A one-two punch strategy for diabetic wound management based on an antibiotic-hybrid biomineralized iron sulfide nanoparticle.

Bacterial infection and immune imbalance are the primary culprits behind chronic wounds in individuals with diabetes, impeding the progression of damaged tissues towards normal healing. To achieve a harmonious balance between pro- and anti-inflammation within these infected areas, herein, we propose a one-two punch strategy for on-demand therapy of diabetes-infected wounds, utilizing an azithromycin (AZM)-hybrid nanocomposite termed GOx@FexSy/AZM. During the infective stage, the nanocomposite facilitates the production of ROS, coupled with the burst release of AZM and H2S gas, effectively dismantling biofilms and achieving rapid sterilization. Subsequently, the hyperinflammatory response induced by antibiosis is significantly mitigated through the synergistic action of tissue H2S and the prolonged half-life of AZM. These components inhibit the activity of pro-inflammatory transcription factors (AP-1 and NF-κB) within macrophages, thereby promoting the polarization of macrophages towards a reparative M2 phenotype and facilitating tissue remodeling. By catering to the diverse requirements of wound healing at different stages, this nanocomposite accelerates a sensible transition from inflammation to the reparative phase. In summary, this one-two punch strategy gives an instructive instance for procedural treatment of diabetes wound infection. STATEMENT OF SIGNIFICANCE: The treatment of diabetic wound infection presents two major challenges: the diminished antibacterial efficacy arising from biofilm formation and bacterial resistance, as well as the inadequate transition of the wound microenvironment from pro-inflammatory to anti-inflammatory states after bacterial clearance. In this work, a biomineralized iron sulfide nanocomposite was prepared to mediate cascade catalytic (ROS storm) / antibiotic (AZM) / gas (H2S) triple-synergetic antibacterial therapy during the initial stage of bacterial infection, achieving the goal of rapid bactericidal effect; Subsequently, the residual H2S and long half-life AZM would inhibit the key pro-inflammatory transcription factors and promote the macrophages polarization to reparative M2, which effectively mediated tissue repair after hyperinflammatory reactions, leading to orderly treatment of hyperglycemic infected wounds.

A retrospective study of non-equidistant interstitial brain CT perfusion scanning and prediction of time to peak.

Background: Eexploring the limits of CT cranial perfusion scan acquisition intervals and predicting time to peak. Methods: A retrospective analysis was conducted on 45 patients with suspected stroke who underwent brain CTP scans. Different sampling intervals were set based on the TDC. The patients were divided into four groups: Group 1 underwent continuous scanning with a uniform interval of 1.5 s; Group 2 had a uniform interval of 3 s; Group 3 had a 1.5-s interval between arterial and venous peak vertices with 1 point retained before and after the peak for 1.5 s and with a remaining acquisition interval of 4.5 s; and Group 4 had a uniform interval of 4.5 s. Statistical analysis was performed on the perfusion parameters of each group. Additionally, in 286 patients who underwent head and neck CTA examinations, the peak time of contrast medium was recorded, and the peak time was predicted based on factors such as age, height, weight, heart rate, systolic blood pressure, diastolic blood pressure, triglycerides, and total cholesterol. The results compared with Group 1 and Group 2, as well as Group 1 and Group 3, the P values of CBF, CBV, MTT, and Tmax in the left and right cerebral hemispheres of healthy subjects and in the infarct and noninfarct areas of patients were all >0.05. A comparison between Group 1 and Group 4 showed that right cerebral hemisphere CBF and CBV, left cerebral hemisphere CBF, CBV, and Tmax, infarct area CBV and Tmax, and noninfarct area CBF, CBV, and MTT had P values > 0.05, while other groups all had P values < 0.05. Bland‒Altman analysis showed that the perfusion parameters in Group 1 were consistent with those in Group 2, and those in Group 1 were consistent with those in Group 3. The radiation doses in the second and third groups were lower, and the dose in the third group was lower than that in the second group. Conclusion: Continuous acquisition between the peak points of the arterial and venous phases, with 1 point reserved before and after the peak and a 4.5-s interval for the rest, represents the maximum time interval for CTP scanning and can effectively reduce the radiation dose. The formula Tmax (s) = 0.290 × height (cm) - 0.226 × heart rate (times/min) + 0.216 × age (years) - 1.901 × triglycerides (mmol/L) - 0.061 × systolic blood pressure (mmHg) - 7.216 (R2 = 0.449, F = 17.905, P < 0.01) was established for predicting time to peak enhancement.

