Pharmacology of hydrogen sulfide and its donors in cardiometabolic diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well-known modification intricately associated with the pathogenesis of CMDs This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies including multi-omics, intestinal microflora analysis, organoid and single-cell sequencing techniques are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assesse the current literatures to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. Significance Statement The comprehensive review covers recent developments in H2S biology and pharmacology in CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Delayed cerebrovascular reactivity in individuals with spinal cord injury in the right inferior parietal lobe: a breath-hold functional near-infrared spectroscopy study.

Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the brain's vascular health. Individuals with spinal cord injury (SCI) are at an increased risk for autonomic dysfunction in addition to cognitive impairments, which have been linked to a decline in CVR; however, there is currently a lack of brain-imaging studies that investigate how CVR is altered after SCI. In this study, we used a breath-holding hypercapnic stimulus and functional near-infrared spectroscopy (fNIRS) to investigate CVR alterations in individuals with SCI (n = 20, 14M, 6F, mean age = 46.3 ± 10.2 years) as compared to age- and sex-matched able-bodied (AB) controls (n = 25, 19M, 6F, mean age = 43.2 ± 12.28 years). CVR was evaluated by its amplitude and delay components separately by using principal component analysis and cross-correlation analysis, respectively. We observed significantly delayed CVR in the right inferior parietal lobe in individuals with SCI compared to AB controls (linear mixed-effects model, fixed-effects estimate = 6.565, Satterthwaite's t-test, t = 2.663, p = 0.008), while the amplitude of CVR was not significantly different. The average CVR delay in the SCI group in the right inferior parietal lobe was 14.21 s (sd: 6.60 s), and for the AB group, the average delay in the right inferior parietal lobe was 7.08 s (sd: 7.39 s). CVR delays were also associated with the duration since injury in individuals with SCI, in which a longer duration since injury was associated with a shortened delay in CVR in the right inferior parietal region (Pearson's r-correlation, r = -0.59, p = 0.04). This study shows that fNIRS can be used to quantify changes in CVR in individuals with SCI, and may be further used in rehabilitative settings to monitor the cerebrovascular health of individuals with SCI.

Photoinduced decarboxylative germylation of α-fluoroacrylic acids: access to germylated monofluoroalkenes.

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

Mutation characteristics of cancer susceptibility genes in Chinese ovarian cancer patients.

Introduction: The association between mutations in susceptibility genes and the occurrence of ovarian cancer has been extensively studied. Previous research has primarily concentrated on genes involved in the homologous recombination repair pathway, particularly BRCA1 and BRCA2. However, a wider range of genes related to the DNA damage response pathways has not been fully explored. Methods: To investigate the mutation characteristics of cancer susceptibility genes in the Chinese ovarian cancer population and the associations between gene mutations and clinical data, this study initially gathered a total of 1171 Chinese ovarian cancer samples and compiled a dataset of germline mutations in 171 genes. Results: In this study, it was determined that MC1R and PRKDC were high-frequency ovarian cancer susceptibility genes in the Chinese population, exhibiting notable distinctions from those in European and American populations; moreover high-frequency mutation genes, such as MC1R: c.359T>C and PRKDC: c.10681T>A, typically had high-frequency mutation sites. Furthermore, we identified c.8187G>T as a characteristic mutation of BRCA2 in the Chinese population, and the CHEK2 mutation was significantly associated with the early onset of ovarian cancer, while the CDH1 and FAM175A mutations were more prevalent in Northeast China. Additionally, Fanconi anemia pathway-related genes were significantly associated with ovarian carcinogenesis. Conclusion: In summary, this research provided fundamental data support for the optimization of ovarian cancer gene screening policies and the determination of treatment, and contributed to the precise intervention and management of patients.

[Progress of anterior subcutaneous internal fixation in the treatment of anterior pelvic ring injury].

