Publications by authors named "Jin Cao"

236 Publications

GATA binding protein 3 (GATA3) as a marker for metaplastic spindle cell carcinoma of the breast.

Pathol Res Pract 2021 Mar 20;221:153413. Epub 2021 Mar 20.

Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Northwell, United States.

Spindle cell lesions of the breast comprise a diverse set of tumors; harboring significant histological and immunohistochemical (IHC) overlap. Accurate diagnosis and classification of spindle cell lesions in the breast remains challenging, especially in core biopsies. In the current study, we evaluated a spectrum of spindle cell lesion of the breast with a panel of IHC antibodies in an effort to differentiate metaplastic spindle cell carcinoma from its benign and malignant mimickers. Our study included 92 patients who underwent breast core biopsies or breast resections at Northwell Health who were diagnosed with benign and malignant tumor/tumor-like spindle cell lesions. Tumors subtypes in this the study included: angiosarcoma, nodular fasciitis, fibromatosis, myofibroblastoma, phyllodes tumors (benign, borderline and malignant), primary sarcomas and metaplastic spindle cell carcinoma. Our biomarker panel included high molecular weight keratin (HMWK), CAM5.2, AE1/AE3, p63, CD34 and GATA3. GATA3 expression was significantly higher in metaplastic carcinomas (88.9 % vs 4.1 %, p < 0.001), when compared to other spindle cell lesions. The sensitivity and specificity for detecting metaplastic carcinomas reached 84.2 % and 97.3 %, respectively. Regarding cytokeratin panels, none of the three individual markers were as sensitive or specific for metaplastic breast carcinoma. GATA3 is the most specific and sensitive marker forfor the identification of metaplastic spindle cell carcinoma of the breast.
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http://dx.doi.org/10.1016/j.prp.2021.153413DOI Listing
March 2021

Identification and Validation of a Stromal EMT Related LncRNA Signature as a Potential Marker to Predict Bladder Cancer Outcome.

Front Oncol 2021 4;11:620674. Epub 2021 Mar 4.

Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Bladder cancer (BLCA) has become one of the most common malignant tumors in the genitourinary system. BLCA is one of the tumors considered suitable for immunotherapy because of the large proportion of immune cells in TME. Epithelial to mesenchymal transition (EMT) is closely related to tumor immunity through its crosstalk with immune cells. A recent study validated that EMT-related genes were mainly expressed by stromal cells and could influence immunotherapy responsiveness. Stromal EMT-related gene signature was also demonstrated to affect the prognosis of multiple tumors, including BLCA. To further explore the prognostic roles of stromal components, we performed a comprehensive analysis of LncRNAs closely associated with stromal EMT-related genes in the TCGA BLCA cohort. We identified a signature including five stromal EMT gene-related LncRNAs that showed significant prognostic value for BLCA patients. By the CIBERSORT and MCP-COUNTER algorithm, we found the signature was markedly correlated with infiltrated immune cells and stromal components of the tumor microenvironment, which may further influence patient's responsiveness to immune checkpoint blockade therapy. Through immunohistochemical analysis, we confirmed the correlation of the signature with macrophages M2 and CAFs. Meanwhile, key genes related to these LncRNAs, including VIM, MMP2, were also differentially expressed in the stromal components concerning the signature. Our research confirmed the prognostic and immune-associated role of stromal EMT-related LncRNAs. Meantime, we further confirmed that EMT-related genes were mainly expressed in stromal components. Targeting these LncRNAs as well as their related stromal EMT genes may provide potential therapeutic targets for BLCA immunotherapy and precision medicine.
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http://dx.doi.org/10.3389/fonc.2021.620674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970757PMC
March 2021

The significance of enhancer of zeste homolog 2 (EZH2) expression in spindle cell lesions of the breast.

Pathol Int 2021 Mar 17. Epub 2021 Mar 17.

Department of Pathology, Northwell Health Lenox Hill Hospital, New York, NY, USA.

Spindle cell lesions of the breast are rare entities and pose a diagnostic challenge for pathologists due to overlapping morphologic and immunohistochemical features. We evaluated EZH2 expression in various benign (fibromatosis (n = 8), myofibroblastoma (n = 7), neurofibroma (n = 1), nodular fasciitis (n = 5), benign phyllodes tumor (n = 18)) and malignant (malignant phyllodes tumor (n = 8), metaplastic breast carcinoma (n = 16) and angiosarcoma (n = 8)) spindle cell lesions as a potential diagnostic and therapeutic marker. The EZH2 expression was evaluated semi-quantitatively to categorize the cases as 'low' and 'high' expression. All benign lesions showed low EZH2 expression, whereas high EZH2 expression was observed in the majority (28/32; 88%) of malignant lesions. The study results suggest that EZH2 may be used both as an additional diagnostic tool to reach an accurate diagnosis of the spindle cell lesions of the breast and as a therapeutic target for the malignant lesions.
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http://dx.doi.org/10.1111/pin.13093DOI Listing
March 2021

Combined targeting of vascular endothelial growth factor C (VEGFC) and P65 using miR-27b-3p agomir and lipoteichoic acid in the treatment of gastric cancer.

J Gastrointest Oncol 2021 Feb;12(1):121-132

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China.

Background: Gastric cancer is the second leading cancer-related mortality worldwide and more effective treatment strategies are urgently needed to combat the disease. Using lipoteichoic acid (LTA) and miR-27b-3p agomir, we aimed to assess the efficacy of this combination of therapies in treating gastric cancer.

Methods: The RNA levels of miR-27b-3p, FOXO3, MET, KRAS, vascular endothelial growth factor C (VEGFC), TSC1, and P65 were analyzed by quantified-PCR (Q-PCR) and the cell viability of AGS cells was analyzed by MTT. Confirm Luciferase reporter assays were used to explore the putative miR-27b-3p binding sites and Western blot analyzed the protein level of GAPDH, VEGFC, P65, AKT, and phosphorylated-AKT (p-AKT). The level of P65 in both the cytoplasm and nucleus of AGS cells was visualized by immunofluorescence assay. Subcutaneous xenograft models of gastric cancer were established, and mice were treated with miR-27b-3p agomir, LTA, or both. Hematoxylin-eosin staining and Ki-67 immunohistochemistry analysis of tumor tissues were then performed.

Results: The results showed that the decreased expression of miR-27b-3p in gastric cancer cell lines inhibited the viability of AGS cells, and VEGFC was confirmed as the target of miR-27b-3p. In addition, ectopic expression of miR-27b-3p significantly inhibited the AKT pathway in AGS and N87 cells, and LTA suppressed the proliferation of gastric cancer cells by inhibiting the NF-κB pathway. In an established xenograft model, both miR-27b-3p agomir alone and LTA treatment alone inhibited tumor growth and treatment which combined the two showed an even stronger inhibitory effect.

