Scale-Hybrid Group Distillation with Knowledge Disentangling for Continual Semantic Segmentation.

Continual semantic segmentation (CSS) aims to learn new tasks sequentially and extract object(s) and stuff represented by pixel-level maps of new categories while preserving the original segmentation capabilities even when the old class data is absent. Current CSS methods typically preserve the capacities of segmenting old classes via knowledge distillation, which encounters the limitations of insufficient utilization of the semantic knowledge, i.e., only distilling the last layer of the feature encoder, and the semantic shift of background caused by directly distilling the entire feature map of the decoder. In this paper, we propose a novel CCS method based on scale-hybrid distillation and knowledge disentangling to address these limitations. Firstly, we propose a scale-hybrid group semantic distillation (SGD) method for encoding, which transfers the multi-scale knowledge from the old model's feature encoder with group pooling refinement to improve the stability of new models. Then, the knowledge disentangling distillation (KDD) method for decoding is proposed to distillate feature maps with the guidance of the old class regions and reduce incorrect guides from old models towards better plasticity. Extensive experiments are conducted on the Pascal VOC and ADE20K datasets. Competitive performance compared with other state-of-the-art methods demonstrates the effectiveness of our proposed method.

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The lymphatic system of the heart plays an important role in the repair process after myocardial injury and may regulate normal tissue homeostasis and natural regeneration via maintaining fluid homeostasis and controlling the inflammatory response. The lymphatic system in the heart is activated after myocardial injury and is involved in the scarring process of the heart. Recent studies on the lymphatic system and myocardial repair of the heart have developed rapidly, and the mechanisms for lymphangiogenesis and lymphatic endothelial cell secretion have been elucidated by different animal models. A deep understanding of the structural, molecular, and functional characteristics of the lymphatic system of the heart can help develop therapies that target the lymphatic system in the heart. Summarizing the progress in studies on targets related to myocardial repair and the cardiac lymphatic system is helpful to provide potential new targets and strategies for myocardial repair therapy after myocardial infarction.

Research Progress of Chinese Medicine in the Treatment of Myocardial Ischemia-Reperfusion Injury.

Vascular recanalization is the essential procedure in which severe coronary artery stenosis is diagnosed. However, the blood flow recovery associated with this procedure may cause myocardial ischemia-reperfusion injury (MIRI), which aggravates heart failure. Unfortunately, the mechanism of MIRI has historically been poorly understood. As we now know, calcium overloading, oxidative stress, mitochondrial dysfunction, inflammatory responses, and ferroptosis take part in the process of MIRI. Modern medicine has shown through clinical studies its own limited effects in the case of MIRI, whereas Chinese traditional medicine demonstrates a strong vitality. Multiple-target effects, such as anti-inflammatory, anti-oxidant, and cardio-protection effects, are central to this vitality. In our clinic center, Yixin formula is commonly used in patients with MIRI. This formula contains Astragalus, Ligusticum Wallichii, Salvia, Rhodiola Rosea, Radix Angelicae Sinensis, Cyperus Rotundus, and Cassia Twig. Its effects include warming yang energy, activating blood circulation, and eliminating blood stasis. In our previous laboratory studies, we have proved that it can reduce MIRI and oxidative stress injury in rats suffering from ischemia myocardiopathy. It can also inhibit apoptosis and protect myocardium. In this paper, we review the research of Yixin formula and other related herbal medicines in MIRI therapy.

[Meta-analysis of effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention].

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.

Evidence-based traditional Chinese medicine research: Two decades of development, its impact, and breakthrough.

It has been over 20 years since the introduction of evidence-based medicine (EBM) into the research of traditional Chinese medicine (TCM). The development of evidence-based TCM research has profoundly influenced the process of clinical research and decision-making, impelling researchers to pay attention to raise evidence quality, accumulate data, and explore appropriate evaluation methods adaptive to TCM original theories and knowledge. In this paper, the authors aim to summarize and review the existing work and seek promising research interests in this field, expecting to inspire more thoughts leading to breakthroughs in the near future.

Individualized Efficiency of Traditional Chinese Medicine for Non-ST Segment Elevation Acute Coronary Syndrome: Study Protocol for Observational Research by the Evidence-Based Goal Attainment Scale.

