Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

An ITO-Free Kesterite Solar Cell.

Photovoltaic thin film solar cells based on kesterite Cu2 ZnSn(S, Se)4 (CZTSSe) have reached 13.8% sunlight-to-electricity conversion efficiency. However, this efficiency is still far from the Shockley-Queisser radiative limit and is hindered by the significant deficit in open circuit voltage (VOC ). The presence of high-density interface states between the absorber layer and buffer or window layer leads to the recombination of photogenerated carriers, thereby reducing effective carrier collection. To tackle this issue, a new window structure ZnO/AgNW/ZnO/AgNW (ZAZA) comprising layers of ZnO and silver nanowires (AgNWs) is proposed. This structure offers a simple and low-damage processing method, resulting in improved optoelectronic properties and junction quality. The ZAZA-based devices exhibit enhanced VOC due to the higher built-in voltage (Vbi ) and reduced interface recombination compared to the usual indium tin oxide (ITO) based structures. Additionally, improved carrier collection is demonstrated as a result of the shortened collection paths and the more uniform carrier lifetime distribution. These advances enable the fabrication of the first ITO-free CZTSSe solar cells with over 10% efficiency without an anti-reflective coating.

In Situ Generation and High Bioresistance of Trityl-based Semiquinone Methide Radicals under Anaerobic Conditions in Cellular Systems.

Bioreduction of spin labels and polarizing agents (generally stable radicals) has been an obstacle limiting the in-cell applications of pulsed electron paramagnetic resonance (EPR) spectroscopy and dynamic nuclear polarization (DNP). In this work, we have demonstrated that two semiquinone methide radicals (OXQM• and CTQM•) can be easily produced from the trityl-based quinone methides (OXQM and CTQM) via reduction by various reducing agents including biothiols and ascorbate under anaerobic conditions. Both radicals have relatively low pKa's and exhibit EPR single line signals at physiological pH. Moreover, the bioreduction of OXQM in three cell lysates enables quantitative generation of OXQM• which was most likely mediated by flavoenzymes. Importantly, the resulting OXQM• exhibited extremely high stability in the E.coli lysate under anaerobic conditions with 76- and 14.3-fold slower decay kinetics as compared to the trityl OX063 and a gem-diethyl pyrrolidine nitroxide. Intracellular delivery of OXQM into HeLa cells was also achieved by covalent conjugation with a cell-permeable peptide as evidenced by the stable intracellular EPR signal from the OXQM• moiety. Owing to extremely high resistance of OXQM• towards bioreduction, OXQM and its derivatives show great application potential in in-cell EPR and in-cell DNP studies for various cells which can endure short-term anoxic treatments.

Synthesis and Evaluation of a Novel c-Met-Targeting Cyclic Peptide as a Potential Diagnostic Agent for Colorectal Cancer.

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase linked to the proliferation, survival, invasion, and metastasis of several types of cancers, including colorectal cancer (CRC), particularly when aberrantly activated. Our study strategically designs peptides derived from interactions between c-Met and the antibody Onartuzumab. By utilizing a cyclic strategy, we achieved significantly enhanced peptide stability and affinity. Our in vitro assessments confirmed that the cyclic peptide HYNIC-cycOn exhibited a higher affinity (KD = 83.5 nM) and greater specificity compared with its linear counterpart. Through in vivo experiments, [99mTc]Tc-HYNIC-cycOn displayed exceptional tumor-targeting capabilities and minimal absorption in nontumor cells, as confirmed by single-photon emission computed tomography. Notably, the ratios of tumor to muscle and tumor to intestine, 1 h postinjection, were 4.78 ± 0.86 and 3.24 ± 0.47, respectively. Comparable ratios were observed in orthotopic CRC models, recording 4.94 ± 0.32 and 3.88 ± 0.41, respectively. In summary, [99mTc]Tc-HYNIC-cycOn shows substantial promise as a candidate for clinical applications. We show that [99mTc]Tc-HYNIC-cycOn can effectively target and visualize c-Met-expressing tumors in vivo, providing a promising approach for enhancing diagnostic accuracy when detecting c-Met in CRC.

