Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Occult breast cancer (OBC) refers to a type of breast cancer where no primary lesion is detected through physical examination, imaging, and pathology. This report presents a clinical case of OBC with intestinal obstruction as the initial symptom. A 67-year-old female with no underlying conditions presented to Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University with intestinal obstruction. Contrast-enhanced CT of the abdomen showed thickening of the lower rectum and ascending colon, suggestive of a neoplastic lesion. Chest CT showed multiple enlarged lymph nodes in the left axilla. Colonoscopy revealed only mucosal congestion, roughness, and thickening. Suspecting an intestinal tumor, laparoscopic radical resection of the rectal stenosis was performed. Postoperative pathology indicated poorly differentiated adenocarcinoma of the rectum. Immunohistochemistry showed positive expression of estrogen receptor (ER), progesterone receptor (PR), GATA-binding protein 3 (GATA3), and cytokeratin 7 (CK7), suggesting breast cancer metastasis. Breast MRI revealed multiple proliferative nodules in both breasts (breast imaging reporting and data system, BI-RADS 2). Biopsies of the right lower-inner breast, bilateral axillary, and supraclavicular lymph nodes were performed. No carcinoma was found in the right breast tissues; however, small foci of carcinoma was detected in the right axillary lymph nodes, and poorly differentiated carcinoma of suspected breast origin was found in the bilateral supraclavicular and left axillary lymph nodes. The final diagnosis was OBC with lymph node and rectal metastasis. The patient died 16 months postoperatively. OBC often lacks identifiable primary breast lesions, and gastrointestinal metastases are particularly rare. Clinical manifestations are frequently masked by symptoms of metastatic lesions, making diagnosis challenging. Clinicians should maintain a high index of suspicion. Due to rapid disease progression and multiorgan involvement, prognosis is extremely poor. Early identification of the primary lesion in OBC is crucial for improving outcomes.
Humans ; Female ; Aged ; Intestinal Obstruction/etiology* ; Breast Neoplasms/pathology* ; Adenocarcinoma/diagnosis* ; Neoplasms, Unknown Primary/complications* ; Rectal Neoplasms/complications*

OBJECTIVE: To diagnose and fine map a deletion in chromosome region 2q37. METHODS: G-banded chromosomal karyotyping, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism array (SNP-array), and fluorescence in situ hybridization (FISH) were carried out in conjunct for the analysis. RESULTS: The patient was found to have karyotype of 46,XY,del(2)(q3?), MLPA revealed one copy number of both CAPN10-3 and ATG4B-7 genes from the 2q37.3 region, Both parents were found to be normal upon chromosome karyotyping and MLPA. SNP-array has found a 9.7 Mb deletion in the 2q37.1.37.3 region. FISH analysis has confirmed there is a single copy for 2q37.3. CONCLUSION Combination of MLPA, FISH and SNP-array have enabled accurate diagnosis for the patient, and also provided more clues for the correlation of genotype with the phenotype of the disease, and a basis for genetic counseling.
Chromosome Banding ; Chromosome Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Phenotype

Objective:To investigate the characteristics of atelectasis and its relationship with the degree of diaphragm inhibition in elderly patients with artificial pneumoperitoneum under general anesthesia.Methods:Patients of both sexes, aged 20-80 yr, of American society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 20-29 kg/m 2, scheduled for elective laparoscopic cholecystectomy under general anesthesia, were divided into 2 groups ( n=20 each) according to age: young and middle-aged group and elderly group.Total intravenous anesthesia was applied and intraoperative pressure of artificial pneumoperitoneum was set at 10 mmHg.Before anesthesia, at 5 min of mechanical ventilation, at 5 min of artificial pneumoperitoneum, at 20 min of artificial pneumoperitoneum, at 5 min after the end of artificial pneumoperitoneum and at 15 min after extubation, diaphragmatic excursion (DE) was measured at the right diaphragm point using M-mode ultrasound.The minimal DE was recorded and the maximum degree of diaphragm inhibition was calculated.B-mode was used to assess the lung ultrasound images at the upper bedside lung ultrasound in emergency (BLUE) point, the lower BLUE point and the diaphragm point, and the cumulative scores before anesthesia and perioperative maximum cumulative scores of lung ultrasound score (LUS) were recorded. Results:Compared with the young and middle-aged group, the maximum cumulative scores of LUS were significantly increased, the degree of DE before anesthesia, the perioperative maximum degree of diaphragm inhibition were increased ( P<0.05), and no significant change was found in LUS cumulative scores in elderly group ( P>0.05). Conclusion:The degree of atelectasis is more serious in the elderly patients with artificial pneumoperitoneum under general anesthesia, and the mechamism may be related to the increased degree of diaphragm inhibition.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Joint deformity and dysfunction can occur in the late stage of the disease,which is seriously harmful to human health. Anti-inflammatory factors (AIC), as a protective factor, together with pro-inflammatory factors (PIC) play important roles in the pathogenesis and progression of RA. It is widely accepted by the majority of scholars that the decrease of AIC and the increase of PIC in RA can aggravate the systemic and local inflammatory reactions and accelerate the articular cartilage and subchondral bone destruction, resulting in further progress of RA. A new generation of biological therapy for RA targeting at AIC is in the ascendant. Therefore ,it is important to understand the role of AIC in the pathogenesis of RA. From the perspective of the relationship between AIC and RA and the mechanism, this article reviews the research progress in this field, which provides new concepts for the diagnosis and treatment of RA.

Objective To discuss the perioperative nursing norm for patients who are suffering from biliary complications occurred after liver transplantation and who will receive interventional management to treat the complications.Methods Interventional therapies were performed in 20 patients with biliary complications due to liver transplantation.The interventional procedures performed in 20 cases included percutaneous biliary drainage(n = 13), percutaneous biliary balloon dilatation(n = 5) and biliary stent implantation(n = 7).The clinical results were observed and analyzed.Results Biliary tract complications occurred after liver transplantation were seen frequently.Proper interventional management could markedly improve the successful rate of liver transplantation and increase the survival rate of the patients.In accordance with the individual condition, proper nursing measures should be taken promptly and effectively.Conclusion Conscientious and effective nursing can contribute to the early detection of biliary complications and, therefore, to improve the survival rate of both the transplanted liver and the patients.