ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective: Whether dissociation and depression are distinct constructs remains controversial. The aim of this study was to explore the interrelations and associated factors between them. Methods: This study included inpatients with major depressive disorder (MDD) and bipolar disorder with major depressive episode (BD). Clinical rating scales were used to measure levels of depression, dissociation, and psychotic symptoms. Generalized estimating equations were used to estimate interrelations between dissociation and related factors over time, including depression. Moreover, the impacts of individual items of the Hamilton Depression Rating Scale (HAMD) on dissociation were evaluated after multiple adjustments. Results: A total of 91 participants were included into the analysis, of whom 59 had MDD and 32 had BD. After standardized treatment, levels of depression and psychotic symptoms significantly decreased, whereas the level of dissociation did not. However, the level of dissociation significantly decreased in the high-dissociation group, and this was positively associated with the change in depression and psychotic symptoms. Female sex and comorbidity with borderline personality disorder were also positively correlated with dissociation. Among items of the HAMD, insomnia and gastrointestinal symptoms contributed to the association between depression and dissociation. Conclusion We identified a decoupled but intertwined relationship between dissociation and depression. Clinicians should be aware of this comorbidity and provide timely interventions for dissociation during clinical practice.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.