Infralimbic YTHDF1 is necessary for the beneficial effects of acute mild exercise on auditory fear extinction retention.

Exposure therapy is the most effective approach of behavioral therapy for anxiety and post-traumatic stress disorder (PTSD). But fear is easy to reappear even after successful extinction. So, identifying novel strategies for augmenting exposure therapy is rather important. It was reported that exercise had beneficial effects on cognitive and memory deficits. However, whether exercise could affect fear memory, especially for fear extinction remained elusive. Here, our results showed that exposure to acute mild exercise 1 or 2 h before extinction training can augment recent fear extinction retention and 2 h for the remote fear extinction retention. These beneficial effects could be attributed to increased YTHDF1 expression in medial prefrontal cortex (mPFC). Furthermore, by using an AAV-shRNA-based approach to silence YTHDF1 expression via stereotactic injection in prelimbic cortex (PL) or infralimbic cortex (IL), respectively, we demonstrated that silence YTHDF1 in IL, but not in PL, blunted augmentation of exposure therapy induced by acute mild exercise and accompanied with decreased NR2B and GluR1 expression. Moreover, YTHDF1 modulated dendritic spines remodeling of pyramidal neuron in IL. Collectively, our findings suggested that acute mild exercise acted as an effective strategy in augmenting exposure therapy with possible implications for understanding new treatment underlying PTSD.

Ring-Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti-Breast Cancer Evaluation.

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.

Challenges and countermeasures for China's centralised volume-based procurement policy in healthcare.

To reduce the cost of healthcare expenditures in China, the government has developed a centralised volume-based procurement (CVBP) policy for medicines and medical consumables. Based on tracking the development history of centralised procurement in China, this study explores China's CVBP model. By comparing the centralised procurement models and healthcare expenditure data among China, the United States (U.S), the United Kingdom (UK), and Singapore, we find that China still faces many challenges in implementing the CVBP policy. The main challenges are as follows. First, the policy cannot be guaranteed the effectiveness of implementation without a well-coordinated regulatory mechanism. Second, the CVBP rules and quality evaluation standards are imperfect. Third, the interests of healthcare companies cannot be guaranteed. Fourth, the policy affects the benefits of medical institutions, and the government has not built a compensation mechanism for medical institutions. Fifth, it poses a challenge to the operational capacity and innovation level of Chinese companies. Therefore, this paper posits a three-stage strategy and nine measures that could benefit China's progress in implementing the CVBP policy.

Transparent and Ultra-Thin Flexible Checkerboard Metasurface for Radar-Infrared Bi-Stealth.

This paper proposed a single-layer checkerboard metasurface with simultaneous wideband radar cross-section (RCS) reduction characteristics and low infrared (IR) emissivity. The metasurface consists of an indium tin oxide (ITO)-patterned film, a polyethylene terephthalate (PET) substrate and an ITO backplane from the top downwards, with a total ultra-thin thickness of 1.6 mm. This design also allows the metasurface to have good optical transparency and flexibility. Based on phase cancellation and absorption, the metasurface can achieve a wideband RCS reduction of 10 dB from 10.6 to 19.4 GHz under normal incidence. When the metasurface is slightly cylindrically curved, an RCS reduction of approximately 10 dB can still be achieved from 11 to 19 GHz. The polarization and angular stability of the metasurface have also been verified. The filling rate of the top ITO-patterned film is 0.81, which makes the metasurface have a low theoretical IR emissivity of 0.24. Both simulation and experimental results have verified the excellent characteristics of the proposed checkerboard metasurface, demonstrating its great potential application in radar-IR bi-stealth.

An Integrated Sweat Sensor for Synchronous Detection of Multiple Atherosclerosis Biomarkers.

