Construction of Hierarchically Biomimetic Iron Oxide Nanosystems for Macrophage Repolarization-Promoted Immune Checkpoint Blockade of Cancer Immunotherapy.

Cancer immunotherapy is developing as the mainstream strategy for treatment of cancer. However, the interaction between the programmed cell death protein-1 (PD-1) and the programmed death ligand 1 (PD-L1) restricts T cell proliferation, resulting in the immune escape of tumor cells. Recently, immune checkpoint inhibitor therapy has achieved clinical success in tumor treatment through blocking the PD-1/PD-L1 checkpoint pathway. However, the presence of M2 tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) will inhibit antitumor immune responses and facilitate tumor growth, which can weaken the effectiveness of immune checkpoint inhibitor therapy. The repolarization of M2 TAMs into M1 TAMs can induce the immune response to secrete proinflammatory factors and active T cells to attack tumor cells. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were prepared for reprogramming M2 TAMs into M1 TAMs. BMS-202, a small-molecule PD-1/PD-L1 inhibitor that has a lower price, higher stability, lower immunogenicity, and higher tumor penetration ability compared with antibodies, was loaded together with pH-sensitive NaHCO3 inside hollow Fe3O4 NPs, followed by wrapping with macrophage membranes. The formed biomimetic FBN@M could produce gaseous carbon dioxide (CO2) from NaHCO3 in response to the acidic TME, breaking up the macrophage membranes to release BMS-202. A series of in vitro and in vivo assessments revealed that FBN@M could reprogram M2 TAMs into M1 TAMs and block the PD-1/PD-L1 pathway, which eventually induced T cell activation and the secretion of TNF-α and IFN-γ to kill the tumor cells. FBN@M has shown a significant immunotherapeutic efficacy for tumor treatment.

Genetic and non-genetic factors in prediction of early pubertal development in Chinese girls.

Objective: The objective of this study is to develop a combined predictive model for early pubertal development (EPD) in girls based on both non-genetic and genetic factors. Methods: The case-control study encompassed 147 girls diagnosed with EPD and 256 girls who exhibited normal pubertal development. The non-genetic risk score (NGRS) was calculated based on 6 independent biochemical predictors screened by multivariate logistic regressions, and the genetic risk score (GRS) was constructed using 28 EPD related single-nucleotide polymorphisms (SNPs). Area under receiver operator characteristic curve (AROC), net reclassification optimization index (NRI) and integration differentiation index (IDI) were used to evaluate the improvement of adding genetic variants to the non-genetic risk model. Results: Overweight (OR=2.74), longer electronic screen time (OR=1.79) and higher ratio of plastic bottled water (OR=1.01) were potential risk factors, and longer exercise time (OR=0.51) and longer day sleeping time (OR=0.97) were protective factors for EPD, and the AROC of NGRS model was 83.6% (79.3-87.9%). The GRS showed a significant association with EPD (OR=1.90), and the AROC of GRS model was 65.3% (59.7-70.8%). After adding GRS to the NGRS model, the AROC significantly increased to 85.7% (81.7-89.6%) (P=0.020), and the reclassification significantly improved, with NRI of 8.19% (P= 0.023) and IDI of 4.22% (P <0.001). Conclusions: We established a combined prediction model of EPD in girls. Adding genetic variants to the non-genetic risk model brought modest improvement. However, the non-genetic factors such as overweight and living habits have higher predictive utility.

A comparative analysis of the nutrient and phytochemical richness among different varieties of quinoa in China.

Quinoa is a nutrient-dense pseudocereal that has garnered global attention for its potential to bolster food security and nutrition. Despite its celebrated status, the detailed nutritional profiles of various quinoa varieties remain poorly understood, which poses a significant barrier to the strategic cultivation and utilization of quinoa's genetic diversity to combat malnutrition. The impetus for this research lies in the urgent need to identify superior quinoa strains that can be tailored to meet specific nutritional requirements and adapt to diverse agro-ecological zones. Our findings reveal substantial variation in nutrient content across different quinoa varieties, highlighting the variety ZLZX-8 as a particularly nutrient-rich strain with the highest levels of protein, fat, essential fatty acids, amino acids, and key minerals such as Mg, K, and Zn. Moreover, ZLZX-8's exceptional antioxidant capacity suggests it may have additional health benefits beyond its macronutrient profile. In contrast, ZLZX-7 stands out for its dietary fiber and phenolic content, which are critical for digestive health and disease prevention, respectively. Meanwhile, ZLZX-5, with its high starch content, could be better suited for energy production in dietary applications. Notably, the study also uncovers a correlation between grain color and nutrient profile, with colored quinoa varieties exhibiting superior fiber, inositol, phenolic content, and antioxidant activity compared to their white counterparts. This work lays the groundwork for an informed selection of quinoa varieties that can enhance dietary quality, support local and global food systems, and contribute to the fight against malnutrition.

