Hypoxic tumor cell-derived small extracellular vesicle miR-152-3p promotes cervical cancer radioresistance through KLF15 protein.

BACKGROUND: Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited. METHODS: Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated. RESULTS: Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance. CONCLUSION: Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.

Bariatric surgery and mental health outcomes: an umbrella review.

Aims: To evaluate the breadth, depth and effectiveness of the evidence quality of all existing studies on bariatric surgery and mental health outcomes. Design: Umbrella review of existing Systematic review and meta-analyses. Data sources: PubMed, Embase, Web of Science, and the Cochrane Liberally databases of Systematic review and meta-analyses, and hand searching the reference lists of eligible publications. Results: The search identified nine studies and 20 mental health outcomes from 1251 studies. Evidence shows that bariatric surgery is associated with significant improvement in areas such as anxiety, depression and eating disorders (including binge-eating disorder), and there is a significant harmful association with suicide, self-harm and alcohol use disorder (AUD). Among them, the most studied outcome is depression (4 articles). High-quality evidence proves that the score of depressive symptoms can be significantly improved after bariatric surgery within a two-year follow-up period and is not affected by the follow-up time. Low-quality evidence shows that bariatric surgery can significantly reduce depressive symptoms regardless of age and BMI, with an odds ratio (OR) of 0.49. Regardless of the postoperative BMI, the anxiety symptoms of women over 40 still decreased significantly, with an OR of 0.58. Regardless of the type of surgery, surgery can significantly reduce the incidence of eating disorders and symptoms. However, there is no obvious change in the follow-up time of AUD in the first two years after bariatric surgery, and the risk increases obviously in the third year, with an OR of 1.825. The evidence of moderate research shows that the risk of suicide and self-harm increases after bariatric surgery. The odds ratios in the same population and the control group were 1.9 and 3.8 times, respectively. Conclusion: Bariatric surgery is beneficial for improving most mental health-related outcomes. However, we should be cautious about the increased risk of adverse mental health after surgery, such as suicide, self-harm, and AUD.

Inulin ameliorates metabolic syndrome in high-fat diet-fed mice by regulating gut microbiota and bile acid excretion.

Background: Inulin is a natural plant extract that improves metabolic syndrome by modulating the gut microbiota. Changes in the gut microbiota may affect intestinal bile acids. We suggest that inulin may improve metabolism by inducing bile acid excretion by gut microbes. Methods: Male C57/BL mice were fed either a high-fat diet (60% calories) or a regular diet for 16 weeks, with oral inulin (10% w/w). At the end of the experiment, the gene expression levels (FGF15, CD36, Srebp-1c, FASN, and ACC) in the liver and intestines, as well as the serum levels of triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, total cholesterol, and free fatty acids, were collected. The expression of FGF15 was examined using Western blot analysis. The fat distribution in the liver and groin was detected by oil red and hematoxylin and eosin staining. Simultaneously, the levels of serum inflammatory factors (alanine aminotransferase and aspartate aminotransferase) were detected to explore the side effects of inulin. Results: Inulin significantly improved glucose tolerance and insulin sensitivity, and decreased body weight and serum TG and LDL levels, in mice fed normal diet. Furthermore, inulin increased the α-diversity of the gut microbiota and increased the fecal bile acid and TG excretion in inulin-treated mice. In addition, inulin significantly reduced lipid accumulation in liver and inguinal fat, white fat weight, and hepatic steatosis. Western blot analysis showed that inulin reduced the expression of FGF15, a bile acid reabsorption protein. Conclusion: Inulin ameliorates the glucose and lipid metabolic phenotypes of mice fed a normal diet, including decreased intestinal lipid absorption, increased glucose tolerance, increased insulin sensitivity, and decreased body weight. These changes may be caused by an increase in bile acid excretion resulting from changes in the gut microbiota that affect intestinal lipid absorption.

Obesity causally influencing brain cortical structure: a Mendelian randomization study.

