Objective To observe the cardioprotection of Rhizoma Polygonati(RP)in natural aging rat and its molecular mechanism.Methods 16 SD rats aged 2 months were selected as the young group,another 64 SD rats aged 18 months were randomly divided into 4 groups:an old group,a RP-low,a RP-medium and a RP-high dose group,with 16 rats in each group.The RP-low,RP-medium and RP-high dose groups were administered of RP(1,2,4 g·kg-1)by gavage,the old and young groups were given the same amount of distilled water once a day for 12 weeks.At week 4 and 12,eight rats from each group were sacrificed under anesthesia and hearts were isolated.Then cardiac weight index(CI)were measured and the histopathologic observation was assessed.The contents of total antioxidant capacity(T-AOC),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)were measured,and the expression of ataxia-telangiectasia mutated gene(ATM),ATM and Rad3-related kinase(ATR)-related protein in cardiac tissue were detected.Results With the increase of weeks of age,the fibrosis area in the old group was increased.The content of GSH-Px was decreased while MDA was increased;the expressions of Chk1 and Chk2 were also up-regulated(P<0.05).At week 4 or 12,compared to the young group,the CI was reduced,and the contents of T-AOC,SOD,GSH-Px were decreased while MDA was increased;the expression of ATM,ATR-related proteins were all significantly up-regulated in cardiac tissue of old group(P<0.05).After RP treatment,the CI was elevated,the structure of cardiomyocytes were intact and the myocardial fibers were arranged neatly,the fibrosis area was lowered.The contents of T-AOC,GSH-Px,SOD were increased while MDA was decreased.The expression of ATM,ATR-related proteins were significantly down-regulated in cardiac tissue(P<0.05).Conclusion RP could protect the heart in natural aging rats,and its mechanism may be related to the regulation of DNA damage response ATM,ATR signaling pathway.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective To observe the cardioprotection of Rhizoma Polygonati(RP)in natural aging rat and its molecular mechanism.Methods 16 SD rats aged 2 months were selected as the young group,another 64 SD rats aged 18 months were randomly divided into 4 groups:an old group,a RP-low,a RP-medium and a RP-high dose group,with 16 rats in each group.The RP-low,RP-medium and RP-high dose groups were administered of RP(1,2,4 g·kg-1)by gavage,the old and young groups were given the same amount of distilled water once a day for 12 weeks.At week 4 and 12,eight rats from each group were sacrificed under anesthesia and hearts were isolated.Then cardiac weight index(CI)were measured and the histopathologic observation was assessed.The contents of total antioxidant capacity(T-AOC),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)were measured,and the expression of ataxia-telangiectasia mutated gene(ATM),ATM and Rad3-related kinase(ATR)-related protein in cardiac tissue were detected.Results With the increase of weeks of age,the fibrosis area in the old group was increased.The content of GSH-Px was decreased while MDA was increased;the expressions of Chk1 and Chk2 were also up-regulated(P<0.05).At week 4 or 12,compared to the young group,the CI was reduced,and the contents of T-AOC,SOD,GSH-Px were decreased while MDA was increased;the expression of ATM,ATR-related proteins were all significantly up-regulated in cardiac tissue of old group(P<0.05).After RP treatment,the CI was elevated,the structure of cardiomyocytes were intact and the myocardial fibers were arranged neatly,the fibrosis area was lowered.The contents of T-AOC,GSH-Px,SOD were increased while MDA was decreased.The expression of ATM,ATR-related proteins were significantly down-regulated in cardiac tissue(P<0.05).Conclusion RP could protect the heart in natural aging rats,and its mechanism may be related to the regulation of DNA damage response ATM,ATR signaling pathway.

In cardiac ablation procedures,the accuracy of catheter positioning determines the authenticity of the cardiac model and the accuracy of the ablation target.This article reviews the literature on catheter positioning in electrophysiology and summarizes the key technologies for catheter positioning,such as magnetic-electric fusion and interference suppression.Addressing the limitations of electric and magnetic positioning individually,the paper elaborates on the rationale for catheter positioning technology based on magnetic-electric fusion.It also outlines the framework of a complex catheter positioning system.Specifically,the magnetoelectric conversion matrix is established first,followed by the optimization of the catheter shape.The interference factors such as magnetic field interference,body movement,respiration,and heartbeat in catheter positioning and their suppression methods are analyzed and discussed in detail.Finally,the development trend of three-dimensional electrophysiology catheter positioning technology is prospected,offering feasible insights for the research on catheter positioning technology based on magnetic-electric fusion.

Phlegm and dampness are endogenous,rise and fall with Qi,reach the limbs,diffuse the whole body,and form obesity.Regulating phlegm dampness with traditional Chinese medicine can realize the early prevention and treatment of obesity.Intestinal microbiota participates in a variety of human metabolic processes.Regulating intestinal microbiota is a new way to prevent and treat obesity.Taking the close relationship between intestinal flora and its metabolites,obesity and phlegm dampness theory as the breakthrough point,and based on the existing research results,this paper discusses the possible role of intestinal microbiota and its metabolites in the formation of phlegm dampness and the prevention and treatment of obesity,It is considered that the common intestinal microbiota and its metabolites of different individuals with obesity caused by phlegm dampness may be used as specific indicators to become the new micro identification basis of obesity phlegm dampness theory.It is proposed that intestinal microbiota and its metabolites will become the key point of obesity phlegm dampness theory research,which will provide a new explanation for obesity prevention and control research,and expand new research fields for the connotation of TCM phlegm dampness theory.

