Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Cytomegalovirus/physiology* ; Cytomegalovirus Infections ; Gastritis/diagnosis* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy*

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Objective:To validate the effectiveness of the leaf position data of multi-leaf collimator (MLC) recorded in the Infinity medical linear accelerator log file (LF).Methods:In this study, the establishment of the film dose calibration curve involved two steps. Initially, the pixel values obtained from scanning the film were converted into net optical density values. Subsequently, a sixth-order polynomial fit was performed on the net optical density and dose data. The picket fence (PF) tests were performed on the electronic portal imaging device (EPID) and film, and the corresponding acquired PF test images were analyzed using the relative leaf travel distance, relative leaf position, relative leaf pair full-width half -maximum (FWHM), and relative leaf pair neighbor region width analysis index, and compared with the relevant results in LF. In addition, to investigate the effect of gravity on the recorded leaf position data by the Infinity medical linear accelerator LF, the above PF tests were executed at 0°, 90°, 180°, and 270° gantry angles, respectively. Intergroup differences were assessed with the Wilcoxon rank-sum test.Results:The film dose calibration curve demonstrated high goodness-of-fit, with a correlation coefficient ( R2) of 0.9994. Across all gantry angles, the dispersion of overall leaf position data for EBT3 film, EPID, and LF followed a consistent pattern based on four analysis metrics: EBT3 film > EPID > LF. Moreover, for each analysis metric, inter-tool differences in standard deviations of results were consistently below 0.1 mm, and this pattern was invariant to gantry angle. Conclusions:The leaf position data recorded in the Infinity medical linear accelerator LF have a high degree of accuracy, and can be used as reference for the actual position of the MLC leaf. Furthermore, gravitational forces exhibit negligible impact on leaf position data acquired via LF.

Purpose To evaluate the diagnostic accuracy of low-iodine contrast subtraction CT pulmonary angiography(CTPA)combined with iodine maps for acute pulmonary embolism(APE),with a focus on detecting subsegmental emboli.Materials and Methods A retrospective analysis included 48 patients with suspected APE who underwent both pulmonary ventilation/perfusion SPECT/CT and low-iodine subtraction CTPA within one week in Beijing Hospital from September 1,2021 to September 1,2024.Using SPECT/CT as the reference standard,the diagnostic performance of subtraction CTPA with iodine maps was assessed.A retrospective review was performed to identify potential causes of false-positive and false-negative results.Results Subtraction CTPA with iodine maps demonstrated high diagnostic accuracy at the segmental and subsegmental pulmonary artery levels,with a sensitivity of 0.917 and specificity of 0.991.At the segmental level,the detection rate was 100%,while at the subsegmental level,it was 66.7%.The method showed consistently high diagnostic performance(83.3%-100%)across different clinical risk stratifications of APE.Retrospective review identified explicable causes for 85.7%(6/7)of false-positive and 33.3%(2/6)of false-negative cases.Conclusion Low-iodine subtraction CTPA combined with iodine maps exhibits robust diagnostic efficacy for APE.Accurate recognition of characteristic perfusion defects on iodine maps may further enhance diagnostic precision.

Purpose To investigate the correlation between tumor budding in penile squamous cell carcinoma(SCC)and its clinicopathological features.Methods Clinical data and pathological slides from 69 cases of penile SCC were collected.Tumor budding was examined microscopically,and statistical analyses were performed to assess the relationship between tumor budding and various clinicopathological features.Results Among the 69 cases of pe-nile SCC,41 cases exhibited low-grade tumor budding and 28 cases displayed high-grade tumor budding.Tumor bud-ding was significantly correlated with tumor size,urethral invasion,invasion of the urethral corpus spongiosum,inva-sion of the penile corpus cavernosum,tumor necrosis,nerve invasion,vascular tumor thrombus,and pathological T stage(all P＜0.05).In contrast,no significant association was found between tumor budding and HPV-related versus non-HPV-related penile SCC(P＞0.05).Log-rank survival analysis indicated that patients with high-grade tumor bud-ding had a significantly lower survival rate compared to those with low-grade tumor budding(P＜0.05).Conclusion Tumor budding is a distinct pathological feature of penile SCC,and high-grade tumor budding is associated with a more aggressive biological behavior.

