Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Objective:To analyze the clinical characteristics and treatment of patients with acute Q fever in Dali Bai Autonomous Prefecture, Yunnan Province.Methods:A total of 26 patients with acute Q fever admitted to People′s Hospital of Yunnan Dali Bai Autonomous Prefecture from October 2022 to December 2023 were enrolled. A retrospective cross-sectional study analysis was performed to analyze the demographic characteristics, epidemiology, clinical manifestations, laboratory tests and pathogen detection of these patients.Results:Of the 26 patients, 25 were male and one was female. The age ranged from 18 to 82 years with an average age of (45.6±17.2) years. All of them were sporadic cases. The neighbors of eight patients had sheep and cattle, 11 cases had a history of field work, and four cases had a history of field trip. Coxiella burnetii was detected in 26 patients by different molecular diagnostic techniques, including 21 cases by blood quantitative polymerase chain reaction (qPCR), three cases by sputum multi-pathogen targeted next-generation sequencing (tNGS), one case by alveolar lavage fluid tNGS, and one case by cerebrospinal fluid metagenomic next-generation sequencing (mNGS). Routine blood cultures of 19 cases were negative. All 26 patients presented with chills and fever, 21 cases (80.8%) with headache, 19 cases (73.1%) with fatigue, 14 cases (53.8%) with generalized aches and pains, 12 cases (46.2%) with poor appetite, and 14 cases (53.8%) with cough. Twenty-four cases had concurrent hepatitis, 12 cases had pneumonia, one had encephalitis, and 19 cases had myocardial damage. The laboratory tests showed that 23 cases (88.5%) had normal white blood cell count, eight cases (30.8%) had decreased platelet count, 25 cases (96.2%) had C-reactive protein elevated, 24 cases (92.3%) had procalcitonin elevated, 14 out of 17 cases had elevated erythrocyte sedimentation rate, and 19 cases had elevated D-dimer levels. Liver function tests showed that alanine aminotransferase increased in 24 cases (92.3%) (all less than 10 times of upper limit of normal (ULN)), aspartate aminotransferase increased in 23 cases (88.5%) (all less than 10 times of ULN), alkaline phosphatase increased in 10 cases (38.5%)(all less than two times of ULN), and γ-glutamyl transpeptidase increased in 19 cases (73.1%), which were all less than 10 times of ULN. Myocardial enzymes were detected in 21 cases, of which seven cases (33.3%) had elevated lactate dehydrogenase and 12 cases (57.1%) had elevated hydroxybutyrate dehydrogenase (all less than three times of ULN). In terms of treatment, 16 cases were treated with doxycycline alone, and nine cases were treated with doxycycline combined with azithromycin or quinolones or rifampicin, and one with tigecycline. After treatment, the conditions of patients improved. The overall length of hospital stay was (7.7±5.0) d, and that of eight patients treated with doxycycline combined with quinolones or azithromycin was 4.8 to 6.0 days. Conclusions:Acute Q fever often has no clear epidemiological history, and the clinical manifestations and laboratory tests are lack of specificity. qPCR, tNGS, mNGS can provide pathogenic diagnostic evidence for suspected cases. In terms of treatment, doxycycline is the first choice for treatment of acute Q fever, and combined treatment with azithromycin or quinolones could result in a shorter hospital stay.

Objective:To evaluate the effect of terlipressin combined with dopamine on intraoperative renal perfusion and early postoperative renal function in patients undergoing living-donor kidney transplantation.Methods:In this prospective cohort study, 84 patients of either sex, aged 18-64 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, undergoing living-donor kidney transplantation at the First Affiliated Hospital of Zhengzhou University from September 2022 to July 2024, in whom dopamine was continuously infused during operation to maintain fluctuation in the mean arterial pressure within 10% of the baseline value, were selected and divided into dopamine group (group D, n=42) and dopamine+ terlipressin group (group DT, n=42) based on whether terlipressin was used during operation. Terlipressin was continuously infused at a constant rate even before induction in group DT. The renal artery resistance index, intraoperative urine output, urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and delayed postoperative transplanted renal function were recorded. Results:Compared with group D, the intraoperative renal vascular resistance index was significantly reduced, the intraoperative urine output was increased ( P<0.01), and no statistical change was found in the urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and incidence of delayed postoperative transplanted renal function in group DT ( P>0.05). Conclusions:Terlipressin combined with dopamine provides better efficacy than dopamine alone in improving intraoperative renal perfusion and exerts no effect on early postoperative renal function in patients undergoing living-donor kidney transplantation.

