[Effects of Luhong Yixin Granules on myocardial fibrosis in heart failure rats based on TGF-ß1/Smads signaling pathway].

To investigate the effects of Luhong Yixin Granules on myocardial fibrosis in rats with heart failure and its possible mechanism, a total of 60 male Wistar rats were randomly divided into the control group, model group, and low-, medium-and high-dose Luhong Yixin Granules groups, with 12 rats in each group. Except for those in the control group, rats in the other groups were induced by intraperitoneal injection of doxorubicin(DOX) into a rat model. After the Luhong Yixin Granules were dissolved in the same amount of normal saline, they were given by gavage at low, medium and high doses(2.8, 5.6, 11.2 g·kg~(-1)·d~(-1)), and the control group and the model group were given the same amount of normal saline by gavage for 40 days. After the end of dosing, echocardiography was used to measure left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS). Rat body weight(BW) and heart weight(HW) were calculated as HW/BW. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-6(IL-6), interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), transforming growth factor-ß1(TGF-ß1), growth stimulation expressed gene 2 protein(ST2), N-terminal pro-B-type natriuretic peptide(NT-proBNP), galectin-3(Gal-3) and creatine kinase isoenzyme(CK-MB) in serum. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of myocardial tissue. Western blot and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, Smad7, α-smooth muscle actin(α-SMA), and collagen Ⅰ(COL-Ⅰ), respectively. RESULTS:: showed that compared with those in the control group, LVEF, LVFS, and HW/BW in the model group were decreased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3, and CK-MB were increased(P<0.05). HE staining showed inflammatory changes in myocardial tissue; Masson staining showed decreases in the cross-sectional area and ventricular cavity area of the heart, and myocardial fibrosis of varying degrees(P<0.05). The protein and mRNA expression of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-Ⅰ were increased(P<0.05), and the protein and mRNA expression of Smad7 protein was decreased(P<0.01). Compared with those in the model group, LVEF, LVFS and HW/BW of the low-, medium-and high-dose Luhong Yixin Granules groups were increased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3 and CK-MB were decreased(P<0.05). HE staining showed gradually reduced inflammatory changes of myocardial tissue, and Masson staining showed increased cross-sectional area and ventricular cavity area of the heart and decreased area of myocardial fibrosis(P<0.05). The protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-Ⅰ were decreased(P<0.05), while the protein and mRNA expression levels of Smad7 were increased(P<0.05). Luhong Yixin Granules may be of great value in the treatment of heart failure by regulating the TGF-ß1/Smads signaling pathway, inhibiting the expression of inflammation-related proteins, reducing the deposition of extracellular matrix, and alleviating myocardial fibrosis.

The effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke: a meta-analysis.

