NIR-II imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference.

Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to promote cell proliferation and growth, thereby enabling their resistance to external stress. 2-Deoxy-D-glucose (2DG) can eliminate their energy source by inhibiting glucose glycolysis, leading to cancer cell death through starvation. However, a compensatory increase in mitochondrial metabolism inhibits its efficacy. Herein, we propose a synergistic approach that combines photodynamic therapy (PDT) with starvation therapy to address this challenge. To monitor the nanodrugs and determine the optimal triggering time for precise tumor therapy, a multifunctional nano-platform comprising lanthanide-doped nanoparticle (LnNP) cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6 (Ce6) in the mesopore channels. Under 980 nm near-infrared light excitation, the downshifted 1550 nm fluorescence signal in the second near-infrared (NIR-II, 1000-1700 nm) window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors. Furthermore, upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT, which damaged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions. As a result, glucose metabolism reprogramming was inhibited and the efficiency of starvation therapy was significantly enhanced. Overall, the proposed NIR-II bioimaging-guided PDT-augmented starvation therapy, which simultaneously inhibited glycolysis and mitochondria, facilitated the effects of a cancer theranostic system.

The impact of negative pressure wound therapy on surgical wound infection, hospital stay and postoperative complications after spinal surgery: A meta-analysis.

To systematically assess the effect of negative pressure wound therapy (NPWT) on postoperative surgical wound infection, length of hospital stay and postoperative complications after spinal surgery. Relevant studies on the application of NPWT in spinal surgery were conducted via a computerised database search, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang, from inception to June 2023. The identified literature was rigorously screened and data extraction was performed by two investigators independently. The quality of the relevant studies was evaluated using the Newcastle-Ottawa scale (NOS). The effect size for count data was determined by the odds ratio (OR), while the impact size for measurement data was expressed as the standardised mean difference (SMD). The 95% confidence interval (CI) was calculated for each effect magnitude. Stata 17.0 software was used for the meta-analysis. Ten papers, totalling 1448 patients, were finally included. This study demonstrated that NPWT led to a statistically significant reduction in the occurrence of postoperative surgical wound infections (OR: 0.377, 95% CI: 0.238-0.598, p < 0.001), fewer postoperative complications (OR: 0.526, 95% CI: 0.360-0.770, p = 0.001) and a shortened hospital stay (SMD: -0.678, 95%CI: -1.324 to -0.031, p = 0.040) after spinal surgery compared with the control group. When compared with other treatment approaches, NPWT also demonstrated a substantial reduction in surgical wound infections and postoperative complications, as well as a shorter duration of hospitalisation after spinal surgery.

Clinical efficacy and drug resistance of ceftazidime-avibactam in the treatment of Carbapenem-resistant gram-negative bacilli infection.

Objective: To examine the clinical efficacy, safety, and resistance of Ceftazidime-Avibactam (CAZ-AVI) in patients with Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections. Methods: We retrospectively analyzed relevant data of CR-GNB infected patients receiving CAZ-AVI treatment, analyzed relevant factors affecting drug efficacy, and compared the efficacy and safety with patients receiving Polymyxin B treatment. Results: A total of 139 patients were included. Agranulocytosis, septic shock, SOFA score, and CAZ-AVI treatment course were independent risk factors affecting the prognosis of patients with CR-GNB infection treated with CAZ-AVI while prolonging the treatment course of CAZ-AVI was the only protective factor for bacterial clearance. The fundamental indicators showed no statistically significant differences between CAZ-AVI and Polymyxin B treatment groups. At the same time, the proportion of patients treated with monotherapy was significantly higher in the CAZ-AVI group than in the Polymyxin B group (37.2% vs. 8.9%, p < 0.05), the 30-day mortality rate of the CAZ-AVI treatment group (27.7% vs. 46.7%, p = 0.027) was lower than that of the Polymyxin B treatment group. The 30-day clinical cure rate (59.6% vs. 40% p = 0.030) and 14-day microbiological clearance rate (42.6% vs. 24.4%, p = 0.038) were significantly higher in the CAZ-AVI than in the Polymyxin B treatment group. Eighty nine patients were monitored for CAZ-AVI resistance, and the total resistance rate was 14.6% (13/89). The resistance rates of Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) to CAZ-AVI were 13.5 and 15.4%, respectively. Conclusion: CAZ-AVI has shown high clinical efficacy and bacterial clearance in treating CR-GNB infections. Compared with Polymyxin B, CAZ-AVI significantly improved the outcome of mechanical ventilation in patients with septic shock, agranulocytosis, Intensive Care Unit (ICU) patients, bloodstream infection, and patients with SOFA score > 6, and had a lower incidence of adverse events. We monitored the emergence of CAZ-AVI resistance and should strengthen the monitoring of drug susceptibility in clinical practice and the rational selection of antibiotic regimens to delay the onset of resistance.

Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer with Reduced Phototoxic Skin Injury.

Intratumoral pathogens can contribute to cancer progression and affect therapeutic response. Fusobacterium nucleatum, a core pathogen of colorectal cancer (CRC), is an important cause of low therapeutic efficacy and metastasis. Thus, the modulation of intratumoral pathogens may provide a target for cancer therapy and metastasis inhibition. Herein, we propose an intratumoral F. nucleatum-modulating strategy for enhancing the therapeutic efficacy of CRC and inhibiting lung metastasis by designing an antibacterial nanoplatform (Au@BSA-CuPpIX), which produced reactive oxygen species (ROS) under ultrasound and exhibited strong antibacterial activity. Importantly, Au@BSA-CuPpIX reduced the levels of apoptosis-inhibiting proteins by inhibiting intratumoral F. nucleatum, thereby enhancing ROS-induced apoptosis. In vivo results demonstrated that Au@BSA-CuPpIX effectively eliminated F. nucleatum to enhance the therapeutic efficacy of sonodynamic therapy (SDT) for orthotopic CRC and inhibit lung metastasis. Notably, entrapped gold nanoparticles reduced the phototoxicity of metalloporphyrin accumulated in the skin during tumor treatment, preventing severe inflammation and damage to the skin. Therefore, this study proposes a strategy for the elimination of F. nucleatum in CRC to enhance the therapeutic effect of SDT, thus providing a promising paradigm for improving cancer treatment with fewer toxic side effects and promoting the clinical translational potential of SDT.

Engineered procyanidin-Fe nanoparticle alleviates intestinal inflammation through scavenging ROS and altering gut microbiome in colitis mice.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.