This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

OBJECTIVES: To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. METHODS: Forty male SD rats were randomly assigned to control group, model group, Najia group and Nazi group (n=10). In the latter 3 groups, rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test. After modeling, the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine. Pathological changes in the hypothalamic tissue of the rats were examined with HE staining, and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Immunohistochemistry was used to detect the expressions of GABAA receptors (GABAARs) in the hypothalamus, and the expression levels of glutamate decarboxylase (GAD65/67) and glutamine synthetase (GS) were determined with Western blotting. RESULTS: Compared with the model group, the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus. Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia. CONCLUSIONS Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; gamma-Aminobutyric Acid/metabolism* ; Sleep Initiation and Maintenance Disorders/therapy* ; Glutamine/metabolism* ; Glutamic Acid/metabolism* ; Acupuncture Therapy ; Hypothalamus/metabolism* ; Receptors, GABA-A/metabolism* ; Acupuncture Points

Objective To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid(Glu)/γ-aminobutyric acid(GABA)-glutamine(Gln)metabolic loop.Methods Forty male SD rats were randomly assigned to control group,model group,Najia group and Nazi group(n=10).In the latter 3 groups,rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test.After modeling,the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine.Pathological changes in the hypothalamic tissue of the rats were examined with HE staining,and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography(HPLC)-mass spectrometry(MS)/MS.Immunohistochemistry was used to detect the expressions of GABAA receptors(GABAARs)in the hypothalamus,and the expression levels of glutamate decarboxylase(GAD65/67)and glutamine synthetase(GS)were determined with Western blotting.Results Compared with the model group,the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus.Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia.Conclusion Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To investigate the impact of lupeol on periodontal tissue injury in periodontitis rats by regulating Ras homolog gene family member A(RhoA)/Rho associated coiled coil containing protein kinase(ROCK)signal pathway.Methods:SD rats were randomly divided into control group(NC group),Model group,Lupeol of low(Lupeol-L group,16.67 μg/kg),medium(Lupeol-M group,33.34 μg/kg)and high-dose(Lupeol-H group,66.68 μg/kg)groups,vitamin C(VC)group(100 mg/kg),Rhosin(RhoA inhibitor)group(40 mg/kg)and Lupeol-H+Rhosin group(66.68 μg/kg+40 mg/kg)groups(n=18).Except NC group,the rats in other groups were used to establish periodontitis models.After modeling,the drugs were administered to the mice of the groups respectively,once a day for 21 days.Serum levels of IL-1β and TNF-α were detected by ELISA.Alveolar bone resorption in rats was detected by methylene blue staining.HE staining was used to detect the pathological changes of periodontal tissues.The expres-sion of OPG protein in periodontal tissue was detected by immunohistochemistry.TRAP staining was used to detect the osteoclasts in rat periodontal tissue,and the expression of OPG,RANKL,RhoA,ROCK1 and ROCK2 proteins in periodontal tissue was detected by Western blot.Results:Compared with NC group,pathological injury of periodontal tissue was serious,TNF-α and IL-1β levels,the distance from alveolar crest to enamel cementum junction(CEJ),osteoclasts number and RANKL protein increased,the num-ber of osteoblasts,and the expression of OPG,RhoA,ROCK1 and ROCK2 proteins decreased in model group(P＜0.05).Compared with model group,pathological injury of periodontal tissue in all Lupeol groups and VC group was reduced,the levels of TNF-α and IL-1β,the distance from alveolar crest to CEJ,osteoclasts number and RANKL protein decreased,the number of osteoblasts,and the expression of OPG,RhoA,ROCK1 and ROCK2 proteins increased,the cor-responding indexes of Rhosin group showed the opposite trend(P＜0.05).Rhosin reversed improvement effect of high dose Lupeol on periodontal tissue injury in rats with periodontitis.Conclusion:Lupeol may reduce periodontal tissue injury in rats with peri-odontitis by activating RhoA/ROCK signaling pathway.

Objective To explore the associations of dietary patterns with bone mineral density(BMD)and osteoporosis(OP)in patients with knee osteoarthritis(KOA)in south China,identify the dietary patterns that could reduce the risk of OP,and provide a reference for prevention of OP.Methods Data from 600 KOA patients who were enrolled in the Pearl River Osteoarthritis Cohort(PROC)between April 2020 and April 2024 were extracted,including general characteristics,dietary questionnaire and BMD test.Factor analysis was employed to identify dietary patterns.Scores of dietary pattern were treated as continuous or categorical variables(quartile-based groups).Multivariable linear regression was used to assess associations between scores of dietary pattern and BMD,while the relationships with OP were analysed by binary logistic regression.Results The prevalence of OP in KOA patients was 19.8%.Factor analysis extracted eight dietary patterns:seafood-nuts,livestock-poultry meats,coarse grains-fruits,wheat-eggs,fish-dairy-vegetables,legumes-fruits,rice-wheat flour,and soy-dairy.After adjusting for confounders,it was found that the pattern of coarse grains-fruits was positively correlated with the BMD of left femoral neck and lumbar spine(P<0.01)and the fish-dairy-vegetables pattern was positively correlated with the BMD of lumbar spine(P<0.01).When pattern scores were discretized into quartiles,the legumes-fruits pattern(Q3 vs.Q1)was found in association with a 68.2%reduction in the risk of OP(P<0.05).Conclusion This study has identified that the pattern of legumes-fruits may lower a risk of OP,while the patterns of coarse grains-fruits and fish-dairy-vegetables correlate with higher BMD.The diet patterns are potentially beneficial to prevention of OP.For bone health,a balanced diet rich in legumes,fruits,vegetables,coarse grains,fish,nuts and dairy is recommended.

Objective To explore the associations of dietary patterns with bone mineral density(BMD)and osteoporosis(OP)in patients with knee osteoarthritis(KOA)in south China,identify the dietary patterns that could reduce the risk of OP,and provide a reference for prevention of OP.Methods Data from 600 KOA patients who were enrolled in the Pearl River Osteoarthritis Cohort(PROC)between April 2020 and April 2024 were extracted,including general characteristics,dietary questionnaire and BMD test.Factor analysis was employed to identify dietary patterns.Scores of dietary pattern were treated as continuous or categorical variables(quartile-based groups).Multivariable linear regression was used to assess associations between scores of dietary pattern and BMD,while the relationships with OP were analysed by binary logistic regression.Results The prevalence of OP in KOA patients was 19.8%.Factor analysis extracted eight dietary patterns:seafood-nuts,livestock-poultry meats,coarse grains-fruits,wheat-eggs,fish-dairy-vegetables,legumes-fruits,rice-wheat flour,and soy-dairy.After adjusting for confounders,it was found that the pattern of coarse grains-fruits was positively correlated with the BMD of left femoral neck and lumbar spine(P<0.01)and the fish-dairy-vegetables pattern was positively correlated with the BMD of lumbar spine(P<0.01).When pattern scores were discretized into quartiles,the legumes-fruits pattern(Q3 vs.Q1)was found in association with a 68.2%reduction in the risk of OP(P<0.05).Conclusion This study has identified that the pattern of legumes-fruits may lower a risk of OP,while the patterns of coarse grains-fruits and fish-dairy-vegetables correlate with higher BMD.The diet patterns are potentially beneficial to prevention of OP.For bone health,a balanced diet rich in legumes,fruits,vegetables,coarse grains,fish,nuts and dairy is recommended.