Endoplasmic reticulum stress refers to a cellular stress response triggered when cells are stimulated,which is manifested as the disruption of endoplasmic reticulum homeostasis and dysfunction in various pathological conditions,resulting in the accumulation of a large number of misfolded and unfolded proteins within the endoplasmic reticulum and an imbalance of calcium ions.Macrophages are the most abundant immune cells in the liver and play an important role in maintaining liver homeostasis and various liver diseases.Recent studies have confirmed that the unfolded protein response caused by endoplasmic reticulum stress plays an important role in regulating macrophage immune response.This article reviews the mechanisms of endoplasmic reticulum stress regulating macrophage immune response and its role in liver diseases such as ischemia-reperfusion injury during organ transplantation,liver fibrosis,and hepatocellular carcinoma,in order to deepen the understanding of the mechanism of macrophage immune regulation and provide new ideas for research and interventional treatment related to liver diseases.

Objective:To construct the risk management model of ultrasonic scalpel based on logistic regression(LR)algorithm,and to improve the quality of ultrasonic risk management.Methods:Based on the LR algorithm,the risk management model of ultrasonic scalpel use was constructed and the model was verified.A total of 28 ultrasonic scalpels in clinical use in Shanghai Pulmonary Hospital from January 2022 to December 2023 were selected.Based on the time,the conventional management model was adopted during the use of the equipment in 2022,and the LR risk management model(referred to as risk management)was applied during the use of the equipment in 2023.The risk management quality score,risk warning score and experience score of the management personnel involved in the use of the equipment between the two management modes were compare by using the self-made evaluation scale.Results:The average scores of ultrasonic scalpel maintenance record,usage record,data filing,maintenance card hanging and scrapping treatment using risk management were(9.54±0.37),(9.67±0.34),(9.73±0.21),(9.18±0.35)and(9.92±0.31),respectively,which were higher than those of the conventional management,the difference was statistically significant(t=55.666,32.235,49.511,40.311,23.122,P<0.05).The average scores of ultrasonic scalpel risk identification accuracy,early warning timeliness and comprehensive prevention and control using risk management were(9.66±1.20),(9.92±1.48),and(9.87±1.04),respectively,which were higher than those of the conventional management mode,the difference was statistically significant(t=11.840,8.371,8.032,P<0.05).The average scores of ultrasonic scalpel preventive maintenance personnel,maintenance personnel and operators on the use experience of ultrasonic scalpel in risk management mode were(96.61±6.08),(95.07±5.19)and(97.73±5.93),respectively,which were higher than those in the conventional management mode,the difference was statistically significant(t=4.991,4.156,4.870,P<0.05).Conclusion:The application of ultrasonic scalpel risk management model based on LR algorithm to the use management of ultrasonic scalpel can improve the quality of ultrasonic scalpel risk management,avoid risk hazards,and enhance the safety and stability of clinical use of ultrasonic scalpel.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

Objective To investigate the metabolic outcomes of primary aldosteronism(PA)patients receiving adrenalectomy(ADX)or spironolactone treatment and the contributing factors to the metabolic outcomes.Methods The clinical data of 70 patients with aldosterone-producing adenoma(APA)and 86 patients with idiopathic hyperaldosteronism(IHA)were retrospectively analyzed.All subjects received confirmatory diagnosis of APA or IHA at the Department of Endocrinology and Metabolism,West China Hospital between March 2018 and October 2020.APA patients underwent ADX,while IHA patients were given spironolactone,a mineralocorticoid receptor antagonist(MRA).After ADX or spironolactone treatment,the outcomes of the metabolic indicators and the inter-group differences between the APA patients and IHA patients were studied.Results There was no significant difference between the baseline data of the APA group and those of the IHA group in terms of age,sex,duration of hypertension,maximum systolic blood pressure(SBP-max),maximum diastolic blood pressure(DBP-max),body mass index(BMI),fasting blood glucose(FBG),lipid parameters,and renal function.IHA patients had higher waist circumference,serum potassium,and plasma renin activity(PRA)than those of the APA patients(all P＜0.05).All patients showed significant improvement in blood pressure,blood potassium,and plasma aldosterone at follow-up.However,they also showed increased triglycerides(TG)accompanied by deterioration in renal function(P≤0.001).Multiple regression showed that TG levels were associated with spironolactone treatment for IHA patients and post-treatment BMI and creatinine levels.Furthermore,APA patients showed improvement in their FBG after ADX(P=0.041),while IHA patients showed elevated levels of FBG after spironolactone treatment(P=0.037).Conclusion After treatment,PA patients still may experience abnormal lipid metabolism and deteriorating renal function.Spironolactone therapy may give rise to worse glucolipid metabolism than ADX therapy does.

