Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction.

Background: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. Methods: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF. Results: In 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P < 0.001), despite analogous action potential durations. Furthermore, isolated ventricular myocytes from male mice showed a distinctly lower sodium current density (-29.20 ± 3.04 pA/pF, n = 6) in comparison to female mice (-114.05 ± 6.41 pA/pF, n = 6, P < 0.001). This decreased sodium current density was paralleled by a reduced membrane expression of Nav1.5 protein (0.38 ± 0.06 vs. 0.89 ± 0.09 A.U., P < 0.001) and increased cytosolic Nav1.5 levels (0.59 ± 0.06 vs. 0.29 ± 0.04 A.U., P = 0.001) in male mice. Furthermore, it was observed that the overall expressions of sorting nexin 27 (SNX27) and vacuolar protein sorting 26 (VPS26) were significantly diminished in male mice as compared to female littermates (0.91 ± 0.15 vs. 1.70 ± 0.28, P = 0.02 and 0.74 ± 0.09 vs. 1.57 ± 0.13, P < 0.01, respectively). Conclusions: Our findings reveal that male STEMI patients with early VT/VF are associated with elevated L5 levels. The gender-based discrepancy in early VT/VF predisposition might be due to compromised sodium channel trafficking, possibly linked with increased LDL electronegativity.

Effectiveness of Chinese herbal medicine compared with angiotensin II receptor blockers in patients with diabetic kidney disease: A hospital-based matched cohort study.

Angiotensin II receptor blockers (ARBs) are one of the standard treatments for diabetic kidney disease (DKD). Some patients may opt for Chinese herbal medicine (CHM) of their own free will. However, there is no real-world evidence regarding the effectiveness and safety of CHM. We aimed to explore the effectiveness of CHM for DKD in comparison to ARBs. We enrolled 732 DKD patients (72 used only CHM and 661 used ARBs) from 2007 to 2016, and all patients were followed until December 2016 at China Medical University Hospital in Taiwan. A total of 355 ARB users and 71 CHM users were analyzed after propensity score matching. The estimated glomerular filtration rate (eGFR) after treatment was 84.9 ± 28.1 ml/min/1.73 m2 in CHM users, which was higher than that (67.8 ± 35.4 ml/min/1.73 m2) in ARB users (p < 0.001). The change in the eGFR was -6.0 ± 21.4 ml/min/1.73 m2 in CHM users and -12.9 ± 24.8 ml/min/1.73 m2 in ARB users (p = 0.029). The blood urea nitrogen (BUN) and creatinine levels of patients taking CHM were 22 ± 16 mg/dl and 0.9 ± 0.4 mg/dl, respectively, and were lower than those (30 ± 28 mg/dl and 1.7 ± 2.0 mg/dl) of patients taking ARBs (p = 0.025 and p = 0.003). Using linear regression with adjustments for age, sex, BMI, baseline eGFR, and HbA1c levels, we found that the declines in the eGFR/baseline eGFR and changes in the urine albumin-creatinine ratio (ACR) were comparable between the two groups (p = 0.86 and 0.73). This study suggests that CHM may have comparable effectiveness to ARBs, which provides insights for further investigations.

Effect of acupuncture on ischaemic stroke in patients with rheumatoid arthritis: a nationwide propensity score-matched study.

OBJECTIVE: To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA). DESIGN: A propensity score-matched cohort study. SETTING: A nationwide population-based study. PARTICIPANTS: Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan. INTERVENTIONS: Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort. PRIMARY OUTCOME MEASURES: A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models. RESULTS: After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p<0.001; immortal time (period from initial diagnosis of RA to index date) 1065 days; mean number of acupuncture visits 9.83. In the end, 341 patients in the acupuncture cohort (5.95 per 1000 person-years) and 605 patients in the no-acupuncture cohort (12.4 per 1000 person-years) experienced ischaemic stroke (adjusted SHR 0.57, 95% CI 0.50 to 0.65). The advantage of lowering ischaemic stroke incidence through acupuncture therapy in RA patients was independent of sex, age, types of drugs used, and comorbidities. CONCLUSIONS: This study showed the beneficial effect of acupuncture in reducing the incidence of ischaemic stroke in patients with RA.

The Association between Acupuncture Therapy and the Risk of Disability Development in Dementia Patients: A Nationwide Cohort Study.

Purpose: Disability is the comorbidity of dementia for which there is no available preventive measure. The aim of this study was to investigate the association between acupuncture treatment and the risk of disability development in dementia patients. Patients and Methods: A cohort study was performed using a nationwide health database in Taiwan. The included dementia patients were divided into acupuncture and non-acupuncture cohorts based on whether they received acupuncture treatment during the follow-up period. The variables in the two cohorts were controlled by 1:1 propensity-score matching. The difference in disability development in dementia patients between the acupuncture and non-acupuncture cohorts was also analyzed. Subgroup analyses were performed using socioeconomic variables, comorbidities and anti-dementia agents (donepezil, rivastigmine, galantamine and memantine) used for dementia treatment. Results: A total of 9,760 dementia patients met our inclusion criteria, and patients were divided into an equal number (n=2,422) of acupuncture and non-acupuncture groups, respectively, after 1:1 propensity-score matching. The dementia patients had a lower risk of disability development after acupuncture treatment than those who did not receive acupuncture treatment (adjusted hazard ratio 0.65, 95% confidence interval 0.60-0.70, p < 0.001). The results were independent of basic variables or comorbidities in the two cohorts. Patients who did not use anti-dementia agents had a lower risk of developing disability after receiving acupuncture intervention than those who used anti-dementia agents. Conclusion: Our results revealed the relationship between acupuncture intervention and decreased risk of developing disability in dementia patients. The results are useful for dementia treatment, trial design and further planning of care programs.

Green synthesis of gardenia seeds-based carbon dots for bacterial imaging and antioxidant activity in aqueous and oil samples.

In this work, luminescent carbon dots with gardenia seeds as carbon precursors (GCDs) were synthesized using a one-step mild pyrolysis process and were then used as probes for imaging of bacterial (Escherichia coli). The GCDs showed a strong emission at 430 nm when excited at 370 nm. The relative fluorescence quantum yield of GCDs was found to be 1.13% in an aqueous medium. Rapid internalization of the GCDs by bacteria was confirmed by three colors (blue, green, and yellow) images that were obtained using confocal fluorescence microscopy. In addition, GCDs were noted to exhibit potent scavenging activities against DPPH˙, ˙OH, and ˙O2- free radicals. GCDs were also assayed as antioxidants in an oil sample by volumetric determination of the peroxide value. Thus, GCDs exhibited good antioxidant properties both in aqueous and oil media. In addition, a free fatty acid quantification kit in the presence of GCDs showed enhanced fluorescence detection of palmitic acid with a remarkably good limit of detection of 0.08 µM, which is lower than that in the absence of GCDs (0.76 µM). The proposed fluorescence method was then successfully used to determine the concentration of palmitic acid spiked in milk powder samples, with spiked recoveries of 82.6-109.6% and relative standard deviations of 0.9-4.6%.

The association between acupuncture therapy and the risk of reduced pressure ulcers in dementia patients: A retrospective matched cohort study.

Background: The pressure ulcer is a complication developed from dementia. The aim of this study is to study the association between the development of pressure ulcers and the use of acupuncture therapy in patients with dementia. Methods: We performed a retrospective 1:1 propensity score-matched cohort study to investigate the association between acupuncture therapy and the risk of pressure ulcers in patients with dementia. Results: A total of 8,994 patients were identified, 237 patients in the acupuncture cohort and 362 patients in the no-acupuncture cohort developed pressure ulcers. A reduced cumulative incidence of pressure ulcers was observed in the acupuncture cohort (P<0.001). The association between acupuncture and reducing the incidence of pressure ulcers was not affected by sex, age, residence, income, or comorbidities. The variables of etiologies to cause dementia did not change the final result. In the subgroups analyses, the patients without medication for dementia control had a significantly lower rate of pressure ulcers development when they had accepted acupuncture therapy (log-rank test, P<0.001). Conclusion: Our results revealed the association between acupuncture therapy and a reduced incidence of pressure ulcer development in patients with dementia. This finding offers important ideas for further research.

