Tumor habitat-based MRI features assessing early response in locally advanced nasopharyngeal carcinoma.

OBJECTIVE: The early response to concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) is closely correlated with prognosis. In this study, we aimed to predict early response using a combined model that combines sub-regional radiomics features from multi-sequence MRI with clinically relevant factors. METHODS: A total of 104 patients with LA-NPC were randomly divided into training and test cohorts at a ratio of 3:1. Radiomic features were extracted from subregions within the tumor area using the K-means clustering method, and feature selection was performed using LASSO regression. Four models were established: a radiomics model, a clinical model, an Intratumor Heterogeneity (ITH) score-based model and a combined model that integrates the ITH score with clinical factors. The predictive performance of these models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Among the models, the combined model incorporating the ITH score and clinical factors exhibited the highest predictive performance in the test cohort (AUC=0.838). Additionally, the models based on ITH score showed superior prognostic value in both the training cohort (AUC=0.888) and the test cohort (AUC=0.833). CONCLUSION: The combined model that integrates the ITH score with clinical factors exhibited superior performance in predicting early response following concurrent chemoradiotherapy in patients with LA-NPC.

Induction chemotherapy regimes in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: A network meta-analysis and cost-effectiveness analysis.

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.

A Network Meta-Analysis of the Systemic Therapies in Unresectable Head and Neck Squamous Cell Carcinoma.

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. METHODS: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. RESULTS: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. CONCLUSION: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.

The current standard treatment for advanced head and neck cancer involves combining radiation therapy with chemotherapy. However, there are ongoing trials exploring alternative therapies. In this study, we conducted a comprehensive analysis of existing treatments using a statistical method called network meta-analysis. Our analysis included data from randomized controlled trials published between January 2000 and July 2023. We focused on overall survival and progression-free survival as key outcome measures. The results of our analysis showed that none of the alternative treatments demonstrated significant advantages over the standard concurrent chemoradiotherapy. Nevertheless, there is potential for improved outcomes when targeted therapy or induction chemotherapy is combined with concurrent chemoradiotherapy.

Self-Disassembling and Oxygen-Generating Porphyrin-Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy.

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.

Treatment for T1 colorectal cancers substratified by site and size: "horses for courses".

Background: Owing to advances in diagnostic technology, the diagnosis of T1 colorectal cancers (CRCs) continues to increase. However, the optimal management of T1 CRCs in the Western Hemisphere remains unclear due to limited population-based data directly comparing the efficacy of endoscopic therapy (ET) and surgical resection (SR). The purpose of this study was to report outcome data from a large Western cohort of patients who underwent ET or SR for early CRCs. Methods: The SEER-18 database was used to identify patients with T1 CRCs diagnosed from 2004 to 2018 treated with ET or SR. Multivariable logistic regression models were employed to identify variables related to lymph node metastasis (LNM). Rates of ET and 1-year relative survival were calculated for each year. Effect of ET or SR on overall survival and cancer-specific survival was compared using Kaplan-Meier method stratified by tumor size and site. Results: A total of 28,430 T1 CRCs patients were identified from 2004 to 2018 in US, with 22.7% undergoing ET and 77.3% undergoing SR. The incidence of T1 CRCs was 6.15 per 100,000 person-years, with male patients having a higher incidence. Left-sided colon was the most frequent location of tumors. The utilization of ET increased significantly from 2004 to 2018, with no significant change in 1-year relative survival rate. Predictors of LNM were age at diagnosis, sex, race, tumor size, histology, grade, and location. The 5-year relative survival rates were 91.4 and 95.4% for ET and SR, respectively. Subgroup analysis showed that OS and CSS were similar between ET and SR in T1N0M0 left-sided colon cancers with tumors 2 cm or less and in rectal cancers with tumors 1 cm or less. Conclusion: Our study showed that ET was feasible and safe for patients with left-sided T1N0M0 colon cancers and tumors of 2 cm or less, as well as T1N0M0 rectal cancers and tumors of 1 cm or less. Therefore, the over- and under-use of ET should be avoided by carefully selecting patients based on tumor size and site.

Survival prediction of hepatocellular carcinoma by measuring the extracellular volume fraction with single-phase contrast-enhanced dual-energy CT imaging.