Obesity and its related metabolic diseases have become a global public health challenge. Traditional weight loss methods have limited efficacy in patients with moderate to severe obesity, while bariatric surgery, although effective, carries a relatively high risk. Endoscopic weight loss techniques, due to their minimally invasive nature, safety, and reversibility, have gradually become an important supplement to obesity treatment. This article systematically reviews the research progress of gastric and small intestine-related endoscopic bariatric procedures, including intragastric balloon therapy, endoscopic sleeve gastroplasty, gastric bypass stents, and duodenal mucosal resurfacing.The authors believe that gastric-related procedures are suitable for patients whose primary goal is weight loss. Among these, the adjustable intragastric balloon offers the highest flexibility, being non-invasive and reversible with good short-term weight loss effects, making it suitable for bridging to bariatric surgery in patients with severe obesity. Endoscopic sleeve gastroplasty achieves weight loss effects closest to those of bariatric surgery, with favorable long-term weight loss outcomes, and is suitable for weight loss treatment in patients with contraindications to bariatric surgery. Gastric drainage procedures result in poor patient experience due to issues related to fistula tubes; moreover, the small sample size of studies on gastric-related endoscopic procedures means they are not considered representative. In contrast, small intestine-related procedures are more suitable for patients focusing on the improvement of metabolic diseases. Overall, endoscopic techniques exhibit significant short-term efficacy, but their long-term efficacy and standardization still require further research. In the future, it will be necessary to integrate artificial intelligence-assisted operations and individualized treatment strategies to optimize efficacy and expand clinical application.

Objective:To evaluate the effect of terlipressin combined with dopamine on intraoperative renal perfusion and early postoperative renal function in patients undergoing living-donor kidney transplantation.Methods:In this prospective cohort study, 84 patients of either sex, aged 18-64 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, undergoing living-donor kidney transplantation at the First Affiliated Hospital of Zhengzhou University from September 2022 to July 2024, in whom dopamine was continuously infused during operation to maintain fluctuation in the mean arterial pressure within 10% of the baseline value, were selected and divided into dopamine group (group D, n=42) and dopamine+ terlipressin group (group DT, n=42) based on whether terlipressin was used during operation. Terlipressin was continuously infused at a constant rate even before induction in group DT. The renal artery resistance index, intraoperative urine output, urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and delayed postoperative transplanted renal function were recorded. Results:Compared with group D, the intraoperative renal vascular resistance index was significantly reduced, the intraoperative urine output was increased ( P<0.01), and no statistical change was found in the urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and incidence of delayed postoperative transplanted renal function in group DT ( P>0.05). Conclusions:Terlipressin combined with dopamine provides better efficacy than dopamine alone in improving intraoperative renal perfusion and exerts no effect on early postoperative renal function in patients undergoing living-donor kidney transplantation.

Obesity and its related metabolic diseases have become a global public health challenge. Traditional weight loss methods have limited efficacy in patients with moderate to severe obesity, while bariatric surgery, although effective, carries a relatively high risk. Endoscopic weight loss techniques, due to their minimally invasive nature, safety, and reversibility, have gradually become an important supplement to obesity treatment. This article systematically reviews the research progress of gastric and small intestine-related endoscopic bariatric procedures, including intragastric balloon therapy, endoscopic sleeve gastroplasty, gastric bypass stents, and duodenal mucosal resurfacing.The authors believe that gastric-related procedures are suitable for patients whose primary goal is weight loss. Among these, the adjustable intragastric balloon offers the highest flexibility, being non-invasive and reversible with good short-term weight loss effects, making it suitable for bridging to bariatric surgery in patients with severe obesity. Endoscopic sleeve gastroplasty achieves weight loss effects closest to those of bariatric surgery, with favorable long-term weight loss outcomes, and is suitable for weight loss treatment in patients with contraindications to bariatric surgery. Gastric drainage procedures result in poor patient experience due to issues related to fistula tubes; moreover, the small sample size of studies on gastric-related endoscopic procedures means they are not considered representative. In contrast, small intestine-related procedures are more suitable for patients focusing on the improvement of metabolic diseases. Overall, endoscopic techniques exhibit significant short-term efficacy, but their long-term efficacy and standardization still require further research. In the future, it will be necessary to integrate artificial intelligence-assisted operations and individualized treatment strategies to optimize efficacy and expand clinical application.

