To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Objective:To evaluate the efficacy and safety of Rituximab (RTX) combined with short-term use of glucocorticoids in the treatment of the initial episode of steroid-sensitive nephrotic syndrome (SSNS).Methods:A retrospective case summary.A total of 30 children with SSNS treated in the Department of Intrarenal Rheumatism and Immunology, Xuzhou Children′s Hospital from December 2021 to March 2023, were enrolled in this study.They were given a standard dose of RTX (375 mg/m 2) and glucocorticoids for a short term.The patients were followed up for 1 year, and the general condition, changes in CD19 + B lymphocytes expression after RTX treatment, the relapse rate, the median relapse-free survival and adverse reactions of RTX were recorded.Kaplan-Meier method was used to analyze the relapse-free survival time. Results:CD19 + B lymphocytes were depleted 2 weeks after RTX treatment, and the median time required for CD19 + B lymphocytes reconstitution was 5 months after RTX treatment.The 1-year relapse-free rate was 90.00%, and the median relapse-free survival was 11 months.The glucocorticoid discontinuation rate was 93.33% in 3 months after RTX treatment, and 100% in 6 and 12 months after RTX treatment.Adverse reactions included infusion reactions in 7 cases (23.33%), neutropenia/leukopenia in 5 cases (16.67%), hypoimmunoglobulinemia in 10 cases (33.33%), infections in 4 cases.One case was complicated with severe influenza A virus infection after CD19 + B lymphocytes reconstruction. Conclusions:A standard dose of RTX can significantly reduce the relapse frequency, maintain long-term remission of proteinuria, and reduce the dose of glucocorticoids in patients at the initial episode of SSNS.Thus, it is worthy of clinical promotion.

Objective:To explore the application value of Jiedu Jiangtang Futan Decoction combined with acupuncture and moxibustion in the treatment of acute cerebral infarction patients with diabetes(qi deficiency and blood stasis type).Methods:All pa-tients with acute cerebral infarction complicated with diabetes(type of qi deficiency and blood stasis)were treated in Hongdu Tradi-tional Chinese Medicine Hospital from October 2020 to September 2022 and randomly divided into two groups,with 69 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Jiedu Jiangtang Futan Decoction and acupuncture and moxibustion,and the efficacy was compared after two weeks of treatment.Results:Compared with before treatment,the serum levels of superoxide dismutase(SOD),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were increased in the two groups after treatment.The levels of serum matrix metalloproteinase-9(MMP-9),IL-6,fasting blood glucose(FBG),2-hour postprandial glucose(2 h PG)and glycated hemoglobin(HbA1c)were decreased.The Barthel index(BI)was increased,and the modified Rankin score(mRS)and National Institutes of Health Stroke Scale(NIHSS)were decreased(P<0.05).Compared with the control group,the levels of SOD,VEGF,BDNF and other indicators in the observation group were higher after treatment.The levels of MMP-9,IL-6,FBG,2 h PG and HbA1c were lower.BI was higher,mRS and NIHSS were lower,the difference were statistically significant(P<0.05).The total effective rate in the observation group was 94.20%(65/69),higher than 84.06%(58/69)in the control group(P<0.05).Conclusion:For patients with acute cerebral infarction complicated with diabetes(type of qi deficiency and blood stasis),the combination of Jiedu Jiangtang Futan Decoction and acupuncture and moxi-bustion treatment is helpful to promote blood supply to the brain,correct the imbalance of oxidative stress,regulate blood sugar level and improve clinical efficacy.

Objective To explore the application value of Kaiqiao Xingshen acupuncture combined with Buyang Huanwu decoction in the treatment of patients with cerebral hemorrhage in the recovery period(Qi defi-ciency and blood stasis syndrome),and to observe its impact on inflammatory indicators and neurokines.Method A total of 166 patients with cerebral hemorrhage in the recovery period(Qi deficiency and blood stasis syndrome)treated in Hongdu Traditional Chinese Medicine Hospital from September 2021 to October 2023,were randomly divided into control group(83 cases treated with conventional western medicine),and observation group(83 cases treated with a combination of Kaiqiao Xingshen acupuncture and Buyang Huanwu decoction).The therapeutic effect in the two groups was compared after 8 weeks of treatment.Results After treatment,the serum levels of matrix metalloproteinase-9(MMP-9),endothelin-1(ET-1),interleukin-2(IL-2),homocysteine(Hcy),and Bcl-2-associated X protein(bax)decreased in both groups,while brain-derived neurotrophic factor(BDNF)increased,and the improvement was more significant in the observation group,showing statistical significance(P<0.05);the average cerebral vascular flow and flow velocity in the observation group increased,while peripheral vascular resistance decreased,and the improvement in the observation group was more significant(P<0.05);the total symptom score of traditional Chinese medicine in the observation group decreased,while the Fuel Meyer functional score(FMA score)increased,and the improvement in the observation group was more significant(P<0.05);The total effective rate of the observation group was 93.98%(78/83),which was higher than that of the control group(80.72%,67/83)(P<0.05).Conclusion For patients with cerebral hemorrhage in the recovery period(Qi deficiency and blood stasis syndrome),Kaiqiao Xingshen acupuncture and Buyang Huanwu decoction help alleviate inflammatory reactions,promote the recovery of the blood-brain barrier,improve cerebral blood flow,promote neurological function recovery,and enhance clinical efficacy.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.