BACKGROUND: Respiratory muscle training is a continuous and standardized training of respiratory muscles, but the evidence of the effects on early stroke patients is not clear. This meta-analysis aimed to investigate the effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke. METHODS: PubMed, Embase, PEDro, ScienceDirect, AMED, CINAHL, and China National Knowledge Infrastructure databases were searched from inception to December 8, 2023 for articles about studies that 1) stroke patients with age ≥ 18 years old. Early stroke < 3 months at the time of diagnosis, 2) respiratory muscle training, including inspiratory and expiratory muscle training, 3) the following measurements are the outcomes: respiratory muscle strength, respiratory muscle endurance, pulmonary function testing, dyspnea fatigue score, and functional capacity, 4) randomized controlled trials. Studies that met the inclusion criteria were extracted data and appraised the methodological quality and risk of bias using the Physiotherapy Evidence Database scale and the Cochrane Risk of Bias tool by two independent reviewers. RevMan 5.4 with a random effect model was used for data synthesis and analysis. Mean differences (MD) or standard mean differences (SMD), and 95% confidence interval were calculated (95%CI). RESULTS: Nine studies met inclusion criteria, recruiting 526 participants (mean age 61.6 years). Respiratory muscle training produced a statistically significant effect on improving maximal inspiratory pressure (MD = 10.93, 95%CI: 8.51-13.36), maximal expiratory pressure (MD = 9.01, 95%CI: 5.34-12.69), forced vital capacity (MD = 0.82, 95%CI: 0.54-1.10), peak expiratory flow (MD = 1.28, 95%CI: 0.94-1.63), forced expiratory volume in 1 s (MD = 1.36, 95%CI: 1.13-1.59), functional capacity (SMD = 0.51, 95%CI: 0.05-0.98) in patients with early stroke. Subgroup analysis showed that inspiratory muscle training combined with expiratory muscle training was beneficial to the recovery of maximal inspiratory pressure (MD = 9.78, 95%CI: 5.96-13.60), maximal expiratory pressure (MD = 11.62, 95%CI: 3.80-19.43), forced vital capacity (MD = 0.87, 95%CI: 0.47-1.27), peak expiratory flow (MD = 1.51, 95%CI: 1.22-1.80), forced expiratory volume in 1 s (MD = 0.76, 95%CI: 0.41-1.11), functional capacity (SMD = 0.61, 95%CI: 0.08-1.13), while inspiratory muscle training could improve maximal inspiratory pressure (MD = 11.60, 95%CI: 8.15-15.05), maximal expiratory pressure (MD = 7.06, 95%CI: 3.50-10.62), forced vital capacity (MD = 0.71, 95%CI: 0.21-1.21), peak expiratory flow (MD = 0.84, 95%CI: 0.37-1.31), forced expiratory volume in 1 s (MD = 0.40, 95%CI: 0.08-0.72). CONCLUSIONS: This study provides good-quality evidence that respiratory muscle training is effective in improving respiratory muscle strength, pulmonary function, and functional capacity for patients with early stroke. Inspiratory muscle training combined with expiratory muscle training seems to promote functional recovery in patients with early stroke more than inspiratory muscle training alone. TRIAL REGISTRATION: Prospero registration number: CRD42021291918.

[Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure].

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

The BRAFV600E mutation maintains the aggressiveness of papillary thyroid cancers requiring downregulation of primary cilia.

Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.

Development and validation of a nomogram to predict cardiac death after radiotherapy for esophageal cancer.

Background: Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision-making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods: A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5- and 10-year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C-index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan-Meier (K-M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five- and ten-year survival rates for the two groups were shown using K-M curves. Results: The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C-indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5- and 10-year risk of cardiac death. The model exhibited moderate predictive power for 5- and 10-year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions: Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Effects of an Omaha System-based follow-up regimen on self-care and quality of life in gastrointestinal surgery patients.

BACKGROUND: Currently, a variety of new nursing methods and routine nursing have been widely used in the nursing of gastrointestinal surgery patients. AIM: To investigate the effect of follow-up protocol based on the Omaha System on self-care ability and quality of life of gastrointestinal surgery patients. METHODS: A total of 128 patients with inflammatory bowel disease in gastrointestinal surgery in gastrointestinal surgery from March 2019 to August 2021 were divided into A (n = 64) and B (n = 64) groups according to different nursing methods. The group A received a follow-up program Omaha System-based intervention of the group B, whereas the group B received the routine nursing intervention. Medical Coping Modes Questionnaire, Crohn's and Colitis Knowledge Score (CCKNOW), inflammatory bowel disease questionnaire (IBDQ), Exercise of Self-nursing Agency Scale (ESCA), The Modified Mayo Endoscopic Score, and Beliefs about Medicine Questionnaire (BMQ) were compared between the two groups. RESULTS: Following the intervention, the group A were facing score significantly increased than group B, while the avoidance and yield scores dropped below of group B (all P < 0.05); in group A, the level of health knowledge, personal care abilities, self-perception, self-awareness score and ESCA total score were more outstanding than group B (all P < 0.05); in group A the frequency of defecation, hematochezia, endoscopic performance, the total evaluation score by physicians and the disease activity were lower than group B (all P < 0.05); in the group A, the total scores of knowledge in general, diet, drug, and complication and CCKNOW were higher than group B (all P < 0.05); in group A, the necessity of taking medicine, score of medicine concern and over-all score of BMQ were more significant than group B (all P < 0.05); at last in the group A, the scores of systemic and intestinal symptoms, social and emotional function, and IBDQ in the group A were higher than group B (all P < 0.05). CONCLUSION: For gastrointestinal surgery patients, the Omaha System-based sequel protocol can improve disease awareness and intervention compliance, help them to face the disease positively, reduce disease activity, and improve patients' self-nursing ability and quality of life.

