Research hotspots and trends on acupuncture treatment for headache: a bibliometric analysis from 2003 to 2023.

Background: While acupuncture treatment has gained extensive usage in addressing headaches, there remains a notable gap in the literature analysis for this field. Therefore, this study aims to conduct a literature review using Citespace, VOSviewer, and Bibliometrix, aiming to examine the current status, strengths, and potential future directions in the utilization of acupuncture for headache treatment. Methods: Relevant literature on acupuncture treatment for headaches between 2003 and 2023 was retrieved from the Web of Science (WoS) core database. Utilizing CiteSpace 6.1.R6, VOSviewer 1.6.18, and Bibliometrix 4.1.4, we conducted bibliometric analyses across various categories, including countries/regions, institutions, authors, journals, references, and keywords. Results: A total of 808 research reports were included. China and the United States have significantly contributed to this field. Chengdu University of Chinese Medicine holds the record for the highest number of published papers. Liu Lu has the highest publication output, while Linde K has the highest citation rate. MEDICINE leads in publication frequency, while CEPHALALGIA holds the highest citation rate. The Long-term Effect of Acupuncture for Migraine Prophylaxis a Randomized Clinical Trial is the most cited reference. Migraine was the most researched type. Filiform needle acupuncture was the most widely used stimulation method. The safety and efficacy of acupuncture have received significant attention. Modern mechanism research shows that depression, brain functional connectivity, and neuroimaging technology have become research hotspots in the acupuncture treatment of headaches. Conclusion: Acupuncture treatment for headaches has established a stable trend with a promising developmental trajectory. Research in this field mainly focuses on different acupuncture prevention and treatment for various types of headaches, the safety and efficacy of acupuncture, etc. Research on the mechanism of action mainly focuses on interpreting bidirectional and holistic regulation between pain and emotion by acupuncture and the regulation of brain function connection and neuroimaging technology by acupuncture. Future research should expand on the advantages and indications of acupuncture treatment for different headaches and their modern mechanisms.

A nomogram for predicting echocardiogram prescription in outpatients: an analysis of the NAMCS database.

Background and objective: Cardiovascular disease is the leading cause of morbidity and mortality globally. Echocardiography is a commonly used method for assessing the condition of patients with cardiovascular disease. However, little is known about the population characteristics of patients who are recommended for echocardiographic examinations. Methods: The National Ambulatory Medical Care Survey was a cross-sectional survey previously undertaken in the USA. In this study, publicly accessible data from the National Ambulatory Medical Care Survey database (for 2007-2016 and 2018-2019; data for 2017 was not published) were utilized to create a nomogram based on significant risk predictors. The study was performed in accordance with the relevant guidelines and regulations stipulated in the National Ambulatory Medical Care Survey database. Patients were randomly assigned to one of two groups: training cohort or validation cohort. The latter was used to assess the reliability of the prediction nomogram. Decision curve analysis was performed to evaluate the net benefit. Propensity score matching analysis was used to evaluate the relevance of echocardiography to clinical decision-making. Results: A total of 217,178 outpatients were enrolled. Multivariable logistic regression analysis demonstrated that hypertension, hyperlipidemia, coronary artery disease/ischemic heart disease/history of myocardial infarction, congestive heart failure, major reason for visit, metropolitan statistical area, cerebrovascular disease/history of stroke or transient ischemic attack, previously assessed, insurance, referred, diagnosis, and reason for visit were all predictors of echocardiogram prescription in outpatients. The reliability of the predictive nomogram was confirmed in the validation cohort. After propensity score matching, there was a significant difference in new cardiovascular agent prescriptions between the echocardiogram and no echocardiogram groups (P < 0.01). Conclusion: In this cohort study, a nomogram based on the characteristics of outpatients was developed to predict the possibility of prescribing echocardiography. The echocardiogram group was more likely to be prescribed new cardiovascular agents. These findings may contribute to providing information about the gap between actual utilizations and guidelines and the actual outpatient practice, as well as meeting the needs of outpatients.

Effects of perioperative exercise on cardiorespiratory endurance in children with congenital heart disease in plateau areas after surgical repair.

