Regulation of optimized new Shengmai powder on cardiomyocyte apoptosis and ferroptosis in ischemic heart failure rats: The mediating role of phosphatidylinositol-3-kinase/protein kinase B/tumor protein 53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.

Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases.

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field.

The Best Exercise Modality and Dose for Reducing Pain in Adults With Low Back Pain: A Systematic Review With Model-Based Bayesian Network Meta-analysis.

OBJECTIVE: To quantify the dose-response relationship between overall and specific exercise modalities and pain, in patients with nonspecific chronic low back pain (LBP). DESIGN: Systematic review with Bayesian network meta-analysis. LITERATURE SEARCH: We searched the Medline, Embase, Web of Science, Cochrane Library, Scopus, and SPORTDiscus databases from inception to June 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials of exercise interventions in adults with nonspecific chronic LBP and at least 1 pain outcome reported at the main trial end point. DATA SYNTHESIS: A random-effects network meta-analysis was conducted. We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0, and used the GRADE approach to judge the certainty of evidence for each outcome. RESULTS: Eighty-two trials were included (n = 5033 participants). We found a nonlinear dose-response relationship between total exercise and pain in patients with nonspecific chronic LBP. The maximum significant response was observed at 920 MET minutes (standardized mean difference = -1.74; 95% credible intervals: -2.43, -1.04). The minimal clinically important difference for achieving meaningful pain improvement was 520 MET minutes per week. The dose to achieve minimal clinically important difference varied by type of exercise; Pilates was the most effective. The certainty of the evidence was very low to moderate for all outcomes. CONCLUSION: The dose-response relationship of different exercise modalities to improve pain in patients with nonspecific chronic LBP had a U-shaped trajectory and low- to moderate-certainty evidence. The clinical effect was most pronounced with Pilates exercise. J Orthop Sports Phys Ther 2024;54(5):1-13. Epub 8 March 2024. doi:10.2519/jospt.2024.12153.

Characterization and childhood exposure assessment of toxic heavy metals in household dust under true living conditions from 10 China cities.

Health hazards caused by metal exposure in household dust are concerning environmental health problems. Exposure to toxic metals in household dust imposes unclear but solid health risks, especially for children. In this multicenter cross-sectional study, a total of 250 household dust samples were collected from ten stratified cities in China (Panjin, Shijiazhuang, Qingdao, Lanzhou, Luoyang, Ningbo, Xi'an, Wuxi, Mianyang, Shenzhen) between April 2018 and March 2019. Questionnaire was conducted to gather information on individuals' living environment and health status in real-life situations. Multivariate logistic regression and principal component analysis were conducted to identify risk factors and determine the sources of metals in household dust. The median concentration of five metals in household dust from 10 cities ranged from 0.03 to 73.18 µg/g. Among the five heavy metals, only chromium in household dust of Mianyang was observed significantly both higher in the cold season and from the downwind households. Mercury, cadmium, and chromium were higher in the third-tier cities, with levels of 0.08, 0.30 and 97.28 µg/g, respectively. There were two sources with a contribution rate of 38.3 % and 25.8 %, respectively. Potential risk factors for increased metal concentration include long residence time, close to the motorway, decoration within five years, and purchase of new furniture within one year. Under both moderate and high exposure scenarios, chromium showed the highest level of exposure with 6.77 × 10-4 and 2.28 × 10-3 mg·kg-1·d-1, and arsenic imposed the highest lifetime carcinogenic risk at 1.67 × 10-4 and 3.17 × 10-4, respectively. The finding highlighted the priority to minimize childhood exposure of arsenic from household dust.

Targeting MAPK-ERK/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure.

Myocardial fibrosis is a significant pathological basis of heart failure. Overactivation of the ERK1/2 and JNK1/2 signaling pathways of MAPK family members synergistically promotes the proliferation of myocardial fibroblasts and accelerates the development of myocardial fibrosis. In addition to some small molecule inhibitors and Western drugs, many Chinese medicines can also inhibit the activity of ERK1/2 and JNK1/2, thus slowing down the development of myocardial fibrosis, and are generally safe and effective. However, the specific biological mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis still need to be fully understood, and there is no systematic review of existing drugs and methods to inhibit them from improving myocardial fibrosis. This study aims to summarize the roles and cross-linking mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis and to systematically sort out the small-molecule inhibitors, Western drugs, traditional Chinese medicines, and non-pharmacological therapies that inhibit ERK1/2 and JNK1/2 to alleviate myocardial fibrosis. In the future, we hope to conduct more in-depth research from the perspective of precision-targeted therapy, using this as a basis for developing new drugs that provide new perspectives on the prevention and treatment of heart failure.

