Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective To explore the predictive value of the triglycerides/high-density lipoprotein cholesterol(TG/HDL-C)ratio com-bined with the mean platelet volume/platelet count(MPV/PC)ratio for in-stent restenosis(ISR)after percutaneous coronary intervention(PCI)in elderly patients with coronary heart disease.Methods A total of 240 elderly patients with coronary heart disease admitted at the Pingmei Shenma Medical Group General Hospital from January 2021 to January 2023 were selected and divided into the ISR(36 cases)and non-ISR(204 cases)groups based on whether ISR occurred 6 months after PCI.The clinical data,TG/HDL-C ratio,and MPV/PC ratio of the two groups were compared,and Pearson's correlation analysis was used to analyze the correlation between the TG/HDL-C and MPV/PC ratios.Multivariate logistic regression analysis was used to analyze the relationship between the TG/HDL-C ratio,MPV/PC ratio,and ISR after PCI.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive value of the TG/HDL-C and MPV/PC ratios for ISR after PCI in older patients with coronary heart disease.Results There were statisti-cally significant differences in the comparisons of diabetes,hypertension,the degree of coronary artery stenosis,and stent diameter between the two groups(P<0.05);the ISR group had higher TG levels,MPV levels,TG/HDL-C ratios,and MPV/PC ratios,and lower HDL-C and PC levels compared to the non-ISR group(P<0.05);the TG/HDL-C ratio was positively correlated with the MPV/PC ratio(P<0.05);the TG/HDL-C and MPV/PC ratios were independently associated with ISR after PCI in older patients with coronary heart disease(P<0.05);and the AUC for predicting ISR after PCI in older patients with coronary heart disease was 0.759 and 0.784 for the TG/HDL-C and MPV/PC ratios,respectively,and the combined prediction showed an AUC of 0.921,which was superior to that of either alone.Conclusion The TG/HDL-C and MPV/PC ratios were significantly correlated with ISR in elderly patients with coronary heart disease after PCI,and their combined predictive value was reliable.

Objective To explore the predictive value of the triglycerides/high-density lipoprotein cholesterol(TG/HDL-C)ratio com-bined with the mean platelet volume/platelet count(MPV/PC)ratio for in-stent restenosis(ISR)after percutaneous coronary intervention(PCI)in elderly patients with coronary heart disease.Methods A total of 240 elderly patients with coronary heart disease admitted at the Pingmei Shenma Medical Group General Hospital from January 2021 to January 2023 were selected and divided into the ISR(36 cases)and non-ISR(204 cases)groups based on whether ISR occurred 6 months after PCI.The clinical data,TG/HDL-C ratio,and MPV/PC ratio of the two groups were compared,and Pearson's correlation analysis was used to analyze the correlation between the TG/HDL-C and MPV/PC ratios.Multivariate logistic regression analysis was used to analyze the relationship between the TG/HDL-C ratio,MPV/PC ratio,and ISR after PCI.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive value of the TG/HDL-C and MPV/PC ratios for ISR after PCI in older patients with coronary heart disease.Results There were statisti-cally significant differences in the comparisons of diabetes,hypertension,the degree of coronary artery stenosis,and stent diameter between the two groups(P<0.05);the ISR group had higher TG levels,MPV levels,TG/HDL-C ratios,and MPV/PC ratios,and lower HDL-C and PC levels compared to the non-ISR group(P<0.05);the TG/HDL-C ratio was positively correlated with the MPV/PC ratio(P<0.05);the TG/HDL-C and MPV/PC ratios were independently associated with ISR after PCI in older patients with coronary heart disease(P<0.05);and the AUC for predicting ISR after PCI in older patients with coronary heart disease was 0.759 and 0.784 for the TG/HDL-C and MPV/PC ratios,respectively,and the combined prediction showed an AUC of 0.921,which was superior to that of either alone.Conclusion The TG/HDL-C and MPV/PC ratios were significantly correlated with ISR in elderly patients with coronary heart disease after PCI,and their combined predictive value was reliable.

Objective:To investigate the clinical effect of early bronchoalveolar lavage on patients with aspiration pneumonia.Methods:A retrospective study was conducted on 55 patients with aspiration pneumonia who met inclusion criteria but not exclusion criteria in the Intensive Care Department of our hospital from January 2020 to April 2021. The patients were divided into the control group (32 cases) and the bronchoscopic lavage group (23 cases) according to whether they received bronchoscopic lavage within 24 h after aspiration. Basic information (sex, age, body mass index, chest X-ray score, oxidation index, temperature, heart rate, respiratory rate, white blood cells, PCT, IL-6, CPR and APACHE Ⅱ score), etiology changes at the early stage (≤ 3 d) and later stage (4-7 d after admission), and changes in prognostic indexes (mechanical ventilation time, length of ICU stay, length of stay and mortality) were compared between the two groups. The clinical efficacy of early endoscopy lavage for aspiration pneumonia was evaluated.Results:The positive rate of early etiological culture was 85.2%, the bacterial positive rate was 72.9% and the fungal positive rate was 14.6%. Pseudomonas aeruginosa accounted for 20.8%, Klebsiella pneumoniae accounted for 14.6%, Staphylococcus aureus and Streptococcus accounted for 12.5%, and there was no significant difference in the distribution between the bronchoscopic lavage group and the control group (all P>0.05). The positive rate of late etiological culture was 88.6%, the bacterial positive rate was 85.7% and the fungal positive rate was 2.9%. The positive rate of late bacterial culture was significantly decreased in the bronchoscopic lavage group ( P < 0.05), and the other results were not significantly different from the control group (all P>0.05). After early bronchoscopic lavage, the duration of mechanical ventilation, length of ICU stay and length of stay were significantly shortened, and the fifth day CPIS score was significantly decreased (all P< 0.05). Conclusions:Early endotracheal lavage can reduce mechanical ventilation time, length of ICU stay and length of stay of aspiration pneumonia, and reduce the positive rate of bacterial culture in the lung at the later stage, which needs to be further verified by a large randomized controlled study.