Obesity may lead to cognitive impairment and psychiatric disorders, which are associated with alterations in the brain cortical structure. However, the exact causality remains inconclusive. We aimed to conduct two-sample Mendelian randomization (MR) analysis to identify the causal associations of obesity [body mass index (BMI), waist-hip ratio (WHR), and waist-hip ratio adjusted for BMI ((WHRadjBMI)) and brain cortical structure (cortical thickness and cortical surface area). Inverse-variance weighted (IVW) method was used as the main analysis, whereas a series of sensitivity analyses were employed to assess heterogeneity and pleiotropy. The main MR results showed that higher BMI significantly increased the cortical surface area of the transverse temporal (ß = 5.13 mm2, 95% confidence interval [CI]: 2.55-7.71, P = 9.9 × 10-5); higher WHR significantly decreased cortical surface area of the inferior temporal (ß = -38.60, 95% CI: -56.67- -20.54, P = 1.2 × 10-5), but significantly increased cortical surface area of the isthmus cingulate (ß = 14.25, 95% CI: 6.97-21.54, P = 1.2 × 10-4). No significant evidence of pleiotropy was found in the MR analyses. This study supports that obesity has a causal effect on the brain cortical structure. Further studies are warranted to understand the clinical outcomes caused by these effects.

Characterization of fecal microbiota in cervical cancer patients associated with tumor stage and prognosis.

Cervical cancer (CC) is the fourth most frequent malignancy among women worldwide, and its prevention and treatment are evolving rapidly. The gut microbiota has been reported to play a crucial role both in the preservation of homeostasis and the development of cervical cancer. In this study, we collected fecal samples to investigate the microbial signatures in cervical cancer patients compared with healthy controls using 16S rRNA sequencing analysis and metagenomic next-generation sequencing (mNGS) testing. Our findings demonstrated a substantial difference in the gut microbiota composition of cervical cancer patients and healthy controls. The disease and stage were most significantly negatively correlated with Ruminococcus 2, which might be considered a potential clinically relevant biomarker. Functions of differential microbiomes were also analyzed, indicating significant differences in metabolisms and biosynthesis between the two groups. These findings demonstrate that patients with cervical cancer have certain species of gut microbiota that are exclusive to them and particular species have the potential to be used in the prognosis of cervical cancer.

Construction of a Prognostic Model for Predicting Colorectal Cancer Prognosis and Response to Immunotherapy Based on Cuproptosis-Associated lncRNAs.

Colorectal cancer (CRC) is a common and highly lethal gastrointestinal malignancy. Immunotherapy has shown positive efficacy in the treatment of CRC; however, only a minority of patients benefit from immunotherapy. The aim of this study is to construct a cuproptosis-related lncRNA (CRLs) risk score model to predict the prognosis and immune infiltration of CRC patients. Firstly, we synthetically analyzed 19 cuproptosis-related genes (CRGs) from CRC samples derived from the TCGA and obtained 33 CRLs that were significantly associated with prognosis. Next, we defined three cuproptosis modification patterns via consensus clustering analysis (C1, C2, and C3). Further analysis showed that there were significant differences in the abundance of B cells, NK cells, fibroblasts, monocytes, CD8+ cells, bone marrow dendritic cells, and cytotoxic lymphocytes in different clusters. In addition, the LASSO regression screened out 6 individual CRLs (AC009315.1, PLS3-AS1, ZEB1-AS1, AC007608.3, AC010789.2, and AC010207.1) closely related to the prognosis of CRC. We found that the low-risk group had better survival prognoses in patients. Furthermore, the high-risk group had lower immune scores and exhibited lower CD8+ T cell infiltration. Moreover, the low-risk group had lower immune exclusion, immune dysfunction and TIDE scores than the high-risk group. Interestingly, the lncRNAs in our risk model were positively associated with most immune checkpoints. CD274 (PD-L1), CTLA4, and HAVCR2 (TIM3) were positively correlated with risk scores. Moreover, MSI-H patients had lower risk scores than MSI-L patients, and IPS scores were significantly higher in the low CRLs score group. In conclusion, we constructed a novel risk score model with6 lncRNAs related to cuproptosis, which may be a potential biomarker for evaluating the prognosis and immune treatment for CRC.

Significant fibrosis assessed by liver biopsy among Chinese bariatric surgery patients: A prospective cross-sectional study.