Metallic artifacts-free spectral computed tomography angiography based on renal clearable bismuth chelate.

Computed tomography angiography (CTA) is one of the most important diagnosis techniques for various vascular diseases in clinic. However, metallic artifacts caused by metal implants and calcified plaques in more and more patients severely hinder its wide applications. Herein, we propose an improved metallic artifacts-free spectral CTA technique based on renal clearable bismuth chelate (Bi-DTPA dimeglumine) for the first time. Bi-DTPA dimeglumine owns the merits of ultra-simple synthetic process, approximately 100% of yield, large-scale production capability, good biocompatibility, and favorable renal clearable ability. More importantly, Bi-DTPA dimeglumine shows superior contrast-enhanced effect in CTA compared with clinical iohexol at a wide range of X-ray energies especially in higher X-ray energy. In rabbits' model with metallic transplants, Bi-DTPA dimeglumine assisted-spectral CTA can not only effectively mitigate metallic artifacts by reducing beam hardening effect under high X-ray energy, but also enables accurate delineation of vascular structure. Our proposed strategy opens a revolutionary way to solve the bottleneck problem of metallic artifacts in CTA examinations.

The analysis of immunogenic cell death induced by ablation at different temperatures in hepatocellular carcinoma cells.

Introduction: Ablation therapy is a commonly used tool in the management of hepatocellular carcinoma (HCC). After ablation, dying cancer cells release a variety of substances that trigger subsequent immune responses. Immunogenic cell death (ICD) has been a trending topic in recent years and has been discussed many times along with oncologic chemotherapy. However, the subject of ablative therapy and ICDs has been little discussed. The purpose of this study was to investigate whether ablation treatment induces ICD in HCC cells and whether different types of ICDs arise because of different ablation temperatures. Methods: Four different HCC cell lines (H22, Hepa-16, HepG2 and SMMC7221) were cultured and treated under different temperatures (-80°C, -40°C, 0°C, 37°C, and 60°C). Cell Counting Kit-8 assay was performed to analyze the viability of different cell lines. Apoptosis was detected by flow cytometry assay, and a few ICD-related cytokines (calreticulin, ATP, high mobility group box 1, and CXCL10) were detected by immunofluorescence or enzyme-linked immunosorbent assay. Results: The apoptosis rate of all kinds of cells increased significantly in -80°C group (p < 0.01) and 60°C group (p < 0.01). The expression levels of ICD-related cytokines were mostly significantly different between the different groups. For calreticulin, Hepa1-6 cells and SMMC7221 cells showed significantly higher protein expression levels in 60°C group (p < 0.01) and significantly lower protein expression levels -80°C group (p < 0.01). The ATP, high mobility group box 1 and CXCL10 expression levels were significantly higher in 60°C, -80°C and -40°C group of all four cell lines (p < 0.01). Conclusion: Different ablative treatments could induce different types of ICDs in HCC cells, providing a promising track for the development of individualized cancer therapies.

Electrochemical regioselective C-H selenylation of 2H-indazole derivatives.

Selenium-substituted heteroarenes are biologically active compounds and useful building blocks. In this study, we have developed a metal- and oxidant-free, environmentally friendly protocol for the regioselective selenylation of 2H-indazole derivatives by an electrochemical strategy. A number of selenylated 2H-indazoles with a wide range of functional groups have been synthesized in moderate to good yields under mild and environment-friendly reaction conditions.

