Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Coronary heart disease （CHD） has a distinct circadian rhythmicity in its onset， which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind"， this paper explores the pathogenic evolution rules of qi-blood disharmony， channel obstruction， interacting as cause and effect with circadian rhythm disorders in CHD. Clinically， CHD can be observed to attack in the early morning， at night， in the afternoon， and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation， yin deficiency with yang floating， qi and yin deficiency， and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time， regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages， and select the appropriate timing for administration to harness natural timing. At the Mao （卯） hour， yang ascends while yin descends， and taking medication at this time conforms to the ascending of yang qi. At the Wu （午） hour， the heart meridian is active， and taking medication at this time warms the channel passages and assists heart yang， which can be treated with modified Buzhong Yiqi Decoction （补中益气汤） or Shengyang Yiwei Decoction （升阳益胃汤）. At night， blood should be harmonized， when the channel passages are unblocked through nourishing， restraining， and searching， with Lianmei Decoction （连梅汤） combined with Dahuang Zhechong Pill （大黄䗪虫丸）. Following the temporal rhythm， the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises， resonating and corresponding with the natural rhythm.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Porcine reproductive and respiratory syndrome (PRRS), caused by the porcine reproductive and respiratory syndrome virus (PRRSV), is one of the major diseases threatening the swine industry. This study aims to rationally design and optimize natural antimicrobial peptides to identify antiviral candidates with potent inhibitory activity against PRRSV, thereby establishing a foundation for the development of novel preventive and therapeutic agents targeting PRRS. In this study, with cecropin D (CD) as the parent peptide, three derivatives (CD-2, CD-3, and CD-4) were designed through amino acid substitutions. CD and derived peptides were obtained by solid-phase peptide synthesis. MS and reversed-phase (RP)-HPLC were employed for sequence identification, purification, and purity analysis. The secondary structures of the peptides were investigated by circular dichroism spectroscopy. CellTiter 96^® AQueous one solution cell proliferation assay was used to evaluate the cytotoxicity of the peptides. The inhibitory activities and mechanisms of the peptides against PRRSV were studied by Western blotting, RT-qPCR, and indirect immunofluorescence assay. The MS and RP-HPLC results showed that CD and derived peptides were successfully synthesized, with the purity reaching up to 95%. Circular dichroism analysis revealed that the CD derivatives exhibited more stable and abundant α-helices in a cell membrane-mimicking environment. The MTS assay indicated that all tested peptides at 100 μg/mL had negligible cytotoxicity. The experimental results of the action phase of the peptide against PRRSV demonstrated that the derived peptides significantly enhanced antiviral activities at the viral entry stage compared with the parent peptide. This enhancement was attributed to the introduction of lysine, tryptophan, and phenylalanine, which increased the hydrophobicity and positive charge of the peptides. These findings provide a theoretical basis for the application and structural optimization of antiviral peptides and may offer a new strategy for preventing and controlling PRRSV.
Porcine respiratory and reproductive syndrome virus/physiology* ; Animals ; Swine ; Antiviral Agents/chemistry* ; Porcine Reproductive and Respiratory Syndrome/virology* ; Virus Internalization/drug effects* ; Antimicrobial Peptides/chemistry*