Purpose: This study aimed to investigate the value of quantified extracellular volume fraction (fECV) derived from dual-energy CT (DECT) for predicting the survival outcomes of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Materials and methods: A total of 63 patients with HCC who underwent DECT before treatment were retrospectively included. Virtual monochromatic images (VMI) (70 keV) and iodine density images (IDI) during the equilibrium phase (EP) were generated. The tumor VMI-fECV and IDI-fECV were measured and calculated on the whole tumor (Whole) and maximum enhancement of the tumor (Maximum), respectively. Univariate and multivariate Cox models were used to evaluate the effects of clinical and imaging predictors on overall survival (OS) and progression-free survival (PFS). Results: The correlation between tumor VMI-fECV and IDI-fECV was strong (both p< 0.001). The Bland-Altman plot between VMI-fECV and IDI-fECV showed a bias of 5.16% for the Whole and 6.89% for the Maximum modalities, respectively. Increasing tumor VMI-fECV and IDI-fECV were positively related to the effects on OS and PFS (both p< 0.05). The tumor IDI-fECV-Maximum was the only congruent independent predictor in patients with HCC after TACE in the multivariate analysis on OS (p = 0.000) and PFS (p = 0.028). Patients with higher IDI-fECV-Maximum values had better survival rates above the optimal cutoff values, which were 35.42% for OS and 29.37% for PFS. Conclusion: The quantified fECV determined by the equilibrium-phase contrast-enhanced DECT can potentially predict the survival outcomes of patients with HCC following TACE treatment.

Mussel-inspired "plug-and-play" hydrogel glue for postoperative tumor recurrence and wound infection inhibition.

Currently, clinical tumor resection is faced with two options: open and minimally invasive surgery. Open surgery is easy to completely remove the lesion but is prone to infection, while minimally invasive surgery recovers faster but may cause tumor recurrence. To fill the shortcomings of the two surgical modes and make the choice for tumor resection more effortlessly, we developed a postoperative black phosphorus-Ag nanocomposites-loaded dopamine-modified hyaluronic acid-Pluronic® F127 (BP-Ag@HA-DA-Plu) hydrogel implantation system that can prevent tumor recurrence and wound infection simultaneously. Experiments have shown that the hydrogel system combined with 808 nm near-infrared (NIR) irradiation has excellent anti-tumor, antibacterial, and wound healing abilities. Additionally, unlike existing surgical hydrogel products that require inconvenient in-situ cross-linking, the BP-Ag@HA-DA-Plu hydrogel system offers "plug-and-play" functionality during surgery due to its thermo-responsiveness, injectability, and adhesion, thereby greatly improving the efficiency of surgery.

Polydopamine-Coated Radiolabeled Microspheres for Combinatorial Radioembolization and Photothermal Cancer Therapy.

Transarterial radioembolization (TARE) is a local radionuclide therapy and is successfully used in hepatocellular carcinoma (HCC) treatment. Radioactive microspheres have been widely studied for TARE. Preparation of ideal radioactive microspheres is significant for clinical research and patient treatment. In this study, we have designed a novel multifunctional microsphere, i.e., polydopamine (PDA)-coated 177Lu-radiolabeled silica microspheres (MS) denoted as 177Lu-MS@PDA, which can be used for TARE and photothermal therapy (PTT). The radiostability of 177Lu-MS@PDA was significantly improved by coating 177Lu-MS with PDA. In addition, the coating of PDA makes microspheres have excellent photothermal performance. MicroSPECT/CT images showed that 177Lu-MS@PDA was accurately embolized and remained in the tumor during the observation time. At the time, it also showed that 177Lu-MS@PDA was very stable in vivo. Furthermore, the anti-tumor results demonstrated that TARE combined with PTT of 177Lu-MS@PDA can significantly inhibit tumor growth without obvious side effects. 177Lu-MS@PDA holds great potential as a promising radioactive microsphere for HCC.

Nuclear receptor modulators inhibit osteosarcoma cell proliferation and tumour growth by regulating the mTOR signaling pathway.

