Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs.

Background: It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods: Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results: Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13-27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions: Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.

Comprehensive analysis reveals that LTBR is a immune-related biomarker for glioma.

Glioma is a common malignant brain tumor with great heterogeneity and huge difference in clinical outcomes. Although lymphotoxin (LT) beta receptor (LTBR) has been linked to immune system and response development for decades, the expression and function in glioma have not been investigated. To confirm the expression profile of LTBR, integrated RNA-seq data from glioma and normal brain tissues were analyzed. Functional enrichment analysis, TMEscore analysis, immune infiltration, the correlation of LTBR with immune checkpoints and ferroptosis, and scRNAseq data analysis in gliomas were in turn performed, which pointed out that LTBR was pertinent to immune functions of macrophages in gliomas. In addition, after being trained and validated in the tissue samples of the integrated dataset, an LTBR DNA methylation-based prediction model succeeded to distinguish gliomas from non-gliomas, as well as the grades of glioma. Moreover, by virtue of the candidate LTBR CpG sites, a prognostic risk-score model was finally constructed to guide the chemotherapy, radiotherapy, and immunotherapy for glioma patients. Taken together, LTBR is closely correlated with immune functions in gliomas, and LTBR DNA methylation could serve as a biomarker for diagnosis and prognosis of gliomas.

Antibody-drug conjugates targeting HER2 for the treatment of urothelial carcinoma: potential therapies for HER2-positive urothelial carcinoma.

Urothelial carcinoma (UC) is a common cancer characterized by high morbidity and mortality rates. Despite advancements in treatment, challenges such as recurrence and low response rates persist. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach for various cancers, although their application in UC is currently limited. This review focuses on recent research regarding ADCs designed to treat UC by targeting human epidermal growth factor receptor 2 (HER2), a surface antigen expressed on tumor cells. ADCs comprise three main components: an antibody, a linker, and a cytotoxic payload. The antibody selectively binds to tumor cell surface antigens, facilitating targeted delivery of the cytotoxic drug, while linkers play a crucial role in ensuring stability and controlled release of the payload. Cleavable linkers release the drug within tumor cells, while non-cleavable linkers ensure stability during circulation. The cytotoxic payload exerts its antitumor effect by disrupting cellular pathways. HER2 is commonly overexpressed in UCs, making it a potential therapeutic target. Several ADCs targeting HER2 have been approved for cancer treatment, but their use in UC is still being tested. Numerous HER2 ADCs have demonstrated significant growth inhibition and induction of apoptosis in translational models of HER2-overexpressing bladder cancer. Ongoing clinical trials are assessing the efficacy and safety of ADCs targeting HER2 in UC, with the aim of determining tumor response and the potential of ADCs as a treatment option for UC patients. The development of effective therapies with improved response rates and long-term effectiveness is crucial for advanced and metastatic UC. ADCs targeting HER2 show promise in this regard and merit further investigation for UC treatment.

Linc01588 deletion inhibits the malignant biological characteristics of hydroquinone-induced leukemic cells via miR-9-5p/SIRT1.

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9-5p, miR-9-5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9-5p, miR-9-5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9-5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9-5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9-5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.

Eukaryotic Initiation Factor 3C Can Affect the Proliferation and Invasion of Ovarian Cancer by Regulating the p53 Signalling Pathway.