Effect of high-intensity interval training on cardiorespiratory in children and adolescents with overweight or obesity: a meta-analysis of randomized controlled trials.

Objective: This meta-analysis aimed to examine the effect of high-intensity interval training on cardiorespiratory fitness in children and adolescents with overweight or obesity, and to explore the optimal dose of high-intensity interval training to improve cardiorespiratory fitness in children and adolescents with overweight or obesity. Methods: Randomized controlled trials on the effects of HIIT on cardiorespiratory fitness in children and adolescents with overweight or obesity were retrieved from six electronic databases, including PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. The quality assessment of the included studies was conducted following the revised quality evaluation method based on the PRISMA principles. Keywords for literature search mainly include high-intensity interval, cardiorespiratory fitness, overweight, obese, children, and adolescent, etc. Results: (1) A total of 18 studies, comprising 581 participants (288 in the intervention group and 293 in the control group), were included and all of them were of moderate to high quality. (2) HIIT had a positive effect on the cardiorespiratory fitness levels of in children and adolescents with overweight or obesity (SMD = 0.91; 95% CI: 0.66, 1.15; p < 0.00001). (3) The improvement in cardiorespiratory fitness was more significant when the HIIT intervention lasted for more than 10 weeks (SMD = 1.04; 95% CI: 0.74, 1.34; p < 0.00001), was conducted 3 times per week, with 2 to 8 sets per session (SMD = 1.13; 95% CI: 0.71, 1.55; p < 0.00001), and maintained a ratio of approximately 1:1 between exercise and rest intervals (SMD = 1.11; 95% CI: 0.73, 1.50; p < 0.00001). Conclusion and recommendations: (1) Long-term HIIT can improve cardiorespiratory fitness in children and adolescents with overweight or obesity. (2) To achieve significant improvements in cardiorespiratory fitness in a short period, children and adolescents with overweight or obesity can engage in HIIT programs lasting for more than 10 weeks, conducted 3 times per week, with 2 to 8 sets per session, and a ratio of approximately 1:1 between exercise and rest intervals. Systematic Review Registration: Identifier: INPLASY202350033.

Optimized New Shengmai Powder modulation of cAMP/Rap1A signaling pathway attenuates myocardial fibrosis in heart failure.

BACKGROUND: Optimized New Shengmai Powder (ONSMP) is a traditional Chinese medicine formula with significant anti-heart failure and myocardial fibrosis effects, but the specific molecular biological mechanisms are not fully understood. METHODS: In this study, we first used network pharmacology to analyze the ONSMP's active ingredients, core signaling pathways, and core targets. Second, calculate the affinity and binding modes of the ONSMP components to the core targets using molecular docking. Finally, the heart failure rat model was established by ligating the left anterior descending branch of the coronary artery and assessing the effect of ONSMP on myocardial fibrosis in heart failure using echocardiography, cardiac organ coefficients, heart failure markers, and pathological sections after 4 weeks of drug intervention. The cAMP level in rat myocardium was determined using Elisa, the α-SMA and FSP-1 positive expression determined by immunohistochemistry, and the protein and mRNA levels of the cAMP/Rap1A signaling pathway were detected by Western Blotting and quantitative real-time PCR, respectively. RESULTS: The result shows that the possible mechanism of ONSMP in reducing myocardial fibrosis also includes the use of 12 active ingredients such as baicalin, vitamin D, resveratrol, tanshinone IIA, emodin, 15,16-dihydrotanshinone-i to regulate ß1-AR, AC6, EPAC1, Rap1 A, STAT3, and CCND1 on the cAMP/Rap1A signaling pathway, thereby inhibiting the proliferation of cardiac fibroblasts and reduce the excessive secretion of collagen, effectively improve cardiac function and ventricular remodeling in heart failure rats. CONCLUSION: This research shows that ONSMP can inhibit myocardial fibrosis and delay heart failure through the cAMP/Rap1A signaling pathway.

Potential dosimetric error in the adaptive workflow of a 1.5 T MR-Linac from patient movement relative to immobilisation systems.