Anterior subcutaneous internal fixation (INFIX) is one of the current representatives of minimally invasive fixation of injuries to the anterior pelvic ring. The nail insertion point of this technique is located at the anterior inferior iliac spinous screw, with an angle of 30° outward and 20° backward. Screw in at an angle, and note that the screw head should be above the deep fascia and maintain a safe distance of 20 to 25 mm from the bone surface. Its improved versions include 3 or 4 nails INFIX with added pubic tubercle screws, unilateral INFIX, short-rod INFIX, and double INFIX. These improvements further enhance stability. The lateral femoral cutaneous nerve (LFCN) is relatively easy to be damaged during anatomy, so special attention should be paid during the operation. Biomechanical stability has advantages over external fixation, and its application is flexible. It is not limited to pubic ramus fracture, symphyseal separation, etc. It also plays an important role in combined anterior and posterior ring fixation. It can be combined with posterior sacroiliac screws, iliac lumbar screws, etc. Fixed etc. Good clinical results have also been reported in children, pregnant women, and people with contraindications for subcutaneous connecting rods. In addition, the current application of robots, reduction frames and other technologies has greatly reduced the difficulty of reduction and improved the quality of closed reduction, making it possible to fix complex pelvic fracture. This technique has high reduction quality and is as effective as traditional steel plates. A common complication is LFCN injury. Careful exposure and adjustment of the position and depth of internal fixation during surgery can effectively avoid this complication.

Risk Factors of New Symptomatic Fractures After Vertebroplasty: A Retrospective Cohort Study of 268 Patients with Painful Osteoporotic Vertebral Compression Fracture.

OBJECTIVE: To evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: From January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, body mass index, bone mineral density (BMD), history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage, and regular antiosteoporosis treatment. RESULTS: A total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. Forty-nine levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (adjusted odds ratio [OR]: 6.812, 95% confidence interval {CI}: [1.096, 42.337], P = 0.040), lower BMD (adjusted OR: 0.477, 95% CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (adjusted OR: 16.145, 95% CI: [5.319, 49.005], P = 0.000), and regular antiosteoporosis treatment (adjusted OR: 0.258, 95% CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. CONCLUSION: Female, lower BMD (T-score of lumbar), prior vertebral fractures, and regular antiosteoporosis treatment were independent influencing factors. BMD (T-score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.

[Interaction between root exudates of medicinal plants and rhizosphere microorganisms and its application in ecological planting of Chinese medicinal materials].

The rhizosphere is an important place for material exchange between medicinal plants and soil. Root exudates are the medium of material and signal exchange between plants and soil and are the key factors in the regulation of rhizosphere microecology. Rhizosphere microorganisms are an important part of the rhizosphere microecology of medicinal plants, and the interaction between root exudates and rhizosphere microorganisms has an important influence on the growth and quality formation of medicinal plants. Rational utilization of the interaction between root exudates and rhizosphere microorganisms of medicinal plants is one of the important ways to ensure the healthy growth of medicinal plants and promote the development of ecological planting of Chinese medicinal materials. In the paper, the research status of root exudates and rhizosphere microorganisms of medicinal plants in recent years was summarized. The interaction mechanism between root exudates and rhizosphere microorganisms of medicinal plants, as well as the influence of rhizosphere microorganisms on the growth of medicinal plants, were analyzed. In addition, the advantages and promoting effects of intercropping ecological planting mode on rhizosphere microecology of medicinal plants and quality improvement of Chinese medicinal materials were explained, providing a good basis for the study of the interaction among medicinal plants, microorganisms, and soil. Furthermore, it could produce important theoretical and practical significance for the ecological planting and sustainable utilization of medicinal plants.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

Cichoric acid ameliorates sepsis-induced acute kidney injury by inhibiting M1 macrophage polarization.

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.

A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family.

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.

Three-Dimensional-Printed Template-Guided Radioactive Seed Brachytherapy via a Submental Approach for Recurrent Base of Tongue and Floor of Mouth Cancer.

Background: This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer. Methods: Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated. Results: The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis. Conclusions: 3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.

"Ion-imprinting" strategy towards metal sulfide scavenger enables the highly selective capture of radiocesium.

