Pulmonary vein isolation using pulsed field ablation vs. high-power short-duration radiofrequency ablation in paroxysmal atrial fibrillation: efficacy, safety, and long-term follow-up (PRIORI study).

AIMS: Pulsed field ablation (PFA) is a novel, non-thermal, cardiac tissue-selective ablation modality. To date, radiofrequency (RF)-guided high-power short-duration (HPSD) ablation represents the gold standard besides cryo-ablation for pulmonary vein isolation (PVI). This single-centre, retrospective study investigated the efficacy of PFA-PVI vs. HPSD-RF PVI in terms of single-procedure arrhythmia-free outcome and safety in a real-world setting. METHODS AND RESULTS: Consecutive, paroxysmal atrial fibrillation (AF) patients who underwent PVI using PFA or HPSD-RF were enrolled. In group PFA, PVI was performed using a pentaspline PFA catheter. The ablation procedure in group HPSD-RF was performed with RF energy (45 W, ablation index). A total of 410 patients (group PFA, 201; group HPSD-RF, 209) were included. There was no difference between both groups regarding age, gender, and CHA2DS2-VASc score. The procedure time was significantly shorter in group PFA [61 (44-103) vs. 125 (105-143) min; P < 0.001]; fluoroscopy time and dose area product were significantly higher in group PFA [16 (13-20) vs. 4 (2-5) min; P < 0.01 and 412 (270-739) vs. 129 (58-265) µGym2; P < 0.01]. The overall complication rates were 2.9% in group PFA and 6.2% in group HPSD (P = 0.158). There was one fatal stroke in the PFA group. The 1-year Kaplan-Meier estimated freedom from any atrial tachyarrhythmia was 85% with PFA and 79% with HPSD-RF (log-rank P = 0.160). In 56 repeat ablation procedures, the PV reconnection rate was 30% after PFA and 38% after HPSD-RF (P = 0.372). CONCLUSION: Both PFA and HPSD-RF were highly efficient and effective in achieving PVI in paroxysmal AF patients. The arrhythmia-free survival is comparable. The PV reconnection rate was not different.

Combined healthy lifestyle behaviours and incident dementia: A systematic review and dose-response meta-analysis of cohort studies.

BACKGROUND: The associations of combined healthy lifestyle behaviours and incident dementia have not been systematically reviewed and the dose-response relationship was uncertain. OBJECTIVES: To evaluate the associations of combined healthy lifestyle behaviours with incident dementia and other cognitive outcomes, assess the dose-response relationship between the number of lifestyle behaviours and incident dementia, and summarise the adherence to healthy lifestyle behaviours. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, Web of Science and PsycINFO were searched from inception to 20 Jan 2024. Cohort studies reporting associations of combined healthy lifestyle behaviours with incident dementia or other cognitive outcomes were included. We used the random-effects meta-analysis to pool the risk estimates and the robust error meta-regression method to examine the dose-response relationship. The methodological quality was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 22 articles including 25 cohort studies mostly from high-income economics were included, with all assessed as high methodological quality. Adherence to a healthy lifestyle was associated with a decreased risk of incident dementia, either per healthy lifestyle behaviour increase (pooled hazard ratio 0.89, 95 % confidence interval 0.85-0.94) or the highest level versus the lowest level (pooled hazard ratio 0.61, 95 % confidence interval 0.49-0.76). An inverse, linear dose-response relationship (Pnon-linear = 0.845) between the number of healthy lifestyle behaviours and incident dementia was observed, with an 11 % risk reduction for each healthy behaviour increase. A relatively limited number of included studies indicated that adherence to a healthy lifestyle combination could yield benefits for cognitive decline, global cognition, memory and executive function. In addition, the adherence rates typically decreased as the number of healthy lifestyle behaviours increased. CONCLUSIONS: Adherence to a healthy lifestyle was associated with a lower risk of incident dementia and other cognitive outcomes. It is important to find a subtle balance between the benefits and adherence. Further large cohort studies for combined lifestyle behaviours with specific cognitive outcomes and dose-response relationships are required, especially based on middle- and low-income populations. REGISTRATION: The study was registered in PROSPERO (CRD42023418509). TWEETABLE ABSTRACT: Engaging in a greater number of healthy lifestyle behaviours yields increased benefits in preventing dementia, albeit with lower adherence rates as a trade-off. Finding a delicate balance between the benefits and adherence is crucial.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.

