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

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective To investigate the effect of hypertensive disorders of pregnancy(HDP)on the adverse growth and development outcomes of premature infants with gestational age<32 weeks.Methods Premature infants with gestational age<32 weeks admitted to the neonatal intensive care unit of Yinchuan Maternal and Child Health Hospital General Hospital and Yuehai Branch from 2017 to 2024 were selected as the study sub-jects,and general information of premature infants and mothers was collected to analyze the relationship be-tween HDP and adverse growth and development outcomes in these infants.Results A total of 173 premature infants were included,including 88 males(50.9%)and 85 females(49.1%).There were 41 cases(23.7%)of small for gestational age infants(SGA)and 132 cases(76.3%)of non SGA infants.A total of 65 cases(37.6%)had HDP mothers and 108 cases(62.4%)had non HDP mothers.Among SGA premature infants,75.6%(31/41)had a mother with HDP,while among non SGA premature infants,25.8%(34/132)had a mother with HDP.Regardless of whether premature infants were born with SGA or not,compared with the non HDP group,the HDP group had a higher incidence of extrauterine growth retardation(EUGR),congeni-tal hypothyroidism(CH),and parenteral nutrition associated cholestasis(PNAC)(P<0.05).In non SGA premature infants,compared with the non HDP group,the HDP group had a higher incidence of metabolic bone disease(MBD),and the difference was statistically significant(P<0.05).Multivariate logistic regres-sion analysis showed that HDP was an independent factor affecting the occurrence of EUGR in SGA preterm infants(P<0.05).HDP was an independent risk factor for CH,EUGR,and PNAC in non SGA preterm in-fants(P<0.05).Conclusion Maternal HDP can increase the risk of EUGR,CH,and PNAC in premature in-fants with gestational age<32 weeks,and is associated with poor postnatal growth and development out-comes in offspring.

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.

Ivonescimab is a humanized bispecific antibody targeting human vascular endothelial growth factor-A(VEGF-A)and programmed death protein-1(PD-1).It was approved by National Medi-cal Products Administration on May 24th,2024,and can be used in combination with pemetrexed and carboplatin for locally advanced or positive EG-FR gene mutation after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhib-itor.This paper mainly introduces the research progress of the world's first PD-1/VEGF bispecific antibody ivonescimab,and summarizes the mecha-nism of action,pharmacokinetics,phase Ⅰ-Ⅲ clinical trials and drug safety.

Objective:To deeply understand newly employed nurses' cognition and experience of reflective practice (RP) and explore its application in clinical settings, providing a scientific basis for constructing an RP training system.Methods:A descriptive phenomenological research method was used, with purposive sampling to select newly employed nurses from the Affiliated Hospital of Yangzhou University between October and December 2023. Semi-structured interviews were conducted, and traditional content analysis was used to analyze the data.Results:Fourteen newly employed nurses were interviewed, including 3 males and 11 females, aged 22-25 (22.92 ± 0.92) years old. A total of 190 000 words of interview data were transcribed. Four themes and eight sub-themes were extracted: understanding of RP, attitudes toward RP, differences in RP abilities, and challenges in the clinical application of RP.Conclusions:Newly employed nurses have some understanding of RP, but there are issues such as insufficient learning pathways, negative attitudes toward RP, differences in RP abilities, and challenges in clinical application. RP learning should be incorporated into the training of newly employed nurses to promote the improvement of their RP abilities.

This article summarized the overview of voice training, common training forms, and the application effect of voice training in the treatment of speech disorders in Parkinson′s disease patients, analyzed the shortcomings of its application and put forward prospects for future research, aiming to provide valuable references for both patients and healthcare workers.

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.