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy.

Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

[Network Meta-analysis of six Chinese patent medicines for replenishing Qi and activating blood in treatment of chronic heart failure].

The efficacy of six commonly used Chinese patent medicines for replenishing Qi and activating blood in the treatment of chronic heart failure was evaluated systematically by network Meta-analysis. Randomized controlled trials(RCTs) about the treatment of chronic heart failure were searched against CNKI, Wanfang, SinoMed, PubMed, and Cochrane library. Network Meta-analysis was performed in Stata 16. A total of 154 RCTs involving 15 620 patients were eventually included. The network Meta-analysis showed that Qili Qiangxin Capsules+conventional western medicine had the highest total effective rate, followed by Tongxinluo Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, Naoxintong Capsules+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Yangxinshi Tablets+conventional western medicine, and conventional western medicine. As for left ventricular ejection fraction(LVEF), Yangxinshi Tablets+conventional western medicine had the highest value, followed by Shexiang Tongxin Drop Pills+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Tongxinluo Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, Naoxintong Capsules+conventional western medicine, and conventional western treatments. As for N-terminal pro-B type natriuretic peptide(NT-proBNP), Qishen Yiqi Drop Pills+conventional western medicine was the most effective treatment, followed by Yangxinshi Tablets+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Tongxinluo Capsules+conventional western medicine, and conventional the most effective treatment was. As for left ventricular end-diastolic diameter(LVEDD), Naoxintong Capsules+conventional western medicine was the best therapy, followed by Tongxinluo Capsules+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Yangxinshi Tablets+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, and conventional western medicine. In summary, the combination of Chinese patent medicines for replenishing Qi and activating blood with western medicines is superior to conventional western medicine alone in the treatment of chronic heart failure. It effectively improves cardiac function indicators such as LVEF, NT-proBNP, and LVEDD, and thus is worthy of popularization in clinical practice. The results of this study provide evidence-based options for the clinical treatment of chronic cardiac failure by combining the Chinese patent medicines for replenishing Qi and activating blood with western medicine.

A Very rare case report of male invasive micropapillary breast carcinoma in China and review of literature.

INTRODUCTION: To report a rare case of male breast micropapillary carcinoma (MBMC) with early metastasis of axillary lymph nodes, the molecular characteristics were further studied in both primary and metastatic foci. In addition, we have reviewed similar published cases in the literature and tried to outline the molecular characteristics of this disease. PRESENTATION OF CASE: A 63-year-old male patient presented with a painless mass on the medial side of left breast and was pathologically diagnosed with MBMC. Postoperative examination revealed 80 % invasive ductal carcinoma (IDC) and 20 % invasive micropapillary carcinoma (IMPC) in the mass, with a histological grade WHO III. There were 25 axillary lymph nodes, 11 of which were metastatic, including 5 macrometastasis and 1 micrometastasis, with a lymph node metastasis rate of 44 % (11/25). Pathological TNM stage: pT2N2M0. Immunohistochemical results in primary foci: AR (90 %, +), HER- 2 (1 +) and ER (90 %, +), PR (60 %, +), E - cadherin (+), EGFR (-), GATA - 3 (90 %, 3 +), Ki - 67 (50 %). Lymph node metastasis: AR (40 %, strong +), HER-2 (2+), ER (90 %, strong +), PR (40 %, strong +), Ki-67 (50 %). AR and Ki-67 were obviously expressed in both primary and metastatic foci. A mixture of IDC and IMPC was found in lymph node metastases, both of which expressed varying degrees of AR and Ki-67. CLINICAL DISCUSSION: MBMC is easy to early metastasized to lymph node. In this case, there was no significant difference between primary and metastatic cancer in molecular results. It is positive for ER and PR, but negative for HER-2 in this patient. There is few data on male HER-2 expression, HER-2 expression is deficient in this case. AR is found to be positive in 50 % of MBMC cases, although their clinical relevance has not been established yet. The significance of EGFR in the prognosis of MBMC remains unclear, however, EGFR positive expression is not found in this patient. CONCLUSIONS: MBMC is a rare disease characterized by early lymph node metastasis, high histological grade, positive ER and PR, and generally negative HER-2. The molecular biological characteristics and prognostic significance of MBMC need to be further studied in order to develop the optimal treatment strategy.

Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.

[Study on the mechanism of paeonol in improving low-density lipoprotein-induced human vascular endothelial cell injury].

OBJECTIVE: To investigate the effects of paeonol on low-density lipoprotein-induced human vascular endothelial cell injury and its molecular mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into 9 groups, normal control (NC) group, ox-LDL group (100 ng/L ox-LDL), low, medium, and high-dose paeonol groups (60 µmol/L, 120 µmol/L, 240 µmol/L paeonol+100 ng/L ox-LDL), ox-LDL+small interfering RNA negative control (si-NC) group, ox-LDL+circ_0003204 small interfering RNA (si-circ_0003204) group, middle dose group+ox-LDL+circ_0003204 overexpression negative control (pcDNA-NC) group, middle dose group+ox-LDL+circ_0003204 overexpression (pcDNA-circ_0003204) group, three replicate wells in each group. MTT flow cytometry, and Western blot were used to detect cell proliferation, apoptosis and protein (CDK2, Bcl2, p27, Bax) expressions, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) kit were used to detect MDA content and SOD activity; real-time quantitative PCR (RT-qPCR) was used to detect the expression of circ_0003204. RESULTS: Compared with the NC group, the proliferation activity, protein expressions of CDK2 and Bcl2, and SOD activity of HUVECs in the ox-LDL group were decreased significantly (P＜0.05), and the apoptosis rate, protein expressions of p27 and Bax, MDA content, and circ_0003204 expression were increased significantly (P＜ 0.05). Compared with the ox-LDL group, the proliferation activity, protein (CDK2, Bcl2) expressions and SOD activity of HUVECs in the low, medium and high dose paeonol groups were increased significantly (P＜0.05), and the apoptosis rate, protein (p27, Bax) expressions, MDA content And circ_0003204 expression were decreased significantly (P＜ 0.05). Compared with ox-LDL+si-NC group, the proliferation activity, protein (CDK2, Bcl2) expressions, SOD activity of HUVECs in ox-LDL+si-circ_0003204 group were increased significantly (P＜0.05), the apoptosis rate, protein (p27, Bax) expressions, and the content of MDA were decreased significantly (P＜0.05). Compared with the middle-dose+ox-LDL+pcDNA-NC group, the HUVECs proliferation activity, protein (CDK2, Bcl2) expressions, and SOD activity in the middle-dose+ox-LDL+pcDNA-circ_0003204 group were decreased significantly (P＜0.05), and the levels of circ_0003204, apoptosis rate, protein (p27, Bax) expressions and MDA content were increased significantly (P＜0.05). CONCLUSION: Paeonol can inhibit ox-LDL-induced apoptosis and oxidative stress of human umbilical vein endothelial cells, and alleviate human umbilical vein endothelial cell injury. The mechanism of action may be related to the down-regulation of circ_0003204 expression.

The Role of Primary Cilia in Thyroid Cancer: From Basic Research to Clinical Applications.

Primary cilia (PC) are microtubule-based organelles that are present on nearly all thyroid follicle cells and play an important role in physiological development and in maintaining the dynamic homeostasis of thyroid follicles. PC are generally lost in many thyroid cancers (TCs), and this loss has been linked to the malignant transformation of thyrocytes, which is regulated by PC-mediated signaling reciprocity between the stroma and cancer cells. Restoring PC on TC cells is a possible promising therapeutic strategy, and the therapeutic response and prognosis of TC are associated with the presence or absence of PC. This review mainly discusses the role of PC in the normal thyroid and TC as well as their potential clinical utility.

