The association between smoking exposure and endothelial function evaluated using flow-mediated dilation values: a meta-analysis.

BACKGROUND: Tobacco use is recognized as a major cause of cardiovascular disease, which is associated with endothelial dysfunction. Endothelial function is evaluated using flow-mediated dilation (FMD), which is a noninvasive method. This meta-analysis aimed to investigate the association between smoking exposure and endothelial function evaluated using FMD values. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for cohort studies of smokers or passive smokers that used FMD to assess endothelial function. The primary outcome of the study was the change in the rate of FMD. The risk of bias was evaluated using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. Further, the weighted mean difference was used to analyze the continuous data. RESULTS: Overall, 14 of 1426 articles were included in this study. The results of these articles indicated that smoking is a major cause of endothelial dysfunction and altered FMD; a pooled effect size of - 3.15 was obtained with a 95% confidence interval of (- 3.84, - 2.46). Notably, pregnancy status, Asian ethnicity, or health status did not affect heterogeneity. CONCLUSIONS: We found that smoking has a significant negative impact on FMD, and measures such as medication or education for smoking cessation may improve endothelial function and reduce the risk of cardiovascular disease. TRIAL REGISTRATION: The meta-analysis was registered with PROSPERO on April 5th, 2023 (CRD42023414654).

Ji-Ni-De-Xie ameliorates type 2 diabetes mellitus by modulating the bile acids metabolism and FXR/FGF15 signaling pathway.

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats. Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg-1) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1ß, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR. Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1ß, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX. Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway.

CD276 regulates the immune escape of esophageal squamous cell carcinoma through CXCL1-CXCR2 induced NETs.

BACKGROUND: CD276 (B7-H3), a pivotal immune checkpoint, facilitates tumorigenicity, invasiveness, and metastasis by escaping immune surveillance in a variety of tumors; however, the underlying mechanisms facilitating immune escape in esophageal squamous cell carcinoma (ESCC) remain enigmatic. METHODS: We investigated the expression of CD276 in ESCC tissues from patients by using immunohistochemistry (IHC) assays. In vivo, we established a 4-nitroquinoline 1-oxide (4NQO)-induced CD276 knockout (CD276wKO) and K14cre; CD276 conditional knockout (CD276cKO) mouse model of ESCC to study the functional role of CD276 in ESCC. Furthermore, we used the 4NQO-induced mouse model to evaluate the effects of anti-CXCL1 antibodies, anti-Ly6G antibodies, anti-NK1.1 antibodies, and GSK484 inhibitors on tumor growth. Moreover, IHC, flow cytometry, and immunofluorescence techniques were employed to measure immune cell proportions in ESCC. In addition, we conducted single-cell RNA sequencing analysis to examine the alterations in tumor microenvironment following CD276 depletion. RESULTS: In this study, we elucidate that CD276 is markedly upregulated in ESCC, correlating with poor prognosis. In vivo, our results indicate that depletion of CD276 inhibits tumorigenesis and progression of ESCC. Furthermore, conditional knockout of CD276 in epithelial cells engenders a significant downregulation of CXCL1, consequently reducing the formation of neutrophil extracellular trap networks (NETs) via the CXCL1-CXCR2 signaling axis, while simultaneously augmenting natural killer (NK) cells. In addition, overexpression of CD276 promotes tumorigenesis via increasing NETs' formation and reducing NK cells in vivo. CONCLUSIONS: This study successfully elucidates the functional role of CD276 in ESCC. Our comprehensive analysis uncovers the significant role of CD276 in modulating immune surveillance mechanisms in ESCC, thereby suggesting that targeting CD276 might serve as a potential therapeutic approach for ESCC treatment.

Stem cell therapies: a new era in the treatment of multiple sclerosis.

Multiple Sclerosis (MS) is an immune-mediated condition that persistently harms the central nervous system. While existing treatments can slow its course, a cure remains elusive. Stem cell therapy has gained attention as a promising approach, offering new perspectives with its regenerative and immunomodulatory properties. This article reviews the application of stem cells in MS, encompassing various stem cell types, therapeutic potential mechanisms, preclinical explorations, clinical research advancements, safety profiles of clinical applications, as well as limitations and challenges, aiming to provide new insights into the treatment research for MS.

