Structural engineering of mitochondria-targeted Au-Ag2S photosensitizers for enhanced photodynamic and photothermal therapy.

Much effort has been devoted to designing diverse photosensitizers for efficient photodynamic therapy (PDT) and photothermal therapy (PTT) performance. However, the effect of PS morphology on the PDT and PTT performance needs to be further explored. In this work, a photosensitizer, Au-Ag2S nanoparticles functionalized with indocyanine green, caspase-3 recognition peptides, and mitochondria-targeting peptides (AICM NPs) with different morphologies, including core-shell, eccentric core-shell-I, eccentric core-shell-II, and Janus morphologies, were synthesized to enhance PDT and PTT performance. Among them, AICM Janus NPs with enhanced charge-transfer efficiency and photothermal conversion demonstrate superior PDT and PTT performance compared to those of other morphologies. In addition, AICM NPs exhibit satisfactory surface-enhanced Raman scattering performance for in situ SERS monitoring of caspase-3 during PDT and PTT processes. After PDT and PTT treatment with AICM Janus NPs, the damaged mitochondria released caspase-3. AICM Janus NPs achieved a superior apoptosis rate in tumor cells in vitro. Furthermore, AICM Janus NPs treat the tumors in vivo within only 10 days, which is half the time reported in other work. The AICM NPs demonstrated superior therapeutic safety both in vitro and in vivo. This study investigates the effects of morphology-property-performance of photosensitizers on the PDT and PTT performances, which opens a new pathway toward designing photosensitizers for efficient PDT and PTT.

Risk factors for hemoglobin decline in gastric cancer patients undergoing postoperative chemotherapy: a retrospective analysis.

OBJECTIVE: To investigate the independent risk factors for a decreased hemoglobin level in gastric cancer patients undergoing adjuvant chemotherapy. METHODS: A retrospective study was conducted on 142 gastric cancer patients who received chemotherapy between May 2017 and May 2021 at the Gansu Provincial Cancer Hospital. All patients were subjected to the same regimen of adjuvant chemotherapy combining platinum/taxane and fluorouracil. The correlation between patients' clinicopathological features and the decreased hemoglobin during adjuvant chemotherapy was analyzed. Logistic and LASSO regression analyses were employed to screen for independent risk factors for decreased hemoglobin during adjuvant chemotherapy. RESULTS: Univariate analysis revealed that intraoperative bleeding, pre-chemotherapy anemia, and hypoalbuminemia were risk factors for the decreased hemoglobin in patients during adjuvant chemotherapy (all P < 0.05). Both logistic and LASSO regression analyses corroborated these factors as influential factors in the decrease of hemoglobin (P < 0.05). In addition, both logistic and LASSO regression models demonstrated similar performance in this aspect. The nomogram model was subjected to internal validation, resulting in a C-index of 0.712 (0.629-0.796). The calibration curves exhibited satisfactory alignment with the ideal curve. CONCLUSION: Intraoperative blood loss, pre-chemotherapy anemia, and hypoalbuminemia are independent risk factors for hemoglobin reduction following chemotherapy. Moreover, both the logistic and LASSO regression models exhibited equivalent performance in this context. These findings bear substantial clinical implications, aiding physicians in the management of anemia in patients undergoing chemotherapy.

Dual-Aptamer-Assisted Ratiometric SERS Biosensor for Ultrasensitive and Precise Identification of Breast Cancer Exosomes.