Sympathetic Modulation in Cardiac Arrhythmias: Where We Stand and Where We Go.

The nuance of autonomic cardiac control has been studied for more than 400 years, yet little is understood. This review aimed to provide a comprehensive overview of the current understanding, clinical implications, and ongoing studies of cardiac sympathetic modulation and its anti-ventricular arrhythmias' therapeutic potential. Molecular-level studies and clinical studies were reviewed to elucidate the gaps in knowledge and the possible future directions for these strategies to be translated into the clinical setting. Imbalanced sympathoexcitation and parasympathetic withdrawal destabilize cardiac electrophysiology and confer the development of ventricular arrhythmias. Therefore, the current strategy for rebalancing the autonomic system includes attenuating sympathoexcitation and increasing vagal tone. Multilevel targets of the cardiac neuraxis exist, and some have emerged as promising antiarrhythmic strategies. These interventions include pharmacological blockade, permanent cardiac sympathetic denervation, temporal cardiac sympathetic denervation, etc. The gold standard approach, however, has not been known. Although neuromodulatory strategies have been shown to be highly effective in several acute animal studies with very promising results, the individual and interspecies variation between human autonomic systems limits the progress in this young field. There is, however, still much room to refine the current neuromodulation therapy to meet the unmet need for life-threatening ventricular arrhythmias.

Humoral and cellular immunity in three different types of COVID-19 vaccines against SARS-CoV-2 variants in a real-world data analysis.

BACKGROUND: An effective vaccine response is currently a critical issue in the control of COVID-19. Little is known about humoral and cellular immunity comparing protein-based vaccine with other types of vaccines. The relevance of basal immunity to antibody production is also unknown. METHODS: Seventy-eight individuals were enrolled in the study. The primary outcome were the level of spike-specific antibodies and neutralizing antibodies measured by ELISA. Secondary measures included memory T cells and basal immunity estimated by flow cytometry and ELISA. Correlations for all parameters were calculated using the nonparametric Spearman correlation method. RESULTS: We observed that two doses of mRNA-based Moderna mRNA-1273 (Moderna) vaccine produced the highest total spike-binding antibody and neutralizing ability against the wild-type (WT), Delta, and Omicron variants. The protein-based MVC-COV1901 (MVC) vaccine developed in Taiwan produced higher spike-binding antibodies against Delta and Omicron variants and neutralizing ability against the WT strain than the adenovirus-based AstraZeneca-Oxford AZD1222 (AZ) vaccine. Moderna and AZ vaccination produced more central memory T cells in PBMC than the MVC vaccine. However, the MVC vaccine had the lowest adverse effects compared to the Moderna and AZ vaccines. Surprisingly, the basal immunity represented by TNF-α, IFN-γ, and IL-2 prior to vaccination was negatively correlated with the production of spike-binding antibodies and neutralizing ability. CONCLUSION: This study compared memory T cells, total spike-binding antibody levels, and neutralizing capacity against WT, Delta, and Omicron variants between the MVC vaccine and the widely used Moderna and AZ vaccines, which provides valuable information for future vaccine development strategies.

Correlations between myocardial injury current and lead performance in His bundle pacing compared with left bundle branch area pacing and right ventricular septum pacing.