Repeated acute coronary syndrome caused by a mind-bending mural thrombus in ascending aorta: a case report and review of the literature.

BACKGROUND: Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). CASE PRESENTATION: We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. CONCLUSIONS: Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.

Knockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis.

BACKGROUND: Lung cancer is a serious threat to human health and is the first leading cause of cancer death. Ferroptosis, a newly discovered form of programmed cell death associated with redox homeostasis, is of particular interest in the lung cancer, given the high oxygen environment of lung cancer. NADPH has reducing properties and therefore holds the potential to resist ferroptosis. Resistance to ferroptosis exists in lung cancer, but the role of NADK in regulating ferroptosis in lung cancer has not been reported yet. METHODS: Immunohistochemistry (IHC) was used to analyse the expression of NADK in 86 cases of lung adenocarcinoma(LUAD) and adjacent tissues, and a IHC score was assigned to each sample. Chi-square and kaplan-meier curve was performed to analyse the differences in metastasis and five-year survival between the two groups with NADK high or low scores. Proliferation of NADK-knockdown LUAD cell lines was detected in vivo and vitro. Furthermore, leves of ROS, MDA and Fe2+ were measured to validate the effect and mechanism of NADK on ferroptosis in LUAD. RESULTS: The expression of NADK was significantly evaluated in LUAD tissues as compared to adjacent non-cancerous tissues. The proliferation of NADK-knockdown cells was inhibited both in vivo and vitro, and increasing levels of intracellular ROS, Fe2+ and lipid peroxide products (MDA) were observed. Furthermore, NADK-knockdown promoted the ferroptosis of LUAD cells induced by Erastin/RSL3 by regulating the level of NADPH and the expression of FSP1. Knockdown of NADK enhanced the sensitivities of LUAD cells to Erastin/RSL3-induced ferroptosis by regulating NADPH level and FSP1 expression. CONCLUSIONS: NADK is over-expressed in LUAD patients. Knockdown of NADK inhibited the proliferation of LUAD cells both in vitro and in vivo and promotes the Erastin/RSL3-induced ferroptosis of LUAD cells by down-regulating the NADPH/FSP1 axis.

Pengzhenrongella phosphoraccumulans sp. nov., isolated from high Arctic glacial till, and emended description of the genus Pengzhenrongella.

A yellow pigmented, Gram-stain-positive, motile, facultatively anaerobic and irregular rod-shaped bacteria (strain M0-14T) was isolated from a till sample collected from the foreland of a high Arctic glacier near the settlement of Ny-Ålesund in the Svalbard Archipelago, Norway. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that M0-14T formed a lineage within the family Cellulomonadaceae, suborder Micrococcineae. M0-14T represented a novel member of the genus Pengzhenrongella and had highest 16S rRNA gene sequence similarity to Pengzhenrongella sicca LRZ-2T (97.3 %). Growth occurred at 4-25 °C (optimum 4-18 °C), at pH 6.0-9.0 (optimum pH 7.0), and in the presence of 0-5 % (w/v) NaCl. The predominant menaquinone was MK-9(H4) and the major fatty acids were anteiso-C15 : 0, C16 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The major polar lipids were phosphatidylglycerol, phosphatidylinositol mannosides, phosphatidylinositol, one undefined phospholipid and five undefined phosphoglycolipids. The cell-wall diamino acid was l-ornithine whereas rhamnose and mannose were the cell-wall sugars. Polyphosphate particles were found inside the cells of M0-14T. Polyphosphate kinase and polyphosphate-dependent glucokinase genes were detected during genomic sequencing of M0-14. In addition, the complete pstSCAB gene cluster and phnCDE synthesis genes, which are important for the uptake and transport of phosphorus in cells, were annotated in the genomic data. According to the genomic data, M0-14T has a metabolic pathway related to phosphorus accumulation. The DNA G+C content of the genomic DNA was 70.8 %. On the basis of its phylogenetic relationship, phenotypic properties and chemotaxonomic distinctiveness, strain M0-14T represents a novel species of the genus Pengzhenrongella, for which the name Pengzhenrongella phosphoraccumulans sp. nov. is proposed. The type strain is M0-14T (= CCTCC AB 2012967T = NRRL B-59105T).