Conclusions: Taken together, the combined use of LTA and miR-27b-3p agomir exhibited a synergistic effect in the treatment of gastric cancer.
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http://dx.doi.org/10.21037/jgo-21-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944161PMC
February 2021

Surgical treatment for insertional Achilles tendinopathy and retrocalcaneal bursitis: more than 1 year of follow-up.

J Int Med Res 2021 Mar;49(3):300060521992959

Centre for Joint Surgery, Southwest Hospital, 12525Third Military Medical University (Army Medical University), Chongqing, China.

Objective: To analyse the imaging changes in bone marrow oedema of the calcaneal prominence, retrocalcaneal bursa and degenerative Achilles tendon after the surgical treatment of insertional Achilles tendinopathy (IAT).

Methods: This retrospective study analysed patients with IAT and retrocalcaneal bursitis that were diagnosed based on their symptoms and radiographic and magnetic resonance imaging (MRI) examinations. For patients that had received 3 months of conservative treatment but still presented with symptoms, arthroscopic debridement of the retrocalcaneal bursa and resection of calcaneal prominence were undertaken. Patients with degeneration of the Achilles tendon underwent debridement of Achilles tendon calcification with an open incision. The last follow-up included radiographic and MRI imaging, Visual Analogue Scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS)-Ankle and Hindfoot scores.

Results: Thirty patients were included (mean ± SD follow-up, 3.1 ± 0.5 years). The VAS pain and AOFAS-Ankle and Hindfoot scores were significantly improved after surgery. MRI showed that bone marrow oedema of the calcaneal prominence and the retrocalcaneal bursa was significantly reduced compared with preoperative values. There was no significant change in the high signal area of the IAT.

Conclusion: Surgical treatment of IAT and retrocalcaneal bursitis effectively alleviated local pain and restored function.
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http://dx.doi.org/10.1177/0300060521992959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944541PMC
March 2021

Phycocyanin Nanoparticle as a Novel Sonosensitizer for Tumor Sonodynamic Therapy of Michigan Cancer Foundation-7 Cells .

J Nanosci Nanotechnol 2021 May;21(5):3035-3040

School of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China.

The development of novel sonosensitizers with safety and efficiency is a key problem in anti-tumor sonodynamic therapy. Phycocyanin (PC) has been proved to have the singlet oxygen radicals (ROS) generation ability, and the potential of PC as a novel sonosensitizer has been investigated. To overcome the disadvantages of PC , such as poor stability and low half-life, PC nanoparticles (PCNP) were prepared by the cross-linking method. According to the results, PCNP has been found with good morphology, good particle size distribution and good stability. Human breast cancer cell line MCF-7 was used to investigate PCNP cell uptake ability. ROS generation and cytotoxicity under ultrasonic irradiation (sonotoxicity) were also studied on this cell. Under the condition of 0.75 w/cm² ultrasound, PCNP has a good ROS productivity and is equivalent to the sonotoxicity of the known sonosensitizer hematoporphyrin monomethyl Ether (HMME). In conclusion, PCNP is expected to be developed as an effective sonosensitizer for the sonodynamic therapy of tumors.
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http://dx.doi.org/10.1166/jnn.2021.19139DOI Listing
May 2021

Facile Fabrication of Flexible Pressure Sensor with Programmable Lattice Structure.

ACS Appl Mater Interfaces 2021 Mar 19;13(8):10388-10396. Epub 2021 Feb 19.

New Materials Institute, Department of Mechanical, Materials and Manufacturing Engineering, University of Nottingham Ningbo China, Ningbo 315100, China.

Flexible pressure sensors have attracted intense attention because of their widespread applications in electronic skin, human-machine interfaces, and healthcare monitoring. Conductive porous structures are always utilized as active layers to improve the sensor sensitivities. However, flexible pressure sensors derived from traditional foaming techniques have limited structure designability. Besides, random pore distribution causes difference in structure and signal repeatability between different samples even in one batch, therefore limiting the batch production capabilities. Herein, we introduce a structure designable lattice structure pressure sensor (LPS) produced by bottom-up digital light processing (DLP) 3D printing technique, which is capable of efficiently producing 55 high fidelity lattice structure models in 30 min. The LPS shows high sensitivity (1.02 kPa) with superior linearity over a wide pressure range (0.7 Pa to 160 kPa). By adjusting the design parameters such as lattice type and layer thickness, the electrical sensitivities and mechanical properties of LPS can be accurately controlled. In addition, the LPS endures up to 60000 compression cycles (at 10 kPa) without any obvious electrical signal degradation. This benefits from the firm carbon nanotubes (CNTs) coating derived from high-energy ultrasonic probe and the subsequent thermal curing process of UV-heat dual-curing photocurable resin. For practical applications, the LPS is used for real time pulse monitoring, voice recognition and Morse code communication. Furthermore, the LPS is also integrated to make a flexible 4 × 4 sensor arrays for detecting spatial pressure distribution and a flexible insole for foot pressure monitoring.
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http://dx.doi.org/10.1021/acsami.0c21407DOI Listing
March 2021

Bone Marrow Edema Syndrome of the Foot Treated with Extracorporeal Shock Wave Therapy: A Retrospective Case Series.

J Foot Ankle Surg 2020 Oct 7. Epub 2020 Oct 7.

Associate Professor, Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address:

To determine the validity and safety of extracorporeal shock wave therapy (ESWT) in the treatment of bone marrow edema syndrome (BMES) of the foot. Patients diagnosed as foot BMES in our Center were followed and treated by ESWT for 1 to 2 courses. The target of the ESWT treatment was the most obvious foot tenderness, or the most obvious part of bone edema on magnetic resonance imaging (MRI). One course of ESWT was 1 time/week, 5 times in total, with the shock wave energy flow density 0.18 mJ/mm. The visual analog scale (VAS) and the American Orthopedic Foot and Ankle Society (AOFAS) scores of the foot were recorded before treatment, at 3 months after treatment and the last follow-up; the areas of BME before treatment and at the last follow-up were measured by the fat suppression MRI. Complications during treatment were also recorded. Twenty follow-up patients were obtained. Compared with the pretreatment, the patients had significant improvement in various indicators at 3 months after treatment (p < 0.01). The sagittal MRI at the last follow-up showed that the BME area decreased significantly (p < 0.01). Two patients developed transient erythema on their skin after treatment and alleviated after 2 days of rest. No serious complications were found during treatment. Our findings show that for patients with foot BMES, the use of ESWT treatment can effectively relieve local pain, improve the motor function of the foot and ankle. Two courses of treatment may be required for some patients.
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http://dx.doi.org/10.1053/j.jfas.2020.10.007DOI Listing
October 2020

Protein-Activatable Diarylethene Monomer as a Smart Trigger of Noninvasive Control Over Reversible Generation of Singlet Oxygen: A Facile, Switchable, Theranostic Strategy for Photodynamic-Immunotherapy.