Functional Connectivity Changes of the Visual Cortex in the Cervical Spondylotic Myelopathy Patients: A Resting-State fMRI Study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To analyze altered functional connectivity (FC) in the visual cortex of cervical spondylotic myelopathy (CSM) patients using resting-state functional magnetic resonance imaging (fMRI). SUMMARY OF BACKGROUND DATA: We previously showed changes in visual cortex neural activity in CSM patients. METHODS: Thirty CSM patients and 20 healthy controls were recruited. MR data were collected using a 3.0 T MR. FC of the regions of interest (ROI) (Brodmann areas [BA] 17/18/19/7) were calculated in a voxel-wise manner and compared between groups. Correlation analyses were performed between preoperative Japanese Orthopaedic Association (JOA) scores and altered FC, as well as between preoperative best corrected visual acuity (BCVA) and altered FC. Furthermore, the FC where was compared between the preoperative and the postoperative CSM patients in an ROI-wise manner. RESULTS: Increased FC was found between BA19 and the cerebellum inferior lobe; between the left BA7 and bilateral calcarine, right lingual, right fusiform gyrus, and left precuneus (BA17); between the left BA7 and right fusiform gyrus and right inferior occipital gyrus (right BA19); and between the right BA7 and right superior lobe of cerebellum (right BA19) in CSM patients (P < 0.05). A negative correlation was found between JOA score and FC of the left and right BA19, and a positive correlation was found between the BCVA and FC of the left and right BA7 (P < 0.05). ROI analysis demonstrated statistically significant FC differences in between the preoperative and the postoperative CSM patients (P < 0.05). CONCLUSION: FC changes were present in the visual cortex of CSM patients, which negatively correlated with preoperative JOA scores and positively correlated with preoperative BCVA. Significant recovery of FC in the visual cortex was detected in CSM patients postoperatively. LEVEL OF EVIDENCE: 4.

Assessment of an advanced virtual monoenergetic reconstruction technique in cerebral and cervical angiography with third-generation dual-source CT: Feasibility of using low-concentration contrast medium.

OBJECTIVES: To investigate the feasibility of low-concentration contrast media (LC-CM) in cerebral and cervical dual-energy CT angiography (DE-CTA) using an advanced monoenergetic (Mono+) reconstruction technique. METHODS: Sixty-five consecutive patients prospectively selected to undergo cerebral and cervical DE-CTA were randomised into two groups: 32 patients (63.7 ± 9.7 years) in the high-concentration contrast medium (HC-CM) group with iopromide 370 and 33 patients (60.7 ± 10.8 years) in the low-concentration contrast medium (LC-CM) group with iodixanol 270. Traditional monoenergetic (Mono) and Mono+ images from 40 to 100 keV levels (at 10-keV intervals) and the standard mixed (Mixed, 120 kVp equivalent) images were reconstructed. Subjective image quality parameters included the contrast-to-noise ratio (CNR) and objective image quality parameters were evaluated and compared between the two groups. RESULTS: The 40-keV Mono+ images in the LC-CM group showed comparable objective CNR (common carotid arteries: 83.7 ± 24.5 vs. 78.1 ± 23.2; internal carotid arteries: 82.2 ± 26.8 vs. 76.8 ± 24.1; middle cerebral arteries: 72.5 ± 24.6 vs. 70.6 ± 19.2; all p > 0.05) and subjective image scores (3.95 ± 0.19 vs. 3.83 ± 0.35; p > 0.05) compared with Mixed images in the HC-CM group. CONCLUSION: The Mono+ reconstruction technique could reduce the concentration of iodinated CM in the diagnosis of cerebral and cervical angiography. KEY POINTS: • Mono+ shows decreased noise and superior CNR compared with Mono. • The 40-keV Mono+ images show the highest CNR in the LC-CM group. • The Mono+ reconstruction technique could reduce the concentration of iodinated CM.

Tripterygium wilfordii Inhibiting Angiogenesis for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a serious pre-vascular inflammatory phase, followed by significant increase in vessel growth. Inhibition of angiogenesis is a novel therapeutic strategy against RA. The Chinese herbal remedy Tripterygium wilfordii, Hook. f. (TwHf) has been reported to be therapeutically efficacious in the treatment of RA. Recent studies have revealed that treatment with TwHf extracts inhibit angiogenesis of RA, thereby elaborately attenuation RA symptom. This review mainly addresses the anti-angiogenesis effect of TwHf in treatment of RA.

