Background: Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus that significantly impairs patients’ quality of life. Traditional Chinese medicine (TCM), as a major component of complementary and alternative medicine, has accumulated numerous effective formulas for the clinical management of DPN. However, systematic approaches for optimizing TCM formulas remain limited. Objective: To establish a pathway-oriented approach for TCM formula optimization and to evaluate the efficacy and mechanisms of the optimized formula in DPN. Methods: We developed 2 formula optimization algorithms that defined pathway-oriented herbal correlation (HC) and herbal contribution (HO) to screen and construct a new herbal formula, Qihongtongbi (QHTB), for treating Qi deficiency and blood stasis syndrome complicated with DPN. An animal experiment was subsequently conducted to evaluate the therapeutic effectiveness of QHTB. A total of 32 specific-pathogen-free male ob/ob mice (18–20 g) were randomly divided into 4 groups: model, Mudan Granules (MDG), QHTB low- and high-dose groups (n = 8). Ten male C57BL/6J mice (18–20 g) served as the control group. Metabolomics analysis was further employed to elucidate the biological mechanisms underlying the effects of QHTB. Results: Based on our previous study on TCM medication patterns for treating DPN, 22 candidate herbs were selected for formula optimization. The top 5 candidate herbs (total HC = 25.24 × 10 ) exhibited HC values comparable to those of MDG (total HC = 26.1 × 10 ). These herbs were Carthamus tinctorius L. (HC = 5.40 × 10 ), Astragalus mongholicus Bunge (HC = 5.23 × 10 ), Salvia miltiorrhiza Bunge (HC = 5.15 × 10 ), Commiphora myrrha (T. Nees) Engl. (HC = 5.02 × 10 ), and Glycyrrhiza glabra L. (HC = 4.44 × 10 ). HO analysis showed that the cumulative HO of these 5 herbs exceeded 50%. In vivo experiments demonstrated that, compared with the model group, QHTB significantly lowered blood glucose (P < 0.05), enhanced nerve conduction velocity (P < 0.01), improved nociceptive hypersensitivity (P < 0.01), and ameliorated sciatic nerve morphology, with efficacy comparable to MDG. Serum and fecal metabolomics further revealed that QHTB exerted multipathway regulatory effects, among which nicotinate and nicotinamide metabolism represented a key mechanism. Conclusion: In summary, this study provides a methodological reference for the systematic optimization of TCM formulas.

Objective: To observe the distribution characteristics of sex differences in physical growth among children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024, so as to provide clues for improving growth assessment standards and promoting the health of children and adolescents. Methods: Using publicly available height and weight data for children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024 released by the statistics agency of the Taiwan education authorities, sex difference indices were analyzed. Growth curve charts and Pearson correlation were used to analyze the correlation between height/weight and year, as well as trends of change with age and year. These were compared with data from the 8th National Survey on Students Constitution and Health in 2019, covering Han and ethnic minority groups aged 6-15 years in mainland China. Results: The sex difference index for height among children and adolescents in Taiwan, China ranged from -1.20% to 6.67%, showed a trend of decreasing first and then increasing with age. The sex difference index for weight ranged from 3.76% to 19.15%, exhibited an age related trend of a slight initial increase, followed by a decrease, and then an increase. The sex difference indices for height in the 12-15 age groups and for weight in the 15-year-old group were positively correlated with the year ( r =0.74, 0.66, 0.61, 0.92 ; 0.63), while the sex difference indices for weight in the 6-8 age groups were negatively correlated with the year ( r =-0.71, -0.77, -0.53) (all P <0.05). In 2024, the height of children and adolescents in Taiwan, China increased gradually with age, but the growth rate for girls slowed down after age 12. A "two crossover" was observed in height between boys and girls, with boys being taller than girls in the 6-9 age range and after age 12. Weight for both sexes gradually increases with age, but boys have greater weight than girls at all ages. In 2019, the sexual differences in body size among children and adolescents in the Taiwan region, China (the sex difference indices for height:-0.96% to 6.49%；the sex difference indices for weight:4.69%-17.89%) fell within the variation ranges of counterparts in mainland China (the sex difference indices for height:-5.43% to 7.69%；the sex difference indices for weight:-10.12% to 21.56%). Conclusion The sex differences in physical growth among children and adolescents in Taiwan, China are dynamically changing with age and over the long term.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Artificial intelligence （AI） is gradually being applied in the field of decision-making support for the daily care of the older adults with disabilities. However， due to their limited cognitive functions， information asymmetry with medical staff and technical parties， and a certain degree of emotional deprivation， the older adults with disabilities are in a structurally vulnerable position. Against this background， several ethical dilemmas arise when AI technology intervenes in care decision-making. First， the informed consent process is difficult to genuinely implement. Second， algorithms based on average models tend to ignore individual differences， leading to “de-personalization” of services. Third， over-reliance on technology may further weaken humanistic care， thereby undermining the individual dignity of the older adults with disabilities. Fourth， in the care decision-making involving the joint participation of the older adults with disabilities， caregivers， medical teams， and AI systems， the boundaries of responsibility among all parties remain unclear， making it difficult to assign accountability when adverse outcomes occur. Drawing on the theories of vulnerability ethics， interactive ethics， and care ethics， this paper proposes a “vulnerability-interaction-care” path and put forward three-tiered countermeasures. The first was baseline safeguards， preventing the exploitation of the vulnerability of the older adults with disabilities and their caregivers， and requiring further safeguards for their dignity. The second was process protection， enhancing transparency and accountability within the human-machine collaboration framework， as well as establishing a multi-party consultation mechanism. The third was capacity empowerment， improving the subjectivity of the older adults with disabilities through age-appropriate interaction， structured expression of intentions， and caregiver participation.