Due to the heterogeneity of breast cancer, its early accurate diagnosis remains a challenge. Exosomes carry abundant genetic materials and proteins and are ideal biomarkers for early cancer detection. Herein, a ratiometric surface-enhanced Raman scattering (SERS) biosensor for exosome detection was constructed using a regularly arranged Au@Ag nanoparticles/graphene oxide (Au@Ag NPs/GO) substrate with 4-nitrothiophenol (4-NTP) molecules as an internal standard. Aptamers of two overexpressed proteins (epithelial cell adhesion molecule and human epidermal growth factor receptor 2) were linked by a short complementary DNA with rhodamine X modified at the 3'-terminal to form V-shaped double-stranded DNA, which attached to the surface of Au@Ag NPs/GO substrate for the selective recognition of breast cancer cell-derived exosomes. In the presence of exosomes, a competitive reaction occurred, resulting in the formation of the V-shaped double-stranded DNA/exosomes complex, and the V-shaped double-stranded DNA separated from the SERS substrate. The SERS signal of rhodamine X on the V-shaped double-stranded DNA decreased with the concentration of exosomes increasing, whereas the SERS signal of 4-NTP on the substrate remained stable. The ratiometric SERS strategy provides huge electromagnetic enhancement and abundant DNA adsorbing sites on the GO layer, achieving a wide detection range of 2.7 × 102 to 2.7 × 108 particles/mL and an ultralow limit of detection down to 1.5 × 102 particles/mL, without the requirement of any nucleic acid amplification. Particularly, the proposed method has significant applications in early cancer diagnosis as it can accurately identify breast cancer cell-derived exosomes in clinical serum samples and can differentiate pancreatic cancer patients and healthy individuals.

Effect of Silver Nanoparticles With Thermoplastic Polyurethane on Postoperative Rehabilitation of Diabetic Patients With Open Fracture of Lower Extremities.

Objective: This retrospective study aims to explore the effect of silver nanoparticles with thermoplastic polyurethane (TPU/NS) on the rehabilitation of diabetic patients with open fracture of lower extremities. Methods: Diabetic patients (n = 98) with open fracture of lower extremities treated in our hospital were analyzed retrospectively from June 2015 to December 2021. TPU/NS nanocomposites were prepared for postoperative treatment of diabetic patients with open fracture of lower extremities. First, the cultured Staphylococcus aureus and Escherichia coli were used to test the antibacterial effect of TPU/NS dressing in vitro. After using TPU/NS dressing (observation group) and traditional dressing (control group), the inflammatory reaction, clinical treatment, functional rehabilitation, and adverse reactions in patients were compared. Results: TPU/NS dressing effectively inhibited the growth of bacteria with a minimum inhibitory concentration of 2 µg/mL. The usage of TPU/NS dressing reduced the inflammatory reaction by reducing positive rate of bacteria after the dressing on the seventh day postoperatively. Besides, the times of dressing, stopping time of wound exudation, wound healing time, length of hospital stay, and VAS score in the observation group were lower than those in the control group; the incidence of adverse reactions after treatment was lower in the observation group as compared with the control group (17.07% vs. 35.09%). Meanwhile, the functional rehabilitation and life quality of patients in the observation group were better TPU/NS dressing treatment. Conclusion: TPU/NS dressing has the function of promoting the postoperative recovery of patients by inhibiting the bacterial infection of the wound, thus improving the limb function and life quality. As a result, there was a tremendous potential to apply the constructed TPU/NS membrane to diabetic patients with open fractures, especially those with soft tissue injury.

In situ SERS monitoring of intracellular H2O2 in single living cells based on label-free bifunctional Fe3O4@Ag nanoparticles.

Visualization of signaling molecules in single living cells is crucial for understanding cellular metabolism and physiology, which can provide valuable insights into early diagnoses and treatments of diseases. Highly sensitive in situ monitoring of intracellular analytes released from single living cells by virtue of label-free nanosensors is urgently needed, which can avoid interferences from molecular labeling. Here, we proposed an ultrasensitive strategy for in situ imaging of intracellular H2O2 in single living cancer cells by surface-enhanced Raman scattering (SERS) spectroscopy with the utilization of label-free Fe3O4@Ag core-satellite nanoparticles (NPs). The Fe3O4@Ag NPs can efficiently and selectively catalyze the oxidation of the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. Additionally, they exhibit excellent SERS activity that allows for in situ monitoring of intracellular H2O2 in living cells through establishing the correlation between the H2O2 level and the SERS intensity of the catalytic oxidation product of TMB. The H2O2 concentration is revealed through the SERS intensity of oxidized TMB with a good linear response in a wide range from 1 fM to 1 mM. Moreover, the intracellular H2O2 level in live cancer cells and imaging of the distribution of H2O2 inside single cells can be achieved by using such a label-free nanosensor based strategy. Our work demonstrates that the label-free Fe3O4@Ag NP-based SERS imaging and quantification strategy is a promising and powerful approach to assess intracellular H2O2 in living cells and allows us to monitor single-cell signaling molecules with nanoscale resolution.