Effect of transcutaneous electrical acupoint stimulation based on the theory of "qi ascending and descending movement" on autonomic nervous system and gastrointestinal function in patients after general anesthesia laparoscopic cholecystectomy. / 基于"气机升降"ç†è®ºç»çš®ç©´ä½ç”µåˆºæ¿€å¯¹å ¨éº»è ¹è ”é•œèƒ†å›Šåˆ‡é™¤æœ¯åŽæ‚£è€ è‡ªä¸»ç¥žç»å’Œèƒƒè‚ åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) based on the theory of "qi ascending and descending movement" in patients after general anesthesia laparoscopic cholecystectomy, so as to explore the impact of TEAS on the autonomic nervous system and gastrointestinal function of patients. METHODS: A total of 204 patients scheduled to undergo general anesthesia laparoscopic cholecystectomy were selected and randomly divided into control, double acupoints and multiple acupoints groups, with 68 cases in each group. For patients in the multiple acupoints group, TEAS was applied at Zusanli (ST36), Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12), Taichong (LR3), and Neiguan (PC6) 30 min before anesthesia induction until the end of the surgery. In the double acupoints group, TEAS was applied only at ST36 and PC6. No electrical stimulation was applied in the control group. The postoperative bloating, bowel sound recovery time, first farting time, first defecation time, length of hospital stay, nausea and vomiting were compared among the three groups. Heart rate variability was monitored by twelve-lead electrocardiogram to evaluate the autonomic nervous function of the patients, including the low frequency power/high frequency power ratio (LF/HF), the standard deviation of all sinus RR intervals (SDNN), and the root mean square of difference between successive normal RR intervals (RMSSD). RESULTS: At 6 h and 24 h after surgery, the symptoms of bloating, nausea and vomiting in the multiple acupoints group and double acupoints group were significantly improved compared to the control group (P<0.05), and the multiple acupoints group was superior to the double acupoints group (P<0.05). Compared with the control group, the bowel sound recovery time, first farting time, first defecation time, and length of hospital stay were significantly shorter (P<0.05) in the multiple acupoints group and double acupoints group, and the multiple acupoints group was superior to the double acupoints group (P<0.05). At 1 d and 2 d after surgery, compared with the control group, LF/HF was decreased (P<0.05) while SDNN and RMSSD were increased (P<0.05) in the multiple acupoints group and double acupoints group, and there was a significant difference between the two groups (P<0.05). CONCLUSIONS: TEAS treatment based on the theory of "qi ascending and descending movement" can relieve gastrointestinal dysfunction, reduce early postoperative sympathetic nerve excitement and maintain parasympathetic nerve tension in patients after general anesthesia laparoscopic cholecystectomy, thereby promoting gastrointestinal function recovery.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Beneficial endophytic fungi improve the yield and quality of Salvia miltiorrhiza by performing different ecological functions.