BACKGROUND: Eukaryotic Initiation Factor 3C (EIF3C) represents a pivotal translational initiation factor in eukaryotes and has been shown to facilitate the progression of various neoplasms. However, its mechanistic role in ovarian cancer remains elusive. METHODS: In this research, the expression of EIF3C in ovarian cancer tissues was investigated using immunohistochemistry. In addition, the assessments were made on changes in cellular proliferation, invasion, and apoptotic abilities by reducing the expression of EIF3C in ovarian cancer cells. By utilizing microarray analysis, a comparison was performed between the downregulated EIF3C group and the control group of ovarian cancer cells, revealing the genes that were expressed differently. Furthermore, the signalling pathways associated with cellular proliferation were validated. The functional role of EIF3C in vivo was investigated using a xenograft tumour model. RESULTS: The immunohistochemical analysis showed that elevated levels of EIF3C are linked to a negative prognosis in patients with ovarian cancer. Suppression of EIF3C greatly hindered the growth and spread of SK-OV-3 and HO-8910 cells while enhancing cellular programmed cell death. Following KEGG and GSEA enrichment analyses of differentially expressed genes, the p53 signalling pathway was found to be associated with EIF3C. Suppression of EIF3C resulted in the upregulation of the p53 signalling pathway, leading to the inhibition of cell proliferation and invasion and the promotion of apoptosis. In vivo experiments demonstrated that EIF3C knockdown suppressed the growth of subcutaneous tumours in nude mice. CONCLUSION: There is a correlation between overexpression of EIF3C in tumour tissues of ovarian cancer patients and this is associated with a poorer prognosis. By influencing the p53 signaling pathway, EIF3C facilitates the growth and infiltration of cells in ovarian cancer.

A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments.

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review.

Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1ß/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.

Clinicopathologic assessment of secondary syphilis avoids misdiagnosis: results of comprehensive evaluation of 114 cases.

Introduction: Secondary syphilis is well-known for its protean cutaneous manifestations and therefore very easy to be misdiagnosed. Aim: The current study was to observe the frequency of histopathological features characterizing secondary syphilis, and summarize the diseases most likely to be misdiagnosed. Material and methods: In this study a total of 129 pathological specimens from 114 patients with biopsy-proven secondary syphilis were retrospectively analysed and categorized according to clinicopathologic characteristics. The frequency of histopathological features characterizing secondary syphilis were analysed by comparison with clinical features. Results: We found that in a single sample there is at least one feature or at most 13 features exist concurrently, and most demonstrated between 5 and 9 diagnostic features. Plasma cells (97.6% overall vs. 94.0% ≤ 6 features), endothelial swelling (86.8% vs. 74.0%), epidermis hyperplasia (73.6% vs. 62.0%) especially irregular acanthosis, lymphocytes infiltration (71.3% vs. 52.0%) and interstitial patterns (69% vs. 72.0%) were the most common findings in all cases as well as in cases with ≤ 6 features. Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis (12.4%). The rash morphologies of our biopsies mainly manifesting as macules and maculopapules were more likely to have 6 or fewer features, which were not only easily misdiagnosed for pityriasis rosea, tinea and erythema multiforme, but also mostly taken from the trunk and genitalia. Atypical morphologies can be combined with plasma cell infiltration and T. pallidum immunohistochemical stain to confirm the diagnosis. Conclusions: In this study plasma cells from superficial and deep perivascular distribution to nodular infiltration were a crucial clue for diagnosis of secondary syphilis.

Failure of lipid control by PCSK9 inhibitors in compound heterozygous familial hypercholesterolemia complicated with premature myocardial infarction: A case report.

Key Clinical Message: A certain level of low-density lipoprotein receptor activity is crucial for the efficacy of PCSK9i. Therapeutic strategies for familial hypercholesterolemia patients should consider drug efficacy, and genetic testing will be helpful. Abstract: Familial hypercholesterolemia (FH) is a serious autosomal dominant disorder. Managing blood lipids in FH patients poses greater challenges for clinicians. Drug therapy may not always yield satisfactory results, particularly in individuals with low-density lipoprotein receptor (LDLR) negative mutations. Herein, we report a young female harboring an LDLR frameshift mutation. This patient developed xanthomas at 7 months old and underwent several years of treatment involving four classes of lipid-lowering drugs, including PCSK9i. However, the response to drug therapy was limited in this patient and eventually culminated in premature myocardial infarction. The efficacy of PCSK9i depends on the activity of LDLR. The inefficacy of PCSK9i may arise from the extensive mutations which leading to loss of LDLR activity. Therapy plans for these patients should take into account the efficacy of drug therapy. Early genetic testing is crucial for clinicians to make informed decisions regarding therapy options.

Red blood membrane camouflaging Bismuth nanoflowers designed for radio-photothermal therapy in lung cancer.