The effectiveness of a co-management care model on older hip fracture patients in China - A multicentre non-randomised controlled study.

BACKGROUND: Clinical guidelines recommend orthogeriatric care to improve older hip fracture patients' outcomes, but few studies have been conducted in China. This study evaluated the effects of an orthogeriatric co-management care model in six Chinese hospitals. METHODS: This non-randomised controlled study was designed as an exploratory trial and was conducted in 3 urban and 3 suburban hospitals. Eligible patients were aged ≥ 65 years with X-ray confirmed hip fracture and admitted to hospital within 21 days of injury. All patients received three times follow-ups within one year (1-month, 4-month and 12-month post admission). Co-management care was implemented in 1 urban hospital, while usual care continued in 5 urban and suburban hospitals. Patient demographics, pre-, peri- and post-operative information, complications and mortality were collected at baseline and follow-ups. The primary outcome was proportion of patients receiving surgery within 48 hours from ward arrival. Secondary outcomes included osteoporosis assessment, in-hospital rehabilitation, length of hospital stay, in-hospital mortality and one-year cumulative mortality. FINDINGS: There were 2,071 eligible patients enrolled (1,110 intervention, 961 control). Compared to usual care, a significantly higher proportion of intervention patients received surgery within 48 hours (75% vs 27%, p<0.0001), osteoporosis assessment (99.9% vs 60.6%, p<0.0001), rehabilitation (99.1% vs 3.9%, p<0.0001) and shorter length of hospital stay (6.1 days vs 12.0 days, p<0.0001). The intervention group saw a significant lower in-hospital mortality rate than the control group (adjusted relative risk 0.021, 95% CI 0.001 to 0.45, P=0.01). One-year cumulative mortality was also significantly reduced in the intervention group (hazard ratio 0.59, 95% CI 0.38 to 0.80, p=0.01). INTERPRETATION: Co-management care of older hip fracture patients resulted in better outcomes, including decreased time to surgery, improved clinical management, and reduced one-year mortality. A randomised controlled trial is needed to provide definitive evidence. FUNDING: The study is supported by Capital's Funds for Health Improvement and Research (2018-1-2071).

Effects of zoledronic acid and ibandronate in the treatment of cancer pain in rats with lung cancer combined with bone metastases.

The aim of the study was to investigate the efficiency and safety of zoledronic acid and ibandronate in the treatment of rats with lung cancer combined with bone metastases. A total of 124 rats with lung cancer bone metastasis were established. Rats were randomly divided into A, B and C groups (n=30). Rats in group A were treated with ibandronate combined with zoledronic acid, rats in group B were treated with zoledronic acid monotherapy, and rats in group C were treated with ibandronate monotherapy. Rats in group A were injected subcutaneously with zoledronic acid 0.1 mg/kg and ibandronate 10 µg/kg, once per week for 12 weeks; rats in group B were injected subcutaneously with zoledronic acid, and rats in group C were injected subcutaneously with ibandronate, the same method as the treatment group. The remaining 34 SD rats were not treated to serve as the control group. Treatment efficacy and physical improvement in 8 weeks were observed, and improvement of pain behavior in rats was evaluated to reflect the effect of drug treatment. Of the 30 rats in group A, 25 showed different degrees of remission, 5 rats showed no improvement and the effective rate was 83.3%. Of the 30 rats in group B, 21 showed different degrees of remission, 9 rats showed no improvement and the effective rate was 70%. Of the 30 rats in group C, 20 showed different degrees of remission, 10 rats showed no improvement and the effective rate was 66.7%. Statistically significant differences in total effective rate were found among three groups, and the combined method showed the highest effective rate (P<0.05). Ibandronate combined with zoledronic acid has a good therapeutic effect on cancer pain caused by bone metastases from lung cancer.

Alternative lengthening of telomeres phenotype and loss of ATRX expression in sarcomas.

