Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Objective To investigate the effect of programmed death ligand-1(PD-L1)overexpression on epithelial mesenchymal transformation(EMT)in endometrial cancer cells and its possible mechanism.Methods Ishikawa/PD-L1,a PD-L1 stable overexpression cell line constructed in the laboratory and the control Ishikawa/EV were used.The efficiency of PD-L1 overexpression was detected by qPCR and Western blot assay.The cell migration ability and invasion activity were detected by scratch assay and Transwell assay.The EMT-related protein and the phosphorylation level of nuclear transcription factor-κB(NF-κB)were detected by Western blot.Results Compared with the control group,the migration ability and invasion activity of Ishikawa/PD-L1 were significantly enhanced,and the expression of E-cadherin was significantly down-regulated,whereas vimentin,N-cadherin and p-p65 were significantly increased.Conclusion PD-L1 can promote EMT by inducing the activation of NF-κB pathway,and thus enhance the migration and invasion ability of endometrial cancer cells.

Objective To observe the effect of Selinexor(SEL)combined with Imatinib(IM)on the proliferation and apoptosis of Imatinib-resistant chronic myeloid leukemia K562/G01(KG)cells and explore the possible mechanisms.Methods K562 cells and KG cells were treated with SEL or IM respectively or in combination.Cells viability was examined by MTT assay.Apoptosis was assessed by flow cytometry.BCR-ABL mRNA was detected by RT-PCR.XPO1 was detected by Western blotting.Results IM and SEL both inhibited the proliferation of K562 cells and KG cells;half maximal inhibitory concentration(IC50)for 48 h was 0.16 μmol/L vs.6.48 μmol/L for IM and 132.0 nmol/L vs.275.9 nmol/L for SEL.Compared with SEL or IM alone,SEL combined with IM significantly inhibited the proliferation of KG cells(P＜0.05),induced KG cells apoptosis(P＜0.05),downregulated the levels of BCR-ABL mRNA(P＜0.05),and inhibited the expressions of XPO1 in KG cells(P＜0.05).Conclusion SEL combined with IM can synergistically inhibit the proliferation and induce apoptosis of KG cells,and then inhibit the expressions of BCR-ABL mRNA and XPO1 to exert an anti-leukemia effect.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

Objective:To study the life characteristics and related risk factors of patients with depression in Shandong Province.Methods:Based on the 2015 mental epidemiological survey database in Shandong Province,a total of 832 patients with depression,807 high-risk individuals with depression,and 819 low-risk individuals were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)and the Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders,Research Version(SCID-I/P).In 2020,SCID-I/P was used for re diagnosis,and the General Health Questionnaire(GHQ-12),Simple Quality of Life question-naire,Pittsburgh sleep quality index(PSQI),Childhood Trauma Questionnaire(CTQ),Social Support Rating Scale(SSRS),Global Pain Scale(GPS),Montreal Cognitive Assessment(MoCA),Simplified Coping Style Question-naire(SCSQ)were used for evaluation.Compare changes in the quality of life of depression patients and construct a risk factor model.Results:Patients with depression had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in the high-and low-risk groups,those in remission of depression had higher scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in non-re-mission,and those with new-onset disorder in the high-and low-risk groups had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those with no-onset disorder(Ps＜0.001).Depres-sion diagnosis and PSQI scale scores at baseline negatively predicted at retest after 5 years(β=-0.06,-0.15),while coping style tendencies at baseline positively predicted(β=0.06).The simple quality of life questionnaire at baseline negatively predicted depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,and PSQI scale scores at retest after 5 years(β=-0.11,-0.17,-0.09),while the simple quality of life question-naire at baseline positively predicted coping style tendencies at retest after 5 years(β=0.13).Depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,PSQI scale scores at retest after 5 years,coping style tendencies at retest after 5 years,SSRS scale scores,CTQ scale scores,GPS scale scores,and the simple quality of life questionnaire at baseline all influenced the simple quality of life questionnaire at retest after 5 years through ei-ther direct or indirect pathways.Conclusion:It suggest that the quality of life is lower in patients with depression than in the general population.Depression diagnosis,sleep,mental health,pain,social support,childhood trauma and coping are direct and indirect risk factors affecting life.

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases.The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared.The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group,while the postoperative satisfaction was higher in the endoscopic group than in the open group.This set of instruments has advantage of novel design,scientific structure,safe application.It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures,which can promote the development and popularization of laparoscopic technology.