The doctor-patient relationship in modern medical practice faces the limitations of evidence-based medicine under the “biomedical” model， as well as “four major gaps” in communication between doctors and patients who inhabit the two separate worlds of “medicine” and “life.” These issues not only pose challenges to the doctor-patient relationship but also constitute topics that medical ethical practice needs to address. The doctor-patient relationship is essentially an interpersonal relationship mediated by “illness.” It includes， but is not limited to， a consumer relationship and a contractual relationship， and the exceeding part lies in the content of “doctors’ humanistic care to patients.” Throughout the history of medical development， it is not difficult to find that medicine is never short of humanistic spirit and ethical principles， but lacks the tools to put them into practice. “Active listening，” proposed by humanistic psychologist Rogers， is not only an active and conscious communication method， but also a therapeutic concept and the most complete practice of the core assumption of “client-centeredness.” The focus of mutually trusting doctor-patient relationships lies in “mutual trust.” The premise of mutual trust represents honest communication and mutual understanding between both parties， while the “unconditional positive regard， acceptance， and empathy” emphasized by active listening are precisely the conditions that foster honest communication and mutual understanding. Therefore， it is necessary to incorporate active listening into the modern medical system as a theoretical weapon and practical tool for building mutually trusting doctor-patient relationships. Theoretically， it is conducive to advancing the reflection on the nature of mutually trusting doctor-patient relationships. Practically， it contributed to improving the level of trust between doctors and patients， promoting the establishment of mutually trusting doctor-patient relationships， and thus creating a favorable medical environment.

ObjectiveTo explore the long-term dynamic trajectories of fasting blood glucose （FBG） and insulin resistance （IR） in patients with type 2 diabetes mellitus （T2DM） and their influencing factors. MethodsThis retrospective cohort study included 1 896 T2DM patients registered at Tongren Hospital from May 2020 to May 2025. Based on longitudinal follow-up data of FBG and fasting insulin， joint latent class mixed models （JLMM） were applied to identify FBG-IR trajectories. Univariate and multinomial logistic regression was used to examine demographic characteristics， lifestyle， and clinical determinants of trajectory type. ResultsFour distinct FBG-IR trajectories were identified： stable FBG-IR （9.76%）， rising FBG-stable IR （5.01%）， stable FBG-elevated IR （75.90%）， and elevated FBG-IR （9.34%）. Compared with the stable FBG-IR group， age ≥60 years was protective against the elevated FBG-stable IR trajectory （OR=0.55， 95%CI：0.33-0.92， P=0.023）. Highereducation increased the risk of stable FBG-elevated IR （OR=1.40， 95%CI：1.01-1.94， P=0.046）. Abnormal blood pressure was associated with lower risks of stable FBG-elevated IR （OR=0.66， 95%CI：0.48-0.92， P=0.013） and elevated FBG-IR （OR=0.48， 95%CI：0.31-0.74， P=0.001）. Non-drinkers were less likely to belong to the stable FBG-elevated IR trajectory （OR=0.39， 95%CI：0.16-0.95， P=0.038）. ConclusionsThe evolution trajectory of FBG and IR in T2DM patients shows significant heterogeneity. The majority of patients have a deterioration of IR first. Age， education level， blood pressure， and alcohol consumption are the main influencing factors. Joint assessment of FBG and IR is helpful for early identification of high-risk individuals and guiding individualized intervention.

