Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.

Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.

S100a8/9 (S100 Calcium Binding Protein a8/9) Promotes Cardiac Hypertrophy Via Upregulation of FGF23 (Fibroblast Growth Factor 23) in Mice.

BACKGROUND: S100a8/9 (S100 calcium binding protein a8/9) belongs to the S100 family and has gained a lot of interest as a critical regulator of inflammatory response. Our previous study found that S100a8/9 homolog promoted aortic valve sclerosis in mice with chronic kidney disease. However, the role of S100a8/9 in pressure overload-induced cardiac hypertrophy remains unclear. The present study was to explore the role of S100a8/9 in cardiac hypertrophy. METHODS AND RESULTS: Cardiomyocyte-specific S100a9 loss or gain of function was achieved using an adeno-associated virus system, and the model of cardiac hypertrophy was established by aortic banding-induced pressure overload. The results indicate that S100a8/9 expression was increased in response to pressure overload. S100a9 deficiency alleviated pressure overload-induced hypertrophic response, whereas S100a9 overexpression accelerated cardiac hypertrophy. S100a9-overexpressed mice showed increased FGF23 (fibroblast growth factor 23) expression in the hearts after exposure to pressure overload, which activated calcineurin/NFAT (nuclear factor of activated T cells) signaling in cardiac myocytes and thus promoted hypertrophic response. A specific antibody that blocks FGFR4 (FGF receptor 4) largely abolished the prohypertrophic response of S100a9 in mice. CONCLUSIONS: In conclusion, S100a8/9 promoted the development of cardiac hypertrophy in mice. Targeting S100a8/9 may be a promising therapeutic approach to treat cardiac hypertrophy.

Tailoring hypervalent Nickel induced by oxygen vacancy toward enhanced oxygen evolution reaction performance in self-supporting NiFe-(oxy)hydroxides electrodes.

NiFe-(oxy)hydroxides are the most active transition metal oxide electrocatalysts for oxygen evolution reaction (OER) under the alkaline media. Herein, we controllably manipulated oxygen vacancy (VO)-tunable NiFe-(oxy) hydroxides that their OER performances possessed a volcano-type relationship with VO concentration, positively-correlated with Ni3+/Ni2+ ratio. Theoretical simulations further unearthed the enhanced activation and dissociation of H2O by the inserting of VO. As a result, the optimal sample featuring the Ni3+/Ni2+ ratio of 30.3 % and VO of 23.8 % exhibited the overpotential of 243 mV at the current density of 100 mA cm-2, simultaneously lasting 120 h durability without any attenuation, exceding the most reported NiFe-(oxy)hydroxides. This work offers an innovative view to understand the OER performance using hypervalent Ni ratio induced by VO defects.

Photoperiodic and lighting treatments for flowering control and its genetic regulation in sugarcane breeding.

Improvement of sugarcane is hampered due to its narrow genetic base, and the difficulty in synchronizing flowering further hinders the exploitation of the genetic potential of available germplasm resources. Therefore, the continuous evaluation and optimization of flowering control and induction techniques are vital for sugarcane improvement. In view of this, the review was conducted to investigate the current understanding of photoperiodic and lighting treatment effects on sugarcane flowering and its genetic regulation. Photoperiod facilities have made a significant contribution to flowering control in sugarcane; however, inductive photoperiods are still unknown for some genotypes, and some intended crosses are still impossible to produce because of unresponsive varieties. The effectiveness of lower red/far-red ratios in promoting sugarcane flowering has been widely understood. Furthermore, there is vast potential for utilizing blue, red, and far-red light wavelengths in the flowering control of sugarcane. In this context, light-emitting diodes (LEDs) remain efficient sources of light. Therefore, the combined use of photoperiod regimes with different light wavelengths and optimization of such treatment combinations might help to control and induce flowering in sugarcane parental clones. In sugarcane, FLOWERING LOCUS T (ScFT) orthologues from ScFT1 to ScFT13 have been identified, and interestingly, ScFT3 has evidently been identified as a floral inducer in sugarcane. However, independent assessments of different FT-like gene family members are recommended to comprehensively understand their role in the regulation of flowering. Similarly, we believe this review provides substantial information that is vital for the manipulation of flowering and exploitation of germplasm resources in sugarcane breeding.

A simplified electrochemical model for lithium-ion batteries based on ensemble learning.

The mass transfer in lithium-ion batteries is a low-frequency dynamic that affects their voltage and performance. To find an effective way to describe the mass transfer in lithium-ion batteries, a simplified electrochemical lithium-ion battery model based on ensemble learning is proposed. The proposed model simplifies lithium-ion transfer in electrode particles with ensemble learning which ensembles discrete-time realization algorithm (DRA), fractional-order Padé approximation model (FOM), and three parameters (TPM) parabolic. The lithium-ion transfer in the electrolyte is simplified by the first-order inertial element (FIE). The results show that the proposed model achieves not only accurate lithium-ion concentration prediction in solid and electrolyte phase but also precise voltage prediction with low computational complexity.

Adipose triglyceride lipase suppresses noncanonical inflammasome by hydrolyzing LPS.

Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1ß, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.

IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice.

Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in male mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.

Feasibility and safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in a center in Hong Kong.

INTRODUCTION: The left distal trans-radial approach is not only more convenient for the operator than the conventional left forearm radial approach, it is also more comfortable for right-hand patients during the peri-procedural period. Comparing with conventional approach, it has lower bleeding risk, less pain and lower risk of radial artery occlusion. The aim of this study was to determine the feasibility and the safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in Hong Kong Chinese who had smaller body built and therefore smaller radial arterial size. METHOD: In this single-center prospective study, 72 patients undergoing elective coronary angiography and/or percutaneous coronary intervention were recruited from August to October 2018. All right-handed patients aged 18 or above undergoing elective procedures during the period were recruited. Exclusion criteria were non-palpable radial arteries, pregnancies, incapability to consent, abnormal Allen's test, and emergency procedures. Sixty patients (42 males, age ranging from 45 to 86 years old) were recruited and underwent the procedures via left distal radial approach. The measurements during access establishment, the procedure details, complications, patients' satisfaction, and arterial occlusion rate were studied. RESULTS: The procedures with left distal radial approach were successful in 51 patients (85%). Crossover rate to conventional right radial approach was 15% (nine patients). Among successful cases, the mean patients' satisfaction was 8.32/10 and the mean pain score was 1.6/10. Post-procedural radial artery occlusion was not encountered. CONCLUSION: Left distal radial approach is a feasible alternative for patients undergoing coronary angiography and/or percutaneous coronary intervention in Hong Kong Chinese patients. It provides good comfortability with minimal pain in right-handed patients. The risk of radial artery occlusion is minimal.

Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice.

The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury.

Mapping current research and identifying hotspots of ferroptosis in cardiovascular diseases.

Objective: Ferroptosis is a unique cell death depended on iron metabolism disorder which is different from previous apoptosis-regulated cell death. Early studies have proposed that ferroptosis is closely associated with multiple cardiovascular diseases (CVDs). However, the relationship of ferroptosis and CVDs has not been summarized by using bibliometric analysis. We intended to illustrate the development of ferroptosis in CVDs over the past years and provide relevant valuable information. Materials and methods: The authoritative database of Web of Science Core Collection was collected for retrieving ferroptosis studies in CVDs. In this work, statistical and visualization analysis were conducted using VOSviewer and Citespace. Results: A total of 263 studies were included in the final study. From the perspective of the overall literature, the study maintains an increased trend year by year and most manuscripts belonged to original article. China was the most productive country with the utmost scientific research output, as well as the institutions and authors, followed by Germany and the United States of America (USA). Jun Peng from China contributes to the most publications. Collaborative efforts between institutes and authors were limited and there was little widespread cooperation. In addition, burst keywords analysis discovered that ischemia-reperfusion (I/R) injury, heart failure (HF), and atherosclerosis were the top three research directions of ferroptosis in CVDs. The burst investigation and timeline views also indicated that endothelial injury and gut microbiota may also serve as new research topics in the future. Conclusion: This study provided comprehensive and specific information about the most influential articles on ferroptosis in CVDs. The relationship between ferroptosis and CVDs had attracted the scholar's concerns especially in China. Cooperations and communications between countries and institutions should be emphasized and future directions can be concentrated on endothelial disorder and gut microbiota.

Fibronectin type III domain-containing 5 improves aging-related cardiac dysfunction in mice.

Aging is an important risk factor for cardiovascular diseases, and aging-related cardiac dysfunction serves as a major determinant of morbidity and mortality in elderly populations. Our previous study has identified fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, as the cardioprotectant against doxorubicin-induced cardiomyopathy. Herein, aging or matched young mice were overexpressed with FNDC5 by adeno-associated virus serotype 9 (AAV9) vectors, or subcutaneously infused with irisin to uncover the role of FNDC5 in aging-related cardiac dysfunction. To verify the involvement of nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) and AMP-activated protein kinase α (AMPKα), Nlrp3 or Ampkα2 global knockout mice were used. Besides, young mice were injected with AAV9-FNDC5 and maintained for 12 months to determine the preventive effect of FNDC5. Moreover, neonatal rat cardiomyocytes were stimulated with tumor necrosis factor-α (TNF-α) to examine the role of FNDC5 in vitro. We found that FNDC5 was downregulated in aging hearts. Cardiac-specific overexpression of FNDC5 or irisin infusion significantly suppressed NLRP3 inflammasome and cardiac inflammation, thereby attenuating aging-related cardiac remodeling and dysfunction. In addition, irisin treatment also inhibited cellular senescence in TNF-α-stimulated cardiomyocytes in vitro. Mechanistically, FNDC5 activated AMPKα through blocking the lysosomal degradation of glucagon-like peptide-1 receptor. More importantly, FNDC5 gene transfer in early life could delay the onset of cardiac dysfunction during aging process. We prove that FNDC5 improves aging-related cardiac dysfunction by activating AMPKα, and it might be a promising therapeutic target to support cardiovascular health in elderly populations.

Underlying the Mechanisms of Doxorubicin-Induced Acute Cardiotoxicity: Oxidative Stress and Cell Death.

Cancer is a destructive disease that causes high levels of morbidity and mortality. Doxorubicin (DOX) is a highly efficient antineoplastic chemotherapeutic drug, but its use places survivors at risk for cardiotoxicity. Many studies have demonstrated that multiple factors are involved in DOX-induced acute cardiotoxicity. Among them, oxidative stress and cell death predominate. In this review, we provide a comprehensive overview of the mechanisms underlying the source and effect of free radicals and dependent cell death pathways induced by DOX. Hence, we attempt to explain the cellular mechanisms of oxidative stress and cell death that elicit acute cardiotoxicity and provide new insights for researchers to discover potential therapeutic strategies to prevent or reverse doxorubicin-induced cardiotoxicity.

CHOP overexpression sensitizes human non-small cell lung cancer cells to cisplatin treatment by Bcl-2/JNK pathway.

C/EBP homologous protein (CHOP), a 29 kDa cellular protein, plays a role in regulating tumor proliferation, differentiation, metabolism, cell death, and in tumor resistance to chemotherapy. Non-small cell lung cancer (NSCLC) is a tumor of the respiratory system and drug resistance is prevalent among NSCLC clinical cell cultures. Herein, our study elucidated the effect of CHOP on NSCLC cells with cisplatin resistance and its mechanism. In a NSCLC cell line with cisplatin-resistance, CHOP expression was decreased, compared with A549 cells. Overexpression of CHOP decreased the cell viability and enhanced cell apoptosis in the cells treated with cisplatin. Expression of CHOP also inhibited the cell proliferation and metastasis. CHOP increased the therapeutic effect of cisplatin on NSCLC cells through the Bcl-2/JNK pathway. In summary, CHOP regulated cisplatin resistance in cells of NSCLC by promoting the expression of apoptotic proteins and inhibiting the Bcl-2/JNK signaling pathway, indicating the antitumor effects of CHOP.

