Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To investigate the clinical efficacy of fasting nasogastric administration of sesame oil combined with multi-frequency vibrational abdominal massage in stroke patients with consti-pation undergoing nasogastric feeding.Methods A total of 50 stroke patients with nasogastric feeding were selected as study subjects and randomly divided into control group and study group,with 25 pa-tients in each group.The control group received routine nursing care plus multi-frequency vibrational abdominal massage,while the study group received fasting nasogastric administration of 20 mL of sesa-me oil on the basis of the control group's treatment.After 15 days of intervention,the defecation condi-tions[constipation clinical symptom score(CSS),stool consistency(Bristol stool scale),and stool volume]were compared between the two groups.Results After treatment,the CSS score in the study group was lower than that in the control group[(6.52±2.52)versus(12.64±3.32),P＜0.05].The normal stool consistency(types Ⅳ and Ⅴ on the Bristol stool scale)in the study group was higher than that in the control group(76.0％versus 8.0％,P＜0.05).The stool volume in the study group was higher than that in the control group[(303.00±93.79)g versus(196.40±60.27)g,P＜0.05].The total effective rate of defecation in the study group was 96.0％,which was higher than 32.0％in the control group(P＜0.05).The Patient Assessment of Constipation-Quality of Life(PAC-QOL)score in the study group was lower than that in the control group[(40.07±5.67)versus(63.07±7.46),P＜0.05].Conclusion Fasting nasogastric administration of sesame oil com-bined with multi-frequency vibrational abdominal massage can promote the recovery of intestinal function and improve constipation symptoms in stroke patients with nasogastric feeding.

Objective:To explore the effect of Taichi motor imagination therapy combined with resistance exercise on the recovery of heart function and quality of life in patients with chronic heart failure(CHF).Methods:A total of 118 elderly CHF patients admitted to Huangshan Shoukang Hospital between January 2020 and December 2023 were included in this randomized controlled trial.Participants were randomly divided into intervention group(n=59)and control group(n=59).Participants in the control group received conventional anti-heart failure treatment,while those in the intervention group received additional Taichi motor imagination therapy and resistance exercise.The in-tervention lasted for 3 months.Cardiac function[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd)and interventricular septal thickness at diastole(IVSTd)],quality of life[Minnesota Living with Heart Failure Questionnaire(MLHFQ)],markers of heart failure and neurohormones[B-type natri-uretic peptide(BNP),norepinephrine(NE),aldosterone(ALD)and angiotensin Ⅱ(AngⅡ)]levels and the inci-dence of major adverse cardiovascular events(MACE)during intervention were compared between the two groups.Results:Compared to those in the control group,participants in the intervention group had significant higher LVEF[(50.52±1.96)％vs.(45.84±2.21)％],and significant lower LVEDd[(57.12±1.72)mm vs.(60.45±2.14)mm],IVSTd[(8.84±0.82)mm vs.(10.00±1.19)mm],MLHFQ score[(28.86±5.34)points vs.(34.51±6.57)points],BNP[(9.23±1.35)pg/ml vs.(13.62±1.49)pg/ml],NE[(13.09±0.93)pmol/L vs.(16.63±0.86)pmol/L],ALD[(1.82±0.12)ng/L vs.(2.35±0.15)ng/L],AngⅡ[(0.75±0.07)ng/L vs.(0.90±0.06)ng/L]and incidence of MACE(6.90％vs.26.32％)(P＜0.01 all).Conclusion:Taichi motor imagination therapy combined with resistance exercise may improve the cardiac function and quality of life in CHF patients.

Accurate analysis of metal nanoparticles(MNPs)in sediments is a prerequisite for assessing the ecological risks of MNPs in aquatic environmental sediments.In this study,an analytical method for quantitative detection of concentration and particle size distribution of silver-containing nanoparticles(Ag-NPs),zinc-containing nanoparticles(Zn-NPs),cerium-containing nanoparticles(Ce-NPs),and titanium-containing nanoparticles(Ti-NPs)in sediments was established based on ultrasonic extraction-single particle inductively coupled plasma mass spectrometry(SP-ICP-MS).The effects of sample preparation conditions such as extraction solvent type,solid-liquid ratio,ultrasonic time,and settling time on the recovery of MNPs were investigated.The results showed that the extraction of MNPs from sediment by distilled water could effectively eliminate the high background signal interference introduced by the extractant under the conditions of solid-liquid ratio of 1∶400(g∶mL),ultrasonic extraction time of 1 h and settling time of 3 h.The detection limits for particle size of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 31,35,26 and 85 nm,respectively,while the detection limits of particle concentrations were 1.21×104,1.90×104,5.26×107 and 1.48×107 particles/g,respectively.The spiking recoveries of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 62.1％-108.7％,with relative standard deviations below 10％.This method could rapidly,accurately and simultaneously determine the concentration and particle size distribution of various MNPs in sediments,and was successfully applied to analysis of Ag-NPs,Zn-NPs,Ce-NPs,and Ti-NPs in authentic marine sediments.