Background: Endophytic fungi can enhance the growth and synthesis of secondary metabolites in medicinal plants. Salvia miltiorrhiza Bunge is frequently employed for treating cardiovascular and cerebrovascular ailments, with the primary bioactive components being salvianolic acid and tanshinone. However, their levels in cultivated S. miltiorrhiza are inferior to that of the wild herbs, so the production of high-quality medicinal herbs is sharply declining. Consequently, the utilization of beneficial endophytic fungi to improve the yield and quality of S. miltiorrhiza holds great significance for the cultivation of medicinal plants. Methods: In this study, nine non-pathogenic, endophytic fungal strains were introduced into sterile S. miltiorrhiza seedlings and cultivated both in vitro and in situ (the greenhouse). The effects of these strains on the growth indices, C and N metabolism, antioxidant activity, photosynthesis, and content of bioactive ingredients in S. miltiorrhiza were then evaluated. Results: The results showed that the different genera, species, or strains of endophytic fungi regulated the growth and metabolism of S. miltiorrhiza in unique ways. These endophytic fungi primarily exerted their growth-promoting effects by increasing the net photosynthetic rate, intercellular CO2 concentration, and the activities of sucrose synthase, sucrose phosphate synthase, nitrate reductase, and glutamine synthetase. They also enhanced the adaptability and resistance to environmental stresses by improving the synthesis of osmoregulatory compounds and the activity of antioxidant enzymes. However, their regulatory effects on the growth and development of S. miltiorrhiza were affected by environmental changes. Moreover, the strains that significantly promoted the synthesis and accumulation of phenolic acids inhibited the accumulation of tanshinones components, and vice versa. The endophytic fungal strains Penicillium meloforme DS8, Berkeleyomyces basicola DS10, and Acremonium sclerotigenum DS12 enhanced the bioaccumulation of tanshinones. Fusarium solani DS16 elevated the rosmarinic acid content and yields in S. miltiorrhiza. The strain Penicillium javanicum DS5 improved the contents of dihydrotanshinone, salvianolic acid B, and rosmarinic acid. The strains P. meloforme DS8 and B. basicola DS10 improved resistance. Conclusion: Various endophytic fungi affected the quality and yield of S. miltiorrhiza by regulating different physiological and metabolic pathways. This study also provides a novel and effective method to maximize the effects of beneficial endophytic fungi by selecting specific strains to design microbial communities based on the different ecological functions of endophytic fungi under varying environments and for specific production goals.

Development and validation of frailty and malnutrition knowledge assessment scale for community-dwelling older adults.

There is a lack of reliable tools to assess the knowledge of frailty and malnutrition in community-dwelling older adults. To develop and validate reliable frailty and malnutrition knowledge assessment scales for this population, two scales were developed and validated through five phases. Phase 1: the item pools were constructed through a literature review and research panel based on the symptom interpretation model. Phase 2: the expert consultation was performed to select the items. Phase 3: a pilot survey was conducted to assess the clarity of the items and further revise the scales. Phase 4: 242 older adults were surveyed to finalize the items. Phase 5: 241 older adults were surveyed to test the psychometric properties. The two scales each comprise 3 dimensions (symptoms, risk factors, and management strategies) and 11 items. They had good construct validity, with all indicators of correlation analysis and confirmatory factor analysis meeting their specific criteria. The reliability of the frailty and malnutrition knowledge assessment scales was good, with composite reliability coefficients all >0.60, Cronbach's alpha being 0.81 and 0.83, and the Spearman-Brown coefficient being 0.74 and 0.80, respectively. Their acceptability was good, with both having a completion rate of 92.18% and an average completion time of 3 min. The two scales are reliable tools to assess the knowledge of frailty and malnutrition among community-dwelling older adults, especially for large-scale surveys. They can help identify knowledge gaps in older adults and provide a basis for developing targeted educational interventions.

High-dimensional single-cell analysis unveils distinct immune signatures of peripheral blood in patients with pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with poor response to immune checkpoint inhibitors. The mechanism of such poor response is not completely understood. Methods: We assessed T-cell receptor (TCR) repertoire and RNA expression at the single-cell level using high-dimensional sequencing of peripheral blood immune cells isolated from PDAC patients and from healthy human controls. We validated RNA-sequencing data by performing mass cytometry (CyTOF) and by measuring serum levels of multiple immune checkpoint proteins. Results: We found that proportions of T cells (CD45+CD3+) were decreased in PDAC patients compared to healthy controls, while proportion of myeloid cells was increased. The proportion of cytotoxic CD8+ T cells and the level of cytotoxicity per cell were increased in PDAC patients, with reduced TCR clonal diversity. We also found a significantly enriched S100A9+ monocyte population and an increased level of TIM-3 expression in immune cells of peripheral blood in PDAC patients. In addition, the serum level of soluble TIM-3 (sTIM-3) was significantly higher in PDAC patients compared to the non-PDAC participants and correlated with worse survival in two independent PDAC cohorts. Moreover, sTIM-3 exhibited a valuable role in diagnosis of PDAC, with sensitivity and specificity of about 80% in the training and validation groups, respectively. We further established an integrated model by combining sTIM-3 and carbohydrate antigen 19- 9 (CA19-9), which had an area under the curve of 0.974 and 0.992 in training and validation cohorts, respectively. Conclusion: Our RNA-seq and proteomic results provide valuable insight for understanding the immune cell composition of peripheral blood of patients with PDAC.

Development and validation of knowledge assessment scales on sarcopenia and fall for Chinese community-dwelling older adults.

AIM: This study aimed to develop and validate sarcopenia and fall knowledge assessment scales for community-dwelling older adults. METHODS: A five-phase, systematic and standardized process was used. Phase 1: item pools were constructed based on the Symptom Interpretation Model. Phase 2: the Delphi expert consultation was carried out for items selection and revision. Phase 3: a pilot survey was carried out to further select and revise the items. Phase 4: older adults were surveyed to finalize the items. Phase 5: older adults were surveyed to test the psychometric properties of the two developed scales, including construct validity, reliability and acceptability. RESULTS: Both scales comprise three dimensions (symptom, risk factor and management strategy), with 10 items for the sarcopenia knowledge assessment scale and 14 items for the fall knowledge assessment scale. They had acceptable construct validity, with all indicators meeting their specific criteria. Their reliability was acceptable, with the Cronbach's α coefficients being 0.82 for both scales, the value of spilt-half reliability being 0.86 for the sarcopenia knowledge assessment scale and 0.85 for the fall knowledge assessment scale. Their acceptability was good, with both scales having a completion rate of 94.35% and an average completion time of 5 min. DISCUSSION: Two Chinese knowledge assessment scales with acceptable validity, reliability and acceptability have been developed, which will facilitate the assessment of the knowledge on sarcopenia and fall among community-dwelling older adults, especially for large-scale surveys. Geriatr Gerontol Int 2023; 23: 430-436.

[Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy].

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION: For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism.

PURPOSE: Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS. METHODS: A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference. RESULTS: In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy. CONCLUSION: The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.

Promotion of Hair Regrowth by Transdermal Dissolvable Microneedles Loaded with Rapamycin and Epigallocatechin Gallate Nanoparticles.

Interest in transdermal delivery methods for stimulating hair regrowth has been increasing recently. The microneedle approach can break the barrier of the stratum corneum through puncture ability and improve drug delivery efficiency. Herein, we report a dissolvable microneedle device for the co-delivery of rapamycin and epigallocatechin gallate nanoparticles that can significantly promote hair regeneration. Compared with the mice without any treatment, our strategy can facilitate hair growth within 7 days. Higher hair shaft growth rate and hair follicle density with inconspicuous inflammation were exhibited in C57BL/6 mice, elucidating its potential for clinical application.

Trial-level characteristics associate with treatment effect estimates: a systematic review of meta-epidemiological studies.

BACKGROUND: To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates. METHODS: A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots. RESULTS: Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results). CONCLUSIONS: Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.

Cerebral safety after pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Pulsed field ablation (PFA) is a novel, nonthermal ablation modality that can ablate myocardial tissue with minimal effects on surrounding tissue. Preclinical data show an absence of cerebral emboli after extensive PFA. However, clinical data on silent cerebral lesions (SCLs) and/or silent cerebral events (SCEs) after PFA are lacking. OBJECTIVES: The purpose of this study was to investigate the occurrence of neurological deficits and SCL and/or SCE after PFA in paroxysmal atrial fibrillation (AF) using National Institutes of Health Stroke Scale (NIHSS) scores and magnetic resonance imaging (MRI). METHODS: In patients with symptomatic paroxysmal AF, pulmonary vein isolation (PVI) using PFA was performed. NIHSS scores were assessed before and 2 days and 30 days after PVI. One day after PVI, patients underwent cerebral 1.5-T MRI scanning using diffusion-weighted imaging and fluid-attenuated inversion recovery sequences to document the occurrence of SCL/SCE. RESULTS: PFA was performed in 30 patients (age 63 ± 10 years). No patient showed neurological deficits. All NIHSS scores showed the minimum value of 0. Cerebral MRI scans were normal in 29 of 30 patients (97%). In 1 patient (3%), a single 7-mm cerebellar lesion was observed. Forty days after the procedure, follow-up cerebral MRI scan showed complete regression of the lesion. CONCLUSION: In patients treated with PFA for symptomatic paroxysmal AF, the incidence of MRI-detected asymptomatic thromboembolic cerebral events or lesions was as low as 3%. No neurological deficits occurred in any of the patients.