Different exercise therapies for treating heart failure: A protocol for overview of systematic reviews and network meta-analysis.

BACKGROUND: Exercise therapies has been shown to be safe and effective as a non-pharmacological management for treating heart failure, At the same time, many clinical trials, systematic review, and meta-analyses have demonstrated the advantages of exercise therapies in heart failure. However, the methodological quality of these systematic reviews and the differences in efficacy between different exercise modes are unclear. Therefore, this study intends to overview of systematic reviews and network meta-analysis of exercise therapies intervention in heart failure, and finally to rank the effects of exercise therapies in the intervention of heart failure, so as to provide certain reference for clinical decision-making. METHODS: From the seven databases: PubMed, EMBASE.com, Web of Science, the Cochrane Library, Chinese biomedical literature database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wan fang Database, and Chongqing VIP (CQVIP) databases. To search for systematic or meta-analysis of different exercise therapies for heart failure from inception to August 2020. According to the inclusion criteria and exclusion criteria, the two researchers independently selected articles and extracted data. In case of differences, a third party shall be sought for settlement. The AMSTAR2 scale, PRISMA scale and GRADE were used to assess the quality and evidence grade of the literature. The eligible randomized controlled trials (RCTs) were selected from the included systematic reviews and updated RCTs from the above systematic reviews to August 2020. GRADE was used for the risk of bias of the included RCTs. Pairwise meta-analyses were performed using the random-effects model, and network meta-analysis of the included RCTs were performed the frequentist framework. All data analyses were completed in Stata 15.0. RESULTS: Finally, a total of 33 articles related to systematic review and meta-analysis were included, there are 28 articles in Chinese and 5 articles in English. The results of this overview and network meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This review will provide a comprehensive overview of existing systematic reviews of exercise therapies interventions for heart failure and provide recommendations for clinical practice or guidelines. PROTOCOL REGISTRATION: INPLASY202080118.

New therapeutic insights into radiation-induced myocardial fibrosis.

Radiation therapy (RT) for the treatment of thoracic tumors causes radiation-induced heart disease (RIHD). Radiation-induced myocardial fibrosis (RIMF) is both an acute and chronic stage of RIHD, depending on the specific pathology, and is thought to be a major risk factor for adverse myocardial remodeling and vascular changes. With the use of more three-dimensional conformal radiation regimens and early screenings and diagnoses for RIMF, the incidence of RIHD is declining, but it still must be carefully investigated to minimize the mortality and morbidity of patients with thoracic malignancies after RT treatment. Effective methods for preventing RIMF involve a decrease in the direct radiation dose in the heart, and early screening and diagnosis. Medications remain as a useful adjunct for preventing or treating RIMF. This review mainly discusses the cellular and molecular mechanisms underlying RIMF, and new therapeutic drugs that can potentially be developed from this knowledge.

Astragalus Saponins and Liposome Constitute an Efficacious Adjuvant Formulation for Cancer Vaccines.

Cancer vaccines mostly aim to induce cytotoxic T lymphocytes (CTLs) against tumors. An appropriate adjuvant is of fundamental importance for inducing cellular immune response. Since the antigen in particulate form is substantially more immunogenic than soluble form antigen, it is beneficial to interact with antigen-presenting cells membrane to induce robust CD8+ T cell activation following vaccination. Based on previous research, we designed an adjuvant formulation by combining Astragalus saponins, cholesterol, and liposome to incorporate antigen into a particulate delivery system, so as to enhance cellular immune response. Meanwhile, angiogenesis contributes to tumor growth and metastasis, and basic fibroblast growth factor (bFGF) is involved in tumor angiogenesis. Therefore, using lipo-saponins adjuvant formulation and a human recombinant bFGF antigen protein, we tried to induce bFGF-specific CTL response to inhibit tumor angiogenesis to achieve antitumor activity. After five immunizations, the lipo-saponins/bFGF complex elicited robust antibody response and markedly higher amount of interferon-γ in BALB/c mice, resulting in superior antitumor activities. Decreased microvessel density in CD31 immunohistochemistry and the lysis of vascular endothelial cells by the T lymphocytes from the immunized mice indicated that the immunity inhibited the angiogenesis of tumors and further led to the inhibition of tumors. Our data suggest that the approach to construct adjuvant formulation between liposome and Astragalus saponins appeared highly desirable, and that Astragalus saponins may be utilized as a valuable additive for enhancing the effectiveness of vaccines and stimulating an appropriate immune response that can benefit tumor therapy.