Background: Fibrosis stages affect clinical prognoses related to nonalcoholic fatty liver disease (NAFLD). However, data on the prevalence and clinical features of significant fibrosis are scarce in Chinese bariatric surgery patients. We aimed to investigate the prevalence of significant fibrosis in bariatric surgery patients and to identify its predictors. Methods: We prospectively enrolled the patients performing intra-operative liver biopsies during bariatric surgery from a bariatric surgery center in a university hospital between May 2020 and January 2022. Anthropometric characteristics, co-morbidities, laboratory data and pathology reports were collected and analyzed. The performance of non-invasive models was evaluated. Results: Of 373 patients, 68.9%% had non-alcoholic steatohepatitis (NASH) and 60.9% exhibited fibrosis. Significant fibrosis was present in 9.1% of patients, advanced fibrosis in 4.0%, and cirrhosis in 1.6%. Multivariate logistic regression showed that increasing age (odds ratio [OR], 1.06; p=0.003), presence of diabetes (OR, 2.62; p=0.019), elevated c- peptide (OR, 1.26; p=0.025) and elevated aspartate aminotransferase (AST) (OR, 1.02; p=0.004) were independent predictors of significant fibrosis. The non-invasive models, AST to Platelet ratio (APRI), Fibrosis-4 (FIB-4), and Hepamet fibrosis scores (HFS) provided greater accuracy for predicting significant fibrosis, compared to the NAFLD Fibrosis Score (NFS) and BARD score. Conclusion: More than two-thirds of bariatric surgery patients had NASH and the prevalence of significant fibrosis was high. Elevated levels of AST and c- peptide, advanced age and diabetes indicated a higher risk of significant fibrosis. Non-invasive models, APRI, FIB-4 and HFS can be used to identify significant liver fibrosis in bariatric surgery patients.

A Novel Nomogram and Online Calculator for Predicting the Risk of Obesity Hypoventilation Syndrome in Bariatric Surgery Candidates.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is frequently misdiagnosed and undertreated, increasing the risk of perioperative complications. We aimed to determine the predictors of OHS and to develop and validate a novel nomogram and online calculator for identifying patients at risk of OHS in bariatric surgery candidates. METHODS: We retrospectively analyzed the data of patients undergoing bariatric surgery between March 2017 and June 2020. Predictors were identified using univariate and multivariate analyses to establish the nomogram. The discriminative ability, calibration, and clinical value of the nomograms were tested using C-statistics, calibration plots, and decision curve analysis. The nomogram was internally validated using bootstrap resampling. RESULTS: A total of 577 patients were enrolled, and OHS was presented in 17.9% (103/577). Body mass index (BMI) (odds ratio [OR], 1.11; 95% confidence interval (CI), 1.04-1.18; p = 0.001), neck circumference (OR, 1.09; 95% CI, 1.01-1.18; p = 0.035), type 2 diabetes (T2D) (OR, 2.02; 95% CI, 1.17-3.45; p = 0.011), serum bicarbonate (OR, 1.47; 95% CI, 1.30-1.67; p < 0.001), and C-reactive protein (CRP) (OR, 1.03; 95% CI, 1.01-1.06; p = 0.017) were independent risk factors for OHS and incorporated to develop the nomogram. The nomogram revealed good discrimination, with a C-index of 0.830 (95% CI: 0.784-0.876) (0.8227 through internal validation), and good calibration. Decision curve analysis further confirmed the nomogram's clinical usefulness. CONCLUSIONS: The novel nomogram and online calculator provided an excellent preoperative individualized prediction of OHS in patients undergoing bariatric surgery, hereby potentially assisting clinicians and surgeons in the early detection and intensive monitoring of OHS.

Easily automated radiosynthesis of [18F]P10A-1910 and its clinical translation to quantify phosphodiesterase 10A in human brain.

Our previous work showed that [18F]P10A-1910 was a potential radioligand for use in imaging phosphodiesterase 10A (PDE10A). Specifically, it had high brain penetration and specific binding that was demonstrated in both rodents and non-human primates. Here, we present the first automatic cGMP-level production of [18F]P10A-1910 and translational PET/MRI study in living human brains. Successful one-step radiolabeling of [18F]P10A-1910 on a GE TRACERlab FX2N synthesis module was realized via two different methods. First, formulated [18F]P10A-1910 was derived from heating spirocyclic iodonium ylide in a tetra-n-butyl ammonium methanesulfonate solution. At the end of synthesis, it was obtained in non-decay corrected radiochemical yields (n.d.c. RCYs) of 12.4 ± 1.3%, with molar activities (MAs) of 90.3 ± 12.6 µmol (n = 7) (Method I). The boronic pinacol ester combined with copper and oxygen also delivered the radioligand with 16.8 ± 1.0% n. d.c. RCYs and 77.3 ± 20.7 GBq/µmol (n = 7) MAs after formulation (Method II). The radiochemical purity, radionuclidic purity, solvent residue, sterility, endotoxin content and other parameters were all validated for human use. Consistent with the distribution of PDE10A in the brain, escalating uptake of [18F]P10A-1910 was observed in the order of cerebellum (reference region), substantial nigra, caudate and putamen. The non-displaceable binding potential (BP ND) was estimated by simplified reference-tissue model (SRTM); linear regressions demonstrated that BP ND was well correlated with the most widely used semiquantitative parameter SUV. The strongest correlation was observed with SUV(50-60 min) (R 2 = 0.966, p < 0.01). Collectively, these results indicated that a static scan protocol could be easily performed for PET imaging of PDE10A. Most importantly, that [18F]P10A-1910 is a promising radioligand to clinically quantify PDE10A.

