ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

Objective To explore the pharmacodynamic material basis and mechanism of Tanyu Tongzhi Optimized Prescription in the treatment of atherosclerosis(AS)using network pharmacology and animal experiments.Methods UPLC-Q-TRAP-MS/MS was used to identify the blood-entering components of Tanyu Tongzhi Optimized Prescription and conduct network pharmacological analysis.Important components and their core targets for the treatment of AS were screened,and molecular docking was conducted.The AS model mice were constructed and treated with Tanyu Tongzhi Optimized Prescription.HE staining and oil red O staining were used to observe aortic tissue morphology.The blood lipid status was detected by an automatic blood biochemical analyzer.The contents of serum inflammatory factors were detected by ELISA,and the mRNA expressions of aortic core targets were detected by RT-qPCR.Results It was identified and predicted that 30 blood-entering components of Tanyu Tongzhi Optimized Prescription might exert therapeutic effects on AS by regulating core targets such as IL6,TNF,IL1B,AKT1 and NFKB1,and regulating the TNF signaling pathway,Toll-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Animal experiments showed that Tanyu Tongzhi Optimized Prescription could reduce aortic plaque area and inflammatory cell infiltration,alleviate lipid deposition and vascular stenosis,improve blood lipid levels,and significantly reduce the serum contents of TNF-α,IL-1β,and mRNA expressions of TNF-α,IL-6,AKT1 and NF-κB in aortic tissue(P<0.05,P<0.01).Conclusion The effect of Tanyu Tongzhi Optimized Prescription may regulate TNF,Toll-like receptor and other signaling pathways by acting on core targets such as IL6,TNF,IL1B,and inhibit inflammatory response,so as to treat AS.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective To explore the pharmacodynamic material basis and mechanism of Tanyu Tongzhi Optimized Prescription in the treatment of atherosclerosis(AS)using network pharmacology and animal experiments.Methods UPLC-Q-TRAP-MS/MS was used to identify the blood-entering components of Tanyu Tongzhi Optimized Prescription and conduct network pharmacological analysis.Important components and their core targets for the treatment of AS were screened,and molecular docking was conducted.The AS model mice were constructed and treated with Tanyu Tongzhi Optimized Prescription.HE staining and oil red O staining were used to observe aortic tissue morphology.The blood lipid status was detected by an automatic blood biochemical analyzer.The contents of serum inflammatory factors were detected by ELISA,and the mRNA expressions of aortic core targets were detected by RT-qPCR.Results It was identified and predicted that 30 blood-entering components of Tanyu Tongzhi Optimized Prescription might exert therapeutic effects on AS by regulating core targets such as IL6,TNF,IL1B,AKT1 and NFKB1,and regulating the TNF signaling pathway,Toll-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Animal experiments showed that Tanyu Tongzhi Optimized Prescription could reduce aortic plaque area and inflammatory cell infiltration,alleviate lipid deposition and vascular stenosis,improve blood lipid levels,and significantly reduce the serum contents of TNF-α,IL-1β,and mRNA expressions of TNF-α,IL-6,AKT1 and NF-κB in aortic tissue(P<0.05,P<0.01).Conclusion The effect of Tanyu Tongzhi Optimized Prescription may regulate TNF,Toll-like receptor and other signaling pathways by acting on core targets such as IL6,TNF,IL1B,and inhibit inflammatory response,so as to treat AS.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective:To analyze the global incidence and mortality of cancer from 1990 to 2019.Methods:The Global Burden of Disease Study 2019 (GBD2019) database was utilized to analyze the global incidence and mortality of cancer, the order of incidence and mortality of cancer, the incidence and mortality of different age groups, and the trend of incidence and mortality from 1990 to 2019. Standardized incidence and mortality rates were derived by utilizing the world standard population age structure.Results:In 1990, global cancer cases numbered 10.295 9 million with an incidence rate of 192.45/100 000, leading to 5.732 6 million deaths and a mortality rate of 107.16/100 000. While in 2019, global cancer cases escalated to 23.568 5 million with an incidence rate of 304.60/100 000, resulting in 10.022 8 million deaths and a mortality rate of 129.54/100 000, all higher than those in 1990. In 2019, lung cancer showed the highest incidence rate of both sexes combined in the world (29.21/100 000), followed by colorectal cancer, breast cancer, prostate cancer and gastric cancer. The incidence of lung cancer was highest among males (39.24/100 000), while the incidence of breast cancer was highest among females (51.27/100 000). Lung cancer also had the highest mortality rate worldwide in both sexes combined (26.40/100 000), followed by colorectal cancer, gastric cancer, breast cancer and pancreatic cancer. Lung cancer had the highest mortality among males (35.72/100 000), while breast cancer had the highest mortality among females (17.85/100 000). In 2019, the global cancer incidence rate showed an upward trend with age. The incidence rate was low before the age of 25, and increased rapidly after the age of 25. The incidence rates of both sexes combined, males and females all reached the peak in the age group of over 85 years old, which were 3 084.18/100 000, 4 434.81/100 000 and 2 353.07/100 000 respectively; The incidence rate of females in the age group of 20-50 years old was higher than that of males, but the incidence rate of males in the age group of over 55 years old was higher than that of females. Compared with 1990, the incidence rates of both sexes combined in the age group of over 20, of males over 55 years old, as well as of females over 15 years old, were all higher than those in 2019. In 2019, the global tumor mortality rate showed an upward trend with age. The mortality rate was relatively low before the age of 35, and increased rapidly after the age of 35. The mortality rates for both sexes combined, as well as for males and females, reached the peak in the age group of over 85 years old, which were 1 787.84/100 000, 2 509.87/100 000, and 1 369.99/100 000 respectively; The mortality rate of females in the age group of 20-40 years old was higher than that of males, and the mortality rate of males in the age group of over 45 years old was higher than that of females; For the age of 0-80 years old, the mortality rates for both sexes combined, males, and females were lower in 2019 than 1990, but higher in the age of 85 years old and above. The global standardized incidence rate of cancer showed an overall upward trend, with an average annual increase of 0.30% from 1990 to 2019. The global standardized mortality rate of cancer showed an overall downward trend, with an average annual decrease of 0.60% from 1990 to 2019.Conclusion:From 1990 to 2019, the global standardized incidence rate of cancers shows an overall upward trend, while the global standardized mortality rate of cancers has an overall downward trend, and the global incidence and mortality rate of cancers increases with age. The global burden of cancer disease is still heavy. Lung cancer is the cancer with the highest incidence and mortality rate in the world. The highest incidence rate is lung cancer among males, and breast cancer among females. Different countries or regions need to take corresponding cancer prevention and treatment strategies according to their actual conditions.