Objective:To explore the value of ultrasonic measurement of optic nerve sheath diameter (ONSD) in predicting the risk of death in patients with severe brain injury.Methods:This was a prospective observational study based on 84 postoperative patients with severe brain injury from January 2020 to September 2020 in our department. The patients were divided into two groups: the survival group and the deceased group. The clinical features between the two groups were compared. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of ONSD, neuron-specific enolase (NSE) and the combination of the two in predicting death in patients with severe brain injury. Binary logistic regression was used to analyze the independent risk factors for death. A prediction model for the risk of death was constructed.Results:There were 61 cases (72.6%) in the survival group and 23 cases (27.4%) in the deceased group. There were significant differences in age, Glasgow coma score (GCS), ONSD and NSE at 12 h after surgery between the two groups. According to the ROC curve, the optimal cutoff levels of ONSD and NSE for predicting death were 5.5 mm and 21.75 ng/mL, respectively. When the two indicators were combined, the area under the curve was 0.897 ( P<0.01). At this threshold, the sensitivity and specificity were 100% and 70.5%, respectively. ONSD ( OR=9.713; 95% CI: 1.192-79.147) and GCS scores ( OR=0.492; 95% CI: 0.318-0.763) at 12 h after surgery were independent risk factors for death in patients with severe brain injury (both P<0.05). Conclusions:Early postoperative ONSD is an independent risk factor for death in patients with severe brain injury. The combination of ONSD and NSE has the best predictive effect.

Objective: To study the clinicopathologic features, immunophenotype, characteristic FISH pattern and prognosis of renal cell carcinoma (RCC) associated with chromosome X inversion harboring gene fusions involving TFE3. Methods: Ten cases of NONO-TFE3 RCC and four cases of RBM10-TFE3 RCC were investigated at Nanjing Jinling Hospital from 2009 to 2016 by clinicopathological findings, immunohistochemistry, and genetic analysis. Results: Morphologically, the distinct pattern of secretory endometrioid subnuclear vacuolization was overlapped with clear cell papillary RCC, and often accompanied by sheets of epithelial cells in NONO-TFE3 RCC. Most cases of RBM10-TFE3 RCC presented with the biphasic feature that acinar, tubular and papillary patterns of epithelioid cells combined with sheets of small cells with "pseudorosette-like" architectures. In addition, cytoplasmic vacuolization, nuclear groove, and psammoma bodies were also observed. Immunohistochemically, all NONO-TFE3 RCC cases were immunoreactive for TFE3, CD10, RCC markers, and PAX8, and negative for CK7, Cathepsin K, Melan A, HMB45, Ksp-cadherin, vimentin, and CD117. All 4 cases of RBM10-TFE3 RCC showed moderate to strong immunoreactivity for TFE3, Cathepsin K, CD10, Ksp-cadherin, E-cadherin, P504s, RCC marker, PAX8, and vimentin but negative for TFEB, HMB45 and CK7. CKpan and Melan A were at least focally expressed. The antibody to Ki-67 showed labeling of 3%-8% (mean 5%). There were some expression discrepancies of immunochemistry between different histological patterns. PAX8, CKpan, P504s, and Ksp-cadherin were expressed in epithelioid areas but not in small-cell areas. Ki-67 labeling index of epithelioid areas was higher than that in small-cell areas. In molecular analysis, NONO-TFE3 fusion transcripts were identified in 6 patients. The fusion points were between exon 7 of NONO and exon 6 of TFE3 in 5 patients and between exon 9 of NONO and exon 5 of TFE3 in one patient. All 4 cases of RBM10-TFE3 RCC demonstrated to have RBM10-TFE3 fusion transcripts and the fusion points were between exon 5 of TFE3 and exon 17 of RBM10. Using TFE3 break-apart FISH assay, all 10 cases of NONO-TFE3 RCC showed characteristic patterns of equivocal split signals with a distance of nearly 2 signal diameters. All 4 cases of RBM10-TFE3 RCC showed colocalized or subtle split signals with a distance of <1 signal diameter, which was considered as negative results. Long-term follow-up was available for 7 patients of NONO-TFE3 RCC and 4 patients of RBM10-TFE3 RCC. All patients were alive with no evidence of disease. Conclusions Two rare genotypes, NONO-TFE3 RCC and RBM10-TFE3 RCC, are reported in this study. Both of these two tumors show specific morphology and good prognosis, along with the positive TFE3 staining and the equivocal or false-negative TFE3 FISH results, which could be missed. PCR detection or next-generation sequencing can determine the genotype.