We aimed to explore the effects of perioperative exercise on cardiorespiratory endurance in children with congenital heart disease (CHD) in plateau areas after surgical repair. Fifty children with CHD in the plateau admitted to our hospital were randomly divided into the exercise and control groups. The exercise group received a perioperative exercise intervention beginning within 24 h postoperatively, while the control group received routine nursing and treatment alone. To assess the 6 min walk distance (6MWD) at baseline and at end of intervention, children participated in a 6-min walk test before cardiac repair and at 1 week after general ward transfer. A subset of children in the study underwent the cardiopulmonary exercise test pre-operatively. The 6MWD of children with CHD at baseline was positively correlated with the peak oxygen uptake pre-operatively. No significant difference was reported in the preoperative baseline data of both groups. The 6MWD of the exercise group was significantly higher than that of the control group. Early exercise therapy after cardiac repair could significantly improve the cardiorespiratory endurance and exercise capacity of children with CHD in plateau areas.

One-stop interventional procedure for bicuspid aortic stenosis in a patient with coexisting aortic coarctation: a case report.

Introduction: Coarctation of the aorta (CoA) is usually diagnosed and corrected early in life. Most untreated patients with CoA usually die before 50 years of age. Adult patients with concomitant CoA and severe bicuspid aortic stenosis are relatively rare and present complex management challenges without standard guidelines. Case summary: A 63-year-old female patient with uncontrolled hypertension was admitted due to chest pain and dyspnea upon exertion (NYHA grades III). Echocardiogram showed a severely calcified and stenotic bicuspid aortic valve (BAV). A severe stenotic calcified eccentric aortic coarctation 20 mm distal to the left subclavian artery (LSA) was discovered by computed tomography (CT) angiography. Following consultation with the cardiac team and patient willingness, we performed a one-stop interventional procedure to repair both defects. First, a cheatham-platinum (CP) stent was implanted via the right femoral access, immediately distal to the LSA. Due to the markedly twisted and angled descending aortic arch, we chose to perform transcatheter aortic valve replacement (TAVR) via the left common carotid artery. The patient was discharged and followed up for 1 year without symptoms. Discussion: Although surgery is still the main treatment for these diseases, it is not suitable for high-risk surgical patient. Transcatheter intervention for patients with severe aortic stenosis complicated with CoA simultaneously is rarely reported. The success of this procedure depends on the patient's vascular condition, the skills of the heart team, and the availability of the technical platform. Conclusion: Our case report demonstrates the feasibility and efficacy of a one-stop interventional procedure in an adult patient with concurrent severely calcified BAV and CoA via two different vascular approaches. Transcatheter intervention, in contrast to traditional surgical approaches or two-stop interventional procedures, as a minimally invasive and novel method, offers a wider range of therapeutic methods for such diseases.

Echocardiographic phenotype for refined risk stratification and treatment selection in light chain amyloidosis with heart failure.

AIMS: Light chain amyloidosis (AL) patients with heart failure (HF) are usually with revised Mayo (rMayo) stage III/IV disease and have a poor prognosis. We sought to investigate whether and what echocardiographic phenotype provides value for further risk stratification and guiding optimal risk-adapted treatment in this subgroup of AL patients. METHODS AND RESULTS: 95 AL patients who presented with HF and were on rMayo stage III/IV were retrospectively included. Of them, 51 patients (53.7%) were with stage III, 44 (46.3%) were with stage IV, and 44 (46.3%) underwent chemotherapy. Laboratory and echocardiographic measurements were acquired before the initiation of chemotherapy. The relevance of different variables with survival was assessed in the entire cohort, chemotherapy, and non-chemotherapy group. By Multivariate Cox regression analysis, right ventricular wall thickness (RVT) [HR 1.145, 95% confidence interval (CI) 1.026-1.279, P = 0.016], relative wall thickness (RWT) (HR 6.709, 95% CI 1.101-40.877, P = 0.039), and left ventricular ejection fraction (LVEF) < 50% (HR 1.939, 95% CI 1.048-3.590, P = 0.035) were found to be independently associated with survival in the entire cohort, RWT (HR 15.488, 95% CI 2.045-117.292, P = 0.008) in the non-chemotherapy group, and RVT (HR 1.331, 95% CI 1.054-1.681, P = 0.016) in the chemotherapy group, respectively. Kaplan-Meier survival analysis revealed that survival was significantly reduced in the presence of RVT ≥ 6.5 mm or LVEF < 50% in the entire cohort, and the significance of RVT ≥ 6.5 mm was irrespective of rMayo stages. In the chemotherapy group, survival was decreased if RVT ≥ 6.5 mm alone or together with RWT ≥ 0.67 were present, particularly in patients on rMayo stage IV. CONCLUSIONS: Echocardiographic phenotype provides incremental value beyond rMayo staging for predicting survival and could further guide treatment in advanced AL with HF. Those with high-risk echocardiographic phenotypes as higher RVT and RWT and lower LVEF had a worse prognosis.

