Advances in objective assessment of ergonomics in endoscopic surgery: a review.

Background: Minimally invasive surgery, in particular endoscopic surgery, has revolutionized the benefits for patients, but poses greater challenges for surgeons in terms of ergonomics. Integrating ergonomic assessments and interventions into the multi-stage endoscopic procedure contributes to the surgeon's musculoskeletal health and the patient's intraoperative safety and postoperative recovery. Objective: The purpose of this study was to overview the objective assessment techniques, tools and assessment settings involved in endoscopic procedures over the past decade and to identify the potential factors that induce differences in high workloads in endoscopic procedures and ultimately to design a framework for ergonomic assessment in endoscopic surgery. Methods: Literature searches were systematically conducted in the OVID, pubmed and web of science database before October 2022, and studies evaluating ergonomics during the process of endoscopic procedures or simulated procedures were both recognized. Results: Our systematic review of 56 studies underscores ergonomic variations in endoscopic surgery. While endoscopic procedures, predominantly laparoscopy, typically incur less physical load than open surgery, extended surgical durations notably elevate ergonomic risks. Surgeon characteristics, such as experience level and gender, significantly influence these risks, with less experienced and female surgeons facing greater challenges. Key assessment tools employed include electromyography for muscle fatigue and motion analysis for postural evaluation. Conclusion: This review aims to provide a comprehensive analysis and framework of objective ergonomic assessments in endoscopic surgery, and suggesting avenues for future research and intervention strategies. By improving the ergonomic conditions for surgeons, we can enhance their overall health, mitigate the risk of WMSDs, and ultimately improve patient outcomes.

Mitochondrial Micropeptide STMP1 Enhances Mitochondrial Fission to Promote Tumor Metastasis.

Micropeptides are a recently discovered class of molecules that play vital roles in various cellular processes, including differentiation, proliferation, and apoptosis. Here, we sought to identify cancer-associated micropeptides and to uncover their mechanistic functions. A micropeptide named short transmembrane protein 1 (STMP1) that localizes at the inner mitochondrial membrane was identified to be upregulated in various cancer types and associated with metastasis and recurrence of hepatocellular carcinoma. Both gain- and loss-of-function studies revealed that STMP1 increased dynamin-related protein 1 (DRP1) activation to promote mitochondrial fission and enhanced migration of tumor cells. STMP1 silencing inhibited in vivo tumor metastasis in xenograft mouse models. Overexpression of STMP1 led to redistribution of mitochondria to the leading edge of cells and enhanced lamellipodia formation. Treatment with a DRP1 inhibitor abrogated the promotive effect of STMP1 on mitochondrial fission, lamellipodia formation, and tumor cell migration in vitro and metastasis in vivo. Furthermore, STMP1 interacted with myosin heavy chain 9 (MYH9), the subunit of nonmuscle myosin II, and silencing MYH9 abrogated STMP1-induced DRP1 activation, mitochondrial fission, and cell migration. Collectively, this study identifies STMP1 as a critical regulator of metastasis and a novel unit of the mitochondrial fission protein machinery, providing a potential therapeutic target for treating metastases. SIGNIFICANCE: This study identifies the mitochondrial micropeptide STMP1 as a regulator of metastasis that promotes mitochondrial fission and tumor cell migration via DRP1 and MYH9.

Mitochondrial micropeptide STMP1 promotes G1/S transition by enhancing mitochondrial complex IV activity.

The roles of micropeptides in cell cycle regulation and cancer development remain largely unknown. Here we found that a micropeptide STMP1 (small transmembrane protein 1) was up-regulated in multiple malignancies including hepatocellular carcinoma (HCC), and its high level was associated with short recurrence-free survival of HCC patients. Gain- and loss-of-function analyses revealed that STMP1 accelerated cell proliferation and clonogenicity in vitro and tumor growth in vivo, and silencing STMP1 blocked G1/S transition. Mechanistically, STMP1 promoted the mRNA and protein levels of CCNE2, CDK2, and E2F1. STMP1 was localized in the inner membrane of mitochondria and interacted with mitochondrial complex IV and then enhanced its activity. Moreover, treatment with the mitochondrial complex IV inhibitor tetrathiomolybdate dramatically abrogated the promoting effect of STMP1 on cell proliferation and the expression of cyclin E2, CDK2, and E2F1. These results suggest that STMP1 may promote G1/S transition and cell proliferation by enhancing mitochondrial complex IV activity, which highlights STMP1 as a new regulator of the cell cycle and a potential target for anti-cancer therapy.

Opposing roles of C/EBPα and eEF1A1 in Sp1-regulated miR-122 transcription.

We previously showed that miR-122 was frequently downregulated in hepatocellular carcinoma (HCC) and C/EBPα transactivated miR-122 expression. In this study, we found that Sp1 bound to the miR-122 promoter at two different sites. Interestingly, either inhibition or overexpression of Sp1 could decrease the miR-122 promoter activity and the cellular miR-122 level in hepatoma cells. Further investigations disclosed that Sp1 cooperated with C/EBPα to induce miR-122 transcription by binding to the positive regulatory site D in the miR-122 promoter, whereas eEF1A1 interacted with Sp1 to bind to the negative regulatory site E and inhibit miR-122 transcription. Significantly, both Sp1 and eEF1A1 levels were enhanced, but C/EBPα and miR-122 expression were reduced in HCC tissues. Knockdown of eEF1A1 enhanced miR-122 level and inhibited cell growth, and these effects were abrogated when Sp1 was silenced. Consistently, the promoter activity enhanced by site E deletion was attenuated by silencing Sp1. Moreover, reduction of miR-122 resulted from Sp1 overexpression was rescued by coexpressing C/EBPα. These data suggest that C/EBPα and eEF1A1 may play opposing roles in Sp1-regulating miR-122 transcription, and the eEF1A1 upregulation accompanied by C/EBPα downregulation in HCC may switch the regulatory functions of Sp1 and led to reduced miR-122 transcription. These findings highlight the complex regulatory network of miR-122 expression and its significance in hepatocarcinogenesis.Abbreviations: MiRNA: microRNA; HCC, hepatocellular carcinoma; eEF1A1: eukaryote translation elongation factor 1A1; siRNA: small interfering RNA; qPCR: real-time quantitative RT-PCR; EMSA: electrophoretic mobility shift assay; ChIP: chromatin immunoprecipitation; TSS: transcription start site.