Atherosclerosis conditions are often assessed in the clinic by measuring blood viscosity, blood flow, and blood lesion levels. In alignment with precision medicine, it is essential to develop convenient and noninvasive approaches for atherosclerosis diagnostics. Herein, an integrated electrochemical sensor was successfully demonstrated for simultaneously detecting cholesterol, transferrin, and K+ in sweat, all biomarker indicators of atherosclerosis. The sensing substrate was based on carbon quantum dots integrated within multiwalled carbon nanotubes, creating a hybrid framework with low electron transfer resistance and highly efficient electron transfer rate, yielding a highly electrochemical active platform for ultrasensitive detection of trace sweat biomarkers. To ensure specificity to corresponding targets, the sensing mechanisms were based on molecular recognition reactions of cholesterol and ß-cyclodextrin, transferrin and molecular cavities, and K+ and ion-selective permeation membrane. Moreover, the integrated nonenzymatic sensor exhibited excellent long-term stability. Furthermore, the practical utility of the sensor was successfully demonstrated by the simultaneous detection of three atherosclerosis biomarkers in sweat from volunteers who underwent predesigned daily activities. The sensor shows promise for convenient indexing of atherosclerosis conditions in a noninvasive way.

DNA-Encoded and Spatial Proximity Replaced Glycoprotein Analysis Reveals Glycosylation Heterogeneity of Extracellular Vesicles.

Glycosylation of proteins is an essential feature of extracellular vesicles (EVs). However, while the glycosylation heterogeneity focusing on specific EV subtypes and proteins will better reveal the functions of EVs, the determination of their specific glycans remains highly challenging. Herein, we report a method of protein-specific glycan recognition using DNA-encoded affinity ligands to label proteins and glycans. Manipulating the sequences of DNA tags and employing a DNA logic gate to trigger a spatial proximity-induced DNA replacement reaction enabled the release of glycan-representative DNA strands for the quantitative detection of multiple glycoforms. After size-dependent isolation of EV subgroups and decoding of three typical glycoforms on the epithelial growth factor receptor (EGFR), we found that the different EV subgroups of the EGFR glycoprotein varied with respect to glycan types and abundance. The distinctive glycoforms of the EV subgroups could interfere with the EGFR-related EV functions. Furthermore, the sialylation of small EVs possessed the potential as a cancer biomarker. This method provides new insights into the role of protein-specific glycoforms in EV functions.

Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

Analysis of an image noise sensitivity mechanism for matrix-operation-mode-decomposition and a strong anti-noise method.

Mode decomposition (MD) based on the matrix operation (MDMO) is one of the fastest mode decomposition methods in fiber laser which has great potential for optical communications, nonlinear optics and spatial characterization applications. However, we found that the image noise sensitivity is the main limit to the accuracy of the original MDMO method, but improving the decomposition accuracy by using conventional image filtering methods is almost ineffective. By using the norm theory of matrices, the analysis result shows that both the image noise and the coefficient matrix condition number determine the total upper-bound error of the original MDMO method. Besides, the greater the condition number, the more sensitive of MDMO method is to noise. In addition, it is found that the local error of each mode information solution in the original MDMO method is different, which depends on the L2-norm of each row vector of the inverse coefficient matrix. Moreover, a more noise-insensitive MD method is achieved by screening out the information corresponding to large L2-norm. In particular, selecting the higher accuracy among the original MDMO method and such noise-insensitive method as the result in a single MD process, a strong anti-noise MD method was proposed in this paper, which displays high MD accuracy in strong noise for both near-filed and far-filed MD cases.

CYP3A4 and CYP3A5 Expression is Regulated by CYP3A4*1G in CRISPR/Cas9-Edited HepG2 Cells.

