Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

BACKGROUND: No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS: A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS: 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS: There was a significant association of LE8 with death and cancer risk, especially for the young population.

Pyrite from acid mine drainage promotes the removal of antibiotic resistance genes and mobile genetic elements in karst watershed with abundant calcium carbonate.

More information is needed to fully comprehend how acid mine drainage (AMD) affects the phototransformation of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in karst water and sewage-irrigated farmland soil with abundant carbonate rocks (CaCO3) due to increasing pollution of AMD formed from pyrite (FeS2). The results showed FeS2 accelerated the inactivation of ARB with an inactivation of 8.7 log. Notably, extracellular and intracellular ARGs and mobile genetic elements (MGEs) also experienced rapid degradation. Additionally, the pH of the solution buffered by CaCO3 significantly influenced the photo-inactivation of ARB. The Fe2+ in neutral solution was present in Fe(II) coordination with strong reducing potential and played a crucial role in generating •OH (7.0 µM), which caused severe damage to ARB, ARGs, and MGEs. The •OH induced by photo-Fenton of FeS2 posed pressure to ARB, promoting oxidative stress response and increasing generation of reactive oxygen species (ROS), ultimately damaging cell membranes, proteins and DNA. Moreover, FeS2 contributed to a decrease in MIC of ARB from 24 mg/L to 4 mg/L. These findings highlight the importance of AMD in influencing karst water and sewage-irrigated farmland soil ecosystems. They are also critical in advancing the utilization of FeS2 to inactivate pathogenic bacteria.

Difference of ventricular synchrony between LBBP, LBFP and LVSP: A speckle tracking echocardiographic study.

PURPOSE: Left bundle branch area pacing (LBBAP) has emerged as a physiological and stable form of pacing. We aim to compare the mechanical ventricular synchrony of LBBP, LBFP, and LVSP. METHODS: Proximal Left bundle branch pacing (LBBP), left bundle fascicular pacing (LBFP) and left ventricular septal pacing (LVSP) were identified in patients with bradycardia who successfully underwent LBBAP. Patients with left ventricular ejection fraction (LVEF) < 50% or QRS duration (QRSd) ≥ 120 ms were excluded. By using electrocardiograms, the left ventricular activation time (LVAT) and QRS duration (QRSd) were measured to examine electrophysiological synchrony. As indications of mechanical synchrony, global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and peak strain dispersion (PSD) were evaluated by using 2-dimensional speckle tracking echocardiography (2D-STE). RESULTS: In 56 patients, data were collected during LBBP (n = 18), LBFP (n = 16), and LVSP (n = 22). LVSP resulted in a longer LVAT (91.3 ± 14.9 ms) than LBBP (77.1 ± 10.8 ms, P < 0.05) and LBFP (72.1 ± 9.6 ms, P < 0.05), but all three groups had similar QRSd. There were no differences in GLS, GCS, GRS, or PSD between LBBP, LBFP, and LVSP. CONCLUSIONS: In patients with normal cardiac function and narrow QRS, though LBBAP with LBB capture resulted in better electrophysiological synchrony than without, the mechanical synchrony of the three groups was comparable.

Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma.

The heterogeneity of lung adenocarcinoma (LUAD) indicated that target therapies and immunotherapies may not be effective in all patients. The exploration of the feature of the immune landscape of different gene mutations may provide novel perspectives. In this study, we obtained LUAD samples from The Cancer Genome Atlas. By applying ESTIMATE and ssGSEA, KRAS-mutated group was discovered to be associated with lower immune infiltration, lower expression of immune checkpoints, especially, a lower abundance of B cell, CD8+ T cell, dendritic cell, natural killer cell, and macrophage, higher abundance of neutrophil and endothelial cell. Through ssGSEA, we found that the process of antigen-presenting cell co-inhibition and co-stimulation were inhibited, cytolytic activity and human leukocyte antigen molecules were downregulated in the KRAS-mutated group. And KRAS mutation is negatively related to antigen presentation and procession, cytotoxic lymphocyte activity, cytolytic activities, and cytokine interaction signaling pathway via gene function enrichment analysis. Finally, 24 immune-related genes were identified to establish an immune-related gene signature with excellent prognostic prediction capacity, whose 1-, 3- and 5-year AUCs were 0.893, 0.986, and 0.999. Our findings elucidate the features of the immune landscape of KRAS-mutated groups and successfully established a prognostic signature on the basis of immune-related genes in LUAD.

Stage 1 Hypertension and the 10-Year and Lifetime Risk of Cardiovascular Disease: A Prospective Real-World Study.

Background The 10-year and lifetime cardiovascular disease risk in the population with stage 1 hypertension and the effects of recovery from and progression of stage 1 hypertension remain undetermined. Methods and Results This prospective cohort study included 96 268 individuals with blood pressure measurements obtained in 2006 and again in 2010. The 10-year cardiovascular disease risk was estimated using the multivariable Cox proportional hazards model, and the lifetime risk was calculated using a modified survival analysis that accounted for the competing risk of death. Stage 1 hypertension was detected in 30.83% of the cohort. The 10-year cardiovascular disease risk was 2.80%, and the lifetime risk was 16.61%. Compared with the normal blood pressure group, the stage 1 hypertension group had a 35% higher 10-year risk (hazard ratio [HR], 1.35 [95% CI, 1.19-1.52]) and a 36% higher lifetime risk (HR, 1.36 [95% CI, 1.25-1.49]). By 2010, 12.57% of the participants with stage 1 hypertension had progressed to stage 2, with a significant 156% increase in 10-year risk (HR, 2.56 [95% CI, 2.11-3.11]) and an increased lifetime risk of 129% (HR, 2.29 [95% CI, 1.89-2.77]). There was no appreciable change in risk in those with stage 1 hypertension whose blood pressure returned to the normal-elevated range. Conclusions Stage 1 hypertension was associated with a significant increase in 10-year and lifetime cardiovascular disease risk. Progression to stage 2 hypertension was associated with a marked increase in lifetime risk. The current guidelines require revision to promote early detection and appropriate management of blood pressure.

Is the pacing site closer to the left ventricular septal endocardium in left bundle branch pacing or in left ventricular septal pacing?

PURPOSE: Distinguishing between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) is challenging. This study aimed to compare the echocardiographic distance from the pacing lead tip to the left ventricular (LV) septal endocardium between patients who underwent LBBP and those who underwent LVSP successfully. METHODS: Fifty-nine consecutive patients (age 71.9 ± 12.0 years, 35.6% male) with traditional indications for permanent cardiac pacing were included (LBBP group, n = 46; LVSP group, n = 13). Unipolar pacing from the final pacing sites generated narrow QRS complexes with a right bundle branch block pattern in all patients. After the procedure, a physician blinded to the group allocation performed echocardiographic measurements of the distance between the lead tip and the LV septal endocardium. RESULTS: The mean paced QRS duration was comparable between the LBBP group and the LVSP group (105.3 ± 15.6 ms vs. 109.2 ± 9.6 ms, P = 0.287). In the LBBP group, the interval from the left bundle branch potential to QRS onset was 28.7 ± 9.0 ms. During diastole, the mean distance between the lead tip and the LV septal endocardium was 0.6 ± 0.9 mm in the LBBP group and 3.0 ± 1.6 mm in the LVSP group (P < 0.001). During systole, the distance was 1.5 ± 1.4 mm in the LBBP group and 4.3 ± 2.6 mm in the LVSP group (P < 0.001). CONCLUSIONS: The landing zone of the lead tip was closer to the LV septal endocardium in the patients who underwent LBBP. There is a need for real-time intraprocedural monitoring of the distance between the lead tip and the LV septal endocardium when performing LBBP.

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer.