BACKGROUND: Non-ST segment elevation acute coronary syndrome has been one of the most serious diseases threatening human health. Long-term cardiac rehabilitation and secondary prevention is the essential method to control the recurrence and mortality of the disease. Traditional Chinese medicine has proved the efficiency on the treatment of non-ST segment elevation acute coronary syndrome, but there is a lack of appropriate methodological design to reflect the characteristics of individualized diagnosis and treatment of it. Therefore, this study used the evidenced-based Goal Attainment Scale to evaluate the clinical effectiveness of traditional Chinese medicine on the treatment of non-ST segment elevation acute coronary syndrome. METHOD: This is observational research with the prospective feature. A total of 200 patients will be recruited and observed in the three months by telephone or door visit, collecting the individualized intervention of traditional Chinese medicine and evaluating through the method of evidence-based Goal Attainment Scale. Participants will be included according to the inclusion and exclusion criteria. Any reasons for loss to follow-up and adverse events will be recorded strictly. Discussion. The evidence-based Goal Attainment Scale provides a personalized method of evaluation based on the Goal Attainment Scale and combined with evidence-based medicine, which can better reflect the characteristics and superiority of individualized and dynamic intervention for traditional Chinese medicine on the long-term prevention and treatment of non-ST segment elevation acute coronary syndrome than other methods of design. It is of great significance to explore and promote this method of design in the future.

The Application of Traditional Chinese Medicine Injection on Patients with Acute Coronary Syndrome during the Perioperative Period of Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: TCMI with the effect of Liqihuoxue and Yiqihuoxue has been applied as complementary therapies during the perioperative period of PCI for patients with ACS, while the recommended time points and plans of TCMI are still short of the support of evidence-based medicine. METHODS: A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of TCMI on patients with ACS during the perioperative period of PCI. RCTs were searched based on standardized searching rules in seven medical databases from the inception up to August 2019. Two reviewers conducted the study selection, data extraction, and quality analysis independently. Data were analysed with the support of software RevMan and Stata. RESULTS: A total of 68 articles with 6,043 patients were enrolled. The result of meta-analysis showed that the TCMI combined with western medicine was superior to the western medicine alone on clinical efficiency (before the PCI, before and after the PCI, or overall, P < 0.05), the occurrence of MACE (myocardial infarction and stenocardia: before the PCI, before and after the PCI, or overall, P < 0.05; arrhythmia: before and after the PCI, P < 0.05), and the level of inflammatory factors (hs-CRP: before the PCI, before and after the PCI, or overall, P < 0.05; IL-6: after the PCI, P < 0.05). The TCMI with the effect of Liqihuoxue obtained more support compared with Yiqihuoxue based on the result of meta-analysis. CONCLUSIONS: TCMI with the effect of Liqihuoxue or Yiqihuoxue combined with western medicine generally showed the potential advantage on the treatment of ACS during the perioperative period of PCI. However, the optimal time point of intervention and recommended plan based on the effect still needs more clinical evidence. We consider that the research of precise and standardized application of TCMI will be a promising direction for TCM in the future.

Initiate Danhong Injection before or after percutaneous coronary intervention for microvascular obstruction in ST-elevation myocardial infarction (DIRECTION): study protocol for a randomized controlled trial.

BACKGROUND: No treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain. METHODS: The DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators. DISCUSSION: This trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019.

Clinical Efficacy and Safety of Electroacupuncture in Migraine Treatment: A Systematic Review and Network Meta-Analysis.

Considering the heavy burden of migraine, it is essential to update insufficient and/or outdated clinical evidence supporting electroacupuncture (EA) in migraine therapy. In this study, a literature search of seven medical databases was performed. After data extraction and quality evaluation, 13 randomized controlled trials, including 1559 patients, were assessed in this analysis. Results demonstrated that EA was superior to control treatment (Western medicine, sham-EA, blank control, acupuncture, and acupoint catgut embedding) according to the visual analog scale (VAS) score, frequency of headache attack (Western medicine, sham-EA, blank control), self-rating anxiety scale (SAS [blank control]), self-rating depression score (SDS [Western medicine and blank control]), and clinical efficiency (Western medicine and sham-EA) after treatment (P<0.05). Results of network meta-analysis (for VAS, SAS, and SDS) demonstrated statistically significant differences in VAS scores for EA compared with sham-EA, acupuncture with sham-EA, acupoint catgut embedding with sham-EA, and acupoint catgut embedding with blank control. Rank probability analysis of VAS, SAS, and SDS scores all demonstrated that EA ranked first. Most studies were symmetrically distributed on both sides of the midline in funnel plots for VAS, SAS, and SDS, which indicated a low likelihood of small sample effects. Sensitivity analysis confirmed the stability of the studies included in this research. EA is one of several effective treatments for migraine pain symptoms, and, to some extent, anxiety and depression. Nevertheless, multi-center studies with large sample sizes and/or well-designed randomized controlled trials (RCTs) will be needed in the future.

