Synthesis and structural characterization of ß -cyclodextrin butenate.

ß-cyclodextrin butenate was synthesized by using N, N'-Carbonyldiimidazole (CDI) activating reagent and 4-Dimethylaminopyridine (DMAP) as catalyst. The best preparation condition of ß-CD butenate was described as below: reaction temperature was 25°C, concentration of 2-butenoic acid was 450 mmol/L, concentration of DMAP was 12.5 mmol/L and reaction time was 20 minutes and at this condition the yield of ß-CD butenate was 0.83 mmol/g. According to the results of FT-IR spectrum, NMR spectroscopy and HPLC-QTof-mass spectrum of ß-CD butenate, there were four types ß-CD butenate synthesized, which were ß-CD-2-butenoic acid monoester, ß-CD-2-butenoic acid diester, ß-CD-2-butenoic acid triester and ß-CD-2-butenoic acid tetraester, respectively.

BMSC reduces ROS and inflammation levels by inhibiting TLR4/MYD88/NF-κB signaling axis to alleviate dry eye.

Objective To investigate the therapeutic effect of Bone marrow mesenchymal stem cells (BMSCs) on dry eye mice, and to investigate the mechanism of TLR4/MYD88/NF-κB signaling pathway on corneal injury repair in dry eye mice. Methods To establish a hypertonic dry eye cell model. Western blot for measureing the protein expressions of caspase-1, IL-1ß，NLRP3 and ASC，and Rt-qpcr for mRNA expression. Flow cytometry for detecting the ROS content and apoptosis rate. CCK-8 for detecting the proliferation activity of cells, and ELISA for the levels of inflammation-related factors.The levels of inflammation-related factors were detected by ELISA. The dry eye mouse model of benzalkonium chloride was established. Three clinical parameters used to evaluate ocular surface damage, namely tear secretion, tear film rupture time and corneal sodium fluorescein staining, were measured with phenol cotton thread. Flow cytometry and TUNEL staining are both for he apoptosis rate. Western blot also for detecting the protein expressions of TLR4, MYD88, NF-κB, inflammation-related factors and apoptosis-related factors . The pathological changes were evaluated by HE and PAS staining. Results In vitro, BMSCs and inhibitors of TLR4, MYD88 and NF-κB showed decreased ROS content, decreased inflammatory factor protein level, decreased apoptotic protein level and increased mRNA expression compared with NaCl group. BMSCS partially reversed cell apoptosis induced by NaCl and improved cell proliferation. In vivo, it reduces corneal epithelial defects, goblet cell loss and inflammatory cytokine production, and increases tear production. In vitro, BMSC and inhibitors of TLR4, MYD88 and NF-κB could protect mice from apoptosis induced by hypertonic stress. In terms of mechanism, NACL-induced NLRP3 inflammasome formation, caspase-1 activation and IL-1ß maturation can be inhibited. Conclusion BMSCs treatment can reduce ROS and inflammation levels and alleviate dry eye by inhibiting TLR4/MYD88/NF-κBsignaling pathway.

Cell penetrating peptides: Highlighting points in cancer therapy.

Cell-penetrating peptides (CPPs), first identified in HIV a few decades ago, deserved great attention in the last two decades; especially to support the penetration of anticancer drug means. In the drug delivery discipline, they have been involved in various approaches from mixing with hydrophobic drugs to the use of genetically conjugated proteins. The early classification as cationic and amphipathic CPPs has been extended to a few more classes such as hydrophobic and cyclic CPPs so far. Developing potential sequences utilized almost all methods of modern science: choosing high-efficiency peptides from natural protein sequences, sequence-based comparison, amino acid substitution, obtaining chemical and/or genetic conjugations, in silico approaches, in vitro analysis, animal experiments, etc. The bottleneck effect in this discipline reveals the complications that modern science faces in drug delivery research. Most CPP-based drug delivery systems (DDSs) efficiently inhibited tumor volume and weight in mice, but only in rare cases reduced their levels and continued further processes. The integration of chemical synthesis into the development of CPPs made a significant contribution and even reached the clinical stage as a diagnostic tool. But constrained efforts still face serious problems in overcoming biobarriers to reach further achievements. In this work, we reviewed the roles of CPPs in anticancer drug delivery, focusing on their amino acid composition and sequences. As the most suitable point, we relied on significant changes in tumor volume in mice resulting from CPPs. We provide a review of individual CPPs and/or their derivatives in a separate subsection.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

TFAP2C inhibits cell autophagy to alleviate myocardial ischemia/reperfusion injury by regulating miR-23a-5p/SFRP5/Wnt5a axis.