Based on amino acid metabolism-related genes (AAMRGs), this study aimed at screening out key prognosis-related genes and finding the underlying correlation between the amino acid metabolism and tumor immune microenvironment of colorectal cancer. A total of 448 amino acid metabolism-related genes were obtained from MsigDB. The risk signature was built based on differential expression genes, univariate Cox, and LASSO analyses with 403 patients' data downloaded from the TCGA database. Survival analysis and independence tests were performed to confirm the validity of the risk signature. Single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), the score of tumor immune dysfunction and exclusion (TIDE), the immunophenoscore obtained from The Cancer Immunome Atlas database, and the IC50 of drugs were used to find the relationship among the risk signature, immune status, immunotherapy response, and drug sensitivity of colorectal cancer. We identified five amino acid metabolism-related genes for the construction of the risk signature, including ENOPH1, ACAT1, ALDH4A1, FAS, and ASPG. The low-risk group was significantly associated with a better prognosis (p < 0.0001). In the entire set, the area under the curve (AUC) for 1, 3, and 5 years was 0.717, 0.734, and 0.764, respectively. We also discovered that the low-risk subgroup was related to more activity of immune cells, had higher expression of some immune checkpoints, and was more likely to benefit from immunotherapy. ssGSEA revealed that except the processes of glutamine histidine, lysine, tyrosine, and L-phenylalanine metabolism, the other amino acid metabolism pathways were more active in the samples with the low risk scores, whereas the activities of synthesis and transportation of most amino acids were similar. Hedgehog signaling, WNT/ß-catenin signaling, mitotic, notch signaling, and TGF-ß signaling were the top five pathways positively associated with the risk score. To sum up, AAMRGs were associated with the immune microenvironment of CRC patients and could be applied as biomarkers to predict the prognosis and immunotherapy response of patients.

Necroptosis-Related Genes Associated With Immune Activity and Prognosis of Colorectal Cancer.

This study aims at screening out the key necroptosis-related genes in colorectal cancer and elucidating the role of necroptosis-related genes in the immune activity and prognosis of colorectal cancer (CRC). The CRC patients' data were downloaded from The Cancer Genome Atlas (TCGA). The non-negative matrix factorization method was applied to identify new molecular subgroups. Survival analysis and single sample Gene Set Enrichment Analysis were performed to determinate the differences in the overall survival time and immune status of the subgroups. Prognostic model was constructed on the basis of univariate Cox regression and LASSO analysis. Functional analyses were used to explore the potential mechanisms. Based on prognostic related necroptosis genes, we identify two molecular subgroups with significantly different survival. The better prognosis was associated with more active immune infiltration and upregulated expression of immune checkpoints. We screened nine necroptosis related genes as key prognostic genes and established a risk model, which showed a good potential for survival prediction in colorectal cancer. Nomogram assessment showed that the model had high reliability for predicting the prognosis of colorectal cancer patients. The high-risk and low-risk group also has different sensitivity to immunotherapy and commonly used drugs for colorectal cancer. Overall, necroptosis related genes were involved in the immune microenvironment of colorectal cancer patient, could be utilized to predict the prognosis of colorectal cancer and develop more individualized treatment.

MRG Chip: A High-Throughput qPCR-Based Tool for Assessment of the Heavy Metal(loid) Resistome.

Bacterial metal detoxification mechanisms have been well studied for centuries in pure culture systems. However, profiling metal resistance determinants at the community level is still a challenge due to the lack of comprehensive and reliable quantification tools. Here, a novel high-throughput quantitative polymerase chain reaction (HT-qPCR) chip, termed the metal resistance gene (MRG) chip, has been developed for the quantification of genes involved in the homeostasis of 9 metals. The MRG chip contains 77 newly designed degenerate primer sets and 9 published primer sets covering 56 metal resistance genes. Computational evaluation of the taxonomic coverage indicated that the MRG chip had a broad coverage matching 2 kingdoms, 29 phyla, 64 classes, 130 orders, 226 families, and 382 genera. Temperature gradient PCR and HT-qPCR verified that 57 °C was the optimal annealing temperature, with amplification efficiencies of over 94% primer sets achieving 80-110%, with R2 > 0.993. Both computational evaluation and the melting curve analysis of HT-qPCR validated a high specificity. The MRG chip has been successfully applied to characterize the distribution of diverse metal resistance determinants in natural and human-related environments, confirming its wide scope of application. Collectively, the MRG chip is a powerful and efficient high-throughput quantification tool for exploring the microbial metal resistome.

The best strategy for metastatic colorectal cancer (mCRC) patients in second-line treatment: A network meta-analysis.