Radio-photothermal therapy is an effective modality for cancer treatment. To overcome the radio-resistance in the hypoxic microenvironment and improve the sensitivity of radiotherapy, metal nanoparticles, and radio-photothermal therapy are widely used in the research of improving the curative effect and reducing the side effects of radiotherapy. Here, we developed red blood membrane camouflaging bismuth nanoflowers (RBCM-BNF) with outstanding physiological stability and biodegradability for lung tumours. In vitro data proved that the RBCM-BNF had the greatest cancer cell-killing ability combined with X-ray irradiation and photo-thermal treatment. Meanwhile, in vivo studies revealed that RBCM-BNF can alleviate the hypoxic microenvironment and promote tumour cell apoptosis by inhibiting HIF-1α expression and increasing caspase-3 expression. Therefore, RBCM-BNF had a good radio-sensitising effect and might be a promising biomimetic nanoplatform as a therapeutic target for cancer.

Negative prognostic impact of Co-mutations in TGFß and TP53 pathways in surgically resected rectal tumors following neoadjuvant chemoradiotherapy.

BACKGROUND: Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified. METHODS: The comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results. RESULTS: The top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-ß and TP53 pathways were significantly associated with worse DFS. CONCLUSIONS: Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-ß and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.

BACKGROUND: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear. METHODS: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography. RESULTS: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'­adenosine monophosphate­activated protein kinase (p­AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C). CONCLUSIONS: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.

Related cellular signaling and consequent pathophysiological outcomes of ubiquitin specific protease 24.

Ubiquitin-specific protease 24 (USP24) is an essential member of the deubiquitinating protease family found in eukaryotes. It engages in interactions with multiple proteins, including p53, MCL-1, E2F4, and FTH1, among others. Through these interactions, USP24 plays a critical role in regulating vital cellular processes such as cell cycle control, DNA damage response, cellular iron autophagy, and apoptosis. Increased levels of USP24 have been observed in various cancer types, including bladder cancer, lung cancer, myeloma, hepatocellular carcinoma, and gastric cancer. However, in certain tumors like kidney cancer, USP24 is significantly downregulated, and the specific mechanism behind this remains unclear. Currently, there are no officially approved USP24 inhibitors available for clinical use. Some existing inhibitors targeting USP24 have shown promising effects in treating malignancies; however, their precise mode of action and information regarding binding sites are not well understood. Moreover, further optimization is required to enhance the selectivity and efficacy of these inhibitors. This review aims to provide a comprehensive overview of recent advancements in understanding the cellular functions of USP24, its association with various diseases, and the development of small-molecule inhibitors that target this protein. In conclusion, USP24 represents a promising therapeutic target for various diseases, and ongoing research will contribute to validating its role and facilitating the development of effective treatments.

The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis.

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

Variant histology is associated with more non-urothelial tract recurrence but less intravesical recurrence for upper tract urothelial carcinoma after radical nephroureterectomy.

PURPOSE: To investigate the prognostic impact of variant histology (VH) on oncological outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy (RNU). PATIENTS AND METHODS: A total of 1239 patients with clinically localized UTUC who underwent RNU at a single institution between January 2005 and June 2020 were included. The VH was reviewed by a uro-pathologist at our institution. The Cox regression model was used to perform multivariate analysis, including VH and other established prognostic factors for post-RNU oncological outcomes (intravesical recurrence [IVR], non-urothelial recurrence, and cancer-specific death). RESULTS: Of the 1239 patients with UTUC, 384 patients (31%) were found to have VH. Advanced tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, open surgery, and renal pelvis had a significantly larger proportion of UTUC with VH compared to pure UTUC (all p < 0.05). VH was an independent prognostic factor associated with less IVR identified by multivariate analysis, more non-urothelial recurrence, and more cancer-specific mortality. CONCLUSION: Patients with VH account for 31% with UTUC treated with RNU in this cohort. VH was an independent prognostic factor associated with more non-urothelial recurrence and cancer-specific mortality but less IVR.

Synthesis and Evaluation of Novel 99mTc-Labeled FGFR2-Targeting Peptides.

