The philosophy of “treating disease before its onset” is a fundamental concept of traditional Chinese medicine (TCM), permeating its diagnostic and therapeutic framework, and is central to clinical practice. However, current TCM diagnostic and treatment models for the “pre-disease to disease” window period face several limitations, including the lack of comprehensive clinical parameters, difficulties in characterizing and integrating heterogeneous multimodal data, and insufficient dynamic precision in interventions and efficacy evaluations. To address these issues, guided by Professor Candong Li’s theory of TCM stateology, this study focuses on integrating objective multimodal data. It proposes a new model for personalized TCM diagnosis and treatment targeting the “pre-disease to disease” window period. This approach first proposes the idea of restructuring the conceptual framework of “symptom” and integrating multi-source heterogeneous data at macroscopic, mesoscopic, and microscopic levels to form a three-dimensional assessment indicator system. By integrating graph neural networks, convolutional neural networks, attention mechanisms, and knowledge graph-guided weight allocation, this approach enables collaborative representation, alignment, and fusion of multi-source data. Subsequently, it plans to construct a multimodal fusion model at both feature and decision levels, in order to establish mappings between indicators and TCM state elements, and to screen key indicators characterizing pathological evolution during the window period. Furthermore, it proposes a technical path for enhancing model interpretability using methods such as SHapley Additive exPlanations (SHAP) and Ablation-CAM++. Finally, with state assessment as the core, it proposes the concept of constructing a dynamic evaluation method for individualized diagnosis and treatment based on time-series data analysis using algorithms such as long short-term memory (LSTM) networks and gated recurrent units (GRUs). Moreover, a causal inference framework and semi-supervised learning strategies are introduced to enable quantitative evaluation of individual intervention effects and to provide interpretable therapeutic feedback, forming a complete technical path from data representation and fusion, weight adjustment, and interpretability analysis, to dynamic diagnosis feedback. This study aims to address deficiencies in the current TCM diagnosis and treatment model during the “pre-disease to disease” window period and to provide an operational framework for the clinical practice of TCM’s “treating disease before its onset”.

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 knowledge, attitudes, practices (KAP) and the situation of home blood pressure monitoring (HBPM) among hypertension patients in rural areas of Shanghai Municipality, so as to provide a basis for enhancing blood pressure management in this population. Methods: From June to October 2021, hypertension patients under management in Luodian Town and Luojing Town of rural areas of Shanghai Municipality were selected as survey subjects using a multistage random sampling method. Demographic information, KAP related to hypertension, and HBPM status were collected through questionnaire surveys. Patients were categorized into short disease duration (≤5 years), medium disease duration (6-10 years), and long disease duration (≥11 years) groups. KAP and HBPM status across different disease duration groups were analyzed statistically. Results: A total of 2 894 hypertensive patients were surveyed, including 1 317 (45.51%) males and 1 577 (54.49%) females. The median age was 69.00 (interquartile range, 10.00) years. There were 610 cases with short disease duration, accounting for 21.08%; 629 cases with medium duration, accounting for 21.73%; and 1 655 cases with long duration, accounting for 57.19%. The awareness of "hypertension control measures" was relatively high (97.89%), while awareness of "hypertension complications" was relatively low (71.70%). The adherence rate of "not perceiving difficulty in remembering to take medication on time and in correct doses" was relatively low (78.89%), and the proportion of participants who "walked ≥10 minutes per session at least once in the past 7 days" was relatively high (80.48%). A total of 1 209 cases (41.78%) engaged in HBPM, including 233 cases with short disease duration (19.27%), 252 cases with medium disease duration (20.84%), and 724 cases with long disease duration (59.88%). Compared with long disease duration hypertension patients, those with short disease duration had a alower awareness of "principles of pharmacological treatment for hypertension", a lower adherence rate of "medication should not be stopped after blood pressure control", and a lower proportion of providing their blood pressure measurement results to doctors (all P<0.017). However, they had higher proportions of alcohol consumption and daily salt intake >6 g/d (both P<0.017). Conclusions Short disease duration hypertension patients exhibit poorer performance in hypertension-related KAP and HBPM compared to long disease duration patients in rural areas of Shanghai Municipality. It is recommended to implement tailored health education based on disease duration, promote HBPM, and enhance blood pressure control rate.