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway.

PURPOSE: Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at Dazhui (GV14) and Jiaji points (T10), Yaoyangguan (GV3), Zusanli (ST36), and Ciliao (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested. RESULTS: After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI. CONCLUSION: Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

Establishment of a meta-analysis based novel aortic dissection mouse model.

Aortic dissection (AD) is a life-threatening disease and the detailed mechanism remains unclear. Thus, proper animal models are urgently required to better understand its pathogenesis. Our current study aims to establish a reliable, time and cost-effective mouse AD model. To conduct the meta-analysis, we searched PubMed for related studies up to 2021 and statistical analysis was conducted using Review Manager 5.4. For the animal experiment, 6-week-old male ApoE-/- mice were given ß-aminopropionitrile (BAPN) at a concentration of 1 g/L for 3 weeks before being infused with saline, 1000 ng/kg/min or 2500 ng/kg/min angiotensin II (AngII) via osmotic mini pumps for 2 or 4 weeks. To determine the presence of AD, we performed B-ultrasonography, hematoxylin and eosin (H&E) staining, and van Gieson staining. The result of the meta-analysis showed that the use of BAPN and more than 2000 ng/kg/min AngII can increase the rate of AD formation, whereas administrating Ang II for more than 28 days has no significant effect on the rate of AD formation when compared with the less than 14 days group. In the present study, mice treated with BAPN combined with 2500 ng/kg/min AngII for 2 weeks (12/20) had a significantly higher AD formation rate than mice treated with BAPN combined with 1000 ng/kg/min Ang II for 4 weeks (2/10), and had a similar model formation rate compared with the mice treated withß-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks (6/10). There were 3 mice (3/10) and 6 mice (6/20) who died in the group treated with ß-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks and 2 weeks respectively, and only one mouse (1/10) died in the group treated with ß-aminopropionitrile combined with 1000 ng/kg/min AngII for 4 weeks. In 6-week-old male ApoE-/- mice that received with 1 g/L BAPN in the drinking water for 3 weeks along with 2500 ng/kg/min AngII infusion via osmotic mini pumps for 2 weeks, the highest model formation rate and relative lower cumulative mortality were noted.

A New Coronavirus Estimation Global Score for Predicting Mortality During Hospitalization in Patients with COVID-19.

Objective: Coronavirus disease 2019 (COVID-19) exists as a pandemic. Mortality during hospitalization is multifactorial, and there is urgent need for a risk stratification model to predict in-hospital death among COVID-19 patients. Here we aimed to construct a risk score system for early identification of COVID-19 patients at high probability of dying during in-hospital treatment. Methods: In this retrospective analysis, a total of 821 confirmed COVID-19 patients from 3 centers were assigned to developmental (n = 411, between January 14, 2020 and February 11, 2020) and validation (n = 410, between February 14, 2020 and March 13, 2020) groups. Based on demographic, symptomatic, and laboratory variables, a new Coronavirus estimation global (CORE-G) score for prediction of in-hospital death was established from the developmental group, and its performance was then evaluated in the validation group. Results: The CORE-G score consisted of 18 variables (5 demographics, 2 symptoms, and 11 laboratory measurements) with a sum of 69.5 points. Goodness-of-fit tests indicated that the model performed well in the developmental group (H = 3.210, P = 0.880), and it was well validated in the validation group (H = 6.948, P = 0.542). The areas under the receiver operating characteristic curves were 0.955 in the developmental group (sensitivity, 94.1%; specificity, 83.4%) and 0.937 in the validation group (sensitivity, 87.2%; specificity, 84.2%). The mortality rate was not significantly different between the developmental (n = 85,20.7%) and validation (n = 94, 22.9%, P = 0.608) groups. Conclusions: The CORE-G score provides an estimate of the risk of in-hospital death. This is the first step toward the clinical use of the CORE-G score for predicting outcome in COVID-19 patients.