In magnetic resonance- (MR-) based adaptive workflows for an MR-linac, the treatment plan is optimized and recalculated online using the daily MR images. The Unity MR-linac is supplied with a patient positioning device (ppd) using pelvic and abdomen thermoplastic masks attached to a board with high-density components. This study highlights the dosimetric effect of using this in such workflows when there are relative patient-ppd displacements, as these are not visualized on MR imaging and the treatment planning system assumes the patient is fixed relative to the ppd. The online adapted plans of two example rectum cancer patients treated at a Unity MR-linac were perturbed by introducing relative patient-ppd displacements, and the effect was evaluated on plan dosimetry. Forty-eight perturbed clinical adapted plans were recalculated, based on online MR-based synthetic computed tomography, and compared with the original plans, using dose-volume histogram parameters and gamma analysis. The target volume covered by the prescribed dose ( D pre ) and by at least 107% of D pre varied up to - 1.87% and + 3.67%, respectively for 0.5 cm displacements, and to - 3.18% and + 4.96% for 2 cm displacements; whilst 2%-2 mm gamma analysis showed a median value of 92.9%. The use of a patient positioning system with high-density components in a Unity MR-based online adaptive treatment workflow can introduce unrecognized errors in plan dosimetry and it is recommended not to use such a device for such treatments, without modifying the device and the workflow, followed by careful clinical evaluation, or alternatively to use other immobilization methods.

Convenient determination of serum HER-2 status in breast cancer patients using Raman spectroscopy.

Given the significant therapeutic efficacy of anti-HER-2 treatment, the HER-2 status is a crucial piece of information that must be obtained in breast cancer patients. Currently, as per guidelines, HER-2 status is typically acquired from breast tissue of patients. However, there is growing interest in obtaining HER-2 status from serum and other samples due to the convenience and potential for dynamic monitoring. In this study, we have developed a serum Raman spectroscopy technique that allows for the rapid acquisition of HER-2 status in a convenient manner. The established HER-2 negative and positive classification model achieved an area under the curve of 0.8334. To further validate the reliability of our method, we replicated the process using immunohistochemistry and in situ hybridization. The results demonstrate that serum Raman spectroscopy, coupled with artificial intelligence algorithms, is an effective technical approach for obtaining HER-2 status.

Physical activity on executive function in sedentary individuals: Systematic review and meta-analysis of randomized controlled trials.

Physical activity has been demonstrated to promote cognitive performance. However, the relationship between physical activity and executive function (EF) in sedentary individuals is not fully understood. This meta-analysis examined the impact of physical activity on EF in sedentary individuals and evaluated potential moderators of the relationship between physical activity and EF. In accordance with the PRISMA guidelines, the electronic databases MEDLINE, Embase, PsycINFO and Web of Science were searched. Included studies had to report sedentary individuals randomized to either a physical activity group or a control group. Subgroup analyses of EF sub-domains, exercise prescription and age were conducted alongside the overall meta-analysis. Thirteen RCT studies were included, with a total of 752 participants. Results showed a small to moderate beneficial effect of physical activity on EF (SMD = 0.24, 95% CI 0.08 to 0.40). In subgroup analysis by EF sub-domains, physical activity enhanced inhibitory control (SMD = 0.38, 95% CI 0.12 to 0.63) and working memory (SMD = 0.22, 95% CI -0.05 to 0.49), but not cognitive flexibility (SMD = 0.11, 95% CI -0.18 to 0.41). Interventions with an intervention length > 12 weeks improved overall EF (SMD = 0.26, 95% CI 0.06 to 0.46), but intervention length ≤ 12 weeks did not (SMD = 0.20, 95% CI -0.08 to 0.47). Interventions with session time ≥ 45 minutes improved overall EF (SMD = 0.47, 95% CI 0.22 to 0.77), but session time < 45 minutes did not (0.17, 95% CI -0.11 to 0.44). Physical activity improves EF for older adults (age ≥ 60 years) (SMD = 0.25, 95% CI 0.08 to 0.42), but not for younger individuals (age < 60 years) (SMD = 0.17, 95% CI -0.25 to 0.59). Overall, physical activity has a beneficial effect on EF in sedentary individuals, although the influence may be domain specific and influenced by exercise prescription and age. These findings have practical implications for those seeking to improve EF in sedentary individuals through physical activity.

Entropy-driven reactions for controlling CRISPR/Cas12a and constructing an electrochemical biosensor for cardiac biomarkers detection.

