Gut microbiota influence frailty syndrome in older adults: mechanisms and therapeutic strategies.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

Supramolecular salicylic acid combined with niacinamide in chloasma: A randomized controlled trial.

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

Efficacy and safety of supramolecular active zinc in the treatment of scalp psoriasis: a multicentre, randomized, observed-blind, parallel-group, placebo- and active-controlled noninferiority trial.

BACKGROUND: Controlling the relapses of scalp psoriasis is a clinical issue. OBJECTIVES: To evaluate the efficacy and safety of a supramolecular active zinc antidandruff hair conditioner in managing scalp psoriasis (SP). METHODS: This multicentre randomized, observed-blind, parallel-group, placebo- and active-controlled noninferiority trial enrolled 211 patients with SP between October 2018 and June 2019. The participants were randomized 1 : 1 : 1 to the experimental (supramolecular active zinc antidandruff hair conditioner), placebo (supramolecular hydrogel) or positive control (calcipotriol ointment) group. The primary efficacy endpoint was the disease control rate at the end of the fourth week of treatment, measured using the Investigator's Global Assessment score. RESULTS: This study included 70, 70 and 71 participants in the experiment, control and placebo groups, respectively. The disease control rates of SP at the end of week 4 of treatment in the full-analysis set (FAS) were 39%, 25% and 37% in the experimental, placebo and control groups. The margin of superiority between the experimental and placebo groups was > 0 [96% confidence interval (CI) 13.22% (0.43% to ∞)] in the FAS. The experimental group was superior to the placebo group. The noninferiority margin between the experiment and control groups was > -15% [96% CI -1.43% (-14.91% to ∞)] in the FAS. The experimental group was not inferior to the control group. CONCLUSIONS: Supramolecular active zinc antidandruff hair conditioner was helpful for the treatment of SP, and it has good clinical efficacy in maintaining therapeutic effect and assisting in preventing the recurrence of psoriasis.

QiShenYiQi pill for myocardial collagen metabolism and apoptosis in rats of autoimmune cardiomyopathy.

CONTEXT: QiShenYiQi pill (QSYQ) is a traditional Chinese medicine with a myocardial protective effect. OBJECTIVE: To explore the effect of QSYQ on myocardial collagen metabolism in rats with autoimmune cardiomyopathy and explore the underlying mechanism from the aspect of apoptosis. MATERIALS AND METHODS: We established an autoimmune cardiomyopathy model using Lewis rats. The rats were then randomly divided into six groups (n = 8): control, model, 3-methyladenine (15 mg/kg, intraperitoneal injection), QSYQ low-dose (135 mg/kg, gavage), QSYQ medium dose (270 mg/kg, gavage), and QSYQ high-dose (540 mg/kg, gavage) for four weeks. Van Gieson staining was applied for myocardial pathological characteristics, TUNEL fluorescence for myocardial cell apoptosis, enzyme-linked immunosorbent assay (ELISA) for serum PICP, PIIINP, and CTX-I levels, and western blot analysis for type I/III myocardial collagen, Bcl-2, Bax, and caspase-3 proteins. RESULTS: Results showed that QSYQ (135, 270, or 540 mg/kg) significantly reduced the expression of myocardial type I/III collagen, and concentrations of serum PICP, PIIINP, and CTX-I in rats. Moreover, QSYQ could alleviate myocardial fibrosis more effectively at a higher dose. QSYQ could also inhibit myocardial apoptosis via downregulating Bcl-2 expression, and upregulating Bax and caspase-3 expression levels. DISCUSSION AND CONCLUSIONS: The QSYQ can improve myocardial collagen metabolism by inhibiting apoptosis, which provides a potential therapeutic approach for autoimmune cardiomyopathy.

QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy.

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is well known for improving the myocardial remodelling, but the dose-effect relationship of its intervention in the reparative myocardial fibrosis is still unclear. We investigated the effect of QSYQ on the reparative myocardial fibrosis in cardiac myosin-induced rats and explored its mechanism of action by regulating autophagy. The results indicated that QSYQ increased LVEF and LVFS, and decreased the LVEDD, LVESD, HMI, LVMI, myocardial inflammation histology score, and collagen volume fraction in a dose-dependent manner. In addition, QSYQ declined the number of autophagosomes, down-regulated the expression of myocardial Beclin-1 and LC3B, up-regulated the expression of myocardial p62 and increased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR. We provided evidence for that QSYQ could inhibit excessive myocardial autophagy by regulating the PI3K/Akt-mTOR pathway and can be a potential therapeutic approach in treating the cardiovascular diseases such as myocarditis and dilated cardiomyopathy.