Highly selective capture of radiocesium is an urgent need for environmental radioactive contamination remediation and spent fuel disposal. Herein, a strategy is proposed for construction of "inorganic ion-imprinted adsorbents" with ion recognition-separation capabilities, and a metal sulfide Cs2.33Ga2.33Sn1.67S8·H2O (FJSM-CGTS) with "imprinting effect" on Cs+ is prepared. We show that the K+ activation product of FJSM-CGTS, Cs0.51K1.82Ga2.33Sn1.67S8·H2O (FJMS-KCGTS), can reach adsorption equilibrium for Cs+ within 5 min, with a maximum adsorption capacity of 246.65 mg·g-1. FJMS-KCGTS overcomes the hindrance of Cs+ adsorption by competing ions and realizes highly selective capture of Cs+ in complex environments. It shows successful cleanup for actual 137Cs-liquid-wastes generated during industrial production with removal rates of over 99%. Ion-exchange column filled with FJMS-KCGTS can efficiently treat 540 mL Cs+-containing solutions (31.995 mg·L-1) and generates only 0.12 mL of solid waste, which enables waste solution volume reduction. Single-crystal structural analysis and density functional theory calculations are used to visualize the "ion-imprinting" process and confirm that the "imprinting effect" originates from the spatially confined effect of the framework. This work clearly reveals radiocesium capture mechanism and structure-function relationships that could inspire the development of efficient inorganic adsorbents for selective recognition and separation of key radionuclides.

Age-Related Conservation in Plant-Soil Feedback Accompanied by Ectomycorrhizal Domination in Temperate Forests in Northeast China.

This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant-soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant-soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant-soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant-soil consortia.

Highly Curved Defect Sites: How Curvature Effect Influences Metal-Free Defective Carbon Electrocatalysts.

Topological defects are widely recognized as effective active sites toward a variety of electrochemical reactions. However, the role of defect curvature is still not fully understood. Herein, carbon nanomaterials with rich topological defect sites of tunable curvature is reported. The curved defective surface is realized by controlling the high-temperature pyrolytic shrinkage process of precursors. Theoretical calculations demonstrate bending the defect sites can change the local electronic structure, promote the charge transfer to key intermediates, and lower the energy barrier for oxygen reduction reaction (ORR). Experimental results convince structural superiority of highly-curved defective sites, with a high kinetic current density of 22.5 mA cm-2 at 0.8 V versus RHE for high-curvature defective carbon (HCDC), ≈18 times that of low-curvature defective carbon (LCDC). Further raising the defect densities in HCDC leads to the dual-regulated products (HCHDC), which exhibit exceptionally outstanding ORR activity in both alkaline and acidic media (half-wave potentials: 0.88 and 0.74 V), outperforming most of the reported metal-free carbon catalysts. This work uncovers the curvature-activity relationship in carbon defect for ORR and provides new guidance to design advanced catalysts via curvature-engineering.

Photoinduced Decarboxylative Difluoroalkylation and Perfluoroalkylation of α-Fluoroacrylic Acids.

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

Albiflorin ameliorates thioacetamide-induced hepatic fibrosis: The involvement of NURR1-mediated inflammatory signaling cascades in hepatic stellate cells activation.

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-ß), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.

Chronic infectious unilateral giant thyroid cyst related to diabetes mellitus: A case report.

BACKGROUND: Patients rarely develop complicated infections in thyroid cysts. Here, we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus (DM). CASE SUMMARY: A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of DM. Doppler ultrasound and computed tomography scan showed a giant lump in the left thyroid gland lobe. He was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical indications. Surgical exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles, the nodule and glandular tissue. Fortunately, inflammatory lesions did not affect major neck vessels. Finally, a left partial thyroidectomy was performed. Macroscopic observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent matter. Postoperative pathology confirmed benign thyroid cyst with chronic infection. CONCLUSION: The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM, and identifying blood vessels involvement can prevent serious complications during operation.