Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

ObjectiveTo compare the protective effects of water extracts from fresh and dried Dendrobium huoshanense on gastric mucosa in chronic atrophic gastritis （CAG）. MethodsMale SD rats （n=72） were randomly divided into 9 groups， with 8 rats in each group， which were normal group， model group， Yangwei Shu （4 g·kg^-1） group， low-， medium-， and high-dose fresh D. huoshanense （3.5， 7， and 14 g·kg^-1） groups， and low-， medium-， and high-dose dried D. huoshanense （0.7， 1.4， 2.8 g·kg^-1） groups. The CAG rat model was successfully established by inducing with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） and other factors for a total of 11 weeks. Then， the rats were intervened with fresh and dried D. huoshanense for 4 weeks. The serum and gastric tissues of the rats were collected. The changes in gastric juice secretion volume and gastric acid pH value in each group were observed. The gastric mucosal injury was observed by naked eyes and hematoxylin-eosin（HE） staining. The gastric mucus secretion level was determined by Alcian blue and periodic acid-Schiff staining（AB-PAS） staining. The expression levels of tight junction proteins Occludin and ZO-1 in gastric tissues were determined by immunofluorescence. The expression levels of serum pepsinogen Ⅰ （PG Ⅰ）， pepsinogen Ⅱ （PG Ⅱ）， gastrin 17 （G-17）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， and aquaporin 4 （AQP4） in gastric tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed an obviously reduced gastric juice secretion volume （P0.05）， significantly increased gastric acid pH value （P0.01）， gastric mucosa with obvious atrophy， and a significantly reduced gastric mucus secretion volume （P0.01）. The expression of Occludin and ZO-1 in the gastric mucosal barrier was significantly decreased （P0.01）. The levels of PG Ⅰ and PG Ⅱ in the serum were obviously decreased （P0.05， P0.01）， and the levels of G-17， IL-1β， IL-6， and TNF-α were significantly increased （P0.01）. The expression level of AQP1 in the gastric tissue was significantly upregulated （P0.01）， and the expression levels of AQP3 and AQP4 were significantly downregulated （P0.01）. Compared with the model group， each drug administration group could improve the gastric mucosal atrophy of CAG model rats to varying degrees， obviously increase the gastric juice secretion volume of the model rats （P0.05， P0.01）， significantly decrease the gastric acid pH value （P0.01）， obviously increase the gastric mucus secretion volume （P0.05， P0.01）， obviously decrease the expression levels of G-17， IL-6， IL-1β， and TNF-α （P0.05， P0.01）， obviously increase the expression levels of Occludin， ZO-1， PG Ⅰ， and PG Ⅱ （P0.05， P0.01）， obviously upregulate the expression levels of AQP3 and AQP4 （P0.05， P0.01）， and obviously downregulate the expression level of AQP1 （P0.05， P0.01）. ConclusionThe water extracts of fresh and dried D. huoshanense can exert therapeutic effects on CAG by improving gastric mucosal injury， reducing inflammation， and regulating water metabolism. Moreover， the dried D. huoshanense has a better effect.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

The extraction process of traditional Chinese medicine(TCM) is an important part in the production and processing of TCM products. The modeling of this process is of great significance for achieving intelligent production. This paper summarizes the modeling methods for the extraction process of TCM, which mainly include mechanism modeling, empirical formula modeling, data-driven modeling, and mixed modeling. Among them, mechanism modeling and data-driven modeling are widely used. Furthermore, this paper suggests that the future research on the modeling of the extraction process of TCM can be carried out from the following five aspects: in-depth research and development of the extraction process of TCM compound prescriptions, complete description of the whole extraction process of TCM, development of methods for accurate determination of the properties of TCM decoction pieces before extraction, development of adaptive self-optimization technology for models, and construction of models based on a new generation of artificial intelligence methods.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Models, Theoretical ; Artificial Intelligence ; Humans