Relationship between Coronary Artery Tortuosity and Cardiorespiratory Fitness in Patients without Obstructed Coronaries.

OBJECTIVE: This study aimed to analyze the relationship between cardiorespiratory fitness (CRF) and the increasing severity of coronary artery tortuosity (CAT) in patients with non-stenosed coronaries. METHODS: A total of 396 patients who underwent coronary angiography and cardiopulmonary exercise testing (CPET) between August 2020 and July 2021 were included in this single-center retrospective study after excluding patients with significant coronary artery disease (≥50% stenosis). Patients were divided into two groups: no or mild coronary artery tortuosity (N/M-CAT) and moderate to severe coronary artery tortuosity (M/S-CAT) and laboratory electrocardiographic, echocardiographic, and CPET parameters were compared between two groups. RESULTS: M/S-CAT was found in 46.9% of the study participants, with 66.7% being women. M/S-CAT was significantly associated with advanced age (P=0.014) and females (P=0.001). Diastolic dysfunction parameters, E velocity (P=0.011), and E/A ratio (P=0.004) also revealed significant differences between the M/S-CAT group and N/M-CAT group. VO2@peak (1.22±0.39 vs. 1.07±0.39, P<0.01) and VO2@AT (0.77±0.22 vs. 0.71±0.21, P=0.017) were significantly lower in the M/S-CAT group than in the N/M-CAT group. Multivariate logistic regression analysis identified females (OR=0.448; 95% CI, 0.296-0.676; P=0.000) and E/A ratio (OR=0.307; 95% CI, 0.139-0.680; P=0.004) to be independent risk factors of M/S-CAT and showed no association of CPET parameters to M/S-CAT. CONCLUSION: The results indicate that increasing severity of CAT is strongly associated with female gender and E/A ratio and is not directly correlated with decreasing CRF. Further research with a larger patient population and a longer follow-up time is required to fully comprehend the impact of CAT on CRF.

Coronavirus disease 2019 death prediction by electrocardiographic abnormalities and elevated D-dimer levels.

Background: Electrocardiography (ECG) plays a very important role in various cardiovascular diseases and elevated D-dimer in serum associated with thrombosis. In patients with coronavirus disease 2019 (COVID-19), immense pieces of evidence showed that ECG abnormalities or elevated D-dimer in serum occurred frequently. However, it remains unclear whether ECG abnormalities combined with elevated D-dimer could be a new risk predictor in patients with COVID-19. Methods and results: This retrospective cohort study enrolled 416 patients with COVID-19 at Wuhan Tongji Hospital from 1 February to 20 March 2020. ECG manifestations, D-dimer levels, and in-hospital deaths were recorded for all patients. Logistic regression analysis was performed to examine the association between ECG manifestations and in-hospital mortality in patients with elevated D-dimer levels. In patients hospitalized for COVID-19, ST-T abnormalities (34.3%) were the most frequent ECG manifestations, whereas sinus tachycardia (ST) (13.3%) and atrial arrhythmias with rapid rhythms (8.5%) were the two most common cardiac arrhythmias. Compared to severely ill patients with COVID-19, ST-T abnormalities, ST and atrial arrhythmias (p<0.001) with rapid rhythms, D-dimer levels, and in-hospital deaths were significantly more frequent in critically ill patients with COVID-19. Moreover, elevated D-dimer levels were observed in all the patients who died. In the subgroup of 303 patients with elevated serum D-dimer levels, the patient's age, the incidence of ST-T abnormalities, ST, atrial fibrillation (AF), and atrial premature beat were significantly higher than those in the non-elevated D-dimer subgroup. Multivariate logistic regression analysis further revealed that ST and AF were risk factors for in-hospital mortality in COVID-19 patients with elevated D-dimer levels. Conclusions: ECG abnormalities and elevated D-dimer levels were associated with a higher risk of critical illness and death in patients hospitalized for COVID-19. ECG abnormalities, including ST and AF, combined with elevated D-dimer levels, can be used to predict death in COVID-19.