J Am Chem Soc 2021 Feb 28;143(5):2413-2422. Epub 2021 Jan 28.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 120-750, Korea.

The development of activatable photosensitizers to allow for the reversible control of singlet oxygen (O) production for photodynamic therapy (PDT) faces great challenges. Fortunately, the flourishing field of supramolecular biotechnology provides more effective strategies for activatable PDT systems. Here, we developed a new reversible PDT on a switch that controls the O generation of self-assembled albumin nanotheranostics in vitro and in vivo. A new molecular design principle of aggregation-induced self-quenching photochromism and albumin on-photoswitching was demonstrated using a new asymmetric, synthetic diarylethene moiety . The photosensitizer porphyrin and were incorporated as building blocks in a glutaraldehyde-induced covalent albumin cross-linking nanoplatform, (NPs). More importantly, the excellent photoswitching property of enables the resultant nanoplatform to act as a facile, switchable strategy for photodynamic-immunotherapy.
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http://dx.doi.org/10.1021/jacs.0c12851DOI Listing
February 2021

Ultrasound-Mediated Long-Circulating Nanopolymer Delivery of Therapeutic siRNA and Antisense MicroRNAs Leads to Enhanced Paclitaxel Sensitivity in Epithelial Ovarian Cancer Chemotherapy.

ACS Biomater Sci Eng 2020 07 3;6(7):4036-4050. Epub 2020 Jun 3.

Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Epithelial ovarian cancer (EOC) is one of the leading malignant tumors that seriously threaten women's health. The development of new drugs or increasing the sensitivities of current chemotherapy drugs is critically needed. The purpose of this study was to assess the synergistic effects of two silencing RNAs [salt-inducible kinase 2 (SIK2) siRNA and antisense-microRNA21 (anti-miR21)] encapsulated in long-circulating folate-lipid-poly(lactic--glycolic acid) (PLGA) hybrid nanopolymers (FaLPHNPs) administered using an ultrasound- and microbubble (US-MB)-mediated approach to sensitize human EOC xenografts to paclitaxel (PTX). In the assays, this lipid-PLGA hybrid nanopolymer exhibited an extended circulation profile (: ∼8.5 h); US-MB-mediated complementary delivery of FaLPHNPs resulted in a significant reduction in EOC cell (OVCR3, A2780, and SKOV3) proliferation. , there was a 2.5-fold increase ( < 0.05) in RNA delivery in EOC xenografts, which resulted in a notable inhibition of tumor growth compared with that in the non-ultrasound-mediated and PTX alone-treated controls. We validated the therapeutic roles of SIK2, the target gene in treating advanced ovarian cancer, and anti-miR21 by evaluating the significant inhibition of tumor growth upon SIK2 silencing and inhibition of endogenous miR21 function. In summary, the results of this study revealed that US-MB-mediated codelivery of SIK2 siRNA, and anti-miR21 encapsulated in a folate-lipid-PLGA hybrid polymer nanoparticle could significantly improve the sensitivity of EOC tumors to PTX and is a highly effective approach for treating EOC in complementary experiments. Further research of this strategy could lead to better treatment results for patients with EOC.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00330DOI Listing
July 2020

Visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system against immune-associated nephropathy without glucocorticoid side effect.

Theranostics 2021 1;11(6):2670-2690. Epub 2021 Jan 1.

Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Glucocorticoids are widely used in the treatment of nephritis, however, its dose-dependent side effects, such as the increased risk of infection and metabolic disturbances, hamper its clinical use. This study reports a visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system (named as Dex/PFP@LIPs-BMS-α), which specific delivers dexamethasone (Dex) to podocyte targets and reduces systemic side effects. The glucocorticoid nano-delivery system was synthesized by a lipid thin film and a simple facile acoustic-emulsification method. This glucocorticoid nano-delivery system used BMS-470539 (BMS-α), a synthetic compound, as a "navigator" to specifically identify and target the melanocortin-1 receptor (MC-1R) on podocytes. The loaded perfluoropentane (PFP) realizes the directed "explosion effect" through ultrasound-targeted microbubble destruction (UTMD) technology under the coordination of low intensity focused ultrasound (LIFU) to completely release Dex. Both and experiments have demonstrated that Dex/PFP@LIPs-BMs-α accurately gathered to podocyte targets and improved podocyte morphology. Moreover, , proteinuria and serum creatinine levels were significantly reduced in the group treated with Dex/PFP@LIPs-BMS-α, and no severe side effects were detected. Furthermore, Dex/PFP@LIPs-BMS-α, with capabilities of ultrasound, photoacoustic and fluorescence imaging, provided individualized visual guidance and the monitoring of treatment. This study provides a promising strategy of Dex/PFP@LIPs-BMS-α as effective and safe against immune-associated nephropathy.
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http://dx.doi.org/10.7150/thno.53083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806481PMC
January 2021

Proliferation ability of particulated juvenile allograft cartilage.

J Orthop Surg Res 2021 Jan 14;16(1):56. Epub 2021 Jan 14.

Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Background: Particulated juvenile allograft cartilage (PJAC) has a good short-term clinical efficacy in repairing articular cartilage defects, but the proliferation ability of PJAC and the biological characteristics of transplanted cells after transplantation are still unclear.

Purpose: To study the cartilage proliferation ability of PJAC in repairing full-thickness cartilage defects and the reasons for proliferation to provide experimental evidence for its clinical application.

Study Design: Controlled laboratory study.

Methods: Twenty Guizhou minipigs were randomly divided into the experimental group and control group. In all minipigs, an 8-mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of one knee. The experimental group received PJAC transplantation from five juvenile donors of Guizhou minipigs (PJAC group; n = 10) and the control group received transplantation of autologous cartilage chips (ACC group; n = 10). Both groups were followed at 1 and 3 months after surgery, immunohistochemical evaluation of the tissue sections Ki-67 and Lin28 was conducted, the positive rate was calculated according to the staining, and the proliferation ability of PJAC was analyzed.

