ObjectiveTo investigate the mechanism of Si Junzitang in treating liver injury in rats with spleen Qi deficiency syndrome based on transcriptomics and to experimentally verify its effects. MethodsSixty male SD rats were randomly divided into blank group， model group， low-dose Si Junzitang （6 g·kg^-1·d^-1）， medium-dose Si Junzitang group （12 g·kg^-1·d^-1）， high-dose Si Junzitang group （24 g·kg^-1·d^-1）， and natural recovery group， with 10 rats in each group. A composite multifactorial modeling method （forced swimming + intragastric administration of Xiao Chengqitang + irregular diet） was used to establish a spleen Qi deficiency model. After 30 days of continuous intervention， body weight and 3-hour food intake were measured， and macroscopic symptom scores for spleen Qi deficiency syndrome were evaluated. Serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in each group were detected， and hematoxylin and eosin （HE） staining was used to observe histopathological changes in liver tissue. Transcriptome sequencing （RNA-Seq） was used to identify differentially expressed genes （DEGs） among the blank， model， and high-dose Si Junzitang groups. Gene ontology（GO） and Kyoto encyclopedia of genes and genome（KEGG） enrichment analyses were performed on the DEGs. Immunofluorescence （IF） and Western blot were used to detect NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein （ASC）， Caspase-1， and the N-terminal domain of gasdermin D （GSDMD-N）. Immunohistochemistry （IHC） was used to detect the expression of downstream inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and interleukin-18 （IL-18）. ResultsCompared with the blank group， the model group showed significantly reduced body weight and 3-hour food intake， significantly increased macroscopic symptom scores， and elevated serum AST and ALT levels （P<0.01）， with mild inflammatory liver injury observed histologically. Compared with the model group， Si Junzitang at all doses significantly improved these parameters and alleviated liver injury in a dose-dependent manner （P<0.05，P<0.01）. RNA-Seq analysis revealed 1 254 DEGs between the blank and model groups， and 842 DEGs between the model and high-dose Si Junzitang groups. GO and KEGG enrichment analyses indicated that the NOD-like receptor signaling pathway was activated in liver injury associated with spleen Qi deficiency， suggesting that the NLRP3 inflammasome may be a key target. Results from IF， IHC， and Westernblot showed that compared with the blank group， the expression of NLRP3， ASC， Caspase-1， GSDMD-N， and the downstream inflammatory cytokines IL-1β， IL-6， and IL-18 were significantly increased in the model group （P<0.01）， while these levels were markedly decreased in the high-dose Si Junzitang group （P<0.01）. ConclusionSi Junzitang effectively improves mild inflammatory liver injury in rats with spleen Qi deficiency syndrome in a dose-dependent manner. Its mechanism may be associated with inhibition of the NLRP3/ASC/Caspase-1 signaling pathway， downregulation of the pyroptosis executioner protein GSDMD-N， and reduction of pyroptosis-related inflammatory cytokine release.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions. Mitochondria are vital organelles that function in diverse metabolic processes in the body, including redox reactions, lipid metabolism, and cell death. Mitophagy, a specific form of autophagy for damaged mitochondria, plays a critical role in the pathophysiology of liver diseases. In this review, we explain in detail the roles of the Nrf2 signaling pathway and mitophagy, and the relationship between them, in various hepatic diseases (nonalcoholic fatty liver disease, viral hepatitis, alcoholic liver disease, drug-induced liver injury, autoimmune hepatitis, hepatic ischemia‒reperfusion injury, and liver cancer). We also offer some potential insights and treatments relevant to clinical applications.
Humans ; NF-E2-Related Factor 2/metabolism* ; Mitophagy/physiology* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; Liver Diseases/etiology* ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Non-alcoholic Fatty Liver Disease ; Liver Neoplasms

Peripheral arterial disease is one of the common complications of diabetes. At present, the pathogenesis of diabetic peripheral arterial diseases is not completely clear, and there is a lack of effective treatment methods and drugs. Adipokines have profound impact on the occurrence and development of diabetes mellitus and its complications, and are directly or indirectly involved in the progression of diabetic peripheral arterial diseases. Different adipokines may inhibit or promote the occurrence of vascular diseases with the mechanisms that are complex and controversial. Adipokines are expected to be a new target for the treatment of diabetic peripheral arterial disease, which is worthy of further study. This article mainly reviews the relationship between some common adipokines and new adipokines and diabetic vascular disease, aiming to provide new methods for the clinical treatment of diabetic peripheral arterial disease.