BACKGROUND: Conduction system pacing by implanting the lead in the His bundle (HBP) region or in the left bundle branch area (LBBAP) has gained popularity. Myocardial injury current (IC) is useful for predicting adequate lead fixation in right ventricular septal pacing (RVSP). OBJECTIVES AND METHODS: We compared the correlations between IC and lead performance among patients receiving HBP (n = 41), LBBAP (n = 53), and historical RVSP (n = 88). LBBAP was an alternative if optimal HBP was not achieved. A positive IC (STpost-screw-in - STpre-screw-in) was defined as > 0.2 mV or a > 25% ST elevation and prolongation of the ventricular electrograms > 10 ms from baseline. RESULTS: HBP patients with a positive IC (48%, 0.84 ± 0.4 V/0.4 ms) exhibited a similar pacing threshold to their LBBAP counterparts (76%, 0.75 ± 0.3 V/0.4 ms, p = 0.329), but a higher pacing threshold than their RVSP counterparts (67%, 0.50 ± 0.1 V/0.4 ms, p < 0.001) at implantation. The R-wave (5.70 ± 3.4 mV) and impedance (660.91 ± 140.8 Ω) were both lower than those of LBBAP (10.35 ± 6.0 mV, p = 0.002; 822.36 ± 235.8 Ω, p = 0.005) and RVSP (11.24 ± 4.9 mV, p < 0.001; 754.27 ± 126.4 Ω, p = 0.006) patients respectively at implantation. The trend of electrical parameter comparisons remained unchanged during follow-up (3.56 ± 1.4 months). Notably, HBP patients without ICs had a higher pacing threshold (1.24 ± 0.6 V/0.4 ms) compared to their LBBAP (0.73 ± 0.3 V/0.4 ms, p = 0.009) and RVSP (0.53 ± 0.1 V/0.4 ms, p < 0.001) counterparts at implantation and during follow-up. CONCLUSIONS: The detection of positive changes of myocardial ICs during HBP was associated with a better capture threshold equivalent to the LBBAP counterpart both at implantation and during short-term follow-up. Further large-scale studies with longer follow-up are necessary to confirm these findings.

PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Corrigendum: Artificial intelligence-assisted remote detection of ST-elevation myocardial infarction using a mini-12-lead electrocardiogram device in prehospital ambulance care.

[This corrects the article DOI: 10.3389/fcvm.2022.1001982.].

Implementation of an All-Day Artificial Intelligence-Based Triage System to Accelerate Door-to-Balloon Times.

OBJECTIVE: To implement an all-day artificial intelligence (AI)-based system to facilitate chest pain triage in the emergency department. METHODS: The AI-based triage system encompasses an AI model combining a convolutional neural network and long short-term memory to detect ST-elevation myocardial infarction (STEMI) on electrocardiography (ECG) and a clinical risk score (ASAP) to prioritize patients for ECG examination. The AI model was developed on 2907 twelve-lead ECGs: 882 STEMI and 2025 non-STEMI ECGs. RESULTS: Between November 1, 2019, and October 31, 2020, we enrolled 154 consecutive patients with STEMI: 68 during the AI-based triage period and 86 during the conventional triage period. The mean ± SD door-to-balloon (D2B) time was significantly shortened from 64.5±35.3 minutes to 53.2±12.7 minutes (P=.007), with 98.5% vs 87.2% (P=.009) of D2B times being less than 90 minutes in the AI group vs the conventional group. Among patients with an ASAP score of 3 or higher, the median door-to-ECG time decreased from 30 minutes (interquartile range [IQR], 7-59 minutes) to 6 minutes (IQR, 4-30 minutes) (P<.001). The overall performances of the AI model in identifying STEMI from 21,035 ECGs assessed by accuracy, precision, recall, area under the receiver operating characteristic curve, F1 score, and specificity were 0.997, 0.802, 0.977, 0.999, 0.881, and 0.998, respectively. CONCLUSION: Implementation of an all-day AI-based triage system significantly reduced the D2B time, with a corresponding increase in the percentage of D2B times less than 90 minutes in the emergency department. This system may help minimize preventable delays in D2B times for patients with STEMI undergoing primary percutaneous coronary intervention.