Results: All 20 Guizhou minipigs were followed, and there was no infection or incision healing disorder after surgery. By Ki-67 and Lin28 immunohistochemical tests, the positive rate of Ki-67 was 88.9 ± 0.2% in the PJAC group and 28.3 ± 3.6% in the ACC group at 1 month, and the difference was statistically significant (P < 0.05); the positive rate of Lin28 was 34.6 ± 3.3% in the PJAC group and 7.6 ± 1.4% in the ACC group at 1 month, and the difference was statistically significant (P < 0.05). At 3 months, the positive rates of Ki-67 in the PJAC group and ACC group were 53.6 ± 6.9% and 1.97 ± 0.3%, respectively (P < 0.05); the positive rates of Lin28 were 86.6 ± 3.3% and 1.4 ± 0.3%, respectively (P < 0.01).

Conclusion: A large animal model was established with Guizhou minipigs, and the expressions of Ki-67 protein and Lin28 protein detected by immunohistochemistry in the repaired transplanted tissue of the PJAC group were stronger than those of adult cartilage. The proliferation of PJAC within 3 months of transplantation was stronger than that of adult cartilage. The enhanced expression of Lin28 may be one of the mechanisms by which PJAC achieved stronger proliferation ability than adult cartilage. PJAC technology has shown good application prospects for repairing cartilage defects.
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http://dx.doi.org/10.1186/s13018-020-02199-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809761PMC
January 2021

Endoscopic Treatment of Symptomatic Foot and Ankle Bone Cyst with 3D Printing Application.

Biomed Res Int 2020 26;2020:8323658. Epub 2020 Dec 26.

Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Objective: To study the efficacy of arthroscopy for treating symptomatic bone cysts of the foot and ankle through the follow-up of patients and to further explore the application value of 3D printing technology in this treatment.

Methods: Twenty-one patients with symptomatic bone cysts in the foot and ankle who underwent arthroscopic surgery in our Center from March 2010 to December 2018 were enrolled, including 11 in the experimental group and 10 in the control group. For the control group, C-arm fluoroscopy was used intraoperatively to confirm the positioning of the cysts; for the experimental group, a 3D model of the lesion tissue and the 3D-printed individualized guides were prepared to assist the positioning of the cysts. Debridement of the lesion tissues was conducted under an arthroscope. Regular follow-ups were conducted. The time of establishing arthroscopic approaches and the times of intraoperative fluoroscopy between the two groups were compared. Significance was determined as < 0.05.

Results: The postoperative pathology of the patients confirmed the diagnosis. No significant perioperative complications were observed in either group, and no recurrence of bone cysts was seen at the last follow-up. The VAS scores and AOFAS scores of the two groups at the last follow-up were significantly improved compared with the preoperative data, but there was no statistical difference between the two groups. All surgeries were performed by the same senior surgeon. The time taken to establish the arthroscopic approaches between the two groups was statistically significant ( < 0.001), and the times of intraoperative fluoroscopy required to establish the approach were also statistically significant ( < 0.001). The intraoperative bleeding between the two groups was statistically significant ( < 0.01). There was 1 case in each group whose postoperative CT showed insufficient bone grafting, but no increase in cavity volume was observed during the follow-up.

Conclusion: With the assistance of the 3D printing technology for treating symptomatic bone cysts of the ankle and foot, the surgeon can design the operation preoperatively and perform the rehearsal, which would make it easier to establish the arthroscopic approach, better understand the anatomy, and make the operation smoother. This trial is registered with http://www.clinicaltrials.govNCT03152916.
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http://dx.doi.org/10.1155/2020/8323658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781683PMC
December 2020

Increased photodynamic therapy sensitization in tumors using a nitric oxide-based nanoplatform with ATP-production blocking capability.

Theranostics 2021 1;11(4):1953-1969. Epub 2021 Jan 1.

Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P. R. China.

Photodynamic therapy (PDT) efficacy in cancer cells is affected by sub-physiological hypoxia caused by dysregulated and "chaotic" tumor microvasculature. However, current traditional O-replenishing strategies are undergoing their own intrinsic deficiencies. In addition, resistance mechanisms activated during PDT also lead the present situation far from satisfactory. We propose a nitric oxide (NO)-based theranostic nanoplatform by using biocompatible poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) as carriers, in which the outer polymeric layer embeds chlorin e6 (Ce6) and incorporates L-Arginine (L-Arg). This nanoplatform (L-Arg@Ce6@P NPs) can reduce hyperactive O metabolism of tumor cells by NO-mediated mitochondrial respiration inhibition, which should raise endogenous O tension to counteract hypoxia. Furthermore, NO can also hinder oxidative phosphorylation (OXPHOS) which should cause intracellular adenosine triphosphate (ATP) depletion, inhibiting tumor cells proliferation and turning cells more sensitive to PDT. When the L-Arg@Ce6@P NPs accumulate in solid tumors by the enhanced permeability and retention (EPR) effect, locally released L-Arg is oxidized by the abundant HO to produce NO. experiments suggest that NO can retard hypoactive O metabolism and save intracellular O for enhancing PDT efficacy under NIR light irradiation. Also, lower intracellular ATP hinders proliferation of DNA, improving PDT sensitization. PDT phototherapeutic efficacy increased by combining these two complementary strategies . We show that this NO-based nanoplatform can be potentially used to alleviate hypoxia and sensitize tumor cells to amplify the efficacy of phototherapy guided by photoacoustic (PA) imaging.
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http://dx.doi.org/10.7150/thno.52997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778583PMC
January 2021

Androgen Receptor Immunohistochemical Expression in Undifferentiated/Dedifferentiated Endometrial Carcinoma.

Int J Gynecol Pathol 2021 Jan 4;Publish Ahead of Print. Epub 2021 Jan 4.

Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell School of Medicine, Hempstead, New York.

