Roller-like Spore Carbon Sphere-Orientated Graphene Fibers Prepared via Rheological Engineering for Lithium Sulfur Batteries.

Flexible batteries with large energy densities, lightweight nature, and high mechanical strength are considered as an eager goal for portable electronics. Herein, we first propose free-standing graphene fiber electrodes containing roller-like orientated spore carbon spheres via rheological engineering. With the help of the orientated microfluidic cospinning technology and the plasma reduction method, spore carbon spheres are self-assembled and orientedly dispersed into numerous graphene flakes, forming graphene fiber electrodes enriched with internal rolling woven structures, which cannot only enhance the electrical contact between active materials but also effectively improve the mechanical strength and structure stability of graphene fiber electrodes. When the designed graphene fibers are combined with the active sulfur cathode and lithium metal anode, the assembled flexible lithium sulfur batteries possess superior electrochemical performance with high capacity (>1000 mA h g-1) and excellent cycling life as well as good mechanical properties. According to density functional theory and COMSOL simulations, the roller-like spore carbon sphere-orientated graphene fiber hosts provide reinforced trapping-catalytic-conversion behavior to soluble polysulfides and nucleation active sites to lithium metal, thus synergistically suppressing the shuttle effect of polysulfides at the cathode side and lithium dendrite growth at the anode side, thereby boosting the whole electrochemical properties of lithium sulfur batteries.

Plasma Coupled Electrolyte Additive Strategy for Construction of High-Performance Solid Electrolyte Interphase on Li Metal Anodes.

High-performance lithium metal anodes are crucial for the development of advanced Li metal batteries. Herein, this work reports a novel plasma coupled electrolyte additive strategy to prepare high-quality composite solid electrolyte interphase (SEI) on Li metal to achieve enhanced performance and stability. With the guidance of calculations, this work selects diethyl dibromomalonate (DB) as an additive to optimize the solvation structure of electrolytes to modify the SEI. Meanwhile, this work groundbreakingly develops DB plasma technology coupled with DB electrolyte additive to construct a combinatorial SEI: inner plasma-induced SEI layer composed of LiBr and Li2CO3 plus additive-reduced SEI containing LiBr/Li2CO3/organic lithium compounds as an outer compatible layer. The optimized hybrid SEI has strong affinity toward Li+ and good mechanical properties, thereby inducing horizontal dispersion and uniform deposition of Li+ and keep structure stable. Accordingly, the symmetrical cells exhibit enhanced cycling stability for 1200 h at an overpotential of 23.8 mV with average coulombic efficiency (99.51%). Additionally, the full cells with LiNi0.8Co0.1Mn0.1O2 cathode deliver a capacity retention of 81.7% after 300 cycles at 0.5 C, and the pouch cell achieves a volumetric specific energy of ≈664 Wh L‒1. This work provides new enlightenment on plasma technology for fabrication of advanced metal anodes for energy storage.

Ultrafast-Loaded Nickel Sulfide on Vertical Graphene Enabled by Joule Heating for Enhanced Lithium Metal Batteries.

The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

AßPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.

Juice Vesicles Bioreactors Technology for Constructing Advanced Carbon-Based Energy Storage.

The construction of high-quality carbon-based energy materials through biotechnology has always been an eager goal of the scientific community. Herein, juice vesicles bioreactors (JVBs) bio-technology based on hesperidium (e.g., pomelo, waxberry, oranges) is first reported for preparation of carbon-based composites with controllable components, adjustable morphologies, and sizes. JVBs serve as miniature reaction vessels that enable sophisticated confined chemical reactions to take place, ultimately resulting in the formations of complex carbon composites. The newly developed approach is highly versatile and can be compatible with a wide range of materials including metals, alloys, and metal compounds. The growth and self-assembly mechanisms of carbon composites via JVBs are explained. For illustration, NiCo alloy nanoparticles are successfully in situ implanted into pomelo vesicles crosslinked carbon (PCC) by JVBs, and their applications as sulfur/carbon cathodes for lithium-sulfur batteries are explored. The well-designed PCC/NiCo-S electrode exhibits superior high-rate properties and enhanced long-term stability. Synergistic reinforcement mechanisms on transportation of ions/electrons of interface reactions and catalytic conversion of lithium polysulfides arising from metal alloy and carbon architecture are proposed with the aid of DFT calculations. The research provides a novel biosynthetic route to rational design and fabrication of carbon composites for advanced energy storage.