Mesenchymal stem cell therapy on top of triple therapy with remdesivir, dexamethasone, and tocilizumab improves PaO2/FiO2 in severe COVID-19 pneumonia.

Background: Despite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19. Methods: Hospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables. Results: Four out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34-126.75) to 227.50 (185.25-237.50) and then 349.56 (293.03-367.92) within 7 days after hUC-MSC infusion (P < 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50-237.61]; day 3: 100.00 [72.00-232.68]; day 7: 250.00 [71.00-251.43], P = 0.923). Conclusion: Transplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.

The effect of Tai Chi in elderly individuals with sarcopenia and frailty: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The potential role of Tai Chi in improving sarcopenia and frailty has been shown in randomized controlled trials (RCTs). This systematic review and meta-analysis aimed to examine the effect of Tai Chi on muscle mass, muscle strength, physical function, and other geriatric syndromes in elderly individuals with sarcopenia and frailty. METHODS: Systematic searches of the PubMed, Cochrane Library, PEDro, EMBASE, Web of Science, CINAHL, and Medline databases for RCTs published between 1989 and 2022 were conducted; the database searchers were supplemented with manual reference searches. The inclusion criteria were as follows: (1) the study was designed as a RCT; (2) Tai Chi was one of the intervention arms; (3) the participants had a minimum age of ≥ 60 years and were diagnosed with frailty or sarcopenia, and the diagnostic guidelines or criteria were mentioned; (4) the number of participants in each arm was ≥ 10; and (5) the outcome reports included ≥ 1 item from the following primary or secondary outcomes. The exclusion criteria were as follows: (1) non-RCT studies; (2) nonhuman subjects; (3) participants aged < 60 years; (4) no description of the diagnostic guidelines or criteria for frailty or sarcopenia in the text; and (5) reported outcomes not among the following primary or secondary outcomes. The primary outcomes were muscle mass, grip strength and muscle performance (gait speed, 30-second chair stand test (30CST), sit-to-stand test (SST), Timed up and go test (TUGT), balance, and the Short Physical Performance Battery (SPPB)). The secondary outcomes included the number of falls and fear of falling (FOF), diastolic blood pressure (DBP), Mini-Mental State Examination (MMSE) score, and depression and quality of life (QOL) assessments. RESULTS: Eleven RCTs were conducted from 1996 to 2022 in 5 countries that investigated 1676 sarcopenic or frail elderly individuals were included in the review. There were 804 participants in the Tai Chi exercise cohort and 872 participants in the control cohort (nonexercised (n = 5)/ exercise (n = 8)). The mean age of participants was 70-89.5 years and the numbers of participants from each arm in each study were 10-158. The majority of the participants practiced Yang-style Tai Chi (n = 9), and the numbers of movement ranged from 6 to 24. The prescriptions of training were 8-48 weeks, 2-7 sessions per weeks, and 30-90 min per session. Most studies used Tai Chi expert as instructor (n = 8). The lengths of follow-up period were 8-48 weeks. The results from our meta-analysis revealed significant improvements for Tai Chi compared to control group (nonexercise/ exercise) on measures of the 30CST (weighted mean difference (WMD): 2.36, 95% confidence interval (CI) 1.50-3.21, p < 0.00001, I2 = 87%), the TUGT (WMD: -0.72, 95% CI -1.10 to -0.34, p = 0.0002, I2 =0%), numbers of fall (WMD: -0.41, 95% CI -0.64 to -0.17, p = 0.0006, I2 =0%) and FOF (standardized MD (SMD): -0.50, 95% CI -0.79 to -0.22, p = 0.0006, I2 = 57%); and for Tai Chi compared to 'nonexercise' controls on measures of SST (WMD: -2.20, 95% CI -2.22 to -2.18, p < 0.00001), balance (SMD: 9.85, 95% CI 8.88-10.82, p < 0.00001), DBP (WMD: -7.00, 95% CI -7.35 to -6.65, p < 0.00001), MMSE (WMD: 1.91, 95% CI 1.73-2.09, p < 0.00001, I2 =0%), depression (SMD: -1.37, 95% CI -1.91 to -0.83, p < 0.00001) and QOL (SMD: 10.72, 95% CI 9.38-12.07, p < 0.00001). There were no significant differences between Tai Chi and control groups on any of the remaining 4 comparisons: body muscle mass (WMD: 0.53, 95% CI -0.18 to 1.24; P = 0.14; I2 =0%), grip strength (WMD: -0.06, 95% CI -1.98 to 1.86; P = 0.95; I2 =0%), gait speed (WMD: 0.05, 95% CI -0.11 to 0.20; P = 0.55; I2 =99%), and SPPB (WMD: 0.55, 95% CI -0.04 to 1.14; P = 0.07). The variables of bias summary, Tai Chi instructor, Tai Chi movements, and Tai Chi training duration without significant association with the 30CST or the TUGT through meta-regression analyses. CONCLUSIONS: Our results demonstrated that patients with frailty or sarcopenia who practiced Tai Chi exhibited improved physical performance in the 30-second chair stand test, the Timed up and go test, number of falls and fear of falling. However, there was no difference in muscle mass, grip strength, gait speed, or Short Physical Performance Battery score between the Tai Chi and control groups. Improvements in the sit-to-stand test, balance, diastolic blood pressure, Mini-Mental State Examination score, and depression and quality of life assessments were found when comparing the Tai Chi cohort to the nonexercise control cohort rather than the exercise control cohort. To explore the effectiveness of Tai Chi in sarcopenic and frail elderly individuals more comprehensively, a standardized Tai Chi training prescription and a detailed description of the study design are suggested for future studies.

Artificial intelligence-assisted remote detection of ST-elevation myocardial infarction using a mini-12-lead electrocardiogram device in prehospital ambulance care.

Objective: To implement an all-day online artificial intelligence (AI)-assisted detection of ST-elevation myocardial infarction (STEMI) by prehospital 12-lead electrocardiograms (ECGs) to facilitate patient triage for timely reperfusion therapy. Methods: The proposed AI model combines a convolutional neural network and long short-term memory (CNN-LSTM) to predict STEMI on prehospital 12-lead ECGs obtained from mini-12-lead ECG devices equipped in ambulance vehicles in Central Taiwan. Emergency medical technicians (EMTs) from the 14 AI-implemented fire stations performed the on-site 12-lead ECG examinations using the mini portable device. The 12-lead ECG signals were transmitted to the AI center of China Medical University Hospital to classify the recordings as "STEMI" or "Not STEMI". In 11 non-AI fire stations, the ECG data were transmitted to a secure network and read by available on-line emergency physicians. The response time was defined as the time interval between the ECG transmission and ECG interpretation feedback. Results: Between July 17, 2021, and March 26, 2022, the AI model classified 362 prehospital 12-lead ECGs obtained from 275 consecutive patients who had called the 119 dispatch centers of fire stations in Central Taiwan for symptoms of chest pain or shortness of breath. The AI's response time to the EMTs in ambulance vehicles was 37.2 ± 11.3 s, which was shorter than the online physicians' response time from 11 other fire stations with no AI implementation (113.2 ± 369.4 s, P < 0.001) after analyzing another set of 335 prehospital 12-lead ECGs. The evaluation metrics including accuracy, precision, specificity, recall, area under the receiver operating characteristic curve, and F1 score to assess the overall AI performance in the remote detection of STEMI were 0.992, 0.889, 0.994, 0.941, 0.997, and 0.914, respectively. During the study period, the AI model promptly identified 10 STEMI patients who underwent primary percutaneous coronary intervention (PPCI) with a median contact-to-door time of 18.5 (IQR: 16-20.8) minutes. Conclusion: Implementation of an all-day real-time AI-assisted remote detection of STEMI on prehospital 12-lead ECGs in the field is feasible with a high diagnostic accuracy rate. This approach may help minimize preventable delays in contact-to-treatment times for STEMI patients who require PPCI.

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization. Objectives: This phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention. Methods: Consenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period. Results: Eight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline. Conclusion: This pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Association of a Common NOS1AP Variant with Attenuation of QTc Prolongation in Men with Heroin Dependence Undergoing Methadone Treatment.

Background: The effects of methadone-induced severe prolongation of the corrected QT interval (QTc) and sudden cardiac death appear unpredictable and sex-dependent. Genetic polymorphisms in the nitric oxide synthase 1 adaptor protein (NOS1AP) have been implicated in QTc prolongation in general populations. We investigated whether common NOS1AP variants interact with methadone in relation to QTc prolongation in patients with heroin dependence. Methods: We genotyped 17 NOS1AP variants spanning the entire gene in heroin-dependent patients who received a 12-lead electrocardiography (ECG) examination both at baseline and during maintenance methadone treatment in Cohort 1 and only during maintenance methadone treatment in Cohort 2. The QT interval was measured automatically by the Marquette 12SL program, and was corrected for heart rate using Bazett's formula. Results: Cohort 1 consisted of 122 patients (age: 37.65 ± 8.05 years, 84% male, methadone dosage: 42.54 ± 22.17 mg/day), and Cohort 2 comprised of 319 patients (age: 36.9 ± 7.86 years, 82% male, methadone dosage: 26.08 ± 15.84 mg/day), with complete genotyping data for analyses. Before methadone, the QTc intervals increased with increasing age (r = 0.3541, p < 0.001); the age-adjusted QTc showed dose-dependent prolongation in men (r = 0.6320, p < 0.001), but abbreviation in women (r = −0.5348, p = 0.018) in Cohort 1. The pooled genotype-specific analysis of the two cohorts revealed that the QTc interval was significantly shorter in male carriers of the rs164148 AA variant than in male carriers of the reference GG genotype (GG: n = 262, QTc = 423 ± 1.4 ms; AA: n = 10, QTc = 404.1 ± 7 ms, p = 0.009), according to univariate analysis. The QTc remained shorter in male carriers of the rs164148 AA variant compared to GG genotype (423 ± 1.4 ms vs. 405.9 ± 6.9 ms, p = 0.016) in multivariate analysis after adjusting for age and methadone dosage. A cut-off QTc interval of <410 ms identifies 100% of AA carriers compared to none of GG carriers when receiving a daily methadone dosage of 30.6 ± 19.3 mg. There was no significant gene-drug interaction in contributing to the adjusted QTc (p = 0.2164) in male carriers of the rs164148 variants. Conclusions: Carriers of a common NOS1AP rs164148 AA genotype variant were associated with a shorter QTc interval in men receiving maintenance methadone treatment. This genetic polymorphism attenuates the QTc-prolonging effect by methadone, and thus may explain at least in part the unpredictable and heterogeneous risks for severe QTc prolongation and sudden cardiac death in patients on methadone.

Adoptive transfer of IL-4 reprogrammed Tc17 cells elicits anti-tumour immunity through functional plasticity.

Ability of IL-17-producing CD8+ T cells (Tc17) to transform into cytotoxic anti-tumour effectors makes them a promising candidate for immune effector cell (IEC) therapy. However, key factors regulating Tc17 reprogramming remain poorly defined, hindering translation of Tc17-based IEC use from bench to bedside. We probed the effects of multiple cytokines and underlying signalling pathways on Tc17 cells and identified pivotal role for IL-4 and PI3K/AKT in promoting Tc17 transformation into cytotoxic IFN-γ-producing IECs, an effect dependent on Eomes expression. IL-4 not only triggered Tc17 cytotoxicity, but also induced cell expansion, which significantly improved the antitumour potential of Tc17 cells compared to that of IFN-γ-producing CD8+ T cells (Tc1) in a murine model. Furthermore, IL-4/AKT signalling drove the upregulation of the T-cell receptor-associated transmembrane adaptor 1 (Trat1) in Tc17 cells to promote IL-4-induced T-cell receptor stabilization and Tc17 cytotoxicity. Finally, we proposed a possible procedure to expand human Tc17 from peripheral blood of cancer patients, and confirmed the function of IL-4 in Tc17 reprogramming. Collectively, these results document a novel IL-4/AKT/Eomes/Trat1 axis that promotes expansion and transformation of Tc17 cells into cytotoxic effectors with a therapeutic potential. IL-4 priming of Tc17 cells should be further explored as a cell therapy engineering strategy to generate IECs to augment anti-tumour responses.

The Association Between Acupuncture Therapies and Reduced Fracture Risk in Patients with Osteoarthritis: A Nationwide Retrospective Matched Cohort Study.

Objective: The aim of this study is to investigate the association between acupuncture therapy and the risk of fracture in patient with osteoarthritis (OA). Design: The authors performed a 1:1 propensity score-matched cohort study to analyze patient with OA between January 1, 1997 and December 31, 2010 through the Taiwanese National Health Insurance Research Database. Patients who received acupuncture therapy from the initial date of diagnosis of OA to December 31, 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture during the same follow-up period were defined as the no-acupuncture cohort. A Cox regression model was used to adjust for sex, age, comorbidities, prescription, and surgical experiences. Hazard ratios (HRs) were compared between the two cohorts. Results: A total of 3416 patients were identified after 1:1 propensity score matching. The patients had similar basic characteristics. In the final analysis, 292 patients in the acupuncture cohort (30.06 per 1000 person-years) and 431 patients in the no-acupuncture cohort (56.08 per 1000 person-years) developed fractures (adjusted HRs 0.57, 95% confidence interval 0.49-0.67). A reduced cumulative incidence of fracture was found in the acupuncture cohort (log-rank test, p < 0.001). The association between acupuncture and reducing the fracture incidence was independent of sex, comorbidities, drugs use, and surgical experiences. Conclusion: Their results revealed the association between acupuncture therapies and a reduced incidence of fracture development in patients with OA. This finding provides noteworthy ideas for further research.

Adjunctive Chinese Herbal Medicine Treatment is Associated With an Improved Survival Rate in Patients With Cervical Cancer in Taiwan: A Matched Cohort Study.

BACKGROUND: Cervical cancer is one of the most common cancers in Taiwan. Some patients take Chinese herbal medicine (CHM). However, very few current studies have ascertained the usage and efficacy of CHM in patients with cervical cancer. The aim of this study was to investigate the benefits of complementary CHM among patients with cervical cancer in Taiwan. METHODS: We included the newly diagnosed cervical cancer patients who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 2000 and 2010. The end of follow-up period was December 31, 2011. Patients who were less than 20 years old, had missing information for age, withdrew from the National Health Insurance (NHI) program during the follow-up period, or only received other TCM interventions such as acupuncture or tuina massage were excluded from our study. After performing 1:1 frequency matching by age and index date, we enrolled 7521 patients in both CHM and non-CHM user groups. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. RESULTS: According to the Cox hazard ratio model mutually adjusted for CHM use, age, comorbidity, treatment, and chemotherapeutic agents used, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.29, 95%CI = 0.27-0.31). The survival probability was higher for patients in the CHM group. Bai-Hua-She-She-Cao (Herba Oldenlandiae, synonym Herba Hedyotis diffusae) and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and Chinese herbal formula, respectively. CONCLUSIONS: Adjunctive CHM may have positive effects of reducing mortality rate and improving the survival probability for cervical cancer patients. Further evidence-based pharmacological investigations and clinical trials are warranted to confirm the findings in our study.