Objective:To analyze the clinical characteristics and treatment of patients with acute Q fever in Dali Bai Autonomous Prefecture, Yunnan Province.Methods:A total of 26 patients with acute Q fever admitted to People′s Hospital of Yunnan Dali Bai Autonomous Prefecture from October 2022 to December 2023 were enrolled. A retrospective cross-sectional study analysis was performed to analyze the demographic characteristics, epidemiology, clinical manifestations, laboratory tests and pathogen detection of these patients.Results:Of the 26 patients, 25 were male and one was female. The age ranged from 18 to 82 years with an average age of (45.6±17.2) years. All of them were sporadic cases. The neighbors of eight patients had sheep and cattle, 11 cases had a history of field work, and four cases had a history of field trip. Coxiella burnetii was detected in 26 patients by different molecular diagnostic techniques, including 21 cases by blood quantitative polymerase chain reaction (qPCR), three cases by sputum multi-pathogen targeted next-generation sequencing (tNGS), one case by alveolar lavage fluid tNGS, and one case by cerebrospinal fluid metagenomic next-generation sequencing (mNGS). Routine blood cultures of 19 cases were negative. All 26 patients presented with chills and fever, 21 cases (80.8%) with headache, 19 cases (73.1%) with fatigue, 14 cases (53.8%) with generalized aches and pains, 12 cases (46.2%) with poor appetite, and 14 cases (53.8%) with cough. Twenty-four cases had concurrent hepatitis, 12 cases had pneumonia, one had encephalitis, and 19 cases had myocardial damage. The laboratory tests showed that 23 cases (88.5%) had normal white blood cell count, eight cases (30.8%) had decreased platelet count, 25 cases (96.2%) had C-reactive protein elevated, 24 cases (92.3%) had procalcitonin elevated, 14 out of 17 cases had elevated erythrocyte sedimentation rate, and 19 cases had elevated D-dimer levels. Liver function tests showed that alanine aminotransferase increased in 24 cases (92.3%) (all less than 10 times of upper limit of normal (ULN)), aspartate aminotransferase increased in 23 cases (88.5%) (all less than 10 times of ULN), alkaline phosphatase increased in 10 cases (38.5%)(all less than two times of ULN), and γ-glutamyl transpeptidase increased in 19 cases (73.1%), which were all less than 10 times of ULN. Myocardial enzymes were detected in 21 cases, of which seven cases (33.3%) had elevated lactate dehydrogenase and 12 cases (57.1%) had elevated hydroxybutyrate dehydrogenase (all less than three times of ULN). In terms of treatment, 16 cases were treated with doxycycline alone, and nine cases were treated with doxycycline combined with azithromycin or quinolones or rifampicin, and one with tigecycline. After treatment, the conditions of patients improved. The overall length of hospital stay was (7.7±5.0) d, and that of eight patients treated with doxycycline combined with quinolones or azithromycin was 4.8 to 6.0 days. Conclusions:Acute Q fever often has no clear epidemiological history, and the clinical manifestations and laboratory tests are lack of specificity. qPCR, tNGS, mNGS can provide pathogenic diagnostic evidence for suspected cases. In terms of treatment, doxycycline is the first choice for treatment of acute Q fever, and combined treatment with azithromycin or quinolones could result in a shorter hospital stay.

Objective To investigate the accuracy and feasibility of shear wave elastography(SWE)combined with superb microvascular imaging(SMI)for the differential diagnosis of benign and malignant thyroid nodules.Methods A total of 190 patients with thyroid nodu-les detected in the Ultrasound Department of our hospital from January 2021 to December 2022 who underwent ultrasound-guided fine-needle aspiration biopsy or exhibited postoperative histopathological improvement were selected as the study subjects.Among them,a total of 224 thyroid nodules(74 benign and 150 malignant nodules)were detected,all of whom underwent thyroid ultrasonography,SWE,and SMI.The parameters related to the Young's modulus of the tissue as well as the condition of fine blood flow and perforating vessels were calculated.Using histopathological results as the gold standard to construct receiver operating characteristic(ROC)curves,observe the effectiveness of SWE combined with SMI in the differential diagnosis of thyroid nodules,and compare the efficacy of different examination methods in the diagnosis of thyroid nodules.Results There were significant differences in the internal composition,echo,margin,cal-cification,and aspect ratio between the benign and malignant thyroid nodules(all P<0.05);however,there was no significant difference in the average diameter of the benign and malignant nodules(P>0.05).There were statistically significant differences in maximum elas-ticity,mean elasticity,elasticity ratio,microvascular score,peak shear wave velocity,and average shear wave velocity between the benign and malignant thyroid nodules(all P<0.05).The ROC curve showed that the area under the curve of the maximum elastic value was the highest,while the optimal diagnostic threshold was 29.52 kPa.The optimal diagnostic threshold for the microvascular flow score was 2.3 points.In terms of diagnostic efficacy,SWE combined with SMI showed the highest sensitivity(94.67%)and specificity(94.59%).Conclusion SWE combined with SMI can further improve the diagnostic efficiency of benign and malignant thyroid nodules and achieve quantitative evaluation and dynamic observation of lesions,which has application and promotion value.

Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors