Biomedical Journal最新文献

Background

Dysregulation of long non-coding RNAs (lncRNAs) is an important component of tumorigenesis. Aberrant expression of lncRNA taurine upregulated gene 1 (lncTUG1) has been reported in various tumors; however, its precise role and key targets critically involved in osteosarcoma (OS) progression remain unclear.

Methods

The expression profiles of lncRNAs and their regulated miRNAs related to OS progression were assessed by bioinformatics analysis and confirmed by qRT-PCR of OS cells. The miRNA targets were identified by transcriptome sequencing and verified by luciferase reporter and RNA pull-down assays. Several in vivo and in vitro approaches, including CCK8 assay, western blot, qRT-PCR, lentiviral transduction and OS cell xenograft mouse model were established to validate the effects of lncTUG1 regulation of miRNA and the downstream target genes on OS cell growth, apoptosis and progression.

Results

We found that lncTUG1 and miR-26a-5p were inversely up or down-regulated in OS cells, and siRNA-mediated lncTUG1 knockdown reversed the miR-26a-5p down-regulation and suppressed proliferation and enhanced apoptosis of OS cells. Further, we identified that an oncoprotein ZBTB7C was also upregulated in OS cells that were subjected to lncTUG1/miR-26a-5p regulation. More importantly, ZBTB7C knockdown reduced the ZBTB7C upregulation and ZBTB7C overexpression diminished the anti-OS effects of lncTUG1 knockdown in the OS xenograft model.

Conclusions

Our data suggest that lncTUG1 acts as a miR-26a-5p sponge and promotes OS progression via up-regulating ZBTB7C, and targeting lncTUG1 might be an effective strategy to treat OS.

Background

Epigenetics and clinical observations referring to Betacoronavirus lead to the conjecture that Sarbecovirus may have the ability to infect lymphocytes using a different way than the spike protein. In addition to inducing the death of lymphocytes, thus drastically reducing their population and causing a serious immune deficiency, allows it to remain hidden for long periods of latency using them as a viral reservoir in what is named Long-Covid Disease. Exploring possibilities, the hypothesis is focused on that N protein may be the key of infecting lymphocytes.

Method

The present article exhibits a computational assay for the latest complete sequences reported to GISAID, correlating N genotypes with an enhancement in the affinity of the complex that causes immune deficiency in order to determine a good docking with the N protein and some receptors in lymphocytes.

Results

A novel high-interaction coupling of N-RBD and CD147 is presented as the main way of infecting lymphocytes, allowing to define those genotypes involved in their affinity enhancement.

Conclusion

The hypothesis is consistent with the mutagenic deriving observed on the in-silico assay, which reveals that genotypes N/120 and N/152 are determinant to reduce the Immune Response of the host infecting lymphocytes, allowing the virus persists indefinitely and causing an Acquire Immune Deficiency Syndrome.

Obesity, type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are three common metabolic diseases with high prevalence worldwide. Emerging evidence suggests that gut dysbiosis may influence the development of metabolic diseases, in which gut fungal microbiome (mycobiome) is actively involved. In this review, we summarize the studies exploring the composition changes of gut mycobiome in metabolic diseases and mechanisms by which fungi affect the development of metabolic diseases. The current mycobiome-based therapies, including probiotic fungi, fungal products, anti-fungal agents and fecal microbiota transplantation (FMT), and their implication in treating metabolic diseases are discussed. We highlight the unique role of gut mycobiome in metabolic diseases, providing perspectives for future research on gut mycobiome in metabolic diseases.

Background

Endovascular management is the gold standard for cavernous sinus dural arteriovenous fistulas (CS-dAVFs) in patients with signs of ophthalmoplegia, visual defects, or intolerable clinical symptoms. Although the efficacy of embolization has been confirmed, complications during post-endovascular management have not been compared in a more extensive CS-dAVFs case series. Therefore, we compared the effectiveness and peri-procedural complications of transvenous coiling with those of transarterial embolization (TAE) using liquid embolic agents.

Methods

We reviewed 71 patients with CS-dAVFs in one medical center from 2005/7 to 2016/7. We performed seventy-seven procedures on 71 patients, including six recurrent cases. We compared the efficacy and peri-procedural complications of transvenous coiling and TAE.

Results

The complete occlusion rate for transvenous coiling was 79.2%, and that for TAE was 75.0%. Findings revealed (1) similar ophthalmoplegia complication rates (p = 0.744); (2) more frequent and permanent CN5 or CN7 neuropathy with liquid embolic agent use (p = 0.031 and 0.028, respectively); and (3) a higher risk of infarction or ICH (p = 0.002 and 0.028, respectively) in response to aggressive TAE.

Conclusion

Transvenous cavernous sinus coiling resulted in a similar occlusion rate and lower complication risk than transarterial Onyx/n-butyl cyanoacrylate (NBCA). We can access via an occluded inferior petrosal sinus (even contralateral), and direct transorbital puncture was a safe alternative. TAE with Onyx/NBCA was helpful in cases of oligo-feeders, but multidisciplinary treatment and multi-session TAE were usually needed for patients with multiple feeders and complex fistulas.

Background

Peri-intubation cardiac arrest (PICA) is an uncommon yet serious complication of intubation. Although some associated risk factors have been identified, the results have been inconsistent. The aim of this study was to systematically review the relevant research and examine the associated risk factors of PICA through meta-analysis.