CTA Characteristics of the Circle of Willis and Intracranial Aneurysm in a Chinese Crowd with Family History of Stroke.

BACKGROUND AND PURPOSE: The vascular morphology in crowd with family history of stroke remains unclear. The present study clarified the characteristics of the intracranial vascular CoW and prevalence of intracranial aneurysms in subjects with family history of stroke. METHODS: A stratified cluster, random sampling method was used for subjects with family history of stroke among rural residents in Jixian, Tianjin, China. All the subjects underwent a physical examination, head computed tomography (CT) scan, and cephalic and cervical computed tomography angiography (CTA) scan. Anatomic variations in the Circle of Willis and cerebrovascular disease in this population were analyzed. RESULTS: In the crowd with similar living environment, stable genetic background, and family history of stroke and without obvious nerve function impairment (1) hypoplasia or absence of A1 segment was significantly different in gender (male versus female: 9.8% versus 18.8%, p = 0.031), especially the right-side A1 (male versus female: 5.9% versus 16.4%, p = 0.004). (2) Hypoplasia or absence of bilateral posterior communicating arteries was more common in men than women (58.2% versus 45.3%, p = 0.032). Unilateral fetal posterior cerebral artery was observed more often in women than men (17.2% versus 8.5%, p = 0.028). (3) The percentage of subjects with incomplete CoW did not increase significantly with age. Compared to healthy Chinese people, the crowd had a higher percentage of incomplete CoW (p < 0.001). (4) No obvious correlation between risk factors and CoW was found. (5) The prevalence of aneurysm was 10.3% in the special crowd. CONCLUSIONS: The certain variations of CoW showed significant relation to gender, but not to age in people with family history of stroke. The incomplete circle may be a dangerous factor that is independent of common risk factors for stroke and tend to lead to cerebral ischemia in the crowd with family history of stroke. The prevalence of intracranial aneurysm is comparatively high in the present subjects compared to other people.

Analysis for the mechanism between the small cell lung cancer and non-small cell lung cancer combing the miRNA and mRNA expression profiles.

BACKGROUND: We investigated the relationship between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on micro ribonucleic acid (miRNA) and messenger (m)RNA expression profiles. METHODS: Utilizing the differentially expressed mRNAs and the targeting miRNAs, the mRNA-miRNA network for the two cancers was constructed. By integrating the miRNA expression profile, drug, and drug targets, miRNA-drug target-drug networks were established and the mechanisms in drug therapy efficacy were compared between SCLC and NSCLC. RESULTS: Drug targets of different expressed miRNAs of SCLC are mainly located in the organelle, act in the electron carrier activity, and consist of the synapse; while drug targets of NSCLC are the membrane-enclosed lumen, mainly distributed in the extracellular region and synapse, and function in the binding. Drug targets of miRNA expressed commonly in the two cancers are involved in the reproduction multi-organism process. In SCLC, the miR-16 in the miRNA-drug target-drug network is significant and follows the result of the mRNA-miRNA network. The pigmentation and rhythmic process of SCLC is different from NSCLC, while the process of cellular component biogenesis and cellular component organization are important for the occurrence of NSCLC. miR-16 in the miRNA-mRNA-drug network of SCLC is significant and we acquired 11 potential drugs, such as dexamethasone and budesonide. The miR-124 for NSCLC is important in the network and 17 potential drugs were screened, including dexamethasone and budesonide. CONCLUSIONS: These findings suggest that miR-16 and miR-124 might be novel diagnostic and prognostics markers for SCLC and NSCLC, respectively.

Renal Oxygenation Characteristics in Healthy Native Kidneys: Assessment with Blood Oxygen Level-Dependent Magnetic Resonance Imaging.

