ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

Objective: To explore the management of blood donors tested reactive to HCV in blood screening based on confirmation of HCV infection. Methods: Multiple HCV antibody assays, repeating HCV RNA testing, follow-up of blood donors and retesting of archive samples were performed to confirm HCV infection, identify infection status, and exclude false positives in blood donors reactive to HCV in blood screening. Results: From 2011 to 2024, the unqualified rate of HCV detection in blood screening was 2.45‰(2 751/1 122 026). Among these, anti-HCV+-&NAT-accounted for 1.85‰, followed by anti-HCV++ at 0.60‰. The proportion of anti-HCV+-&NAT-and HCV RNA yields was extremely low (0.007‰). The positive rate of anti-HCV+-&NAT-samples tested by electrochemiluminescence method (ELCIA) was approximately 7.5%, differing among reagents (P<0.05). The follow-up of anti-HCV+-&NAT-donors showed that 96.2% (202/210) were false positives, but 51.4% of donors remained anti-HCV+-&NAT-during follow-up. Among them, 8 donors (3.8%) could not be ruled out from HCV infection due to positive retesting by ELCIA. Of the anti-HCV+-&NAT-donors who were reactive at the first follow-up, 86.8% remained anti-HCV+-&NAT-at the second follow-up. The sampling confirmation data showed that all of 260 anti-HCV++ donors were confirmed as anti-HCV positive, and the proportion of false positives or missed detections by NAT was very low. Two occult HBV infections (OBIs) and one HBsAg carrier were identified among the 3 anti-HCV +-&NAT+ donors, and no HCV infection was confirmed in 5 anti-HCV--&HCV RNA + donors. Conclusion: The prevalence of HCV among blood donors in Dalian was about 0.06%, with extremely low proportion of window-period infection and slightly higher proportion of resolved infections than that of current infections. The majority of anti-HCV+-&NAT-were false positive. Blood donors confirmed as false positive should be qualified in blood screening 3 months later before next donation. In order to reduce the false positive results, it was advisable to avoid the same type of supplementary reagents as the initial reagents when performing confirmation.

In response to the high risk of recurrence and metastasis after breast cancer surgery， this paper proposes a six-dimensional integrated preventive and therapeutic model， namely the "disease-syndrome-constitution-trend-strategy-efficacy" framework， including disease identification， syndrome differentiation， constitution differentiation， trend assessment， strategy implementation， and effect evaluation. This model builds upon the traditional three-dimensional approach of disease identification， syndrome differentiation and constitution differentiation， and introduces "trend" to dynamically capture the evolving tendencies of disease progression and the transformation of syndrome and constitution， thereby operationalizing the concept of "treating before disease onset". The "strategy" dimension enables the organic integration and individualized regulation of TCM and western medical interventions， while the "efficacy" dimension establishes a multidimensional evaluation system integrating TCM and western medicine to assess the efficacy of the "strategy"， so as to promote the systematic， dynamic， and precise development of treating before disease onset in TCM.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

[Objective] To explore the effects of different methods on antibody detection through investigating the causes of cross-matching incompatible in a patient with gastric malignant tumor, and to establish flow cytometry protocol for confirming hemolytic transfusion reaction (HTR). [Methods] Antibodies in the patient's serum were identified by red blood cells (RBCs) blood grouping, antibody screening and identification, acid elution test and PEG enhancement test. To confirm HTR, patient RBCs, proximal and distal ends RBCs, separated by capillary centrifugation, were tested by direct antiglobulin test (DAT) and Jk^a antigen single label and double label flow cytometry. [Results] Routine serological technology revealed the presence of anti-C, e (titer:2) and anti-Jka (titer >1) in the patient’s serum. After separation using capillary centrifugation technology, both the proximal and distal DAT and Jk^a antigen tests were negative. Both DAT and Jk^a antigen positive red blood cells (0.21%, 6/6 327) were found in the patient's blood samples by flow cytometry. After separation of blood samples by capillary centrifugation, there were significantly more DAT and Jk^a antigen double-positive RBCs in the distal end (0.43%, 33/7 707) than in the proximal end (0.09%, 15/7 225). Two blood samples were screened from over 100 donor blood samples that are compatible with the patient's cross-matching, and the transfusion effect was favorable. [Conclusion] Serological methods combined with flow cytometry could improve the sensitivity of antibody detection, provide a more accurate basis for the diagnosis of HTRs, and guarantee the safety of blood transfusion.