Functional CYP3A4*1G (G>A, rs2242480) in cytochrome P450 3A4 (CYP3A4) regulates the drug-metabolizing enzyme CYP3A4 expression. The objective of this study was to investigate whether CYP3A4*1G regulates both basal and rifampicin (RIF)-induced expression and enzyme activity of CYP3A4 and CYP3A5 in gene-edited human HepG2 cells. CYP3A4*1G GG and AA genotype HepG2 cells were established using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) single nucleotide polymorphism technology and homology-directed repair in the CYP3A4*1G GA HepG2 cell line. In CYP3A4*1G GG, GA, and AA HepG2 cells, CYP3A4*1G regulated expression of CYP3A4 and CYP3A5 mRNA and protein in an allele-dependent manner. Of note, significantly decreased expression level of CYP3A4 and CYP3A5 was observed in CYP3A4*1G AA HepG2 cells. Moreover, the results after RIF treatment showed that CYP3A4*1G decreased the induction level of CYP3A4 and CYP3A5 mRNA expression in CYP3A4*1G AA HepG2 cells. At the same time, CYP3A4*1G decreased CYP3A4 enzyme activity and tacrolimus metabolism, especially in CYP3A4*1G GA HepG2 cells. In summary, we successfully constructed CYP3A4*1G GG and AA homozygous HepG2 cell models and found that CYP3A4*1G regulates both basal and RIF-induced expression and enzyme activity of CYP3A4 and CYP3A5 in CRISPR/Cas9 CYP3A4*1G HepG2 cells. SIGNIFICANCE STATEMENT: Cytochrome P450 (CYP) 3A4*1G regulates both basal and rifampicin (RIF)-induced expression and enzyme activity of CYP3A4 and CYP3A5. This study successfully established CYP3A4*1G (G>A, rs2242480), GG, and AA HepG2 cell models using CRISPR/Cas9, thus providing a powerful tool for studying the mechanism by which CYP3A4*1G regulates the basal and RIF-induced expression of CYP3A4 and CYP3A5.

Generating the 1.5†kW mode-tunable fractional vortex beam by a coherent beam combining system.

As an essential component of the vortex beam, the fractional vortex beam has significantly advanced various applications, such as optical imaging, optical communication, and particle manipulation. However, practical applications face a significant challenge as generating high average power fractional vortex beams remains difficult. Here, we proposed and experimentally demonstrated a high average power mode-tunable fractional vortex beam generator based on an internally sensed coherent beam combining (CBC) system. We presented the first, to the best of our knowledge, successful generation of a 1.5 kW continuous wave fractional vortex beam. Moreover, real-time tuning of the topological charge (TC) from -2/3 to +2/3 was easily achieved using the programmable liquid crystals (LCs). More importantly, the fractional vortex beam copier was presented as well, and the generated fractional vortex beam could be easily transformed into a fractional vortex beam array by changing the fill factor of the laser array. This work can pave the path for the practical implementation of high average power structured light beams.

High-mobility group box 1 accelerates distraction osteogenesis healing via the recruitment of endogenous stem/progenitor cells.

BACKGROUND AIMS: While distraction osteogenesis (DO) achieves substantial bone regeneration, prolonged fixation may lead to infections. Existing stem cell and physical therapies have limitations, requiring the development of novel therapeutic approaches. Here, we evaluated high-mobility group box 1 (HMGB1) as a novel therapeutic target for DO treatment. METHODS: Micro-computed tomography (Micro-CT) analysis and histological staining of samples obtained from tibial DO model mice was performed. Transwell migration, wound healing, and proliferation assays were also performed on cultured human mesenchymal stem cells (hMSCs) and human umbilival vein endothelial cells (HUVECs). Tube formation assay was performed on HUVECs, whereas osteogenic differentiation assay was performed on hMSCs. RESULTS: Micro-CT analysis and histological staining of mouse samples revealed that HMGB1 promotes bone regeneration during DO via the recruitment of PDGFRα and Sca-1 positve (PαS+) cells and endothelial progenitor cells. Furthermore, HMGB1 accelerated angiogenesis during DO, promoted the migration and osteogenic differentiation of hMSCs as well as the proliferation, migration and angiogenesis of HUVECs in vitro. CONCLUSIONS: Our findings suggest that HMGB1 has a positive influence on endogenous stem/progenitor cells, representing a novel therapeutic target for the acceleration of DO-driven bone regeneration.

Trajectory engineering of directrons in liquid crystals via photoalignment.

As electrically generated solitons in liquid crystals, directrons represent intriguing structures promising extensive application prospects in the areas of microcargo vehicles, microreactors, and logic devices. However, manipulating directrons along elaborate predetermined trajectories still remains to be largely explored. In this work, the strategy of constructing high-resolution periodic alignment fields for directrons via the polarization holography photoalignment technique is presented. The optimum exposure dose for directrons to form over a broad range of electric fields is determined to be 32.4 J cm-2 for the alignment layers with 1 wt% azo dye SD1. Zigzag and fishhook-shaped trajectories of directrons are realized with two orthogonal polarized beams. The resolution for zigzag steering of directrons is evaluated to be approximately 56 µm to 80 µm, about three to four times the length of directrons. These results not only enrich the forms of motion of directrons, but also lay the foundations for customized trajectories of directrons in future developments.