ObjectiveTo evaluate the clinical effectiveness and safety of Modified Zhigancao Granules （炙甘草汤加味颗粒） for preventing the early recurrence following radiofrequency ablation in patients with atrial fibrillation （AF） of qi-yin deficiency syndrome. MethodsA multi-center， randomized， double-blind， placebo-controlled trial was designed. A total of 116 patients with atrial fibrillation of qi-yin deficiency syndrome who underwent radiofrequency ablation for the first time were enrolled from 3 centers， and they were randomly divided into a treatment group （59 cases） and a control group （57 cases）. Both groups received basic western medicine treatment after surgery. In addition， the treatment group was given oral Modified Zhigancao Granules， while the control group was given oral placebo granules. The dosage for both groups was 20 g each time， twice a day， with continuous treatment for 12 weeks. The recurrence of atrial fibrillation in both groups was recorded at 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery. The serum levels of B-type natriuretic peptide （BNP）， interleukin-6 （IL-6）， high-sensitivity C-reactive protein （hs-CRP）， and tumor necrosis factor-α （TNF-α） were detected before treatment and 12 weeks after treatment in both groups. The scores of Atrial Fibrillation Effect on QualiTy-of-life （AFEQT） Questionnaire （including scores of the daily life dimension， symptom dimension， treatment worry dimension， treatment satisfaction dimension， and total score） and traditional Chinese medicine （TCM） syndrome scores were compared before treatment and at 4 weeks， 8 weeks， and 12 weeks between groups. Safety indicators such as blood routine， urine routine， liver function， and renal function were monitored before and after treatment. ResultsNine of the treatment group and seven of the control group dropped out. Finally， 50 patients in each group were included in the statistical analysis. At 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery， the recurrence rates of AF in the treatment group were 2.0% （1/50）， 2.0% （1/50）， 4.0% （2/50）， and 10.0% （5/50）， respectively； while those in the control group were 2.0% （1/50）， 26.0% （13/50）， 28.0% （14/50）， and 34.0% （17/50）， respectively. Compared with the control group at the same time points， the early recurrence rates of AF in the treatment group were significantly lower at 4 weeks， 8 weeks， and 12 weeks after surgery （P＜0.01）. Compared with the baseline within group， BNP， hs-CRP， IL-6， and TNF-α in the treatment group all decreased after 12 weeks of treatment （P＜0.05）； the difference in hs-CRP levels （before vs. after treatment） in the treatment group was higher than that in the control group （P＜0.01）. Compared with the baseline within group， both groups showed decreases in the total score of AFEQT Questionnaire， scores of the daily life dimension， treatment worry dimension， symptom dimension， and TCM syndrome scores at 4 weeks， 8 weeks， and 12 weeks after treatment. Meanwhile， the score of the treatment satisfaction dimension of AFEQT increased in both groups （P＜0.01）， and the improvements in all the above scores in the treatment group were superior to those in the control group at all time points （P＜0.05 or P＜0.01）. All safety indicators of patients in both groups were within the normal range before treatment and at 12 weeks after treatment， and no adverse reactions or adverse events occurred in either group. ConclusionModified Zhigancao Granules can reduce the early recurrence rate following radiofrequency ablation in AF patients with qi-yin deficiency syndrome， improve clinical symptoms and quality of life， suppress inflammatory response， and show good safety.

Objective To observe the clinical efficacy of Lingnan fire needling in the treatment of plaque psoriasis.Methods A total of 60 cases of patients with plaque psoriasis admitted to Bao'an Hospital of Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from August 2021 to January 2023 were selected,and the patients were randomly divided into the observation group and the control group according to the random number table method,with 30 cases in each group.The observation group was given Lingnan fire needling for treatment,and the control group was given topical application of Calcipotriol Ointment.The course of treatment covered eight weeks continuously.After eight weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Psoriasis Area and Severity Index(PASI)scores and Dermatology Life Quality Index(DLQI)scores,as well as the diameter of glomus under dermoscopy of the patients in the two groups were observed before the treatment and after 2,4,6,and 8 weeks of treatment.Changes in Generalized Anxiety Disorder Scale(GAD-7)scores before treatment and after 2,4,6,and 8 weeks of treatment were compared between the two groups.Results(1)After 2,4,6 and 8 weeks of treatment,the scores of PASI,DLQI and GAD-7 of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(2)The cured and markedly rate of the observation group was 86.67%(26/30);and that of the control group was 66.67%(20/30).The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(3)After 2,4,6,and 8 weeks of treatment,the diameter of glomus under dermoscopy of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).Conclusion Lingnan fire needling therapy for plaque psoriasis can effectively improve the clinical symptoms of the patients,relieve the anxiety symptoms induced by skin lesions and itching,so as to improve their quality of life.

This article aims to summarize the clinical experiences of Professor Zhou Peng in treating post-thoracotomy pain syndrome(PTPS)by application of integrated acupuncture and moxibustion based on spirit-regulating and essence-consolidating therapy.In the view of Professor Zhou Peng,PTPS is prone to disturb the heart and spirit due to recurrent attacks,thus over consumption of the"spirit of the body";and various factors during and after the operation damage the"essence of the body",so the treatment is based on the principle of spirit-regulating and essence-consolidating,the disease can be treated from the perspective of heart,liver,spleen,and kidneys.Clinical use of multi-dimensional integration of acupuncture and moxibustion mode of external treatment,with local encircled acupuncture,plum-blossom needling to relieve the patient's urgent needs,and then use the spirit-regulating and essence-consolidating therapy,refined moxibustion,embedding needling for comprehensive treatment,treating symptom and root cause simultaneously,so as to exert certain therapeutic effect.

ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation， migration， and aerobic glycolysis of hepatocellular carcinoma （HCC） using cell experiments， as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected， and Sprague-Dawley rats were randomly divided into blank serum group， inhibitor group， and high-， middle-， and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells； glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells； RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression， related proteins， and phosphorylation of the protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group， the Biejia Decoction Pill groups had significant reductions in OD value， migration rate during different periods of time， glycolytic rate-limiting enzymes （hexokinase， phosphofructokinase， pyruvate kinase）， and glycolytic metabolites （pyruvate， lactic acid， ATP） （all P<0.05）. RT-qPCR results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR， and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT （all P<0.05）. Western blot results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins， and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins （all P<0.05）. ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells， thereby inhibiting their proliferation and migration， possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.