Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

This study aims to determine the nephrotoxic effects of 3-monochloropropanel-1,2-diol(3-MCPD)on female and male SD rats.A nephrotoxicity model was established by gavage of dif-ferent doses of 3-MCPD,and 80 SD rats were randomly divided into four groups:the control group(0 mg/kg 3-MCPD),low-dose group(15 mg/kg 3-MCPD),medium-dose group(30 mg/kg 3-MCPD),high-dose group(60 mg/kg 3-MCPD),with half female and half male.The body mass and food intake of the rats were recorded weekly,and the urine and blood and kidney tissues were col-lected after 28 consecutive days of gavage,and the blood erythrocyte count(WBC),white blood cell count(RBC),hemoglobin(HGB),erythrocyte-compaction-transfer-value(HCT),creatinine(CREA),serum urea nitrogen(BUN),and the indexes of blood phosphorus(P)and calcium(Ca)were detected;the level of kidney injury molecule(KIM-1)was measured by ELISA kit;the renal pathological changes was observed by histopathology method;and transcriptome sequencing was used to analyze differential genes in female and male rats.The results showed that 3-MCPD did not significantly affect the growth of male rats,but high doses significantly reduced the weight and food intake of female rats.The high-dose group of 3-MCPD caused a significant decrease in RBC,HGB,and HCT levels in both male and female rats,resulting in a significant increase in KIM-1 and P,and a significant decrease in Ca,but only a significant increase in CREA and BUN in female rats.Histopathology showed that in the high-dose group of male rats,only mild renal tubular dilation,epithelial cell edema,and clear tubular type were observed in the kidneys,while in female rats,a large number of renal sacs,clear tubular type,and interstitial inflammatory cells with fibrosis were observed in the kidneys.Transcriptome sequencing showed 1 712 differentially expressed genes in the high-dose group of female rats and 1 153 differentially expressed genes in the high-dose group of male rats.KEGG enrichment analysis showed that both male and female rats in the high-dose group experienced oxidative stress and cell apoptosis,but 3-MCPD may also participate in the process of kidney damage in females by inhibiting autophagy and inducing iron death pathways.The above results indicate that high-dose 3-MCPD has a more significant nephrotoxic effect on fe-male rats.

To understand the epidemiological and clinical features of patients with non-tuberculous mycobacteria(NTM)lung disease in a hospital for infectious diseases in Xinjiang,and to provide basis for prevention and control of NTM in Xinjiang.The strain distribution,epidemiological features and clinical features of 78 patients with NTM lung disease in the Sixth People′s Hospital of Xinji-ang Uygur Autonomous Region were analysed from June 2021 to June 2024,and a comparative analysis of the clinical features of 156 patients with pulmonary tuberculosis in this hospital during the same period was performed.Among 78 patients with NTM lung disease,the bacteria identified by molecular biology accounted for the top three cases:24 cases of Mycobacterium avium intracellulare complex,16 cases of Mycobacterium Kansaii and 11 cases of Mycobacterium Gordonae.There was no statistically significant difference in gender(χ2=0.009),age(χ2=2.670),smoking history(χ2=0.064),and BMI(χ2=0.896)between the NTM lung disease group and the pulmonary tuberculosis group(P>0.05).However,there were statistically significant differences in the combined bronchiectasis(χ2=19.068),immune-related indicators CD4(Z=-3.498)and CD3(Z=-3.187),and chest CT cavities on imaging(χ2=9.308)be-tween the two groups(P<0.05).There was no statistically significant difference in clinical symptoms such as cough(χ2=0.188)and expectoration(χ2=0.044)between the two groups(P>0.05).The common underlying diseases of NTM lung disease were diabetes mellitus(23.08%),hypertension(21.79%),bronchiectasis(20.51%)and others.The common clinical symptoms of NTM lung disease include cough,sputum,fatigue,poor appetite and others.The common manifestations of chest CT in NTM lung disease were Patchy cord shadows(62.82%),nodule(51.28%),pleural thickening(46.15%),calcification(41.03%)and others.Multivariate Logistic regression analysis showed that bronchiectasis(OR=8.019)is risk factor for NTM lung disease.The dominant strains of NTM in this study were My-cobacterium avium intracellulare complex,Mycobacterium kansasii and Mycobacterium Gordonae.NTM lung disease and pulmonarytuber-culosis have similar clinical manifestations and are difficult to distinguish,especially for patients with bronchiectasis,it is necessary to actively investigate NTM lung disease,provide basis for early diagnosis and treatment of NTM lung disease,and gradually form a system-atic and standardized NTM lung disease diagnosis and treatment system according to local conditions.

