Association between body shape index and coronary heart disease in individuals over 20 years old with obese.

BACKGROUND: While body mass index (BMI) defines obesity as a well-established risk factor for cardiovascular disease, the paradoxical theory of BMI suggests that obesity may indeed have a favorable impact on the prognosis of cardiovascular disease. Therefore, this study aims to assess the correlation between body shape index (ABSI), which is a novel measure of obesity, and coronary heart disease (CHD) among obese individuals in the United States. METHODS: The data from the National Health and Nutrition Examination Survey (NHANES) were evaluated by us for 5046 patients. We assessed the exposure variable ABSI, which includes waist circumference (WC), height, and BMI. The outcome variable was CHD. RESULTS: The cross-sectional study included a total of 5046 obese adults aged over 20 years, with an average age (standard deviation: SD) of 49.86 (16.24) years and a male proportion of 44.57%.The odds ratio (OR) values for CHD in Model 1, Model 2, 3 were found to be 2.45 (95%CI: 2.12, 2.83), 1.53 (95%CI:1.30, 1.81) and 1.31 (95%CI:1.09, 1.56) per SD increase in ABSI, respectively. In the fully adjusted model, we designated participants in the T1 group as the reference group. Our findings indicate a significant increase in the prevalence of CHD (OR:1.82, 95%CI: 1.07-3.10) only within the T3 group. Although there is an increased prevalence of CHD (OR:1.32, 95%CI: 0.77-2.29) in the T2 group, no statistically significant difference was observed. CONCLUSIONS: The increase in ABSI is strongly associated with the rise in CHD prevalence among obese individuals in the United States.

The feedback loop between MTA1 and MTA3/TRIM21 modulates stemness of breast cancer in response to estrogen.

The metastasis-associated protein (MTA) family plays a crucial role in the development of breast cancer, a common malignancy with a high incidence rate among women. However, the mechanism by which each member of the MTA family contributes to breast cancer progression is poorly understood. In this study, we aimed to investigate the roles of MTA1, MTA3, and tripartite motif-containing 21 (TRIM21) in the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stem cell-like properties of breast cancer cells in vivo and in vitro. The molecular mechanisms of the feedback loop between MTA1 and MTA3/TRIM21 regulated by estrogen were explored using Chromatin immunoprecipitation (ChIP), luciferase reporter, immunoprecipitation (IP), and ubiquitination assays. These findings demonstrated that MTA1 acts as a driver to promote the progression of breast cancer by repressing the transcription of tumor suppressor genes, including TRIM21 and MTA3. Conversely, MTA3 inhibited MTA1 transcription and TRIM21 regulated MTA1 protein stability in breast cancer. Estrogen disrupted the balance between MTA1 and MTA3, as well as between MTA1 and TRIM21, thereby affecting stemness and the EMT processes in breast cancer. These findings suggest that MTA1 plays a vital role in stem cell fate and the hierarchical regulatory network of EMT through negative feedback loops with MTA3 or TRIM21 in response to estrogen, supporting MTA1, MTA3, and TRIM21 as potential prognostic biomarkers and MTA1 as a treatment target for future breast cancer therapies.

Nonlinear Chiral Metasurfaces Based on Structured van der Waals Materials.

Nonlinear chiral photonics explores the nonlinear response of chiral structures, and it offers a pathway to novel optical functionalities not accessible through linear or achiral systems. Here we present the first application of nanostructured van der Waals materials to nonlinear chiral photonics. We demonstrate the 3 orders of magnitude enhancement of the third-harmonic generation from hBN metasurfaces driven by quasi-bound states in the continuum and accompanied by strong nonlinear circular dichroism at the resonances. This novel platform for chiral metaphotonics can be employed for achieving large circular dichroism combined with high-efficiency harmonic generation in a broad frequency range.

Blue light photobiomodulation induced osteosarcoma cell death by facilitating ferroptosis and eliciting an incomplete tumor cell stress response.

To investigate the potential of blue light photobiomodulation (PBM) in inducing ferroptosis, a novel form of regulated cell death, in OS cells, considering its known effectiveness in various cancer models. In this investigation, we exposed human OS cell lines, HOS and MG63, to different wavelengths (420, 460 and 480 nm) of blue light at varying irradiances, and examined cellular responses such as viability, apoptosis, levels of reactive oxygen species (ROS), and mitochondrial membrane potential (MMP). Transcriptome sequencing was employed to unravel the molecular mechanisms underlying blue light-induced effects, with validation via quantitative real-time PCR (qRT-PCR). Our findings revealed a wavelength- and time-dependent decrease in cell viability, accompanied by increased apoptosis and oxidative stress. Transcriptomic analysis identified differential expression of genes associated with ferroptosis, oxidative stress, and iron metabolism, further validated by qRT-PCR. These results implicated ferroptosis as a significant mechanism in the blue light-induced death of OS cells, potentially mediated by ROS generation and disruption of iron homeostasis. Also, An incomplete stress response was observed in MG63 cells induced by blue light exposure. Hence, blue light PBM holds promise as a therapeutic approach in OS clinical investigations; however, additional exploration of its underlying mechanisms remains imperative.