Myocardial ischemia/reperfusion (MI/R) injury contributes to severe injury for cardiomyocytes. In this study, we aimed to explore the underlying mechanism of TFAP2C on cell autophagy in MI/R injury. MTT assay measured cell viability. The cells injury was evaluated by commercial kits. IF detected the level of LC3B. Dual luciferase reporter gene assay, ChIP or RIP assay were performed to verify the interactions between crucial molecules. We found that TFAP2C and SFRP5 expression were decreased while miR-23a-5p and Wnt5a increased in AC16 cells in response to H/R condition. H/R induction led to cell injury and induced autophagy, which were reversed by TFAP2C overexpression or 3-MA treatment (an autophagy inhibitor). Mechanistically, TFAP2C suppressed miR-23a expression through binding to miR-23a promoter, and SFRP5 was a target gene of miR-23a-5p. Moreover, miR-23a-5p overexpression or rapamycin reversed the protective impacts of TFAP2C overexpression on cells injury and autophagy upon H/R condition. In conclusion, TFAP2C inhibited autophagy to improve H/R-induced cells injury by mediating miR-23a-5p/SFRP5/Wnt5a axis.

Is Convolutional Neural Network Accurate for Automatic Detection of Zygomatic Fractures on Computed Tomography?

PURPOSE: Zygomatic fractures involve complex anatomical structures of the mid-face and the diagnosis can be challenging and labor-consuming. This research is aimed to evaluate the performance of an automatic algorithm for the detection of zygomatic fractures based on convolutional neural network (CNN) on spiral computed tomography (CT). MATERIALS AND METHODS: We designed a cross-sectional retrospective diagnostic trial study. Clinical records and CT scans of patients with zygomatic fractures were reviewed. The sample consisted of two types of patients with different zygomatic fractures statuses (positive or negative) in Peking University School of Stomatology from 2013 to 2019. All CT samples were randomly divided into three groups at a ratio of 6:2:2 as training set, validation set, and test set, respectively. All CT scans were viewed and annotated by three experienced maxillofacial surgeons, serving as the gold standard. The algorithm consisted of two modules as follows: (1) segmentation of the zygomatic region of CT based on U-Net, a type of CNN model; (2) detection of fractures based on Deep Residual Network 34(ResNet34). The region segmentation model was used first to detect and extract the zygomatic region, then the detection model was used to detect the fracture status. The Dice coefficient was used to evaluate the performance of the segmentation algorithm. The sensitivity and specificity were used to assess the performance of the detection model. The covariates included age, gender, duration of injury, and the etiology of fractures. RESULTS: A total of 379 patients with an average age of 35.43 ± 12.74 years were included in the study. There were 203 nonfracture patients and 176 fracture patients with 220 sites of zygomatic fractures (44 patients underwent bilateral fractures). The Dice coefficientof zygomatic region detection model and gold standard verified by manual labeling were 0.9337 (coronal plane) and 0.9269 (sagittal plane), respectively. The sensitivity and specificity of the fracture detection model were 100% (p＞.05). CONCLUSION: The performance of the algorithm based on CNNs was not statistically different from the gold standard (manual diagnosis) for zygomatic fracture detection in order for the algorithm to be applied clinically.

Tumor Microenvironment-Inspired Glutathione-Responsive Three-Dimensional Fibrous Network for Efficient Trapping and Gentle Release of Circulating Tumor Cells.

Detection of circulating tumor cells (CTCs) is important for early cancer diagnosis, prediction of postoperative recurrence, and individualized treatment. However, it is still challenging to achieve efficient capture and gentle release of CTCs from the complex peripheral blood due to their rarity and fragility. Herein, inspired by the three-dimensional (3D) network structure and high glutathione (GSH) level of the tumor microenvironment (TME), a 3D stereo (3D-G@FTP) fibrous network is developed by combining the liquid-assisted electrospinning method, gas foaming technique, and metal-polyphenol coordination interactions to achieve efficient trapping and gentle release of CTCs. Compared with the traditional 2D@FTP fibrous scaffold, the 3D-G@FTP fibrous network could achieve higher capture efficiency (90.4% vs 78.5%) toward cancer cells in a shorter time (30 min vs 90 min). This platform showed superior capture performance toward heterogeneous cancer cells (HepG2, HCT116, HeLa, and A549) in an epithelial cell adhesion molecule (EpCAM)-independent manner. In addition, the captured cells with high cell viability (>90.0%) could be gently released under biologically friendly GSH stimulus. More importantly, the 3D-G@FTP fibrous network could sensitively detect 4-19 CTCs from six kinds of cancer patients' blood samples. We expect this TME-inspired 3D stereo fibrous network integrating efficient trapping, broad-spectrum recognition, and gentle release will promote the development of biomimetic devices for rare cell analysis.

Clinical application and efficacy analysis of partial cystectomy combined with intravesical chemotherapy in muscle-invasive bladder cancer.

OBJECTIVES: Comparing the long-term tumor control results of partial cystectomy(PC)and radical cystectomy(RC)in the treatment of muscle-invasive bladder cancer, and to explore the feasible method of bladder preservation therapy (BPT)in patients with MIBC. METHODS: We retrospectively analyzed the clinical data of 102 patients with muscle-invasive bladder cancer in our hospital between January 2012 and December 2018, of whom 32 cases in the partial cystectomy group and 70 cases in the radical cystectomy group. We performed a comparative analysis of patient general information, perioperative-related indicators and postoperative follow-up data, comparing OS, PFS, and DSS at 1, 2, 3, 4, and 5 years in both groups, and comparing tumour recurrence and metastasis in postoperative patients. RESULTS: All the 102 cases in this study were successfully completed. Partial cystectomy group and Radical cystectomy group median operating time (169.50(130.00 ~ 225.25) min and 420.00(343.75 ~ 483.75) min, p < 0.001), median intraoperative blood loss was (100(50 ~ 100)ml and 400(200 ~ 1000)ml, p < 0.001), median perioperative blood transfusion volume (0(0 ~ 0)ml and 600(150.00 ~ 906.25)ml, p < 0.001), median total hospital stay (18(14.25 ~ 20.00) and 24.5(20.00 ~ 34.25) days, p < 0.001), median preoperative preparation time (7(4.25 ~ 8.00) and 10(8.00 ~ 13.00) days, p < 0.001), median postoperative hospital stay (9(8.00 ~ 13.50) and 14(11.00 ~ 21.25) days, p < 0.001), the incidence of perioperative blood transfusion was (15.6% and 75.7%, p < 0.001), the incidence of surgical complications was(28.1%(9/32) and 50.0%(35/70), p = 0.033), average hospitalization cost ((26435.76 ± 9877.82) yuan and (58464.36 ± 19753.13) yuan, p < 0.001), the differences were statistically significant (p < 0.05). Perioperative mortality (0 vs. 2.9%(2/70), p = 1), and OS at 1, 2, 3, 4, and 5 years after surgery were (80.0%, 59.8%, 56.1%, 51.0%, 44.6% vs. 76.5%, 67.4%, 64.9%, 57.9%, 52.6%, p = 0.524), PFS (68.2%, 64.6%, 60.3%, 54.8%, 54.8% vs. 82.7%, 78.3%, 75.4%, 67.3%, 62.1%, p = 0.259). DSS (89.9%, 72.4%, 68.6%, 68.6%, 62.4% vs. 87.3%, 83.4%, 80.9%, 73.6%, 68.0%, p = 0.424), and the incidence of tumor recurrence or metastasis was (40.0%(12/30) vs. 25.4%(16/63), p = 0.151), the differences were not statistically significant (p > 0.05). CONCLUSION: In patients with limited solitary T2N0M0 and T3N0M0 muscle-invasive bladder cancer, partial cystectomy plus bladder instillations treatment can achieve comparable tumour control to radical cystectomy. However, patients in the PC group have significant advantages in terms of operative time, intraoperative bleeding, intraoperative and postoperative blood transfusion, preoperative preparation time, total hospital stay, postoperative recovery time, operative costs and operative complications. This option may be considered for such patients with a need for bladder preservation.

Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.

The theranostic value of acetylation gene signatures in obstructive sleep apnea derived by machine learning.

Epigenetic modifications are implicated in the onset and progression of obstructive sleep apnea (OSA) and its complications through their bidirectional relationship with long-term chronic intermittent hypoxia (IH). However, the exact role of epigenetic acetylation in OSA is unclear. Here we explored the relevance and impact of acetylation-related genes in OSA by identifying molecular subtypes modified by acetylation in OSA patients. Twenty-nine significantly differentially expressed acetylation-related genes were screened in a training dataset (GSE135917). Six common signature genes were identified using the lasso and support vector machine algorithms, with the powerful SHAP algorithm used to judge the importance of each identified feature. DSCC1, ACTL6A, and SHCBP1 were best calibrated and discriminated OSA patients from normal in both training and validation (GSE38792) datasets. Decision curve analysis showed that patients could benefit from a nomogram model developed using these variables. Finally, a consensus clustering approach characterized OSA patients and analyzed the immune signatures of each subgroup. OSA patients were divided into two acetylation patterns (higher acetylation scores in Group B than in Group A) that differed significantly in terms of immune microenvironment infiltration. This is the first study to reveal the expression patterns and key role played by acetylation in OSA, laying the foundation for OSA epitherapy and refined clinical decision-making.