Joint association of overweight/obesity, high electronic screen time, and low physical activity time with early pubertal development in girls: a case-control study.

To examine the joint association of electronic screen time (EST), moderate-to-vigorous physical activity time (MVPA) and overweight/obesity with early pubertal development (EPD) in girls. A case-control study of 177 EPD girls and 354 girls with normal pubertal development was conducted between October 2019 and August 2022. Overweight/obesity was defined as body mass index ≥ 85th percentiles for age and sex. We found a non-significant increase of EPD risk among girls with high EST alone [OR: 2.75 (0.65-11.58)] or low MVPA alone [OR: 2.54 (0.74-8.69)], but a significant increase of EPD risk among girls with overweight/obesity alone [OR: 4.91 (1.01-23.92)], compared to girls without any of the three risk factors (low MVPA, high EST and overweight/obesity). Girls with any two of the three risk factors faced increased risk of EPD, and girls with all three risk factors faced the highest risk of EPD [OR and 95% CI: 26.10 (6.40-106.45)]. Being overweight/obesity might be more important than having low MVPA or high EST as a correlate of EPD compared to girls without any of the three risk factors, but the co-presence of low MVPA, high EST and overweight/obesity would largely increase the risk of EPD in girls.

Mesoscale size-promoted targeted therapy for acute kidney injury through combined RONS scavenging and inflammation alleviation strategy.

Acute kidney injury (AKI) is a heterogeneous, high-mortality clinical syndrome with diverse pathogenesis and prognosis, but it lacks the effective therapy clinically. Its pathogenesis is associated with production of reactive oxygen/nitrogen species and infiltration of inflammatory cells. To overcome these pathogenic factors and improve the therapeutic efficiency, we synthesized triptolide-loaded mesoscale polydopamine melanin-mimetic nanoparticles (MeNP4TP) as the antioxidant plus anti-inflammatory therapeutic platform to synergistically scavenge reactive oxygen/nitrogen species (RONS), inhibit the activity of macrophages and dendritic cells, and generate Treg cells for AKI therapy. It was demonstrated that mesoscale size was beneficial for MeNP4TP to specifically accumulate at renal tubule cells, and MeNP4TP could significantly attenuate oxidative stress, reduce proinflammatory immune cells in renal, and repair renal function in cisplatin-induced AKI mouse model. MeNP4TP might be a potential candidate to inhibit oxidative damages and inflammatory events in AKI.

TaCRT3 Is a Positive Regulator of Resistance to Blumeria graminis f. sp. tritici in Wheat.

Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most prevalent diseases of wheat worldwide and can lead to severe yield reductions. Identifying genes involved in powdery mildew resistance will be useful for disease resistance breeding and control. Calreticulin (CRT) is a member of multigene family widely found in higher plants and is associated with a variety of plant physiological functions and defense responses. However, the role of CRT in wheat resistance to powdery mildew remains unclear. TaCRT3 was identified from the proteomic sequence of an incompatible interaction between the wheat (Triticum aestivum) cultivar Xingmin 318 and the Bgt isolate E09. Following analysis of transient expression of the GFP-TaCRT3 fusion protein in Nicotiana benthamiana leaves, TaCRT3 was localized in the nucleus, cytoplasm, and cell membrane. Transcript expression levels of TaCRT3 were significantly upregulated in the wheat-Bgt incompatible interaction. More critically, knockdown of TaCRT3 using virus-induced gene silencing resulted in attenuated resistance to Bgt in wheat. Histological analysis showed a significant increase in Bgt development in TaCRT3-silenced plants, whereas the pathogen-related gene was significantly downregulated in TaCRT3-silenced leaves. In addition, overexpression of TaCRT3 in wheat enhanced the resistance to powdery mildew, the growth of Bgt was significantly inhibited, and the area of H2O2 near the infection site and the expression of defense-related genes of the salicylic acid pathway significantly increased. These findings imply that TaCRT3 may act as a disease resistance factor that positively regulates resistance to powdery mildew, during which SA signaling is probably activated.

Complexity-based graph convolutional neural network for epilepsy diagnosis in normal, acute, and chronic stages.