Uterine undifferentiated (UC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They tend to pursue an aggressive clinical course with an advanced stage at presentation. It was discovered that androgen receptor (AR) might play a role as a prognostic and therapeutic marker in endometrial carcinoma. However, its expression in UC/DEAC has not been investigated. Herein, the aim of this study is to evaluate the expression of AR along with estrogen receptor (ER), progestin receptor (PR), and HER2 in UC/DEAC and also in other subtypes of high-grade endometrial carcinomas. Review of our pathology database over the period of 2011 to 2019 identified 16 UC/DEAC cases (N=16). We also randomly selected other high-grade endometrial carcinomas including FIGO 3 endometrioid carcinoma (N=9), serous carcinoma (N=8), clear cell carcinoma (N=12) and carcinosarcoma (N=10) for comparison. Immunohistochemical stains for AR, ER, PR, and HER2 were performed on all 55 cases. The protein expression was evaluated both quantitatively and qualitatively. In DEAC cases both the undifferentiated component and the well-differentiated component were recorded separately. Overall, variable degrees of AR reactivity (by Allred scoring method) was present in 63% of UC/DEACs(10/16), 67% of FIGO 3 endometrioid carcinomas (6/9), 88% of serous carcinomas (7/8), 80% of carcinosarcomas (8/10), and 9% of clear cell carcinoma (1/12). AR expression was most often seen with PR (70%) or ER (60%) staining in UC/DEACs. Thirteen cases of UC/DEACs were positive for at least 1 hormonal receptor. HER2 was negative in all UC/DEACs. Almost all other high-grade carcinoma cases were negative for HER2 except 20% carcinosarcoma (2/10) and 13% of serous carcinoma (1/8) which showed 3+ HER2. Loss of AR appears to be associated with worse clinicopathologic parameters in UC/DEAC. AR is highly expressed in UC/DEAC, and in the majority of FIGO 3 endometrioid carcinomas, serous carcinomas, and carcinosarcoma. These findings suggest a potential role for androgen inhibitors in management of patients with these tumors.
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http://dx.doi.org/10.1097/PGP.0000000000000756DOI Listing
January 2021

Traditional Chinese Medicine guidelines for coronavirus disease 2019.

J Tradit Chin Med 2020 12;40(6):891-896

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Objective: To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of coronavirus disease 2019 (COVID-19) and provide timely clinical practice guidance.

Methods: The guidelines were developed in accordance with the World Health Organization rapid guideline process. The evidence on TCM for COVID-19 from published guidelines, direct and indirect published clinical evidence, first hand clinical data, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation (GRADE) method was used to grade the evidence and make the recommendations.

Results: Based on the available evidence, the guidelines recommended 17 Chinese medicines for COVID-19: 2 Chinese herbal granules, 7 Chinese patent medicines, and 8 Chinese herbal injections.

Conclusion: As the literature search was conducted on March, any subsequent versions of these guidelines require an up-to-date literature review. We hope that the evidence summary in these will be helpful in global efforts to address COVID-19.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20200902.001DOI Listing
December 2020

Magnetic resonance imaging for chronic pain: diagnosis, manipulation, and biomarkers.

Sci China Life Sci 2020 Nov 23. Epub 2020 Nov 23.

CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, 100101, China.

Pain is a multidimensional subjective experience with biological, psychological, and social factors. Whereas acute pain can be a warning signal for the body to avoid excessive injury, long-term and ongoing pain may be developed as chronic pain. There are more than 100 million people in China living with chronic pain, which has raised a huge socioeconomic burden. Studying the mechanisms of pain and developing effective analgesia approaches are important for basic and clinical research. Recently, with the development of brain imaging and data analytical approaches, the neural mechanisms of chronic pain have been widely studied. In the first part of this review, we briefly introduced the magnetic resonance imaging and conventional analytical approaches for brain imaging data. Then, we reviewed brain alterations caused by several chronic pain disorders, including localized and widespread primary pain, primary headaches and orofacial pain, musculoskeletal pain, and neuropathic pain, and present meta-analytical results to show brain regions associated with the pathophysiology of chronic pain. Next, we reviewed brain changes induced by pain interventions, such as pharmacotherapy, neuromodulation, and acupuncture. Lastly, we reviewed emerging studies that combined advanced machine learning and neuroimaging techniques to identify diagnostic, prognostic, and predictive biomarkers in chronic pain patients.
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http://dx.doi.org/10.1007/s11427-020-1822-4DOI Listing
November 2020

A multimodal imaging-guided nanoreactor for cooperative combination of tumor starvation and multiple mechanism-enhanced mild temperature phototherapy.

Biomater Sci 2020 Dec 14;8(23):6561-6578. Epub 2020 Oct 14.

Institute of Ultrasound Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown great promise for cancer treatment in many preclinical studies. This study reports a nanoreactor designed for an enhanced mild temperature phototherapy which utilizes multiple mechanisms including simultaneous glucose consumption, oxygen supply, glutathione (GSH) depletion and heat-resistance relief. The nanoreactor is prepared using an Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme with an intrinsic catalase-like activity coloaded with glucose oxidase (GOx) and indocyanine green (ICG). Evidence shows that glucose plays a vital role in tumor progression. Initiated by the breakdown of glucose into gluconic acid and HO by GOx, Fe-PDAP promotes reoxygenation by catalyzing the reaction-supplied and tumor cell-supplied HO into O, which then enhances the O-dependent PDT. Moreover, Fe-PDAP depletes GSH in tumor cells for more efficient reactive oxygen species (ROS) production. Meanwhile, the heat resistance of tumor cells is relieved by GOx-induced glucose exhaustion and heat shock protein (HSP) reduction, improving the efficiency of PTT. In particular, the nanoreactor also serves as a contrast agent for fluorescence, photoacoustic, and magnetic resonance multimodal imaging. Consequently, this nanoreactor efficiently inhibits tumor growth through mild temperature phototherapy under multimodal imaging guidance, resulting in successful tumor ablation with minimal systemic toxicity.
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http://dx.doi.org/10.1039/d0bm01350aDOI Listing
December 2020

Development of Rapid Advice Guidelines for the Treatment of Coronavirus Disease 2019 with Traditional Chinese Medicine.

Am J Chin Med 2020 5;48(7):1511-1521. Epub 2020 Nov 5.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China.

The worldwide spread of the 2019 novel coronavirus has become a profound threat to human health. As the use of medication without established effectiveness may result in adverse health consequences, the development of evidence-based guidelines is of critical importance for the clinical management of coronavirus disease (COVID-19). This research presents methods used to develop rapid advice guidelines on treating COVID-19 with traditional Chinese medicine (TCM). We have followed the basic approach for developing WHO rapid guidelines, including preparing, developing, disseminating and updating each process. Compared with general guidelines, this rapid advice guideline is unique in formulating the body of evidence, as the available evidence for the treatment of COVID-19 with TCM is from either indirect or observational studies, clinical first-hand data together with expert experience in patients with COVID-19. Therefore, our search of evidence not only focuses on clinical studies of treating COVID-19 with TCM but also of similar diseases, such as pneumonia and influenza. Grading of recommendations assessment, development and evaluation (GRADE) methodology was adopted to rate the quality of evidence and distinguish the strength of recommendations. The overall certainty of the evidence is graded as either high, moderate, low or very low, and to give either "strong" or "weak" recommendations of each TCM therapy. The output of this paper will produce the guideline on TCM for COVID-19 and will also provide some ideas for evidence collection and synthesis in the future development of rapid guidelines for COVID-19 in TCM as well as other areas.
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http://dx.doi.org/10.1142/S0192415X20500743DOI Listing
December 2020

Cancer stem cells and strategies for targeted drug delivery.