Objective To explore the molecular mechanism by which FEZF1-AS1 overexpression promotes progression of non-small cell lung cancer(NSCLC)via the miR-130a-5p/CCND1 axis.Methods TCGA database was used to analyze FEZF1-AS1 expression levels in NSCLC.FEZF1-AS1 expression was detected by qRT-PCR in clinical specimens of NSCLC tissues and NSCLC cell lines,and its correlation with clinical features of the patients were analyzed.The binding sites of FEZF1-AS1 with hsa-miR-130a-5p and those of hsa-miR-130a-5p with CCND1 were predicted.CCK8 assay,clone formation assay,scratch assay,and Transwell assay were employed to examine the effects of FEZF1-AS1 knockdown and hsa-miR-130a-5p inhibitor on proliferation,invasion,and migration abilities of lung cancer cell lines.Dual luciferase assay was used to verify the binding of FEZF1-AS1 with hsa-miR-130a-5p and the binding of hsa-miR-130a-5p with CCND1.Western blotting was performed to detect the changes in CCND1 protein expression level in H1299 and H358 cells following FEZF1-AS1 knockdown and treatment with hsa-miR-130a-5p inhibitor.Results FEZF1-AS1 was highly expressed in NSCLC tissues in close correlation with lymph node metastasis and also in H1299 and H358 cell lines(all P<0.05).FEZF1-AS1 knockdown obviously reduced proliferation,migration,and invasion abilities of NSCLC cells(P<0.05).Dual luciferase assay confirmed the binding of hsa-miR-130a-5p with FEZF1-AS1 and CCND1(P<0.05),and hsa-miR-130a-5p inhibitor significantly inhibited proliferation,migration,and invasion of NSCLC cells(P<0.05).FEZF1-AS1 knockdown significantly reduced CCND1 protein expression in NSCLC cells,and this effect was strongly inhibited by treatment with hsa-miR-130a-5p inhibitor(P<0.05).Conclusion FEZF1-AS1 is highly expressed in NSCLC tissue in close correlation with lymph node metastasis to promote cancer progression through the miR-130a-5p/CCND1 axis.

Objective:To investigate the effect of macrophage-derived exosomes on the morphological transformation of Candida albicans (CA), and to explore the underlying mechanisms.Methods:In vitro cultured human acute monocytic leukemia cell line THP-1 was induced and differentiated into M0 macrophages using the phorbol ester PMA. CA was activated and prepared as the fungal suspension. M0 macrophages were infected with the CA suspension, and the process of cell phagocytosis was observed under a high-content imaging analysis system. M0 macrophage-derived exosomes (exosome group) and CA-infected M0 macrophage-derived exosomes (CA exosome group) were extracted by differential centrifugation; transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis were performed to identify and compare exosomes in the two groups. The exosomes from the two groups were separately co-cultured with CA (exosome-treated group and CA exosome-treated group), and independently cultured CA served as the blank control group; the morphological changes of CA were observed under an inverted microscope, the intracellular cyclic adenosine monophosphate (cAMP) contents were detected by the enzyme-linked immunosorbent assay (ELISA), and the expression levels of cAMP-related genes, RAS1 and CDC35 (also known as Cyr1), were detected by real-time quantitative PCR (RT-qPCR) . Results:Western blot analysis showed that exosomes from the exosome group and CA exosome group both expressed the tumor susceptibility gene 101 protein (TSG101, an exosome marker), and did not express calnexin (a negative marker) ; transmission electron microscopy and nanoparticle tracking analysis showed no significant differences in the morphology or size of the exosomes between the two groups. Compared with the blank control group, the exosome-treated group and CA exosome-treated group both showed obvious inhibition of the yeast-to-mycelial phase transition of CA, with a noticeable reduction in the length of the hyphae under the inverted microscope. ELISA revealed that the intracellular cAMP content in CA significantly decreased in the exosome-treated group and CA exosome-treated group (16.70 ± 0.84 pmol/ml, 16.82 ± 0.87 pmol/ml, respectively) compared with the blank control group (21.82 ± 1.08 pmol/ml; t = 6.45, 6.23, respectively, both P = 0.003). RT-qPCR revealed that the expression of the cAMP-related genes, RAS1 and CDC35, was down-regulated in the exosome-treated group and CA exosome-treated group compared with the blank control group (all P < 0.01), and the RAS1 mRNA expression was significantly lower in the CA exosome-treated group than in the exosome-treated group ( t = 7.43, P = 0.002) . Conclusion:Both M0 macrophage-derived exosomes and CA-infected M0 macrophage-derived exosomes could effectively inhibit the mycelial growth of CA, and the latter one exhibited a stronger inhibitory effect, possibly by down-regulating cAMP in the cAMP/protein kinase A pathway.