An electrochemical biosensor is reported for controlling CRISPR/Cas12a activity through the utilization of entropy-driven reactions, alongside the construction of a highly sensitive biosensor for B-type natriuretic peptide (BNP) detection. In the biosensor, entropy-driven reactions are employed to regulate the activity of CRISPR/Cas12a - a gene editing tool - capable of nonspecific cleavage of single-stranded DNA (ssDNA). The biosensor architecture encompasses an electrode that is modified with ssDNA probes designed to hybridize with target BNP aptamers. These aptamers, furnished with labeled ssDNA triggers, facilitate the activation of CRISPR/Cas12a through interaction with its guide RNA. Upon the presence of BNP, it associates with the aptamers, subsequently liberating the triggers that instigate the entropy-driven reactions. As a consequence of these reactions, more stable duplexes emerge between the triggers and guide RNA, thereby activating CRISPR/Cas12a. The activated CRISPR/Cas12a subsequently executes cleavage of ssDNA probes residing on the electrode surface, culminating in the generation of an electrochemical signal directly (the calibration plots of differential pulse voltammetric detection were acquired at a working potential of 0.2 V (vs. ref. electrode)) proportional to the BNP concentration. Validation of the biosensor's performance is undertaken, wherein BNP detection is demonstrated in both buffer and human serum samples. Evident in the findings is the biosensor's discernible sensitivity and specificity for BNP detection, exemplified by a detection limit of 13.53 fM and a lack of interference originating from other cardiac biomarkers, respectively. Furthermore, the biosensor's potential to discriminate between healthy individuals and those afflicted by heart failure, predicated on distinctive BNP levels, is illustrated.

[Establishment of a Rat Model of Hypotension Induced by Reserpine].

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.

Risk Prediction Models and Novel Prognostic Factors for Heart Failure with Preserved Ejection Fraction: A Systematic and Comprehensive Review.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have large individual differences, unclear risk stratification, and imperfect treatment plans. Risk prediction models are helpful for the dynamic assessment of patients' prognostic risk and early intensive therapy of high-risk patients. The purpose of this study is to systematically summarize the existing risk prediction models and novel prognostic factors for HFpEF, to provide a reference for the construction of convenient and efficient HFpEF risk prediction models. METHODS: Studies on risk prediction models and prognostic factors for HFpEF were systematically searched in relevant databases including PubMed and Embase. The retrieval time was from inception to February 1, 2023. The Quality in Prognosis Studies (QUIPS) tool was used to assess the risk of bias in included studies. The predictive value of risk prediction models for end outcomes was evaluated by sensitivity, specificity, the area under the curve, C-statistic, C-index, etc. In the literature screening process, potential novel prognostic factors with high value were explored. RESULTS: A total of 21 eligible HFpEF risk prediction models and 22 relevant studies were included. Except for 2 studies with a high risk of bias and 2 studies with a moderate risk of bias, other studies that proposed risk prediction models had a low risk of bias overall. Potential novel prognostic factors for HFpEF were classified and described in terms of demographic characteristics (age, sex, and race), lifestyle (physical activity, body mass index, weight change, and smoking history), laboratory tests (biomarkers), physical inspection (blood pressure, electrocardiogram, imaging examination), and comorbidities. CONCLUSION: It is of great significance to explore the potential novel prognostic factors of HFpEF and build a more convenient and efficient risk prediction model for improving the overall prognosis of patients. This review can provide a substantial reference for further research.

Comparative analysis of dosimetric and radiobiological models of IPSA and HIPO algorithms in combined intra-cavitary/interstitial brachytherapy for cervical cancer.