Drug Deliv Transl Res 2020 Oct 23. Epub 2020 Oct 23.

College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA.

Cancer stem cells (CSCs) are a small proportion of cancer cells with high tumorigenic activity, self-renewal ability, and multilineage differentiation potential. Standard anti-tumor therapies including conventional chemotherapy, radiation therapy, and molecularly targeted therapies are not effective against CSCs, and often lead to enrichment of CSCs that can result in tumor relapse. Therefore, it is hypothesized that targeting CSCs is key to increasing the efficacy of cancer therapies. In this review, CSC properties including CSC markers, their role in tumor growth, invasiveness, metastasis, and drug resistance, as well as CSC microenvironment are discussed. Further, CSC-targeted strategies including the use of targeted drug delivery systems are examined.
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http://dx.doi.org/10.1007/s13346-020-00863-9DOI Listing
October 2020

Artificial Nanotargeted Cells with Stable Photothermal Performance for Multimodal Imaging-Guided Tumor-Specific Therapy.

ACS Nano 2020 10 1;14(10):12652-12667. Epub 2020 Oct 1.

Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.

Organic-inorganic hybrid materials have drawn increasing attention as photothermal agents in tumor therapy due to the advantages of green synthesis, high loading efficiency of hydrophobic drugs, facile incorporation of theranostic iron, and excellent photothermal efficiency without inert components or additives. Herein, we proposed a strategy for biomimetic engineering-mediated enhancement of photothermal performance in the tumor microenvironment (TME). This strategy is based on the specific characteristics of organic-inorganic hybrid materials and endows these materials with homologous targeting ability and photothermal stability in the TME. The hybrid materials perform the functions of cancer cells to target homolytic tumors (acting as "artificial nanotargeted cells (ANTC)"). Inspired by the pH-dependent disassembly behaviors of tannic acid (TA) and ferric ion (Fe) and subsequent attenuation of photothermal performance, cancer cell membranes were self-deposited onto the surfaces of protoporphyrin-encapsulated TA and Fe nanoparticles to achieve ANTC with TME-stable photothermal performance and tumor-specific phototherapy. The resulting ANTC can be used as contrast agents for concurrent photoacoustic imaging, magnetic resonance imaging, and photothermal imaging to guide the treatment. Importantly, the high loading efficiency of protoporphyrin enables the initiation of photodynamic therapy to enhance photothermal therapeutic efficiency, providing antitumor function with minimal side effects.
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http://dx.doi.org/10.1021/acsnano.0c00771DOI Listing
October 2020

Donor Cell Fate in Particulated Juvenile Allograft Cartilage for the Repair of Articular Cartilage Defects.

Am J Sports Med 2020 11 23;48(13):3224-3232. Epub 2020 Sep 23.

Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Background: Particulated juvenile allograft cartilage (PJAC) has demonstrated good clinical efficacy in repairing articular cartilage defects, but the related repair mechanism after transplant and the biological characteristics of the transplanted cells are still unclear.

Purpose: To study the efficacy of PJAC in repairing full-thickness cartilage defects and the specific fate of donor cells to provide experimental evidence for its clinical application.

Study Design: Controlled laboratory study.

Methods: Twenty female Guizhou minipigs were randomly divided into an experimental group and a control group. An 8-mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of 1 knee in all minipigs. The experimental group received transplant of PJAC from 5 male juvenile Guizhou minipigs (PJAC group; n = 10) and the control group received autologous cartilage chips (ACC group; n = 10). Follow-up assessments were conducted at 1 month and 3 months to track the transplanted cells by the male-specific sex-determining region Y-linked (SRY) gene; tissue sections were hybridized in situ, and O'Driscoll histological scoring was performed according to hematoxylin and eosin staining, safranin O and fast green staining, and toluidine blue O staining, as well as immunohistochemical evaluation of aggrecan and Sry-type HMG-box 9 (SOX9).

Results: All 20 Guizhou minipigs were followed; no infection or incision healing disorder occurred after the operation. By SRY in situ hybridization, the SRY signal of the transplanted cells was positive in the repaired tissue of the defect, and the SRY positive signal could still be detected in repaired tissue at 3 months postoperatively. The average number of positive cells was 68.6 ± 11.91 at 1 month and 32.6 ± 3.03 at 3 months (confocal microscope: ×400), and the difference was statistically significant. The O'Driscoll histological scores were 14 ± 0.71 in the ACC group and 9.8 ± 0.84 in the PJAC group at 1 month, and 18 ± 1.20 in the ACC group and 17.4 ± 1.14 in the PJAC group at 3 months. The scores were statistically significant between the ACC group and PJAC group at 1 month. The positive rates of SOX9 in the PJAC and ACC groups at 1 month were 67.6% ± 3.78% and 63.4% ± 5.30%, respectively, and the difference was not statistically significant ( > .05). The positive rates of SOX9 in the PJAC and ACC groups at 3 months were 68.8% ± 2.69% and 17.1% ± 1.26%, respectively, and the difference was statistically significant ( < .05). The positive rates of aggrecan in the PJAC and ACC groups at 1 month were 40.5% ± 2.78% and 42.4% ± 0.54% respectively, and the difference was not statistically significant ( > .05). The positive rates of aggrecan in the PJAC and ACC groups at 3 months were 40.8% ± 1.50% and 30.1% ± 2.44%, respectively, and the difference was not statistically significant ( > .05).

Conclusion: An animal model was established with Guizhou minipigs, and the cartilage defect was repaired with PJAC from male minipigs. The SRY gene positive signal could be detected from the repaired tissue by in situ hybridization, indicating that the transplanted cells survived at least 3 months. The key genes of cartilage formation, SOX9 and aggrecan, were expressed at 1 month and 3 months, and SOX9 expression was stronger in the PJAC group than the ACC group at 3 months.

Clinical Relevance: This study suggests that it is feasible to study the biological characteristics of transplanted cells in the cartilage region by the sex-determining gene.
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http://dx.doi.org/10.1177/0363546520958700DOI Listing
November 2020

[Measurement of femoral neck anteversion of developmental dislocation of hip in children by 3D printing technique].