Growth and non-structural carbohydrates response patterns of Eucommia ulmoides under salt and drought stress.

Introduction: Salinity and droughts are severe abiotic stress factors that limit plant growth and development. However, the differences and similarities of non-structural carbohydrates (NSCs) responses patterns of trees under the two stress conditions remain unclear. Methods: We determined and compared the growth, physiology, and NSCs response patterns and tested the relationships between growth and NSCs concentrations (or pool size) of Eucommia ulmoides seedlings planted in field under drought and salt stress with different intensities and durations. Results and discussion: We found that drought and salt stress can inhibit the growth of E. ulmoides, and E. ulmoides tended to enhance its stress resistance by increasing proline concentration and leaf thickness or density but decreasing investment in belowground biomass in short-term stress. During short-term drought and salt stress, the aboveground organs showed different NSCs response characteristics, while belowground organs showed similar change characteristics: the starch (ST) and NSCs concentrations in the coarse roots decreased, while the ST and soluble sugar (SS) concentrations in the fine roots increased to enhance stress resistance and maintain water absorption function. As salt and drought stress prolonged, the belowground organs represented different NSCs response patterns: the concentrations of ST and SS in fine roots decreased as salt stress prolonged; while ST in fine roots could still be converted into SS to maintain water absorption as drought prolonged, resulting in an increase of SS and a decrease of ST. Significant positive relationships were found between growth and the SS and total NSCs concentrations in leaves and branches, however, no significant correlations were found between growth and below-ground organs. Moreover, relationships between growth and NSCs pool size across organs could be contrast. Conclusion: Our results provide important insights into the mechanisms of carbon balance and carbon starvation and the relationship between tree growth and carbon storage under stress, which were of great significance in guiding for the management of artificial forest ecosystem under the context of global change.

The intratumoral microbiota biomarkers for predicting survival and efficacy of immunotherapy in patients with ovarian serous cystadenocarcinoma.

BACKGROUND: Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need. METHODS: In this study, we analyzed the microbial contents of 453 ovarian serous cystadenocarcinoma and 68 adjacent non-cancerous samples. A univariate Cox regression model was used to identify microorganisms significantly associated with survival and a prognostic risk score model constructed using LASSO Cox regression analysis. Patients were subsequently categorized into high-risk and low-risk groups based on their risk scores. RESULTS: Survival analysis revealed that patients in the low-risk group had a higher overall survival rate. A nomogram was constructed for easy visualization of the prognostic model. Analysis of immune cell infiltration and immune checkpoint gene expression in both groups showed that both parameters were positively correlated with the risk level, indicating an increased immune response in higher risk groups. CONCLUSION: Our findings suggest that microbial profiles in ovarian serous cystadenocarcinoma may serve as viable clinical prognostic indicators. This study provides novel insights into the potential impact of intratumoral microbial communities on disease prognosis and opens avenues for future therapeutic interventions targeting these microorganisms.

A case report of small intestinal volvulus caused by lipomatosis of the small intestine successfully treated with enterectomy.

Small intestinal lipomatosis is a rare condition that presents a diagnostic challenge due to the absence of identifiable clinical symptoms and limitations of small intestine examination methods. Consequently, preoperative diagnosis is difficult and only a limited number of cases have been documented in the scientific literature. Here, we report a rare case of volvulus caused by small intestinal lipomatosis. A 58-year-old female patient was tentatively diagnosed with acute ileus. The whirl sign was detected using abdominal three-dimensional enhanced computed tomography, along with marked local intestinal dilation and multiple irregular fat-like containing lesions. During surgery, abnormal dilation of the small intestine between 80 and 220 cm from the ileocecal valve was detected and the affected intestine displayed a folded and twisted configuration. Examination of the resected intestine showed that the inner wall of the diseased intestinal lumen was covered with more than 100 lipomas of different sizes, the largest of which measured ~8.0 cm in diameter. Based on clinical symptoms alone, it was difficult to identify the cause of intestinal volvulus before surgery. Complete resection of the affected small intestine and subsequent pathological analysis yielded a definitive diagnosis of small intestinal lipomatosis. While small intestinal lipomatosis is a rare condition, prognosis is favorable if diagnosed early and treated appropriately. The application of three-dimensional enhanced computed tomography imaging can aid in accurate diagnosis, while complete resection of the affected small intestine is crucial to improve patient prognosis.