ObjectiveTo analyze the "compatibility" relationship of sugars and glycosides and the heat-clearing and blood-cooling effect of the roots of four varieties of Rehmannia glutinosa and provide a basis for research on the pharmacodynamic material basis and quality control of R. glutinosa. MethodsThe content of sugars and glycosides in the roots of four varieties of R. glutinosa was determined during the growth period. The principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， and the "compatibility" relationship of active components were employed to screen out the differential samples. A rat model of bleeding due to blood heat was used to verify the pharmacodynamic differences and the potential active components of differential samples. ResultsThe content and proportion characteristics of various components in roots of the four varieties of R. glutinosa during the expansion stage and the maturity stage had obvious differences. The proportion of phenylethanoid glycosides at the maturity stage was higher than that at the expansion stage. The R. glutinosa variety 85-5 had special quality characteristics among the tested varieties. All the samples alleviated the symptoms in the rat model. The effect of clearing heat and cooling blood was different between the maturity stage and the expansion stage， as well as between 85-5 samples at the maturity stage and other samples. The effect of clearing heat and cooling blood of R. glutinosa roots was the result of the combined action of multiple components in R. glutinosa roots and might be related to the high proportions of polysaccharides， iridoid glycosides， and phenylethanoid glycosides. ConclusionThe growth stage and variety affect the quality of R. glutinosa roots. The effect of clearing heat and cooling blood of R. glutinosa roots was related to the content and proportions of various components. The study can provide a basis for the basic research on the active components and quality control of R. glutinosa.

ObjectiveTo analyze the "compatibility" relationship of sugars and glycosides and the heat-clearing and blood-cooling effect of the roots of four varieties of Rehmannia glutinosa and provide a basis for research on the pharmacodynamic material basis and quality control of R. glutinosa. MethodsThe content of sugars and glycosides in the roots of four varieties of R. glutinosa was determined during the growth period. The principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， and the "compatibility" relationship of active components were employed to screen out the differential samples. A rat model of bleeding due to blood heat was used to verify the pharmacodynamic differences and the potential active components of differential samples. ResultsThe content and proportion characteristics of various components in roots of the four varieties of R. glutinosa during the expansion stage and the maturity stage had obvious differences. The proportion of phenylethanoid glycosides at the maturity stage was higher than that at the expansion stage. The R. glutinosa variety 85-5 had special quality characteristics among the tested varieties. All the samples alleviated the symptoms in the rat model. The effect of clearing heat and cooling blood was different between the maturity stage and the expansion stage， as well as between 85-5 samples at the maturity stage and other samples. The effect of clearing heat and cooling blood of R. glutinosa roots was the result of the combined action of multiple components in R. glutinosa roots and might be related to the high proportions of polysaccharides， iridoid glycosides， and phenylethanoid glycosides. ConclusionThe growth stage and variety affect the quality of R. glutinosa roots. The effect of clearing heat and cooling blood of R. glutinosa roots was related to the content and proportions of various components. The study can provide a basis for the basic research on the active components and quality control of R. glutinosa.

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

The bidirectional closed-loop motor imagery brain-computer interface (MI-BCI) is an emerging method for active rehabilitation training of motor dysfunction, extensively tested in both laboratory and clinical settings. However, no standardized method for evaluating its rehabilitation efficacy has been established, and relevant literature remains limited. To facilitate the clinical translation of bidirectional closed-loop MI-BCI, this article first introduced its fundamental principles, reviewed the rehabilitation training cycle and methods for evaluating rehabilitation efficacy, and summarized approaches for evaluating system usability, user satisfaction and usage. Finally, the challenges associated with evaluating the rehabilitation efficacy of bidirectional closed-loop MI-BCI were discussed, aiming to promote its broader adoption and standardization in clinical practice.
Brain-Computer Interfaces ; Humans ; Imagination/physiology* ; Imagery, Psychotherapy/methods*