From the perspective of biopolitics， brain organoids represent an emerging technological field for life governance， embodying the governmentality logic of biopower and posing challenges to traditional ethical systems and bodily categories. Under the effect of the Foucauldian medical gaze and disciplinary mechanisms， brain organoid technology may objectify life processes and give rise to new forms of subjectivation， with risk governance standing as one of the core logics behind the ethical regulation of brain organoids. This paper further compared existing regulatory paths in China， the United States， and Europe to reveal the underlying disparities in political cultures and power distribution structures. On this basis， it is proposed to introduce institutional proposals into ethical regulation， such as the formulation of ethical regulation， the implementation of ethical review， and the setting of identifiable risks， to balance the governance tension between innovative exploration and disciplinary mechanisms.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

ObjectiveTo investigate the mechanism of Si Junzitang in treating liver injury in rats with spleen Qi deficiency syndrome based on transcriptomics and to experimentally verify its effects. MethodsSixty male SD rats were randomly divided into blank group， model group， low-dose Si Junzitang （6 g·kg^-1·d^-1）， medium-dose Si Junzitang group （12 g·kg^-1·d^-1）， high-dose Si Junzitang group （24 g·kg^-1·d^-1）， and natural recovery group， with 10 rats in each group. A composite multifactorial modeling method （forced swimming + intragastric administration of Xiao Chengqitang + irregular diet） was used to establish a spleen Qi deficiency model. After 30 days of continuous intervention， body weight and 3-hour food intake were measured， and macroscopic symptom scores for spleen Qi deficiency syndrome were evaluated. Serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in each group were detected， and hematoxylin and eosin （HE） staining was used to observe histopathological changes in liver tissue. Transcriptome sequencing （RNA-Seq） was used to identify differentially expressed genes （DEGs） among the blank， model， and high-dose Si Junzitang groups. Gene ontology（GO） and Kyoto encyclopedia of genes and genome（KEGG） enrichment analyses were performed on the DEGs. Immunofluorescence （IF） and Western blot were used to detect NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein （ASC）， Caspase-1， and the N-terminal domain of gasdermin D （GSDMD-N）. Immunohistochemistry （IHC） was used to detect the expression of downstream inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and interleukin-18 （IL-18）. ResultsCompared with the blank group， the model group showed significantly reduced body weight and 3-hour food intake， significantly increased macroscopic symptom scores， and elevated serum AST and ALT levels （P<0.01）， with mild inflammatory liver injury observed histologically. Compared with the model group， Si Junzitang at all doses significantly improved these parameters and alleviated liver injury in a dose-dependent manner （P<0.05，P<0.01）. RNA-Seq analysis revealed 1 254 DEGs between the blank and model groups， and 842 DEGs between the model and high-dose Si Junzitang groups. GO and KEGG enrichment analyses indicated that the NOD-like receptor signaling pathway was activated in liver injury associated with spleen Qi deficiency， suggesting that the NLRP3 inflammasome may be a key target. Results from IF， IHC， and Westernblot showed that compared with the blank group， the expression of NLRP3， ASC， Caspase-1， GSDMD-N， and the downstream inflammatory cytokines IL-1β， IL-6， and IL-18 were significantly increased in the model group （P<0.01）， while these levels were markedly decreased in the high-dose Si Junzitang group （P<0.01）. ConclusionSi Junzitang effectively improves mild inflammatory liver injury in rats with spleen Qi deficiency syndrome in a dose-dependent manner. Its mechanism may be associated with inhibition of the NLRP3/ASC/Caspase-1 signaling pathway， downregulation of the pyroptosis executioner protein GSDMD-N， and reduction of pyroptosis-related inflammatory cytokine release.