ROS-induced imbalance of the miR-34a-5p/SIRT1/p53 axis triggers chronic chondrocyte injury and inflammation.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

Discovery and Manipulation of van der Waals Polarons in Sb2O3 Ultrathin Molecular Crystal.

Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.

The role of digestive system diseases in cerebrovascular disease: a comprehensive Mendelian randomization study.

Background: Cerebrovascular disease, among the most prevalent neurological disorders, poses a substantial threat to human health with its elevated mortality and disability rates, placing considerable strain on healthcare systems. Although several studies in recent years have suggested a potential association between digestive system diseases and cerebrovascular diseases, the findings remain inconsistent. Methods: Genome-wide association study (GWAS) summary data for 12 digestive diseases and cerebrovascular diseases were used to conduct Mendelian randomization (MR) analysis. In this investigation, we endeavored to elucidate the causal relationship between digestive system diseases and cerebrovascular diseases. Employing a comprehensive approach, including two-sample MR (TSMR), multivariate MR (MVMR), and two-step MR analysis, we leveraged summary statistics data obtained from published GWAS. The primary analysis method employed was inverse variance weighted (IVW), with MR-Egger and weighted median (WM) as secondary methods. Sensitivity analysis included heterogeneity testing, horizontal multivariate testing, MR-PRESSO, and a "leave-one-out" method. Additionally, the F-statistic was utilized to assess the strength of instrumental variables, ensuring robust results. Results: In the TSMR analysis, this study found a significant causal relationship between genetically predicted gastroesophageal reflux disease (GERD) and any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), intracranial aneurysm (IA), and subarachnoid hemorrhage (SAH). In MVMR analysis, this study found that even after adjusting for systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes (T2D), the causal relationship remains exist. In the two-step MR mediation analysis, it was found that BMI, SBP and T2D play mediating role in the causal relationship between GERD and cerebrovascular diseases. Conclusion: This study indicates a clear positive causal relationship between GERD and cerebrovascular diseases, and this causal association remains significant even after adjusting for BMI, SBP and T2D. The mediation MR analysis suggests that BMI, SBP and T2D may mediate the causal relationship between GERD and the risk of cerebrovascular diseases.

Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.

Background: The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function. Materials and methods: Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV1, FVC, and FEV1/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results. Results: The MR results confirmed four taxa were found causally associated with the risk of IPF. Order Bifidobacteriales (OR=0.773, 95% CI: 0.610-0.979, p=0.033), Family Bifidobacteriaceae (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and Genus RuminococcaceaeUCG009 (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while Genus Coprococcus2 (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in Class Deltaproteobacteria, Order Desulfovibrionales, Family Desulfovibrionaceae, Class Verrucomicrobiae, Order Verrucomicrobiales and Family Verrucomicrobiaceae being the most prominent beneficial microbiota, while those in Family Lachnospiraceae, Genus Oscillospira, and Genus Parasutterella were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV1 and FVC on the increased abundance of six taxa (Phylum Actinobacteria, Class Actinobacteria, Order Bifidobacteriales, Family Bifidobacteriaceae, Genus Bifidobacterium, and Genus Ruminiclostridium9) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF. Conclusion: The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.

Insight into mitigation mechanisms of N2O emission by biochar during agricultural waste composting.

The effects and mitigation mechanisms of biochar added at different composting stages on N2O emission were investigated. Four treatments were set as follows: CK: control, BB10%: +10 % biochar at beginning of composting, BB5%&T5%: +5% biochar at beginning and + 5 % biochar after thermophilic stage of composting, BT10%: +10 % after thermophilic stage of composting. Results showed that treatment BB10%, BB5%&T5%, and BT10% reduced total N2O emissions by 55 %, 37 %, and 36 %, respectively. N2O emission was closely related to most physicochemical properties, while it was only related to amoA gene and hydroxylamine oxidoreductase. Different addition strategies of biochar changed the contributions of physicochemical properties, functional genes and enzymes to N2O emission. Organic matter and C/N contributed 23.7 % and 27.6 % of variations in functional gene abundances (P < 0.05), respectively. pH and C/N (P < 0.05) contributed 37.3 % and 17.3 % of variations in functional enzyme activities. These findings provided valuable insights into mitigating N2O emissions during composting.

Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma Associated with Epstein-Barr Virus and Hepatitis Virus: Case Report and a Literature Review.

Background: Lymphoepithelioma-like carcinoma of the liver is a rare primary malignancy of the liver. The identification of lymphoepithelioma-like cholangiocarcinoma is very limited as there are currently very few reports of such cases. Although previous studies have reported the lymphoepithelioma-like cholangiocarcinoma pathologic features, few studies have revealed the clinic features, imaging characteristics, and clinical course and outcomes. This study was analyzed from multiple aspects such as contrast-enhanced ultrasound, magnetic resonance imaging, and pathological characteristics, aiming to improve the comprehensive understanding of this rare subtype of disease. Case Presentation: A 43-year-old female with a history of hepatitis B for over 20 years presented with a lesion found in the right lobe of her liver. After discussion by a multidisciplinary team (MDT), malignant tumors cannot be excluded based on contrast-enhanced ultrasound and MRI. Thus, we decided to perform surgery for the patient. Postoperative pathology confirmed lymphoepithelioma-like intrahepatic cholangiocarcinoma. After 3 months of follow-up, the patient was still alive and no recurrence was observed. Conclusion: The purpose of this article is to describe a rare case of lymphoepithelioma-like intrahepatic cholangiocarcinoma and analyze its contrast-enhanced ultrasound and contrast-enhanced MRI features, which will be helpful for physicians in diagnosing this disease. From the perspective of CEUS, the wedge-shaped highly enhanced area around the lesion in the arterial phase appears to be inflammatory but looks malignant based on the extremely fast washout. The lesion showed a low signal on T1WI, a high signal on T2WI and DWI, and an abnormal perfusion shadow can be seen behind the lesion. In particular, this subtype of cholangiocarcinoma has a good prognosis, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Thermal-Stabilized Protonated TiO2 for Heat-Accelerated Photoelectrochemical Water Splitting.

Enhancing the charge separation efficiency is a big challenge that limits the energy conversion efficiency of photoelectrochemical (PEC) water splitting. Surface states generated by protonation of TiO2 are the efficient charge separation passageways to massively accept or transfer the photogenerated electrons. However, a challenge is to avoid the deprotonation of a protonated TiO2 photoelectrode at the operation temperature. Here, we found that the terminal hydroxyl group (OHT) as surface states on the TiO2 surface generated via electrochemical protonation of TiO2 at 90 °C [90-TiO2-x-(OH)x] is thermally stable. As a result, the thermally enhanced photocurrent of the 90-TiO2-x-(OH)x electrode reached 1.05 mA cm-2 under 80 °C, and the stability was maintained up to 10 h with a slight photocurrent decrease of 3%. The thermally stable surface states as charge separation paths provide an effective method to couple the heat field with the PEC process via thermal-stimulating hopping of polarons.

CircST6GAL1 knockdown alleviates pulmonary arterial hypertension by regulating miR-509-5p/multiple C2 and transmembrane domain containing 2 axis.

BACKGROUND: Hypertension is a main contributing factor of cardiovascular diseases; deregulated circular RNAs are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Herein, we evaluated the function and mechanism of circST6GAL1 in PAH process. METHODS: Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic environment for functional analysis. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and flow cytometry assays were used to investigate cell proliferation, migration, and apoptosis. qRT-PCR and Western blotting analyses were used for level measurement of genes and proteins. The binding between miR-509-5p and circST6GAL1 or multiple C2 and transmembrane domain containing 2 (MCTP2) was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays. The monocrotaline (MCT)-induced PAH mouse models were established for in vivo assay. RESULTS: CircST6GAL1 was highly expressed in PAH patients and hypoxia-induced HPASMCs. Functionally, circST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs. Mechanistically, circST6GAL1 directly targeted miR-509-5p, and MCTP2 was a target of miR-509-5p. Rescue assays showed that the regulatory effects of circST6GAL1 deficiency on hypoxia-induced HPASMCs were abolished. Moreover, forced expression of miR-509-5p suppressed HPASMC proliferation and migration and induced cell apoptosis under hypoxia stimulation, while these effects were abolished by MCTP2 overexpression. Moreover, circST6GAL1 silencing improved MCT-induced pulmonary vascular remodeling and PAH. CONCLUSION: CircST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs, and alleviated pulmonary vascular remodeling in MCT-induced PAH mouse models through the miR-509-5p/MCTP2 axis, indicating a potential therapeutic target for PAH.

Construction of porphyrinic manganese-organic frameworks based on structural regulation for electrochemical determination of nitrobenzene in water and vegetable samples.