As green, sustainable, and environmentally friendly material processing processes using biological cells or enzymes to achieve substance conversion, bioprocesses play an increasingly important role in biomanufacturing. It is difficult to optimize bioprocesses because of the complex relationship at multiple levels and multiple scales. The knowledge of mesoscale behaviors is the key to understanding the dynamics of bioprocesses and to sort out the complex relationships of parameter variations in the spatial-temporal domain. Mesoscale numerical simulation paves a way for understanding these phenomena, and the integration of artificial intelligence (AI) and mesoscale simulation offers new vitality into the optimization of bioprocesses. This article reviews the progress in mesoscale simulation and AI optimization of bioprocesses and discusses the possible development directions, aiming to promote the development of this field.
Artificial Intelligence ; Biotechnology/trends* ; Computer Simulation

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

This article focuses on the application of artificial intelligence in clinical hematology laboratory teaching. By analyzing the current situation of clinical hematology test teaching and combining the advantages of artificial intelligence technology, this paper explores its application prospects in clinical hematology laboratory teaching from multiple perspectives, such as case library construction, atlas resource library construction, virtual simulation training, auxiliary teaching, and clinical thinking training, and analyzes the possible problems of artificial intelligence in teaching practice.

Objective:To observe any effect of electroacupuncture on the urodynamics of rats modeling chronic urinary retention after a sacral cord injury (SCI), and to explore its regulatory effect on interstitial Cajal cells (ICCs) in the bladder and the mechanism.Methods:Seventy-five female Sprague-Dawley rats were randomly divided into a sham operation group, a model group, an electroacupuncture group, an inhibitor group, and an inhibitor plus electroacupuncture group, each of 15. On day 1 of the experiment the sacral spinal cord was completely transected at the level of the 3rd lumbar vertebra in all groups except the sham operation group. In that group the spinous processes and laminae of L 2-4 were exposed but not injured, and then sutured. On day 16, both the inhibitor group and the inhibitor plus electroacupuncture group were given intraperitoneal injections of imatinib mesylate, while the electroacupuncture group and the inhibitor plus electroacupuncture group began 14 consecutive days of electroacupuncture. After the intervention, urodynamic testing was performed on the rats in all five groups, and they were then sacrificed. Hematoxylin-eosin staining was used to observe any morphological changes in the bladder. Transmission electron microscopy was employed to assess the ultrastructure and quantity of ICCs in the bladder. And the gene and protein expression of c-Kit and stem cell factor (SCF) in bladder tissue were detected using polymerase chain reactions and western blotting. Western blotting was also applied to detect the relative expression of c-Kit phosphorylated proteins. Results:Compared with the sham group, the model and inhibitor groups showed significant differences in their urination rates, residual urine volumes, bladder volumes and compliance on the 30th day of the experiment. Compared with the model group, the rats who received electroacupuncture displayed more complete voiding, lower residual urine volume, greater bladder volume and better compliance. Compared with the electroacupuncture group, the urodynamic evaluation of the inhibitor plus electroacupuncture group indicated a significant decrease in urination rate, but a significant increase in residual urine volume, bladder volume and compliance. The SCI modeling had destroyed the morphology of the bladder detrusor muscle and the ultrastructure of the ICCs. And the number of Cajal interstitial cells and the relative expression of c-Kit, SCF, and p-c-Kit had decreased significantly. Compared with the model group, a significant improvement was observed in all urodynamic indicators, the morphology of the detrusor muscle, the ultrastructure and number of ICCs, and the relative expression of c-Kit, SCF, and p-c-Kit in the electroacupuncture groups. There were poorer urodynamic indicators, detrusor muscle morphology, ultrastructure and number of ICCs in the inhibitor plus electroacupuncture group compared with the group which received electroacupuncture alone, but there was a significant decrease in the relative expression of p-c-Kit.Conclusions:Electroacupuncture can improve the urodynamics of chronic urinary retention after sacral cord injury, at least in rats. The mechanism may be related to the benign regulation of ICCs through the bladder′s c-kit/SCF signal system.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.

Objective:The aim of this study is to explain the key role of chondrocyte ferroptosis in TMJ OA and demonstrate that abnormal occlusion stimulation is an important causative factor of ferroptosis.Methods:We observed the morphological changes of mouse condylar cartilage in unilateral anterior crossbite(UAC,an abnormal occlusion stimulation)and bilateral anterior elevation(BAE,a proliferation occlusion stimulation)mice by HE and SO staining,and analyzed the expression of intracellular GPX4 by im-munofluorescence staining,and analyzed the changes in the content of mitochondria and reactive oxygen species by JC-1 and ROS staining.Results:The UAC caused degeneration of condylar cartilage and ferroptosis of chondrocytes in mice.The accumulation of iron ions and the dysfunction of mitochondria in chondrocytes significantly upregulated.The expression of GPX4,which is a key reg-ulator in the regulation of ferroptosis was lowered in UAC mice condyle cartilage.Moreover,in BAE model the condylar cartilage hy-perplasia was observed,but not the ferroptosis of chondrocytes.Conclusion:This study revealed that the abnormal biological force caused by abnormal occlusion could induce ferroptosis of chondrocytes,and ferroptosis is one of the main factors leading to the de-generation and thinning of condylar cartilage.GPX4 could regulate the ferroptosis of chondrocytes.