[Research progress on activities and mechanisms of anti-hepatitis B virus drugs].

Hepatitis B virus(HBV) is the pathogen causing hepatitis B, which is characterized by strong infectivity, high incidence, and widespread prevalence and has seriously threatened human health and affected their quality of life. Anti-HBV drugs in western medicine mainly include nucleosides(nucleic acids) and interferons, among which nucleosides(nucleic acids) are used more often. Due to the easy development of drug resistance, their therapeutic effects are not remarkable. Interferons can easily cause serious adverse reactions such as liver injury. Anti-HBV drugs in traditional Chinese medicine mainly include single Chinese herbs(Artemisiae Scopariae Herba, Artemisiae Annuae Herba, Salviae Miltiorrhizae Radix et Rhizoma, etc.) and Chinese herbal compounds(Yinchenhao Decoction, Xiaochaihu Decoction, Tiaogan Huaxian Pills, etc.), whose chemical compositions and action targets have not been fully identified. The combined medication is better than single medication, in that the former can improve drug resistance, make up each other's deficiencies, reduce adverse reactions, and prolong the action time. This study reviewed the anti-HBV activities and mechanisms of western drugs, Chinese herbs, and combined medications, in order to provide reference for the development and research of new anti-HBV drugs.

Improved Therapeutic Efficiency against Obesity through Transdermal Drug Delivery Using Microneedle Arrays.

In this paper, we prepared patches that were composed of a degradable microneedle (MN) array with a soft backing provided for the skin tissue. We then performed a transdermal delivery of anti-obesity drugs to evaluate the effectiveness of ß3 adrenergic receptor CL316243 in obesity treatment in overweight mice induced by a high-fat diet. Eighty male National Institutes of Health (NIH) mice were randomly divided into four obese groups or the control group. The obesity groups were given a high-fat diet for 15-18 weeks to establish an obese model. Afterward, the obese groups were divided into the following four groups: the control group, the unloaded MN group, the CL-316243 MN group, and the injection group. For the injection group, the group of mice was injected subcutaneously with CL316243 (1 mg/(kg·day)) for 15 days. Furthermore, the CL-316243 MN group was given a lower dose (0.1 mg/(kg·day)) for 15 days. After weighing the mice, we used Western blotting to detect the expression of uncoupling protein 1 (UCP1) in the adipose tissue around the mouse viscera. The results stated that the weight of the CL-316243 MN group and the injection group dropped, and the UCP1 protein expression of brown adipose tissue (BAT) significantly increased. The results demonstrated the ß3 adrenergic receptor agonist CL316243 could be carried into the body through MN, and the dose applied was considerably smaller than the injection dose. The reason for this may arise from the CL-316243 being delivered by MN arrays to subcutaneous adipose tissue more efficiently, with an even distribution, compared to that of the injection dose. This technique provides a new and feasible way to treat obesity more effectively.

[Effect of electroacupuncture at Neiguan (PC 6) on pulmonary function during one-lung ventilation in patients with lobectomy].

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism. METHODS: Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO2), oxygenation index (OI), compliance of lung (CL), respiratory index (RI)] and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were observed before surgery (T0), 30 min into OLV (T1), 60 min into OLV (T2) and after operation (T3). The total incidence of complications, pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay were compared between the two groups. RESULTS: Compared with T0, the PaO2, OI, CL and serum SOD at T1, T2 and T3 in the two groups were decreased (P<0.05), and those in the observation group were higher than those in the control group (P<0.05). The RI and serum levels of MDA, IL-6, TNF-α at T1, T2 and T3 in the two groups were increased, and those in the observation group were lower than those in the control group (P<0.05). The total incidence of complications in the observation group was lower than that in the control group [3.3% (1/30) vs 23.3% (7/30), P<0.05]. The pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay in the observation group were less than those in the control group (P<0.05). CONCLUSION: EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.

Non-Genetic Risk Factors for Parkinson's Disease: An Overview of 46 Systematic Reviews.

BACKGROUND: Numerous systematic reviews (SRs) and meta-analyses on non-genetic risk factors for Parkinson's disease (PD) development have been published with inconsistent conclusions. OBJECTIVE: This overview of SRs aimed to summarize evidence on non-genetic factors for the development of PD from the published SRs, and explore the reasons behind the conflicting results. METHODS: Three international databases were searched for SRs with meta-analyses summarized evidence on non-genetic factors for PD development. The Assessing the Methodological Quality of Systematic Reviews 2 tool was used to appraise the methodological quality of included SRs. Pooled effect estimations were extracted from each meta-analysis. RESULTS: Forty-six SRs covered six categories, and more than 80 factors were included in this overview. Thirty-nine SRs (84.7%) were judged to be of critically low methodological quality. Evidence from prospective studies showed that physical activity, smoking, coffee, caffeine, tea, fat intake, ibuprofen use, calcium channel blocker use, statin use, thiazolidinediones, and high serum urate levels significantly reduced the risk of PD, while dairy intake, diabetes, hormone replacement therapy, depression, mood disorder, bipolar disorder, and aspirin use significantly increased the risk of PD. Differences in study designs (e.g., cohort studies, case-control studies) accounted for the conflicting results among included SRs. CONCLUSION: Modifiable lifestyle factors such as physical activity and tea and coffee drinking may reduce the risk of PD, which may offer PD prevention strategies and hypotheses for future research. However, the designs of primary studies on PD risk factors and related SRs need to be improved and harmonized.

The methodological quality of individual participant data meta-analysis on intervention effects: systematic review.

OBJECTIVE: To assess the methodological quality of individual participant data (IPD) meta-analysis and to identify areas for improvement. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, and Cochrane Database of Systematic Reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with IPD meta-analyses of randomised controlled trials on intervention effects published in English. RESULTS: 323 IPD meta-analyses covering 21 clinical areas and published between 1991 and 2019 were included: 270 (84%) were non-Cochrane reviews and 269 (84%) were published in journals with a high impact factor (top quarter). The IPD meta-analyses showed low compliance in using a satisfactory technique to assess the risk of bias of the included randomised controlled trials (43%, 95% confidence interval 38% to 48%), accounting for risk of bias when interpreting results (40%, 34% to 45%), providing a list of excluded studies with justifications (32%, 27% to 37%), establishing an a priori protocol (31%, 26% to 36%), prespecifying methods for assessing both the overall effects (44%, 39% to 50%) and the participant-intervention interactions (31%, 26% to 36%), assessing and considering the potential of publication bias (31%, 26% to 36%), and conducting a comprehensive literature search (19%, 15% to 23%). Up to 126 (39%) IPD meta-analyses failed to obtain IPD from 90% or more of eligible participants or trials, among which only 60 (48%) provided reasons and 21 (17%) undertook certain strategies to account for the unavailable IPD. CONCLUSIONS: The methodological quality of IPD meta-analyses is unsatisfactory. Future IPD meta-analyses need to establish an a priori protocol with prespecified data syntheses plan, comprehensively search the literature, critically appraise included randomised controlled trials with appropriate technique, account for risk of bias during data analyses and interpretation, and account for unavailable IPD.

Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer.

OBJECTIVE: V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. METHODS: Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. RESULTS: The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. CONCLUSION: VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.