The Role of Pyroptosis in Coronary Heart Disease.

The incidence and mortality of cardiovascular diseases, of which coronary heart disease (CHD) is a significant cardiovascular burden, are on the rise. Pyroptosis as an incipient programmed cell death mediated by inflammasomes can sense cytoplasmic contamination or interference and is typically marked by intracellular swelling, plasma membrane blistering and intense inflammatory cytokine release. As research on pyroptosis continues to progress, there is mounting evidence that pyroptosis is a vital participant in the pathophysiological basis of CHD. Atherosclerosis is the major pathophysiological basis of CHD and involves pyroptosis of endothelial cells, macrophages, vascular smooth muscle cells, and other immune cells, often in association with the release of pro-inflammatory factors. When cardiomyocytes are damaged, it will eventually lead to heart failure. Previous studies have covered that pyroptosis plays a critical role in CHD. In this review, we describe the properties of pyroptosis, summarize its contribution and related targets to diseases involving angina pectoris, myocardial infarction, myocardial ischemia in perfusion injury and heart failure, and highlight potential drugs for different heart diseases.

RuZn NPs with electroactivity and oxidase-like property for dual-mode anti-cancer drug monitoring.

6-mercaptopurine (6-MP) as the effective anti-cancer drug was used for the treatment of Crohn's disease and acute lymphoblastic leukaemia, but the response to maintenance therapy was variable with individual differences. In order to control the dosage and decrease the side effects of 6-MP, a sensitive and stable assay was urgently needed for 6-MP monitoring. Herein, RuZn NPs with electrochemical oxidation property and oxidase-like activity was proposed for dual-mode 6-MP monitoring. Burr-like RuZn NPs were prepared and explored to not only exhibit an electrochemical oxidation signal at 0.78 V, but also displayed excellent oxidase-like performances. RuZn NPs were utilized for the dual-mode monitoring of 6-MP, attributing to the formation of Ru-SH covalent bonding. The colorimetric method showed good linearity from 10 µM to 5 mM with the limit of detection (LOD) of 300 nM, while the electrochemical method provided a higher sensitivity with the LOD of 37 nM in range from 100 nM to 200 µM. This work provided a new way for the fabrication of dual-functional nanotags with electroactivity and oxidase-like property, and opened a dual-mode approach for the 6-MP detection applications with complementary and satisfactory results.

Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.

Effects of dietary water-soluble extract of rosemary supplementation on growth performance and intestinal health of broilers infected with Eimeria tenella.

This study was conducted to explore the effect of dietary supplementation of water-soluble extract of rosemary (WER) on growth performance and intestinal health of broilers infected with Eimeria tenella (E. tenella), and evaluate the anticoccidial activity of WER. 360 1-d-old Chinese indigenous male yellow-feathered broiler chickens were randomly allocated to six groups: blank control (BC) group and infected control (IC) group received a basal diet; positive control (PC) group, received a basal diet supplemented with 200 mg/kg diclazuril; WER100, WER200, and WER300 groups received a basal diet containing 100, 200, and 300 mg/kg WER, respectively. On day 21, all birds in the infected groups (IC, PC, WER100, WER200, and WER300) were orally gavaged with 1 mL phosphate-buffered saline (PBS) of 8 × 104 sporulated oocysts of E. tenella, and birds in the BC group were administrated an aliquot of PBS dilution. The results showed that dietary supplementation of 200 mg/kg WER increased the average daily gain of broilers compared to the IC group from days 22 to 29 (P < 0.001). The anticoccidial index values of 100, 200, and 300 mg/kg WER were 137.49, 157.41, and 144.22, respectively, which indicated that WER exhibited moderate anticoccidial activity. Compared to the IC group, the groups supplemented with WER (100, 200, and 300 mg/kg) significantly lowered fecal oocyst output (P < 0.001) and cecal coccidia oocysts, alleviated intestinal damage and maintained the integrity of intestinal epithelium. Dietary supplementation with WER significantly improved antioxidant capacity, elevated the levels of secretory immunoglobulin A, and diminished inflammation within the cecum, particularly at a dosage of 200 mg/kg. The results of this study indicated that dietary supplementation with 200 mg/kg WER could improve broiler growth performance and alleviate intestinal damage caused by coccidiosis.

