Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

OBJECTIVES: To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) in a mouse model of asthma. METHODS: SPF-grade BALB/c mice were randomly divided into 7 groups (n=8 each group): normal control group, ovalbumin (OVA) group, dimethyl sulfoxide+corn oil group, budesonide (BUD) group, and low, medium, and high dose 2,6-DMBQ groups. An asthma mouse model was established by OVA induction, followed by corresponding drug interventions. Non-invasive lung function tests were performed to measure airway hyperresponsiveness, and enzyme-linked immunosorbent assay was used to determine levels of interleukin (IL)-17, IL-10, and serum immunoglobulin E in bronchoalveolar lavage fluid. A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid, while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes. Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway (p-AKT/AKT and p-p70S6K/p70S6K), and a fully automated biochemical analyzer was used to evaluate liver and kidney functions. RESULTS: Compared with the normal control group, the OVA group showed increased enhanced pause values, inflammation scores from hematoxylin-eosin staining, positive area from periodic acid-Schiff staining, percentage of eosinophils, IL-17/IL-10 ratio, serum immunoglobulin E levels, and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K (P<0.05). The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group (P<0.05). CONCLUSIONS 2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice, possibly by mitigating the imbalance between Th17 and regulatory T cells.
Animals ; Asthma/pathology* ; Mice, Inbred BALB C ; Signal Transduction/drug effects* ; Mice ; TOR Serine-Threonine Kinases/physiology* ; Female ; Benzoquinones/pharmacology* ; Immunoglobulin E/blood* ; Interleukin-10/analysis* ; Interleukin-17/analysis* ; Bronchoalveolar Lavage Fluid ; Lung/pathology*

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.

Objectives:To investigate the safety and efficacy of Cuffstent in the treatment of immediate type Ia endoleak during endovascular aneurysm repair(EVAR)of abdominal aortic aneurysm.Methods:The clinical data of 24 patients with immediate type Ia endoleak during EVAR treated with Cuffstent at the Second Xiangya Hospital of Central South University from January 2019 to December 2022 were retrospectively analyzed.There were 18 males and 6 females with a mean age of(70.3±7.1)years.Results:Of the 24 patients,22 underwent conventional proximal Cuffstent implantation,and 2 underwent fenestrated Cuffstent to preserve unilateral renal artery.Emergency EVAR was performed in 7 patients.The procedure was technically successful in all patients.Immediate disappearance of type Ia endoleak was achieved in 23 patients,whereas 1 patient exhibited mild persistent type Ia endoleak,which was managed conservatively with watchful follow-up.All the 24 patients finished an average of(39.0±15.1)months follow-up,and all patients were alive during the follow-up period.Two patients received aortic reintervention,and one patient received thoracic aortic stent graft implantation due to thoracic aortic penetrating ulcer,and one patient received abdominal aortic aneurysm resection and iliac artery stent implantation due to type II endoleak and iliac artery rupture,respectively.There were no other aorta-related complications and reintervention.Conclusions:Proximal addition of Cuffstent for the management of immediate type Ia endoleak during EVAR is safe and effective.

Objective To explore the mechanism underlying the role of disulfidptosis-related genes(DRGs)in the disease progression of metabolically associated fatty liver disease(MAFLD)based on bioinformatics.Methods In this study,the GEO database was utilized to screen for eligible MAFLD expression data,conduct differential gene analysis,and identify DRGs through consistent clustering to subtype MAFLD patients.The immune infiltration status among subtypes was further evaluated,and the infiltration of immune cells was analyzed using the CIBERSORT algorithm.The gene modules related to the disease were selected through weighted gene co-expression network analysis(WGCNA).Subsequently,a diagnostic model was constructed based on DRGs using machine learning models,and the performance of the model was verified.Finally,the stability of DRGs among different subtypes was evaluated using an external dataset,and the significance of the results was analyzed using statistical tests.Results Through the analysis of the dataset GSE31803,six disulfide death genes,namely,SLC3A2,NCKAP1,CYFIP1,FLNA,MYL6 and MYH10,which were closely related to the clinical characteristics of MAFLD,were screened out.MAFLD patients were classified into two subtypes,with subtype 1 having a higher level of immune cell infiltration.Key gene modules were identified through WGCNA.Through machine learning screening,the support vector machine(SVM)model was determined as the optimal classification model.External validation confirmed the stability and effectiveness of the key genes in different subtypes of MAFLD.Conclusion Based on DRGs,two highly heterogeneous subtypes of MAFLD were identified,which exhibited significant differences in clinical characteristics,biological processes and immune status,indicating that DRGs play a crucial role in the occurrence and development of MAFLD.