Introduction: The automatic precision detection technology based on electroencephalography (EEG) is essential in epilepsy studies. It can provide objective proof for epilepsy diagnosis, treatment, and evaluation, thus helping doctors improve treatment efficiency. At present, the normal and acute phases of epilepsy can be well identified through EEG analysis, but distinguishing between the normal and chronic phases is still tricky. Methods: In this paper, five popular complexity indicators of EEG signal, including approximate entropy, sample entropy, permutation entropy, fuzzy entropy and Kolmogorov complexity, are computed from rat hippocampi to characterize the normal, acute, and chronic phases during epileptogenesis. Results of one-way ANOVA and principal component analysis both show that utilizing complexity features, we are able to easily identify differences between normal, acute, and chronic phases. We also propose an innovative framework for epilepsy detection based on graph convolutional neural network (GCNN) using multi-channel EEG complexity as input. Results: Combining information of five complexity measures at eight channels, our GCNN model demonstrate superior ability in recognizing the normal, acute, and chronic phases. Experiments results show that our GCNN model reached the high prediction accuracy above 98% and F1 score above 97% among these three phases for each individual rat. Discussion: Our research practice based on real data shows that EEG complexity characteristics are of great significance for recognizing different stages of epilepsy.

A case report of solitary fibrous tumor of the thyroid gland and literature review.

RATIONALE: A solitary fibrous tumor (SFT) is an uncommon soft tissue tumor that was first discovered in the pleura. Although SFTs have been documented in other extra-pleural sites, an SFT in the thyroid gland is highly unusual. An SFT of the thyroid gland can be difficult to diagnose, and there is little information about their Underlying biological behavior. PATIENT CONCERNS: We present a case of a 63-year-old man with a progressively growing left-neck mass detected 1 month ago, which was pathologically confirmed to be a benign SFT of the thyroid gland. DIAGNOSIS: Postoperative pathological examination of the tumor revealed an SFT. Immunopathological examination was consistent with the diagnosis of an SFT. INTERVENTIONS: The patient underwent surgical resection of the SFT. OUTCOMES: The patient was recurrence-free during 1.5 years of follow-up. LESSONS: Surgical excision is beneficial in SFTs that show no histological signs of malignancy, such as pleomorphism, enhanced mitotic activity, necrosis, bleeding, or capsular invasion. However, because the biologic activity remains unknown, meticulous long-term monitoring is required.

Bacterial Magnetosome-Hitchhiked Quick-Frozen Neutrophils for Targeted Destruction of Pre-Metastatic Niche and Prevention of Tumor Metastasis.

Premetastatic niche (PMN) is a prerequisite for tumor metastasis. Destruction of PMN can significantly suppress the tumor metastasis. Bone marrow-derived cells are usually recruited into the premetastatic organs to support PMN formation, which can be orchestrated by tumor-derived secreted factors. Neutrophils can chemotactically migrate towards the inflammatory sites and consume tumor-derived secreted factors, capable of acting as therapeutic agents for a broad-spectrum suppression of PMN formation and metastasis. However, neutrophils in response to inflammatory signals can release neutrophil extracellular traps (NETs), promoting the tumor metastasis. Herein, live neutrophils are converted into dead neutrophils (C NE) through a quick-frozen process to maintain PMN-targeting and tumor-derived secreted factor-consuming abilities but eliminate NET-releasing shortcomings. Considering macrophages-regulated remodeling of the extracellular matrix in PMN, bacterial magnetosomes (Mag) are further hitchhiked on the surface of C NE to form C NEMag , which can repolarize macrophages from M2 to M1 phenotype for further disruption of PMN formation. A series of in vitro and in vivo assessments have been applied to confirm the effectiveness of C NEMag in suppression of PMN formation and metastasis. This study presents a promising strategy for targeted anti-metastatic therapy in clinics.

Laryngocele: Report of two rare cases and review of the literature.

Laryngocele is a rare clinical condition characterized by an abnormal dilation of the laryngeal saccule. The present study focused on two separate cases of diagnosed patients. The first patient suffered from internal laryngocele and complained of hoarseness for almost 1 year. Plasma was used to treat the internal laryngocele and the outcomes were satisfying. The patient did not undergo any tracheostomy due to previous endoscopic surgery. The second patient included in the present study was diagnosed with mixed laryngocele and complained of swelling on the left side of the upper aspect of the neck with considerable pain for >1 month. The patient was prepped for excision by an external transcervical technique under general anesthesia. None of the two patients had any recurrence or other changes during follow-up. The purpose of reporting these two cases of laryngocele was to increase awareness of this condition. Surgery is still the first-line treatment for diagnosed cases, but with the advent of new microscopic techniques, the use of plasma in an inter-pharynx setting has become more common. The results observed after using plasma to treat one internal laryngocele may be relevant to better understanding the application of this method and confirm that it may be a new suitable approach to treat this condition.

