Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

This study aimed to investigate the effect and underlying mechanisms of Zexie Decoction against liver injury in rats with hyperlipidemic acute pancreatitis(HLAP). The network pharmacology-related databases were used to screen the active components and potential targets of Zexie Decoction, as well as the disease targets of HLAP. A protein-protein interaction(PPI) network of the overlapping targets was constructed. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis and Gene Ontology(GO) functional enrichment analysis were performed on the overlapping targets. Sprague-Dawley(SD) rats were randomly divided into sham group, model group, low-dose Zexie Decoction group, and high-dose Zexie Decoction group. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect serum biochemical indicators. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the pancreas and liver tissues, while oil red O staining was employed to assess hepatic steatosis. Immunofluorescence staining was used to detect the expression of IL-1β and NLRP3 in pancreatic tissues. Western blot analysis was conducted to evaluate the expression levels of proteins related to oxidative stress, endoplasmic reticulum stress, the PI3K/AKT signaling pathway, and autophagy. Network pharmacology predictions identified 721 targets of Zexie Decoction and 2 486 targets associated with HLAP, with 279 overlapping targets. GO enrichment analysis yielded 1 112 entries, and KEGG enrichment analysis identified 179 signaling pathways. Experimental results showed that Zexie Decoction could reduce the levels of lipid metabolites, serum enzymes, and inflammatory cytokines in HLAP rats, alleviate pathological damage to the pancreas and liver, decrease hepatic lipid accumulation, and decrease the expression of IL-1β and NLRP3 in pancreatic tissues. In addition, Zexie Decoction significantly upregulated the expression of antioxidant stress-related proteins NRF2 and HO-1, downregulated the expression of endoplasmic reticulum stress-related proteins BiP, xBP1s, p-eIF2α, eIF2α, and ATF4, inhibited the expression of PI3K and phosphorylation of AKT, increased the expression of autophagy-related proteins Beclin1, ATG3, ATG5, and ATG12, and reduced the expression of p62. In conclusion, Zexie Decoction can improve HLAP, and its mechanism may be associated with alleviating oxidative stress and endoplasmic reticulum stress, inhibiting the PI3K/AKT pathway, and inducing autophagy in hepatocytes.
Animals ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Rats ; Pancreatitis/genetics* ; Hyperlipidemias/genetics* ; Male ; Liver/injuries* ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-1beta/genetics* ; Humans

Portal vein thrombosis (PVT) secondary to blunt abdominal trauma associated with liver injury is extremely rare in healthy individuals as well as in minor liver injury, and it carries a high rate of morbidity and mortality. Moreover, acute asymptomatic PVT is difficult to diagnose. We present a young trauma patient with isolated minor liver injury associated with acute PVT. A 27-year-old man presented to the emergency department after a motor vehicle collision. His primary survey findings were unremarkable. His secondary survey showed a large contusion (7 × 7 cm²) at the epigastrium with marked tenderness and localized guarding. The CT angiography of the whole abdomen revealed liver injury grade 3 in hepatic segments 2/3 and 4b (according to the American Association for the Surgery of Trauma classification) extending near the porta hepatis with patent hepatic and portal veins and without other solid organ injury. The follow-up CT of the whole abdomen on post-injury day 7 showed a 1.8-cm thrombus in the left portal vein with patent right portal and hepatic veins, and a decreased size of the hepatic lacerations. A liver function test was repeated on post-injury day 4, and it revealed improved transaminitis. The patient received intravenous anticoagulant therapy with low-molecular-weight heparin according to weight-based dosing for treatment. The CT of the whole abdomen performed 2 weeks after anticoagulant therapy showed small residual thrombosis in the left portal vein. The patient received intravenous anticoagulant therapy for a total of 3 months. On the follow-up visits at 1 month, 2 months, 6 months, and 1 year after the injury, the patients did not have any detectable abnormal symptoms. PVT post-blunt minor liver injury is an extremely rare complication. If the thrombosis is left untreated, serious morbidity and mortality can ensue. However, its diagnosis in asymptomatic patients is still challenging. Periodic imaging is necessary for highly suspected PVT, especially in liver injury with lacerations close to the porta hepatis, even in cases of a minor injury.
Humans ; Portal Vein ; Male ; Adult ; Wounds, Nonpenetrating/complications* ; Venous Thrombosis/diagnostic imaging* ; Liver/injuries* ; Acute Disease ; Accidents, Traffic

PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.19 ± 0.29 vs. 1.89 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.38 ± 0.32 vs. 0.05 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.68 ± 0.21 vs. 1.94 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.
Animals ; Rabbits ; Resuscitation/methods* ; Liver/injuries* ; Seawater ; Blast Injuries/therapy* ; Fibrinogen/administration & dosage* ; Male ; Tranexamic Acid/administration & dosage* ; Immersion ; Hydroxyethyl Starch Derivatives/administration & dosage*

PURPOSE: Non-operative management (NOM) has been validated for blunt liver and splenic injuries. Literature on continuous intra-abdominal pressure (IAP) monitoring as a part of NOM remains to be equivocal. The study aimed to find any correlation between clinical parameters and IAP, and their effect on the NOM of patients with blunt liver and splenic injury. METHOD: A prospective cross-sectional study conducted at a level I trauma center from October 2018 to January 2020 including 174 patients who underwent NOM following blunt liver and splenic injuries. Hemodynamically unstable patients or those on ventilators were excluded, as well as patients who suffered significant head, spinal cord, and/or bladder injuries. The study predominantly included males (83.9%) with a mean age of 32.5 years. IAP was monitored continuously and the relation of IAP with various parameters, interventions, and outcomes were measured. Data were summarized as frequency (percentage) or mean ± SD or median (Q₁, Q₃) as indicated. χ² or Fisher's exact test was used for categorical variables, while for continuous variables parametric (independent t-test) or nonparametric tests (Wilcoxon rank sum test) were used as appropriate. Clinical and laboratory correlates of IAP < 12 with p < 0.200 in the univariable logistic regression analysis were included in the multivariable analysis. A p < 0.05 was used to indicate statistical significance. RESULTS: Intra-abdominal hypertension (IAH) was seen in 19.0% of the study population. IAH was strongly associated with a high injury severity score (p < 0.001), and other physiological parameters like respiratory rate (p < 0.001), change in abdominal girth (AG) (p < 0.001), and serum creatinine (p < 0.001). IAH along with the number of solid organs involved, respiratory rate, change in AG, and serum creatinine was associated with the intervention, either operative or non-operative (p = 0.001, p = 0.002, p < 0.001, p < 0.001, p = 0.013, respectively). On multivariable analysis, IAP (p = 0.006) and the mean change of AG (p = 0.004) were significantly associated with the need for intervention. CONCLUSION As a part of NOM, IAP should be monitored as a continuous vital. However, the decision for any intervention, either operative or non-operative cannot be guided by IAP values alone.
Humans ; Male ; Adult ; Female ; Wounds, Nonpenetrating/physiopathology* ; Spleen/injuries* ; Prospective Studies ; Cross-Sectional Studies ; Liver/injuries* ; Middle Aged ; Monitoring, Physiologic/methods* ; Pressure ; Abdominal Injuries/physiopathology* ; Intra-Abdominal Hypertension ; Young Adult