Ischemia-reperfusion injury (IRI) is a pathophysiological process, which widely exists in organ transplantation and surgery. IRI is mainly manifested with hypoxia injury of organs or tissues during the ischemia period, which could be further aggravated after reperfusion. Ischemia-reperfusion induces tissue cell injury, releases damage-associated molecular pattern and further activates multiple immune cells via pattern recognition receptor, leading to aseptic inflammation and aggravating tissue injury. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), as a critical member of pattern recognition receptor, could activate the stimulator of interferon genes (STING) signal pathway and play an important regulatory role in innate immune response. At present, increasing evidences have shown that cGAS-STING signal pathway plays a significant role in organ IRI. In this article, STING signaling pathway, its role and mechanism in IRI of different organs were reviewed, aiming to provide novel ideas for clinical interventions.

Objective:To investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of irritable bowel syndrome (IBS), and to explore the effects of FMT on the gut microbiota of IBS patients.Methods:From September 2016 to August 2017, at Guangzhou First People′s Hospital, 28 hospitalized IBS patients who underwent FMT treatment were enrolled. Before FMT, four and 12 weeks after FMT, all the IBS patients completed the irritable bowel syndrome quality of life scale (IBS-QOL), irritable bowel syndrome severity scoring system (IBS-SSS) and gastrointestinal symptom rating scale (GSRS). 16S rDNA sequencing was performed before FMT and four weeks after FMT. The effects of FMT on gut microbiota diversity and microbiota structure of IBS patients were analyzed respectively from the level of phylum, family and genus, and linear discriminant analysis effect size (LEfSe) was further used to screen the different bacteria. Paired t test and paired rank sum test were used for statistical analysis. Results:Twelve weeks after FMT, the scores of the six dimensions of IBS-QOL including dysthymia, behavioral disorder, auto imagery, health concerns, eating avoidance, and relationship expansion were all lower than those before FMT (43.750, 22.656 to 56.250 vs. 48.438, 32.031 to 60.938; 37.500, 18.750 to 56.250 vs. 46.429, 21.429 to 62.500; 31.250, 14.063 to 42.188 vs. 31.250, 18.750 to 50.000; 41.667, 27.083 to 56.250 vs. 50.000, 41.667 to 66.667; 54.167, 43.750 to 72.917 vs. 66.667, 58.333 to 83.333; 8.333, 0.000 to 33.333 vs. 16.667, 8.333 to 33.333, respectively), and the differences were statistically significant ( Z=-2.157, -3.429, -2.274, -3.197, -3.042 and -2.329, all P<0.05). Twelve weeks after FMT, the scores of the two dimensions of IBS-QOL including behavioral disorder and relationship expansion were both lower than those of four weeks after FMT (37.500, 18.750 to 56.250 vs. 39.286, 19.643 to 62.500 and 8.333, 0.000 to 33.333 vs. 16.670, 2.083 to 41.667, respectively), and the differences were statistically significant ( Z=-1.998 and -2.110, both P<0.05). Four and 12 weeks after FMT, the scores of IBS-SSS and GSRS were both lower than those before FMT ((190.32±106.51), (201.43±102.48) vs. (245.93±86.10) and 5.50, 4.00 to 9.00 and 5.50, 4.00 to 8.75 vs. 7.00, 6.00 to 9.75), and the differences were statistically significant ( t=4.402 and 3.848, Z=-3.081 and -3.609; all P<0.01). No serious adverse reactions occurred in the patients after FMT. At the phylum level, after FMT the abundance of Verrucomicrobia in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the family level, after FMT the abundance of Verrucomicrobiaceae in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the genus level, after FMT the abundance of Akkermansia was richer than that before FMT (6.74% vs. 0.37%); and the differences were statistically significant (all Z=-2.589, all P=0.010). The results of LEfSe method indicated that four weeks after FMT the abundance of Akkermansia in the gut microbiota of IBS patients was richer than that before FMT (6.74% vs. 0.37%), and the difference was statistically significant (linear discriminant analysis value=4.5, P=0.049). Conclusions:FMT is safe and effective in the treatment of IBS. The mechanism may be through upregulating the diversity of gut microbiota and changing the structure of gut microbiota of IBS patients.