TFE3/TFEB translocation renal cell carcinoma(TFE3/TFEB tRCC)occupies a prominent position in the molecular pathological classification of renal cancers due to its distinctive genetic abnormalities and its clinical pre-dilection for younger patients.Over nearly two decades of research,the spectrum of TFE3/TFEB fusion partner genes has expanded,highlighting the increasing morphological heterogeneity of TFE3/TFEB tRCC.This article reviews the clinicopathological and molecular features of TFE3/TFEB tRCC,emphasizing the associations between the major fusion subtypes and their morphological manifestations as well as immunophenotypes.Additionally,the practical value of an-cillary diagnostic techniques,such as molecular testing,is summarized,aiming to provide a reference for the routine and differential diagnosis of TFE3/TFEB tRCC.

Objective:To investigate the effects of low tube voltage, automatic tube current modulation technology combined with noise index(NI), and forward projected model-based iterative reconstruction solution(FIRST)on radiation dose and image quality in low iodine contrast agent CT pulmonary angiography(CTPA)among elderly patients.Methods:This retrospective study continuously collected imaging and clinical data from elderly patients suspected of having acute pulmonary embolism (APE)who underwent low-iodine contrast CTPA at the emergency department and inpatient department of Beijing Hospital from February 2022 to July 2023.A total of 80 patients were included in the study.Based on the reconstruction algorithm utilized during the CTPA examination, the patients were divided into two groups: the adaptive iterative dose reduction using three-dimensional processing(AIDR 3D)group and the FIRST group, with 40 cases in each group.We measured the average CT value and noise value of the pulmonary artery at various positions in both groups on axial images, calculated the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR), and recorded the average tube current and effective radiation dose for both patient groups.Two observers independently performed subjective scoring on the display of the pulmonary artery in each group using a blind method.Results:There were no statistically significant differences in age, body mass index (BMI), gender, and the extent of pulmonary embolism between the AIDR 3D group and the FIRST group (all P>0.05).In comparison to the AIDR 3D group, the FIRST group exhibited a significantly lower tube current[(220.2±84.5) mA vs.(264.1±81.2) mA, t=0.463, P=0.020], resulting in an effective radiation dose reduction of 15.7%[(1.39±0.49) mSv vs.(1.65±0.41) mSv, t=0.072, P=0.043].No statistically significant differences were observed in the mean CT values, noise values, and SNR values of the main pulmonary artery, left and right pulmonary trunks, and lobar and segmental pulmonary arteries between the AIDR 3D group and the FIRST group (all P>0.05).The CNR of the AIDR 3D group was lower than that of the FIRST group in both the left and right segmental pulmonary arteries( Z=-2.473, -1.973; P=0.013, 0.049), while no significant differences were found in the other pulmonary arteries(all P>0.05).In patients with normal BMI, the FIRST group demonstrated higher CNR values in both the left and right segmental pulmonary arteries compared to the AIDR 3D group( Z=-2.008, -2.662, P=0.046, 0.007), whereas the improvement in CNR was not significant in overweight and obese patients(all P>0.05).The two radiologists provided consistent subjective evaluations in scoring(Kappa=0.744, P<0.001), and there was no statistically significant difference in subjective scores between the AIDR 3D group and the FIRST group ( χ2=0.346, P=0.770). Conclusions:The imaging technique that integrates automatic tube current modulation technology with NI, the FIRST reconstruction algorithm, and a low tube voltage of 100 kVp effectively ensures image quality by providing clear visualization of pulmonary arteries at all levels.Moreover, it reduces radiation dose during low-iodine contrast agent CTPA examinations in elderly patients with APE.