BACKGROUND: Varieties of systemic treatments in second-line treatment for metastatic colorectal cancer (mCRC) patients have showed an improvement on survival. In this study, we performed a systematic review with a pairwise and bayesian network meta-analysis to rank the best strategy for mCRC patients in second-line treatment. METHODS: A systematic literature search through 2007 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) in mCRC patients. Data were carried out and pooled into a statistical indirect comparison with Bayesian network meta-analysis (NMA). RESULTS: 10 trials totally comprised 4183 patients were included in our study. In NMA, For PFS, Doublet+Bev showed benefits in comparing with Doublet, Doulblet+placebo and Doublet+Ramucirumab. Also, Doublet+Aflibercept demonstrated its superiority in comparing with Doulblet+placebo. For OS, Doublet+Bev represented its superiority when comparing with Double and Doublet+placebo. Doublet+Aflibercept and Doublet+Ramucirumab also done well when opposed to Doublet+placebo. For DCR, Doublet+bev showed unique superiority when compared with Doublet, And Doublet+targeted agent did not represent benefits to each other in DCR. Doublet+bev ranked highest in terms of PFS, OS and DCR followed by Doublet+panitumumab, Doublet+placebo was the lowest in terms of PFS and OS. CONCLUSIONS: Our study shows that Doublet+Bev has the major probability to provide an improvement of survival in patients with mCRC.

[In silico cloning, expression and bioinformatics analysis of NtODB from common tobacco].

It has been reported that ODB genes play an important role in homologous recombination-directed DNA repair, suggesting their potential applications in plant breeding. To analyze the expression characteristics of tobacco NtODB gene, the cDNA sequence of NtODB was obtained using in silico cloning technique. The physicochemical properties, signal peptide, and advanced structures of the predicted protein were analyzed using bioinformatics tools. The results showed that the NtODB gene has a 579-bp open reading frame which encodes a protein with 192 amino acid residues. The protein NtODB is predicted to be alkaline and hydrophilic. Real-time quantitative PCR showed that NtODB was constitutively expressed in different tissues. Subcellular localization showed that NtODB was mainly expressed in cell membrane and chloroplast. These results may help us to better understand and elucidate the roles of ODB genes in the homologous recombination-directed DNA repair.

The complete chloroplast genome of Agave fourcroydes.

Agave fourcroydes (henequen) is the only cultivated Agave species in the Yucatan Peninsula, which is mainly used for fiber production. In the present study, we have successfully assembled the chloroplast (cp) genome of A. fourcroydes. The full length of the cp genome is 157,291 bp with a GC content at 37.8%. The cp genome is constructed with an inverted repeat region a (IRa) of 26,573 bp, a small single copy region (SSC) of 18,230 bp, an inverted repeat region b (IRb) of 26,573 bp and a large single copy region (LSC) of 85,915 bp. The annotation result reveals 132 genes on the cp genome, including 86 protein-coding genes, 38 tRNAs and 8 rRNAs. Phylogenetic tree reveals that A. fourcroydes is closely related with A. sisalana.

The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis.

A dynamically regulated microenvironment, which is mediated by crosstalk between adipocytes and neighboring cells, is critical for adipose tissue homeostasis and function. However, information on key molecules and/or signaling pathways regulating the crosstalk remains limited. In this study, we identify adipocyte miRNA-182-5p (miR-182-5p) as a crucial antiobesity molecule that stimulated beige fat thermogenesis by promoting the crosstalk between adipocytes and macrophages. miR-182-5p was highly enriched in thermogenic adipocytes, and its expression was markedly stimulated by cold exposure in mice. In contrast, miR-182-5p expression was significantly reduced in adipose tissues of obese humans and mice. Knockout of miR-185-5p decreased cold-induced beige fat thermogenesis whereas overexpression of miR-185-5p increased beiging and thermogenesis in mice. Mechanistically, miR-182-5p promoted FGF21 expression and secretion in adipocytes by suppressing nuclear receptor subfamily 1 group D member 1 (Nr1d1) at 5'-UTR, which in turn stimulates acetylcholine synthesis and release in macrophages. Increased acetylcholine expression activated the nicotine acetylcholine receptor in adipocytes, which stimulated PKA signaling and consequent thermogenic gene expression. Our study reveals a key role of the miR-182-5p/FGF21/acetylcholine/acetylcholine receptor axis that mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis. Activation of the miR-182-5p-induced signaling pathway in adipose tissue may be an effective approach to ameliorate obesity and associated metabolic diseases.

[Roles of Myeloid-derived Suppressor Cells in Breast Cancer Metastasis].

