Incidence and risk factors for recurrent primary spontaneous pneumothorax after video-assisted thoracoscopic surgery: a systematic review and meta-analysis.

Background: The incidence and risk factors for recurrent primary spontaneous pneumothorax (PSP) after video-assisted thoracoscopic surgery (VATS) remain controversial. A systematic review and meta-analysis were conducted to determine the incidence and risk factors for recurrence of PSP after VATS. Methods: A systematic search of PubMed, Web of Science, Embase, and Cochrane Library databases was conducted to identify studies that reported the rate and risk factors for recurrence of PSP after VATS published up to December 2023. The pooled recurrence rate and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model. In addition, risk factors were similarly included in the meta-analysis, and sources of heterogeneity were explored using meta-regression analysis. Results: A total of 72 studies involving 23,531 patients were included in the meta-analysis of recurrence. The pooled recurrence rate of PSP after VATS was 10% (95% CI: 8-12%). Male sex (OR: 0.61; 95% CI: 0.41-0.92; P=0.02), younger age [mean difference (MD): -2.01; 95% CI: -2.57 to -1.45; P<0.001), lower weight (MD: -1.57; 95% CI: -3.03 to -0.11; P=0.04), lower body mass index (BMI) (MD: -0.73; 95% CI: -1.08 to 0.37; P<0.001), and history of contralateral pneumothorax (OR: 2.46; 95% CI: 1.56-3.87; P<0.001) were associated with recurrent PSP, whereas height, smoking history, affected side, stapling line reinforcement, and pleurodesis were not associated with recurrent PSP after VATS. Conclusions: The recurrence rate of PSP after VATS remains high. Healthcare professionals should focus on factors, including sex, age, weight, BMI, and history of contralateral pneumothorax, that may influence recurrence.

Electrical Synchrony Optimization for Left Bundle Branch Area Pacing in Patients With Bradycardia and Heart Failure.

Left bundle branch area pacing (LBBAP) has emerged as a promising physiological pacing modality. This study was designed to investigate the acute impact of the atrioventricular delay (AVD) on cardiac electrical characteristics and identify an optimal range of AVDs for LBBAP to achieve electrical atrioventricular and interventricular synchrony. Patients indicated for ventricular or biventricular pacing were studied during routine follow-ups at least 3 months after LBBAP implantation. Patients were excluded if they had a complete AV block or persistent atrial fibrillation. AVD was programed from 40 to 240 ms or until intrinsic conduction occurred. Optimal AVD was determined by the electrocardiography criteria, including QRS duration, reduced R-wave in lead V1, reduced notching or slurring in lateral leads, and more desirable precordial QRS transition. A total of 38 patients (age 68.7 ± 10.3 years; 16 male (42%); 18 dual-chamber pacemakers and 20 cardiac resynchronization therapy devices; average follow-up period 15.1 ± 10.2 months) were included. The fusion of LBBAP and intrinsic right ventricular conduction occurred in 21 patients with corresponding optimal AVD determined. A great proportion (∼85%) of the optimal AVDs ranged from 50% to 80% of the observed atrium-to-left bundle branch-sensing (A-LBBS) intervals. The linear correlation between the optimal AVD and corresponding A-LBBS interval (optimal AVD = 0.84 × [A-LBSs interval] - 36 ms) produced R = 0.86 and p <0.0001. In conclusion, AVD selection during LBBAP greatly impacted the ventricular electrical characteristics and the optimal AVD was linearly correlated with the corresponding A-LBBS interval.

Comprehensive analyses of molecular features, prognostic values, and regulatory functionalities of m6A-modified long non-coding RNAs in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has a high incidence and recurrence rate. N6-methyladenosine (m6A) modification of RNA has become a promising epigenetic marker in tumors. The dysregulation of both RNA m6A levels and m6A regulator expression levels reportedly affects essential biological processes in various tumors. Long non-coding RNAs (lncRNAs), a subgroup of RNAs over 200 nucleotides in length that do not code for protein, can be modified and regulated by m6A, but the relevant profile in LUAD remains unclear. RESULTS: The m6A levels of total RNA were decreased in LUAD tumor tissues and cells. Multiple m6A regulators were abnormally expressed at both the RNA and protein levels, and were related in expression patterns and functionally synergistic. Our microarray revealed 2846 m6A-modified lncRNA transcripts as well as its molecular features, 143 of which were differentially m6A-modified and manifested a negative correlation between expression levels and m6A modification levels. More than half of the differentially m6A-modified lncRNAs associated with dysregulated expression. The 6-MRlncRNA risk signature was a reliable indicator for assessing survival time of LUAD patients. The competitive endogenous regulatory network suggested a potential m6A-induced pathogenicity in LUAD. CONCLUSIONS: These data have demonstrated that differential RNA m6A modification and m6A regulator expression levels were identified in LUAD patients. In addition, this study provides evidence increasing the understanding of molecular features, prognostic values, and regulatory functionalities of m6A-modified lncRNAs in LUAD.

Prevalence of hand-foot syndrome following chemotherapy for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the prevalence of hand-foot syndrome (HFS) in patients with colorectal cancer undergoing chemotherapy. METHODS: The PubMed, Embase, and Cochrane Library databases were searched, from their inception to September 20, 2022, to identify studies on the prevalence of HFS in patients with colorectal cancer receiving chemotherapy. Comprehensive retrieval of literature was performed using the literature tracing method. We calculated the prevalence of HFS in patients with colorectal cancer undergoing chemotherapy based on meta-analyses. Subgroup analysis and meta-regression analyses were performed to determine the sources of heterogeneity. RESULTS: A total of 20 studies were included, involving 4773 cases. Meta-analysis of the random effects model showed that the total prevalence of HFS in patients with colorectal cancer undergoing chemotherapy was 49.1% (95% confidence interval [CI]: 0.332, 0.651). Subgroup analysis demonstrated that the most frequent grades of HFS were grades 1 and 2, accounting for 40.1% (95% CI: 0.285, 0.523) of cases; this rate was markedly higher than that of grades 3 and 4 (5.8%; 95% CI: 0.020, 0.112). The meta-regression results illustrated that the type of research, country of the study population, type of drug, and year of publication were not sources of heterogeneity in this setting (P > 0.05). CONCLUSION: The present findings showed that the prevalence of HFS in patients with colorectal cancer receiving chemotherapy was high. Healthcare professionals should provide knowledge to such patients regarding the prevention and management of HFS.

Resynchronization effects and clinical outcomes during left bundle branch area pacing with and without conduction system capture.

BACKGROUND: Left bundle branch area pacing (LBBAP) includes left bundle branch pacing (LBBP) and left ventricular (LV) septal myocardial pacing (LVSP). HYPOTHESIS: The study aimed to assess resynchronization effects and clinical outcomes by LBBAP in heart failure (HF) patients with cardiac resynchronization therapy (CRT) indications. METHODS: LBBAP was successfully performed in 29 consecutive patients and further classified as the LBBP-group (N = 15) and LVSP-group (N = 14) based on the LBBP criteria and novel LV conduction time measurement (LV CT, between LBBAP site and LV pacing (LVP) site). AV-interval optimized LBBP or LVSP, or LVSP combined with LVP (LVSP-LVP) was applied. LV electrical and mechanical synchrony and clinical outcomes were assessed. RESULTS: All 15 patients in the LBBP-group received optimized LBBP while 14 patients in the LVSP-group received either optimized LVSP (5) or LVSP-LVP (9). The LV CT during LBBP was significantly faster than that during LVP (p < .001), while LV CT during LVSP were similar to LVP (p = .226). The stimulus to peak LV activation time (Stim-LVAT, 71.2 ± 8.3 ms) and LV mechanical synchrony (TSI-SD, 35.3 ± 9.5 ms) during LBBP were significantly shorter than those during LVSP (Stim-LVAT 89.1 ± 19.5 ms, TSI-SD 49.8 ± 14.4 ms, both p < .05). Following 17(IQR 8) months of follow-up, the improvement of LVEF (26.0%(IQR 16.0)) in the LBBP-group was significantly greater than that in the LVSP-group (6.0%(IQR 20.8), p = .001). CONCLUSIONS: LV activation in LBBP propagated significantly faster than that of LVSP. LBBP generated superior electrical and mechanical resynchronization and better LVEF improvement over LVSP in HF patients with CRT indications.

Noninvasive evaluation of pulmonary hypertension using the second heart sound parameters collected by a mobile cardiac acoustic monitoring system.

Background: Pulmonary hypertension (PH) is linked to higher rates of morbidity and mortality worldwide. Early diagnosis of PH is important for clinical treatment. The estimated pulmonary artery systolic pressure (ePASP ≥ 35 mmHg) measured by echocardiography helps screen PH patients. In this paper, we report a novel PH screening method through a mobile cardiac acoustic monitoring system. Methods: In the retrospective study, patients admitted to our hospital between January 2022 and April 2023 were classified into PH and control groups using ePASP and compared with acoustic cardiographic parameters. According to ePASP, PH severity was classified as mild, moderate, and severe. We analyzed the first and second heart sound (S1, S2) characteristics, including amplitude (S1A, S2A), energy (S1E, S2E), and frequency (S1F, S2F). Results: The study included 209 subjects, divided into PH (n = 121) and control (n = 88) groups. Pearson correlation analysis confirmed the positive correlation between S2F and ePASP. The diagnostic performance of S2F as assessed by the area under the ROC curve was 0.775 for PH. The sensitivity and specificity of diagnosing ePASP ≥ 35 mmHg when S2F ≥ 36 Hz were found to be 79.34% and 67.05%, respectively, according to ROC analysis. Severity classification was performed using S2F, the area under the ROC curve was 0.712-0.838 for mild PH, 0.774-0.888 for moderate PH, and 0.826-0.940 for severe PH. Conclusions: S2F collected by the mobile cardiac acoustic monitoring system offers a convenient method for remote PH screening, potentially improving PH management and outcomes.

PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer.

Background: The polypyrimidine tract-binding protein (PTBP) nuclear ribonucleoprotein family of proteins, including PTBP1, PTBP2 and PTBP3, regulate the process of cell proliferation, differentiation, apoptosis and carcinogenesis. PTBPs exhibit oncogenic effects in certain tumors. However, the role of PTBPs in pan-cancer remains unclear. Our study examined the clinical significance and mechanism of PTBPs in pan-cancer. Methods: We compared the expression of PTBPs in paired and unpaired tissue samples from the Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression, Kaplan-Meier curves, and time-dependent receiver operating characteristic (ROC) curves were used to assess the prognostic significance of PTBPs in pan-cancer. The cBioPortal database also identified genomic abnormalities in PTBPs. TISIDB, TCGA, and Cellminer were used to investigate the relationship between PTBP expression and immune subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating immune cells, and chemosensitivity. cBioPortal was used to search for PTBP co-expressing genes in pan-cancer, and GO and KEGG enrichment analyses were performed to search for PTBP-related signaling pathways. Results: PTBPs were shown to be widely upregulated in human tumor tissues. PTBP1 showed good prognostic value in ACC, KIRP, and LGG; PTBP2 in ACC and KICH; and PTBP3 in ACC, LGG, and PAAD, with AUC >0.7. PTBPs were differentially expressed in tumor immune subtypes and had a strong correlation with tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME). In addition, PTBP expressions were related to ICP, TMB, and MSI, suggesting that these three PTBPs may be potential tumor immunotherapeutic targets and predict the efficacy of immunotherapy. Enrichment analysis of co-expressed genes of PTBPs showed that they may be involved in alternative splicing, cell cycle, cellular senescence, and protein modification. Conclusion: PTBPs are involved in the malignant progression of tumors. PTBP1, PTBP2 and PTBP3 may be potential biomarkers for prognosis and immunotherapy in pan-cancer and may be novel immunotherapeutic targets.

Left bundle branch potential predicts better electrical synchrony in bradycardia patients receiving left bundle branch pacing.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel physiological pacing technology. We aim to explore the relation between LBB potential (LBB Po) and left ventricular (LV) electrical/mechanical synchrony in bradycardia patients without heart failure (HF) receiving LBBP. METHODS: A total of 62 patients undergoing LBBP were categorized by LBB Po: the LBB Po positive (+) group and the LBB Po negative (-) group. The perioperative electrocardiographic and echocardiography parameters related to cardiac synchrony were analyzed. RESULTS: There were 42 (67.74%) patients in the LBB Po (+) group and 20 patients in the LBB Po (-) group. Paced QRS duration (113.50 ± 17.65 ms vs. 123.40 ± 13.18 ms, P = 0.031) and stimulus left ventricular activation time (71.76 ± 3.53 ms vs. 74.45 ± 3.12 ms, P = 0.005) were shorter in the LBB Po (+) group than in the LBB Po (-) group. No significant differences in the LV mechanical synchrony (Ts-SD-12, 36.55 ± 19.76 vs. 39.95 ± 16.04, P = 0.505; PSD, 51.14 ± 17.69 vs. 45.65 ± 10.55, P = 0.205) between the two groups. There was not statistically difference in ventricular lead parameters measured intraoperative between the two groups. Compared with the LBB Po (-) group, the LBB Po (+) group showed a dramatically higher total procedure duration time (93.52 ± 9.18 min vs. 86.25 ± 10.54 min, p = 0.007) and fluoroscopy time for ventricle lead implantation (18.95 ± 3.43 min vs. 14.00 ± 3.16 min, p < 0.001). CONCLUSIONS: The appearance of LBB Po may suggest better electrical synchrony during LBBP, but similar in LV mechanical synchrony. However, the total operation duration and fluoroscopy time of ventricular lead implantation in the LBB Po (+) group were longer. Therefore, it may be unnecessary to deliberately recognize the LBB Po when it is difficult to detect LBB Po and meet the LBBP criterion.

Mobile Cardiac Acoustic Monitoring System to Evaluate Left Ventricular Systolic Function in Pacemaker Patients.

The mobile cardiac acoustic monitoring system is a promising tool to enable detection and assist the diagnosis of left ventricular systolic dysfunction (LVSD). The objective of the study was to evaluate the diagnostic value of electromechanical activation time (EMAT), an important cardiac acoustic biomarker, in quantifying LVSD among left bundle branch pacing (LBBP) and right ventricular apical pacing (RVAP) patients using a mobile acoustic cardiography monitoring system. In this prospective single-center observational study, pacemaker-dependent patients were consecutively enrolled. EMAT, the time from the start of the pacing QRS wave to first heart sound (S1) peak; left ventricular systolic time (LVST), the time from S1 peak to S2 peak; and ECG were recorded simultaneously by the mobile cardiac acoustic monitoring system. LVEF was measured by echocardiography. A logistic regression model was applied to evaluate the association between EMAT and reduced EF (LVEF < 50%). A total of 105 pacemaker-dependent patients participated. The RVAP group (n = 58) displayed a significantly higher EMAT than the LBBP group (n = 47) (150.95 ± 19.46 vs. 108.23 ± 12.26 ms, p < 0.001). Pearson correlation analysis revealed a statistically significant negative correlation between EMAT and LVEF (p < 0.001). Survival analysis showed the sensitivity and specificity of detecting LVEF to be < 50% when EMAT ≥ 151 ms were 96.00% and 96.97% in the RVAP group. In LBBP patients, the sensitivity and specificity of using EMAT ≥ 110 ms as the cutoff value for the detection of LVEF < 50% were 75.00% and 100.00%. There was no significant difference in LVST with or without LVSD in the RVAP group (p = 0.823) and LBBP group (p = 0.086). Compared to LVST, EMAT was more helpful to identify LVSD in pacemaker-dependent patients. The cutoff point of EMAT for diagnosing LVEF < 50% differed regarding the pacing type. Therefore, the mobile cardiac acoustic monitoring system can be used to identify the progress of LVSD in pacemaker patients.

Urinary Exosomal Long Noncoding RNA TERC as a Noninvasive Diagnostic and Prognostic Biomarker for Bladder Urothelial Carcinoma.

PURPOSE: Bladder cancer is one of the most common urological malignancies worldwide, and approximately 90% of bladder cancer cases are histologically typed as bladder urothelial carcinoma (BLCA). Exosomes are 30 to 200 nm extracellular vesicles that transport microRNAs, long noncoding RNAs (lncRNAs), mRNAs, circular RNAs, and proteins across tissues and through circulation. Urinary exosomes may contain genetic information from tumor cells. Herein, we explored the clinical significance of urinary exosomal lncRNA telomerase RNA component (TERC) levels to provide an urgently needed diagnostic and prognostic biomarker for BLCA. MATERIALS AND METHODS: In this study, we used RNA-sequencing of samples from four BLCA patients and three healthy controls to identify that TERC was differentially expressed in urinary exosomes. We then used quantitative PCR in different types of clinical samples to validate the biomarker and analyzed results using receiver operating characteristic curves. RESULTS: We found that TERC was significantly upregulated in urinary exosomes from BLCA patients compared with those from healthy controls (P < 0.0001). Urinary exosomal TERC showed higher sensitivity (78.65%) and accuracy (77.78%) than existing indicators including nuclear matrix protein-22 and urine cytometry. Using the cut-off value 4.302, the area under the curve for urinary exosomal TERC was 0.836 (95% confidence interval: 0.768-0.891, P < 0.0001). Furthermore, this noninvasive assay could distinguish low-grade and high-grade tumors (P = 0.0153). CONCLUSIONS: TERC is enriched in urinary exosomes from BLCA patients. Urinary exosomal TERC could become a diagnostic and prognostic biomarker for BLCA that allows clinicians to realize noninvasive detection of BLCA.

Prediction of response after cardiac resynchronization therapy with machine learning.

AIMS: Nearly one third of patients receiving cardiac resynchronization therapy (CRT) suffer non-response. We intend to develop predictive models using machine learning (ML) approaches and easily attainable features before CRT implantation. METHODS AND RESULTS: The baseline characteristics of 752 CRT recipients from two hospitals were retrospectively collected. Nine ML predictive models were established, including logistic regression (LR), elastic network (EN), lasso regression (Lasso), ridge regression (Ridge), neural network (NN), support vector machine (SVM), random forest (RF), XGBoost and k-nearest neighbour (k-NN). Sensitivity, specificity, precision, accuracy, F1, log-loss, area under the receiver operating characteristic (AU-ROC), and average precision (AP) of each model were evaluated. AU-ROC was compared between models and the latest guidelines. Six models had an AU-ROC value above 0.75. The LR, EN and Ridge models showed the highest overall predictive power compared with other models with AU-ROC at 0.77. The XGBoost model reached the highest sensitivity at 0.72, while the highest specificity was achieved by Ridge model at 0.92. All ML models achieved higher AU-ROCs that those derived from the latest guidelines (all P < 0.05). The effect size analysis identified left bundle branch block, left ventricular end-systolic diameter, and history of percutaneous coronary intervention as the most crucial predictors of CRT response. An online tool to facilitate the prediction of CRT response is freely available at http://www.crt-response.com/. CONCLUSIONS: ML algorithms produced efficient predictive models for evaluation of CRT response with features before implantation. Tools developed accordingly could improve the selection of CRT candidates and reduce the incidence of non-response.

Improvement of LV Reverse Remodeling Using Dynamic Programming of Fusion-Optimized Atrioventricular Intervals in Cardiac Resynchronization Therapy.

Background: The patient-tailored SyncAV algorithm shortens the QRS duration (QRSd) beyond what conventional biventricular (BiV) pacing can. However, evidence of the ability of SyncAV to improve the cardiac resynchronization therapy (CRT) response is lacking. The aim of this study was to evaluate the impact of CRT enhanced by SyncAV on echocardiographic and clinical responses. Methods and Results: Consecutive heart failure (HF) patients from three centers treated with a quadripolar CRT system (Abbott) were enrolled. The total of 122 patients were divided into BiV+SyncAV (n = 68) and BiV groups (n = 54) according to whether they underwent CRT with or without SyncAV. Electrocardiographic, echocardiographic, and clinical data were assessed at baseline and during follow-up. Echocardiographic response to CRT was defined as a ≥15% decrease in left ventricular end-systolic volume (LVESV), and clinical response was defined as a NYHA class reduction of ≥1. At the 6-month follow-up, the baseline QRSd and LVESV decreased more significantly in the BiV+SyncAV than in the BiV group (QRSd -36.25 ± 16.33 vs. -22.72 ± 18.75 ms, P < 0.001; LVESV -54.19 ± 38.87 vs. -25.37 ± 36.48 ml, P < 0.001). Compared to the BiV group, more patients in the BiV+SyncAV group were classified as echocardiographic (82.35 vs. 64.81%; P = 0.036) and clinical responders (83.82 vs. 66.67%; P = 0.033). During follow-up, no deaths due to HF deterioration or severe procedure related complications occurred. Conclusion: Compared to BiV pacing, BiV combined with SyncAV leads to a more significant reduction in QRSd and improves LV remodeling and long-term outcomes in HF patients treated with CRT.

