ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

Hypercoagulable state (HCS) after kidney transplantation is one of the common and serious complications in kidney transplant recipients, which has attracted increasing attention in recent years. HCS refers to the abnormal and excessive activation of blood coagulation function, leading to the increased risk of thrombosis. After kidney transplantation, the combined effects of hemodynamic changes, surgical trauma and severe rejection increase the incidence of HCS, not only raising the risk of thrombosis but also potentially causing graft failure and affecting the postoperative survival rate of patients. This article reviews the influencing factors, clinical manifestations, diagnostic methods and preventive strategies of HCS after kidney transplantation, aiming to provide a theoretical basis for optimizing perioperative management and improving the prognosis of patients.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

This study aims to explore whether Albiziae Cortex-Tribuli Fructus can exert an anti-hepatic fibrosis effect by regulating the nuclear factor E2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)/cysteine protease-1(caspase-1) pathway and analyze its potential mechanism. In the in vivo experiment, a mouse model of hepatic fibrosis was established by subcutaneous injection of carbon tetrachloride. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), collagen type Ⅳ(ColⅣ), laminin(LN), procollagen type Ⅲ(PCⅢ), and hyaluronic acid(HA) in the serum of mice were measured using a fully automated biochemical analyzer and ELISA. Hematoxylin and eosin(HE) and Masson staining were used to observe inflammation and collagen fiber deposition in the liver tissue. Western blot and RT-qPCR were employed to detect the protein and mRNA expression of collagen type Ⅰ(collagen Ⅰ), α-smooth muscle actin(α-SMA), Nrf2, NLRP3, gasdermin D(GSDMD), and caspase-1 in the hepatic tissue. In the in vitro experiment, human hepatic stellate cells(HSC-LX2) were pretreated with Nrf2 agonist or inhibitor, followed by the addition of blank serum, AngⅡ + blank serum, and AngⅡ + Albiziae Cortex-Tribuli Fructus-containing serum for intervention. Western blot was used to detect the protein expression of Nrf2, NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, and apoptosis-associated speck-like protein(ASC) in cells. DCFH-DA fluorescence probe was used to detect the cellular ROS levels. The results from the in vivo experiment showed that, compared with the model group, Albiziae Cortex-Tribuli Fructus significantly reduced the serum levels of AST, ALT, ColⅣ, LN, PCⅢ, and HA, reduced the infiltration of inflammatory cells and collagen fiber deposition in the liver tissue, significantly upregulated the protein and mRNA expression of Nrf2 in the liver tissue, and significantly downregulated the protein and mRNA expression of collagen I, α-SMA, NLRP3, GSDMD, and caspase-1 in the liver tissue. The results from the in vitro experiment showed that Nrf2 activation decreased the protein expression of NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, ASC, and ROS levels in HSC-LX2, while Nrf2 inhibition showed the opposite trend. Furthermore, Albiziae Cortex-Tribuli Fructus-containing serum directly decreased the expression of the above proteins and ROS levels. In conclusion, Albiziae Cortex-Tribuli Fructus can effectively improve hepatic fibrosis, and its mechanism of action may involve inhibiting pyroptosis through the regulation of the Nrf2/NLRP3/caspase-1 pathway.
Animals ; NF-E2-Related Factor 2/genetics* ; Liver Cirrhosis/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Signal Transduction/drug effects* ; Humans ; Liver/metabolism* ; Mice, Inbred C57BL ; Plant Extracts ; Tribulus

Objective:To investigate the clinical diagnosis and treatment of IgG4-related disease（IgG4-RD） primarily involving the nasal cavity and skull base. Methods:A retrospective analysis was conducted on the clinical data of 8 patients with IgG4-RD primarily involving the nasal cavity and skull base who visited the Nasal and Skull Base Surgery Department at Xiangya Hospital from October 2017 to January 2024. The cohort comprised 4 males and 4 females, aged 8 to 69 years. Clinical data, laboratory examination results, imaging findings, histopathological results, and treatment plans were collected. The clinical manifestations, diagnosis, treatment and follow-up results of IgG4-RD primarily involving nasal cavity and skull base were summarized and previous literature were also reviewed. Results:The initial symptoms in the 8 patients included nasal congestion, headache, sensory function decline, and facial deformities. Three patients also had parotid and pulmonary involvement. Among the 8 patients, 4 underwent partial surgical resection combined with glucocorticoid therapy; 1 underwent partial surgical resection combined with glucocorticoid and immunosuppressant therapy; 1 received glucocorticoid therapy alone; and 2 received glucocorticoid combined with immunosuppressant therapy. Follow-up was conducted one month after treatment, lasting from 5 to 79 months. During the follow-up period, recurrence was observed in 1 patient treated with glucocorticoid combined with immunosuppressants and in 1 patient treated with glucocorticoid alone, while the other 6 patients achieved significant remission. Conclusion:The diagnosis of nasal cavity and skull base IgG4-RD requires the combination of histopathology, laboratory tests, and imaging results. Treatment primarily includes glucocorticoids or combined immunosuppressants. For patients with significant compression symptoms, sensory function impairment, or facial deformities, surgical resection is an important treatment option. Given the high risk of recurrence, early intervention, active treatment, and long-term follow-up are crucial.
Humans ; Male ; Skull Base/pathology* ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Nasal Cavity/pathology* ; Adult ; Immunoglobulin G4-Related Disease/therapy* ; Immunoglobulin G ; Child ; Young Adult ; Adolescent

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*