An echo score raises the suspicion of cardiac amyloidosis in Chinese with heart failure with preserved ejection fraction.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) has been realized as an important cause of heart failure with preserved ejection fraction (HFpEF). We aim to provide insights into its prevalence in Chinese HFpEF patients, which is not known to date, using increased wall thickness (IWT) score by echocardiography. METHODS: Consecutive patients with HFpEF (EF ≥ 40%) and IWT (≥12 mm) were prospectively screened. Echocardiography was performed, and the IWT score incorporated relative wall thickness, E/e' ratio, longitudinal strains, and tricuspid annular plane systolic excursion, and septal apical-to-base ratio was calculated. ATTR-CA was defined as score ≥8 in the absence of serum and urine free light chain. RESULTS: Six hundred twenty-four HFpEF patients from January 2019 to December 2021 were enrolled, of which 65.2% were males and the median (interquartile range [IQR]) age was 66 (IQR 57, 73) years. Thirty-three patients (5.3%, 95% CI 3.5-7.0%) were with score ≥8, and 33.3% were females. They were younger (58 vs. 69 years, P < 0.001), had higher NT-proBNP (6525.0 vs. 1741.5 pg/mL, P < 0.001) and troponin I (105.2 vs. 27.7 pg/mL, P = 0.001) level, and lower LVEF (47% vs. 57%, P < 0.001) compared with the patients with score <5. In the internal cohort (82 patients) who had undergone scintigraphy, the IWT score ≥8 was shown to have a sensitivity of 85.7% (95% CI 56.2-97.5%) and a specificity of 92.6% (95% CI 83.0-97.3%) for diagnosing CA, and the IWT score <5 had great accuracy in excluding CA with the negative predictive value of 100%, supporting the clinical usefulness of the IWT score to guide further dedicated testing for ATTR-CA. CONCLUSIONS: The IWT score by echocardiography was an excellent tool for screening ATTR-CA in HFpEF. In Chinese HFpEF patients associated with a hypertrophic phenotype, the proportion of highly suspected ATTR-CA as detected by IWT score ≥8 was 5.3%, lower than the reported prevalence of ATTR-CA in non-Asian patients with the disease.

The Value of Cardiopulmonary Exercise Testing in Predicting the Severity of Coronary Artery Disease.

Background: There have been a limited number of quantitative studies on the relationship between coronary artery disease (CAD) and cardiorespiratory fitness (CRF), as measured by cardiopulmonary exercise testing (CPET). Thus, we aimed to investigate the association between CRF and the severity of coronary artery disease from the most comprehensive perspective possible, and to affirm the predictive value of CPET in the severity assessment of CAD. Methods: Our study included 280 patients with coronary angiography, who had undergone CPET in Tongji Hospital. The patients' CRF was measured through their peak oxygen uptake (VO2@peak), their oxygen uptake at the anaerobic threshold (VO2@AT) and through other parameters of CPET on a bicycle ergometer. The severity of the coronary artery disease was assessed in the following three layers: functionally significant lesions (quantitative flow ratio [QFR] ≤ 0.8), the number of stenotic coronary arteries (SCA, stenosis ≥ 50%) and the Gensini score. The correlation analyses were carried out between the CRF and the severity of the coronary artery disease. A ROC curve was plotted, and the AUC was calculated to distinguish the severe CAD and the non-severe CAD patients, as measured by the QFR, the number of SCA, and the Gensini score. Results: The VO2@AT and VO2@peak were inversely associated with the QFR. The VO2@AT, VO2@peak and VO2/kg@peak were associated with the number of SCA. Meanwhile, the VO2@AT, VO2/kg@AT, VO2@peak and VO2/kg@peak were associated with the Gensini score. An ROC analysis proved that a combination of traditional clinical risk factors and the VO2@peak/VO2prediction is valuable in predicting CAD severity. Conclusions: Our study demonstrated a strong and inverse association between CRF and the severity of CAD. A combination of traditional clinical risk factors and CRF is valuable in predicting CAD severity.

ERK/RSK-mediated phosphorylation of Y-box binding protein-1 aggravates diabetic cardiomyopathy by suppressing its interaction with deubiquitinase OTUB1.