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Chemoresistance leads to poor responses to conventional therapy in patients with osteosarcoma. The discovery of novel effective therapeutic targets and drugs is still the main focus of osteosarcoma research. Nuclear receptors (NRs) have shown substantial promise as novel therapeutic targets for various cancers. In the present study, we performed a drug screen using 29 chemicals that specifically target 17 NRs in several different human osteosarcoma and osteoblast cell lines. The retinoic acid receptor beta (RARb) antagonist LE135, peroxisome proliferator activated receptor gamma (PPARg) antagonist T0070907, liver X receptor (LXR) agonist T0901317 and Rev-Erba agonist SR9011 significantly inhibited the proliferation of malignant osteosarcoma cells (U2OS, HOS-MNNG and Saos-2 cells) but did not inhibit the growth of normal osteoblasts. The effects of these NR modulators on osteosarcoma cells occurred in a dose-dependent manner and were not observed in NR-knockout osteosarcoma cells. These NR modulators also significantly inhibited osteosarcoma growth in vivo and enhanced the antitumour effect of doxorubicin (DOX). Transcriptomic and immunoblotting results showed that these NR modulators may inhibit the growth of osteosarcoma cells by regulating the PI3K/AKT/mTOR and ERK/mTOR pathways. DDIT4, which blocks mTOR activation, was identified as one of the common downstream target genes of these NRs. DDIT4 knockout significantly attenuated the inhibitory effects of these NR modulators on osteosarcoma cell growth. Together, our results revealed that modulators of RARb, PPARg, LXRs and Rev-Erba inhibit osteosarcoma growth both in vitro and in vivo through the mTOR signaling pathway, suggesting that treatment with these NR modulators is a novel potential therapeutic strategy.

Downhill running induced DNA damage enhances mitochondrial membrane permeability by facilitating ER-mitochondria signaling.

To observe whether downhill running can lead to DNA damage in skeletal muscle cells and changes in mitochondrial membrane permeability and to explore whether the DNA damage caused by downhill running can lead to changes in mitochondrial membrane permeability by regulating the components of the endoplasmic reticulum mitochondrial coupling structure (MAM). A total of 48 male adult Sprague-Dawley rats were randomly divided into a control group (C, n = 8) and a motor group (E, n = 40). Rats in Group E were further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48) and 72 h (E72) after prescribed exercise, with 8 rats in each group. At each time point, flounder muscle was collected under general anaesthesia. The DNA oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) was detected by immunofluorescence. The expression levels of the DNA damage-related protein p53 in the nucleus and the EI24 protein and reep1 protein in whole cells were detected by Western blot. The colocalization coefficients of the endoplasmic reticulum protein EI24 and the mitochondrial protein Vdac2 were determined by immunofluorescence double staining, and the concentration of Ca2+ in skeletal muscle mitochondria was detected by a fluorescent probe. Finally, the opening of the mitochondrial membrane permeability transition pore (mPTP) was detected by immunofluorescence. Twelve hours after downhill running, the mitochondrial membrane permeability of the mPTP opened the most (P < 0.05), the content of 8-OHdG in skeletal muscle peaked (P < 0.05), and the levels of the regulatory protein p53, mitochondrial Ca2+, and the EI24 and reep1 proteins peaked (P < 0.01). Moreover, the colocalization coefficients of EI24 and Vdac2 and the Mandes coefficients of the two proteins increased first and then recovered 72 h after exercise (P < 0.05). (1) Downhill running can lead to DNA damage in skeletal muscle cells, overload of mitochondrial Ca2+ and large opening of membrane permeability transformation pores. (2) The DNA damage caused by downhill running may result in p53 promoting the transcriptional activation of reep1 and EI24, enhancing the interaction between EI24 and Vdac2, and then leading to an increase in Ca2+ in skeletal muscle mitochondria and the opening of membrane permeability transition pores.

Characterization of Pleurotus citrinopileatus hydrolysates obtained from Actinomucor elegans proteases compared with that by commercial proteases.