OBJECTIVE: To explore the early changes in various liver function indicators in critically injured trauma patients assessed by intelligent calculation method, aiming to develop more advantageous diagnostic and treatment strategies for traumatic liver injury. METHODS: A retrospective study was conducted. Critically injured trauma patients [injury severity score (ISS) ≥ 16, age > 18 years old] admitted to the Emergency Medical Center of Tianjin Fifth Central Hospital from January 1, 2022, to December 1, 2023 were enrolled. ISS score and acute physiology and chronic health evaluation II (APACHE II) assessed by intelligent calculation method were collected upon patient admission to the emergency medical center. Trends in liver function indicators in fasting venous serum were analyzed at 6, 24 and 72 hours after admission, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), total bilirubin (TBil), prothrombin time (PT). Patients were grouped based on APACHE II scores into those with APACHE II < 15 and APACHE II ≤ 15, and liver function indicators within 6 hours of admission were compared between the two groups. RESULTS: A total of 112 critically injured trauma patients were included, with 83 males and 29 females, an average age of (47.78±14.84) years old. The median ISS score was 21.0 (18.0, 26.0). The most common cause of injury for critically injured trauma patients was road traffic accidents (68 cases, accounting for 60.71%), followed by falls from heights, compression injuries, heavy object injuries, knife stabs, and explosion injuries. The most common injured areas was the limbs and pelvis (97 cases, accounting for 86.61%), followed by chest injuries, surface skin and soft tissue injuries, abdominal and pelvic organ injuries, head injuries, and facial injuries. The proportion of elevated LDH, AST, and ALT within 6 hours of admission was 77.68%, 79.46%, and 52.68%, respectively, while the proportion of decreased ALB was 75.89%, the abnormal rates of ALP, GGT, TBil, and PT were all below 50%. The ALT and AST levels of patients at 24 hours and 72 hours after admission were significantly lower than those at 6 hours after admission [ALT (U/L): 37.0 (22.0, 66.0), 31.0 (21.2, 52.0) vs. 41.0 (25.0, 71.0), AST (U/L): 55.5 (30.0, 93.5), 40.0 (27.0, 63.2) vs. 69.5 (39.0, 130.8), all P < 0.05]. There was no statistically significant difference in ISS score between APACHE II > 15 group (45 cases) and APACHE II ≤ 15 group [67 cases; 21.0 (18.5, 26.5) vs. 20.0 (17.0, 22.0), P > 0.05]. Nevertheless, compared with patients with APACHE II ≤ 15, patients with APACHE II > 15 have a higher abnormality rate of ALT and AST within 6 hours of admission [ALT abnormal rate: 66.44% (29/45) vs. 44.78% (30/67), AST abnormal rate: 93.33% (42/45) vs. 70.15% (47/67), both P < 0.05], and the levels of ALT and AST were higher [ALT (U/L): 56.0 (30.0, 121.0) vs. 35.0 (21.0, 69.0), AST (U/L): 87.0 (48.0, 233.0) vs. 52.0 (31.0, 117.0), both P < 0.05]. CONCLUSIONS Severe trauma patients frequently exhibit a high incidence of reversible early liver function impairment. Based on intelligent calculation method, the utilization of both the ISS and APACHE II scores demonstrates a distinct advantage in the assessment of their early liver injury.
Humans ; Retrospective Studies ; Liver/physiopathology* ; Risk Assessment ; APACHE ; Wounds and Injuries ; Adult ; Injury Severity Score ; Male ; Middle Aged ; Female ; Liver Function Tests ; Alanine Transaminase/blood* ; Young Adult ; Aspartate Aminotransferases/blood*

Diquat is a kind of conductive contact-killing herbicides. The damage of central nervous system is relatively common, but the peripheral neuropathy caused by diquat has not been reported yet. In September 2021, we treated a patient with diquat poisoning. During the hospitalization, the patient was diagnosed with peripheral neuropathy. Therapy for peripheral nerve injury was given on the basis of conventional treatment of poisoning. The patient was discharged after his condition was stable. The follow-up showed that the peripheral neuropathy of patient was better than before. According to the condition of this patient, it is suggested that we should not only protect the function of gastrointestinal tract, liver, kidney, and central nervous system early, but should also pay attention to the damage of peripheral nervous system in clinical work. We should intervene earlier to improve the prognosis of patients.
Humans ; Diquat ; Herbicides ; Kidney ; Liver ; Peripheral Nerve Injuries ; Poisoning