Diabetic cardiomyopathy (DCM) is a major complication of diabetes, but its underlying mechanisms still remain unclear. The multifunctional protein Y-box binding protein-1 (YB-1) plays an important role in cardiac pathogenesis by regulating cardiac apoptosis, cardiac fibrosis, and pathological remodeling, whereas its role in chronic DCM requires further investigation. Here, we report that the phosphorylation of YB-1 at serine102 (S102) was markedly elevated in streptozotocin-induced diabetic mouse hearts and in high glucose-treated cardiomyocytes, whereas total YB-1 protein levels were significantly reduced. Coimmunoprecipitation experiments showed that YB-1 interacts with the deubiquitinase otubain-1, but hyperglycemia-induced phosphorylation of YB-1 at S102 diminished this homeostatic interaction, resulting in ubiquitination and degradation of YB-1. Mechanistically, the high glucose-induced phosphorylation of YB-1 at S102 is dependent on the upstream extracellular signal-regulated kinase (ERK)/Ras/mitogen-activated protein kinase (p90 ribosomal S6 kinase [RSK]) signaling pathway. Accordingly, pharmacological inhibition of the ERK pathway using the upstream kinase inhibitor U0126 ameliorated features of DCM compared with vehicle-treated diabetic mice. We demonstrate that ERK inhibition with U0126 also suppressed the phosphorylation of the downstream RSK and YB-1 (S102), which stabilized the interaction between YB-1 and otubain-1 and thereby preserved YB-1 protein expression in diabetic hearts. Taken together, we propose that targeting the ERK/RSK/YB-1 pathway could be a potential therapeutic approach for treating DCM.

Pharmacologic IRE1α kinase inhibition alleviates aortic dissection by decreasing vascular smooth muscle cells apoptosis.

Aortic dissection (AD) is a rare but catastrophic disorder, and associated with significant morbidity among survivors. This study aimed to target IRE1α-XBP1s pathway pharmacologically, and evaluate its therapeutic potential in the occurrence and progression of AD. Western Blot and immunohistochemistry results showed that expression of XBP1s was significantly increased in the human aorta samples of AD group in compared with the control group, and exclusively in aortic vascular smooth muscle cells (VSMCs). Further in vitro study revealed that Angiotensin II (Ang II) could increase the expression of XBP1s and promote its nuclear translocation in cultured VSMCs, which leads to numerous gene transcription, including gp91phox, Chop, Cleaved-caspase 3, Bax, and Bcl-2. These genes contribute to the production of reactive oxygen species (ROS), VMSCs phenotypic switch and apoptosis. Whereas an IRE1α endoribonuclease domain inhibitor MKC-3946 could reverse it. Finally, the efficacy of MKC-3946 was tested in a mouse AD model. As shown in vitro, MKC-3946 could reduce the expression of XBP1s and protect against AD by suppressing XBP1s associated ROS production and apoptosis in VSMCs in vivo. The current study revealed the relevant role of IRE1α-XBP1s signaling pathway in AD occurrence and progression. MKC-3946 could be of great potential in clinical application.

Acupuncture combined with moxibustion promote the recovery of spinal cord injury in correlation with Shh/Gli-1 signaling pathway.

Objective: Acupuncture combined with moxibustion (AM) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The present study aimed to confirm the effect and mechanism of AM treatment on the recovery of SCI.Design: Male Sprague-Dawley rats were used to establish the SCI model by impact method. SCI rat models were subjected to AM treatment at Dazhui (GV14) and Jiaji points (T7-T12), Yaoyangguan (GV3), Zusanli (ST36) and Ciliao (BL32).Outcome measures: Motor function and cell apoptosis in rats after SCI. The mRNA and protein expression levels of Shh and Gli-1 were determined by real-time quantitative polymerase chain reaction, western blot and immunohistochemistry.Results: After AM treatment, the hindlimb motor function of SCI rats was significantly increased than the SCI group at 7, 9, 11, 14 days (P < 0.05). AM treatment 7 d and 14 d significantly preserved the nissl-stained positive neurons and significantly decreased number of apoptotic cells, compared to that of SCI 7 and 14 d groups (P < 0.05). AM treatment improved the mRNA protein levels of Shh and Gli-1 after 7 and 14 days treatment compared to the SCI group (P < 0.05).Conclusion: AM could improve the expression of Shh and Gli-1 in injured spinal cord of rats. That could be part of underlying mechanisms of AM treatment including recover motor function and preserve the neuron cells and alleviate the apoptosis of nerve cells in rats after SCI.