An Overview of Systematic Reviews of Randomized Controlled Trials on Acupuncture Treating Migraine.

Objectives: To review the evidence of acupuncture for acute and preventive treatment of migraine for further awareness of the effect of acupuncture for migraine. Design: An overview of systematic reviews and meta-analyses (SR/MAs) for randomized controlled trials. Material and Methods: We searched PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, VIP Chinese Journal Full Text Database, WANFANG Data, and China Biology Medicine disc from their establishment to May 27, 2018. SR/MAs of randomized controlled trials comparing the effect of the acupuncture intervention with another treatment control in migraine patients were included. Results: 428 SRs were identified, and 15 of them were included. Only 4 SR/MAs were assessed by GRADE, which showed certainty of most evidence being low or very low. Assessed by AMSTAR-2, fourteen was critically low rating overall confidence in the results, and 1 was low rating overall confidence in the results. Evidence suggested that acupuncture has a significant advantage of pain improvement, efficacy, and safety relative to blank control, sham acupuncture, or drug treatment, but some of these results are contradictory. Conclusions: We found that acupuncture on treating migraine has the advantage for pain improvement and safety, but the quality of SR/MAs of acupuncture for migraine remains to be improved.

Effects of coenzyme Q10 intervention on diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: The diabetic kidney disease (DKD) has become a seriously kidney disease that commonly caused by diabetes mellitus (DM). Oxidative stress response plays an essential role in the genesis and worsening of DKD and Coenzyme Q10 (CoQ10) has been reported the promising clinical effectiveness on DKD treatment. However, there is lack of relative evidence-based medical evidence currently. OBJECTIVE: The systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, which conducted to evaluate the effectiveness of CoQ10 in combination with other western medicine for DKD therapy through the randomized controlled trials (RCTs) and experimental studies. METHODS: RCTs and experimental studies were searched based on standardized searching rules in 12 medical databases from the inception up to June 2018 and a total of 8 articles (4 RCTs and 4 experimental studies) were enrolled in the meta-analysis. RESULTS: The results revealed that CoQ10 combined with other western medicine show statistical differences in the laboratory parameters of fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and malondialdehyde (MDA) amelioration after DKD therapy compared with control group. However, LDL-C and Urea level for RCTs and Urine output and Glucose for experimental studies on DKD was not superior to control group. CONCLUSION: We need to make conclusion cautiously for the effectiveness of CoQ10 application on DKD therapy. More standard, multicenter, double-blind RCTs, and formal experimental studies of CoQ10 treatment for DKD were urgent to be conducted for more clinical evidence providing in the future. The underlying pharmacological mechanism of CoQ10 needs to be researched and revealed for its future application on DKD therapy.

Sustained nicorandil administration reduces the infarct size in ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention.

OBJECTIVE: Currently, there is still no effective strategy to diminish the infarct size (IS) in patients with ST-segment elevation myocardial infarction (STEMI). According to a previous animal study, nicorandil treatment is a promising pharmaceutical treatment to limit the infarct area. In this study, we aim to investigate the effects of continual nicorandil administration on the IS and the clinical outcomes in patients with STEMI who underwent primary percutaneous coronary intervention (pPCI). METHODS: One hundred seventeen patients with STEMI and undergoing pPCI were randomly divided into the sustained nicorandil group (5 mg, three times daily) or the control group (only single nicorandil before PCI). The primary endpoint was the IS, evaluated by single-photon emission computed tomography (SPECT) 3 months after pPCI. RESULTS: Eighty-five patients completed the IS assessment via SPECT, and 99 participants were available for follow-up after 6 months. Finally, there was a statistical difference in the IS between the nicorandil and control groups {13% [interquartile range (IQR), 8-17] versus 16% [IQR, 12-20.3], p=0.027}. Additionally, we observed that maintained nicorandil administration significantly improved the left ventricular ejection fraction at 3 months and enhanced the activity tolerance (physical limitation and angina stability) at 6 months after PCI. CONCLUSION: Sustained nicorandil treatment reduced the IS and improved the clinical outcomes compared to the single nicorandil administration for patients with STEMI undergoing the pPCI procedure. Continuous cardioprotective therapy may be more beneficial for patients with STEMI.

Scorpion inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant diseases worldwide. The unfavorable clinical outcome and poor prognosis are due to high rates of recurrence and metastasis after treatments. Some scholars of traditional Chinese medicine suggested that endogenous wind-evil had played an important role in metastasis of malignant tumor. Therefore, the drug of dispelling wind-evil could be used to prevent cancer metastasis and improve the poor prognosis. So we wondered whether Scorpion, one of the most important wind calming drugs, has antitumor effect especially in epithelial-mesenchymal transition (EMT) and metastasis of HCC in this research. We found that Scorpion-medicated serum could inhibit proliferation, induce apoptosis, and decrease migration and invasion capacity of Hepa1-6 cells in vitro. Meanwhile, we observed that water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT, which is characterized by increased epithelial marker E-cadherin expression and decreased mesenchymal markers N-cadherin and Snail expression following Scorpion treatment both in vitro and in vivo. These results suggested that the Scorpion could inhibit Hepa1-6 cells' invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis. Impact statement The unfavorable clinical outcome and poor prognosis of hepatocellular carcinoma (HCC) are due to high rates of recurrence and metastasis after treatments. Here we found Scorpion, one of the most important wind calming drugs, has antitumor effect. Scorpion-medicated serum inhibited the proliferation, induced apoptosis, and decreased migration and invasion capacity of Hepa1-6 cells in vitro. Water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT of HCC both in vitro and in vivo. Our results suggested that the Scorpion could inhibit Hepa1-6 cells' invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis.

Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1.

BACKGROUND: Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI. METHODS: A cardiac MI injury model was constructed by ligating the left anterior descending (LAD) coronary artery. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of nicorandil on MI-induced injury. RESULTS: Nicorandil reduced cardiac enzyme release, mitigated left ventricular enlargement and cardiac dysfunction after MI, as evaluated by echocardiography and hemodynamic measurements. According to the results of the western blot analysis and immunofluorescence staining, nicorandil enhanced autophagic flux and reduced apoptosis in cardiomyocytes subjected to hypoxic injury. Interestingly, nicorandil increased Mst1 and p-Mst1 levels in cardiomyocytes subjected to MI injury. Mst1 knockout abolished the protective effects of nicorandil on cardiac remodeling and dysfunction after MI. Mst1 knockout also abolished the beneficial effects of nicorandil on cardiac enzyme release and cardiomyocyte autophagy and apoptosis. CONCLUSIONS: Nicorandil alleviates post-MI cardiac dysfunction and remodeling. The mechanisms were associated with enhancing autophagy and inhibiting apoptosis through Mst1 inhibition.

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. OBJECTIVE: The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. METHODS: Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. RESULTS: The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. CONCLUSION: We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future.

A systematic review and meta-analysis of traditional insect Chinese medicines combined chemotherapy for non-surgical hepatocellular carcinoma therapy.

On the background of high morbidity and mortality of hepatocellular carcinoma (HCC) and rapid development of traditional Chinese medicine (TCM), we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess the clinical effectiveness and safety of traditional insect Chinese medicine and related preparation for non-surgical HCC. RCTs were searched based on standardized searching rules in mainstream medical databases from the inception up to May 2016. Ultimately, a total of 57 articles with 4,651 patients enrolled in this meta-analysis. We found that traditional insect Chinese medicine and related preparation combined chemotherapy show significantly effectiveness and safety in objective response rate (P < 0.001), survival time extension [12 months (P < 0.001); 18 months (P < 0.001); 24 months (P < 0.001); 36 months (P < 0.001)], amelioration for life quality [QoL scores improvement (P < 0.001); KPS improvement (P < 0.001); AFP improvement (P < 0.001)] and reduction of therapeutic toxicity [WBC decrease (P = 0.04); gastrointestinal adverse reactions (P < 0.001)]. In conclusion, traditional insect Chinese medicine and related preparations could be recommended as auxiliary therapy combined chemotherapy for HCC therapy.