Objective:To analyze functional changes in macrophages in mouse models of vulvovaginal candidiasis (VVC) by modulating indoleamine 2,3-dioxygenase 1 (IDO1) .Methods:Forty specific-pathogen-free female ICR mice were randomly divided into 4 groups using a complete randomization method: a blank group, a VVC model group, a VVC model + 1-methyltryptophan (1-MT) group (referred to as the 1-MT group), a VVC model + interferon-γ (IFN-γ) group (referred to as the IFN-γ group), with 10 mice in each group. Except for the blank group, all the mice were injected subcutaneously with estradiol benzoate oil solution in the abdomen every other day for 6 days prior to modeling to induce pseudoestrus; after successful induction of pseudoestrus, the mice were inoculated vaginally with Candida albicans suspensions at a concentration of 2 × 10 9 CFU/ml once a day for 5 days to establish VVC mouse models, and subcutaneous injections of estradiol benzoate oil solution were continued simultaneously to maintain the pseudoestrus state; 1 day before inoculation with fungal suspensions, mice in the 1-MT group and IFN-γ group were pretreated with 1-MT and IFN-γ respectively, followed by once-daily same intervention for 6 consecutive days; mice in the blank group and VVC model group were intraperitoneally injected with physiological saline solution once a day for 6 consecutive days. On the 5th day of modeling, vaginal conditions in mice were observed and vaginal symptoms were scored; the vaginal lavage fluid was collected for smear microscopy and fungal colony counting; then, the mice were sacrificed, the vaginal tissues were collected and subjected to hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining, and the expression of IDO1 and the macrophage surface marker F4/80 was determined in the vaginal tissues by an immunofluorescence method; real-time fluorescence-based quantitative PCR (qPCR) was performed to determine mRNA expression levels of IDO1, inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1) in the vaginal tissues, and Western blot analysis to determine the IDO1 protein expression in the vaginal tissues. One-way analysis of variance was used to analyze the differences in indices among groups, and Tukey test was used for multiple comparisons. Results:Smear microscopic examination of the vaginal lavage fluid on the 5th day of modeling showed elongated hyphae with a few spores in the VVC model group, a large number of elongated hyphae aggregating in clusters with surrounding spores in the 1-MT group, and a few thin and short hyphae with a large number of spores in the IFN-γ group. Compared with the VVC model group (360.0 ± 15.9), the fungal colony counts in the vaginal lavage fluid significantly increased in the 1-MT group (523.7 ± 67.7, P = 0.002), but significantly decreased in the IFN-γ group (258.3 ± 27.57, P = 0.026). HE staining and PAS staining showed small abscess formation in the epidermis and predominant infiltration of neutrophils throughout the epidermal and dermal layers with a large number of spores and a few hyphae in the VVC model group; thickened epidermis and diffuse inflammatory infiltration predominated by neutrophils in the dermis were seen in the 1-MT group, with a large number of hyphae and spores aggregating into clusters, which were predominated by hyphae; in the IFN-γ group, spores aggregated in the epidermis without obvious hyphae, and a small amount of inflammatory cells predominated by neutrophils infiltrated the dermis. Immunofluorescence assay revealed that the relative fluorescence intensities of IDO1 and F4/80 were highest in the IFN-γ group and the 1-MT group, respectively. Western blot analysis revealed that the IDO1 protein expression in the VVC model group was significantly higher than that in the blank group ( P < 0.001) and the 1-MT group ( P < 0.05), but significantly lower than that in the IFN-γ group ( P < 0.05). qPCR showed that iNOS mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.01), and increased in the IFN-γ group compared with the blank group, VVC model group and 1-MT group (all P < 0.001); Arg-1 mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.001) and IFN-γ group ( P < 0.01), and increased in the 1-MT group compared with the blank group, VVC model group, and IFN-γ group (all P < 0.001) . Conclusion:In the VVC mouse models, upregulation of IDO1 may cause macrophage polarization toward the M1 phenotype, and inhibition of IDO1 may cause increased macrophage recruitment and exacerbate the inflammatory response.

Objective To explore the molecular mechanism by which FEZF1-AS1 overexpression promotes progression of non-small cell lung cancer(NSCLC)via the miR-130a-5p/CCND1 axis.Methods TCGA database was used to analyze FEZF1-AS1 expression levels in NSCLC.FEZF1-AS1 expression was detected by qRT-PCR in clinical specimens of NSCLC tissues and NSCLC cell lines,and its correlation with clinical features of the patients were analyzed.The binding sites of FEZF1-AS1 with hsa-miR-130a-5p and those of hsa-miR-130a-5p with CCND1 were predicted.CCK8 assay,clone formation assay,scratch assay,and Transwell assay were employed to examine the effects of FEZF1-AS1 knockdown and hsa-miR-130a-5p inhibitor on proliferation,invasion,and migration abilities of lung cancer cell lines.Dual luciferase assay was used to verify the binding of FEZF1-AS1 with hsa-miR-130a-5p and the binding of hsa-miR-130a-5p with CCND1.Western blotting was performed to detect the changes in CCND1 protein expression level in H1299 and H358 cells following FEZF1-AS1 knockdown and treatment with hsa-miR-130a-5p inhibitor.Results FEZF1-AS1 was highly expressed in NSCLC tissues in close correlation with lymph node metastasis and also in H1299 and H358 cell lines(all P<0.05).FEZF1-AS1 knockdown obviously reduced proliferation,migration,and invasion abilities of NSCLC cells(P<0.05).Dual luciferase assay confirmed the binding of hsa-miR-130a-5p with FEZF1-AS1 and CCND1(P<0.05),and hsa-miR-130a-5p inhibitor significantly inhibited proliferation,migration,and invasion of NSCLC cells(P<0.05).FEZF1-AS1 knockdown significantly reduced CCND1 protein expression in NSCLC cells,and this effect was strongly inhibited by treatment with hsa-miR-130a-5p inhibitor(P<0.05).Conclusion FEZF1-AS1 is highly expressed in NSCLC tissue in close correlation with lymph node metastasis to promote cancer progression through the miR-130a-5p/CCND1 axis.