Diabetic foot ulcer （DFU） is one of the most severe and costly complications of diabetes， with its refractory nature largely attributed to the persistent vicious cycle of inflammation and oxidative stress. Conventional single-target therapeutic strategies often fail to effectively break this cycle. Traditional Chinese medicine （TCM）， leveraging its unique philosophy of ''holistic regulation and multi-target intervention''， has demonstrated significant advantages in promoting DFU healing. This review introduced a ''systemic intervention'' perspective to systematically elucidate how TCM， through multi-component synergistic networks， precisely deconstructs and intervenes in this pathological loop. Firstly， this study provided an in-depth analysis of how， under hyperglycemic conditions， the crosstalk between the nuclear factor-kappa B （NF-κB） and NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） inflammasome pathways， the imbalance in macrophage polarization and the disruption of redox homeostasis interact to form a self-sustaining vicious cycle that impedes wound repair. Subsequently， the core content systematically discussed the strategies by which TCM breaks this deadlock： （1） Active ingredients from single herbs （e.g.， luteolin and astragaloside Ⅳ） can precisely modulate key nodes such as the phosphatidylinositol 3‑kinase/protein kinase B （PI3K/Akt） and TLR4/NF-κB pathways， thereby suppressing inflammation and oxidative stress. （2） Classical compound formulas （e.g.， Simiao Yong'an decoction and Taohong Siwu decoction） synergistically improve microcirculation and the immune microenvironment through multi-component cooperation. （3） External preparations （e.g.， Shengji Yuhong Ointment and Jinhuang powder） potently exert local anti-inflammatory and pro-repair effects by activating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase 1 （Nrf2/HO-1）. Collectively， these three modalities embody a synergistic mechanism characterized by ''internal treatment modulating the internal milieu to address the root cause， and external treatment targeting the lesion to alleviate symptoms''.” Existing clinical evidence has confirmed that the aforementioned multi-target interventions can effectively promote healing and improve symptoms. However， this field still faces persistent challenges， including an unclear material basis for the efficacy of compound formulas， and insufficient standardization in quality control and clinical protocols. These challenges stem from the inherent tension between the complex systems-based characteristics of TCM and the requirements of modern standardization. Future efforts urgently require to leverage cutting-edge technologies， such as network pharmacology， spatial multi-omics， and artificial intelligence to propel the paradigm shift in the prevention and treatment of DFU with TCM from ''empirical multi-target approaches'' toward ''precise systems regulation''. This will provide a theoretical foundation for developing innovative strategies for managing difficult-to-heal wounds based on an integrated traditional Chinese and Western medicine approach.

Traditional Chinese medicine （TCM）， through its multi-target and systematic regulatory effects， has demonstrated unique advantages in the treatment of gastric precancerous lesions （GPL）. At present， TCM theoretical research on GPL is mainly reflected in three aspects， the integration of macroscopic syndrome differentiation， the inflammation-carcinoma transformation mechanism， as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL， and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways， gene expression regulation， cellular epigenetics， histone modification， and intestinal microecology. It is proposed that future research on GPL should focus on four key directions， establishing multi-omics data， exploring targeted intervention strategies on key regulatory nodes， advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies， and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system， coupled with interdisciplinary research， will provide valuable references for the clinical treatment and scientific research of GPL.

Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Background Cadmium (Cd) is a highly toxic heavy metal. Chronic low-dose cadmium exposure can lead to renal tubular dysfunction. However, the precise mechanisms by which cadmium induces renal tubular injury through disruption of intracellular metabolic networks remain incompletely understood. Objective To investigate the toxic effects of cadmium exposure on human renal tubular epithelial cells (HK-2) and to elucidate the associated metabolic regulatory network from the perspective of metabolic reprogramming. Methods An in vitro HK-2 cell injury model was established using 5 μmol·L⁻¹ cadmium chloride (CdCl₂). The expression of the renal injury marker kidney injury molecule-1 (KIM-1) was determined by Western blot (WB). Glycolytic capacity was evaluated by metabolic flux analysis. Mitochondrial reactive oxygen species (ROS) production was assessed with a fluorescent probe. Mitochondrial membrane potential (MMP) was evaluated after JC-1 staining. Intracellular adenosine triphosphate (ATP) levels were measured using an ATP assay kit. In addition, untargeted metabolomics analysis was conducted to characterize alterations in the intracellular metabolic fingerprint profile and to explore the metabolic pathway changes underlying cadmium-induced renal tubular epithelial cell injury. Results Cadmium exposure induced injury in HK-2 cells, as indicated by mitochondrial membrane depolarization, increased mitochondrial ROS levels, and decreased intracellular ATP levels. Metabolic flux analysis further revealed significant metabolic reprogramming, characterized by compensatory increases in basal glycolytic rate and maximal glycolytic capacity. Untargeted metabolomics showed depletion of the long-chain acylcarnitine pool and deficiency of key metabolic cofactors, suggesting impaired fatty acid oxidation and mitochondrial energy metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the differential metabolites were mainly enriched in oxidative phosphorylation and glycerophospholipid metabolism. Correlation analysis showed that acylcarnitines were negatively correlated with nucleic acid metabolism-related metabolites, whereas ATP was positively correlated with lysophosphatidylcholine, suggesting that cadmium exposure-induced mitochondrial dysfunction may be accompanied by abnormal DNA metabolism and lipid peroxidation. Conclusion Cadmium exposure could induce impaired mitochondrial function, and promote glycolytic metabolic reprogramming in renal tubular epithelial cells. These findings provide new insights into the metabolic mechanisms underlying cadmium-induced nephrotoxicity and may help identify potential metabolic targets for intervention.

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

The paper reports acupuncture treatment for one case of oculomotor nerve palsy after cranial-orbital communicating tumor surgery. The acupoint prescription was composed of the local acupoints of the eyes (Yansanzhen, Tijian, Cuanzhu [BL2], Yuyao [EX-HN4] and Sizhukong [TE23]), the acupoints on the head, face and neck (Yangbai [GB14], Sibai [ST2] and Fengchi [GB20]), Guanyuan (CV4) on the abdomen, and those on the four limbs (Hegu [LI4], Zusanli [ST36], Shenmai [BL62] and Zhaohai [KI6]). The point-to-point needling technique with the eyelid lifted was operated at Tijian, Cuanzhu (BL2), Yuyao (EX-HN4), and Sizhukong (TE23). Warm needling with moxa cone placed on the needle handle was operated at Guanyuan (CV4) and Zusanli (ST36), and the usual needling technique was delivered at the rest acupoints. The treatment was given once daily, discontinued for 1 day after every 6 treatments. One course of treatment was composed of 7 days, and 6 courses were required. After treatment completion, the upper eyelids were basically symmetrical and the bilateral eye cracks were equal, the double vision appeared occasionally. No recurrence and no aggravation were reported in 1 month of follow up visit.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Oculomotor Nerve Diseases/etiology* ; Orbital Neoplasms/surgery* ; Postoperative Complications/etiology*

This paper reviews the published articles of recent years on the application of deep learning methods in automatic localization of acupoint, and summarizes it from 3 key links, i.e. the dataset construction, the neural network model design, and the accuracy evaluation of acupoint localization. The significant progress has been obtained in the field of deep learning for acupoint localization, but the scale of acupoint detection needs to be expanded and the precision, the generalization ability, and the real-time performance of the model be advanced. The future research should focus on the support of standardized datasets, and the integration of 3D modeling and multimodal data fusion, so as to increase the accuracy and strengthen the personalization of acupoint localization.
Deep Learning ; Acupuncture Points ; Humans ; Neural Networks, Computer