Methods

Studies examining the risk factors for PICA before 1 Nov. 2022 were identified through searches in MEDLINE (OvidSP) and EMBASE. The reported adjusted or unadjusted odds ratios (ORs) and risk ratios (RRs) were recorded. We calculated pooled ORs and created forest plots using a random-effects model to identify the statistically significant risk factors. We assessed the certainty of evidence for each risk factor.

Results

Eight studies were included in the meta-analysis. Pre-intubation hypotension, with a pooled OR of 4.96 (95% confidence interval [C.I.]: 3.75–6.57), pre-intubation hypoxemia, with a pooled OR of 4.43 (95% C.I.: 1.24–15.81), and two or more intubation attempts, with a pooled OR of 1.88 (95% C.I.: 1.09–3.23) were associated with a significantly higher risk of PICA. The pooled incidence of PICA was 2.1% (95% C.I.: 1.5%–3.0%).

Conclusions

Pre-intubation hypotension, hypoxemia, and more intubation attempts are significant risk factors for PICA. The findings could help physicians identify patients at risk under the acute setting.

Background

This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models.

Methods

The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan.

Results

A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68–0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53–2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60–2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63–6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group.

Conclusion

The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention.

This issue of the Biomedical Journal features a special section exploring mycobiota. Three articles examine the role of fungi in common metabolic disorders in, Clostridium difficile infection, and in immunocompromised patients. Additionally, the potential and challenges of the metaverse in healthcare are reviewed, alongside a holistic approach to improve patient outcomes in pancreatic cancer. In this issue also possible mechanism contributing to long COVID are discussed, as well as biomarkers that effectively predict sepsis outcomes, and key targets in osteosarcoma progression. Moreover, factors leading to peri-intubation cardiac arrest are analyzed, healthcare strategies from various regions are employed to predict cardiovascular events in Asian populations, two approaches to cavernous sinus dural arteriovenous fistula are compared, and a combination therapy against soft tissue sarcoma is presented.

Background

Biomarker dynamics in different time-courses might be the primary reason why a static measurement of a single biomarker cannot accurately predict sepsis outcomes. Therefore, we conducted this prospective hospital-based cohort study to simultaneously evaluate the performance of several conventional and novel biomarkers of sepsis in predicting sepsis-associated mortality on different days of illness among patients with suspected sepsis.

Methods

We evaluated the performance of 15 novel biomarkers including angiopoietin-2, pentraxin 3, sTREM-1, ICAM-1, VCAM-1, sCD14 and 163, E-selectin, P-selectin, TNF-alpha, interferon-gamma, CD64, IL-6, 8, and 10, along with few conventional markers for predicting sepsis-associated mortality. Patients were grouped into quartiles according to the number of days since symptom onset. Receiver operating characteristic curve (ROC) analysis was used to evaluate the biomarker performance.

Results

From 2014 to 2017, 1483 patients were enrolled, of which 78% fulfilled the systemic inflammatory response syndrome criteria, 62% fulfilled the sepsis-3 criteria, 32% had septic shock, and 3.3% developed sepsis-associated mortality. IL-6, pentraxin 3, sCD163, and the blood gas profile demonstrated better performance in the early days of illness, both before and after adjusting for potential confounders (adjusted area under ROC curve [AUROC]:0.81–0.88). Notably, the Sequential Organ Failure Assessment (SOFA) score was relatively consistent throughout the course of illness (adjusted AUROC:0.70–0.91).

Conclusion

IL-6, pentraxin 3, sCD163, and the blood gas profile showed excellent predictive accuracy in the early days of illness. The SOFA score was consistently predictive of sepsis-associated mortality throughout the course of illness, with an acceptable performance.

Background

Given the heterogeneity and high mortality associated with metastatic soft tissue sarcoma, this study aims to evaluate the therapeutic efficacy of combining ¹⁷⁷Lu-FAPI-46 with Pazopanib against this malignancy.

Methods

Patient-derived xenograft (PDX)-bearing mice were randomly divided into three groups: the control group, the ¹⁷⁷Lu-FAPI-46 monotherapy group, and the ¹⁷⁷Lu-FAPI-46 combined with Pazopanib therapy group. Therapeutic efficacy was regularly monitored.

Results

The microPET imaging showed a 0.84-fold decrease in the T/M ratio of 68Ga-FAPI-46 on day 7/8 post combination therapy, while the control group exhibited a 1.23-fold increase. Combination therapy significantly inhibited tumor proliferation, as evidenced by reduced Ki-67 and increased caspase 3 expressions. Notably, there was no significant body weight loss observed in any group.

Conclusion

This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of ¹⁷⁷Lu-FAPI-46 with Pazopanib.

The Metaverse has gained wide attention for being the application interface for the next generation of Internet. The potential of the Metaverse is growing, as Web 3·0 development and adoption continues to advance medicine and healthcare. We define the next generation of interoperable healthcare ecosystem in the Metaverse. We examine the existing literature regarding the Metaverse, explain the technology framework to deliver an immersive experience, along with a technical comparison of legacy and novel Metaverse platforms that are publicly released and in active use. The potential applications of different features of the Metaverse, including avatar-based meetings, immersive simulations, and social interactions are examined with different roles from patients to healthcare providers and healthcare organizations. Present challenges in the development of the Metaverse healthcare ecosystem are discussed, along with potential solutions including capabilities requiring technological innovation, use cases requiring regulatory supervision, and sound governance. This proposed concept and framework of the Metaverse could potentially redefine the traditional healthcare system and enhance digital transformation in healthcare. Similar to AI technology at the beginning of this decade, real-world development and implementation of these capabilities are relatively nascent. Further pragmatic research is needed for the development of an interoperable healthcare ecosystem in the Metaverse.