Objective:To investigate the effects of Clostridium butyricum on colitis and intestinal microbiota in mice with or without antibiotic pretreatment. Methods:Thirty specific pathogen free BALB/c mice were randomly divided into the blank control group, dextran sulfate sodium (DSS) group, antibiotic + DSS group, Clostridium butyricum + DSS group and antibiotic+ Clostridium butyricum + DSS group, with 6 mice in each group. After the mice were pretreated with quadruple antibiotics (ampicillin 1 g/L, neomycin 1 g/L, metronidazole 1 g/L, and vancomycin 0.5 g/L) in normal drinking water for 30 d, the mice colitis model was induced with DSS. At the same time, the mice in Clostridium butyricum + DSS group and antibiotics+ Clostridium butyricum + DSS group were given 1×10 6colony-forming unit (CFU) Clostridium butyricum by gavage. The effect of Clostridium butyricum on mice with colitis was evaluated by disease activity index (DAI), colon length and histopathological score. The level of serum inflammatory factors was detected by enxyme linked immunosorbent assay, and the effect of Clostridium butyricum on gut microbita in mice was determined by fecal 16S rRNA sequencing. Results:The general condition of mice of the blank control group were good, and their DAI scores fluctuated around 0. Since the fourth day after DSS drinking water was given, the mice of the DSS group showed signs of colitis such as weight loss, unformed stools and bloody stools. On the fourth day after intervention, the DAI score of Clostridium butyricum + DSS group was lower than that of DSS group (0.000±0.000 vs. 0.444±0.111), and the difference was statistically significant ( t=4.000, P=0.016 1). On the tenth and twelfth day after the intervention, the DAI scores of antibiotic+ Clostridium butyricum + DSS group were both lower than those of antibiotic+ DSS group (0.000±0.000 vs. 1.111±0.222, 0.667±0.000 vs. 1.889±0.222), and the differences were statistically significant ( t=5.000 and 5.500, both P<0.05). The histopathological score of mice colon tissue of Clostridium butyricum + DSS group was lower than that of DSS group (2.50±1.73 vs. 5.50±1.00), and the histopathological score of mice colon tissue of antibiotic+ Clostridium butyricum+ DSS group was lower than that of antibiotic+ DSS group (1.25±0.96 vs. 5.00±0.82), and the differences were statistically significant ( t=3.000 and 5.960, both P<0.05). The serum level of interleukin (IL)-1β Clostridium butyricum+ DSS group was higher than that of blank control group ((4.464±0.075) ng/L vs. (3.907±0.080) ng/L), the serum levels of tumor necrosis factor-α, IL-6 and IL-1β of Clostridium butyricum+ DSS group and antibiotic+ Clostridium butyricum + DSS group were all lower than those of DSS group ((2.402±0.383) ng/L , (1.845±0.345) ng/L vs. (6.958±1.084) ng/L, (1.752±0.146) ng/L, (1.307±0.048) ng/L vs. (3.537±0.608) ng/L, (4.464±0.075) ng/L, (4.066±0.190) ng/L vs. (7.477±0.339) ng/L), and the differences were statistically significant ( t=5.005, 3.964, 4.495, 4.693, 6.294, 8.674 and 8.774 , all P<0.05). The results of 16S rRNA sequencing showed that there were a significantly large number of anti-inflammatory or short-chain fatty acid producing bacteria in the gut microbiota of mice intervened by Clostridium butyricum, among which the dominant bacteria genus in Clostridium butyricum + DSS group and antibiotic+ Colstridium butyicum+ DSS group were Mucispirillum (linear discriminant analysis (LDA)=3.667 log10, P=0.004) and Stenotrophomonas (LDA=2.778 log10, P=0.044). In the antibiotic+ Clostridium butyricum+ DSS group, the dominant bacteria genus were Peptococcus (LDA=2.685 log10, P=0.018), Butyricimonas (LDA=2.712 log10, P=0.011), Bilophila (LDA=3.204 log10, P=0.014), Intestinimonas (LDA=3.346 log10, P=0.010), Candidatus- Saccharimonas (LDA=3.363 log10, P=0.029), Desulfovibrio (LDA=3.402 log10, P=0.025), Oscillibacter (LDA=2.870 log10, P=0.019) and Akkermansia (LDA=4.031 log10, P=0.005). Conclusions:Clostridium butyricum can effectively improve colitis in mice and regulate the intestinal microbial structure of mice, whlie antibiotic pretreatment can strengthen its regulation of intestinal microbiota to and enhance the efficacy of Clostridium butyricum.

