Electroacupuncture alleviates intestinal inflammation via a distinct neuro-immune signal pathway in the treatment of postoperative ileus.

BACKGROUND: The induction of intestinal inflammation as a result of abdominal surgery is an essential factor in postoperative ileus (POI) development. Electroacupuncture (EA) at ST36 has been demonstrated to relieve intestinal inflammation and restore gastrointestinal dysmotility in POI. This study aims to elucidate the neuroimmune pathway involved in the anti-inflammatory properties of EA in POI. METHODS: After intestinal manipulation (IM) was performed to induce POI, intestinal inflammation and motility were assessed 24 h post-IM, by evaluating gastrointestinal transit (GIT), cytokines expression, and leukocyte infiltration. Experimental surgery, pharmacological intervention, and genetic knockout mice were used to elucidate the neuroimmune mechanisms of EA. RESULTS: EA at ST36 significantly improved GIT and reduced the expression of pro-inflammatory cytokines and leukocyte infiltration in the intestinal muscularis following IM in mice. The anti-inflammatory effectiveness of EA treatment was abolished by sub-diaphragmatic vagotomy, whereas splenectomy did not hinder the anti-inflammatory benefits of EA treatment. The hexamethonium chloride (HEX) administration contributes to a notable reduction in the EA capacity to suppress inflammation and enhance motility dysfunction, and EA is ineffective in α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. CONCLUSIONS: EA at ST36 prevents intestinal inflammation and dysmotility through a neural circuit that requires vagal innervation but is independent of the spleen. Further findings revealed that the process involves enteric neurons mediating the vagal signal and requires the presence of α7nAChR. These findings suggest that utilizing EA at ST36 may represent a possible therapeutic approach for POI and other immune-related gastrointestinal diseases.

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.

Forsythiaside A ameliorates sepsis-induced acute kidney injury via anti-inflammation and antiapoptotic effects by regulating endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis is a systemic inflammatory response syndrome caused by an infection in the body, and accompanying acute kidney injury (AKI) is a common complication of sepsis. It is associated with increased mortality and morbidity. Forsythia Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a commonly used traditional Chinese medicine. AIMS OF THE STUDY: This study aimed to elucidate the protective effect of Forsythiaside A (FTA) on sepsis-induced AKI by downregulating inflammatory and apoptotic responses, and exploring its underlying mechanism. METHODS: Septic AKI was induced through intraperitoneal injection of LPS (10 mg/kg) using male C57BL/6 mice and pretreated with FTA or control saline. First, we assessed the degree of renal injury by creatinine, blood urea nitrogen measurement, and HE staining of renal tissue; secondly, the inflammation and apoptosis were measured byELISA, qPCR, and TUNEL immunofluorescence; finally, the mechanism was explored by computer molecular docking and Western blot. RESULTS: Our data showed that FTA markedly attenuated pathological kidney injuries, alleviated the elevation of serum BUN and Creatinine, suggesting the renal protective effect of FTA. Notably, FTA significantly inhibited the renal expression of proinflammatory cytokine IL-1ß, IL-6, and TNF-α both at protein and mRNA levels and attenuated cell apoptosis in the kidney, as measured by caspase-3 immunoblot and TUNEL assay, indicating its anti-Inflammation and antiapoptotic properties. Mechanistically, administration of LPS resulted in robust endoplasmic reticulum (ER) stress responses in the kidney, evidenced by glucose-regulated protein 78(GRP78) upregulation, protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation, eukaryotic initiation factor 2 alpha (elF2α) phosphorylation and C/EBP homologous protein (CHOP) overexpression, which could be significantly blocked by FTA pretreatment. Dynamic simulation and molecular docking were performed to provide further insight. CONCLUSIONS: Collectively, our data suggest that FTA ameliorates sepsis-induced acute kidney injury via its anti-inflammation and antiapoptotic properties by regulating PERK signaling dependent ER stress responses.

Improvement of the sepsis survival rate by adenosine 2a receptor antagonists depends on immune regulatory functions of regulatory T-cells.

Adenosine shows a significant immunosuppressive effect in sepsis via binding to the adenosine 2a receptor (A2aR). Both genetic deletion and pharmacological inhibition of the A2aR may improve survival in sepsis. However, available research on this protective mechanism is quite limited. We used an A2aR antagonist (ZM241385) to treat a cecal ligation and puncture model of normal mice or regulatory T-cell (Treg)-depletion mice and found that the protective effect of ZM241385 is dependent on Tregs. Mechanically, A2aR inactivation was associated with decreased frequencies and reduced function of Foxp3+ Tregs, as evidenced by Foxp3 and CTLA-4 expression and classical effector T-cell proliferative assays, suggesting Treg modulation is a potential protective mechanism against sepsis. Simultaneously, the function and quantity of abdominal neutrophils were improved with ZM241385 treatment. To see if a link exists between them, Tregs and neutrophils were co-cultured, and it was found that ZM241385 blocked the inhibitory effect of Tregs on neutrophils. According to our research, Tregs play a key role in how A2aR antagonists improve sepsis prognosis and bacterial clearance.

The effect of warfarin knowledge on anticoagulation control among patients with heart valve replacement.

Background Although novel oral anticoagulants have been applied into clinical practice, warfarin remains the only approved oral anticoagulant for heart valve replacement. Currently, an increasing number of Chinese clinical pharmacists provide patients with warfarin education. However, little research to date has been carried out to evaluate the relationship between warfarin knowledge level and anticoagulation control among patients with heart valve replacement. Objective To evaluate knowledge of warfarin and the relationship between knowledge level and anticoagulation control among patients with heart valve replacement. Setting Fujian Medical University Union Hospital, China. Method A prospective and cross-sectional study was designed to evaluate the warfarin education of inpatients new to warfarin therapy using a validated Anticoagulation Knowledge Assessment questionnaire. Included patients were followed up for at least 3 months. Data were retrieved from hospital databases and telephone follow up. Main outcome measure Spearman's rho correlation analysis was used to assess the relationships between time in therapeutic range and warfarin knowledge level. Results 383 patients were included. The mean age of patients was 50.3 ± 7.9 years. The mean knowledge questionnaire score was 62.3 ± 8.8%. The majority of incorrect answers related to drug-warfarin interaction. Five of the frequently incorrect questions covered drugs, herbs and diet that affect warfarin therapy. There were significant correlations between total questionnaire score and time in therapeutic range (rho = 0.539, P < 0.001), or percentage of international normalized ratio measurements within range (rho = 0.416, P < 0.001). There were significant correlations between patients' educational level and total questionnaire score (rho = 0.357, P = 0.001). No significant correlations were found between income or living area and total questionnaire score (rho = 0.110, P = 0.435; rho = 0.161, P = 0.149). Conclusion Patient knowledge level of anticoagulation therapy affects anticoagulation control. Education for patients new to warfarin and the evaluation of knowledge by validated questionnaire is recommended for better INR control.