A novel [1, 2, 4]triazolo[5,1-b]quinazoline derivative as a fluorescent probe for highly selective detection of Fe3+ ions.

A novel [1, 2, 4]triazolo[5,1-b]quinazoline fluorescent probe (VIi) for Fe3+ was developed, featuring with rapid response (< 5 s) and specific selectivity to Fe3+, low detection limit (1.3 × 10-5 M), as well as the ability to resist interference of chelating agent (e.g. EDTA). VIi-based fluorescent test paper can quickly recognize Fe3+ under irradiation at the wavelength of 365 nm. The fluorescence probe VIi has potential application prospects for the detection of Fe3+ in real circumstance.

Plasma Technology for Advanced Electrochemical Energy Storage.

"Carbon Peak and Carbon Neutrality" is an important strategic goal for the sustainable development of human society. Typically, a key means to achieve these goals is through electrochemical energy storage technologies and materials. In this context, the rational synthesis and modification of battery materials through new technologies play critical roles. Plasma technology, based on the principles of free radical chemistry, is considered a promising alternative for the construction of advanced battery materials due to its inherent advantages such as superior versatility, high reactivity, excellent conformal properties, low consumption and environmental friendliness. In this perspective paper, we discuss the working principle of plasma and its applied research on battery materials based on plasma conversion, deposition, etching, doping, etc. Furthermore, the new application directions of multiphase plasma associated with solid, liquid and gas sources are proposed and their application examples for batteries (e. g. lithium-ion batteries, lithium-sulfur batteries, zinc-air batteries) are given. Finally, the current challenges and future development trends of plasma technology are briefly summarized to provide guidance for the next generation of energy technologies.

Hyphae Carbon Coupled with Gel Composite Assembly for Construction of Advanced Carbon/Sulfur Cathodes for Lithium-Sulfur Batteries.

The design and fabrication of novel carbon hosts with high conductivity, accelerated electrochemical catalytic activities, and superior physical/chemical confinement on sulfur and its reaction intermediates polysulfides are essential for the construction of high-performance C/S cathodes for lithium-sulfur batteries (LSBs). In this work, a novel biofermentation coupled gel composite assembly technology is developed to prepare cross-linked carbon composite hosts consisting of conductive Rhizopus hyphae carbon fiber (RHCF) skeleton and lamellar sodium alginate carbon (SAC) uniformly implanted with polarized nanoparticles (V2O3, Ag, Co, etc.) with diameters of several nanometers. Impressively, the RHCF/SAC/V2O3 composites exhibit enhanced physical/chemical adsorption of polysulfides due to the synergistic effect between hierarchical pore structures, heteroatoms (N, P) doping, and polar V2O3 generation. Additionally, the catalytic conversion kinetics of cathodes are effectively improved by regulating the 3D carbon structure and optimizing the V2O3 catalyst. Consequently, the LSBs assembled with RHCF/SAC/V2O3-S cathode show exceptional cycle stability (capacity retention rate of 94.0% after 200 cycles at 0.1 C) and excellent rate performance (specific capacity of 578 mA h g-1 at 5 C). This work opens a new door for the fabrication of hyphae carbon composites via fermentation for electrochemical energy storage.

Investigation of the Binding Interaction of Mfsd2a with NEDD4-2 via Molecular Dynamics Simulations.