Novel dual-reference approach facilitates the activation mapping and catheter ablation of premature atrial complexes with non-pulmonary vein and non-superior vena cava origins.

AIMS: Activation mapping of premature atrial complexes (PACs) proves challenging due to interference by mechanical bumping and non-targeted ectopies. This study aims to compare the mapping efficacy, instant success, and long-term recurrence of catheter ablation for PACs with non-pulmonary vein (PV) and non-superior vena cava (SVC) origins between the novel dual-reference approach (DRA) and the routine single-reference approach (SRA) of mapping. METHODS AND RESULTS: Patients with symptomatic, drug-refractory PACs, or frequent residual PACs after atrial tachyarrhythmia ablation were enrolled. During activation mapping, the coronary sinus (CS) catheter was used as the only timing reference in the SRA group. In the DRA group, another catheter, which was spatially separated from the CS catheter, was used as the second reference. The timing difference between the two references was used to discriminate the targeted PACs from the uninterested rhythms. Procedural parameters and long-term recurrence were compared. A total of 188 patients (109 in SRA and 79 in DRA) were enrolled. The baseline characteristics were similar. Compared with the SRA group, the DRA group had less repeated mapping (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.004), shorter mapping (15 ± 6 vs. 23 ± 7 min, P < 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P > 0.999), higher instant success (96.2 vs. 87.2%, P = 0.039), and lower recurrence rate (15.2 vs. 29.3%, hazard ratio 1.943, P = 0.033) during a 24-month follow-up. CONCLUSION: As a novel strategy, the DRA shortens the procedural time and improves both instant and long-term success of PAC ablation, serving as a promising approach in mapping PACs with non-PV and non-SVC origins.

A novel esophageal retractor with eccentric balloon during atrial fibrillation ablation.

BACKGROUND: Due to the anatomically adjacent relationship between the left atrium (LA) and esophagus, energy delivery on the posterior wall of LA is limited. The aim of this study was to evaluate the feasibility of a novel esophageal retractor (SAFER) with an inflatable C-curve balloon during atrial fibrillation (AF) ablation. METHOD: Nine patients underwent AF ablation assisted with the SAFER. After inflation, the esophagus was deviated laterally away from the intended ablation site of the posterior wall under local anesthesia. The extent of mechanical esophageal deviation (MED) was evaluated under fluoroscopy, defined as the shortest distance from the trailing esophageal edge to the closest point of the ablation line. Gastroscopy was performed before and after ablation. The target ablation index used in all LA sites including the posterior wall was 400-450 after effective MED. All adverse events during the periprocedural period were recorded. RESULTS: The mean deviation distance achieved 16.2 ± 9.6 mm away from the closest ablation point of the pulmonary vein lesion set. With respect to the individual left and right pulmonary vein lesion sets, the deviation distance was 19.7 ± 11.5 and 12.7 ± 6.8 mm, respectively. The extent of deviation was 0 to 5 mm, 5.1 to 10 mm, or >10 mm in 0(0%), 7(38.9%), and 11(61.1%), respectively. Procedural success was achieved in all patients without acute reconnection. There was only one esophageal complication which manifested as esophageal erosion and this patient experienced throat pain possibly related to the SAFER retractor with no clinical sequelae. CONCLUSION: Esophageal deviation with the novel eccentric balloon is a novel feasible choice during AF ablation, enabling adequate energy delivery to the posterior wall of LA. Additional prospective randomized controlled studies are required for further validation.

Infection Characteristics and Drug Susceptibility of Multidrug-Resistant Bacteria in Patients with Diabetic Foot Ulcers.