Zhongguo Gu Shang 2020 Aug;33(8):741-4

Department of Orthopaedics, Ningbo No.6 Hospital, Ningbo 315040, Zhejiang, China.

Objective: To explore the method and accuracy of measuring the femoral neck anteversion in children with developmental dislocation of the hip by using 3D printing technology, so as to find out the method of measuring the femoral neck anteversion accurately and guide the formulation of the operation plan.

Methods: From June 2016 to September 2018, 17 patients with unilateral developmental dislocation of the hip were enrolled in the study, including 2 males and 15 females, aged 2 to 13 (5.47±0.81) years old, 11 on the left and 6 on the right. The methods of CT, 3D printing and intraoperative anteversion of femoral neck were used to measure the anteversion of femoral neck respectively. The intraoperative measurement was used as the standard reference value forstatistical analysis, and the accuracy of the first two methods was compared.

Results: The average value of CT was (36.00±1.66)°, the average value of model method was(43.91±1.62)°, and the average value of intraoperative method was(44.21±1.62)°. There were significant differences in CT measurement, model measurement and intraoperative measurement(<0.05). There was no significant difference between model method and intraoperative method (>0.05).

Conclusion: Compared with the traditional CT method, the 3D printing model method is simpler, more accurate and more repeatable, and can simulate the operation before operation. It is an ideal method to measure the femoral neck anteversion.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2020.08.011DOI Listing
August 2020

Iron(II) phthalocyanine Loaded and AS1411 Aptamer Targeting Nanoparticles: A Nanocomplex for Dual Modal Imaging and Photothermal Therapy of Breast Cancer.

Int J Nanomedicine 2020 11;15:5927-5949. Epub 2020 Aug 11.

Department of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China.

Purpose: A multi-functional nanoplatform with diagnostic imaging and targeted treatment functions has aroused much interest in the nanomedical research field and has been paid more attention in the field of tumor diagnosis and treatment. However, some existing nano-contrast agents have encountered difficulties in different aspects during clinical promotion, such as complicated preparation process and low specificity. Therefore, it is urgent to find a nanocomplex with good targeting effect, high biocompatibility and significant therapeutic effect for the integration of diagnosis and treatment and clinical transformation.

Materials And Methods: Nanoparticles (NPs) targeting breast cancer were synthesized by phacoemulsification which had liquid fluorocarbon perfluoropentane(PFP) in the core and were loaded with Iron(II) phthalocyanine (FePc) on the shell. The aptamer (APT) AS1411 was outside the shell used as a molecular probe. Basic characterization and targeting abilities of the NPs were tested, and their cytotoxicity and biological safety in vivo were evaluated through CCK-8 assay and blood bio-chemical analysis. The photoacoustic (PA) and ultrasound (US) imaging system were used to assess the effects of AS1411-PLGA@FePc@PFP (A-FP NPs) as dual modal contrast agent in vitro and in vivo. The effects of photothermal therapy (PTT) in vitro and in vivo were evaluated through MCF-7 cells and tumor-bearing nude mouse models.

Results: A-FP NPs, with good stability, great biocompatibility and low toxicity, were of 201.87 ± 1.60 nm in diameter, and have an active targeting effect on breast cancer cells and tissues. With the help of PA/US imaging, it was proved to be an excellent dual modal contrast agent for diagnosis and guidance of targeted therapy. Meanwhile, it can heat up under near-infrared (NIR) laser irradiation and has achieved obvious antitumor effect both in vitro and in vivo experiments.

Conclusion: As a kind of nanomedicine, A-FP NPs can be used in the integration of diagnosis and treatment. The treatment effects and biocompatibility in vivo may provide new thoughts in the clinical transformation of nanomedicine and early diagnosis and treatment of breast cancer.
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http://dx.doi.org/10.2147/IJN.S254108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429213PMC
November 2020

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma.

Appl Immunohistochem Mol Morphol 2021 03;29(3):201-208

Department of Pathology and Laboratory Medicine, Zucker School of Medicine at Hofstra Northwell, Hempstead, NY.

Colorectal cancer is a heterogenous disease with striking biological diversity. Colorectal carcinoma (CRC) is one of the most common malignancies, accounting for over 9% of all cancers worldwide. To put it in perspective, 5% of people will develop CRC in their lifetime. Biomarkers specific to a particular cancer type can assist in the evaluation of survival probability and help clinicians assess treatment modalities, an example being programmed death ligand-1 (PD-L1). With regards to PD-L1, this is the first study to evaluate the SP-142 antibody clone in CRC. The Ventana PD-L1 (SP-142) assay for PD-L1 expression identifies patients who may benefit from treatment with atezolizumab. SP-142 was chosen as large stage 3 clinical trials are being undertaken with atezolizumab in CRC. Indoleamine 2,3-dioxygenase (IDO-1) was also chosen as there are several ongoing trials for Epacadostat, the best-in-class oral IDO-1 enzyme inhibitor, in many solid tumors. For solid tumors, IDO-1-based immune escape has the potential to inhibit monotherapeutic efficacy of PD-L1-based therapeutics. In this study, a total of 223 cases of CRC were retrospectively reviewed and clinicopathologic data were analyzed in relation to PD-L1 and IDO-1 protein expression. Moreover, tumor-infiltrating lymphocytes, mismatch repair deficiency, high mitotic index, and worse survival outcomes were found in cohorts with significant PD-L1 and IDO-1 expression. Both PD-L1 and IDO-1 are actionable biomarkers, with potential therapeutic implications in CRC. Our findings support the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needs verification in well-designed robust clinical trials.
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http://dx.doi.org/10.1097/PAI.0000000000000868DOI Listing
March 2021

Neuroimaging-Based Scalp Acupuncture Locations for Dementia.

J Clin Med 2020 Aug 1;9(8). Epub 2020 Aug 1.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Building 120, 2nd AVE, Charlestown, MA 02129, USA.

Scalp acupuncture is a modality of acupuncture in which acupuncture needles are inserted into a certain layer of the scalp in order to affect the function of corresponding areas of the cerebral cortex and relieve symptoms. Clinical studies have demonstrated the potential of scalp acupuncture as a non-pharmacological treatment for dementia. Unfortunately, recent findings from brain neuroimaging studies on dementia have not been incorporated into scalp acupuncture. This study aims to integrate meta-analysis, resting-state functional connectivity, and diffusion tensor imaging (DTI) to identify potential locations of scalp acupuncture for treatment of dementia. We found that the prefrontal cortex, the medial prefrontal cortex, the middle and superior temporal gyrus, the temporal pole, the supplementary motor area, the inferior occipital gyrus, and the precuneus are involved in the pathophysiology of dementia and, therefore, may be the target areas of scalp acupuncture for dementia treatment. The neuroimaging-based scalp acupuncture protocol developed in this study may help to refine the locations for the treatment of dementia. Integrating multidisciplinary methods to identify key surface cortical areas associated with a certain disorder may shed light on the development of scalp acupuncture and other neuromodulation methods such as transcranial electrical current stimulation, particularly in the domain of identifying stimulation locations.
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http://dx.doi.org/10.3390/jcm9082477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463942PMC
August 2020

Simultaneous Quantification of -Hydroxybutyrate, -Butyrolactone, and 1,4-Butanediol in Four Kinds of Beverages.