Major facilitator superfamily domain-containing 2a (Mfsd2a) is a sodium-dependent lysophosphatidylcholine cotransporter that plays an important role in maintaining the integrity of the blood-brain barrier and neurological function. Abnormal degradation of Mfsd2a often leads to dysfunction of the blood-brain barrier, while upregulation of Mfsd2a can retrieve neurological damage. It has been reported that Mfsd2a can be specifically recognized and ubiquitinated by neural precursor cell-expressed developmentally downregulated gene 4 type 2 (NEDD4-2) ubiquitin ligase and finally degraded through the proteasome pathway. However, the structural basis for the specific binding of Mfsd2a to NEDD4-2 is unclear. In this work, we combined deep learning and molecular dynamics simulations to obtain a Mfsd2a structure with high quality and a stable Mfsd2a/NEDD4-2-WW3 interaction model. Moreover, molecular mechanics generalized Born surface area (MM-GBSA) methods coupled with per-residue energy decomposition studies were carried out to analyze the key residues that dominate the binding interaction. Based on these results, we designed three peptides containing the key residues by truncating the Mfsd2a sequences. One of them was found to significantly inhibit Mfsd2a ubiquitination, which was further validated in an oxygen-glucose deprivation (OGD) model in a human microvascular endothelial cell line. This work provides some new insights into the understanding of Mfsd2a and NEDD4-2 interaction and might promote further development of drugs targeting Mfsd2a ubiquitination.

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients.

Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.

Interleukin-6 promotes the dedifferentiation of papillary thyroid cancer cells.

Radioiodine treatment is a fundamental therapy for patients with papillary thyroid cancer (PTC). Sodium/iodide symporter (NIS)-mediated iodine uptake is a prerequisite for the efficacy of radioiodine therapy. Interleukin-6 (IL-6) is a pro-tumor cytokine, but its regulation of NIS expression in PTC has not been elucidated. In this study, we found that IL-6 enhanced the proliferation ability of PTC cells. Moreover, the negative association between IL-6 and NIS expression in thyroid cancer tissues was demonstrated. IL-6 downregulated thyroid-specific genes such as NIS, thyroid peroxidase, and thyroid-stimulating hormone receptor and thyroid-specific transcription factors including thyroid transcription factor-1 (TTF-1) and paired box protein-8 (PAX-8). The inhibitory effects of IL-6 on NIS expression were alleviated by mitogen-activated protein kinase and Janus kinase inhibitors. Depletion of c-Jun or STAT3 also rescued IL-6-induced NIS downregulation, with STAT3 depletion exerting a stronger effect. TTF-1 protein expression was also restored by depleting c-Jun or STAT3. STAT3 depletion, but not c-Jun depletion, alleviated the inhibitory effect of IL-6 on PAX-8 expression. Moreover, the downregulation of NIS by IL-6 was rescued by overexpressing TTF-1 and PAX-8. Tocilizumab, an IL-6 receptor blocker, did not have any cytostatic activity in PTC cells, and it also failed to induce redifferentiation in vitro. However, we found that the drug blocked the inhibitory effect of IL-6 on NIS expression. In summary, IL-6 inhibits NIS transcription in PTC cells by activating mitogen-activated protein kinase and Janus kinase signaling.

Clinical characteristics and long-term outcomes for parapharyngeal metastases of well-differentiated thyroid cancer during 131 I therapy and follow-up.

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.

Ultrasound features affecting the sample adequacy after fine-needle aspiration of thyroid nodules with different risk stratification.

BACKGROUND: The inadequacy samples caused by the internal characteristic structure of thyroid nodules are difficult to be solved. OBJECTIVE: To evaluate the ultrasound features affecting the sample adequacy after fine-needle aspiration (FNA) of thyroid nodules with different risk stratification. METHODS: 592 thyroid nodules that underwent ultrasound-guided FNA were included in this retrospective study. The sample obtained by FNA were classified as inadequacy and adequacy according to the cytopathological results. Ultrasound features (ie., size, position, cystic predominance, composition, echo, shape, margin, and superficial annular calcification status) of the nodules were recorded and compared between the inadequacy sample group and adequacy sample group. RESULTS: Multiple logistic regression shows that preponderant cystic proportion (OR, 0.384; P = 0.041), extremely hypoechogenicity and hypoechogenicity (OR, 6.349; P = 0.006) were the independent influencing factors of inadequate samples after FNA in benign expected nodules. In addition, nodule size ≤10 mm (OR, 1.960; P = 0.010) and superficially annular calcification (OR, 4.600; P < 0.001) were independent influencing factors for inadequate samples after FNA in malignant expected nodules. CONCLUSION: The ultrasound features of hypoechogenicity or high cystic proportion in benign expected nodules and that of small size or annular calcification in malignant expected nodules were the risk factors for inadequacy samples by US-guided FNA.