Zero-contrast PTRA and stenting for child with TRAS: A case report.

BACKGROUND: Kidney transplantation is often complicated by TRAS, and PTRA can effectively treat it. However, PTRA is not appropriate for patients with CKD because iodinated contrast agent may induce nephropathy. METHODS: This article reports about a 14-year-old boy with a history of kidney transplantation complicated by RAS. He initially underwent percutaneous balloon dilation to relieve the stenosis. One and half a year after dilation, he received zero-contrast PTRA and stenting under the guidance of external and IVUS with reference to previous PAG image. RESULTS: After successful stent implantation, the cross-sectional area of the renal artery lumen was significantly increased.The blood pressure and level of creatinine also decreased and kept stable during follow-up. CONCLUSION: This report suggests the feasibility of external ultrasound and IVUS guided, zero-contrast PTRA in patients with poor renal function or iodinated contrast allergy.

Activated Protein C Ameliorates Diabetic Cardiomyopathy via Modulating OTUB1/YB-1/MEF2B Axis.

Aims: The pathogenesis of diabetic cardiomyopathy (DCM) is complex and the detailed mechanism remains unclear. Coagulation protease activated Protein C (aPC) has been reported to have a protective effect in diabetic microvascular disease. Here, we investigated whether aPC could play a protective role in the occurrence and development of major diabetic complication DCM, and its underlying molecular mechanism. Methods and Results: In a mouse model of streptozotocin (STZ) induced DCM, endogenous aPC levels were reduced. Restoring aPC levels by exogenous administration of zymogen protein C (PC) improved cardiac function of diabetic mice measured by echocardiography and invasive hemodynamics. The cytoprotective effect of aPC in DCM is mediated by transcription factor Y-box binding protein-1 (YB-1). Mechanistically, MEF2B lies downstream of YB-1 and YB-1/MEF2B interaction restrains deleterious MEF2B promoter activity in DCM. The regulation of YB-1 on MEF2B transcription was analyzed by dual-luciferase and chromatin immunoprecipitation assays. In diabetic mice, aPC ameliorated YB-1 degradation via reducing its K48 ubiquitination through deubiquitinating enzyme otubain-1 (OTUB1) and improving the interaction between YB-1 and OTUB1. Using specific agonists and blocking antibodies, PAR1 and EPCR were identified as crucial receptors for aPC's dependent cytoprotective signaling. Conclusion: These data identify that the cytoprotective aPC signaling via PAR1/EPCR maintains YB-1 levels by preventing the ubiquitination and subsequent proteasomal degradation of YB-1 via OTUB1. By suppressing MEF2B transcription, YB-1 can protect against DCM. Collectively, the current study uncovered the important role of OTUB1/YB-1/MEF2B axis in DCM and targeting this pathway might offer a new therapeutic strategy for DCM. Translational Perspective: DCM is emerging at epidemic rate recently and the underlying mechanism remains unclear. This study explored the protective cell signaling mechanisms of aPC in mouse models of DCM. As a former FDA approved anti-sepsis drug, aPC along with its derivatives can be applied from bench to bed and can be explored as a new strategy for personalized treatment for DCM. Mechanistically, OTUB1/YB-1/MEF2B axis plays a critical role in the occurrence and development of DCM and offers a potential avenue for therapeutic targeting of DCM.

The MEK inhibitor U0126 ameliorates diabetic cardiomyopathy by restricting XBP1's phosphorylation dependent SUMOylation.