Prevention and treatment of chronic heart failure through traditional Chinese medicine: Role of the gut microbiota.

In recent years, although the concept and means of modern treatment of chronic heart failure(CHF) are continually improving, the readmission rate and mortality rate are still high. At present, there is evidence that there is a link between gut microbiota and heart failure, so the intervention of gut microbiota and its metabolites is expected to become a potential new therapeutic target in heart failure. Traditional Chinese medicine(TCM) has apparent advantages in stabilizing the disease, improving heart function, and improving the quality of life. It can exert its effect by operating in the gut microbiota and is an ideal intestinal micro-ecological regulator. Therefore, this article will mainly discuss the advantages of traditional Chinese medicine in treating CHF, the relationship between traditional Chinese medicine and gut microbiota, the relationship between CHF and gut microbiota, and the ways of regulating gut microbiota by traditional Chinese medicine to prevent and treat CHF. It will specify the target and mechanism of traditional Chinese medicine treating heart failure by acting gut microbiota and provide ideas for the treatment of heart failure.

Endocrine organs of cardiovascular diseases: Gut microbiota.

Gut microbiota (GM) is a collection of bacteria, fungi, archaea, viruses and protozoa, etc. They inhabit human intestines and play an essential role in human health and disease. Close information exchange between the intestinal microbes and the host performs a vital role in digestion, immune defence, nervous system regulation, especially metabolism, maintaining a delicate balance between itself and the human host. Studies have shown that the composition of GM and its metabolites are firmly related to the occurrence of various diseases. More and more researchers have demonstrated that the intestinal microbiota is a virtual 'organ' with endocrine function and the bioactive metabolites produced by it can affect the physiological role of the host. With deepening researches in recent years, clinical data indicated that the GM has a significant effect on the occurrence and development of cardiovascular diseases (CVD). This article systematically elaborated the relationship between metabolites of GM and its effects, the relationship between intestinal dysbacteriosis and cardiovascular risk factors, coronary heart disease, myocardial infarction, heart failure and hypertension and the possible pathogenic mechanisms. Regulating the GM is supposed to be a potential new therapeutic target for CVD.

Crystallization control toward colorless cerium-doped scintillating glass.

The construction of cerium-doped materials is of great technological importance for various applications, including smart lighting, biological shielding and high-energy ray and particle detection. A major challenge is the efficient prevention of the undesired colorization after cerium doping. Here we present the nanocrystallization method for constructing colorless cerium-doped glass with extremely high cerium concentration (15 mol%). The structure and optical characterizations confirm that the notable color change of glass is associated with the precipitation of CeF3 crystalline phase during heat-treatment. The chemical state investigation shows that most of cerium ions exist in the form of Ce3+ in both the glass and glass-ceramic samples. The chemical environment study indicates a dramatic change in the local structure unit from -Ce-O- to -Ce-F-, which is believed to dominate the decoloring phenomenon in cerium doped glass. As a result, a significant improvement in the ultraviolet excited luminescence (~35 times enhancement in intensity) and scintillating performance can be achieved, pointing to potential applications in X-ray detection.

Fabrication of microchannels by space-selective control of phase separation in glass.

Microchannels have important scientific applications in many fields, because they enable precise control, manipulation, and analysis of fluid on a micrometer scale. Herein, we demonstrate an effective strategy for fabrication of microchannels, based on the space-selective phase separation in glass induced by a femtosecond laser. The proposed method shows its abilities in fabrication of three-dimensional microchannels with ∼5 mm length scale and a uniform cross section. Moreover, we also achieve the modulation of the morphology on the inner surface of microchannels by using objective lenses with various numerical-apertures. The physical mechanism of the phase separation and microstructure evolution is discussed. Our method provides new opportunities to fabricate microchannels with complex structures and multifunctional integration.

