Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study.

INTRODUCTION: Anemia is a common manifestation of chronic liver diseases. It is a predictor of severe disease, a high risk of complications, and poor outcomes in various liver diseases. However, it remains unclear whether anemia serves as a similar indicator in patients with Wilson disease (WD). Therefore, this study aimed to investigate the relationship between anemia and severity, hepatic complications, and the progression of WD. METHODS: Medical data were collected retrospectively from January 1, 2016, to December 31, 2020. Univariate and multivariate analyses were carried out to investigate the relationship between anemia and liver-associated disease severity, hepatic complications, and the progression of WD. RESULTS: A total of 288 WD patients (48 with and 240 without anemia) were enrolled in the study. Multivariate linear regression revealed that WD patients with anemia had significantly higher levels of bilirubin, alanine transaminase, prothrombin time, international normalized ratio, type Ⅳ collagen, and hyaluronic acid and significantly lower levels of albumin, total cholesterol, and high-density lipoprotein-cholesterol (all p < 0.05). Multivariate logistic regression showed that anemia was a risk factor for gastric varices and ascites (all p < 0.05). Fully adjusted Cox regression revealed that anemia was an independent risk factor for advanced Child-Pugh classification (p = 0.034). CONCLUSIONS: Anemia was common in WD patients and was associated with greater disease severity, a higher risk of hepatic complications, and a faster progression.

[A minimally invasive approach in the treatment of complicated anal fistula through spatium intermuscular of anal sphincter].

OBJECTIVE: To investigate the optimal operative approach for the complicated anal fistula. METHODS: One hundred and ninety-two cases with complicated anal fistula were randomly divided into minimally invasive operation group (through spatium intermuscular of anal sphincter) and fistula resection group. The operation time, bleeding time during and after operation, pain lasting time, healing time of incision, area of anal scar, anal malformation and function and post operative recurrence were observed and compared between the two groups. RESULTS: Compared to those of fistula resection group, the operative time was (36.5+/- 15.3)min, bleeding time during and after operation (2.0+/- 0.5)d, postoperative pain lasting time (1.5+/- 0.5)d, healing time of incision (18.5+/- 5.5)d in minimally invasive operation group. All were shortened (P< 0.05), and the incidence of anal malformation (5.2%, P< 0.01) and partial anal incontinence (2.1%, P< 0.01) was lower. There was no significant difference in postoperative recurrence between the two groups. CONCLUSIONS: The minimally invasive operation through spatium in termuscular of anal sphincter is superior to fistula resection on the management of complicated fistula.

Mild hypothermia protects liver against ischemia and reperfusion injury.

AIM: To determine whether mild hypothermia could protect liver against ischemia and reperfusion injury in pigs. METHODS: Twenty-four healthy pigs were randomly divided into normothermia, mild hypothermia and normal control groups. The experimental procedure consisted of temporary interruption of blood flow to total hepatic lobe for different lengths of time and subsequent reperfusion. Hepatic tissue oxygen pressure (PtiO2) and aspartate aminotransferase (AST) values were evaluated, and ultrastructural analysis was carried out for all samples. RESULTS: Serum AST was significantly lower, and hepatic PtiO2 values were significantly higher in the mild hypothermia group than in the normothermia group during liver ischemia-reperfusion periods (P=0.032, P=0.028). Meanwhile, the histopathologic injury of liver induced by ischemia-reperfusion was significantly improved in the mild hypothermia group, compared with that in the normothermia group. CONCLUSION: Mild hypothermia can protect the liver from ischemia-reperfusion injury in pigs.

[Expression and transcription of inducible nitric oxide synthase in the liver ischemic preconditioning in rats].

OBJECTIVE: To investigate the changes in transcription and expression of inducible nitric oxide synthase (NOS2) in the liver ischemic preconditioning (IP), and to determine the role of nitric oxide (NO) synthetic pathway in the liver IP in rats. METHODS: We randomly divided 131 Sprague Dawley rats into 3 groups: ischemia/reperfusion (I/R) group (n=52), IP group (n=41), and sham operation (S) group (n=38). Plasm NO concentration and the transcription and expression of NOS2 were detected 2 hours, 24 hours, and 1 week after the operation. RESULTS: (1) In the IP group, the NO concentrations at the 2nd hour, the 24th hour, and 1 week were significantly higher than those in the S group (P < 0.05, P < 0.01, P < 0.01, respectively) and the NO concentrations at the 2nd hour and the 24th hour were obviously higher than those in I/R group (all P < 0.01). In the I/R group, the NO concentration at the 2nd hour was significantly lower than that in the S group (P < 0.05); there was no significant difference between the I/R group and the S group 24 hours after the operation (P > 0.05), and the NO concentration 1 week after the operation was obviously higher than that in the S group (P < 0.05). (2) In the IP group, the transcription of NOS2 2 and 24 hours after the operation were significantly increased compared with that in the I/R group (all P < 0.05) , but after 1 week, the transcription was not statistically different between the IP group and the I/R group (P > 0.05). (3) In the IP group, the expressions of NOS2 after 2 and 24 hours were obviously higher than those in the I/R group (P < 0.05) and the S group (P < 0.05), but the expression between the IR group and the S group was not significantly different (P > 0.05); after 1 week, the expressions of NOS2 in IP group and I/R group were weakly positive (P > 0.05) , and those in S group were negative (P > 0.05). Conclusion The transcription and the expression of liver NOS2 increase after the liver received ischemic preconditioning in rats. That the peak phases of transcription and expression of NOS2 are ahead of time may be related to the early protective effect of the liver IP.