Single-center study of different treatment for advanced or unresectable angiosarcoma patients / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of different medical treatment in advanced or unresectable angiosarcoma. Methods: This study was a single-center retrospective clinical study. Fifty-five advanced or unresectable angiosarcoma patients treated in Sun-Yat Sen University Cancer Center from January 2005 to August 2020 were enrolled. There were 34 patients who received first-line doxorubicin-based chemotherapy (doxorubicin group), 12 patients received first-line doxorubicin or liposome doxorubicin plus paclitaxel or albumin bound paclitaxel chemotherapy (combination therapy group), and 4 patients received first-line paclitaxel-based treatment (paclitaxel group). There were 6 patients who received anti-angiogenesis targeted therapy, another 2 patients received anti-PD-1 antibody plus anti-angiogenesis targeted therapy. Targeted therapy and immunotherapy plus targeted therapy included 5 cases of first-line therapy and 3 cases of second-line therapy. The therapeutic effect was evaluated by RECIST 1.1 standard. The adverse reactions were evaluated by CTCAE4.0 standard. Kaplan-Meier survival analysis was evaluated with Log rank test. Cox proportional hazard model was used to analyze the influencing factors. Results: There were 18 patients achieved partial response (PR) in 34 patients in the doxorubicin group, median progression-free survival (mPFS) was 4.5 months, and median overall survival (mOS) was 15 months. Four patients achieved PR in 12 patients in the combination therapy group, mPFS and mOS were 4 months and 19 months. Two patients achieved PR in 4 patients in the paclitaxel group, mPFS and mOS were 3 months and 9 months. However, only 1 in 6 patients achieved PR for anti-angiogenesis targeted therapy, mPFS and mOS were 3 months and 16 months. Two patients who received anti-PD-1 immunotherapy combined with anti-angiogenesis targeted therapy acquired PR for 17 months and more than 16 months. Median PFS (7.5 months) were longer in those with primary liver, lung and spleen angiosarcoma than in those with other primary site (3.0 months, P=0.028). The mOS (20 months) was longer in females than that in males (12 months, P=0.045). Primary tumor site, sex, age and treatment were not independent prognostic factors for angiosarcoma patients (P>0.05). Grade 3-4 cardiac toxicity was found in 2 patients in the combination therapy group. Conclusions: Doxorubicin-based and paclitaxel-based chemotherapy are the most important treatment for advanced angiosarcoma. Potential efficacy for targeted therapy combined with anti-PD-1 immunotherapy are showed in some patients with long duration of response and moderate adverse event.

Change in Antithyroglobulin Antibody Levels is a Good Predictor of Responses to Therapy in Antithyroglobulin Antibody-Positive Pediatric Papillary Thyroid Carcinoma Patients.

Objective: Antithyroglobulin antibodies (TgAbs) could be used as a surrogate tumor marker of TgAb-positive-differentiated thyroid carcinoma. This study aims to determine whether the change in TgAb levels over time could be used as a predictor of responses to therapy in pediatric papillary thyroid carcinoma (PTC) patients. Methods: We retrospectively analyzed the records of 48 pediatric PTC patients with TgAb levels ≥50 IU/ml 6 months after initial 131I treatment. Suppressed thyroglobulin (Tg) levels 6 months after initial 131I treatment were used to divide the patients into positive Tg (P-Tg, Tg ≥ 0.2 ng/ml) and negative Tg (N-Tg, Tg < 0.2 ng/ml) groups. Responses to therapy were classified as the acceptable response (AR) group and the not acceptable response (NAR) group. Results: Of 48 enrolled patients with 58 months (range, 24-143 months) of follow-up, 28 patients had NAR and 20 patients had AR. TgAb levels were decreasing ≥50% in 28 patients, decreasing <50% in 8 patients, and increasing in 12 patients. Multivariate analysis showed that high initial risk stratification and TgAb levels decreasing <50% or increasing were significantly associated with NAR (p < 0.05). Changes in Tg levels were also associated with NAR in the P-Tg group (p < 0.05). Conclusion: Changes in TgAb levels over time could be used as a predictor of responses to therapy in TgAb-positive pediatric PTC patients. Changes in Tg levels over time are also associated with NAR to therapy in both TgAb-positive and Tg-positive pediatric PTC patients.