Int J Anal Chem 2020 15;2020:8837743. Epub 2020 Jul 15.

Core Facilities Centre, Capital Medical University, 100069 Beijing, China.

-Hydroxybutyrate (GHB) is a neurotransmitter, which exhibits a strong central nervous system depressant effect. The abuse of GHB or its precursor substances (-butyrolactone (GBL) and 1,4-butanediol (1,4-BD)) may cause serious problems. This study developed a fast and effective UHPLC-MS/MS method for the simultaneous quantification of GHB, GBL, and 1,4-BD in four popular beverages, including carbonated drinks, tea, apple cider vinegar, and coffee. The established method overcomes the influence of the in-source collision-induced dissociation of unstable compounds during quantification. The limits of detection were 0.2 g/mL for GBL and 0.5 g/mL for GHB and 1,4-BD with excellent linearity in the range of 0.2-50 g/mL. The recoveries of the three compounds at three spiked levels (2.5, 5.0, and 10.0 g/mL) in the four kinds of beverages studied were between 90 and 110%, while the relative standard deviations (RSDs) were all <10%. The matrix effect was negligible using this simple and appropriate preprocessed procedure. The method established in this study can quickly and reliably detect the GHB content and its analogues in beverages.
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http://dx.doi.org/10.1155/2020/8837743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378593PMC
July 2020

Highly conductive, stretchable, and breathable epidermal electrode based on hierarchically interactive nano-network.

Nanoscale 2020 Aug;12(30):16053-16062

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 100083, China. and School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 100049, China and New Materials Institute, Department of Mechanical, Materials and Manufacturing Engineering, University of Nottingham Ningbo China, Ningbo 315100, China.

Stretchable electrodes have a crucial impact on the development of flexible electronic systems. Most conventionally blended nanocomposite electrodes are incapable of achieving high stretchability, breathability, or durability. In this work, a highly conductive, breathable, and stretchable epidermal electrode (SEE) is demonstrated by designing a hierarchically interactive nano-network that is composed of elastic polymer nano-fibers and multi-level silver nano-wires (AgNWs). The elastic polymer nano-fibers act as a continuous scaffold, and multi-level AgNWs embedded in the nano-fibers form branched conductive pathways. This structure enables high conductivity of the SEE at 4800 S cm-1 (at a significantly low AgNW content of 1.59 vt%), with high stretchability and excellent durability. For example, the SEE remained conductive even at a high strain of 500%, and it also maintained its initial resistance even after 30 000 cycles of strain at 50% or being washed with water for 100 000 cycles. The SEE was prepared by a facile in situ nonequilibrium fabrication process, and can easily be produced into an elastic circuit on a large scale, which provides a foundation for integrated and multifunctional electronic skins. The SEE possesses superior mechanical conformability and permeability of gas and liquid, and therefore, it was successfully applied in measuring electrocardiogram signals and thermal therapy, and exhibited highly robust and comfortable performances even while being washed with water or undergoing complex deformations.
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http://dx.doi.org/10.1039/d0nr03189eDOI Listing
August 2020

EMG-Centered Multisensory Based Technologies for Pattern Recognition in Rehabilitation: State of the Art and Challenges.

Biosensors (Basel) 2020 Jul 26;10(8). Epub 2020 Jul 26.

School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing 100083, China.

In the field of rehabilitation, the electromyography (EMG) signal plays an important role in interpreting patients' intentions and physical conditions. Nevertheless, utilizing merely the EMG signal suffers from difficulty in recognizing slight body movements, and the detection accuracy is strongly influenced by environmental factors. To address the above issues, multisensory integration-based EMG pattern recognition (PR) techniques have been developed in recent years, and fruitful results have been demonstrated in diverse rehabilitation scenarios, such as achieving high locomotion detection and prosthesis control accuracy. Owing to the importance and rapid development of the EMG centered multisensory fusion technologies in rehabilitation, this paper reviews both theories and applications in this emerging field. The principle of EMG signal generation and the current pattern recognition process are explained in detail, including signal preprocessing, feature extraction, classification algorithms, etc. Mechanisms of collaborations between two important multisensory fusion strategies (kinetic and kinematics) and EMG information are thoroughly explained; corresponding applications are studied, and the pros and cons are discussed. Finally, the main challenges in EMG centered multisensory pattern recognition are discussed, and a future research direction of this area is prospected.
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http://dx.doi.org/10.3390/bios10080085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460307PMC
July 2020

miR‑126 regulates the progression of epithelial ovarian cancer in vitro and in vivo by targeting VEGF‑A.

Int J Oncol 2020 Sep 16;57(3):825-834. Epub 2020 Jun 16.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

MicroRNA (miRNA/miR‑126) has been shown to be associated with ovarian cancer in previous studies. In ovarian cancer, however, the specific status of miR‑126 remains largely unknown. In the present study, to clarify its role in ovarian cancer, the levels of miR‑126 were first examined using laser microdissection and RT‑qPCR. It was found that the miR‑126 level was decreased in ovarian tissue samples and the restoration of miR‑126 inhibited cell proliferation, cell invasion and migration in vitro and suppressed tumor growth in vivo. A bioinformatics search revealed that the angiogenesis‑related gene, vascular endothelial growth factor (VEGF)‑A, was among the potential targets of miR‑126. The suppression of invasion and proliferation induced by ectopic miR‑126 expression was nullified by the ectopic expression of VEGF‑A, suggesting that these suppressive effects were largely attributable to the ability of miR‑126 to target VEGF‑A. Moreover, the restoration of miR‑126 suppressed the angiogenic potential of human umbilical vein endothelial cells (HUVECs). On the whole, these findings indicate that the loss of expression of miR‑126 contributes to the abnormal VEGF‑A accumulation and subsequent unchecked cell invasion and cell proliferation in epithelial ovarian cancer.
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http://dx.doi.org/10.3892/ijo.2020.5082DOI Listing
September 2020