Prevalence of metabolic syndrome in patients with rheumatoid arthritis in eastern China-A hospital based study.

OBJECTIVE: The purpose of this hospital clinic based study was to evaluate the potential risk factors associated with the prevalence of MetS in RA population. METHODS: From January 2015 to October 2018, 717 patients with RA and 717 healthy controls who were treated or performed physical examination in Tianjin First Central Hospital were enrolled in this study. The basic disease diagnoses were recorded. A questionnaire was performed on all participants to assess the demographic details of the RA cohort. Moreover, laboratory indicators related to glucose and lipid metabolism in patients with RA were also detected. The potential risk factors for MetS were also analyzed. RESULTS: The prevalence of MetS were 31.2% and 34.2% in case and control groups, respectively (P = .22). There were lower levels of HDL-C, obesity, TG, LDL-C and TC in case group than control group (all P < .05). The hypertension levels in healthy controls was decreased in compared with patients with RA (P < .05). Nevertheless, in patients with RA, complement 3 (OR: 1.02; 95% CI: 1.01-1.03, P = .007) and less glucocorticoids use (OR: 0.63, 95% CI: 0.39-0.99, P = .046) were associated with MetS. CONCLUSION: The prevalence of MetS was not associated with RA. Complement 3 may be associated with the higher prevalence of MetS in patients with RA. Glucocorticoids treatment may be associated with MetS.

Osteocrin, a novel myokine, prevents diabetic cardiomyopathy via restoring proteasomal activity.

Proteasomal activity is compromised in diabetic hearts that contributes to proteotoxic stresses and cardiac dysfunction. Osteocrin (OSTN) acts as a novel exercise-responsive myokine and is implicated in various cardiac diseases. Herein, we aim to investigate the role and underlying molecular basis of OSTN in diabetic cardiomyopathy (DCM). Mice received a single intravenous injection of the cardiotrophic adeno-associated virus serotype 9 to overexpress OSTN in the heart and then were exposed to intraperitoneal injections of streptozotocin (STZ, 50 mg/kg) for consecutive 5 days to generate diabetic models. Neonatal rat cardiomyocytes were isolated and stimulated with high glucose to verify the role of OSTN in vitro. OSTN expression was reduced by protein kinase B/forkhead box O1 dephosphorylation in diabetic hearts, while its overexpression significantly attenuated cardiac injury and dysfunction in mice with STZ treatment. Besides, OSTN incubation prevented, whereas OSTN silence aggravated cardiomyocyte apoptosis and injury upon hyperglycemic stimulation in vitro. Mechanistically, OSTN treatment restored protein kinase G (PKG)-dependent proteasomal function, and PKG or proteasome inhibition abrogated the protective effects of OSTN in vivo and in vitro. Furthermore, OSTN replenishment was sufficient to prevent the progression of pre-established DCM and had synergistic cardioprotection with sildenafil. OSTN protects against DCM via restoring PKG-dependent proteasomal activity and it is a promising therapeutic target to treat DCM.

The Optimal Age to Stop Endoscopic Surveillance of Patients With Barrett's Esophagus Based on Sex and Comorbidity: A Comparative Cost-Effectiveness Analysis.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett's esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

Endothelial ERG alleviates cardiac fibrosis via blocking endothelin-1-dependent paracrine mechanism.

