor occurrence and development.Here,our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism.Methods:The expression levels of CDC20 and NLRP3 genes in ESCA patients were analyzed using The Cancer Genome Atlas(TCGA)detabase and GTEx public database.We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College,and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).We studied the effects of knocking down CDC20 and NLRP3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA(shRNA)technology.Co-immunoprecipitation(Co-IP),proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3,and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).Results:The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues.The immunohistochemistry results further showed that compared with adjacent tissues,the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues.Knocking down CDC20 and NLRP3 genes inhibited the proliferation of ESCA cells.Co-IP,proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat(LRR),and CDC20 stabilized its expression by promoting NLRP3 ubiquitination.Conclusion:CDC20 and NLRP3 are upregulated in ESCA tissues,and CDC20 stabilizes their expression through ubiquitination of NLRP3,promoting ESCA cell proliferation.This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.

Systemic mastocytosis (SM) with RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) is a rare myeloid tumor with no standard treatment. Two cases of SM patients with RUNX1-RUNX1T1 positive AML treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were reported in Henan Cancer Hospital. Mast cell in bone marrow disappeared, C-KIT mutation and RUNX1-RUNX1T1 fusion gene remained negative. Allo-HSCT sequential avapritinib is an effective treatment for SM patients with RUNX1-RUNX1T1 positive AML.

Objective:To investigate the efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia (CBF-AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:We retrospectively analyzed the clinical data of six patients with molecular biologically positive CBF-AML with KIT mutation after allo-HSCT, who were treated with avapritinib at Henan Cancer Hospital from December 2021 to March 2023, and evaluated the efficacy and safety of avapritinib.Results:After 1 month of treatment with avapritinib, the transcription level of the fusion gene decreased in six patients, and the transcription level decreased by ≥1 log in five patients. In four patients who received avapritinib for ≥3 months, the fusion gene turned negative, and the median time to turn negative was 2.0 (range: 1.0-3.0) months. Up to the end of follow-up, four patients had no recurrence. The most common adverse reaction of avapritinib was myelosuppression, including neutropenia in two cases, thrombocytopenia in two cases, and anemia in one case. The non-hematological adverse reactions were nausea in two cases, edema in one case, and memory loss in one case, all of which were grades 1-2.Conclusion:Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

Objective To explore the correlation between thyroid antibody levels and early renal injury in patients with type 2 diabetes mellitus(T2DM)combined with Hashimoto's thyroiditis(HT).Methods A total of 375 T2DM patients hospitalized in The Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022 were selectedas the study subjects,and 197 healthy people were selected as the control subjects.The patients with T2DM were divided into simple T2DM group(n=191)and T2DM combined with HT group(HT,n=184).According to the urinary albumin/creatinine ratio(UACR)level,T2DM patients with HT were divided into microalbuminuria subgroup(MUAlb,30≤UACR≤300 mg/g,n=70)and normal albuminuria subgroup(NUAlb,UACR<30 mg/g,n=114).According to whether the thyroid antibody was positive,they were divided into thyroid peroxides antibody[TPOAb(+)]subgroup(n=56),thyroglobulin antibody[TGAb(+)]subgroup(n=40)and TGAb and TPOAb double antibody positive subgroup(n=88).Results Compared with the NC group,the smoking,drinking,urinary creatinine,alpha 1-microglobulin,UACR,FPG,HbA1c,LDL-C,TC,and TG in the HT and T2DM groups increased(P<0.05),while HDL-C decreased(P<0.05).Compared with the NUAlb subgroup,the MUAlb subgroup showed age,DM duration,FPG,HbA1c,TGAb,TPOAb,thyroid stimulating hormone(TSH)increased(P<0.05),while FT3 and eGFR decreased(P<0.05).Spearman correlation analysis showed that UACR was positively correlated with age,HbA1c,TPOAb,TGAb,TSH(P<0.01),and negatively correlated with FT3(P<0.01).The UACR of the TGAb(+)+TPOAb(+)subgroup was higher than that of the TGAb(+)and TPOAb(+)subgroups(P<0.05).Logistic regression analysis showed that TSH,TGAb,TPOAb,and HbA1c were risk factors for MUAlb,while FT3 was a protective factor for MUAlb.Conclusions In T2DM with HT patients with normal thyroid function,TPOAb and TGAb are closely related to the occurrence of early renal injury.

The kidneys are one of the main excretory organs for drugs and when drugs are not excreted effectively, they can accumulate in the kidneys or in the interstitial tubules, leading to drug-induced kidney injury. The tubulointerstitium accounts for 80% of the volume of the kidney and is the primary site of response to various types of renal injury. This article focuses on drug-induced acute interstitial nephritis, highlighting its clinical symptoms, listing common induction drugs, analysing pathological features, and explaining its pathogenesis from the perspective of immune response, with the aim of providing a basic and clinical evidence for subsequent studies.

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Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m²; lean, BMI < 24 kg/m²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.
Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Overweight/drug therapy* ; Insulin Resistance ; Obesity/drug therapy* ; China ; DNA/therapeutic use*

Objective:To explore the effect of demographic sociological data on the critical thinking of clinical research nurses, in order to provide reference for improving the level of clinical research.Methods:Using the convenient sampling method, a total of 110 clinical research nurses responsible for clinical research related work in three ClassⅢ Grade A hospitals in Zhengzhou City of Henan Province from January to June 2021 were selected as the research objects. Demographic Sociological Data Questionnaire and Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) were used to conduct surveys among nurses. Multiple linear regression was used to analyze the effect of demographic sociological data on critical thinking of clinical research nurses. A total of 110 questionnaires were distributed, and 106 valid questionnaires were recovered. The effective recovery rate of the questionnaires was 96.36% (106/110) .Results:The total score of CTDI-CV of 106 nurses was (296.25±24.12) . The results of multiple linear regression analysis showed that age, education, professional title and working years were the influencing factors of the level of critical thinking of clinical research nurses ( P<0.05) . Conclusions:The critical thinking ability of clinical research nurses is affected by age, professional title, educational background and working years. It is suggested to take effective measures to improve the critical thinking ability of nurses according to the actual situation, and then improve the clinical research level of nurses.