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 prepare polyethylene glycol （PEG）-modified flower lactose （FL） loaded Curcumin （Cur） solid lipid nanoparticle （SLN） inhalable micropowder （referred to as “PEG-Cur-FL”）. METHODS PEG-Cur-FL was prepared by the solvent emulsification diffusion low-temperature solidification method， and its encapsulation efficiency， drug loading capacity， powder properties， aerodynamic particle size， in vitro deposition properties， and in vitro release characteristics were characterized. The mice were divided into Cur-SLN-FL （unmodified with PEG） group and PEG-Cur-FL group， with 55 mice in each group. Both groups of mice were given a single inhalation of 5 mg/kg （calculated as Cur） of the corresponding drug micropowder through an air tube. At 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24， 48 and 72 hours after administration， eyeballs were removed to collect blood and tracheal， lung， liver and kidney tissues were separated. The mass concentration of Cur in mouse plasma and various tissue samples was measured， and the tissue distribution and retention of the drug were analyzed. RESULTS The encapsulation efficiency and drug loading capacity of PEG-Cur-FL were （86.2±1.8）% and （4.2±0.2）%， respectively； the bulk density and tap density were （0.24±0.01） g/cm3 and （0.30±0.01） g/cm3， respectively； the aerodynamic particle size was （2.74±0.64） μm； the in vitro effective site deposition rate （secondary drug deposition rate） was （45.07±2.79）%. Compared with Cur raw materials， Cur-SLN- FL and PEG-Cur-FL had sustained release effects under both leakage and non-leakage conditions， and PEG-Cur-FL had a smoother sustained release in artificial lung fluid， with release characteristics consistent with the Weibull model. The results of in vivo distribution showed that the drug concentration in the lung tissue of PEG-Cur-FL group was significantly lower than that of Cur- SLN-FL group during the same period after 1 hour of administration， while the drug concentration in the lung tissue at 4 to 48 hours was significantly higher than that of Cur-SLN-FL group during the same period （P＜0.05）； the plasma drug concentrations of the PEG-Cur-FL group at all time points from 0.25 to 12 hours were significantly lower than those of the Cur-SLN-FL group during the same period （P＜0.05）， and the drug concentrations in liver and kidney tissues were also lower than those of the Cur-SLN-FL group during the same period （P＜0.05）. CONCLUSIONS PEG-Cur-FL is prepared successfully； the inhalable micropowder has good inhalability and release performance； after administration through the trachea， the effective concentration of Cur in lung tissue can be increased， while reducing its plasma drug concentration and drug distribution concentration in non-target organs.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.

Objective:To investigate the potential mechanism of electroacupuncture(EA)at bilateral Fengchi(GB20)in treating cerebral ischemia-reperfusion injury and to provide a scientific basis for future experimental research and clinical applications. Methods:Forty male specific-pathogen-free Sprague-Dawley rats were randomly divided into four groups:a normal group,a normal with EA group,a model group,and a model with EA group,with 10 rats in each group.The normal group received no intervention.The normal with EA group received EA at bilateral Fengchi(GB20).The model group underwent middle cerebral artery occlusion(MCAO)using the suture.The model with EA group underwent MCAO and received EA at bilateral Fengchi(GB20).Cerebral blood flow was monitored using a laser Doppler cerebral blood flow meter.Neurologic damage was assessed using the neurologic deficit score,and motor ability was observed using the CatWalk gait system.The expression of glial fibrillary acidic protein(GFAP)and neuronal nuclei(NeuN)protein,the neuron markers,was detected by Western blotting.The protein expression levels of GFAP and NeuN,as well as the number of positive cells in the motor cortex,were detected using immunofluorescence. Results:Compared to the normal group,the cerebral blood flow values in the model group and the model with EA group decreased by more than 50%during the modeling process(P<0.01)and returned to pre-modeling levels after reperfusion(P>0.05).The neurologic deficit score increased(P<0.05),the average motor velocity decreased(P<0.05),GFAP protein expression and the number of positive cells in the motor cortex increased(P<0.05),and the NeuN protein expression and the number of positive cells decreased(P<0.05)in the model group.Compared to the model group,the neurologic deficit score decreased(P<0.05),the average motor velocity accelerated(P<0.05),GFAP and NeuN protein expression and the number of positive cells in the motor cortex increased(P<0.01)in the model with EA group. Conclusion:EA at bilateral Fengchi(GB20)can reduce neuronal loss and increase GFAP and NeuN protein expression in the motor cortex of rats after ischemia-reperfusion,improve the motor function after ischemic stroke,and accelerate the recovery of balance and stability of the affected limbs.