OBJECTIVE: To explore the characteristics of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in healthy native kidneys. METHODS: Seventy-nine patients without chronic kidney disease underwent BOLD-MRI with T2* spoiled gradient recalled echo sequences. BOLD images were analyzed using R2*map software to produce an R2* pseudo-color map. Cortical and medullary R2* values were analyzed in both kidneys and in both sexes. Different regional R2* values in the cortex and medulla were also analyzed. Physiological indices including age, height, weight, body mass index, body surface area, and estimated glomerular filtration rate (eGFR) were recorded. Correlations between R2* value and physiological indices were determined. RESULTS: Renal cortical R2* values were lower than values in the medulla (p < 0.001). Female and male cortical R2* values were also lower than the corresponding values in the medulla (p < 0.001). Renal medullary R2* values in the lower renal pole were lower than values in the middle and upper poles (p = 0.001). Age was positively correlated with R2* values in the medulla (r = 0.32, p = 0.004). eGFR was negatively correlated with both cortical R2* values (r = -0.26, p = 0.02) and medullary R2* values (r = -0.29, p = 0.009). CONCLUSIONS: BOLD-MRI can directly visualize renal oxygenation. There was variation in the oxygenation of different regions of the kidney. Renal cortical and medullary oxygenation in healthy kidneys decreased with patient age. eGFR also decreased with patient age.

Role of traditional Chinese medicine and its chemical components in anti-tumor metastasis.

Tumor incidence has become higher and higher in recent years, and it has also become the first killer jeopardizing human health. Tumor metastasis is the major barrier for tumor treatment. Some metastases occur in 5 or 10 years and some even in 20 years after tumor is controlled, but the metastases are impossible to defend effectively till now. Therefore, controlling tumor metastasis is critical in determining tumor patients' outcomes. In consideration of the limitations, toxicity and side effects of chemotherapeutic drugs for antitumor metastasis at present stage, seeking for drugs among traditional Chinese medicines (TCM) that share high safety and can effectively prevent and control metastasis is being paid more and more attention. This article is to expound the mechanisms of tumor metastasis and summarize the researches on antitumor metastasis with TCM.

Network analysis in the identification of special mechanisms between small cell lung cancer and non-small cell lung cancer.

BACKGROUND: To explore the similar and different pathogenesis between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). METHODS: This study used bioinformatics methods, including functional enrichment analysis, compared the topological features of SCLC and NSCLC in the human protein interaction network in a system aspect, and analyzed the highly intense modules from an integrated network. RESULTS: This study included 5082 and 2781 significantly different expression genes for NSCLC and SCLC, respectively. The differently expressed genes of NSCLC are mainly distributed in the extracellular region and synapse. By contrast, the genes of SCLC are located in the organelle, macromolecular complex, membrane-enclosed lumen, cell part, envelope, and synapse. Compared with SCLC, the differently expressed genes of NSCLC act in the biological regulation, multicellular organismal process, and viral reproduction and locomotion, which show that NSCLC is more likely to cause a wide range of cancer cell proliferation and virus infection than SCLC. The network topological properties of SCLC and NSCLC are similar, except the average shortest path length, which indicates that most of the genes of the two lung cancers play a similar function in the entire body. The commonly expressed genes show that all of the genes in the module may also cause NSCLC and SCLC, simultaneously. CONCLUSIONS: The proteins in module will involve the same or similar biological functions and the interactions among them induce the occurrence of lung cancer. Moreover, a potential biomarker of SCLC is the interaction between APIP and apoptotic protease activating factor (APAF)1, which share a common module.

Five-level noncontiguous spinal injuries of cervical region: report of a case and literature review.

The incidence of multiple noncontiguous spinal injuries (MNSI) in the cervical spine is rare but has catastrophic consequences. The patient in this report was a 34-year-old woman with five-level cervical MNSI. CT and MRI showed that injuries included atlantoaxial instability, burst fracture of C6, dislocation of C6/7, rupture of the intervertebal disc or ligamentous complex, and irreversible cord damage. The mechanism for this case was a combined pattern of hyperflexion, compression, and hyperextension injuries. A review of the literature revealed that this case is the first report in the literature of a vehicle related accident causing five-level noncontiguous injuries of the cervical spine.