The prognostic significance and immune correlation of SLC10A3 in low-grade gliomas revealed by bioinformatic analysis and multiple immunohistochemistry.

PURPOSE: Despite the fact that genetic risk factors contribute to low-grade gliomas (LGGs), the role of critical genes as prognostic and theraputic biomarkers is quite limited. This study is designed to comprehensively investigate the prognostic role and predictive ability of solute carrier family 10 member 3 (SLC10A3) for immunotherapy in LGGs. METHODS: We analyzed the prognostic value of SLC10A3 from multiple datasets of LGG patients, and explored its immune correlation via multiple algorithms. Finally, we independently confirmed the clinical significance and its immune correlation using the multiplex staining assay of LGG samples on the tissue microarray. RESULTS: SLC10A3 mRNA was up-regulated in LGGs compared with normal brain tissues, and correlated with tumor grade, histological type, IDH wide type and non-codel 1p19q. Up-regulation of SLC10A3 transcription was remarkably associated with shortened overall survival time compared with down-regulation in TCGA, CGGA and Rembrandt datasets, and SLC10A3 exhibited good predictive ability for survival outcomes among LGGs. Correlation analyses showed that SLC10A3 mRNA expression correlates well with the six immune check points and immune cells. When the expression and immune correlation of SLC10A3 at the translational level were verified via multiplex immunohistochemistry, expression of SLC10A3 protein was higher in LGG compared with normal tissues, and expression of SLC10A3 protein was correlated well with macrophage, CD4 + T cell and B cell. CONCLUSIONS: Up-regulation of SLC10A3 mRNA is statistically associated with adverse survival outcomes and immune infiltration among LGGs. SLC10A3 might be a reliable survival predictor and a promising immunotherapy target for LGG patients.

Three-Component Electrochemical Aminoselenation of 1,3-Dienes.

Azoles and organoselenium compounds are pharmacologically important scaffolds in medicinal chemistry and natural products. We developed an efficient regioselective electrochemical aminoselenation reaction of 1,3-dienes, azoles, and diselenide derivatives to access selenium-containing allylazoles skeletons. This protocol is more economical and environmentally friendly and features a broad substrate scope; pyrazole, triazole, and tetrazolium were all tolerated under the standard conditions, which could be applied to the expedient synthesis of bioactive molecules and in the pharmaceutical industry.

Mixed Ion/Electron Conductive Li3N-Mo Interphase Enabling Stable and Ultrahigh-Rate Lithium Metal Anodes.

Lithium (Li) metal is a promising anode for high-energy-density batteries; however, its practical viability is hampered by the unstable metal Li-electrolyte interface and Li dendrite growth. Herein, a mixed ion/electron conductive Li3N-Mo protective interphase with high mechanical stability is designed and demonstrated to stabilize the Li-electrolyte interface for a dendrite-free and ultrahigh-current-density metallic Li anode. The Li3N-Mo interphase is simultaneously formed and homogeneously distributed on the Li metal surface by the surface reaction between molten Li and MoN nanosheets powder. The highly ion-conductive Li3N and abundant Li3N/Mo grain boundaries facilitate fast Li-ion diffusion, while the electrochemically inert metal Mo cluster in the mosaic structure of Li3N-Mo inhibits the long-range crystallinity and regulates the Li-ion flux, further promoting the rate capability of the Li anode. The Li3N-Mo/Li electrode has a stable Li-electrolyte interface as manifested by a low Li overpotential of 12 mV and outstanding plating/stripping cyclability for over 3200 h at 1 mA cm-2. Moreover, the Li3N-Mo/Li anode inhibits Li dendrite formation and exhibits a long cycling life of 840 h even at 30 mA cm-2. The full cell assembled with LiFePO4 cathode exhibits stable cycling performance with 87.9% capacity retention for 200 cycles at 1C (1C = 170 mA g-1) as well as high rate capability of 83.7 mAh g-1 at 3C. The concept of constructing a mixed ion/electron conductive interphase to stabilize the Li-electrolyte interface for high-rate and dendrite-free Li metal anodes offers a viable strategy to develop high-performance Li-metal batteries.