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Objective:To apply statistical process control (SPC) techniques to the quality assurance of non-normal radiotherapy plans through Johnson transformation, establishing patient-specific tolerance and action limits based on treatment sites and dose/distance assessment criteria, thereby enhancing the intensity-modulated radiation therapy (IMRT) verification accuracy and dose delivery precision.Methods:In this study, 951 gamma analysis data of patient-specific quality assurance (PSQA) executed on the Halcyon accelerator platform were selected and categorized into six groups based on treatment sites, including brain (102 cases), head and neck (100 cases), breast (229 cases), lung (154 cases), esophagus (223 cases), and pelvic (143 cases) groups. The six groups of data were statistically analyzed through Anderson-Darling normality tests ( α = 0.05) using Minitab 21 software. Non-normal data were transformed into normal data through Johnson transformation and then were used to establish treatment site-specific tolerance and action limits, which were compared with the Shewhart control charts based on normal distributions. Results:The PSQA result of the six groups all exhibited non-normal distributions ( P < 0.05). Through Johnson transformation, the tolerance and action limits for the head and neck, breast, lung, esophagus, and pelvic areas under the 3%/2 mm criterion ranged from 95.13% to 96.16% and 94.19% to 95.91%, respectively. In contrast, the tolerance and action limits ranged from 91.15% to 94.86% and 89.94% to 94.78% under the 2%/2 mm criterion. Directly applying Shewhart control charts without normality assumptions yielded higher tolerance limits compared to the application of Johnson transformation, increasing the false positive rate in the non-normal PSQA process. Conclusions:Applying the SPC techniques directly to a non-normal process can lead to an increased false alarm rate and wrong process interpretation. The SPC techniques combined with Johnson transformation enable more effective monitoring of a non-normal PSQA process, facilitating timely identification of potential factors that may lead to an out-of-control process based on the treatment site-specific limits.

Objective:To analyze the dual gain effect of hyperbaric oxygen combined with vestibular rehabilitation training on patients with tinnitus and dizziness.Methods:This study was a retrospective analysis,and 90 patients with tinnitus and dizziness who visited the outpatient department of our hospital from January 2022 to January 2025 were selected to carry out the study,and were divided into observation group and control group according to the treatment methods,with 45 cases in each group.The matched group patients were treated with conventional medication,while the observation group received hyperbaric oxygen combined with vestibular rehabilitation training on the basis of the matched group.The clinical efficacy of the two groups was compared,including the concentration of oxygenated hemoglobin in the cerebral cortex,vestibular function,severity of tinnitus,and severity of dizziness before and after treatment.Results:The total effective rate of the observation group was higher than the matched group(P＜0.05);Post-treatment,there was no significant change in the concentration of oxygenated hemoglobin in the parietal and occipital cortex between the two groups(P＞0.05).However,the concentration of oxygenated hemoglobin in the temporal lobe,dorsolateral prefrontal cortex,and frontal polar cortex increased,and the observation group was higher than the matched group(P＜0.05);Post-treatment,the values of hemiparesis,total area of center of gravity movement(CA),and total length of center of gravity movement(PL)in both groups decreased,and the observation group was lower than the matched group(P＜0.05);Post-treatment,the severity score of tinnitus in both groups decreased,and the observation group was lower than that in the matched group(P＜0.05);Post-treatment,the degree score of vertigo in both groups decreased,and the observation group was lower than that in the matched group(P＜0.05).Conclusion:Hyperbaric oxygen combined with vestibular rehabilitation training has a significant dual gain effect on patients with tinnitus and dizziness,which can improve clinical efficacy,promote cortical neural activity,improve vestibular function,and thereby alleviate the severity of tinnitus and dizziness.