Early Pregnancy (≤ 12 Months) After Bariatric Surgery: Does It Really Influence Maternal and Perinatal Outcomes?

BACKGROUND: Current guidelines do not recommend pregnancy within 12 months after bariatric surgery; however, there is a lack of consensus and scientific evidence to support this. The study is to evaluate the influence of early pregnancy (≤ 12 months) after bariatric surgery on maternal and perinatal outcomes. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for all studies comparing maternal and perinatal outcomes for surgery-to-conception intervals of ≤ 12 months and > 12 months. RESULTS: A total of 13 studies were included. The pooled results showed that early pregnancy was associated with insufficient gestational weight gain (WMD: - 6.04, 95%CI [- 7.39, - 4.15], p < 0.01). No significant difference was found in gestational diabetes, gestational hypertension, preeclampsia, caesarean section, and postpartum hemorrhage between surgery-to-conception intervals of ≤ 12 months and > 12 months. There were also no significant differences between the two groups regarding the neonatal outcomes, including preterm birth, small for gestational age, large for gestational age, macrosomia, birth defect, neonatal intensive care unit admission, and Apgar score ≤ 7 within 5 min. CONCLUSIONS: Early pregnancy (≤ 12 months) after bariatric surgery seems have no significant adverse effects on maternal and perinatal outcomes, with the exception of insufficient gestational weight gain. Pregnancy after bariatric surgery should be personalized based on the individual patient. Further studies on larger cohorts are warranted.

Differentiation between fresh and frozen-thawed scallop adductor muscle as raw materials for sashimi during cold storage.

The changes of sensory and biochemical characteristics on the fresh and frozen-thawed scallop adductor muscle during storage at 4°C were discussed in this study. The Quality Index Method (QIM) scheme for evaluating scallop adductor muscle as raw materials for sashimi was proposed for the first time. The results of sensory evaluation showed that frozen-thawed scallop adductor muscle within zero to one day of refrigeration can be happily accepted by consumers, indicating the superiority of freezing for long-distance transportation, although the triangle test confirmed that there are still sensorial differences between fresh and frozen-thawed scallop adductor muscle. The microscopic observation of myofibrils extracted from scallop adductor muscle suggested that the myofibrillar protein which constitutes myofibrils has suffered some extent change due to freezing and thawing, even though the head region of myosin remained stable judging by the fact that there was no significant difference in Ca2+ -ATPase activity (p > 0.05). The changes of adenosine triphosphate (ATP) and its related compounds, and pH value during storage can be regarded as indicators to differentiate fresh and frozen-thawed scallop adductor muscle. The changes of Mg2+ -ATPase activity indicated that the interaction between myosin and actin was weakened by the freezing and thawing process. Practical Application: The QIM scheme can be used to evaluate the scallop adductor muscle as raw materials for sashimi. The mechanism of quality changes in the frozen-thawed scallop adductor muscle was discussed in combination with the destruction of myofibrils, ATP degradation and the decrease of pH value. This study has positive significance for improving the quality of frozen-thawed scallop adductor muscle by combining the changes of sensory and biochemical characteristics.

LncRNA MEG3 regulates breast cancer proliferation and apoptosis through miR-141-3p/RBMS3 axis.

Maternally expressed 3 (MEG3) and RNA binding motif single stranded interacting protein 3 (RBMS3) are abnormally expressed in breast cancer susceptibility genes (BRCA), but the mechanism of the two in breast cancer (BC) is unclear. By performing in vivo and in vitro experiments, we found that MEG3 and RBMS3 were low-expressed, negatively correlated with high-expressed miR-141-3p, were positively correlated with each other in BC. MEG3 targeted miR-141-3p, and miR-141-3p targeted RBMS3. MEG3, which was mainly distributed in BC cytoplasm, could down-regulate miR-141-3p and up-regulate RBMS3, and reverse effect of miR-141-3p on related gene expressions and on promoting cancer development. Overexpressed MEG3 inhibited growth of xenografts, promoted cell apoptosis via regulating apoptosis related factors, and up-regulated RBMS3 expression but down-regulated miR-141-3p. The findings of this study showed that MEG3 inhibited proliferation and promoted apoptosis of BC cells through the miR-141-3p/RBMS3 axis, and MEG3 inhibited growth of xenografts through miR-141-3p.