Objective:To investigate the clinical features and risk factors of multiple organ dysfunction syndrome (MODS) caused by wasp sting.Methods:A retrospective cohort study was conducted to collect the general data of wasp sting patients who had a clear history of wasp sting disease and clinical manifestations from June 2016 to December 2020 and were first diagnosed as wasp sting in hospital. Patients with hematological diseases, malignant tumors, severe liver and kidney dysfunction, cardiac insufficiency, and patients who had received hormone therapy before admission were excluded. Patients who were unable to obtain effective laboratory results due to hemolysis or other reasons within 48 h of admission were also excluded. The white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), hemoglobin count (HB), myoglobin (Mb/MYO), activated partial thromboplastin time (APTT), albumin (ALB), K, Na, and Cl of the blood samples collected within 48 h after admission were recorded. Patients were divided into the MODS group and non-MODS group according to whether MODS occurred during hospitalization. Uni- and multivariate analysis were used to analyze the factors affecting the occurrence of MODS in wasp sting patients during hospitalization, and the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive effect of myoglobin level on the occurrence of MODS in wasp sting patients during hospitalization.Results:Mb, WBC, NEU, APTT and serum potassium in the MODS group [3890.00 (1416.90-4057.00) ng/mL, (21.99 ± 8.18) × 10 9/L, (19.61 ± 7.33)× 10 9/L, (93.75 ± 45.77) s, and (4.99 ± 0.95) mmol/L] were significantly higher than those in the non-MODS group [73.50 (34.30-264.20) ng/mL, (13.40 ± 4.14)× 10 9/L, (11.18±4.73)× 10 9/L, (37.00 ± 17.16) s, and (4.05 ± 0.56) mmol/L] (all P < 0.05); blood chlorine and ALB [(101.50 (98.25-105.00) mmol/L and (35.36 ± 6.44) g/L)] were significantly lower than those in the non-MODS group [(105.00 (103.00-107.00) mmol/L and (40.71 ± 5.48) g/L)] (all P < 0.05). Multivariate logistic regression analysis showed that NEU ( OR = 0.729, 95% CI: 0.542~0.981), Mb ( OR = 0.999, 95% CI: 0.998~1.000), and APTT ( OR = 0.951, 95% CI: 0.921~0.982) were independent risk factors for MODS in wasp sting patients. ROC curve analysis showed that NEU, Mb and APTT could be used to evaluate the occurrence of MODS in wasp sting patients. Among them, Mb had the highest predictive value (AUC = 0.950, 95 % CI: 0.891~0.982). The optimal cutoff value of Mb for predicting the occurrence of MODS in wasp sting patients was 515.30 ng/mL, and the corresponding sensitivity and specificity were 90.62% and 87.23%, respectively. Conclusion:Mb is an independent risk factor for MODS in wasp sting patients, which can be used as a good predictor of MODS in wasp sting patients.

Retrospective analysis was performed on 1 child with silent inactivation (SI) of asparaginase (ASNas) who was diagnosed with acute lymphoblastic leukemia (ALL) and treated in the First Affiliated Hospital, Sun Yat-Sen University in October 2019.The patient was a 9 years and 3 months old boy who was diagnosed as ALL accompanied with late bone marrow relapse.After pegylated Escherichia coli-Asparaginase (PEG-ASNase) was given, he did not have the expected treatment-related adverse reactions, including hyperammonemia, hypofibrinogenemia, and the low activation of antithrombin Ⅲ (ATⅢ). The plasma asparagine (ASN) concentration failed to meet the depletion criteria and the ASNase activity was 64.5 U/L.Therefore, the SI of ASNase was confirmed.Erwinase was used to replace PEG-ASNase, the lowest level of ATⅢ was 33%, and the lowest level of fibrinogen was 1.20 g/L.Hyperammonemia and decreased ASN were also observed, and the ASNase activity was 1 813.0 U/L.All the above suggested that when, SI occurred, the replacement by Erwinase was effective.The ASNase activity should be monitored in ALL patients who were treated with ASNase.Monitoring the treatment-related adverse reactions such as hyperammonia and coagulation disorders closely has important implications to the SI of ASNase when the detection of ASNase activity was unavailable.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A549 Cells ; Animals ; Apoptosis Regulatory Proteins/immunology* ; DEAD Box Protein 58/immunology* ; Dogs ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype/immunology* ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/pathology* ; Proteolysis ; RAW 264.7 Cells ; Signal Transduction/immunology* ; THP-1 Cells ; TNF Receptor-Associated Factor 3/immunology* ; Ubiquitination/immunology* ; Viral Proteins/immunology*