Objective To elucidate the impact of chronic kidney disease(CKD)on the clinical outcomes of patients with left main coronary artery disease(LMCAD)undergoing intravascular ultrasound(IVUS)-guided percutaneous coronary intervention(PCI).Methods This retrospective study enrolled consecutive patients with LMCAD who underwent IVUS-guided PCI at Wuhan Asia Heart Hospital between January 2017 and December 2020.Patients were stratified into CKD and non-CKD groups according to the presence of CKD.Clinical data were systematically retrieved from the electronic health record system.Demographic,clinical,and angiographic characteristics were compared between groups.The primary endpoint was major adverse cardiovascular events(MACE),defined as a composite of all-cause mortality,myocardial infarction,and ischemic stroke.Results A total of 325 LMCAD patients[mean age(62.56±9.86)years;73.54％male]were included,with 31 patients(9.54％)in the CKD group.During a median follow-up of 5 years,CKD patients exhibited significantly older age[(70.13±9.77)years vs.(61.77±9.54)years,P＜0.001],higher prevalence of three-vessel disease(64.52％vs.38.10％;P=0.040)and left main bifurcation lesion(45.16％vs.37.76％,P=0.011),greater IVUS-detected calcification burden(P=0.029),and higher median SYNTAXⅡ scores[(34.10(30.30,39.25)vs.26.75(22.42,31.58),P＜0.001)].The cumulative incidence of MACE was significantly higher in the CKD group compared to the non-CKD group(32.26％vs.9.18％,P＜0.001).Univariate Cox regression analysis and Kaplan-Meier survival curves confirmed a 5.877-fold increased risk of MACE in CKD patients(95％CI 2.765-12.494).After adjusting for age and cardiac function,CKD remained an independent predictor of MACE(HR 3.611,95％CI 1.634-7.978).Conclusions LMCAD patients with concomitant CKD present with advanced age,impaired cardiac function,more extensive coronary disease,and severe calcification.The presence of CKD is associated with a significantly worse long-term prognosis.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Objective To elucidate the impact of chronic kidney disease(CKD)on the clinical outcomes of patients with left main coronary artery disease(LMCAD)undergoing intravascular ultrasound(IVUS)-guided percutaneous coronary intervention(PCI).Methods This retrospective study enrolled consecutive patients with LMCAD who underwent IVUS-guided PCI at Wuhan Asia Heart Hospital between January 2017 and December 2020.Patients were stratified into CKD and non-CKD groups according to the presence of CKD.Clinical data were systematically retrieved from the electronic health record system.Demographic,clinical,and angiographic characteristics were compared between groups.The primary endpoint was major adverse cardiovascular events(MACE),defined as a composite of all-cause mortality,myocardial infarction,and ischemic stroke.Results A total of 325 LMCAD patients[mean age(62.56±9.86)years;73.54％male]were included,with 31 patients(9.54％)in the CKD group.During a median follow-up of 5 years,CKD patients exhibited significantly older age[(70.13±9.77)years vs.(61.77±9.54)years,P＜0.001],higher prevalence of three-vessel disease(64.52％vs.38.10％;P=0.040)and left main bifurcation lesion(45.16％vs.37.76％,P=0.011),greater IVUS-detected calcification burden(P=0.029),and higher median SYNTAXⅡ scores[(34.10(30.30,39.25)vs.26.75(22.42,31.58),P＜0.001)].The cumulative incidence of MACE was significantly higher in the CKD group compared to the non-CKD group(32.26％vs.9.18％,P＜0.001).Univariate Cox regression analysis and Kaplan-Meier survival curves confirmed a 5.877-fold increased risk of MACE in CKD patients(95％CI 2.765-12.494).After adjusting for age and cardiac function,CKD remained an independent predictor of MACE(HR 3.611,95％CI 1.634-7.978).Conclusions LMCAD patients with concomitant CKD present with advanced age,impaired cardiac function,more extensive coronary disease,and severe calcification.The presence of CKD is associated with a significantly worse long-term prognosis.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.