Targeting mitochondrial circadian rhythms: The potential intervention strategies of Traditional Chinese medicine for myocardial ischaemia‒reperfusion injury.

Coronary artery disease has one of the highest mortality rates in the country, and methods such as thrombolysis and percutaneous coronary intervention (PCI) can effectively improve symptoms and reduce mortality, but most patients still experience symptoms such as chest pain after PCI, which seriously affects their quality of life and increases the incidence of adverse cardiovascular events (myocardial ischaemiareperfusion injury, MIRI). MIRI has been shown to be closely associated with circadian rhythm disorders and mitochondrial dysfunction. Mitochondria are a key component in the maintenance of normal cardiac function, and new research shows that mitochondria have circadian properties. Traditional Chinese medicine (TCM), as a traditional therapeutic approach characterised by a holistic concept and evidence-based treatment, has significant advantages in the treatment of MIRI, and there is an interaction between the yin-yang theory of TCM and the circadian rhythm of Western medicine at various levels. This paper reviews the clinical evidence for the treatment of MIRI in TCM, basic experimental studies on the alleviation of MIRI by TCM through the regulation of mitochondria, the important role of circadian rhythms in the pathophysiology of MIRI, and the potential mechanisms by which TCM regulates mitochondrial circadian rhythms to alleviate MIRI through the regulation of the biological clock transcription factor. It is hoped that this review will provide new insights into the clinical management, basic research and development of drugs to treat MIRI.

Chinese patent medicines for coronary microvascular disease: clinical evidence and potential mechanisms.

Coronary microvascular disease (CMVD) is a high risk factor for many cardiovascular events. Due to the limited understanding of its pathophysiological mechanism, modern medicine still lacks therapeutic drugs for CMVD. Existing clinical studies have shown that traditional Chinese medicine (TCM) can effectively improve the clinical symptoms and quality of life of CMVD patients. As an indispensable part of TCM, Chinese patent medicines (CPMs) are widely used in clinical practice. In the face of numerous oral CPMs for treatment of CMVD, how to choose a reasonable medication regimen is one of the important issues in clinic. Based on this, this paper reviewed the clinical efficacy and recommended level of 12 CPMs in the treatment of CMVD, which are recommended by expert consensus on diagnosis and treatment of coronary microvascular disease with integrated Chinese and Western medicine (WM). In addition, this study also systematically summarized the possible mechanisms of CPMs in the treatment of CMVD by protecting coronary microvascular endothelial cells, improving vascular endothelial function, inhibiting inflammation, reducing oxidative stress, promoting angiogenesis, and improving hemorheology, aiming to provide meaningful information for its clinical application.

Targeting intestinal microecology: potential intervention strategies of traditional Chinese medicine for managing hypertension.

Hypertension has become one of the major public health problems in the world. At present, the pathogenesis of hypertension has still not been completely elucidated. In recent years, an increasing evidence shows that intestinal microecology is closely related to hypertension, which provides a new thinking for the prevention and treatment of hypertension. Traditional Chinese medicine (TCM) has unique advantages in the treatment of hypertension. Taking intestinal microecology as the target, it is possible to interpreting the scientific connotation of TCM prevention and treatment of hypertension by updating the treatment concept of hypertension, so as to improve the therapeutic effect. In our study, the clinical evidence for TCM treatment of hypertension was systematicly summarized. And the relationship among TCM, intestinal microecology and hypertension was analyzed. In addition, the methods by which TCM regulates intestinal microecology to prevent and treat hypertension were presented, to provide new research ideas for prevention and treatment of hypertension.

Traditional Chinese medicine for heart failure with preserved ejection fraction: clinical evidence and potential mechanisms.

Heart failure with preserved ejection fraction accounts for a large proportion of heart failure, and it is closely related to a high hospitalization rate and high mortality rate of cardiovascular disease. Although the methods and means of modern medical treatment of HFpEF are becoming increasingly abundant, they still cannot fully meet the clinical needs of HFpEF patients. Traditional Chinese medicine is an important complementary strategy for the treatment of diseases in modern medicine, and it has been widely used in clinical research on HFpEF in recent years. This article reviews the current situation of HFpEF management, the evolution of guidelines, the clinical evidence and the mechanism of TCM in the treatment of HFpEF. The purpose of this study is to explore the application of TCM for HFpEF, to further improve the clinical symptoms and prognosis of patients and to provide a reference for the diagnosis and treatment of the disease.

Gut microbiota and hypertension: association, mechanisms and treatment.

