OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Artificial intelligence (AI) technology enhances the function of acupuncture clinical decision support system (CDSS) by promoting the accuracy of its diagnosis, assisting the formulation of personalized therapeutic regimen, and realizing the scientific and precise evaluation of its therapeutic effect. This paper deeply analyzes the unique advantages of AI-based acupuncture CDSS, including the intelligence and high efficiency. Besides, it points out the challenges of data security, the lack of model interpretation and the complexity of interdisciplinary cooperation in the development of acupuncture CDSS. With the continuous development and improvement of AI technology, acupuncture CDSS is expected to play a more important role in the fields of personalized medicine, telemedicine and disease prevention, and to further advance the efficiency and effect of acupuncture treatment, drive the modernization of acupuncture, and enhance its position and influence in the global healthcare system.
Humans ; Acupuncture Therapy ; Artificial Intelligence ; Decision Support Systems, Clinical

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.
Humans ; Inflammatory Bowel Diseases/therapy*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of non-Hodgkin lymphoma, is classified as an independent subtype of extranodal diffuse large B-cell lymphoma (DLBCL) in the 2008 World Health Organization (WHO) Classification (Turner et al., 2010). The 5th edition of the World Health Organization (WHO 2022) classification of hematolymphoid tumors retains this subtype (Alaggio et al., 2022). IVLBCL, which is characterized by neoplastic lymphocyte proliferation within the lumen of small blood vessels, tends to invade organs, such as the nervous system, skin, bone marrow (BM), and lung (D'Angelo et al., 2019; Satoh et al., 2019; Vásquez et al., 2019; Fukami et al., 2020).
Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Vascular Neoplasms/therapy*

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

AIM:To investigate the effect of tea polyphenols(TP)on the sensitivity of human gastric cancer cells to oxaliplatin(L-OHP)in vitro and its mechanism.METHODS:Human gastric cancer HGC-27 and N87 cells,and human gastric mucosal GES-1 cells were used in this study.The HGC-27 and N87 cells were randomly assigned into con-trol group,TP(5 μmol/L)group,L-OHP(5.2 μmol/L for HGC-27 cells,7.7 μmol/L for N87 cells)group,and TP(5 μmol/L)combined with L-OHP(5.2 μmol/L for HGC-27 cells,7.7 μmol/L for N87 cells)group,with 3 replicate wells per group.The cell viability was detected by CCK-8 assay,and the IC50 value of L-OHP was calculated.The proliferation of the cells was assessed by colony formation assay.The migration and invasion abilities of the cells were evaluated by scratch test and Transwell assay.Flow cytometry was performed to evaluate the antiapoptotic effect of the treatments.Ade-novirus infection was conducted to evaluate cell autophagy.The levels of intracellular reactive oxygen species(ROS)were assessed using a ROS assay kit.Western blot analysis was performed to evaluate the protein expression levels of microtu-bule-associated protein 1 light chain 3(LC3),nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and superoxide dismutase 1(SOD1).RESULTS:Combination of TP and L-OHP significantly reduced the viability of HGC-27 and N87 cells,and markedly inhibited cell proliferation and migration compared with L-OHP alone.Significant increas-es in autophagosomes and ROS levels were observed in combination group compared with L-OHP alone group.The ratio of LC3-II/LC3-I significantly increased in combination group,whereas the expression of Nrf2,HO-1 and SOD1 significantly decreased compared with L-OHP alone group(P<0.05).CONCLUSION:Treatment with TP enhanced the sensitivity of HGC-27 and N87 cells to L-OHP by inhibiting the Nrf2 pathway,promoting the production of intracellular ROS,and in-ducing cell autophagy.

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.