A vaccine targeting basic fibroblast growth factor elicits a protective immune response against murine melanoma.

Tumor growth and metastasis are closely related to angiogenesis. Basic fibroblast growth factor(bFGF) is an angiogenic factor, and up-regulated expression of bFGF plays a crucial role in the development and metastasis of melanoma. Therefore, in this study, we sought to achieve antitumor activity by immunity targeting bFGF which would inhibit tumor angiogenesis and simultaneously induce bFGF specific cytotoxic T lymphocytes to kill melanoma cells. A human bFGF protein was used as exogenous antigen, coupled with a saponin-liposome adjuvant formulation to enhance CTL response. The results showed that the immunity induced strong immune response and produced prominent anti-cancer activities. CD31 immunohistochemistry and alginate-encapsulated tumor cell assay displayed that tumor angiogenesis was effectively inhibited. Further, the higher production of IFN-γ and cytotoxic T lymphocyte killing assay suggested that the anti-cancer activities may mainly depend on cellular immune response, which could cause the inhibition of tumor angiogenesis and specific killing of tumor cells by bFGF-specific cytotoxic T lymphocytes. We concluded that immunotherapy targeting bFGF may be a prominent strategy for melanoma, and that the adjuvant formulation of saponin-liposome is very desirable in enhancing cytotoxic T lymphocytes response.

Effect of stocking density on growth performance, digestive enzyme activities, and nonspecific immune parameters of Palaemonetes sinensis.

Palaemonetes sinensis is a new breed of shrimp with great potential for aquaculture, which has been confirmed in our previous production tests. However, there are limited reports about this species and its biological information is scarce. This study describes the effect of stocking density on the growth, digestive enzyme activities, and nonspecific immunity of P. sinensis with an initial average body weight was 0.25 ± 0.02 g. Groups of shrimps were reared at four different initial densities (2.5, 5, 10, and 20 individuals·L-1). After 30 days of culture, the results indicated that the final body weight, weight gain, and specific growth rate were higher in shrimps grown in groups of 10 individuals·L-1 than other groups, but the survival rates of these shrimp were significantly lower than those reared in group of 2.5 or 5 individuals·L-1. The trypsin, amylase, and lipase activities of shrimp significantly decreased with increase in stocking density. Nonspecific immune indicators decreased significantly with increase in density, but there were no significant differences between the 2.5 and 5 individuals·L-1 groups in terms of the total haemocyte count (THC), phenoloxidase activity (PO), lysozyme (LZM), catalase (CAT), and superoxide dismutase (SOD). These results suggest that increasing the stocking density from 2.5 to 5 individuals·L-1 did not affect any of the detected indicators of P. sinensis, but there are shelter in farming mode is better for culture of P. sinensis up to 10 individuals L-1.

[Radix Angelicae Sinensis and Radix Hedysari Enhance Radiosensitivity of Human Liver Cancer Cells to ¹²C6⁺Radiation].