Ischemia-reperfusion (I / R) is a complex hemodynamic process that can cause tissue damage through oxidative stress, mitochondrial dysfunction, and inflammatory reactions. It is an important factor leading to poor prognosis in patients, and the exploration of effective prevention and treatment measures is of significant clinical significance. As an endogenous hormone with strong antioxidant and anti-inflammatory properties, Melatonin plays an important role in reducing cell death and improving tissue I / R injury. Therefore, this article reviews the relationship between Melatonin and organ I/R injury in order to provide a theoretical basis for the clinical application of melatonin to alleviate organ I/R injury.

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

This paper reviewed the research on moral injury among foreign medical staff in the background of the COVID -19 pandemic. It was found that foreign medical staff bore multiple moral pressures and impacts in the face of the epidemic, including the collision between medical practice and utilitarian policy, the inability to meet personal needs, the rapid transformation of medical mode, and a variety of comprehensive factors. Therefore, the moral injury of foreign medical staff is particularly prominent. In order to avoid and reduce the occurrence of moral injury, it is necessary to strengthen the cultivation of moral resilience, provide psychological and social support, and carry out personalized treatment for medical staff.

Objective To investigate the value of flexi-rigid thoracoscopy in pleural effusion of unknown causes and the correlation with CEA, TK1 and ADA. Methods The clinical data and results of CEA, TK1 and ADA of 25 patients were retrospective analyzed in our department from 2015 January to November 2015. These patients accepted the examination of flexi-rigid thoracoscopy with pleural effusion of unknown causes. Results In the 25 patients with pleural effusion of unknown causes, definite diagnosis was made in 22 cases (88.00 %), of which 9 cases were malignant pleural effusion (36.00 %), 11 cases were tuberculous pleural effusion (44.00 %), 2 cases were inflammatory pleural effusion (8.00 %), 3 cases were undetermined (12.00 %). The positive rate of TK1 and CEA in malignant group was significantly higher than that in the tuberculosis group and inflammatory group, the positive rate of ADA in the tuberculosis group was significantly higher than that in the malignant group and inflammatory group. Conclusion Flexi-rigid medical thoracoscopy examination is an effective and safe method for diagnosis of unexplained pleural effusion with high exact diagnosis rate, less trauma and less complication. Combination with CEA, TK1 and ADA are helpful to improve diagnostic rate of pleural effusion of unknown causes.

Objective To investigate the effect of paroxetine in the adjuvant treatment of maintenance hemodialysis(MHD)com-plicating depression.Methods 60 patients with MHD complicating depression were randomly divided into the control group and the observation group,30 cases in each group.The control group received the routine therapeutical scheme(hemodialysis,complication treatment and correcting the renal anemia,etc).On the basis of the routine therapy the observation group was given oral paroxetine 10 mg/d,once daily for continuous 8 weeks.The depression level was assessed by the Hamilton depression scale(HAMD).The clinical symptoms,levels of Hb,ALB,Kt/V,iPTH,SF and HAMD scores were statistically analyzed and compared between the two groups.Results The clinical symptoms,levels of Hb,ALB,Kt/V after 8-week treatment in the two groups were significantly im-proved compared with pretherapy(P<0.05);the level of iPTH,SF and the HAMD scores in the two groups were decreased com-pared with pretherapy(P<0.05).The effective rate of depression was 86.67% in the observation group and 23.33% in the control group,the difference between the two groups had statistical significance(P<0.05).Conclusion Paroxetine in the assisted treat-ment of MHD complicating depression symptom can improve the quality of life in MHD patients.

Objective: To determine the pharmacokinetics of ephedrine hydrochloride in rats after intragastric administration of Shegan mixtures. Methods:Shegan mixtures (1. 0 ml/100 g) were administered to each rat by gavage. Blood samples were collected after the administration. Plasma concentration of ephedrine hydrochloride was determined by LC-MS/MS. The pharmacokinetic parame-ters of ephedrine hydrochloride were obtained using the pharmacokinetic software. Urine and fecal samples were collected in 24 hours after the administration using metabolic cage to determine the recovery of ephedrine hydrochloride. Results: The pharmacokinetic pa-rameters of ephedrine hydrochloride were as follows:Tmax of (1. 30 ± 0. 23)h,T1/2 of (21. 17 ± 1. 35)h, Cmax of (278. 86 ± 46. 41)ng ·ml-1,AUC0~∞ of (1221.98 ±412.64)ng·ml-1 and Vc/F of (1.70 ±0.15)L. Totally 85.66% ephedrine hydrochloride could be recovered from urine in 24 hours after the administration;however, it was not detected in the fecal samples. Conclusion: Most of e-phedrine hydrochloride is excreted through kidney in 24h,therefore, Shegan mixtures can't cause the accumulation of ephedrine hydro-chloride in rats.