Diabetes mellitus, characterized by glucose metabolism disorders and marked by insulin deficiency or insulin resistance, has seen a continuous rise in prevalence. In recent years, islet transplantation has matured as a therapeutic approach for diabetes, becoming an important method for glycemic control and the reduction of diabetes-related complications. Donor selection directly influences transplant outcomes, and various research institutions worldwide have proposed multiple scoring systems to optimize donor assessment, such as the University of Alberta scoring system and the North American Islet Donor Score. This article explores the impact of key factors such as donor age, body mass index and ischemia time on islet transplantation. Combining practical experience in pancreatic donor selection from Shanghai Changzheng Hospital, it proposes screening criteria for pancreatic donors suitable for China, aiming to provide new evidence for improving the success rate of islet transplantation.

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

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Hepatitis B cirrhosis is the most significant component of liver cirrhosis in China， and there is a significant increase in the mortality rate of patients after progression from hepatitis to liver cirrhosis. A large number of studies have shown that gut microbiota may influence the progression of hepatitis B cirrhosis， including the impact on the regulation of inflammatory response and intestinal immunity， the inhibition of HBV， and the production of ammonia-like substances. This article reviews the research advances in the changes in gut microbiota in hepatitis B cirrhosis patients and explores new ideas for the treatment of hepatitis B cirrhosis by intervening in gut microbiota.

ObjectiveTo observe the clinical efficacy and safety of Guben Quyu Jiedu prescription in treating nocturnal hypoxemia of chronic obstructive pulmonary disease （COPD） combined with Obstructive sleep apnea hypopnea syndrome （ OSAHS ） （deficiency of lung， spleen and kidney with blood stasis and toxicity）. MethodsThe paper used a forward-looking， random double-blind， placebo-controlled design method to select 96 patients with COPD combined with OSAHS， and their traditional Chinese medicines （TCM） syndrome differentiation was deficiency of lung， spleen and kidney with blood stasis and toxicity. These patients were randomly divided into the observation group and the control group， with 48 cases in each group. Based on conventional Western medicine treatment， the observation group was treated with Guben Quyu Jiedu prescription and the control group was treated with traditional Chinese medicine placebo. Both courses of treatment were 90 days. Then the paper compared the changes in minimum pulse oxygen saturation （SpO₂） during the night， apnea index （AHI）， OSAHS efficacy evaluation， TCM syndrome efficacy evaluation， and TCM symptom score before and after treatment between the two groups. ResultsThere were 5 withdrawals in the observation group and 8 withdrawals in the control group， so 43 cases in the observation group and 40 cases in the control group completed the trial. Compared with the condition before treatment， the minimum SpO₂ during the night and AHI in the observation group were significantly improved at night （P<0.01） and were better than those in the control group （P<0.01）. OSAHS efficacy in the observation group was better than in the control group （χ²=7.085， P<0.05）. In terms of TCM syndrome efficacy， the total effective rate was 81.40% （35/43） in the observation group， significantly higher than that in the control group， which was 15.00% （6/40） （χ²=36.78， P<0.01）. The TCM symptom scores of the two groups were improved compared with the condition before treatment， and the effect of the two groups was similar in the four main symptoms of snoring， choking， lethargy， and cough. However， the observation group was better than the control group in 10 details such as dizziness， headache， chest tightness， chest pain， wheezing， dry mouth， and thirst （P<0.05）. ConclusionUsing Guben Quyu Jiedu prescription combined with conventional Western medicine can treat COPD combined with OSAHS hypoxemia at night （deficiency of lung， spleen and kidney with blood stasis and toxicity）. In this way， the minimum pulse oxygen saturation （SpO₂） of patients， the level of disease control， and the quality of life of patients can be improved， and the clinical symptoms can be relieved.

Objective : To investigate the brain microvascular tissue block culture method for extracting primary rat brain microvascular endothelial cells and identify its effect. Methods : Brain tissue from 4-week-old Sprague Dawley rats was screened, pre-digested and solidified to obtain brain microvascular segments. These segments were subsequently placed in a CO2incubator for primary culture. The target cells were identified by cell morphology and immunocytochemical staining for factor Ⅷ-related antigen. Results : After a 48-hour culture periodin vitro, the short spindle cells crawled out from around the brain microvascular segments. After 72 hours, island-like cell culsters formed. After 96 hours the clusters fused and the cells formed a typical monolayer, cobble stone-like, and mosaic arrangement. Factor Ⅷ-related antigen immunocytochemical staining showed that the cytoplasm of the cells appeared brown-red, indicating positive expression; DAB stained the nucleus, showing blue-dark. Conclusion The brain microvascular tissue block culture method can isolate and culture primary rat brain microvascular endothelial cells.

Objective To explore the effect of residual tissue glue in forceps channels on the disinfection quality of digestive endoscopes. Methods A total of 103 forceps channels of digestive endoscopes in the Digestive Endoscopy Center of the hospital from March 2022 to June 2023 were randomly selected, and the residual situation of tissue glue in the forceps channels of the endoscopes was observed after cleaning and disinfection. The endoscopes were divided into residual group and non-residual group based on the residual situation of tissue glue in the forceps channels, the disinfection quality and microbial conditions of digestive endoscopes in both groups were detected, and the factors affecting the disinfection quality of digestive endoscopes were analyzed. Results Among the 103 forceps channels, 70 channels (67.96%) had residual tissue glue; the disinfection qualification rate and bacteriological qualification rate of the non-residual group were significantly higher than those of the residual group (P<0.05). There were four personnel carrying out disinfection, and the proportion of qualified disinfection water quality was higher than that of poor group (P<0.05). Conclusion The higher the residual rate of tissue glue in forceps channels and the bacterial detection rate are, and the lower the disinfection quality of digestive endoscopes is. The quality of disinfection water and the number of disinfection personnel can affect the disinfection quality of digestive endoscopes.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Humans ; Stroke ; Phagocytosis/physiology* ; Inflammation ; Apoptosis/physiology* ; Animals ; Phagocytes/physiology* ; Brain/metabolism* ; Efferocytosis