N6-Methyladenosine-Regulated mRNAs: Potential Prognostic Biomarkers for Patients With Lung Adenocarcinoma.

Aberrant regulation of m6A mRNA modification can lead to changes in gene expression, thus contributing to tumorigenesis in several types of solid tumors. In this study, by integrating analyses of m6A methylation and mRNA expression, we identified 84 m6A-regulated mRNAs in lung adenocarcinoma (LUAD). Although the m6A methylation levels of total RNA in LUAD patient tumor tissue were reduced, the majority (75.2%) of m6A-regulated mRNAs were hypermethylated. The m6A-hypermethylated mRNAs were mainly enriched in terms related to transcription factor activity. We established a 10-m6A-regulated-mRNA signature score system through least absolute shrinkage and selection operator Cox regression analysis, with its predictive value validated by Kaplan-Meier curve and time-dependent receiver operating characteristic curves. RFXAP and KHDRBS2 from the signature also exhibited an independent prognostic value. The co-expression and interaction network analyses demonstrated the strong correlation between m6A regulators and the genes in the signature, further supporting the results of the m6A methylation modification patterns. These findings highlight the potential utility of integrating multi-omics data (m6A methylation level and mRNA expression) to accurately obtain potential prognostic biomarkers, which may provide important insights into developing novel and effective therapies for LUAD.

Microbiota in Gut, Oral Cavity, and Mitral Valves Are Associated With Rheumatic Heart Disease.

Rheumatic heart disease refers to the long-term damage of heart valves and results from an autoimmune response to group A Streptococcus infection. This study aimed to analyze the microbiota composition of patients with rheumatic heart disease and explore potential function of microbiota in this disease. First, we revealed significant alterations of microbiota in feces, subgingival plaques, and saliva of the patients compared to control subjects using 16S rRNA gene sequencing. Significantly different microbial diversity was observed in all three types of samples between the patients and control subjects. In the gut, the patients possessed higher levels of genera including Bifidobacterium and Eubacterium, and lower levels of genera including Lachnospira, Bacteroides, and Faecalibacterium. Coprococcus was identified as a super-generalist in fecal samples of the patients. Significant alterations were also observed in microbiota of subgingival plaques and saliva of the patients compared to control subjects. Second, we analyzed microbiota in mitral valves of the patients and identified microbes that could potentially transmit from the gut or oral cavity to heart valves, including Streptococcus. Third, we further analyzed the data using random forest model and demonstrated that microbiota in the gut, subgingival plaque or saliva could distinguish the patients from control subjects. Finally, we identified gut/oral microbes that significantly correlated with clinical indices of rheumatic heart disease. In conclusion, patients with rheumatic heart disease manifested important alterations in microbiota that might distinguish the patients from control subjects and correlated with severity of this disease.

Successful application of snare-kissing-catheter technique to implant leadless pacemaker in severely dilated right heart.

Implantation of leadless pacemaker is efficacy and safety compared with the traditional pacemaker in structurally normal hearts. However, delivery experience of leadless pacemaker in patients with severe right heart enlargement remains limited. We present the rare case of a patient with giant right heart and moderate to severe tricuspid regurgitation implanted with a leadless Micra transcatheter pacemaker system. The extension of the Micra delivery catheter can be improved by using a single-loop snare on the catheter proximal to appropriate right ventricle (RV) pacing position. The snare-kissing-catheter technique can aid in successful deployment in the setting of challenging right heart enlargement.

A Synthetic Curcuminoid Analog, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone, Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Increasing miR-146a.

The impairment in diabetic wound healing represents a significant clinical problem, with no efficient targeted treatments for these wound disorders. Curcumin is well confirmed to improve diabetic wound healing, however, its low bioavailability and poor solubility severely limit its clinical application. This study aims to provide the pharmacological basis for the use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66). The results showed that topically applied C66 improved cutaneous wound healing in vivo. Further studies showed that C66 treatment increased the level of microRNA-146a (miR-146a) in the wounds in streptozotocin (STZ)-induced diabetic mice, downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) and phosphorylated nuclear factor-κB (NF-κB) p65 subunit (p-p65) (both p < 0.05), and suppressed the mRNA expression of inflammation-related cytokines, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). The in vitro data obtained in human umbilical vein endothelial cells (HUVECs) showed that C66 could reverse high glucose (HG)-induced NF-κB activation due to upregulation of miR-146a expression, which matched the in vivo findings. In conclusion, the present study indicates that C66 exerts anti-inflammation activity and accelerates skin wound healing of diabetic mice, probably via increasing miR-146a and inhibiting the NF-κB-mediated inflammation pathway. Therefore, C66 may be a promising alternative for the treatment of diabetic wounds.