Primary Surgical Management of Laryngeal Neuroendocrine Neoplasms: A Single Institution Case Series.

Objective: Laryngeal neuroendocrine neoplasms (NENs) are rare diseases. A single institution retrospective study was done of the outcome of patients with laryngeal NENs who undergo primary surgery as the first treatment modality. Methods: Retrospective analysis of medical records of patients with laryngeal NENs between 2009 and 2018. Cases were classified by applying the 2022 World Health organization Classification of Head and Neck Tumors (5th edition). Results: Six patients were eligible at our tertiary center: 1 large cell neuroendocrine carcinoma (NEC), 3 small cell NEC, 1 neuroendocrine tumor grade 1, and 1 neuroendocrine tumor grade 2. All admitted patients received upfront surgeries, including 3 transoral CO2 laser surgeries and 3 total laryngectomies with or without elective neck dissection. Four patients underwent subsequent chemoradiotherapy. Although 3 patients had recurrent disease and distal metastasis, the overall survival was generally improved. Conclusion: According to our institutional experience, upfront surgery in the first-line setting of a multi-modality approach with adjuvant chemoradiotherapy plays a very important role in managing laryngeal NECs, and may confer additional survival benefit in some patients of the large cell carcinoma subgroup.

Targeted hollow pollen silica nanoparticles for enhanced intravesical therapy of bladder cancer.

Bladder cancer (BC), such as non-muscle invasive bladder cancer (NMIBC), has a significantly high recurrence rate even after intravesical therapy because traditional intravesical chemotherapeutic drugs have short retention time in the bladder and lack efficient uptake in BC cells. Pollen structure usually shows potent adhesion ability to tissue surfaces, different from traditional electronic interaction or covalent binding. 4-Carboxyphenylboric acid (CPBA) has high affinity to sialic acid residues that are overexpressed on BC cells. In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs. THP@CHPS NPs showed high adhesion to skin tissues and could be more efficiently internalized by a mouse bladder cancer cell line (MB49) than THP, inducing more significant apoptotic cells. After intravesical instillation into a BC mouse model through an indwelling catheter, THP@CHPS NPs could more significantly accumulate at the bladder than THP at 24 h post-instillation, and after 8 days of intravesical treatments, magnetic resonance imaging (MRI) revealed that the bladders treated with THP@CHPS NPs showed more smooth bladder lining and more reduction in size and weights than those with THP. Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.

Bacteria engineered with intracellular and extracellular nanomaterials for hierarchical modulation of antitumor immune responses.

Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.

GE11-modified carboxymethyl chitosan micelles to deliver DOX·PD-L1 siRNA complex for combination of ICD and immune escape inhibition against tumor.

Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4+ and CD8+ T cells, reduce Tregs (TGF-ß), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.

Wheat Class III Peroxidase TaPOD70 Is a Potential Susceptibility Factor Negatively Regulating Wheat Resistance to Blumeria graminis f. sp. tritici.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most important diseases on wheat worldwide and can lead to a large reduction in wheat production. Class III peroxidases (PODs), a kind of secretory enzyme and members of a multigene family in higher plants, have been linked to various plant physiological functions and defensive responses. However, the role of PODs in wheat resistance to Bgt remains unclear. TaPOD70, a class III POD gene, was identified from the proteomics sequencing of the incompatible interaction between wheat (Triticum aestivum) cultivar Xingmin 318 and Bgt isolate E09. After transient expression of the TaPOD70-GFP fusion protein in Nicotiana benthamiana leaves, TaPOD70 was located in the membrane region. Yeast secretion assay showed that TaPOD70 was a secretory protein. Furthermore, Bax-induced programmed cell death was inhibited by transient expression of TaPOD70 in N. benthamiana. The transcript expression level of TaPOD70 was significantly upregulated in the wheat-Bgt compatible interaction. More crucially, knocking down TaPOD70 using virus-induced gene silencing increased wheat resistance to Bgt compared with the control plants. In response to Bgt, histological analyses indicated that hyphal development of Bgt was significantly reduced, whereas H2O2 production was enhanced in TaPOD70-silenced leaves. These findings imply that TaPOD70 may act as a susceptibility factor, adversely regulating wheat resistance to Bgt.

Gold Nanobipyramid-Mediated Apoptotic Camouflage of Adipocytes for Obesity Immunotherapy.