Effect and Mechanism of QiShenYiQi Pill on Experimental Autoimmune Myocarditis Rats.

BACKGROUND: To observe the effect of QiShenYiQi pill (QSYQ) on experimental autoimmune myocarditis rats, and to explore its mechanism of action. MATERIAL/METHODS: Lewis rats underwent the injection of myocardial myosin mixed with Freund's complete adjuvant were randomized into 3 groups: model, valsartan, and QSYQ groups. Rats injected with phosphate-buffered saline (PBS) mixed with Freund's complete adjuvant were used as the control group. Rats were euthanized at 4 and 8 weeks, and we weighed rat body mass, heart mass, and left ventricular mass. Myocardium sections were stained with hematoxylin and eosin (H&E) and Masson trichrome. Myocardial TGF-ß1 and CTGF protein expression was detected by immunohistochemistry, and myocardial TGF-ß1 and CTGF mRNA expression was detected by real-time qPCR. RESULTS: QSYQ reduced HMI and LVMI, as well as the histological score of hearts and CVF, which further decreased over time, and its effect was significantly greater than that of valsartan at 4 and 8 weeks. After 4 weeks, QSYQ inhibited the protein and mRNA expression of TGF-ß1 and CTGF, and its effect on lowering CTGF was significantly greater than that of valsartan. In addition, after 8 weeks, QSYQ also inhibited the protein and mRNA expression of CTGF, whereas there was no significant difference in the expression of myocardial TGF-ß1. CONCLUSIONS: This study provides evidence that QSYQ can improve cardiac remodeling of experimental autoimmune myocarditis rats. It also effectively improved the degree of myocardial fibrosis, which is related to the mechanism of regulation of TGF-ß1 CTGF.

A new perspective in the prevention and treatment of antitumor therapy-related cardiotoxicity: Intestinal microecology.

The continuous development of antitumor therapy has significantly reduced the mortality of patients with malignancies. However, the antitumor-related cardiotoxicity has become the leading cause of long-term mortality in patients with malignancies. Besides, the pathogenesis of antitumor-related cardiotoxicity is still unclear, and practical means of prevention and treatment are lacking in clinical practice. Therefore, the major challenge is how to combat the cardiotoxicity of antitumor therapy effectively. More and more studies have shown that antitumor therapy kills tumor cells while causing damage to sensitive tissues such as the intestinal mucosa, leading to the increased permeability of the intestine and the dysbiosis of intestinal microecology. In addition, the dysbiosis of intestinal microecology contributes to the development and progression of cardiovascular diseases through multiple pathways. Thus, the dysbiosis of intestinal microecology may be a potential mechanism and target for antitumor-related cardiotoxicity. We summarized the characteristics of intestinal microecology disorders induced by antitumor therapy and the association between intestinal microecological dysbiosis and CVD. And on this basis, we hypothesized the potential mechanisms of intestinal microecology mediating the occurrence of antitumor-related cardiotoxicity. Then we reviewed the previous studies targeting intestinal microecology against antitumor-associated cardiotoxicity, aiming to provide a reference for future studies on the occurrence and prevention of antitumor-related cardiotoxicity by intestinal microecology.

Comparison of a One- versus Two-Week Treatment with Famciclovir Upon Reductions in Pain and Occurrence of Postherpetic Neuralgia in Herpes Zoster: A Randomized Open-Label Trial.

Background: Herpes zoster (HZ) is an acute herpetic skin disease resulting from the varicella-zoster virus. Typically, this condition is treated with a one-week administration of antiviral drugs, including famciclovir, which can effectively control the symptoms during the acute phase and prevent the occurrence of postherpetic neuralgia (PHN). Objective: To investigate whether a longer, two-week, regimen would enhance the capacity for famciclovir to reduce pain and prevent the occurrence of postherpetic neuralgia. Methods: HZ patients were randomly divided into two groups who were treated with famciclovir for either a one- or two-week period. Following their respective famciclovir treatments, patients were assessed for potential differences in pain intensity as evaluated at 1, 2, 4, 8 and 12 weeks post-treatment. In addition, the occurrence of postherpetic neuralgia at three months after treatment was compared between the two groups. Results: Of the 86 patients initially enrolled, 80 completed the study with N=40 randomly assigned to each of the two groups. Pain scores decreased significantly at 1, 2, 4, 8 and 12 weeks after famciclovir treatments. There were no significant differences in pain scores, and the incidence of postherpetic neuralgia occurrence between the two groups. There were no statistically significant differences in reducing pain intensity or frequency of postherpetic neuralgia between the one-week and two-week treatment protocols. Conclusion: It suggests that longer administration of famciclovir has no further benefit in the treatment of herpes zoster in our study.

Shenmai injection ameliorates doxorubicin-induced myocardial injury by suppressing autophagy-apoptosis via miR-30a.

CONTEXT: Autophagy-apoptosis is the core mechanism of doxorubicin-induced myocardial injury. miR-30a is a pivotal factor in the regulation of autophagy and apoptosis. It remains unclear whether SMI exerts cardioprotective effect by regulating autophagy and apoptosis via miR-30a. OBJECTIVE: This study evaluates the effects of SMI on ameliorating doxorubicin-induced myocardial injury. MATERIALS AND METHODS: The level of LDH and CK, and the expression of miR-30a was detected. mCherry-EGFP-LC3B double fluorescence was used to observe autophagy flow. Apoptosis was detected by Annexin V/PI staining. Western Blot was used to estimate the expression of autophagy related proteins and apoptosis-related proteins. RESULTS: Compared with the control group, there were evidently decreased cell viability, elevated level of LDH and CK, down-regulated expression of miR-30a in the model group. Data from Western blot and fluorescence indicated that doxorubicin contributed to the elevated autophagy and apoptosis. Compared with the model group, there were increased cell viability, decreased level of LDH and CK, and up-regulated expression of miR-30a in the Shenmai group and the Shenmai + miR-30a inhibitor group. Meanwhile, the results manifested that there were suppressed autophagy flow accompanied by the down-regulated expression of Beclin-1, LC3-II, LC3-II/LC3-I and up-regulated expression of p62 protein, and declined apoptosis rate accompanied by the up-regulated Bcl2 expression and the down-regulated expression of Bax, Cleaved Caspase-9, Cleaved Caspase-9/Caspase-9, Cleaved Caspase-3, Cleaved Caspase-3/Caspase-3 in the Shenmai group and the Shenmai + miR-30a inhibitor group. DISCUSSION AND CONCLUSION: Shenmai injection inhibited autophagy and apoptosis via miR-30a, thereby alleviating doxorubicin-induced myocardial injury.

NLRP3 Inflammasome: a Novel Insight into Heart Failure.

Among numerous cardiovascular diseases, heart failure is a final and fatal stage, and its morbidity, mortality, and rehospitalization rate remain high, which reduces the exercise tolerance of patients and brings great medical burden and economic pressure to the society. Inflammation takes on a major influence in the occurrence, development, and prognosis of heart failure (HF). The NLRP3 inflammasome is a key node in a chronic inflammatory response, which can accelerate the production of pro-inflammatory cytokines IL-1ß and IL-18, leading to the inflammatory response. Therefore, whether it is possible to suppress the downstream factors of NLRP3 inflammasome and its signaling path is expected to provide a new intervention mediator for the therapy of heart failure. This article synopsizes the research progress of NLRP3 inflammasome in heart failure, to provide a reference for clinical treatment. CLINICAL RELEVANCE: This study explored the downstream factors of NLRP3 inflammasome and its signal pathway. Targeted drug therapy for NLRP3 inflammasome is expected to provide a new intervention target for the treatment of heart failure.

Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling.

Heart Failure (HF) has been one of the leading causes of death worldwide. Though its latent mechanism and therapeutic manipulation are updated and developed ceaselessly, there remain great gaps in the cognition of heart failure. High morbidity and readmission rates among HF patients are waiting to be addressed. Recent studies have found that myocardial energy metabolism was closely related to heart failure, in which substrate utilization, as well as intermediate metabolism disorders, insulin resistance, oxidative stress, and mitochondrial dysfunction, might underlie systolic dysfunction and progression of HF. This article centers on the changes and counteraction of cardiac energy metabolism in the failing heart. Therefore, targeting impaired energy provision is of great potential in the treatment of HF. And shifting the objective from traditional neurohormones to improving the cellular environment is expected to further optimize the management of HF.

[Item selection analysis based on quality of life scale in patients with viral myocarditis].

OBJECTIVE: To further select the items based on the pre-test version of quality of life scale in patients with viral myocarditis. METHODS: Totally 100 patients with viral myocarditis were enrolled in this study. Methodologies including frequency distribution, discrete trend, t-test, Cronbach's α coefficient, correlation coefficient and factor analysis were applied to select items from different perspectives. RESULTS: A total of 17 items were selected by frequency distribution method from the perspective of central tendency, 15 items were selected by discrete trend method from the perspective of sensitivity, 16 items were selected by t-test method from the perspective of sensitivity and discrimination, 16 items were selected by Cronbach's α coefficient method from the perspective of internal consistency, 12 items were selected by correlation coefficient method from the perspective of representation and independence, and 18 items were selected by factor analysis method from the perspective of representation. CONCLUSION: Item selection of quality of life scale in patients with viral myocarditis was successfully conducted based on the clinical epidemiological data using a variety of statistical methods.

Trimethylamine oxide: a potential target for heart failure therapy.

Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial 'water-sodium retention' mode to 'abnormal hemodynamics' mode, and subsequent to 'abnormal activation of neuroendocrine' mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.

The chemical components, action mechanisms, and clinical evidences of YiQiFuMai injection in the treatment of heart failure.

YiQiFuMai injection (YQFM), derived from Shengmai Powder, is wildly applied in the treatment of cardiovascular diseases, such as coronary heart disease and chronic cardiac insufficiency. YiQiFuMai injection is mainly composed of Radix of Panax ginseng C.A. Mey. (Araliaceae), Radix of Ophiopogon japonicus (Thunb.) Ker Gawl (Liliaceae), and Fructus of Schisandra chinensis (Turcz.) Baill (Schisandraceae), and Triterpene saponins, steroidal saponins, lignans, and flavonoids play the vital role in the potency and efficacy. Long-term clinical practice has confirmed the positive effect of YiQiFuMai injection in the treatment of heart failure, and few adverse events have been reported. In addition, the protective effect of YiQiFuMai injection is related to the regulation of mitochondrial function, anti-apoptosis, amelioration of oxidant stress, inhibiting the expression of inflammatory mediators, regulating the expression of miRNAs, maintaining the balance of matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMP/TIMP) and anti-hypoxia.

Structured Scintillators for Efficient Radiation Detection.

Scintillators, which can convert high-energy ionizing radiation into visible light, have been serving as the core component in radiation detectors for more than a century of history. To address the increasing application demands along with the concern on nuclear security, various strategies have been proposed to develop a next-generation scintillator with a high performance in past decades, among which the novel approach via structure control has received great interest recently due to its high feasibility and efficiency. Herein, the concept of "structure engineering" is proposed for the exploration of this type of scintillators. Via internal or external structure design with size ranging from micro size to macro size, this promising strategy cannot only improve scintillator performance, typically radiation stopping power and light yield, but also extend its functionality for specific applications such as radiation imaging and therapy, opening up a new range of material candidates. The research and development of various types of structured scintillators are reviewed. The current state-of-the-art progresses on structure design, fabrication techniques, and the corresponding applications are discussed. Furthermore, an outlook focusing on the current challenges and future development is proposed.

Preparation and Evaluation of Animal Models of Cardiotoxicity in Antineoplastic Therapy.

The continuous development of antineoplastic therapy has significantly reduced the mortality of patients with malignant tumors, but its induced cardiotoxicity has become the primary cause of long-term death in patients with malignant tumors. However, the pathogenesis of cardiotoxicity of antineoplastic therapy is currently unknown, and practical means of prevention and treatment are lacking in clinical practice. Therefore, how to effectively prevent and treat cardiotoxicity while treating tumors is a major challenge. Animal models are important tools for studying cardiotoxicity in antitumor therapy and are of great importance in elucidating pathophysiological mechanisms and developing and evaluating modality drugs. In this paper, we summarize the existing animal models in antitumor therapeutic cardiotoxicity studies and evaluate the models by observing the macroscopic signs, echocardiography, and pathological morphology of the animals, aiming to provide a reference for subsequent experimental development and clinical application.