OBJECTIVE: To investigate the distribution of traditional Chinese medicine (TCM) syndrome types of and influencing factors on ED with hyperuricemia. METHODS: Based on the clinical data on 271 cases of ED with hyperuricemia admitted to our Department of Andrology, we studied the characteristics of syndrome elements, summarized the TCM syndrome types, and investigated the influencing factors on the distribution of the syndrome types by factor analysis and cluster analysis. RESULTS: By factor analysis of the data collected on TCM symptoms, 12 common factors and 15 syndrome type elements were identified, including disease type syndrome elements dampness, phlegm, heat, qi stagnation, blood stasis, qi deficiency, blood deficiency, yin deficiency, yang deficiency and essence deficiency, and disease-location syndrome elements kidney, liver, spleen, limbs and joints. Common factor cluster analysis revealed the main TCM syndrome types kidney deficiency damp-heat syndrome, spleen and kidney deficiency syndrome, liver depression and kidney deficiency syndrome, kidney deficiency and blood stasis syndrome, and the main influencing factors on the distribution of syndrome types including uric acid, systolic blood pressure, urea, obesity and so on. CONCLUSION The main TCM syndrome types of ED with hyperuricemia include kidney deficiency damp-heat syndrome, spleen and kidney deficiency syndrome, liver depression and kidney deficiency syndrome, kidney deficiency and blood stasis syndrome, and the related influencing factors can be used as an objective basis for the differentiation of TCM syndromes.
Humans ; Medicine, Chinese Traditional ; Hyperuricemia/complications* ; Male ; Cluster Analysis

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Trimethylamine N-oxide (TMAO), a metabolite of intestinal flora, can promote Atherosclerosis (AS) in various ways. Current studies have found that it has a close relationship with plaque stability in clinical practice, but its molecular mechanism remains unclear at present. Extracellular matrix metalloproteinase inducers (CD147) / matrix metalloproteinases (MMPs) regulate a signal pathway highly related to plaque stability, which can promote plaque instability and lead to cardiovascular adverse events by weakening the thickness of the fibrous cap. Therefore, in this study, the mouse macrophageRAW264. 7 was stimulated by TMAO to establish a cell model to observe the effects on CD147, MMP2, and MMP9, and the CD147 gene silencing model was further constructed by using the siRNA transfection method to explore the interaction between CD147 and MMP2 and MMP9. Rt-qPCR and Western blotting results showed that there was no significant change in the gene expression level of CD147 in mouse macrophage RAW264. 7, but significantly increased in protein levels (P < 0. 05), while MMP2 andMMP9 were increased in mRNA and protein levels (P<0. 05). The expression of CD147, MMP2, andMMP9 was significantly inhibited in CD147 siRNA transfected cells (P<0. 05). In conclusion, TMAO significantly increases the expression of MMP2 and MMP9 in mouse macrophages RAW264. 7, and this effect may be partially realized through the CD147/ MMP pathway.

OBJECTIVE: To evaluate the effect of sonication, repeated freeze-thaw cycles, calcium salt solution and their combination on the content of related growth factors (GFs) released by platelet rich plasma (PRP). METHODS: Twenty PRPs from healthy blood donors were divided into 9 groups, including sonication group, freeze-thaw group, calcium gluconate group, calcium chloride group, sonication + calcium gluconate group, sonication + calcium chloride group, freeze-thaw + calcium gluconate group, freeze-thaw + calcium chloride group, and sonication + freeze-thaw group. After PRP activated by above 9 methods, the content of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) were detected by ELISA. RESULTS: The platelet concentration of the samples was (966.7±202.6)×10⁹/L. The content of TGF-β1 in sonication + freeze-thaw group was the highest, while the lowest was in freeze-thaw group. The content of VEGF in freeze-thaw + calcium chloride group was the highest, while the lowest was in calcium gluconate group. The content of PDGF-BB in sonication + freeze-thaw group was the highest, while the lowest was in calcium gluconate group. There was no significant differences in the three GFs between calcium gluconate group and calcium chloride group. CONCLUSION Among the 9 activated methods of PRP, there is no difference between two calcium salt solutions. And the combination of repeated freeze-thaw cycles and sonication may be the best treatment method to promote PRP to release GFs, while calcium gluconate is the weakest way.
Humans ; Transforming Growth Factor beta1 ; Vascular Endothelial Growth Factor A ; Calcium Gluconate ; Calcium ; Calcium Chloride ; Becaplermin ; Platelet-Rich Plasma

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To explore the value of phase angle (PA) in constructing a predictive model of nutrition evaluation for tumor patients. Methods: A retrospective analysis was performed on 1 129 patients with malignant tumors hospitalized in the Cancer Center of Changzhi People's Hospital from June 2020 to February 2021. PA values of six parts of the body were measured by the body composition analyzer, including: left arm (LA), right arm (RA), left leg (LL), right leg (RL), the trunk (TR), and the whole body (WB). Patients' body mass index (BMI) was calculated and patient-generated subjective global assessment (PG-SGA) was assessed. The differences of PA values of six parts were compared and their correlations with BMI and PG-SGA in combination with age, gender and tumor disease types were analyzed, binary classification regression on BMI and PG-SGA was performed, and the functions of the best prediction model was fitted. Decision tree, random forest, Akaike information criterion in a Stepwise Algorithm (stepAIC) and generalized likelihood ratio test were used to select appropriate variables, and the logit logistic regression model was used to fit the data. Results: Comparing the PA values of six parts in pairs, it was found that the PA values of LA and RA, LL and RL, and TR and WB were linearly correlated and the coefficient was close to 1 (P<0.001). Binary classification regression was performed for BMI and PG-SGA, respectively. In order to make the data have clinical significance, 18.5 kg/m(2) was used as the classification point for BMI, 4 and 9 were used as the classification points for PG-SGA score, and the models of A, B and C were obtained. Suitable variables including PA-LA, PA-TR and tumor disease types were used as variables to fit BMI classification; BMI, PA-LA and age were used as variables to fit the PG-SGA model with 9 as the classification point. PA-LA, PA-TR, BMI, age and tumor disease types were used as variables to fit the PG-SGA model with 4 as the classification point. In this study, the predicted values of models A, B and C obtained by R-studio were imported into SPSS 26.0 software, and the cut-off values of classification were obtained by the receiver operating characteristic (ROC) curve. The ROC analytic results showed that the best cut-off values of Model A, B and C were 0.155, 0.793 and 0.295. Model A recommended when the probability is >0.155, a patient's nutritiond tatus should be classified as BMI < 18.5 kg/m(2) group. Model B recommended that PG-SGA<9 group be classified as the probability is >0.793. Model C recommended that PG-SGA < 4 group should be classified when probability is >0.295. Conclusions: The PG-SGA classification prediction model is simple to operate, and the nutritional status of patients can be roughly divided into three groups: normal or suspected malnutrition group (PG-SGA<4), moderate malnutrition group (4≤PG-SGA<9), and severe malnutrition group (PG-SGA≥9). This model can more efficiently predict the nutritional status of cancer patients, greatly simplify the nutritional assessment process, and better guide the standardized treatment of clinical malnutrition.
Humans ; Nutrition Assessment ; Retrospective Studies ; Nutritional Status ; Malnutrition ; Neoplasms/complications*