To develop radiolabeled FGFR2-targeting probes for visualizing fibroblast growth factor receptor (FGFR) expression levels in the tumor microenvironment, four novel 99mTc-labeled FGFR2-targeting peptides ([99mTc]Tc-FGFR2-1, [99mTc]Tc-FGFR2-2, [99mTc]Tc-FGFR2-3, and [99mTc]Tc-FGFR2-4) with different amino acid linkers between the targeted peptide moiety and the 99mTc chelating group were designed and synthesized. The in vitro cellular inhibition, internalization, and efflux results demonstrated that the four 99mTc complexes exhibited FGFR2-specific binding and prolonged cellular retention in DU145 human prostate cancer cells, which indicated that modification from the glycine side (N-terminal) of CH02 was feasible. Among them, [99mTc]Tc-FGFR2-1 exhibited the highest in vitro cellular uptake and in vivo tumor uptake at 30 min postinjection, and tumor uptake could be significantly inhibited by the competitor CH02 (53% inhibited, p < 0.05), suggesting the tumor-specific targeting ability of [99mTc]Tc-FGFR2-1. The DU145-xenografted tumor lesions were clearly visualized by single photon emission computed tomography (SPECT)/CT at 30 min postinjection of [99mTc]Tc-FGFR2-1, highlighting its potential as a SPECT imaging probe for tumor FGFR2 detection.

Cow placenta extract ameliorates d-galactose-induced liver damage by regulating BAX/CASP3 and p53/p21/p16 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Placenta is a kind of traditional Chinese medicine, known as "Ziheche", which has the function of tonifying qi and blood, nourishing liver and kidney. Placenta extract (PE) has been used for delaying organismal aging and treating various liver diseases. Cow placenta is a rich natural resource with large mass. Its composition is similar to that of human placenta, but it has not been effectively utilized. However, little is known about the effect of CPE on the liver of aging mice. AIM OF THE STUDY: The aim of this study is to explore the protective effect and mechanism of CPE on the liver of d-galactose (D-gal) induced aging mice. MATERIALS AND METHODS: Statistical methods were used to calculate mouse body weight and liver index. Hematoxylin-eosin (H&E) and transmission electron microscopy (TEM) were used to detect the morphological structure of the liver. Automatic biochemical analyzer was used to measure serum biochemical indicators. Three special staining methods were used to observe hepatocytes apoptosis, senescence and proliferation respectively. Relative kits were used to detect oxidative, inflammatory, and aging markers in the liver. Finally, real-time quantitative polymerase chain reaction and western-blot were used to detect aging related signaling pathways. RESULTS: CPE significantly improved the morphological damage and dysfunction of liver, restored the activities of liver enzymes in serum, and alleviated liver oxidative stress and inflammatory response in D-gal induced aging mice. Furthermore, CPE inhibited hepatocyte apoptosis and senescence, and promoted hepatocyte proliferation by regulating BAX/CASP3 and p53/p21/p16 signaling pathways, ultimately reduced the effects of aging on the liver. CONCLUSION: CPE effectively ameliorated the impact of aging on the liver by inhibiting free radical production or scavenging excessive free radicals, and its mechanism is associated to the regulation of apoptosis and proliferation-related factors.

Adult-type anomalous origin of the left coronary artery from the pulmonary artery and right coronary-right atrial fistula: a case report.

BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital cardiac anomaly, mortality rates in infancy reach approximately 90%, with only a small number of patients surviving into adulthood, therefore, most of the literature reports mainly focus on infantile type. CASE PRESENTATION: A 55-year-old female was admitted due to persistent repeated chest pain experienced and had worsened for unknown reasons. Color doppler echocardiography, coronary computed tomographic angiography, and coronary angiography confirmed the diagnosis of ALCAPA and concurrent right coronary artery-right atrial fistula. The symptoms of chest pain exhibited notable improvement subsequent to corrective surgery for the anomalous origin of the coronary artery. CONCLUSIONS: This report shows an unique case of ALCAPA in an adult patient, characterizing the condition's combination with a right coronary-right atrial fistula, and it is prone to misdiagnosis and misdiagnosis. We aim to provide valuable insights for clinical diagnosis and treatment of ALCAPA.