Sarcoma is a rare and heterogeneous type of cancer with an early mean onset age and a poor prognosis. However, its genetic basis remains unclear. A series of recent genomic studies in sarcomas have identified the occurrence of mutations in the α-thalassemia/mental retardation syndrome X-linked (ATRX) gene. The ATRX protein belongs to the SWI/SNF family of chromatin remodeling proteins, which are frequently associated with α-thalassemia syndrome. Cancer cells depend on telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative programmed mortality. Loss of ATRX is associated with ALT in sarcoma. In the present review, recent whole genome and/or whole exome genomic studies are summarized. In addition ATRX immunohistochemistry and ALT fluorescence in situ hybridization in sarcomas of various subtypes and at diverse sites, including osteosarcoma, leiomyosarcoma, liposarcoma, angiosarcoma and chondrosarcoma are evaluated. The present review involves certain studies associated with the molecular mechanisms underlying the loss of ATRX controlling the activation of ALT in sarcomas. Identification of the loss of ATRX and ALT in sarcomas may provide novel methods for the treatment of aggressive sarcomas.

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis.

Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid cancers; however, its prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore whether ITGB1 expression is correlated with overall survival (OS) and the clinicopathological characteristics of patients with solid cancers. We systematically searched the PubMed, Embase, and Web of Science databases for eligible studies published up to June 1, 2017. In total, 22 studies involving 3,666 patients were included. A sensitivity analysis was performed to assess the validity and reliability of the pooled OS. Among the 22 studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled results showed that high ITGB1 expression was significantly associated with worse OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19-2.65, p<0.05) and breast cancer (pooled HR=1.88, 95% CI: 1.46-2.42, p<0.01). In addition, a significant association was observed between high ITGB1 expression and disease-free survival in breast cancer (pooled HR=1.63, 95% CI: 1.17-2.25, p<0.001) and pancreatic cancer (pooled HR=2.49, 95% CI: 1.35-4.61, p<0.001). However, high ITGB1 expression was not related to OS in colorectal cancer, pancreatic cancer, or melanoma. The pooled HRs used to evaluate the prognostic value of increased ITGB1 expression in lung cancer, breast cancer, and pancreatic cancer were not significantly altered, which indicates that the pooled results were robust. The results of this study indicate that the prognostic value of decreased ITGB1 expression varies among solid cancers.

The effect and underlying mechanism of Timosaponin B-II on RGC-5 necroptosis induced by hydrogen peroxide.

BACKGROUND: Necroptosis is an important mode of cell death, which is due to oxidant stress accumulation. Our previous study indicated that oxidant stresses could be reduced by Timosaponin B-II (TBII), a kind of Chinese herb RhizomaAnemarrhenae monomer extraction. We wonder the possible effect of Timosaponin B-II, whether it can protect cells from necroptosis via reducing the oxidant stress, in RGC-5 following hydrogen peroxide (H2O2) insult. METHODS: RGC-5 cells were grown in DMEM, the model group was exposed in H2O2 with the concentration of 300 µM, and the experimental group was pre-treated with Timosaponin B-II at different concentrations (1 µM, 10 µM, 100 µM and 1000 µM) for 24 hrs. MTT assay was carried out to measure the cytotoxicity of H2O2, MDA concentration assay was executed to evaluate the degree of oxidative stress, TNF-α ELISA Assay was used to measure the concentration of TNF-α, finally, the degree of necrosis were analyzed using flow cytometry. RESULTS: We first constructed the cell injury model of necroptosis in RGC-5 upon H2O2 exposure. Morphological observation and MTT assay were used to evaluate the degree of RGC-5 death. MDA assay were carried out to describe the degree of oxidant stress. Annexin V/PI staining was used to detect necroptotic cells pre-treated with or without Timosaponin B-II following H2O2 injury. TNF-α ELISA was carried out to detect the TNF-α accumulation in RGC-5. Upon using Timosaponin B-II with concentration of 100 µM, the percentage of cell viability was increased from 50% to 75%, and the necrosis of cells was reduced from 35% to 20% comparing with H2O2 injury group. Oxidant stress and TNF-α was reduced upon injury which decreased the ratio of RGC-5 necroptosis. CONCLUSION: Our study found out that Timosaponin B-II might reduce necroptosis via inhibition of ROS and TNF-α accumulation in RGC-5 following H2O2 injury.