Objective:To evaluate the safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) in the treatment of recurrent and refractory malignant tumors.Methods:The data of 14 patients admitted to Xiamen Humanity Hospital from September 2022 to April 2023 were prospectively collected, including 7 patients with primary brain malignancies and 7 patients with locally recurrent inoperable head and neck malignancies. All patients received intravenous infusion of boron drug (NBB-001, p-dihydroxyborylphe nylalanine, a patented freeze-dried formulation) at a total nominal dosage of 500 mg/kg (11 patients) or 750 mg/kg (3 patients), and were irradiated with neutrons (operating with NeuPex system). Adverse events after treatment were recorded and assessed. The primary efficacy endpoint was the 90 d objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS) and complete response rate (CRR). Data were compiled and analyzed by SAS 9.4 software. The rate and 95% CI were calculated using Clopper-Pearson method. Results:The median dose delivered to 80% of the target volume (D 80%) was 16.80 GyE (range: 8.93-23.79 GyE). The most common adverse reactions were hyperamylasemia, alopecia, and hyperprolactinemia. Five patients experienced 8 cases of grade 3 or above adverse events, including 1 case of grade 4 acute kidney injury and 7 cases of grade 3 adverse events. All adverse events were recovered after observation or treatment. At 90 d after treatment, the ORR of all patients was 9/14 (64%, 95% CI: 35%-87%), disease control rate (DCR) was 10/14 (71%, 95% CI: 42%-92%), CRR was 2/14 (14%, 95% CI: 2%-42%); and the best overall response during the entire course included an ORR of 10/14 (71% ,95% CI: 42%-92%), DCR of 13/14 (93%, 95% CI: 66%-100%), and CRR of 3/14 (21% ,95% CI: 5%-51%). The 1-year survival rate for head and neck malignancies was 71.4%, and the 2-year survival rate was 42.8%. The 1-year survival rate for recurrent brain malignancies was 42.8%. Conclusion:AB-BNCT demonstrates favorable safety and promising efficacy in treating primary brain malignancies and recurrent/refractory head and neck malignancies, representing a potential therapeutic option.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To design a remote monitoring and early warning system of ventilators,so as to adapt to data collection for different types of ventilators,and achieve early warning for abnormal status in operation data of ventilators.Methods:A three-layer structure,which used information gateway of Internet of Things(IoTs)with multi communication standard as the core,and integrated with multiple interfaces,was adopted to construct a remote monitoring and early warning system of ventilators.Boolean function was used to determine strings of incorrect data,and extract respiratory information.Using incremental isolated forest algorithm processed ventilators'operation data for realizing anomaly detection.And then,the detection results were presented through a display module,so as to conduct early warning for existing abnormal situations.Results:The remote monitoring and early warning system of ventilator had an accuracy rate of monitoring over 98.0%for abnormity of different types of ventilators,which timely warning rate was over 98.5%.Conclusion:The designed remote monitoring and early warning system of ventilator can provide clear results of remote monitoring and early warning of ventilator,which can timely find abnormal status,and effectively improve management efficiency for ventilator,and promote the intelligent development of medical treatment.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To observe the regulatory effects of Tongfenglian capsule on intestinal flora,inflammatory factors and other indicators of gout in rats with gout arthritis(GA),and to explore possible mechanism of Tongfengli capsule on GA.Methods:A total of 36 male SD rats were randomly divided into blank group,Tongfenglian low,medium and high doses(0.216 g/kg,0.432 g/kg,0.864 g/kg)groups,colchicine group(0.18 mg/kg)and model group.Blank group and model group were given the same amount of distilled water,other groups were given the corresponding drug once a day for 14 days.On the 13th day after gavage,GA rat models were prepared according to Coderre modeling method,0.2 ml normal saline was injected into the right ankle joint for blank group,and general conditions of rats were dynamically observed to determine whether the model was established,and the time was recorded.Rate of foot swelling in each group was calculated.Abdominal aorta blood,colon tissue and intestinal contents of rats were collected,and colon length,pathological changes of colon tissue,serum levels of inflammatory factors(IL-1β,TLR4),mRNA expressions of NF-κB and TLR4 inflammatory pathway in intestinal tissue,and intestinal flora of rats were detected.Results:Compared with blank group,swelling rate of ankle joint,serum IL-1β and TLR4 levels,and mRNA expressions of TLR4 and NF-κB in intestinal tis-sue were significantly increased in model group,and a large number of inflammatory cells were infiltrated in the colon by HE staining,showing typical inflammatory pathological changes,colon length decreased significantly,intestinal flora richness and diversity de-creased,ratio of Firmicutes to Bacteroidetes increased,the abundance of Lactobacillus and Bifidobacterium decreased,and the abun-dance of Prevotella and Escherichia coli-Shigella increased.Compared with model group,all the indexes in all Tongfenglian groups were improved,the richness and diversity of intestinal flora were increased,and the reduction of intestinal microbial diversity and mi-crobial community structure caused by monosodiumurate were changed.Conclusion:Mechanism of Tongfenglian capsule alleviating inflammation may be related to the regulation of TLRs/NF-κB signaling pathway.Through the mediation of intestinal flora,Tongfengli-an capsule plays a role in regulating intestinal homeostasis,improving the abundance and diversity of intestinal microorganisms,and playing an intervention role in GA.This microecological intervention mechanism may be a potential means to prevent and treat GA.