Obesity treatment is a global public health challenge due to inadequate weight loss and weight regain even after endeavors with multimodal treatments. Considering the abundance of resident macrophages in adipose tissues, precise regulation of the interactions between macrophages and adipocytes may provide chances for immunotherapy of obesity. Herein, inspired by the phagocytosis of macrophages to clear apoptotic cells in homeostasis, an immunotherapy strategy for obesity treatment is proposed for the first time through apoptotic camouflage of adipocytes by PA Au BPs to activate macrophages for clearance, where PA Au BPs are gold nanobipyramids engineered with adipose-targeting and apoptotic cell-mimicking functions. During clearance, the macrophage is switched from pro-inflammatory M1 to anti-inflammatory M2, remarkably modulating the immune microenvironment of adipose tissues to prevent weight regain. After inguinal injection with PA Au BPs, the body weights of obese mice are effectively decreased by 24.4% and can be decreased by 33.3% when combined with photothermal lipolysis, and little weight regain is associated with these treatments. This study demonstrates that the strategy of camouflaging adipocytes with apoptotic features holds great potential for obesity immunotherapy.

Integrated physiologic and proteomic analysis of Stropharia rugosoannulata mycelia in response to Cd stress.

Soil Cd pollution seriously threatens environment and human health. Due to its ability to absorb and accumulate Cd in mycelia, Stropharia rugosoannulata could be a potential candidate for bioremediation of Cd-contaminated soils; however, the response mechanism of mycelia to Cd stress is still unclear. In this study, the physiologic and proteomic differences of S. rugosoannulata mycelia under 0.2 mg/L (low) and 2 mg/L (high) Cd stress were investigated. The results showed that Cd accumulation and mycelial growth inhibition exhibited a concentration-depended trend. Analysis of antioxidant system indicated that SOD, GR, GSH, GSSG and ASA played key roles in resisting the toxic effects of Cd. Via proteome analysis, 24 and 267 differentially expressed proteins (DEPs) were observed under low and high Cd stress, respectively. GO and KEGG analysis found that the mycelial growth inhibition might due to the down-regulation of some DEPs involved in "valine, leucine and isoleucine biosynthesis" and "tyrosine metabolism"; the certain tolerance to high Cd stress might attribute to the regulation of DEPs referred to energy metabolism and antioxidant system-related pathways, maintaining cellular energy homeostasis and removing ROS. These results provide a theoretical basis for further elucidation of response mechanisms in S. rugosoannulata to Cd stress.

Harnessing decellularised extracellular matrix microgels into modular bioinks for extrusion-based bioprinting with good printability and high post-printing cell viability.

The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting. A proper bioink not only provides mechanical support for structural fidelity, but also serves as suitable three-dimensional (3D) microenvironment for cell encapsulation and protection. In this study, a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl (GelMA) as the continuous phase and decellularised extracellular matrix microgels (DMs) as the discrete phase. A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput manner. After gentle mixing of the DMs and GelMA, both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature, mechanical properties, and good printability from GelMA. The integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation, but also considerable shear-resistance for high post-printing cell viability. The DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based extrusion. Furthermore, a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs, resulting in a modular co-culture system with distinct cells/materials distribution. Overall, the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.

Perioperative pectoral nerve block type II and postoperative recurrence in breast cancer: a randomized controlled trial.

BACKGROUND: A new technique for analgesia called pectoral nerve block is widely used in surgeries of breast cancer. Pectoral nerve block type II (Pecs II) block has less influence on immunity when compared with general anesthesia method. The purpose of this research is to demonstrate whether Pecs II block has influence on the recurrence of breast cancer after surgical operation. METHODS: 526 breast cancer patients were recruited in this research and randomized into general anesthesia group and general anesthesia with Pecs II block group. Recurrence-free survival (RFS), distant recurrence-free survival (DRFS), and overall survival (OS) were evaluated for the two groups. RESULTS: Based on the statistical data, only the consumption of remifentanil was dramatically reduced by the performance of Pecs II block when compared with general anesthesia method. The performance of Pecs II block had no significant influence on OS, RFS, and DRFS of breast cancer patients after surgery. ASA physical status III, TNM stage 2 + 3, and mastectomy were proved to have association with lower recurrence-free survival. CONCLUSION: In conclusion, the performance of Pecs II block declined the remifentanil consumption during surgery of breast cancer. Meanwhile, the performance of Pecs II block had no significant influence on the OS, RFS, and DRFS of breast cancer patients after surgical resection.

Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1.

The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4+/CD8+ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.