Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.

The role of PD-L1 in the immune dysfunction that mediates hypoxia-induced multiple organ injury

Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea.

Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression

Sepsis is characterized by persistent systemic inflammation, which can cause multi-organ dysfunction. The poly polymerase-1 inhibitor olaparib possesses anti-inflammatory properties. This study aimed to assess the effects of olaparib (pre- and post-treatments) on sepsis, and to investigate whether it could suppress CD14 expression via the ERK pathway in polymicrobial sepsis and peritoneal macrophages models. Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Fifty mice were randomly divided into five groups: The sham group was treated with vehicle or olaparib, the cecal ligation and puncture group with vehicle or with olaparib (5 mg/kg i.p.) 1 h before or 2 h after surgery. Olaparib pretreatment significantly improved the survival of septic mice ( P < 0.001). Pre- and post-treatment of mice with olaparib partly alleviated cecal ligation and puncture-induced organ injury by decreasing the amounts of the pro-inflammatory mediators TNF-α and IL-6 as well as bacterial burden in the serum, peritoneal lavage fluid, and organs ( P < 0.05). The protective effect of olaparib was associated with CD14 suppression via inhibition of ERK activation. Olaparib facilitated negative regulation of ERK-mediated CD14 expression, which may contribute to multi-organ injury in sepsis.

Accident-related hepatic trauma in a medical clinical center in eastern China: a cross-sectional study

Background The treatment of hepatic injury can be complex. Medical clinical centers are often the first line hospitals for the diagnosis and treatment of hepatic trauma in China. The aim of the study is to summarize the experience in the diagnosis and treatment of hepatic trauma in one medical clinical center in China. Methods This retrospective study included patients with hepatic trauma admitted between January 2002 and December 2019 at the Xishan People’s Hospital of Wuxi. The outcomes were cure rate and death within 14 days post-discharge. Results Among the 318 patients with hepatic trauma, 146 patients underwent surgical treatment, and 172 received conservative treatment; three patients were transferred to other hospitals for further treatment; 283 patients were cured, and 35 died. Severe hepatic trauma occurred in 74 patients, with a mortality rate of 31.1% and accounting for 65.7% of total mortality. American Association for the Surgery of Trauma (AAST) grading ≥ III (OR = 3.51, 95%CI: 1.32–9.37, P = 0.012) and multiple organ injury (OR = 7.51, 95%CI: 2.51–22.46, P < 0.001) were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death (OR = 0.08, 95%CI: 0.01–0.45, P = 0.004). Among patients with ASST ≥ III and who underwent surgery, age (OR = 5.29, 95%CI: 1.37–20.33, P = 0.015) and peri-hepatic packing (PHP) (OR = 5.54, 95%CI: 1.43–21.487, P = 0.013) were independently associated with death. Conclusions AAST grading ≥ III and multiple organ injury were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death. Among patients with ASST ≥ III and who underwent surgery, age and PHP were independently associated with death.

A Death Case Report in an Adult Woman With COVID-19 after Septoplasty

The mortality rate of Coronavirus Decease 2019 (COVID-19) is very high, but specific situations can increase the rate including severe hypoxemia, multiple organ injury, and thromboembolic events in various organs. Another factor is the stress caused after surgery that require general anesthesia. This study aims to report a case of death in an adult woman with COVID-19 infection who had underwent septoplasty and admitted to hospital after worsening of her general condition and treated when diagnosed with COVID-19. One day after admission, she was intubated due to progressive respiratory failure and deceased following bradycardia and cardiac arrest. It seems that the elective surgery should be avoided in patients infected with COVID-19 and should be postponed until complete recovery. Moreover, the possibility of this infection should be considered in all candidates for surgery with subtle respiratory symptoms.

Accident-related Hepatic Trauma in a Medical Clinical Center in Eastern China: A Cross-sectional Study

Background: The treatment of hepatic injury can be complicated. Medical clinical hospitals are often the first line hospitals for the diagnosis and treatment of hepatic trauma in China. This paper aimed to summarize the experience in the diagnosis and treatment of hepatic trauma in one medical clinical center in China. Methods: This retrospective study included patients with hepatic trauma admitted between January 2002 and December 2019 at the Xishan People’s Hospital of Wuxi. The outcomes were cure rate and death within 14 days post-discharge. Results: Among the 318 patients with hepatic trauma, 146 patients underwent surgical treatment, and 172 received conservative treatment; three patients were transferred to other hospitals for further treatment; 283 patients were cured, and 35 died. Severe hepatic trauma occurred in 74 patients, with a mortality rate of 31.1%, or 7.2% of all patients. American Association for the Surgery of Trauma (AAST) grading >III (OR=3.51, 95%CI: 1.32-9.37, P=0.012) and multiple organ injury (OR=7.51, 95%CI: 2.51-22.46, P<0.001) were independently associated with death. Among patients with AAST grading >III, surgery was an independent protective factor for death (OR=0.08, 95%CI: 0.01-0.45, P=0.004). Among patients with ASST >III and who underwent surgery, age (OR=5.29, 95%CI: 1.37-20.33, P=0.015) and PHP (OR=5.54, 95%CI: 1.43-21.487, P=0.013) were independently associated with death.Conclusions: AAST grading >III and multiple organ injury were independently associated with death. Among patients with AAST grading >III, surgery was an independent protective factor for death. Among patients with ASST >III and who underwent surgery, age and PHP were independently associated with death.