Effect of post-extubation high-flow nasal cannula combined with respiratory training versus conventional oxygen therapy on postoperative pulmonary complications in patients after major abdominal surgery: protocol for a single-centre randomized controlled trial.

BACKGROUND: Nearly 234 million patients undergo surgery each year, and 1.3 million among them develop complications. Patients undergoing major upper abdominal surgery (operation time > 2 h) have a really high incidence of postoperative pulmonary complications (PPCs). The occurrence of PPCs seriously affects the outcomes of patients. High-flow nasal cannula (HFNC) is as effective as noninvasive ventilation (NIV) in preventing postoperative hypoxaemia and respiratory failure. Respiratory training using positive expiratory pressure (PEP) Acapella (Choice) has been shown to help patients with rapid recovery from postoperative atelectasis. However, no relevant randomized controlled studies have been conducted to clarify the effect of HFNC combined with respiratory training in the prevention of PPCs. This study aims to investigate whether the use of HFNC combined with respiratory training could reduce the incidence of PPCs within 7 days after major upper abdominal surgery compared to that with conventional oxygen therapy (COT). METHODS: This is a randomized controlled single-centre trial. A total of 328 patients who undergo major abdominal surgery will be included. Subjects who fulfil the eligible criteria will be randomly assigned into the combination treatment group (Group A) or COT group (Group B) after extubation. The interventions will begin within 30 min of extubation. Patients in Group A will receive HFNC for at least 48 h and respiratory training three times a day for at least 72 h. Patients in Group B will receive oxygen therapy through a nasal catheter or mask for at least 48 h. Our primary endpoint is the incidence of PPCs within 7 days, and the secondary outcome measures include 28-day mortality, reintubation rate, length of hospital stay, and all-cause mortality within 1 year. DISCUSSION: This trial would help provide evidence on the effectivity of applying HFNC combined with respiratory training for the prevention of PPCs in patients undergoing major upper abdominal surgery. The objective of this study is to determine the optimal treatment approach to improve the prognosis of patients undergoing surgery. TRIAL REGISTRATION: ChiCTR2100047146. Registered on 8 June 2021. Retrospectively registered.

Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.

BACKGROUND: Pyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC. METHODS: Gene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2. RESULTS: In HCC, the expression of UCK2 was upregulated in part by TGFß1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing. CONCLUSIONS: Targeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.