This paper reviews the recent literatures about the clinical and mechanism researches on the treatment of cardiovascular diseases with the principles of treating phlegm and blood stasis together, which showed that phlegm and blood stasis are the key factors for the occurrence and exacerbation of cardiovascular diseases. This method is often used to treat angina pectoris, acute coronary syndrome, hypertension and hyperlipidemia, which could improve the condition of myocardial ischemia, resist myocardial cell apoptosis, improve vascular endothelial function, regulate the level of inflammatory cytokines, improve myocardial energy metabolism and reduce the level of myocardial injury markers. However, there still lacks of large-scale RCT, the effective components and mechanism of effective compound are not clear and the mechanism research lacks TCM characteristics.

Objective To examine the effect of a Caregiving Self-Management Support (C-SMS) Program on self-efficacy, social support for family caregivers of people with dementia and psychological symptom of patients. Methods Using the convenient sampling method, 41 caregivers of dementia patients were selected as the study objects from September 2016 to September 2017 in the Memory Disorders Outpatient Department of two ClassⅢ Grade A hospitals in Shanghai. They were divided into the experimental group(n=26) and control group(n=15) according to their willingness. Totally 4 participants in each of the two groups dropped out of the study in the middle. In the experimental group, a total of 6 times, once in 2 weeks social support group activities were carried out; in the control group, a total of 3 telephone instruction, once a month was carried out, all participants were distributed with the Caregiver Educational Booklet prepared by the research team and participated 3 education seminars during the follow-up visit. Self-Efficacy Questionnaire for Chinese Family Caregivers(SEQCFC) and Medical Outcome Study Social Support Survey(MOS-SSS) and Revised Memory and Behaviour Problems Checklist(RMBPC) were used to compare the effect of intervention. Results The time effect of the total score of SEQCFC was significant (P＜ 0.01). There was a statistically significance in the interaction on social support score between groups and time (P＜ 0.05). After intervention and follow-up, the self-efficacy scores of family caregivers in the experimental group were higher than the baseline (P＜0.05). There were significant time effect in the total score of behavioral and psychological symptom behavioral symptoms, memory and depression related problems (P＜0.05). The total score of behavioral and psychological symptom, score of the disruptive behaviour dimension after follow-up visit, scores of the depression dimension after intervention and follow-up visit in the experimental group were all lower than the baseline (P＜ 0.05). Conclusions The self-management support project of caregivers can improve the self-efficacy of family caregivers and alleviate the behavioral and psychological symptom of dementia patients.

Objective To summarize the clinical and the molecular genetic characteristics of type DYT11 dystonia by analyzing the clinical data and pathogenic gene mutation of type DYT11 dystonia of a myoclonus-dystonia syndrome (MDS) family.Methods A MDS family enrolled in the General Hospital of the People's Liberation Army Rocket Force in January 2018 was retrospectively analyzed.The clinical data of 11 affected family members were collected and genetic testing of four affected family members (including the proband) of the MDS family was conducted using a panel of dystonia-associated genes.Results The affected family members showed great differences in clinical characteristics and obvious clinical heterogeneity.Four affected family members had myoclonus and dystonia,two affected family members only had myoclonus and five affected family members only had dystonia.The results of genetic testing showed that the proband,his father and his grandfather had a mutation (c.835_839delACAAA) in SGCE gene,which is autosomal dominant and belongs to type DYT11 dystonia.Conclusions MDS shows clinical heterogeneity.Gene screening is of great importance for the diagnosis and treatment of dystonia with myoclonus.