Plac8-ERK pathway modulation of monocyte function in sepsis.

Sepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients. Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively. Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes. Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes. In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients.

The role of laparoscopy in closed abdominal injury.

Objective: To investigate the effect of laparoscopy on the diagnosis and treatment of closed abdominal injury. Methods: A total of 26 patients with closed abdominal injury admitted to our hospital from January 2016 to January 2019 were searched. All patients were treated by laparoscopy. All patient reports were made with the informed consent of the patients. Results: All patients were diagnosed clearly during operation. Among them, there were 3 cases of gastric perforation, 2 cases of liver rupture, 13 cases of spleen rupture, 3 cases of small intestine rupture, 1 case of liver round ligament laceration, 2 cases of small mesenteric vascular laceration, 1 case of colon liver mesenteric laceration, and 1 case of retroperitoneal hematoma. Of the 26 patients in this group, 23 (88.5%) completed laparoscopically or laparoscopically assisted; 5 cases (19.3%) only performed laparoscopic exploration without special treatment, and 3 cases (11.5%) switched to laparotomy. The blood loss was 50-2000 ml (mean 500 ml), and the operative time was 60-180min (mean 128min). The length of hospital stay was 3-21 d (mean 9 d). There were no complications or deaths related to laparoscopy in the whole group. Conclusion Laparoscopic technique has the advantages of less trauma, high diagnosis rate and fast recovery. It can also be used for surgical treatment in the diagnosis and treatment of closed abdominal injury, so as to achieve the purpose of comprehensive diagnosis and treatment. The limitations of laparoscopy should also be noted.

Analysis of risk factors for complications after laparoscopic cholecystectomy.

To analyze the risk factors of complications after laparoscopic cholecystectomy in 478 patients in our hospital. METHODS: The clinical data of 478 patients who underwent laparoscopic cholecystectomy in our hospital from March 2018 to September 2022 were collected, and the occurrence of postoperative complications and related risk factors were analyzed. RESULTS: A total of 36 patients (7.53%) had complications, including 9 cases (1.88%) of abdominal hemorrhage, 8 cases (1.67%) of bile duct injury, and 19 cases (3.97%) of biliary fistula. Univariate analysis showed that adhesions of Calot triangle, anatomical variation and gallbladder wall thickness greater than 5 mm were associated with postoperative complications (all P < 0.05). Multivariate analysis showed that: Calot triangle adhesion (OR = 3.041, 95%CI = 1.422-6.507), anatomical variation (OR = 4.368, 95%CI = 1.764-10.813) and gallbladder wall thickening (OR = 2.827, 95%CI = 1.422-6.507). 95%CI = 1.274-6.275) were independent risk factors for complications after laparoscopic cholecystectomy (all P < 0.05). CONCLUSION: In order to reduce the occurrence of postoperative complications, the risk factors of LC should be well understood and the preoperative preparation should be made.

Forsythiaside A Alleviates Lipopolysaccharide-Induced Acute Liver Injury through Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

The liver is the primary site of inflammation caused by bacterial endotoxins in sepsis, and septic acute liver injury (SALI) is usually associated with poor outcomes in sepsis. Forsythiaside A (FTA), an active constituent of Forsythia suspensa, has been reported to have anti-inflammatory properties, antioxidant properties, and protective properties against neuroinflammation, sepsis, and edema. Therefore, the purpose of the present study was to examine FTA's potential effects on lipopolysaccharide (LPS)-induced SALI in mice. Our results indicated that pretreatment with FTA significantly attenuated aspartate aminotransferase (AST) and aminoleucine transferase (ALT) levels in plasma, ameliorated histopathological damage, inhibited hepatocyte apoptosis, diminished the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in the liver from mice exposed to LPS. Furthermore, our data showed that the administration of LPS resulted in robust endoplasmic reticulum (ER) stress response, as evidenced by glucose-regulated protein 78 (GRP78) upregulation, phosphorylated-protein kinase R-like ER kinase (p-PERK) activation, elF2α phosphorylation, and activating transcription factor 4 (ATF4) and CHOP overexpression in the liver. This, in turn, led to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation, including the cleavage of caspase-1, secretion of IL-1ß, and pyroptotic cell death in the liver specimens. Importantly, the ER stress response induced by the LPS challenge was blocked by FTA administration. Correspondingly, NLRP3 inflammasome activation was significantly ameliorated by the pretreatment with FTA. Thus, we demonstrated that FTA pretreatment could protect mice from LPS-induced SALI, and its protective effects were possibly mediated by inhibiting ER stress response and subsequent NLRP3 inflammasome activation.

Genipin Attenuates Sepsis-Induced Splenocyte Apoptosis via the Inhibition of Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.