Pleurotus citrinopileatus, a nutritious and palatable edible mushroom, can be used as an appropriate material to prepare high-grade flavoring agents. Based on this, the current study aimed to investigate the feasibility of a productive protease system from Actinomucor elegans to prepare P. citrinopileatus hydrolysate (PCH). The Actinomucor elegans crude protease (AECP) was prepared from the solid-state fermentation product of P. citrinopileatus by A. elegans. AECP and four commercial proteases (alcalase, neutrase, papain, and protamex) were applied to acquire five kinds of PCHs. The physical-chemical properties of PCHs as well as its concentration and composition of nonvolatile compounds were comparatively analyzed. Sensory evaluation and electronic tongue analysis were utilized to evaluate sensory characteristics. AECP was found to be the most effective protease, with the highest hydrolysis degree (35.91%) and protein recovery (81.46%). The result of molecular weight distribution indicated that peptides below 500 Da were the main fraction of AECP hydrolysates, while AECP hydrolysates showed the highest content of monosodium glutamate-like (20.23 ± 0.16 mg/g) and flavor 5'-nucleotide (4.30 ± 0.07 mg/g) peptides. In summary, the AECP hydrolysate had superior sensory profiles compared with other hydrolysates. In addition, AECP hydrolysates exhibited favorable kokumi taste in which peptides below 500 Da showed the highest correlation with kokumi by the results of partial least-squares regression. These results indicated the feasibility of applying PCHs as flavor additives or seasoning in the food industry. AECP might be used as an alternative enzyme choice because of its low cost and high hydrolysis efficiency. PRACTICAL APPLICATION: Pleurotus citrinopileatus served as a potential raw material for natural seasonings because of its high protein content and appropriate ratio of umami amino acids to total amino acids. Enzymatic hydrolysis was an efficient approach to improve the flavor of P. citrinopileatus, where the choice of enzyme was one of the most critical factors. The research indicated that P. citrinopileatus hydrolysate prepared by A. elegans crude protease (AECP) exhibited an acceptable flavor, which provided theoretical support for the high-value utilization of P. citrinopileatus as food seasoning. AECP might be applied as an alternative enzyme resource because of its low cost and high hydrolysis efficiency.

Endocytosis-mediated triple-activable prodrug nanotherapeutics potentiating therapeutic efficacy and security towards solid tumors.

Self-assembling prodrug nanotherapeutics have emerged as a promising nanoplatform for anticancer drug delivery. The specific and efficient activation of prodrug nanotherapeutics inside tumor cells is vital for the antitumor efficacy and security. Herein, a triple-activable prodrug polymer (TAP) is synthesized by conjugating polyethylene glycol-poly-(caprolactone)-paclitaxel (PTX) polymer with two tumor-responsive bonds, disulfide and acetal. TAP could self-assemble into nanotherapeutics (TAP NTs) free of surfactant with a high drug loading (32.6%). In blood circulation, TAP NTs could remain intact to efficiently accumulate in tumor sites. Thereafter, tumor cells would internalize TAP NTs through multiple endocytosis pathways. Inside tumor cells, TAP NTs could be activated to release PTX and induce tumor cell apoptosis in triple pathways: (i) lysosomal acidity rapid activation; (ii) ROS-acidity tandem activation and (iii) GSH-acidity tandem activation. Compared with Taxol and non-activable control, TAP NTs significantly potentiate the antitumor efficacy and security of PTX against solid tumors including breast cancer and colon cancer.

Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy.

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

Joint Detection of Tap and CEA Based on Deep Learning Medical Image Segmentation: Risk Prediction of Thyroid Cancer.

In recent years, the incidence of thyroid nodules has shown an increasing trend year by year and has become one of the important diseases that endanger human health. Ultrasound medical images based on deep learning are widely used in clinical diagnosis due to their cheapness, no radiation, and low cost. The use of image processing technology to accurately segment the nodule area provides important auxiliary information for the doctor's diagnosis, which is of great value for guiding clinical treatment. The purpose of this article is to explore the application value of combined detection of abnormal sugar-chain glycoprotein (TAP) and carcinoembryonic antigen (CEA) in the risk estimation of thyroid cancer in patients with thyroid nodules of type IV and above based on deep learning medical images. In this paper, ultrasound thyroid images are used as the research content, and the active contour level set method is used as the segmentation basis, and a segmentation algorithm for thyroid nodules is proposed. This paper takes ultrasound thyroid images as the research content, uses the active contour level set method as the basis of segmentation, and proposes an image segmentation algorithm Fast-SegNet based on deep learning, which extends the network model that was mainly used for thyroid medical image segmentation to more scenarios of the segmentation task. From January 2019 to October 2020, 400 patients with thyroid nodules of type IV and above were selected for physical examination and screening at the Health Management Center of our hospital, and they were diagnosed as thyroid cancer by pathological examination of thyroid nodules under B-ultrasound positioning. The detection rates of thyroid cancer in patients with thyroid nodules of type IV and above are compared; serum TAP and CEA levels are detected; PT-PCR is used to detect TTF-1, PTEN, and NIS expression; the detection, missed diagnosis, misdiagnosis rate, and diagnostic efficiency of the three detection methods are compared. This article uses the thyroid nodule region segmented based on deep learning medical images and compares experiments with CV model, LBF model, and DRLSE model. The experimental results show that the segmentation overlap rate of this method is as high as 98.4%, indicating that the algorithm proposed in this paper can more accurately extract the thyroid nodule area.