Objective To investigate the protective effect of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI), and to clarify the critical role and regulating mechanism of transient receptor potential canonical (TRPC) 6/poly adenosine-diphosphate-ribose polymerase (PARP) 1 signaling pathway during this process. Methods The hucMSC-Exo was extracted by ultracentrifugation, and identified by transmission electron microscope (TEM), nanoparticle tracing analysis and Western blot. SD rats were randomly divided into the sham operation group (group S), sham operation+TRPC6 inhibitor SKF96365 group (group SS), renal IRI group (group IRI), exosome treatment group (group EXO) and exosome +TRPC6 inhibitor SKF96365 group (group ES), with 6 rats in each group. Serum creatinine and blood urea nitrogen levels were detected. Pathological changes of renal tissues were observed by hematoxylin-eosin (HE) staining and Paller score was calculated. The expression levels of key molecules of necroptosis in rat renal tissues, including receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL), TRPC6 and PARP1, were detected by Western blot. Results Typical saucer-like structure was observed under TEM. Nanoparticle tracing analysis showed that the average diameter of the extracted substance was 125.9 nm. Western blot revealed that the surface markers of CD9, CD63 and CD81 were positively expressed, confirmed that the extracted substance was exosome. Compared with group S, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was worsened, Paller score was elevated, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group IRI (all P < 0.05). Compared with group IRI, the serum creatinine and blood urea nitrogen levels were down-regulated, the pathological damage of renal tissues was mitigated, Paller score was decreased, the relative expression levels of TRPC6 and PARP1 proteins were up-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were down-regulated in group EXO (all P < 0.05). Compared with group EXO, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was aggravated, Paller score was increased, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group ES (all P < 0.05). Conclusions hucMSC-Exo may alleviate the necroptosis induced by renal IRI in rat models, which is related to the activation of TRPC6/PARP1 signaling pathway.

Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca²⁺ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca²⁺ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation

Objective To explore the correlation between personality characteristics and psychologi-cal craving in methamphetamine addicts,and to provide theoretical basis and empirical experience for the prevention of relapse. Methods Cattell 16 personality factor questionnaire and drug craving questionnaire were administered to 315 cases of methamphetamine addicts,to understand the personality factor of metham-phetamine addicts,psychological craving for drugs in the period of detoxification. Spearman correlation analy-sis was used to explore the relationship between personality traits and psychological craving. Results Intelli-gence(1. 13±2. 86),stability(4. 57±1. 42),perseverance(3. 39±2. 20),independence (4. 16±1. 39)and self-discipline (4. 81±1. 78)of methamphetamine addicts were significantly lower than the norm (P<0. 01), while the strength(7. 01±1. 96),bravity(6. 83±1. 54),sensitivity(6. 18±1. 81),suspicion(6. 31±2. 08), fantasy(8. 98±1. 32),anxiety(6. 33±2. 00) and tension(6. 21±2. 14) were significantly higher than the norm (P<0. 01). The total average score of craving for methamphetamine addicts was (3. 36±1. 85). The correlation between the total average score of craving and intelligence (r=-0. 201,P<0. 01),stability (r=-0. 275,P<0. 01),constant (r=-0. 184,P<0. 05),dominance (r=0. 269,P<0. 01),bravity ( r=0. 210,P< 0. 01),anxiety (r=0. 259,P<0. 01),independent (r=-0. 254,P<0. 01) were significant. Conclusion -Methamphetamine addicts are significantly different from ordinary people's personality traits, physiological withdrawal period still exists a certain degree of psychological craving for drugs. The stability of personality has a negative predictive effect on craving,while aggressiveness has a positive predictive effect on craving.

Objective To study the effect of high quality nursing service on independent living ability and psychological status of post-stroke depression patients.Methods A total of 130 postdepression patients were randomly divided into observation group and control group.The observation group received high quality nursing service and control group received routine nursing.The scores of activity of daily living scale(ADL) and Hamilton depression scale (HAMD) were used to assess the curative effect before and after intervention in two groups.Results Compared with intervention before,the scores of ADL and HAMD in two groups were both decreased after intervention (P ＜ 0.05),but the observation group had lower scores than control group (P ＜ 0.05).Conclusion High quality nursing service can effectively improve independent living ability and relieve the feelings of depression in post-stroke depression patients.