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 analyze the types and distribution of microbiome in intestinal and lung tissues of children with asthma, and to explore the correlation between microbiota changes and asthma. Methods From 2021 to 2023, a total of 28,939 children with asthma who visited Ezhou Central Hospital, Maternal and Child Health Hospital or Ezhou Egang Hospital were selected as the study subjects, and 2,000 healthy children who underwent outpatient physical examinations at these three hospitals during the same period were selected as the control group. The distribution and characteristics of intestinal and pulmonary microbiome in the two groups were analyzed by 16SrDNA sequencing. Logistic regression analysis model was used to analyze the correlation between microbiota distribution and asthma occurrence. Results In the intestinal tissues of children with asthma compared to healthy children, the abundance of Bacteroidetes at the phylum level decreased, while the abundance of Firmicutes and Proteobacteria increased significantly (P<0.05), and the abundance of Prevotalle and Clostridium at the genus level increased significantly. In lung tissues of asthmatic children compared to health children, the abundance of Firmicutes at the phylum level decreased while the abundance of Proteobacteria increased significantly (P<0.05), and the abundance of Neisseria, Prevotella and Actinomyces at the genus level increased significantly. Binary logistic regression results showed that the abundances of Lactobacillus (OR=0.842, 95% CI: 0.533-0.947), Bacteroides fragilis (OR=0.649, 95%CI: 0.377-0.890), Bifidobacterium (OR=0.901, 95% CI: 0.633-0.994), and Parabacteroides distasonis (OR=0.547, 95% CI: 0.192-0.708) in the intestinal tissues were all protective factors for the asthma in children. In the lung tissue, the abundance of Neisseria (OR=2.140, 95% CI: 1.749-3.305) was a risk factor for the asthma in children, and Prevotella (OR=0.691, 95% CI: 0.491-0.926) was a protective factor for the asthma in children (P<0.05). Conclusion The dysbiosis of intestinal and pulmonary microbiome is closely related to the occurrence of asthma in children, and the detection of microbiota is of great significance for the diagnosis of childhood asthma.

Objective To analyze the types and distribution of microbiome in intestinal and lung tissues of children with asthma, and to explore the correlation between microbiota changes and asthma. Methods From 2021 to 2023, a total of 28,939 children with asthma who visited Ezhou Central Hospital, Maternal and Child Health Hospital or Ezhou Egang Hospital were selected as the study subjects, and 2,000 healthy children who underwent outpatient physical examinations at these three hospitals during the same period were selected as the control group. The distribution and characteristics of intestinal and pulmonary microbiome in the two groups were analyzed by 16SrDNA sequencing. Logistic regression analysis model was used to analyze the correlation between microbiota distribution and asthma occurrence. Results In the intestinal tissues of children with asthma compared to healthy children, the abundance of Bacteroidetes at the phylum level decreased, while the abundance of Firmicutes and Proteobacteria increased significantly (P<0.05), and the abundance of Prevotalle and Clostridium at the genus level increased significantly. In lung tissues of asthmatic children compared to health children, the abundance of Firmicutes at the phylum level decreased while the abundance of Proteobacteria increased significantly (P<0.05), and the abundance of Neisseria, Prevotella and Actinomyces at the genus level increased significantly. Binary logistic regression results showed that the abundances of Lactobacillus (OR=0.842, 95% CI: 0.533-0.947), Bacteroides fragilis (OR=0.649, 95%CI: 0.377-0.890), Bifidobacterium (OR=0.901, 95% CI: 0.633-0.994), and Parabacteroides distasonis (OR=0.547, 95% CI: 0.192-0.708) in the intestinal tissues were all protective factors for the asthma in children. In the lung tissue, the abundance of Neisseria (OR=2.140, 95% CI: 1.749-3.305) was a risk factor for the asthma in children, and Prevotella (OR=0.691, 95% CI: 0.491-0.926) was a protective factor for the asthma in children (P<0.05). Conclusion The dysbiosis of intestinal and pulmonary microbiome is closely related to the occurrence of asthma in children, and the detection of microbiota is of great significance for the diagnosis of childhood asthma.

Objective:To investigate the clinical characteristics of omphalocele, and to assess the risk factors associated with adverse outcomes.Methods:A retrospective cohort study was conducted. Clinical data of 224 patients diagnosed with omphalocele, who were hospitalized at Children′s Hospital, Zhejiang University School of Medicine from January 2013 to December 2022, were collected. Based on their discharge outcomes, the patients were classified into 2 groups: favorable outcomes and unfavorable outcomes. Chi-square test or continuity correction χ2 test or Fisher exact probability method, and Mann-Whitney U test were used for intergroup comparisons. Logistic regression analysis was performed to identify risk factors associated with adverse outcomes in omphalocele. Results:Among the 224 patients with omphalocele, 126 were male. A total of 208 patients (92.9%) had favorable outcomes, while 16 patients (7.1%) had unfavorable outcomes. In the unfavorable outcomes group, 14 patients had giant omphaloceles, while 100 patients had giant omphaloceles in the favorable outcomes group. The rates of herniation of more than two intra-abdominal organs in the hernial sac, congenital heart defects, patent ductus arteriosus, pulmonary hypertension, sepsis and infection of the hernial sac, were all higher in the unfavorable outcomes group compared to the favorable outcomes group (all P<0.05). Patients with unfavorable outcomes had longer mechanical ventilation time, duration of oxygen use, duration of parenteral nutrition, hospital stays, and higher rates of parenteral nutrition-associated cholestasis compared to those with favorable outcomes (all P<0.01). Multivariate Logistic regression analysis indicated that pulmonary hypertension ( OR=9.39, 95% CI 1.20-73.32), sepsis ( OR=8.59, 95% CI 1.32-55.86), and congenital heart defects ( OR=6.55, 95% CI 1.11-38.73) were all independent risk factors for adverse outcomes in omphalocele (all P<0.05). Conclusions:Infants with omphalocele are prone to complications such as cardiovascular malformations, infections, and pulmonary hypertension. Adverse outcomes in omphalocele are associated with pulmonary hypertension, sepsis, and congenital heart defects.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.