Avian coccidiosis, a prevalent parasitic disease caused by Eimeria protozoa, leads to significant economic losses in the global poultry industry. Currently, the control of coccidiosis in chickens primarily relies on chemical and ionophore anticoccidials. However, the long-term use of these compounds has resulted in the development of drug-resistant strains, presenting a critical challenge. Additionally, the toxic and side effects of ionophore anticoccidials have become increasingly apparent. Thus, there is an urgent need to find economical and environmentally friendly measures to control coccidiosis in chickens. In this study, we established a model of Eimeria tenella infection in broilers to explore whether the water-soluble extract of rosemary (WER) could serve as an alternative method for controlling avian coccidiosis. Our results showed that dietary supplementation with WER (100, 200, and 300 mg/kg) had a beneficial anticoccidial effect, alleviating intestinal damage caused by coccidiosis by enhancing the intestinal antioxidant defense and activating the immune function of the infected broilers. Specifically, dietary supplementation with 200 mg/kg WER emerged as a promising strategy for controlling avian coccidiosis in the poultry industry.

An effective strategy for biodegradation of high concentration phenol in soil via biochar-immobilized Rhodococcus pyridinivorans B403.

High concentration of phenol residues in soil are harmful to human health and ecological safety. However, limited information is available on the in-situ bioremediation of phenol-contaminated soil using biochar as a carrier for bacteria. In this study, bamboo -derived biochar was screened as a carrier to assemble microorganism-immobilized composite with Rhodococcus pyridinivorans B403. Then, SEM used to observe the micromorphology of composite and its bioactivity was detected in solution and soil. Finally, we investigated the effects of free B403 and biochar-immobilized B403 (BCJ) on phenol biodegradation in two types of soils and different initial phenol concentrations. Findings showed that bacterial cells were intensively distributed in/onto the carriers, showing high survival. Immobilisation increased the phenol degradation rate of strain B403 by 1.45 times (37.7 mg/(L·h)). The phenol removed by BCJ in soil was 81% higher than free B403 on the first day. Moreover, the removal of BCJ remained above 51% even at phenol concentration of 1,500 mg/kg, while it was only 15% for free B403. Compared with the other treatment groups, BCJ showed the best phenol removal effect in both tested soils. Our results indicate that the biochar-B403 composite has great potential in the remediation of high phenol-contaminated soil.

Exploring the association of POSTN+ cancer-associated fibroblasts with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) play a critical role in regulating TNBC tumor development. This study aimed to identify and characterize a specific subtype of CAFs associated with TNBC. Initially, using high-throughput bulk transcriptomic data in two cohorts, we identified three CAF-related subtypes (CS1, CS2, CS3) in TNBC samples. These three CAFs subtypes were closely linked to the tumor microenvironment. The CS1 subtype exhibited a relatively immune-rich microenvironment and a favourable prognosis, whereas the CS3 subtype displayed an immune-deprived tumor microenvironment and an unfavourable prognosis. Through WGCNA analysis, POSTN was identified as a key biomarker for CAFs associated with TNBC. Then, POSTN+CAFs was identified and characterized. Both POSTN and POSTN+CAFs showed significant positive correlations with stromal molecules HGF and MET at both the transcriptional and protein levels. Specifically co-localized with CAFs in the tumor stromal area, POSTN, produced by POSTN+CAFs, could modulate the HGF-MET axis, serving as a bypass activation pathway to regulate tumor cell proliferation in response to EGFR inhibitor and MET inhibitor. This study underscores the significance of POSTN and POSTN+CAFs as crucial targets for the diagnosis and treatment of TNBC.

Primary cardiac angiosarcoma: Imaging characterization.

This case report describes a 35-year-old female patient who presented with palpitations and shortness of breath. Imaging findings suggested a cardiac tumor, histopathology confirmed primary cardiac angiosarcoma. This tumor is highly aggressive, usually occurs in the right atrium, lacks specificity in clinical presentation, is prone to early metastasis, and has a poor prognosis. Echocardiography is the method of choice for early detection and is important in assessing tumor size, location, mode of attachment and whether cardiac function is impaired.