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male

Objective:To establish a complete system for the isolation, purification, identification, and culture of Kaposiform hemangioendothelioma-derived endothelial cells (KHE-ECs), to analyze the phenotype of KHE-ECs, and to explore the possibility of establishing a KHE-EC bank.Methods:A novel digestion solution for KHE tumors (patent number: CN202410500224.2) was formulated using collection fluid, Liberase TM and dispase stock solutions, and was used to process tumor tissues to obtain cells. High-purity KHE-ECs were purified using CD31 + immunomagnetic beads. The EGM-2 complete medium containing 10% fetal bovine serum and 2% penicillin-streptomycin solution was employed for cell culture. To verify the characteristics of KHE-ECs, immunofluorescence assay was conducted to determine the expression of endothelial cell-specific markers CD31 and CD34, KHE disease markers podoplanin (D2-40), prospero-related homeobox 1 (Prox-1), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), as well as an infantile hemangioma-specific diagnostic marker glucose transporter 1 (GLUT-1). Human umbilical vein endothelial cells (HUVECs) served as controls for the phenotype analysis of KHE-ECs, including cell viability, cytoskeleton, proliferation, migration, invasion, tube formation, and sprouting ability. Results:Primary cells were successfully isolated from KHE tumor tissues, and high-purity KHE-ECs were obtained by using CD31 + immunomagnetic beads. The cells exhibited typical spindle-shaped morphology and an adherent growth pattern. Immunofluorescence assay showed that KHE-ECs expressed CD31, CD34, D2-40, Prox-1, and LYVE1, but did not express GLUT-1. There were significant differences in cell morphology, cell viability, and cytoskeletal structures between KHE-ECs and HUVECs. Additionally, the KHE-EC group showed significantly increased percentages of proliferative cells (29.1% ± 2.5%), numbers of migratory cells (114.3 ± 9.4) and invasive cells (110.0 ± 6.1), tube length (32 121.0 ± 892.0 μm), and number of sprouting cells (25.0 ± 3.6) compared with the HUVEC group (13.0% ± 2.2%, 38.0 ± 3.6, 35.3 ± 2.3, 25 345.0 ± 448.1 μm, 5.0 ± 1.0, respectively, all P ≤ 0.001) . Conclusion:An innovative digestion solution specifically for KHE tumors was formulated for the first time, and high-purity and well-growing KHE-EC strains were successfully isolated and purified by using the novel digestion solution in combination with CD31 + immunomagnetic beads, providing a stable and reliable cell source for subsequent experimental studies on KHE and laying the foundation for establishing a KHE-EC bank.

Objective:To investigate the optimal timing of oral propranolol treatment for proliferative infantile hemangiomas (IH) .Methods:A bidirectional cohort study was conducted. Infants with proliferative IH receiving oral propranolol treatment were collected from the Department of Pediatric Surgery, West China Hospital, Sichuan University between June 2015 and May 2019, and their general information and IH-related clinical data were analyzed. The primary outcome was the satisfactory regression rate of IH during 6-12 months of continuous oral propranolol treatment; secondary outcomes included the time to achieve satisfactory regression, incidence of adverse reactions, incidence of IH ulceration, and IH recurrence rate. Multivariate logistic regression was performed to identify factors influencing the satisfactory regression of IH after propranolol treatment, and a receiver operating characteristic (ROC) curve was employed to determine the optimal age for initiating propranolol therapy.Results:A total of 122 IH infants were enrolled in the study, including 32 males (26.2%) and 90 females (73.8%), with ages ( M[ Q1, Q3]) of 8.6 [6.3, 12.3] weeks. IH was located on the head and face in 56 cases (45.9%). There were 57 cases (46.7%) of localized IH, 53 (43.4%) of segmental IH, and 86 (70.5%) of mixed-type IH. Ulceration occurred in 17 cases (13.9%). After 6 months of propranolol treatment, 8 patients (6.6%) experienced treatment failure, and 12 (9.8%) experienced relapse within 6 months after discontinuation of propranolol. During 6 months of oral propranolol treatment, 56 infants (45.9%) experienced mild to moderate adverse reactions, with no drug-related deaths observed. Multivariate logistic regression analysis revealed that the age at initiation of propranolol treatment was an independent factor influencing satisfactory regression of IH ( OR = 0.879, 95% CI: 0.808 - 0.957). ROC curve analysis revealed that the optimal age for starting propranolol therapy was 9.9 weeks, with a sensitivity of 75.7% and a specificity of 61.5%. Infants aged ≤ 9.9 weeks (73 cases) had a significantly higher satisfactory regression rate (72.6% [53/73]) compared with those aged > 9.9 weeks (49 cases, 34.7% [17/49]; χ2 = 17.23, P < 0.001) ; the time to achieve satisfactory regression of IH was significantly shorter in the infants aged ≤ 9.9 weeks ( M[ Q1, Q3]: 46.0 [38.5, 48.0] weeks) than in those aged > 9.9 weeks (57.0 [40.0, 73.5] weeks; Z = -2.01, P = 0.045) . Conclusion:For IH infants requiring systemic therapy, initiation of oral propranolol before the age of 10 weeks appeared to improve the satisfactory regression rate of IH.