Objective To verify the feasibility and maneuverability of fast bare-handed vertical slicing method for dry Chinese herbal medicine, and to provide reference of this method for different types of medicinal materials. Methods Several representative medicinal herbs were randomly selected in the market to make micro-slices using the top-slicing method to observe its cutting effect. Results Experiments showed that microscopic slices can be obtained for most herbs in a few minutes, which can be used for identification and quality testing. Conclusion This method is fast, effective, simple and practical. It meets the requirements of pharmacopoeia for microscopic identification. This method deserves for promotion.

Objective: To investigate the role of short-term starvation (STS) in alleviating hepatic ischemia-reperfusion injury in mice and possible mechanism of action. Methods: Wild-type male C57BL/6 mice aged 8 weeks were randomly divided into 75% hepatic ischemia-reperfusion injury group (IR group), STS+75% hepatic ischemia-reperfusion injury group (STS group), and sirtinol+STS+75% hepatic ischemia-reperfusion injury group (SIR group), using a random number table, and sham-operation groups (IR-Sham group, STS-Sham group, and SIR-Sham group) were also established. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the histomorphological changes of the liver were observed, as well as the expression of Sirt1, LC3B, and P62 proteins in liver tissue and the results of LC3B fluorescence staining. An analysis of variance was used for comparison of data between multiple groups, and the t-test was used for comparison of data between two groups. Results: Compared with the IR group, the STS group had significant reductions in the serum levels of ALT (3 152.7 ± 735.6 U/L vs 8 414.2 ± 1 052.2 U/L, P < 0.01) and AST (3 577.0 ± 714.0 U/L vs 10 845.8 ± 1 145.7 U/L, P < 0.01) and significant alleviation of liver pathological injury (Suzuki score: 1.50±0.55 vs 3.50±0.55, P < 0.01). Compared with the STS group, the SIR group had significant increases in the serum levels of ALT (7 002.7 ± 1 485.2 U/L vs 3 152.7 ± 735.6 U/L, P < 0.01) and AST (8 980.7 ± 1 739.1 U/L vs 3 577.0 ± 714.0 U/L, P < 0.01) and significant exacerbation of liver pathological injury (Suzuki score: 3.33 ± 0.52 vs 1.50 ± 0.55, P < 0.01). Compared with the IR group and the IR-Sham group, the STS group and the STS-Sham group had significant increases in the mRNA and protein expression of Sirt1 and the protein expression of LC3B and a significant reduction in the protein expression of P62, as well as a significant increase in the percentage of LC3B-positive cells in liver tissue (22.83% ± 5.19% / 22.17% ± 4.83% vs 10.16% ± 3.06% / 10.83% ± 1.94%, both P < 0.01). Compared with the STS group and the STS-Sham group, the SIR group and the SIR-Sham group had significant reductions in the expression of Sirt1 and LC3B proteins and a significant increase in the expression of P62 protein, as well as a significant reduction in the percentage of LC3B-positive cells in liver tissue (11.83% ± 9.24% / 14.67% ± 4.68% vs 22.83% ± 5.19% / 22.17% ± 4.83%, both P < 0.01). Conclusion STS can effectively alleviate hepatic ischemia-reperfusion injury, and its protective effect may be associated with increasing the expression of Sirt1, inducing and promoting hepatocyte autophagy, and reducing hepatocyte death.