A case report of pediatric biliary botryoid rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children, and botryoid rhabdomyosarcoma (BRMS) represents a subtype of RMS. BRMS primarily occurs in infants, young children, and adolescent females, with a predilection for mucosa-lined hollow organs such as the bladder, vagina, bile duct, and so on. Its occurrence in the biliary tract is extremely rare. Due to the high malignancy and rapid metastasis of biliary botryoid rhabdomyosarcoma, early diagnosis and treatment are crucial for improving prognosis.

Analysis of cantharidin-induced kidney injury and the protective mechanism of resveratrol in mice determined by liquid chromatography/mass spectrometry-based metabonomics.

Cantharidin (CTD) is the main active component in the traditional Chinese medicine Mylabris and an effective anti-tumor agent. However, it is relatively toxic and exhibits nephrotoxicity, which limits its clinical use. However, its toxic mechanism is not clear. The toxic effects of CTD exposure on the kidney and the protective effect of resveratrol (RES) were studied in a mouse model, by determination of serum biochemical and renal antioxidant indicators, histopathological and ultrastructural observation, and metabonomics. After CTD exposure, serum uric acid, creatinine, and tissue oxidative stress indicators increased, and the renal glomerular and tubular epithelial cells showed clear pathological damage. Ultrastructure observation revealed marked mitochondrial swelling, endoplasmic reticulum dilation, and the presence of autophagy lysosomes in glomerular epithelial cells. RES ameliorated the renal injury induced by CTD. Metabonomics analysis indicated that CTD can induce apoptosis and oxidative damage in kidney cells, mainly by disrupting sphingolipid and glutathione metabolism, increasing sphingosine and sphingomyelin levels, and decreasing glutathione levels. RES counteracts these effects by regulating renal cell proliferation, the inflammatory response, oxidative stress, and apoptosis, by improving the levels of phosphatidylcholine (PC), LysoPC, and lysophosphatidyl glycerol in the glycerophospholipid metabolism pathway, thereby reducing CTD-induced nephrotoxicity. The mechanisms of CTD-induced renal injury and the protective effect of RES were revealed by metabonomics, providing a basis for evaluating clinical treatment regimens to reduce CTD-induced nephrotoxicity.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study.

BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

Impedance sources (Z sources) with inherent fault protection for resilient and fire-free electricity grids.

Modern societies would not survive without electricity and at the same time electrical faults could cause and have caused many catastrophes-mainly deadly fires-to our societies. There are two types of electricity sources: the voltage source such as generators, charged batteries and capacitors, and the current source such as charged inductors, current-regulated rectifiers, and superconducting magnetic energy storage. An "ideal" voltage source-that is often-sought-or-intentionally engineered-generates a constant voltage irrespective of its load current, and an "ideal" current source injects a constant current irrespective of its load voltage. However, two problems exist: (1) voltage or current sources do not represent many emerging natural/renewable energy sources such as wind turbine generators, photovoltaic cells, and fuel cells, whose output voltage and current are strongly dependent on each other, and (2) a short-circuit fault to an artificially-made and controlled "ideal" voltage source or an open-circuit fault to an "ideal" current source can cause catastrophic failures of the source itself and its surrounding circuits due to large (theoretically infinite) short-circuit current or open-circuit voltage. Here we introduce an impedance source concept to represent, characterize, and model those electricity sources whose output voltage and current are strongly dependent on each other. First, we found that many electric sources with no feedback (or active) control of their output voltage and/or current are a natural impedance source with inherent fault protection at short-circuit or open-circuit faults. Second, any electrical source can be artificially controlled to mimic a natural impedance source. Finally, we show how to apply natural impedance sources and nature-mimicking artificially-controlled sources to the electricity grid-the most complex machine ever made by human beings-to realize electricity grids that are naturally stable, self-protected against electrical faults, and resilient to natural and human-made events.

Impact of the gene polymorphisms in the renin-angiotensin system on cardiomyopathy risk: A meta-analysis.

Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.