Purpose: To compare inverse planning simulated annealing (IPSA) and hybrid inverse planning optimization (HIPO) using dosimetric and radiobiological models, and provide a basis for selecting the optimization method for cervical cancer. Material and methods: This was a retrospective study including 32 patients with radical cervical cancer. Brachytherapy treatment plans were re-optimized using IPSA, HIPO1 (with a locked uterine tube), and HIPO2 (with an unlocked uterine tube). Dosimetric data, including isodose lines, HR-CTV (D100, V150%, V200%, HI, and CI), and (bladder, rectum, and intestines) D1cc, D2cc for organs at risk (OARs) were also collected. Additionally, TCP, NTCP, BED, and EUBED were calculated, and differences were analyzed using matched samples t-test and Friedman test. Results: Compared with IPSA and HIPO2, HIPO1 had better V150% and V200% (p < 0.05). Compared with IPSA and HIPO1, HIPO2 had better D100 and CI (p < 0.05). The doses to the bladder D1cc (4.72 ±0.33 Gy)/D2cc (4.47 ±0.29 Gy) and rectum D1cc (4.50 ±0.61 Gy)/D2cc (4.11 ±0.63 Gy) were lower in HIPO2 than in IPSA and HIPO1. EUBEDs for HR-CTV were higher in HIPO1 and HIPO2 than in IPSA by 1.39-1.63%. However, TCPs were not remarkably different among the three plans (p > 0.05). Also, the NTCP for the bladder was lower in HIPO2 than in IPSA and HIPO1 by 13.04% and 16.67%, respectively. Conclusions: Although the dosimetric parameters of IPSA, HIPO1, and HIPO2 are comparable, HIPO2 provides better dose conformability and lower NTCP. Therefore, HIPO2 is recommended as an optimization algorithm in IC/ISBT for cervical cancer.

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.

The criterion for dividing the surrounding rock EDZs of underground caverns based on the energy dissipation degree.

An energy calculation parameter named the energy dissipation degree (RUd) is introduced based on the analysis of the energy dissipation mechanism and energy evolution characteristics during conventional triaxial tests of the granite of Shuangjiangkou. The deviatoric stress‒strain curve of rock can be divided into five stages using four stress thresholds (crack closure stress σcc, crack initiation stress σci, damage stress σcd and peak stress σp), which also correspond to the four RUd thresholds (RUdc, RUdi, RUdd and RUdp) on the energy dissipation degree-strain curve. A given stress threshold increases with increasing confining pressure; however, a given RUd threshold is basically stable under different confining pressures. Then, a new criterion for dividing the excavation damaged zones (EDZs) in the rock surrounding underground caverns based on the monotonically increasing characteristics of the energy dissipation degree‒axial strain relationship curve is proposed, and it allows for the classification of the surrounding rock into five types of zones through quantitative analysis of the RUd thresholds. Based on the criterion for dividing the EDZs of the surrounding rock mass of the underground cavern, the EDZs of the surrounding rocks of the underground cavern group of the Shuangjiangkou Hydropower Station are analyzed. The distribution characteristics of the EDZs of the rock surrounding underground caverns obtained by numerical simulation calculations based on RUd are basically the same as those obtained by in situ elastic wave tests. However, the RUd-based method for classifying the EDZs of the surrounding rock has the obvious advantage of being able to probe the boundaries of the undamaged zone (UDZ) of the surrounding rock more explicitly, while the method based on wave velocity testing is not sufficiently explicit. The damage zoning of the surrounding rock based on RUd can provide support design advice for the excavation of the surrounding rock, such as the support method, the length of the free section and anchor section of the prestressing anchor, etc.

Mechanism of new optimized Sheng-Mai-San Formula to regulate cardiomyocyte apoptosis through NMDAR pathway.

Background and objectives: Ischemic heart failure (HF) has become a disease that seriously endangers people's life and health. As a herbal formula widely used in clinical practice, new optimized Sheng-Mai-San (NO-SMS) has been shown to be significantly effective in improving cardiac function, increasing exercise tolerance, and slowing the progression of myocardial fibrosis in heart failure patients in multi-center clinical studies in various regions of China. In our previous pharmacodynamic and toxicological studies, we found that a medium-dose formulation (8.1 g of raw drug/kg) was the most effective in the treatment of heart failure, but its mechanism of action is still being investigated. The present study is exploring its relationship with cardiomyocyte apoptosis. Materials and methods: We investigated and verified this through two parts of experiments, in vivo and in vitro. Firstly, we prepared male SD rats with heart failure models by ligating the left anterior descending branch of the coronary artery (EF ≤ 50%), which were treated with NO-SMS Formula (8.1 g of raw drug/kg/d), Ifenprodil (5.4 mg/kg/d) or Enalapril (0.9 mg/kg/d) prepared suspensions by gavage for 4 weeks. The cardiac and structural changes were evaluated by echocardiography, H&E, and MASSON staining. The apoptosis of cardiomyocytes in each group was detected by Western blot, qRT-PCR, and ELISA. In vitro cell experiments include H9c2 cardiomyocyte injury induced by H2O2 and NMDA respectively, and the groups were incubated with NO-SMS and Ifenprodil-containing serum for 24 h. Apoptosis was detected by Annexin V-FITC/PI double-staining method, and the rest of the assays were consistent with the in vivo experiments. Results: Compared with the model group, the NO-SMS formula group and the Ifenprodil group could significantly improve cardiac function, delay myocardial fibrosis, reduce the expression of pro-apoptotic proteins, mRNA, and the concentration levels of Ca2+ and ROS in heart failure rats and H9c2 cardiomyocytes with H2O2 and NMDA-induced injury, which could significantly reduce the apoptosis rate of damaged cardiomyocytes and effectively inhibit the apoptosis of cardiomyocytes. Conclusion: NO-SMS Formula improved cardiac function, inhibited ventricular remodeling and cardiomyocyte apoptosis in HF rats, and its mechanism may be related to the regulation of the NMDAR signaling pathway, inhibition of large intracellular Ca2+ inward flow, and ROS production in cardiomyocytes.