Cardiac endothelium communicates closely with adjacent cardiac cells by multiple cytokines and plays critical roles in regulating fibroblasts proliferation, activation, and collagen synthesis during cardiac fibrosis. E26 transformation-specific (ETS)-related gene (ERG) belongs to the ETS transcriptional factor family and is required for endothelial cells (ECs) homeostasis and cardiac development. This study aims at investigating the potential role and molecular basis of ERG in fibrotic remodeling within the adult heart. We observed that ERG was abundant in murine hearts, especially in cardiac ECs, but decreased during cardiac fibrosis. ERG knockdown within murine hearts caused spontaneously cardiac fibrosis and dysfunction, accompanied by the activation of multiple Smad-dependent and independent pathways. However, the direct silence of ERG in cardiac fibroblasts did not affect the expression of fibrotic markers. Intriguingly, ERG knockdown in human umbilical vein endothelial cells (HUVECs) promoted the secretion of endothelin-1 (ET-1), which subsequently accelerated the proliferation, phenotypic transition, and collagen synthesis of cardiac fibroblasts in a paracrine manner. Suppressing ET-1 with either a neutralizing antibody or a receptor blocker abolished ERG knockdown-mediated deleterious effect in vivo and in vitro. This pro-fibrotic effect was also negated by RGD (Arg-Gly-Asp)-peptide magnetic nanoparticles target delivery of ET-1 small interfering RNA to ECs in mice. More importantly, we proved that endothelial ERG overexpression notably prevented pressure overload-induced cardiac fibrosis. Collectively, endothelial ERG alleviates cardiac fibrosis via blocking ET-1-dependent paracrine mechanism and it functions as a candidate for treating cardiac fibrosis. • ERG is abundant in murine hearts, especially in cardiac ECs, but decreased during fibrotic remodeling. • ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. • ERG silence in HUVECs promotes the secretion of endothelin-1, which in turn activates cardiac fibroblasts in a paracrine manner. • Endothelial ERG overexpression prevents pressure overload-induced cardiac fibrosis.

Percutaneous biliary stent combined with brachytherapy using 125I seeds for treatment of unresectable malignant obstructive jaundice: A meta-analysis.

BACKGROUND: Malignant obstructive jaundice (MOJ) is a common pathologic manifestation of malignant biliary obstruction. Recently, several clinical trials have explored the clinical effectiveness of intraluminal 125I seed-based brachytherapy for MOJ patients, and various outcomes have been reported. AIM: To assess the efficacy and safety of percutaneous biliary stents with 125I seeds compared to conventional metal stents in patients with unresectable MOJ. METHODS: A systematic search of English-language databases (PubMed, Embase, Cochrane Library, and Web of Science) was performed to identify studies published prior to June 2020 that compared stents with or without 125I seeds in the treatment of unresectable MOJ. The outcomes analyzed included primary outcomes (stent patency and overall survival) and secondary outcomes (complications and liver function parameters). RESULTS: Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis. Of the 875 included patients, 404 were treated with 125I seed stents, while 471 were treated with conventional stents. Unadjusted pooled analysis demonstrated that compared to conventional stents, 125I seed stents extended the stent patency time [hazard ratio (HR) = 0.36, 95% confidence interval (CI) = 0.28-0.45, P < 0.0001] and overall survival period (HR = 0.52, 95%CI = 0.42-0.64, P < 0.00001). Subgroup analyses based on the type of 125I seed stent and type of study design showed consistent results. However, there were no significant differences in the occurrence of total complications [odds ratio (OR) = 1.12, 95%CI = 0.75-1.67, P = 0.57], hemobilia (OR = 1.02, 95%CI = 0.45-2.3, P = 0.96), pancreatitis (OR = 1.79, 95%CI = 0.42-7.53, P = 0.43), cholangitis (OR = 1.13, 95%CI = 0.60-2.13, P = 0.71), or pain (OR = 0.67, 95%CI = 0.22-2, P = 0.47). In addition, there were no reductions in the levels of serum indices, including total bilirubin [mean difference (MD) = 10.96, 95%CI = -3.56-25.49, P = 0.14], direct bilirubin (MD = 7.37, 95%CI = -9.76-24.5, P = 0.4), alanine aminotransferase (MD = 7.52, 95%CI = -0.71-15.74, P = 0.07), and aspartate aminotransferase (MD = -4.77, 95%CI = -19.98-10.44, P = 0.54), after treatment. Publication bias was detected regarding the outcome overall survival; however, the conclusions were not changed after the adjustment. CONCLUSION: Placement of stents combined with brachytherapy using 125I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage. Thus, it can be considered an effective and safe treatment for unresectable MOJ.