Exploration of the optimal strategy for dietary calcium intervention against the toxicity of liver and kidney induced by cadmium in mice: An in vivo diet intervention study.

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control.

KPNA4 is involved in cataract formation via the nuclear import of p53.

KPNA4 (also called importin-α3) belongs to the importin α adaptor proteins family, which orchestrates classical nuclear transport processes, importin-α/importin-ß1 pathway, and involves in cellular homeostasis. Disruption of balanced transport pathways may result in ectopic nuclear proteins and eventually cause diseases, mainly under the situation of cellular stress, such as oxidative stress. Little evidence is available on its cellular functions for high specific expression in lens. We firstly studied the role of KPNA4 in cataract formation. Lens defects were observed at an early age in kpna4 gene knockout zebrafish, generated by the CRISPR/Cas9 system. Those phenotype, including cloudy center part of the lens, via bright field microscopy, and the thinning of the LE layer, wider space between the adjacent LE and LF cells, irregular cells morphology and the increased number of holes inside the LE cells, which were detected by transmission electron microscopy, recapitulate the clinical features of cataract patients. As the p53-specific adaptor of the nuclear import, KPNA4 upregulated with the same pattern of p53 in hydrogen peroxide-induced apoptosis in human lens epithelia cells. Furthermore, the loss of Kpna4 resulted in the accumulation of p53 in the center of lens. Taken together, we showed that KPNA4 was involved in the formation of cataract, likely by mediating p53 nuclear transport.

Parameters of Capsulorrhexis and Intraocular Lens Decentration After Femtosecond and Manual Capsulotomies in High Myopic Patients With Cataracts.

Purpose: To compare the parameters of capsulorrhexis and intraocular lens decentration after femtosecond laser capsulotomy and manual continuous curvilinear capsulorrhexis in high myopic patients with cataracts. Methods: This is a prospective consecutive non-randomized comparative cohort study. Selected patients with axial length > 26.0 mm were divided into femtosecond laser capsulotomy (FS) group and manual continuous curvilinear capsulorrhexis (CCC) group. Five experienced phacoemulsification surgeons conducted all surgeries. Intraoperative complications and post-operative anterior segment photography were recorded. Intraocular lens decentration, area of capsulorrhexis, circularity, and capsule overlap were measured at 1 week, 1 month, and 2 years after surgery. Between group differences of parameters were determined with independent-sample t-test or the Mann-Whitney U-test, analysis of variance test, Pearson chi-square test, and Spearman rank correlation test. Results: The study included 142 eyes (108 patients), 68 eyes in the FS group, and 74 eyes in the CCC group. At 1 week, 1 month, and 2 years after surgery, the area of capsulorrhexis in the CCC group was significantly larger than in the FS group (P < 0.05), while no significant difference was noted in circularity values. The complete overlap ratio in the FS group was significantly higher than that in the CCC group (P < 0.05) at each measured timepoint. Significant correlations were noted between the anterior chamber depth and the area of capsulorrhexis in the CCC group (R = 0.25, P = 0.04), but did not correlate in the FS group (P > 0.05). In patients with an anterior chamber depth >3 mm, the capsule-intraocular lens (IOL) overlap of the CCC group was less than that of the FS group at all measured timepoints after surgery (P < 0.05). Meanwhile, the IOL decentration in the CCC group was significantly greater than that of the FS group in those patients at 2 years after surgery (P < 0.05). Conclusion: In high myopic patients with cataracts, with anterior chamber depth more than 3 mm, femtosecond laser capsulotomy can achieve better capsulorrhexis sizing and centering. Due to more precise capsulotomy and a better capsule-IOL overlap in the FS group, femtosecond laser capsulotomy resulted in better long-term centration of the IOL.

Versatile labeling of multiple radionuclides onto a nanoscale metal-organic framework for tumor imaging and radioisotope therapy.