OBJECTIVE: To determine the effect of Radix Angelicae Sinensis and Radix Hedysari (RAS-RH) on radiosensitivity of human liver cancer H22 cells to heavy ion ¹²C6⁺and its possible mechanism. METHODS: The experiment involved a comparison of proliferation of H22 cells (detected by CCK-8 assay) between four groups: control,drug (RAS-RH),radiation,and combination (RAS-RH+radiation). H22 cells were treated with different doses of radiation alone or radiation followed by RAS-RH. The radiation enhancement effect of RAS-RH on H22 was detected by Colony forming assay. The effect of RAS-RH on the apoptosis of H22 cells was detected by flow cytometry. The influence of RAS-RH on the expression levels of related protein Survivin and Caspase-9 was investigated by Western blot. RESULTS: RAS-RH inhibited the proliferation of H22 cells,with a time and dose dependency [inhibitory concentration 20% (IC20)=(117.60±2.15) mg/L]. The survival rate of H22 cells decreased significantly with the increase of heavy ion ¹²C6⁺. The two survival curves produced by the Graph Pad Prism 5.0 software were clearly separated. The combination group demonstrated smaller shoulder area at low dosage and lower survival rate of cells compared with radiation group,with a sensitization enhancement ratio (SER) of 1.39±0.07. The combination group (100 mg/L RAS-RH+2 Gy) had higher apoptosis rate and Caspase-9 protein expression level,and lower Survivin protein expression level,compared with other 3 groups ( P<0.01). CONCLUSION: RAS-RH has radiation sensitization effect on human hepatocellular carcinoma H22 cells. The mechanism may be related to down-regulation of Survivin protein expression and up regulation of Caspase-9 protein expression.

[The influences of ultrafiltration and alcohol sedimentation on protective effects of Radix Astragali and Radix Hedyseri against rat's cerebral ischemia].

OBJECTIVE: To investigate the influences of ultrafiltration and alcohol sedimentation on protective effects of Radix Astragali and Radix Hedyseri against rat's cerebral ischemia. METHODS: Using dexamethasone (im.) and ligating common carotid artery, the rat stasis model combined transient cerebral ischemia was established to evaluate the effects of the ultrafiltration and alcohol sedimentation through detecting antioxidant system and other indexes in brain tissue. RESULTS: The results showed that the 6 g/kg water extract(crude drug), ultrafiltration and alcohol sedimentation of Radix Astragali and Radix Hedyseri could upgrade adenosine-triphosphate (ATP), superoxide dismutase (SOD) and catalase (CAT), and degrade malondialdehyde(MDA) and water content of brain tissue in rat stasis model combined transient cerebral ischemia, the water extract and ultrafiltration of them could degrade lactic acid (LD) of brain tissue, and the effects of alcohol sedimentation of Radix Astragali and Radix Hedyseri become weaker than water extract of them. CONCLUSION: The water extract, ultrafiltration and alcohol sedimentation of Radix Astragali and Radix Hedyseri have some protective effects on cerebral ischemia in rats, the effective differences of the extract through the same extraction method are not remarkable, and alcohol precipitation method has obvious influences effect on Radix Astragali and Radix Hedyseri.

Holistic analysis of seven active ingredients by micellar electrokinetic chromatography from three medicinal herbs composing Shuanghuanglian.

A simple and reliable method has been developed with a new strategy named holistic analysis of multiple constituents to evaluate the quality of the well-known traditional Chinese medicine (TCM) Shuanghuanglian (SHL) oral liquid and soft capsule. Seven main constituents of the medicine, i.e., baicalein, baicalin, chlorogenic acid, wogonin, scutellarin, forsythin and hyperin, were selected as the evaluation markers and analyzed by micellar electrokinetic chromatography. The effects of buffer pH, concentration of electrolyte, organic modifier and applied voltage on migration behavior were studied systematically. The optimum conditions for the separation were achieved in a 12.5 mM borate-10 mM sodium dihydrogen phosphate-10 mM sodium dodecyl sulfate buffer at pH 9.1 containing 10% (v/v) acetonitrile under 15 kV. The analytes were identified by their relative time with regard to para-hydroxybenzoic acid migration time used as an internal standard. The method was validated in terms of linearity, limit of detection and quantification, precision, accuracy and recoveries. The correlation coefficient ranged from 0.9962 to 0.9992. The limits of detection (S/N = 3) were from 0.15 to 3.95 µg mL(-1). Recoveries of seven analytes in the SHL samples ranged from 89.00 to 103.04%. The proposed method was successfully applied for the quality control of complicated TCM SHL.