Breast cancer patients with bone,liver and lung metastases tend to have a poor prognosis.According to Paget's "seed and soil" theory,metastatic cancer cell "seeds" must fall on congenial target organ "soil".Studies have shown that myeloid-derived suppressor cells(MDSCs)can be recruited at the site of breast cancer metastasis in advance and play a role in the metastasis of breast cancer cells.This paper reviews the biological characteristics of MDSCs,the roles of MDSCs in peripheral circulation,prometastatic niche,and metastatic site during breast cancer metastasis,as well as the research progress of MDSCs-targeted treatment of breast cancer metastasis.

MMP24 Contributes to Neuropathic Pain in an FTO-Dependent Manner in the Spinal Cord Neurons.

Nerve injury-induced gene expression change in the spinal cord is critical for neuropathic pain genesis. RNA N6-methyladenosine (m6A) modification represents an additional layer of gene regulation. We showed that spinal nerve ligation (SNL) upregulated the expression of matrix metallopeptidase 24 (MMP24) protein, but not Mmp24 mRNA, in the spinal cord neurons. Blocking the SNL-induced upregulation of spinal MMP24 attenuated local neuron sensitization, neuropathic pain development and maintenance. Conversely, mimicking MMP24 increase promoted the spinal ERK activation and produced evoked nociceptive hypersensitivity. Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and RNA Immunoprecipitation (RIP) assay indicated the decreased m6A enrichment in the Mmp24 mRNA under neuropathic pain condition. Moreover, fat-mass and obesity-associated protein (FTO) was colocalized with MMP24 in spinal neurons and shown increased binding to the Mmp24 mRNA in the spinal cord after SNL. Overexpression or suppression of FTO correlates with promotion or inhibition of MMP24 expression in cultured spinal cord neurons. In conclusion, SNL promoted the m6A eraser FTO binding to the Mmp24 mRNA, which subsequently facilitated the translation of MMP24 in the spinal cord, and ultimately contributed to neuropathic pain genesis.

Safety and efficacy of His-bundle pacing/left bundle branch area pacing versus right ventricular pacing: a systematic review and meta-analysis.

BACKGROUND: Recent studies have demonstrated that right ventricular pacing (RVP) has deleterious effects on non-synchronized ventricular contraction, while His-bundle pacing (HBP) or left bundle branch area pacing (LBBaP) contribute to improvements in patients' mid- and long-term outcomes. This meta-analysis aimed to compare the safety and efficacy of physiologic pacing (HBP/LBBaP) versus those of RVP. METHODS: A systematic search of PubMed, Cochrane Library, and Embase was conducted for studies that compared the effects of physiologic pacing and RVP. All eligible studies were published before January 1, 2021 and were conducted in humans. STATA software version 15.0 was used for all the data analyses. RESULTS: Twenty articles (n = 2787 patients) were included in this meta-analysis. Compared to RVP, physiologic pacing was associated with a significantly shorter QRS duration and better cardiac function. Physiologic pacing was also correlated with lower rates of mitral regurgitation, pacing-induced cardiomyopathy, death, heart failure hospitalization, and atrial fibrillation, although the above results were not statistically significant. In addition, RVP led to the achievement of higher success rates than physiologic pacing, a shorter fluoroscopic time and mean procedure duration, a lower pacing threshold: the results were statistically significant. Compared with HBP, LBBaP appeared to have some advantages in R wave amplitudes, pacing threshold, fluoroscopic time, procedure time, and success rate, with statistically significant differences. Whereas HBP was associated with fewer surgical complications and shorter QRS duration, the results were not statistically significant. CONCLUSION: Physiologic pacing (HBP/LBBaP) might be a better strategy than RVP and improve long-term clinical outcomes like cardiac function. Although LBBaP appears to have some advantages over HBP, the long-term benefits are still controversial. More large-scale randomized clinical trials are needed for further verification.

Photocatalytic purification of contaminated air in intensive care units by ZnSn(OH)6 nanoparticles.

The air purification in intensive care units (ICU) involving the removal of smog and volatile organic compounds (VOCs), disinfection, and sterilization are closely linked to important health issues. The environmental photocatalysis technology that could decompose gaseous pollutants into small molecular inorganic substances provides the potential solution. In a chamber of 30-m3 simulated ICU, photocatalytic purifier with ZnSn(OH)6 nanoparticles photocatalyst is set up to treat 10 VOCs with concentration below 2 ppm. Compared with regular purifiers of plasma and activated carbon, the present photocatalytic purifier can completely eliminate 10 varieties of low-concentration irritating VOCs without CO production. The continuous tests show that loading of 600 g ZnSn(OH)6 has capacity to treat large volumes of VOCs and remains high removal efficiencies up to 600-h operation. The results suggest that the photocatalytic purifier could be potentially applied for the treatment of contaminated indoor air particularly ICU. The mechanism of ZnSn(OH)6 photocatalysis is proposed to interpret the high performance and mineralization of the degradation process.

DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production.

Adipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

Effects of Hot Balloon vs. Cryoballoon Ablation for Atrial Fibrillation: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background: Balloon-based catheter ablations, including hot balloon ablation (HBA) and cryoballoon ablation (CBA), have rapidly emerged as alternative modalities to conventional catheter atrial fibrillation (AF) ablation owing to their impressive procedural advantages and better clinical outcomes and safety. However, the differences in characteristics, effectiveness, safety, and efficacy between HBA and CBA remain undetermined. This study compares the characteristic and prognosis differences between HBA and CBA. Methods: Electronic search was conducted in six databases (PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrial.gov, and medRxiv) with specific search strategies. Eligible studies were selected based on specific criteria; all records were identified up to June 1, 2021. The mean difference, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Heterogeneity and risk of bias were assessed using predefined criteria. Results: Seven studies were included in the final meta-analysis. Compared with CBA, more patients in the HBA group had residual conduction and required a higher incidence of touch-up ablation (TUA) [OR (95% CI) = 2.76 (2.02-3.77), P = 0.000]. The most frequent sites of TUA were the left superior pulmonary veins (PVs) in the HBA group vs. the right inferior PVs in the CBA group. During HBA surgery, the left and right superior PVs were more likely to have a higher fluid injection volume. Furthermore, the procedure time was longer in the HBA group than in the CBA group [weighted mean difference (95% CI) = 14.24 (4.39-24.09), P = 0.005]. Patients in the CBA group could have an increased risk of AF occurrence, and accepted more antiarrhythmic drug therapy; however, the result was insignificant. Conclusions: HBA and CBA are practical ablation approaches for AF treatment. Patients who received HBA had a higher incidence of TUA and longer procedure time. Clinical outcomes during the mid-term follow-up between HBA and CBA were comparable. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259487, identifier: CRD42021259487.

Effects of Clinicopathological Characteristics on the Survival of Patients Treated with PD-1/PD-L1 Inhibitor Monotherapy or Combination Therapy for Advanced Cancer: A Systemic Review and Meta-Analysis.

BACKGROUND: PD-1/PD-L1 inhibitors have made unprecedented progress in the treatment of cancer. METHODS: A systemic search was conducted for randomized controlled trials that compared PD-1/PD-L1 inhibitor monotherapy or combination therapy with nonimmunotherapy. Hazard ratios (HRs) of overall survival (OS) according to the sex, age, ECOG PS, smoking status, liver metastasis, PD-L1 expression, EGFR, and KRAS status of patients were analyzed. RESULTS: Totally, 13 studies with monotherapy and 5 with combination regimens were included, and the pooled HRs of OS were 0.74 (P < 0.001) and 0.64 (P < 0.001), respectively. EGFR wild-type patients could benefit from immunotherapy monotherapy (HR, 0.77; P < 0.001) while those of the mutant type had no survival benefit (HR, 1.11; P = 0.54), and the difference was statistically significant (interaction, P = 0.005). KRAS wild-type patients had no survival benefit from monotherapy (HR, 0.89; P = 0.49). For combination therapy, both male and female derived benefits but female had a significantly reduced risk of death (HR, 0.45; P < 0.001) compared with male (HR, 0.73; P < 0.001; interaction, P = 0.004). Nonsmokers derived more survival benefits from combination therapy (HR, 0.29; P < 0.001) than smokers (HR, 0.63; P = 0.001; interaction, P = 0.02). No significant difference was found between age, ECOG PS, liver metastasis, PD-L1 expression, and OS of both PD-1/PD-L1 inhibitor monotherapy and combination therapy. CONCLUSIONS: Both PD-1/PD-L1 inhibitor monotherapy and combination therapy significantly prolonged the OS of patients with advanced malignant tumors. EGFR status for monotherapy and sex and smoking status for combination therapy were important predictors of survival benefits.