Nitrobenzene (NB) is one of the major organic pollutants that has seriously endangered human health and the environment even in trace amounts. Therefore, it is of great significance to detect trace NB efficiently and sensitively. Herein, a porphyrinic metal-organic framework (MOF) of Mn-PCN-222 (PCN, porous coordination network) was first synthesized by the coordination between Zr6 cluster and tetrakis (4-carboxyphenyl)-porphyrin-Mn (Ⅲ) (MnTCPPCl) ligand. To regulate its structure and the electrochemical properties, a phenyl group was inserted in each branched chain of TCPP to form the TCBPP organic ligand. Then, we used Zr6 clusters and manganese metalloporphyrin (MnTCBPPCl) to synthesize a new porphyrin-based MOF (Mn-CPM-99, CPM, crystalline porous material). Due to the extended chains of TCPP, the rod-shaped structure of Mn-PCN-222 was switched to concave quadrangular bipyramid of Mn-CPM-99. Mn-CPM-99 exhibited higher porosity, larger specific surface area, better electrochemical performances than those of Mn-PCN-222. By using modular assembly technique, Mn-CPM-99 film was sequentially assembled on the surface of indium-tin-oxide (ITO) to prepare an electrochemical sensor (Mn-CPM-99/ITO). The proposed sensor showed excellent electrochemical reduction of NB and displayed three linear response ranges in the wide concentration ranges. The obtained low limit of detection (LOD, 1.3 nM), high sensitivity and selectivity, and good reproducibility of the sensor for NB detection fully illustrate that Mn-CPM-99 is an excellent candidate for electrochemical sensor interface material. Moreover, the sensor was successfully applied to the detection of NB in lake water and vegetable samples showing satisfactory recovery of 98.9%-101.8%.

Efficacy and safety of tranexamic acid in the treatment of gastric cancer complicated with upper gastrointestinal bleeding.

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) in preventing upper gastrointestinal (GI) bleeding in patients with gastric cancer. METHODS: The clinical data of patients with gastric cancer complicated with acute non-operative GI bleeding treated in the Fourth Hospital of Hebei Medical University from 2020 to 2022 were collected and retrospectively analyzed. The survival status of the patients was followed up by telephone. The dataset of 168 patients was divided into a control group (n=85) and a TXA group (n=83), at a 1:1 ratio. The patients in the control group were treated with esomeprazole, and the patients in the TXA group received additional TXA. The hemostatic effect, rebleeding rate, and mortality of patients were compared between the two groups. The Cox proportional hazard model was used to evaluate the overall survival of patients as well as the related risk factors. RESULTS: The success rate of hemostasis and the normal blood coagulation rate in the TXA group were significantly higher than those in the control group (P=0.003 and P=0.016). The secondary bleeding rate, thrombus formation rate and digestive tract perforation rate in the TXA group were significantly lower than those in the control group (P=0.002, P=0.003 and P=0.035). The improvement of all indicators in the TXA group was better than that in the control group (all P<0.05). For patients with gastric cancer complicated with acute GI bleeding treated with TXA, the Cox proportional hazard model identified III~IV stage, time of TXA treatment, surgical treatment after hemorrhage, and an increase of D-dimer as independent risk factors for upper GI bleeding (all P<0.05). CONCLUSION: TXA can be an effective treatment for patients with gastric cancer complicated by GI bleeding.

Recent progress in radioactive seed implantation brachytherapy of non-small cell lung cancer: a narrative review.

Background and Objective: Brachytherapy, a new form of radiation therapy, has been used to treat lung cancer and consists of two main forms of treatment: endobronchial brachytherapy and radioactive seed implantation brachytherapy (RSI-BT), the latter of which is used to treat non-small cell lung cancer (NSCLC). The use of RSI-BT in the treatment of NSCLC at our centre has yielded some positive results. Methods: To more fully consider the context of this application, we conducted a search of PubMed from 2018 to March 5, 2023. The search included a combination of the MeSH terms: "brachytherapy" and "lung neoplasm". Key Content and Findings: The majority of NSCLC patients who received RSI-BT achieved positive benefits. Most patients had a progression-free survival (PFS) of between 12 and 18 months. Additionally, radioactive particle stent implantation as a specific RSI-BT has shown therapeutic potential in the treatment of malignant airway obstruction. With the application of new technologies, RSI-BT will become more precise, efficient and inexpensive. Conclusions: This review demonstrates that RSI-BT can be therapeutic in the treatment of both early and advanced NSCLC with manageable complications. There have also been reports on the combination of RSI-BT with other therapies, but more research is needed on the combination of RSI-BT with them.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

Objectives: This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Methods: This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. Results: The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. Conclusions: BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.