PURPOSE: Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE. METHODS: A systematic literature review searched "liver trauma", "hepatic trauma", "conservative management", "non operative management" on MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials databases, EMBASE, and Google Scholar, to identify studies published on the conservative management of traumatic liver injuries between January 1990 and June 2020. Patients with traumatic liver injuries (blunt and penetrating) treated by NOM, described at least one outcome of interests and provided morbidity outcomes from NOM were included in this study. Studies reported the outcome of NOM without separating liver from other solid organs; studies reported NOM complications together with those post-intervention; case reports; studies including less than 5 cases; studies not written in English; and studies including patients who had NOM with AE as primary management were excluded. Efficacy of NOM and overall morbidity and mortality were assessed, the specific causes of morbidity were investigated, and the American Association for the Surgery of Trauma classification was used in all the studies analysed. Statistical significance has been calculated using the Chi-square test. RESULTS: A total of 19 studies qualified for inclusion criteria were in this review. The NOM success rate ranged from 85% to 99%. The most commonly reported complications were hepatic collection (3.1%), followed by bile leak (1.5%), with variability between the studies. Other complications included hepatic haematoma, bleeding, fistula, pseudoaneurysm, compartment syndrome, peritonitis, and gallbladder ischemia, all with an incidence below 1%. CONCLUSION NOM with simple clinical observation showed an overall low incidence of complications, but higher for bile leak and collections. In patients with grade III and above injuries, the incidence of bile leak, collections and compartment syndrome did not show a statistically significant difference with the AE group. However, the latter result is limited by the small number of studies available and it requires further investigations.
Abdominal Injuries/complications* ; Compartment Syndromes ; Humans ; Injury Severity Score ; Liver/injuries* ; Retrospective Studies ; Wounds, Nonpenetrating/complications*

OBJECTIVES: To investigate the effect of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) on liver injury induced by periodontitis in rats. METHODS: Twenty-four male Wistar rats were randomly divided into two groups: control group and periodontitis group, twelve per group. In periodontitis group, the periodontitis models were established for the maxillary first molars in rats by means of "wire ligation+vaccinationwith RESULTS: The probing depth, tooth mobility and sulcus bleeding index in periodontitis group were significantly higher than that in control group. HE staining showed in periodontitis group, hepatic cords ranged disorderly and there were vacuoles in cells and inflammatory cells infiltrated in liver tissues of rats, and there was no obvious abnormality in control group. The qRT-PCR results showed that the mRNA expression levels of CONCLUSIONS PGC-1α may be involved in the process of periodontitis-induced liver injury in rats.
Animals ; Liver/injuries* ; Male ; PPAR gamma ; Periodontitis/pathology* ; Rats ; Rats, Wistar

PURPOSE: Adrenal gland injuries in trauma are rare and usually misdiagnosed or underestimated in an emergency setting because they are asymptomatic and associated with severe abdominal injuries. This paper reviews the clinical characteristics of adrenal injuries. METHODS: A retrospective analysis of trauma patients who visited the authors' emergency center was performed from March, 2010 to December, 2017. The patient demographic data, injury mechanism & associated injuries, injury severity score, hospital stay, and mortality were retrieved and analyzed. RESULTS: Adrenal gland injuries were found in 52 patients: 73.1% (n=38) were males and the mean age was 43.6 years. Of the patients, 84.6% (n=44) had ISS ≥15. Right adrenal gland injuries occurred in 82.7% (n=43). The mechanism of injury was falls in 30.8% (n=16), motor vehicle accidents in 25.0% (n=13), and pedestrian accidents in 23.1% (n=12). Associated injures were liver injury (58.5%), rib fracture (52.8%), kidney injury (24.5%), pelvic bone fracture (20.8%), spine fracture (28.3%), and spleen injury (13.2%). The mean hospital stay was 34.2 days, and the intensive care unit stay was 9 days. The mortality rate was 3.8% (n=2). CONCLUSION: Adrenal gland injuries are common in males and frequent in the right side. Falls are the leading cause of injury. Most injuries have an associated injury at the abdominal or thoracic region. Adrenal injury is accompanied by high injury severity but showed a good prognosis.
Abdominal Injuries ; Accidental Falls ; Adrenal Glands ; Emergencies ; Humans ; Injury Severity Score ; Intensive Care Units ; Kidney ; Length of Stay ; Liver ; Male ; Mortality ; Motor Vehicles ; Pelvic Bones ; Prognosis ; Retrospective Studies ; Rib Fractures ; Spine ; Spleen