Radionuclides for cancer theranostic have confronted problems such as limitation in real-time visualization and unsatisfactory therapeutic effect sacrificed by the nonspecific distribution. Nanoscale metal-organic frameworks (nMOFs) have been widely used in biomedical applications including cancer imaging and drug delivery. However, there have been rare reports utilizing nMOFs as a single nanoplatform to label various radionuclides for tumor imaging and radioisotope therapy (RIT). In this work, we developed polyethylene glycol (PEG) modified zirconium-based nMOFs (PCN-224) with favorable size, water solubility and biocompatibility. Interestingly, without the help of chelating agents, metal radionuclides (technetium-99 m/99mTc, lutetium-177/177Lu) could be efficiently labeled onto nMOFs via chelating with the porphyrin structure and iodine-125 (125I) via chemical substitution of hydrogen in the benzene ring. The radionuclide-labeled PCN-PEG nanoparticles all exhibit excellent radiolabeling stability in different solutions. In accordance with the fluorescence imaging of mice injected with PCN-PEG, SPECT/CT imaging illustrates strong tumor accumulation of 99mTc-PCN-PEG. Moreover, 177Lu-PCN-PEG significantly inhibited the growth of tumor without inducing any perceptible toxicity to the treated mice. Hence, the radionuclide-delivery nanoplatform based on nMOFs would provide more opportunities for precise tumor theranostics and expand the biomedical applications of MOF nanomaterials.

The value of ultrasound in diagnosing metastatic internal mammary lymph nodes in preoperative breast cancer.

BACKGROUND: Internal mammary lymph nodes (IMLNs) metastasis is of great significance for patients with breast cancer (BC), but the diagnosis of metastasis is difficult. The purpose of this study was to explore the characteristics of metastatic internal mammary lymph nodes visualized on breast ultrasound (US) in preoperative breast cancer. METHODS: Between March 2014 and May 2020, a total of 278 patients with primary BC were enrolled in a retrospective study and were divided into a metastatic group (n=224) and a non-metastatic group (n=54) according to IMLN status. Medical records, US findings, and especially IMLN status (long and short diameter, cortical thickness, blood flow) were reviewed, analyzed, and correlated with pathologic results. RESULTS: There were significant differences in long diameter, short diameter, numbers, intercostal space (ICS) distribution, and structure type of IMLN between the two groups (P<0.05), but no statistical difference in the ratio of long to short diameter and blood flow (P>0.05). The best cutoff values of size for differentiating IMLN metastasis from benign LNs were 10.5 mm (long diameter), 4.5 mm (short diameter), and 1.9 mm (cortical thickness), with sensitivities of 62.9%, 71.4%, and 91.4%, respectively and specificities of 90.7%, 77.8%, and 86.7%, respectively. The sensitivity and specificity of long and short diameter combined with structure type of IMLN were 74.1% and 83.3%, respectively. CONCLUSIONS: US is an important tool to evaluate the status of IMLN in patients with BC. US features of metastatic IMLNs include thickened cortex (≥1.9 mm), absent fatty hilum, multiple (n≥2). The size (long or short diameter) combined with structural types of IMLN had good efficacy for diagnosing IMLN metastasis.

Adverse health effects of lead exposure on physical growth, erythrocyte parameters and school performances for school-aged children in eastern China.

We conducted a cross-sectional study with 395 completely matched student samples enrolled from a public primary school in Nanjing of eastern China, including questionnaires, blood samples, growth indexes and school performances, all of which were used for the analysis of variance (ANOVA) and general linear model (GLM). The results showed that factors, such as gender, age, parents' education, residential passive smoking and picky eaters, had significant impacts on the blood lead levels (BPbs). As for the linear and non-linear dose-response relationship between BPbs and erythrocyte parameters, we found a positive association between BPbs and red blood cell count (RBC count) and mean corpuscular hemoglobin concentration (MCHC) but a negative association between BPbs and hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). When BPbs increased by 10 µg/L, the RBC count increased by 0.18 × 1012/L, while HGB and HCT decreased by 1.19 g/L and 0.41% for boys, respectively. As for girls, corresponding increases in RBC count was 0.05 × 1012/L, while HGB and HCT decreased by 0.82 g/L and 0.23%. Meanwhile, for both boys and girls, MCHC increased by 2.55 g/L, while MCV and MCH levels decreased by 0.41 fL and 0.12 pg each. Furthermore, a remarkable adverse effect (p < 0.05) was observed on children's school performances as a result of increased BPbs. As BPbs increased by 10 µg/L, children's scores for Chinese, Math and English decreased by 0.42 points, 0.39 points and 0.87 points, respectively. In summary, our study indicated that lead exposure can have adverse health effects on children's erythrocyte parameters, BMI, and school performances.