Quercetin Promotes Diabetic Wound Healing via Switching Macrophages From M1 to M2 Polarization.

BACKGROUND: For patients with diabetes mellitus, excessive and long-lasting inflammatory reactions at the wound site commonly lead to the delayed refractory wound healing. The polarization of macrophages in terms of M1 and M2 phenotypes is closely related to the production of inflammatory cytokines. Quercetin is traditionally recognized to have anti-inflammatory effect; however, whether quercetin modulates macrophage polarization from M1 to M2 and thus promotes diabetic wound healing remain unknown. MATERIALS AND METHODS: Wounded male diabetic rats were equally divided into five groups: model group, solvent control group (10% DMSO), and three drug groups treated with quercetin (Q) at concentrations of 10 mg/mL (Q-LD [low dose]), 20 mg/mL (Q-MD [medium dose]), and 40 mg/mL (Q-HD [high dose]), respectively. The anti-inflammatory effect of quercetin on diabetic wounds was observed. Immunohistochemistry and quantificational real-time polymerase chain reaction were applied to test the changes in macrophage polarization and inflammatory responses. RESULTS: The wound contraction was fastest in Q-HD group. Hematoxylin and eosin (H&E) and Masson's trichrome staining revealed that fibroblast distribution and collagen deposition in quercetin-treated groups were significantly higher than those in the model group. Immunohistochemistry tests showed more CD206-positive cells and less iNOS-positive cells in quercetin-treated groups. Furthermore, the levels of proinflammatory factors in quercetin-treated groups were lower than those in the model group, whereas the levels of the anti-inflammatory factors and angiogenesis-related factors were relatively higher. CONCLUSIONS: In short, quercetin inhibits inflammatory reactions via modulating macrophage polarization switching from M1 to M2 phenotype, thereby accelerating the diabetic wound repair.

Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.

BACKGROUND: Cardiac resynchronization therapy (CRT) via biventricular pacing has demonstrated clinical benefits in patients with heart failure (HF) and ventricular dyssynchrony. Other approaches of CRT is little known. OBJECTIVE: The purpose of this study was to assess the feasibility, safety, and efficacy of left bundle branch area pacing (LBBAP) in patients with HF and left bundle branch block (LBBB). METHODS: Eleven consecutive patients with HF, reduced left ventricular ejection fraction and LBBB and indicated for CRT were recruited. LBBAP was achieved via transventricular septal approach and characterized by narrower QRS duration, shortened peak left ventricular activation time, and right bundle branch conduction delay on the electrocardiogram. Electrocardiogram, echocardiogram, and cardiac function were evaluated at baseline and follow-up. Interventricular mechanical delay and 3-dimensional tissue synchronization imaging during LBBAP and intrinsic LBBB status were measured by echocardiography at follow-up. RESULTS: LBBAP significantly shortened QRS duration (from baseline 180.00 ± 15.86 ms to 129.09 ± 15.94 ms; P < .01) and left ventricular activation time (from baseline 108.18 ± 15.54 ms to 80.91 ± 9.95 ms; P < .01). Interventricular mechanical delay and the standard deviation of tissue synchronization imaging of 12 left ventricular (LV) segments were significantly shorter during LBBAP than in intrinsic LBBB status (both with P < .01). At a mean follow-up period of 6.7 months, New York Heart Association functional class, plasma level of B-type natriuretic peptide, LV end-systolic diameter, and left ventricular ejection fraction were significantly improved (all with P < .05 vs baseline). CONCLUSION: The study demonstrates that LBBAP is clinically feasible in patients with systolic HF and LBBB. LBBAP can be a new CRT technique to correct LBBB, provide ventricular synchrony, and improve clinical symptoms with LV reverse remodeling.

Correction to: The impact of right ventricular function on prognosis in patients with stage III non-small cell lung cancer after concurrent chemoradiotherapy.

In the original publication of the article, the second author name has been misspelt. The correct name is given in this Correction. The original article has been corrected.