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

OBJECTIVES: To analyze the efficacy and safety of concomitant left atrial appendage clipping during heart valve surgery for valvular heart disease patients with atrial fibrillation. METHODS: Fifty-eight patients who underwent concomitant left atrial appendage clipping during cardiac valve surgery in the Second Affiliated Hospital of Nanchang University from January 2017 to June 2023 were included in the analysis, including 1 case who underwent aortic valve replacement, 49 cases who underwent mitral valve replace-ment (or valvuloplasty)+tricuspid valvuloplasty, and 8 cases who underwent double valve replacement+tricuspid valvuloplasty (3 cases combined with coronary artery bypass grafting). The patients were followed up for 3-36 months [(16.69±6.61) months] after operation, and the changes of cardiac function and the occurrence of serious adverse complications were evaluated. RESULTS: The cardiopulmonary bypass time ranged from 75 to 145 min [(102.50±21.03) min], and the aortic cross-clamp time ranged from 35 to 80 min [(58.02±14.63) min]. The length of postoperative intensive care unit stay was 1 to 5 days [(2.47±0.82) d], and the length of postoperative hospital stay was 7 to 22 days [(10.84±2.69) d]. Cardiac ultrasound indicated complete closure of the left atrial appendage in all cases. During the follow-up, New York Heart Association (NYHA) functional classifications were improved in 54 patients. No left atrial appendage-related bleeding events or other perioperative complications were observed; and no cerebral infarction, limb embolism events, or mortality cases occurred during the follow-up. CONCLUSIONS For valvular heart disease patients with atrial fibrillation, concomitant left atrial appendage clipping during cardiac valve surgery demonstrates efficacy and safety, with no severe adverse events during a medium-term follow-up.
Humans ; Atrial Appendage/surgery* ; Atrial Fibrillation/complications* ; Male ; Female ; Heart Valve Diseases/complications* ; Aged ; Middle Aged ; Heart Valve Prosthesis Implantation/methods* ; Treatment Outcome ; Cardiac Surgical Procedures/methods* ; Mitral Valve/surgery*

Objective To longitudinally analyze the changes in perioperative nutritional indicators in elderly patients with spontaneous intracerebral hemorrhage(ICH)and their correlation with the score of modified Rankin scale(mRS)score.Methods A total of 295 elderly ICH patients ad-mitted to the neurosurgery intensive care unit of North China University of Science and Technolo-gy Affiliated Hospital from June 2022 to November 2024 were consecutively enrolled in this study.The levels of relevant nutritional indicators were measured before(T1),and in 1(T2),3(T3),5(T4)and 7 d(T5)after surgery.According to the mRS score in 90 d after onset of the disease,they were divided into a good prognosis group(mRS score≤ 2,114 cases)and a poor prognosis group(mRS score≥3,181 cases).The general data and levels of nutritional indicators at above time points were compared between the two groups.Binary logistic regression analysis was applied to study the relationship between the perioperative nutritional indicator levels and the prognosis in elderly patients with spontaneous ICH.Results The poor prognosis group had significantly higher SBP,larger proportions of stroke history,hemorrhage in the brainstem and midline dis-placement,and increased NIHSS score than the good prognosis group(P＜0.05,P＜0.01).Obvi-ously lower BMI(56.48±9.54 kg vs 66.62±8.12 kg),decreased serum levels of albumin[40.24(39.10,41.16)g/L vs 43.30(40.65,45.50)g/L],prealbumin[203.00(164.00,261.00)mg/L vs 229.00(180.00,282.00)mg/L]and TC[4.68(4.11,5.39)mmol/L vs 4.91(4.47,5.66)mmol/L],reduced lymphocyte count[1.58(0.95,2.03)× 109/L vs 1.77(1.99,1.91)× 109/L],and reduced GCS[7.00(5.00,10.00)vs 9.00(7.00,13.00)]and Barthel[55.00(43.00,64.00)vs 61.00(52.00,69.00)]scores at admission were observed in the poor prognosis group than the good prognosis group(all P＜0.01).At all different time points,the poor prognosis group also got notably higher Controlling Nutritional Status(CONUT)scores(reaching the highest levels at 3 d after opera-tion),and lower Prognostic Nutritional Index(PNI)score and Geriatric Nutritional Risk Index(GNRI)score(both declining the lowest levels at same time)when compared with the poor prog-nosis group(all P＜0.01).Binary logistic regression analysis showed that COUNT scores,PNI scores and GNRI scores before(T1)and at 1(T2),3(T3),5(T4)and 7 d(T5)after operation were independent risk factors for 90-day poor prognosis in elderly patients with spontaneous ICH.Conclusion The fluctuations of 3 nutritional indicators at different time points in the periopera-tive period are closely associated with the 90-day prognosis of elderly ICH patients.Monitoring the changes in the nutritional indicators can quickly and conveniently predict the prognosis of the pa-tients,which has high clinical application value.