ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ² = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ² = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ² = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ² = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ² = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ² = 5.604, P_adjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Objective To explore the occurrence risk of enteral nutrition intolerance and analyze its influencing factors in 302 elderly critically ill patients. Methods The clinical case data of elderly critically ill patients in department of elderly cadres of the hospital were retrospectively analyzed from January 2019 to January 2024. According to the occurrence of enteral nutrition intolerance or not, they were divided into occurrence group (n=156) and non-occurrence group (n=146). The risk of nutritional intolerance in elderly critically ill patients was evaluated by feeding intolerance risk assessment form, and the influencing factors of enteral nutrition intolerance were analyzed by multivariate logistic regression analysis. Results Among the 302 elderly patients with critical illness, 53.31% (161/302) had high risk of enteral nutrition intolerance, and 51.66% (156/302) had enteral nutrition intolerance. Multivariate logistic analysis revealed that CRP level>10mg/L, APACHE-II score≥20 points, Lac≥3mmol/L and hypoalbuminemia were risk factors in elderly critically ill patients (OR=1.806, 2.977, 8.232, 3.031, P=0.011, 0.001, 0.041, 0.047), and addition of dietary fiber was a protective factor for enteral nutrition intolerance (OR=1.652, P=0.037). Conclusion The risk of enteral nutrition intolerance is high in elderly critically ill patients. Lac level, CRP level, hypoalbuminemia, and APACHE-II score of patients are independent risk factors for enteral nutrition intolerance, and addition of dietary fiber is a protective factor. It is necessary to take targeted interventions for patients according to the above factors to minimize the occurrence of enteral nutrition intolerance.

Background The increasing demand for emergency services coupled with the special working environment has exacerbated occupational stress and work-related rumination among emergency medical dispatchers, which is noteworthy for its impact on dispatchers' sleep quality. Objective To explore the relationship among occupational stress, work-related rumination, and sleep quality of emergency medical dispatchers, so as to provide reference for improving sleep quality and maintaining physical and mental health of this occupational group. Methods A total of 386 emergency medical dispatchers from 16 provinces and municipalities including Beijing, Shanghai, Tianjin, Inner Mongolia, Zhejiang, Shanxi, Jiangxi, Anhui, Hubei, Hebei, Henan, Sichuan, Guizhou, Yunnan, Fujian, and Hainan of China were investigated with the Chinese version of Effort-Reward Imbalance Questionnaire, Work-Related Rumination Questionnaire, and Insomnia Severity Index. Spearman correlation was used to analyze the association among occupational stress, work-related rumination, and sleep quality. A structural equation model was constructed, with occupational stress as independent variable, the two dimensions of work-related rumination as mediating variables, and sleep quality as dependent variable, respectively. Bootstrap testing was then used to verify potential mediating effect of work-related rumination on the relationship between occupational stress and sleep quality among the emergency medical dispatchers. Results Among the enrolled emergency medical dispatchers, the effort-reward imbalance (ERI) index was 1.03, the score of affective rumination was 15.35±5.26, the score of problem-solving rumination was 17.64±4.63, and the total score of sleep quality was 21.10±6.53. Their ERI index was positively correlated with affective rumination scores (r=0.636, P<0.01), but not with problem-solving rumination scores (P>0.05). Their ERI index, affective rumination scores, and problem-solving rumination scores were positively correlated with sleep quality scores (P<0.05). The direct effect size of occupational stress on sleep quality was 0.627, the indirect effect size of affective rumination was 0.124, and the mediating effect of affective rumination accounted for 16.4% of the total effect (0.755), while the problem-solving rumination had no mediating effect on the relationship between occupational stress and sleep quality. Conclusion Occupational stress and affective rumination in emergency medical dispatchers can predict their sleep quality. Occupational stress can directly affect sleep quality, and indirectly affect it through affective rumination. Managers should pay attention to and evaluate the affective rumination level of emergency medical dispatchers, so as to take corresponding intervention measures to reduce their occupational stress and improve their sleep quality.

This article reports a diagnostically and therapeutically challenging case of small intestinal marginal zone lymphoma. The patient presented with recurrent abdominal pain as the chief complaint, and imaging revealed multifocal small bowel wall thickening with high uptake, multisegmental luminal stenosis, and proximal dilation. Initial diagnostic workup, including gastroscopy, colonoscopy, and enteroscopy with biopsy, failed to establish a definitive diagnosis. Empirical anti-tuberculosis therapy was ineffective. A repeat enteroscopic biopsy performed over eight months after symptom onset eventually confirmed the diagnosis of mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma. Despite three different chemotherapy regimens, the patient's intestinal obstruction symptoms persisted, with imaging still showing multifocal bowel wall thickening and hypermetabolic activity. A critical diagnostic dilemma arose regarding whether the PET/CT-positive lesions represented residual lymphoma or fibrotic scarring, whether further chemotherapy adjustments were warranted, and whether surgical resection was necessary. Multidisciplinary discussion concluded that imaging had limited discriminatory value in this scenario and that surgical intervention should be pursued if feasible. The patient successfully underwent partial small bowel resection, with postoperative pathology confirming no residual lymphoma but significant fibrotic changes. The patient has since resumed a normal diet, with body weight nearly restored to pre-illness levels. This case highlights that fibrotic transformation is a common sequela of treated marginal zone lymphoma and that PET/CT may misleadingly suggest residual disease, potentially leading to unnecessary chemotherapy. Timely surgical intervention is crucial in such scenarios.

ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry