Latest Issue
Volume 39 ， Issue 3 ， 2024
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Abstract：ObjectiveThe extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed. In the present study, Mendelian randomization (MR) was employed to examine the potential causal relationship between hypertension and risk of chronic pain.MethodsThe study data were derived from the pooled dataset of the genome-wide association study (GWAS), enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest, abdominal, joint, back, limb, and multisite chronic pain. We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, quantified by odds ratio (OR).ResultsGenetically predicted essential hypertension was associated with an increased risk of chronic headache (OR = 1.007, 95% CI: 1.003‒1.011, P = 0.002) and limb pain (OR = 1.219, 95% CI: 1.033‒1.439, P = 0.019). No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR ( P > 0.05). In addition, there was no potential causal association between secondary hypertension and chronic pain (P > 0.05).ConclusionThis study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain, and no causal relationship was found between secondary hypertension and chronic pain. These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.Keywords：hypertension;chronic pain;Mendelian randomization;health;chronic headache;genetic evidence;limb pain113|29|0Updated：2025-01-08 -
Abstract：ObjectivesTo identify the 5' untranslated region of Zika virus (ZIKV 5'UTR) RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site (IRES) located in ZIKV 5'UTR and virus production.MethodsInteracting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining. Subsequently, liquid chromatography-tandem mass spectrometry (LC-MS/MS), bioinformatics analysis, and Western blot were used to identify the candidate proteins binding to ZIKV 5'UTR. Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production, respecitvely.ResultstRSA RNA pull-down assay, LC-MS/MS, and Western blot analysis showed that polypyrimidine tract-binding protein (PTB) bound to the ZIKV 5'UTR. Furthermore, dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV (t = 10.220, P < 0.001), while PTB knockdown had the opposite effect (t = 4.897, P < 0.01). Additionally, virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer (t = 6.400, P < 0.01), whereas reducing PTB expression level weakened virus infectivity (t = 5.055, P < 0.01).ConclusionPTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.Keywords：internal ribosomal entry site;polypyrimidine tract-binding protein;Zika virus;tRSA RNA pull-down;dual-luciferase reporter assay82|24|0Updated：2025-01-08 -
Abstract：ObjectiveTo screen the target genes that are associated with survival of breast cancer (BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..MethodsThe microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database (GEO) and analyzed to obtain differentially expressed genes (DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. The key gene was determined using R language, STRING, and Cytoscape, and the differential expression of the key gene was verified using external datasets The Cancer Genome Atlas (TCGA) and quantitative real-time PCR (qRT-PCR) for BRCA tissues of 37 patients. The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis (GSEA).ResultsOf 10 hub genes seleceed from 302 DEGS, UBE2C was identified as the gene associated with BRCA survival. The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and qRT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with immune checkpoints genes PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.ConclusionsUBE2C expression in BRCA tissues is closely related to the BRCA immune microenvironment and showes predictive values on the survivals and prognosis of BRCA patients and the effecacy of immunotherapy. UBE2C may be an potential immune-related prognostic biomarker for BRCA.Keywords：UBE2C;breast cancer;prognostic biomarker;immune;bioinformatics analyses;survival50|9|0Updated：2025-01-08 -
Abstract：ObjectiveTo investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization (MR) analysis.MethodsBidirectional MR was used to analyze pooled data from different genome-wide association studies (GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MR-PRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.ResultsPrimary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine (C20) levels were positively associated with osteoporosis (all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results (all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.ConclusionWe found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.Keywords：osteoporosis;plasma metabolites;Mendelian randomization;bidirectional analysis65|20|0Updated：2025-01-08 -
Abstract：ObjectiveTo explore the influence of Linggui Zhugan Decoction (LGZGD) on high glucose induced podocyte autophagy.MethodsLGZGD containing serum was prepared by intragastric administation of 4.2 g/kg (low dose), 8.4 g/kg (medium dose), and 12.6 g/kg (high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.ResultsCompared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect (P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate (P < 0.05) and higher survival rate (P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes (P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD (P < 0.05).ConclusionLGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.Keywords：diabetic nephropathy;podocyte;Linggui Zhugan decoction;apoptosis;autophagy41|20|0Updated：2025-01-08
Research Articles
- Abstract：With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.Keywords：vascular calcification;clinical;pathophysiology;therapeutic strategies;novel findings61|27|0Updated：2025-01-08
- Abstract：Approximately 40% of pheochromocytoma and paraganglioma (PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau (VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2 (MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1 (NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team (MDT) approach is often invaluable in perioperative management.Keywords：pheochromocytoma;paraganglioma;genetic disease;anesthetic management;hemodynamic;perioperative care71|25|0Updated：2025-01-08
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Abstract：Achieving optimal alignment in total knee arthroplasty (TKA) is a critical factor in ensuring optimal outcomes and long-term implant survival. Traditionally, mechanical alignment has been favored to achieve neutral post-operative joint alignment. However, contemporary approaches, such as kinematic alignments and hybrid techniques including adjusted mechanical, restricted kinematic, inverse kinematic, and functional alignments, are gaining attention for their ability to restore native joint kinematics and anatomical alignment, potentially leading to enhanced functional outcomes and greater patient satisfaction. The ongoing debate on optimal alignment strategies considers the following factors: long-term implant durability, functional improvement, and resolution of individual anatomical variations. Furthermore, advancements of computer-navigated and robotic-assisted surgery have augmented the precision in implant positioning and objective measurements of soft tissue balance. Despite ongoing debates on balancing implant longevity and functional outcomes, there is an increasing advocacy for personalized alignment strategies that are tailored to individual anatomical variations. This review evaluates the spectrum of various alignment techniques in TKA, including mechanical alignment, patient-specific kinematic approaches, and emerging hybrid methods. Each technique is scrutinized based on its fundamental principles, procedural techniques, inherent advantages, and potential limitations, while identifying significant clinical gaps that underscore the need for further investigation.Keywords：total knee arthroplasty;hybrid alignment;functional alignment;kinematic alignment;alignment axes;anatomical alignment;mechanical alignment43|21|0Updated：2025-01-08
Reviews
- Abstract：The growing utilization of critical care echocardiography (CCE) by clinicians necessitates a meticulous review of clinical conditions in critically ill patients, both before and during the examination. The reviewing process of clinical conditions minimizes the risk of overlooking or misinterpreting crucial findings. This article proposes a comprehensive strategy, namely BILL strategy, to integrate into the CCE protocol, where "B" represents baseline respiratory and hemodynamic support, "I" signifies information gleaned from invasive monitoring, including central venous pressure and thermodilution-derived cardiac output, the first "L" denotes laboratory results such as central venous oxygen saturation, troponin, and brain natriuretic peptide, and the second "L" refers to lung ultrasound data. Combining the BILL strategy with CCE can enhance comprehensive understanding of critical conditions, potentially leading to improved diagnostic accuracy and patient outcomes.Keywords：echocardiography;critical care;clinical condition75|13|0Updated：2025-01-08
Perspectives
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