Background: Chronic diabetes accelerates vascular dysfunction often resulting in cardiomyopathy but underlying mechanisms remain unclear. Recent studies have shown that the deregulated unfolded protein response (UPR) dependent on highly conserved IRE1α-spliced X-box- binding protein (XBP1s) and the resulting endoplasmic reticulum stress (ER-Stress) plays a crucial role in the occurrence and development of diabetic cardiomyopathy (DCM). In the present study, we determined whether targeting MAPK/ERK pathway using MEK inhibitor U0126 could ameliorate DCM by regulating IRE1α-XBP1s pathway. Method: Three groups of 8-week-old C57/BL6J mice were studied: one group received saline injection as control (n=8) and two groups were made diabetic by streptozotocin (STZ) (n=10 each). 18 weeks after STZ injection and stable hyperglycemia, one group had saline treatment while the second group was treated with U0126 (1mg/kg/day), 8 weeks later, all groups were sacrificed. Cardiac function/histopathological changes were determined by echocardiogram examination, Millar catheter system, hematoxylin-eosin staining and western blot analysis. H9C2 cardiomyocytes were employed for in vitro studies. Results: Echocardiographic, hemodynamic and histological data showed overt myocardial hypertrophy and worsened cardiac function in diabetic mice. Chronic diabetic milieu enhanced SUMOylation and impaired nuclear translocation of XBP1s. Intriguingly, U0126 treatment significantly ameliorated progression of DCM, and this protective effect was achieved through enriching XBP1s' nuclear accumulation. Mechanistically, U0126 inhibited XBP1s' phosphorylation on S348 and SUMOylation on K276 promoting XBP1s' nuclear translocation. Collectively, these results identify that MEK inhibition restores XBP1s-dependent UPR and protects against diabetes-induced cardiac remodeling. Conclusion: The current study identifies previously unknown function of MEK/ERK pathway in regulation of ER-stress in DCM. U0126 could be a therapeutic target for the treatment of DCM.

Warm acupuncture therapy for Primary sciatica: A protocol of systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aims to assess the effectiveness and safety of warm acupuncture therapy for treating Primary sciatica. METHODS: The following 9 databases will be search from their inception to December 6, 2020: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Biomedical Literature Database (CBM), the Chinese Medical Current Content (CMCC), the Wan-Fang Database and the China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCTs) of warm acupuncture for treating Primary sciatica, Chinese or Japanese without restriction of publication status will be included. Two researchers will independently undertake study selection, extraction of data and assessment of study quality. Meta-analysis will be conducted after screening of studies. Data will be analyzed using risk ratio for dichotomous data, and standardized mean difference or weighted mean difference for continuous data. DISSEMINATION: This meta-analysis will be disseminated electronically through a peer-reviewed publication or conference presentations. CONCLUSION: This study will provide evidence to judge whether warm acupuncture. TRIAL REGISTRATION NUMBER: INPLASY2020120109.

Antiviral Abidol is Associated with the Reduction of In-Hospital Mortality in COVID-19 Patients.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global public health crisis. There are no specific antiviral agents for the treatment of SARS-CoV-2. Information regarding the effect of Abidol on in-hospital mortality is scarce. The present study aimed to evaluate the treatment effect of Abidol for patients with COVID-19 before and after propensity score matching (PSM). METHODS: This retrospective cohort study analyzed 1019 patients with confirmed COVID-19 in China from December 22, 2019 to March 13, 2020. Patients were divided to Abidol (200 mg, tid, 5-7 days, n = 788, 77.3%) and No-Abidol (n = 231, 22.7%) groups. The primary outcome was the mortality during hospitalization. RESULTS: Among 1019 COVID-19 patients, the age was (60.4 ±â€Š14.5) years. Abidol-treated patients, compared with No-Abidol-treated patients, had a shorter duration from onset of symptoms to admission, less frequent renal dysfunction, lower white blood cell counts (lymphocytes <0.8) and erythrocyte sending rate, lower interleukin-6, higher platelet counts and plasma IgG and oxygen saturation, and less frequent myocardial injury. The mortality during hospitalization before PSM was 17.9% in Abidol group and 34.6% in No-Abidol (hazard ratio (HR) = 2.610, 95% confident interval (CI): 1.980-3.440), all seen in severe and critical patients. After PSM, the in-hospital death was 13.6% in Abidol and 28.6% in No-Abidol group (HR = 2.728, 95% CI: 1.598-4.659). CONCLUSIONS: Abidol-treatment results in less in-hospital death for severe and critical patients with COVID-19. Further randomized study is warranted to confirm the findings from this study.