BACKGROUND: We aimed to analyze the infection characteristics of multidrug-resistant organisms (MDROs) and their resistance to antibiotics in patients with diabetic foot and provide guidance for the use of antibiotics in clinical practice. METHODS: The clinical data of 737 patients with diabetic foot who were hospitalized at our institution from February 2020 to January 2023 were retrospectively analyzed. Purulent secretions were collected from the patient's ulcers and bacterial culture, identification, and drug susceptibility tests were performed. The multidrug resistance (MDR) rate of different bacteria, composition ratio of MDROs, drug resistance characteristics of the main MDROs, distribution characteristics of multidrug-resistant gram-positive cocci and gram-negative bacilli in patients with different Wagner Grades, MDR in patients with different Wagner Grades, bacterial infection rate, and other indicators were analyzed. RESULTS: Pathogenic bacteria from wound secretions of 505 patients were cultured, and 509 pathogenic bacteria were obtained. Among the pathogenic bacteria, 225 strains were gram-positive cocci, of which 172 (76.44%) were MDROs, and 284 were gram-negative bacilli, of which 232 (81.69%) were MDROs. Among the 404 multidrug-resistant strains, gram-positive cocci and gram-negative bacilli accounted for 42.57% and 57.43%, respectively. The top five dominant MDROs were Staphylococcus aureus (18.56%), coagulase-negative Staphylococcus (10.89%), Escherichia coli (10.15%), Proteus mirabilis (8.17%), Proteus vulgaris (6.19%), and Pseudomonas aeruginosa (6.19%). Staphylococcus aureus and coagulase-negative Staphylococcus were more resistant to penicillin, oxacillin, erythromycin, azithromycin, and clarithromycin, with resistance rates of 50.0 - 95.0%. The resistance rates of E. coli to ampicillin, cefazolin, cefuroxime, ceftriaxone, and cefepime were > 75%. With an increase in Wagner Grade, the proportion of gram-negative bacilli among the pathogenic bacteria of MDROs increased significantly (p < 0.05), as did the infection rate of MDROs in patients with diabetic foot (χ2 = 14.045, p < 0.05). CONCLUSIONS: MDROs in patients with diabetic foot are mainly gram-negative bacilli, followed by gram-positive cocci. The drug resistance of various MDROs varies greatly. With the increase in Wagner Grade and MDR of diabetic foot patients, the infection rate of drug-resistant bacteria has increased significantly. Therefore, clinicians should use drugs rationally according to drug sensitivity results.

Icaritin Promotes Myelination by Simultaneously Enhancing the Proliferation and Differentiation of Oligodendrocyte Precursor Cells.

Myelin repair, which is known as remyelination, is critical to the treatment of neurodegenerative diseases, and myelination depends on not only the differentiation of oligodendrocyte precursor cells toward oligodendrocytes but also the renewal of oligodendrocyte precursor cells under pathological conditions. However, simultaneously promoting the differentiation and proliferation of oligodendrocyte precursor cells in lesions remains an unmet challenge and might affect demyelinating diseases. Kidney-tonifying herbs of traditional Chinese medicine (TCM) are effective in improving the symptoms of degenerative patients. However, herbs or compounds with dual functions are unverified. The purpose of this study was to find a kidney-tonifying TCM that synchronously improved the differentiation and proliferation of oligodendrocyte precursor cells under pathological conditions. Compounds with dual functions were screened from highly frequently used kidney-tonifying TCM, and the effects of the obtained compound on remyelination were investigated in an in vitro oligodendrocyte precursor cell differentiation model under pathological conditions and in demyelinating mice in vivo. The compound icaritin, which is an active component of Yin-Yang-Huo (the leaves of Epimedium brevicornu Maxim), demonstrated multiple effects on the remyelination process, including enhancing oligodendrocyte precursor cell proliferation, facilitating the differentiation of neural progenitor cells toward oligodendrocyte precursor cells and further toward oligodendrocytes, and maturation of oligodendrocytes under corticosterone- or glutamate-induced pathological conditions. Importantly, icaritin effectively rescued behavioral functions and increased the formation of myelin in a cuprizone-induced demyelination mouse model. The multiple effects of icaritin make it a promising lead compound for remyelination therapy.