Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL⁻¹ coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L⁻¹, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.

Objective:To evaluate the efficacy of 3D printing technology combined with computer navigation-assisted screw implantation in the treatment of atlantoaxial instability (AAI) complicated by vertebral artery anomalies.Methods:A retrospective case series study was conducted to analyze the clinical data of 23 patients with AAI complicated by vertebral artery anomalies who were admitted to Honghui Hospital of Xi′an Jiaotong University between January 2019 and January 2023, including 10 males and 13 females, aged 19-70 years [(51.0±13.3)years]. Vertebral artery anomalies were categorized into unilateral high-riding vertebral artery with unilateral dominance ( n=14), bilateral high-riding vertebral arteries with unilateral dominance ( n=6), and ponticulus posticus ( n=3). All the patients underwent preoperative planning using a 3D-printed model of the atlantoaxial complex with the vertebral artery, followed by posterior atlantoaxial pedicle screw fixation with computer-assisted navigation. Operative duration and intraoperative blood loss were recorded. The accuracy of pedicle screw placement was assessed at 3 days postoperatively using the Gertzbein-Robbins classification. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were evaluated preoperatively, at 3 days, 3 months postoperatively, and at the last follow-up. Bony fusion was assessed using cervical CT with 3D reconstruction at the last follow-up. Complications were also observed. Results:All the patients were followed up for 12-19 months [(15.1±1.9)months]. The operative duration was 125-167 minutes [(140.6±10.9)minutes] and intraoperative blood loss was 200-600 ml [(295.7±77.8)ml]. At 3 days postoperatively, all the 66 pedicle screws were safely placed, with 60 screws (91%) rated as Gertzbein-Robbins Grade 0 and 6 screws (9%) as Grade 1. At 3 days and 3 months postoperatively, and at the last follow-up, the VAS scores were (4.0±1.0)points, (2.0±0.6)points, and (1.3±0.5)points, and the JOA scores were (14.2±1.2)points, (16.0±0.8)points, and (16.6±0.5)points, both of which were not only significantly improved compared with preoperative (5.6±1.3)points and (12.8±1.5)points, but also further improved over time ( P<0.05). At the last follow-up, 22 patients (96%) achieved satisfactory atlantoaxial bony fusion. No vertebral artery injury, spinal cord or nerve injury, cerebrospinal fluid leakage, or screw loosening were observed in any patients. Conclusion:For patients with AAI complicated by vertebral artery anomalies, 3D printing combined with computer navigation-assisted navigation for atlantoaxial pedicle screw implantation offers multiple advantages, including minimal surgical trauma, high screw placement accuracy, pain relief, neurological function improvement, high fusion rate, and lowered incidence of complications.

Three-dimensional printed patient-specific instrumentation (3D-PSI) provides a precise and individualized treatment solution for unicompartmental knee arthroplasty (UKA). Currently, this technology is being applied in clinical practice and has demonstrated certain potential. Compared to conventional instrumentation (CI), 3D-PSI offers a broader range of indications, higher-quality preoperative planning, shorter surgical time, a smoother learning curve, more precise osteotomy and prosthesis placement, and better postoperative functional recovery. However, it still has limitations in the rotational alignment of the tibial component. Additionally, the higher cost for patients and increased hospital equipment investment make it less beneficial for surgeons already proficient in CI techniques. Further reliable evidence is needed to compare 3D-PSI with computer navigation and robotic technologies. This review summarizes the advantages and limitations of 3D-PSI assisted UKA and compares 3D-PSI with different auxiliary technologies.

In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural-cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.
Humans ; Neoplasms/metabolism* ; Receptors, Neurotransmitter/physiology* ; Animals ; Tumor Microenvironment/physiology*

Objective:To evaluate the efficacy of 3D printing technology combined with computer navigation-assisted screw implantation in the treatment of atlantoaxial instability (AAI) complicated by vertebral artery anomalies.Methods:A retrospective case series study was conducted to analyze the clinical data of 23 patients with AAI complicated by vertebral artery anomalies who were admitted to Honghui Hospital of Xi′an Jiaotong University between January 2019 and January 2023, including 10 males and 13 females, aged 19-70 years [(51.0±13.3)years]. Vertebral artery anomalies were categorized into unilateral high-riding vertebral artery with unilateral dominance ( n=14), bilateral high-riding vertebral arteries with unilateral dominance ( n=6), and ponticulus posticus ( n=3). All the patients underwent preoperative planning using a 3D-printed model of the atlantoaxial complex with the vertebral artery, followed by posterior atlantoaxial pedicle screw fixation with computer-assisted navigation. Operative duration and intraoperative blood loss were recorded. The accuracy of pedicle screw placement was assessed at 3 days postoperatively using the Gertzbein-Robbins classification. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were evaluated preoperatively, at 3 days, 3 months postoperatively, and at the last follow-up. Bony fusion was assessed using cervical CT with 3D reconstruction at the last follow-up. Complications were also observed. Results:All the patients were followed up for 12-19 months [(15.1±1.9)months]. The operative duration was 125-167 minutes [(140.6±10.9)minutes] and intraoperative blood loss was 200-600 ml [(295.7±77.8)ml]. At 3 days postoperatively, all the 66 pedicle screws were safely placed, with 60 screws (91%) rated as Gertzbein-Robbins Grade 0 and 6 screws (9%) as Grade 1. At 3 days and 3 months postoperatively, and at the last follow-up, the VAS scores were (4.0±1.0)points, (2.0±0.6)points, and (1.3±0.5)points, and the JOA scores were (14.2±1.2)points, (16.0±0.8)points, and (16.6±0.5)points, both of which were not only significantly improved compared with preoperative (5.6±1.3)points and (12.8±1.5)points, but also further improved over time ( P<0.05). At the last follow-up, 22 patients (96%) achieved satisfactory atlantoaxial bony fusion. No vertebral artery injury, spinal cord or nerve injury, cerebrospinal fluid leakage, or screw loosening were observed in any patients. Conclusion:For patients with AAI complicated by vertebral artery anomalies, 3D printing combined with computer navigation-assisted navigation for atlantoaxial pedicle screw implantation offers multiple advantages, including minimal surgical trauma, high screw placement accuracy, pain relief, neurological function improvement, high fusion rate, and lowered incidence of complications.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.