Phase I study of pegylated liposomal doxorubicin and cisplatin in patients with advanced osteosarcoma.

PURPOSE: The repeated use of doxorubicin is limited due to dose-limiting cardiac toxicity. Pegylated liposomal doxorubicin (PEG-LD, Duomeisu) has a reduced cardiac toxicity. This phase I study aimed to investigate the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the PEG-LD and cisplatin combination in patients with metastatic and recurrent osteosarcoma. METHODS: Patients were given PEG-LD at a dose of 40, 50, or 60 mg/m2 on day 1 of each 21-day cycle, according to a 3 + 3 approach for dose escalation. Cisplatin was administered as a fixed dose of 100 mg/m2 for every cycle. Toxicities and tumor response were observed. RESULTS: A total of 15 patients were enrolled in this trial, and nine of the patients had received prior doxorubicin. The MTD of PEG-LD was reached at 50 mg/m2 in this regimen, with neutropenic fever and stomatitis as DTLs. The main adverse event (AE) was myelosuppression. The most common non-hematological AEs were vomiting, hypoproteinemia, stomatitis and transient sinus arrhythmia. Grade 3-4 toxicity was neutropenia, leukopenia, thrombocytopenia, anemia and stomatitis in the whole cohort. All the AEs were relieved after symptomatic and supportive treatment. Totally, the overall response rate was 13.3% and disease control rate was 66.7%. For the six patients who have not received prior doxorubicin, one partial response and five stable diseases were observed. CONCLUSION: We provide the data showing that PEG-LD 50 mg/m2 combined with cisplatin 100 mg/m2 demonstrated an acceptable safety profile and promising clinical activity in advanced osteosarcoma, which merits further evaluation in phase II studies. TRIAL REGISTRATION: ChiCTR1900021550.

Pericytes Regulate Cerebral Perfusion through VEGFR1 in Ischemic Stroke.

Neurons in the penumbra (the area surrounding ischemic tissue that consists of still viable tissue but with reduced blood flow and oxygen transport) may be rescued following stroke if adequate perfusion is restored in time. It has been speculated that post-stroke angiogenesis in the penumbra can reduce damage caused by ischemia. However, the mechanism for neovasculature formation in the brain remains unclear and vascular-targeted therapies for brain ischemia remain suboptimal. Here, we show that VEGFR1 was highly upregulated in pericytes after stroke. Knockdown of VEGFR1 in pericytes led to increased infarct area and compromised post-ischemia vessel formation. Furthermore, in vitro studies confirmed a critical role for pericyte-derived VEGFR1 in both endothelial tube formation and pericyte migration. Interestingly, our results show that pericyte-derived VEGFR1 has opposite effects on Akt activity in endothelial cells and pericytes. Collectively, these results indicate that pericyte-specific expression of VEGFR1 modulates ischemia-induced vessel formation and vascular integrity in the brain.

Unexpected Retrosternal Goiter Interpreted as Hyperfunctioning Metastasis on the Posttherapeutic 131I SPECT/CT.

ABSTRACT: We present a 38-year-old man who underwent total thyroidectomy with radical right neck dissection due to papillary thyroid cancer was referred for 131I treatment. The patient was in subclinical hypothyroidism with remarkable stimulated Tg level after 4 weeks of l-thyroxine withdrawal before 131I treatment, which indicated hyperfunctioning metastasis. Posttherapeutic 131I whole-body scan combined with 131I SPECT/CT performed on day 3 after 131I administration revealed an elevated 131I uptake mass in cervicothoracic region. To our surprise, the mass was histologically confirmed to be a retrosternal goiter.