OBJECTIVES: Hypertension is one of the most important risk factors for cardio-cerebral vascular diseases, which brings a heavy economic burden to society and becomes a major public health problem. At present, the pathogenesis of hypertension is unclear. Increasing evidence has proven that the pathogenesis of hypertension is closely related to the dysbiosis of gut microbiota. We briefly reviewed relevant literature on gut microbiota and hypertension to summarize the relationship between gut microbiota and hypertension, linked the antihypertension effects of drugs with their modulation on gut microbiota, and discussed the potential mechanisms of various gut microbes and their active metabolites to alleviate hypertension, thus providing new research ideas for the development of antihypertension drugs. METHODS: The relevant literature was collected systematically from scientific database, including Elsevier, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of herbal medicine. RESULTS: Hypertension can lead to gut microbiota imbalance and gut barrier dysfunction, including increased harmful bacteria and hydrogen sulfide and lipopolysaccharide, decreased beneficial bacteria and short-chain fatty acids, decreased intestinal tight junction proteins and increased intestinal permeability. Gut microbiota imbalance is closely related to the occurrence and development of hypertension. At present, the main methods to regulate the gut microbiota include fecal microbiota transplantation, supplementation of probiotics, antibiotics, diet and exercise, antihypertensive drugs, and natural medicines. CONCLUSIONS: Gut microbiota is closely related to hypertension. Investigating the correlation between gut microbiota and hypertension may help to reveal the pathogenesis of hypertension from the perspective of gut microbiota, which is of great significance for the prevention and treatment of hypertension.

Gut microbiota: A new target of traditional Chinese medicine for insomnia.

All species have a physiological need for sleep, and sleep is crucial for the preservation and restoration of many physiological processes in the body. Recent research on the effects of gut microbiota on brain function has produced essential data on the relationship between them. It has been discovered that dysregulation of the gut-brain axis is related to insomnia. Certain metabolites of gut microbiota have been linked to insomnia, and disturbances in gut microbiota can worsen insomnia. Traditional Chinese medicine (TCM) has unique advantages for the treatment of insomnia. Taking the gut microbiota as the target and determining the scientific relevance of TCM to the prevention and treatment of insomnia may lead to new concepts for the treatment of sleep disorders and improve the therapeutic effect of sleep. Taking the gut microbiota as an entry point, this paper reviews the relationship between gut microbiota and TCM, the relationship between gut microbiota and insomnia, the mechanism by which gut microbiota regulate sleep, and the mechanism by which TCM regulates gut microbiota for insomnia prevention and treatment. This review provides new ideas for the prevention and treatment of insomnia through TCM and new ideas for drug development.

Resistance to QoI and DMI Fungicides Does Not Reduce Virulence of C. beticola Isolates in North Central United States.

Cercospora leaf spot (CLS) is a destructive disease limiting sugar beet production and is managed using resistant cultivars, crop rotation, and timely applications of effective fungicides. Since 2016, its causal agent, Cercospora beticola, has been reported to be resistant to quinone outside inhibitors (QoIs) and to have reduced sensitive to demethylation inhibitors (DMIs) in sugar beet growing areas in North Dakota and Minnesota. Isolates of C. beticola resistant to QoIs, DMIs, and both QoIs and DMIs were collected from fields in Foxhome, Minnesota, in 2017. Fitness of these resistant isolates was compared with that of QoI- and DMI-sensitive isolates in laboratory and greenhouse studies. In the lab, mycelial growth, spore production, and spore germination were measured. The results showed that resistant isolates had significantly less mycelial growth and spore production than sensitive isolates, while no significant difference in spore germination was detected. In the greenhouse, six leaf-stage sugar beets were inoculated with a spore suspension made from each resistant group and incubated in separate humidity chambers. CLS disease severity was evaluated visually at 7, 14, and 21 days after inoculation (DAI), and the areas under disease progress curve (AUDPC) were calculated. Resistant isolates had significantly smaller AUDPC but still caused as high disease severity as the sensitive ones at 21 DAI. Although QoI- and/or DMI-resistant isolates had a relatively slower disease development, they still caused high disease severity and need to be factored in disease management practices.

A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization.

Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the "guide" to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC.

Traditional chinese medicine in coronary microvascular disease.

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is associated with an increased risk of adverse cardiovascular events. Although the study of CMVD in modern medicine is ongoing, there is still no effective treatment for it. Traditional Chinese medicine (TCM) has some clinical advantages based on syndrome differentiation and individualized treatment. In this review, we review the clinical significance, pathogenesis, and current treatments of CMVD and systematically summarize the clinical efficacy and potential action mechanisms of TCM for CMVD. In addition, the scientific problems that need to be solved urgently and the research strategy of TCM for CMVD are described. CMVD has great clinical significance, but there are still many gaps in the related research. This review aims to attract the attention of clinicians to CMVD and promote research on CMVD in TCM.

Traditional Chinese medicine against COVID-19: Role of the gut microbiota.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has become a public health concern worldwide. In addition to respiratory symptoms, some COVID­19 patients also show various gastrointestinal symptoms and even consider gastrointestinal symptoms to be the first manifestation. A large amount of evidence has shown that SARS-CoV-2 infection could disrupt the gut microbiota balance, and disorders of the gut microbiota could aggravate the condition of COVID-19 patients. Therefore, maintaining the gut microbiota balance is expected to become a potential new therapeutic target for treating COVID-19. Traditional Chinese medicine (TCM) has significant effects in all stages of the prevention and treatment of COVID-19. It can adjust the gut microbiota and is an ideal intestinal microecological regulator. This review summarizes the advantages and clinical efficacy of TCM in the treatment of COVID-19 and expounds on the relationship between TCM and the gut microbiota, the relationship between COVID-19 and the gut microbiota, the mechanism of gut microbiota disorders induced by SARS-CoV-2, the relationship between cytokine storms and the gut microbiota, and the role and mechanism of TCM in preventing and treating COVID-19 by regulating the gut microbiota to provide new research ideas for TCM in the prevention and treatment of COVID-19.

Efficacy and Safety of Traditional Chinese Medicine Injections for Heart Failure With Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Heart failure as an important issue in global public health, has brought a heavy economic burden. Traditional Chinese medicine injections (TCMIs) have significant effects on heart failure with reduced ejection fraction (HFrEF). However, it is difficult for clinicians to identify the differences in clinical efficacy and safety of various TCMIs. The purpose of this study is to compare the efficacy and safety of various TCMIs for treating HFrEF by conducting a Bayesian network meta-analysis (NMA) and to further provide references for clinical decision-making. Methods: The clinical randomized controlled trials of TCMIs for treating HFrEF were searched in seven database from inception to August 3rd, 2021. The Cochrane collaboration's tool was used to assess the risk of bias. NMA was performed in a Bayesian hierarchical framework. The surface under the cumulative ranking curve (SUCRA), the multi-dimensional efficacy analysis, the comparison-adjusted funnel plot, and the node-splitting analysis were conducted using R software. Results: A total of 107 eligible RCTs involving 9,073 HFrEF patients and 6 TCMIs were included. TCMIs include Huangqi injection (HQ) also called Astragalus injection, Shenfu injection (SF), Shengmai injection (SGM), Shenmai injection (SM), Xinmailong injection (XML), and Yiqifumai lyophilized injection (YQFM). The results of NMA and SUCRA showed that with conventional treatment (CT) as a common control, in terms of clinical efficacy, CT + XML was most effective in New York Heart Association cardiac functional classification efficiency, brain natriuretic peptide, and N-terminal pro-brain natriuretic peptide; the CT + SM was most effective in 6-min walking test, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac output; the CT + YQFM was most effective in left ventricular ejection fraction; the CT + HQ was most effective in stroke volume; the CT + SF was most effective in Minnesota Living with Heart Failure Questionnaire. In terms of safety, there was no significant difference between CT + TCMIs and CT. Conclusion: This Bayesian network meta-analysis results show that the combination of qualified TCMIs and CT is more effective for HFrEF patients than CT alone, and CT + XML and CT + SM may be one of the potential optimal treatments. Also, the safety of these TCMIs needs to be further observed. However, due to some limitations, the conclusions need to be verified by more large-sample, double-blind, multi-center RCTs.

Novel three-dimensional bioglass functionalized gelatin nanofibrous scaffolds for bone regeneration.

The clinical use of FDA-approved bone morphogenetic proteins (BMPs) are impeded by high costs, super-high dosage requirement, short half-life, and other undesirable side effects. Therefore, designing a biomaterial that can promote new bone formation without using exogenous BMPs is highly desirable in clinical applications. In the present work, a new kind of nanofibrous scaffold composed of gelatin and 45S5 bioglass (GF/45S5 BG) was prepared through thermally induced phase separation method together with the particle leach technique (TIPS&P). In addition to the significantly higher mechanical strength, the composite scaffolds (GF/45S5 BG) significantly increased osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro compared with the neat scaffold (GF) without adding other biological agents, for example, BMPs or hormones. Most importantly, our in vivo studies also indicated that GF/45S5 BG scaffolds could directly promote ectopic bone regeneration in SD rats without exogenous BMP2. In summary, both in vitro and in vivo results indicated that the novel 45S5 bioglass functionalized GF nanofibrous scaffold is a promising alternative for bone tissue engineering.

A fatal myelosuppression, diarrhea and neurotoxicity induced by combination of irinotecan and tegafur-gimeracil-oteracil potassium in the treatment of colon cancer: a case report.

Chemical treatment is the vital pattern for colon cancer patients after surgery. Irinotecan and tegafur-gimeracil-oteracil potassium (S-1) combined chemotherapy is effective on metastatic colorectal cancer (mCRC). Nevertheless, patients receiving this combined chemotherapy might suffer the adverse drug reaction (ADR), such as myelosuppression and/or diarrhea, which could lead to poor prognosis. Here, we report a 76-year-old Chinese female who died due to the toxicity of combined therapy with irinotecan and S-1. This patient received irinotecan and S-1 combined therapy for 6 sessions after laparoscopic radical operation on colon cancer. After 6 sessions of chemotherapy, myelosuppression and severe diarrhea appeared with delirious accompanied. Antineoplastic agents were stopped immediately due to the appearance of III grade myelosuppression and IV grade diarrhea. Loperamide and octreotide were used to stop diarrhea, while granulocyte colony-stimulating factor (G-CSF) and recombinant human IL (IL-11) were used to improve blood cell count. Meanwhile, intravenous fluid replacement was continuously transfused to maintain water electrolyte balance. The patient remained continuous insanity and died 4 days after admission because of multiple organ failure, cardiac insufficiency, sever myelosuppression and ascending colon cancer. Myelosuppression is the principal toxicity associated with chemotherapy. And delayed-onset diarrhea is most frequently reported ADR of irinotecan, which could also be induced by S-1. Moreover, neurotoxicity is rarely reported as ADR for both irinotecan and S-1. Postoperative adjuvant chemotherapy should be carefully selected according to specific condition of patient. Blood routine examination should be monitored, and clinical manifestations should be carefully observed to ensure the safety and effectiveness of chemotherapy during the treatment.

Age-Dependent Resistance to Rhizoctonia solani in Sugar Beet.

Rhizoctonia crown and root rot of sugar beet (Beta vulgaris L.), caused by Rhizoctonia solani, continues to be one of the important concerns for the beet industry in Minnesota and North Dakota. Use of resistant cultivars is an important strategy in the management of R. solani in combination with seed treatment and timely fungicide application during the growing season. The objective of this greenhouse study was to determine how sugar beet plants responded to increasing age in resistance to R. solani. Each of three seed companies provided three commercial cultivars with varying R. solani resistance levels: susceptible, moderately resistant, and resistant. Seed were planted at a weekly interval to create different plant age groups from seed to 10-week-old plants, with growing degree days (GDD) ranging from 0 to 1,519 thermal time (°Cd). Seed and plants were all simultaneously inoculated with R. solani AG2-2-infested barley grains. Twenty-eight days after inoculation, plants were pulled and washed, and roots were evaluated for disease severity. All cultivars were highly susceptible to R. solani when inoculated at seed to 3 weeks old (0 to 464°Cd). At 4 and 5 weeks of plant age (617 to 766°Cd), resistant cultivars started to show significant resistance to R. solani. Proportion of the affected roots with disease score ≥ 5 followed a sigmoid response, declining with increased GDD in moderately resistant and resistant cultivars, whereas it continued to decline linearly with increased GDD in susceptible cultivars. This study demonstrated that sugar beet cultivars, regardless of their assigned level of R. solani resistance, were highly susceptible to the pathogen before they reached the six- to eight-leaf stage at 4 to 5 weeks (617 to 766°Cd) after planting. Therefore, additional protection in the form of seed treatment or fungicide application may be required to protect sensitive sugar beet seed and seedlings in fields with a history of R. solani under favorable environmental conditions.

[UPLC Fingerprints of Euphorbiae Ebracteolatae Radix and Its Vinegar-Processed Slices].

OBJECTIVE: To compare the qualities of Euphorbiae Ebracteolatae Radix from different original plants and its vinegar-processed slices. METHODS: UPLC fingerprints of Euphoria ebracteolata, Euphoria fischeriana and vinegar-processed slices of Euphoria ebracteolata were established on a Waters ODS column (100 mm x 2.1 mm, 1.8 µm), using jolkinolide B as the reference substance. A mixture of acetonitrile and water was used as the mobile phase in a gradient elution mode, with the flow rate of 0.4 mL/min, the column temperature at 30 degrees C and the UV detector at 210 nm. The UPLC analysis time was no more than 20 min. RESULTS: The qualities of Euphoria ebracteolata and its vinegar-processed slices were stable with similarities over 0.90, respectively. However, the fingerprints of the slices and their original crude drugs exhibited obvious difference on both number and the relative peak area of the common peaks. Meanwhile the similarities of the fingerprints of Euphoria fischeriana and Euphoria ebracteolata were less than 0.72, indicating significant difference of these two plants. CONCLUSION: The developed method is available for quality control of Euphorbiae Ebracteolatae Radix and mechanism exploration of its vinegar-processed slices.