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs.

Fibrous dysplasia (FD) is a skeletal stem cell disease caused by mutations in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene, which results in the abnormal accumulation of cyclic adenosine monophosphate (cAMP) and hyperactivation of downstream signaling pathways. Parathyroid hormone-related protein (PTHrP) is secreted by the osteoblast lineage and is involved in various physiological and pathological activities of bone. However, the association between the abnormal expression of PTHrP and FD, as well as its underlying mechanism, remains unclear. In this study, we discovered that FD patient-derived bone marrow stromal cells (FD BMSCs) expressed significantly higher levels of PTHrP during osteogenic differentiation and exhibited greater proliferation capacity but impaired osteogenic ability compared to normal control patient-derived BMSCs (NC BMSCs). Continuous exogenous PTHrP exposure on the NC BMSCs promoted the FD phenotype in both in vitro and in vivo experiments. Through the PTHrP/cAMP/PKA axis, PTHrP could partially influence the proliferation and osteogenesis capacity of FD BMSCs via the overactivation of the Wnt/ß-Catenin signaling pathway. Furthermore, PTHrP not only directly modulated cAMP/PKA/CREB transduction but was also demonstrated as a transcriptional target of CREB. This study provides novel insight into the possible pathogenesis involved in the FD phenotype and enhances the understanding of its molecular signaling pathways, offering theoretical evidence for the feasibility of potential therapeutic targets for FD.

[Recent Advances in SARS-CoV-2-Induced Immune Thrombocytopenia --Review].

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.

Baicalein ameliorates Alzheimer's disease via orchestration of CX3CR1/NF-κB pathway in a triple transgenic mouse model.

Alzheimer's disease (AD) is a common chronic neurodegenerative disease. Some studies have suggested that dysregulation of microglia activation and the resulting neuroinflammation play an important role in the development of AD pathology. Activated microglia have both M1 and M2 phenotypes and inhibition of M1 phenotype while stimulating M2 phenotype has been considered as a potential treatment for neuroinflammation-related diseases. Baicalein is a class of flavonoids with anti-inflammatory, antioxidant and other biological activities, but its role in AD and the regulation of microglia are limited. The purpose of this study was to investigate the effect of baicalein on the activation of microglia in AD model mice and the related molecular mechanism. Our results showed that baicalein significantly improved the learning and memory ability and AD-related pathology of 3 × Tg-AD mice, inhibited the level of pro-inflammatory factors TNF-α, IL-1ß and IL-6, promoted the production of anti-inflammatory factors IL-4 and IL-10, and regulated the microglia phenotype through CX3CR1/NF-κB signaling pathway. In conclusion, baicalein can regulate the phenotypic transformation of activated microglia and reduce neuroinflammation through CX3CR1/NF-κB pathway, thereby improving the learning and memory ability of 3 × Tg-AD mice.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

Multifunctional and Multicolor Perovskite-CdSe Quantum Dots Diodes for Pulse Oximetry.

A conventional pulse oximeter system is composed of two light sources with different peak emission wavelengths and a photodetector. Integrating these three independent components into one single device will absolutely simplify the system design and create a miniaturized size of the product. Here, we demonstrate a bilayer perovskite-CdSe quantum dot (hereafter perovskite-QD) diode capable of voltage-tunable green/red emission and photodetection. The proposed diode also presents an intriguing feature of simultaneous light emission and detection, which is explored as regards the diode being used as a photoconductor when the positive bias is larger than the built-in voltage. The multifunctional and multicolor diode is further employed in a reflective pulse oximeter system, as either the multicolor light sources or the sensing unit in the system provide accepted and trustful results for heart rate and arterial blood oxygenation. Our work provides a possible avenue for the simplification of the pulse oximetry with a compact and miniaturized design in the future.

Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study.

Background: Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC. Methods: The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage. Results: Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P<0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P<0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P<0.001) than the TNM stage. Conclusion: The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.

Research Advances in the Treatment of Bone Marrow Edema Syndrome.

Bone marrow edema syndrome (BMES) is a relatively uncommon clinical condition. It has been poorly reported in the literature. Hence, doctors are not sufficiently aware of the disease and are prone to misdiagnosis and mistreatment, which can undoubtedly prolong the course of the disease, reduce the quality of life of patients and even affect their function. This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc. This informs clinicians in treating bone marrow edema syndrome, hopefully improving patients' quality of life and shortening the duration of their disease.