The impact of COVID-19 lockdown on the quality of life of Chinese football referees: the chain mediating role of occupational stress and job burnout.

BACKGROUND: COVID-19 lockdown measures have had a great negative impact on the development of sports competition in China, as well as on the quality of life of football referees. This study aims to explore the impact of lockdown measures implemented in response to the COVID-19 pandemic on the quality of life of football referees in China and its mechanism of action. METHODS: The Impact of Event Scale-Revised (IES-R), the Effort-Reward Imbalance Scale (ERI), the Maslach Burnout Inventory General Survey (MBI-GS), and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). The scale was used from August to September 2022. Using an online questionnaire, 350 questionnaires were sent out and 338 were returned, for a return rate of 96.57%. Invalid questionnaires were excluded, and 307 football referees with referee grades in 29 provinces registered with the CFA were surveyed. SPSS 24.0 and Mplus 8.0 were used for data analysis and structural equation model testing in this study. RESULTS: The results showed that the COVID-19 lockdown had no significant impact on the quality of life of Chinese football referees. However, the COVID-19 lockdown can affect the quality of life of Chinese football referees through occupational stress or job burnout. Occupational stress and job burnout also play a chain intermediary role between the COVID-19 lockdown and the quality of life of Chinese football referees. In addition, this study further explores the quality of life by dividing it into four dimensions (physical, social, psychological, and environmental). The results show that all four dimensions satisfy the chain mediation model. CONCLUSIONS: Therefore, the quality of life of Chinese football referees can be improved by reducing their occupational stress and job burnout during the COVID-19 lockdown.

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.

Effect of optimized new Shengmai powder on exercise tolerance in rats with heart failure by regulating the ubiquitin-proteasome signaling pathway.

Introduction: Decreased exercise tolerance is a common symptom in patients with heart failure, which is closely related to protein degradation and apoptosis regulated by the ubiquitin-proteasome signaling (UPS) pathway. In this study, the effect of Chinese medicine, optimized new Shengmai powder, on exercise tolerance in rats with heart failure was investigated via the UPS pathway. Methods: The heart failure model was prepared by ligating the left anterior descending branch of the coronary artery in rats, in which the sham-operated group was only threaded and not ligated. Rats (left ventricular ejection fraction ≤ 45%) were randomly divided into the following groups: model group, YHXSMS group, Benazepril group, and proteasome inhibitor Oprozomib group, and they were administered the corresponding drugs by gavage for 4 weeks. The cardiac function of rats was evaluated by performing an echocardiography examination and a hemodynamic test and the exercise tolerance was done by conducting an exhaustive swimming test. The mechanism was revealed by TUNEL detection, immunohistochemistry, immunofluorescence analysis, Western blot, and quantitative real-time PCR. Results: The study showed that there was a decrease in cardiac function and exercise tolerance of rats in the model group and also destruction of cardiac and skeletal muscle fibers, a proliferation of collagen tissue, and an increment of apoptosis. Our study suggested that optimized new Shengmai powder could exert antiapoptotic effects on myocardial and skeletal muscle cells and improve myocardial contractility and exercise tolerance by inhibiting the overactivation of the UPS pathway, downregulating MAFbx, and Murf-1 overexpression, inhibiting the activation of the JNK signaling pathway, upregulating bcl-2 expression, and decreasing bax and caspase-3 levels. Conclusions: The study showed that the optimized new Shengmai powder could improve cardiac function and exercise tolerance in rats with heart failure through the UPS pathway.