Factors influencing the adhesive behavior of carboxymethyl cellulose-based hydrogel for food applications.

Carboxymethyl cellulose (CMC) hydrogels have been used as adhesive materials for food and other newly emerged innovative applications. To increase the knowledge of CMC hydrogel-based adhesives and optimize the preparation and storage conditions in practical, we prepared CMC hydrogels for cigar wrapper application and investigated their adhesive performance as affected by different CMC type, concentration, pH, temperature, and storage time, etc. Two parameters, initial adhesiveness and peel strength were used to evaluate the adhesive behavior of CMC with paper and tobacco leaf. Sample C2 with relatively medium molecular weight and medium degree of substitution values showed the best adhesive performance. Hydrogels prepared using boiled water at neutral pH presented better adhesive behavior, which was not significantly affected by storage temperature (up to 13 days). The wettability, steady shear flow behavior, dynamic rheological properties, and stress recovery performance of CMC hydrogel were measured, and their correlations to the adhesive behavior were discussed.

The association between interleukin-1 polymorphisms and their protein expression in Chinese Han patients with breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer in women and the second leading cause of cancer-related deaths among women worldwide. Single nucleotide polymorphisms (SNPs) in cytokine genes have been shown to alter their expressions or functions in patients with BC. In recent years, the molecular structure and function of IL-1 have been studied. Its genetic polymorphism could affect the transcription and expression of the IL-1 gene. Moreover, it is closely related to several diseases. This fact and plethora of gene polymorphism data prompted us to investigate the relationship between IL-1 polymorphisms and IL-1 protein expression in Chinese Han BC patients. METHOD: In total, 298 patients with BC and 287 healthy control women were studied. The genetic polymorphisms for IL-1 were analyzed by the MassARRAY sequencing method. Tumor markers and IL-1ß levels were measured by electrochemiluminescence and ELISA, respectively. All gene selection GRCh38 version. RESULTS: The rs1143623 (NC_000002.12:g.112838252C>G) (GC), rs16944 (NC_000002.12:g.112837290A>G)(AG), and rs10490571 (NC_000002.12:g.102100877C>T) (CC) SNPs were found to be significantly lower in the BC group than in the controls. The variant G/C genotype of rs1143623 was associated with a significantly increased risk for BC (OR = 2.34, p < 0.05). The alleles for rs16944 (A/G; OR = 3.15, p < 0.05) and rs10490571 (T/C; OR = 2.48, p < 0.05) were also significantly associated with BC. Moreover, the genotypes of rs1143623, rs16944, and rs10490571 were significantly correlated with serum IL-1ß levels and other tumor markers. CONCLUSION: Our data reveal the association between genetic polymorphisms of IL-1 and BC susceptibility in the Chinese Han population and indicates that IL-1 polymorphisms are closely associated with tumor markers and IL-1ß protein expression in BC patients.

Elevated PD-L1 expression predicts poor survival outcomes in patients with cervical cancer.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression has been shown to associate with poor prognosis in a variety of solid tumors. However, the prognostic value of PD-L1 expression in cervical cancer is still controversial. Therefore, we carried a meta-analysis to investigate the prognostic and clinicopathological impact of PD-L1 in cervical cancer. METHODS: A comprehensive literature search in was performed in PubMed, Embase, Web of Science, and Cochrane Library. The correlation between PD-L1 expression and overall survival (OS), progression-free survival (PFS), and clinicopathological features was analyzed by hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). RESULTS: Seven studies with 783 patients were included in this meta-analysis. The combined HR and 95% CI of OS was 2.52 (1.09-5.83), p = 0.031. The pooled results for PFS were HR = 2.07, 95% CI = 0.52-8.23, p = 0.302. The results of subgroup analysis showed that PD-L1 was a significant prognostic factor of poor OS in Asian patients (HR = 4.77, 95% CI = 3.02-7.54, p < 0.001) and of poor PFS in Asian patients (HR = 4.78, 95% CI = 1.77-12.91, p = 0.002). However, the pooled results suggested that PD-L1 was not significantly correlated with lymph node metastasis, tumor size, FIGO stage, depth of invasion, lymph-vascular invasion, or age. CONCLUSIONS: The results of this meta-analysis suggest that PD-L1 overexpression is related to poor OS in patients with cervical cancer and poor PFS in Asian patients with cervical cancer. This study also suggests that PD-L1 is a promising prognostic indicator for cervical cancer.

Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)-poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy.

Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core-shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy.