Publications by authors named "Zeyu Chen"

130 Publications

3D-Printed Integrated Ultrasonic Microneedle Array for Rapid Transdermal Drug Delivery.

Mol Pharm 2022 Aug 10. Epub 2022 Aug 10.

School of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.

Transdermal drug delivery (TDD) is an attractive alternative to oral and hypodermic injection drug administration, and is poised to increase its impact on medicine and pharmaceutical design. Microneedles (MNs) are a new minimally invasive TDD method widely used in medicine and cosmetology. MNs create a microscale channel from the stratum corneum to the dermis and enable drug delivery of hydrophilic and macromolecular into the skin. Although MNs allow different drugs to penetrate the stratum corneum, they cannot provide an extra driving force for drug transport in tissue. To overcome this limitation and achieve fast, controllable drug delivery, an integrated 3D-printed ultrasonic MN array (USMA) device consisting of hollow MNs and an ultrasonic transducer is proposed. The hollow MNs enable drug to penetrate the stratum corneum, and the ultrasound transmitted through the MNs provides the driving force for drug transportation in tissue. Using methylene blue and bovine serum albumin as model drugs, we tested the drug delivery performance of USMA on porcine skin; the results show that USMA significantly enhanced the delivery efficiency of model drugs. Besides, USMA obviously reduced MNs insertion force and tissue damage, which were well-tolerated and gentle. This study suggests that the integrated ultrasonic MN array has great potential for clinical drug delivery with high efficiency and lessening the suffering of patients.
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http://dx.doi.org/10.1021/acs.molpharmaceut.2c00466DOI Listing
August 2022

Preoperative Free Ferrous Protoporphyrin and Reactive Oxygen Species Status of Voided Urine Predicts Potential Recurrence Risk in NMIBC.

Cancer Manag Res 2022 3;14:2291-2297. Epub 2022 Aug 3.

Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China.

Purpose: This study aimed to assess the relationship between the preoperative reactive oxygen species and free ferrous protoporphyrin (ROS and FH) combined test and the risk of recurrence in a pathologically confirmed non-muscular invasive bladder cancer (NMIBC) patients.

Patients And Methods: The retrospective study included 218 patients, newly diagnosed with NMIBC between January 2019 and February 2022. According to the results of FH and ROS combined test of voided urine, all patients were classified as FH(-)/ROS(-), FH(+)/ROS(-), or FH(+) /ROS(+). We reviewed demographic information, pathological results, and the FH and ROS combined test status. The clinicopathological characteristics were evaluated, and the survival rates of each group were compared. Finally, we also analyzed the association between preoperative free ferrous protoporphyrin and reactive oxygen species status and the tumor stage and grade.

Results: This study included 218 NMIBC patients with a median age of 68 years (interquartile range [IQR] 60-76 years). The number and proportion of patients in FH(-)/ROS(-), FH(+)/ROS(-) and FH(+) /ROS(+) were 95(43.6%), 79(36.2%) and 44(20.2%), respectively. And the pathological stages for those with FH(+) and ROS(+), FH(+) and ROS(-), FH(-) and ROS(-) at diagnosis were 0.5% Tis, 6.4% Ta, 13.3% T1; 2.3% Tis, 20.6% Ta, 13.3% T1; 5.5% Tis, 28.9% Ta, 9.2% T1, respectively. After adjusting for clinical factors, including tumor grade, tumor stage and FH/ROS status were independent risk factors for RFS In the multivariate Cox regression analysis. Through logistics regression analysis, FH(+)/ROS(+) were found to be corelated with high grade and more high stage (T1). Kaplan-Meier analysis showed that 1-year RFS of FH(+)/ROS(+), FH(+)/ROS(-) and FH(-)/ROS(-) were 46.0%, 87.8% and 93.4%, respectively (P=0.000).

Conclusion: In newly diagnosed NMIBC patients, the status of FH(+)/ROS(+) has an association with a higher risk in recurrence. Furthermore, FH(+)/ROS(+) at diagnosis was correlated with high grade and higher stage (T1). Hence, the FH/ROS combined test can help specify treatment options for patients diagnosed with NMIBC.
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http://dx.doi.org/10.2147/CMAR.S371974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357380PMC
August 2022

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Chin Med J (Engl) 2022 Jul 25. Epub 2022 Jul 25.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

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http://dx.doi.org/10.1097/CM9.0000000000002029DOI Listing
July 2022

Dual-Wavelength Photoacoustic Computed Tomography with Piezoelectric Ring-Array Transducer for Imaging of Indocyanine Green Liposomes Aggregation in Tumors.

Micromachines (Basel) 2022 Jun 15;13(6). Epub 2022 Jun 15.

State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.

Recently, indocyanine green (ICG), as an FDA-approved dye, has been widely used for phototherapy. It is essential to obtain information on the migration and aggregation of ICG in deep tissues. However, existing fluorescence imaging platforms are not able to obtain the structural information of the tissues. Here, we prepared ICG liposomes (ICG-Lips) and built a dual-wavelength photoacoustic computed tomography (PACT) system with piezoelectric ring-array transducer to image the aggregation of ICG-Lips in tumors to guide phototherapy. Visible 780 nm light excited the photoacoustic (PA) effects of the ICG-Lips and near-infrared 1064 nm light provided the imaging of the surrounding tissues. The aggregation of ICG-Lips within the tumor and the surrounding tissues was visualized by PACT in real time. This work indicates that PACT with piezoelectric ring-array transducer has great potential in the real-time monitoring of in vivo drug distribution.
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http://dx.doi.org/10.3390/mi13060946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227349PMC
June 2022

Sex Cord-Stromal Tumors of Testis: A Clinicopathologic and Follow-Up Study of 15 Cases in a High-Volume Institute of China.

Front Med (Lausanne) 2022 31;9:816012. Epub 2022 May 31.

Department of Urology, West China Hospital, Institute of Urology, Sichuan University, Chengdu, China.

Objectives: To report the first series of testicular sex cord-stromal tumors (TSCSTs) with detailed clinicopathologic findings and long-term follow-up in the Chinese population.

Patients And Methods: From 2008 to 2018, 15 patients with TSCST were included in our study. The tumors were analyzed for epidemiological parameters, clinical characteristics, tumor markers, therapy, and follow-up data.

Results: The median age of the patients was 28 years (range, 13-80 years). Para-aortic lymph node metastases were detected in 2 patients after radiological evaluation. Orchiectomy was performed in all patients, and the median diameter of the tumor was 1.5 cm (range, 0.5-5.0 cm). Nine Leydig cell tumors (LCTs), 5 Sertoli cell tumors (SCTs), and 1 unclassified type were confirmed after pathologic evaluation. Thirteen patients (86.7%) were categorized as stage I, and 2 patients (13.3%) were categorized as stage II. The median clinical follow-up was 39.0 months (range, 5-97 months), which showed 10 alive patients, such as 1 patient with progression at 40 months after orchiectomy. The 3- and 5-year progression-free survivals were 100 and 90.0%, respectively.

Conclusion: Testicular sex cord-stromal tumor at stages I and II is a rare subtype with benign behavior and a favorable prognosis in the Chinese population. However, lymph node metastases may be the dominant risk factor for patients with TSCST.
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http://dx.doi.org/10.3389/fmed.2022.816012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197338PMC
May 2022

A cationic iridium(III) complex containing a thiosemicarbazide unit: Synthesis and application for turn-on chemiluminescent detection of Hg.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Oct 22;279:121396. Epub 2022 May 22.

Key Laboratory of Green-Chemistry Materials in University of Yunnan Province, National and Local Joint Engineering Research Center for Green Preparation Technology of Biobased Materials, School of Chemistry & Environment, Yunnan Minzu University, Kunming 650500, China.

A novel cationic iridium(III) complex [(ppy)Ir(bPCPC)]PF (ppy: 2-phenylpyridine; bPCPC: 2-([2,2'-bipyridine]-4-carbonyl)-N-phenylhydrazinecarbothioamide) containing a thiosemicarbazide unit was designed and synthesized. The thiosemicarbazide unit was a sensitive functional group to Hg, when it reacted with Hg, it was desulphurized and thus led to the formation of 1,3,4-oxadiazole, [(ppy)Ir(bPCPC)]PF resultantly was used as a "turn-on" chemodosimeter for luminescent detection of Hg in DMF/PBS buffer solution at pH = 7-11. Except for Ag, recognition capability of [(ppy)Ir(bPCPC)]PF to Hg was not interfered by other common metal ions (Co, Li, Zn, Pb, K, Al, Na, Mn, Cu, Fe, Fe, Cr, Ba, Mg, Ni and Ca). The detection limit was 1.83 × 10 mol∙L (0.37 ppb), which indicated the complex was a highly sensitive chemiluminescent detection reagent of Hg.
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http://dx.doi.org/10.1016/j.saa.2022.121396DOI Listing
October 2022

MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection.

Proc Natl Acad Sci U S A 2022 04 21;119(17):e2106083119. Epub 2022 Apr 21.

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

CD8 T cells mediate protection against intracellular pathogens and tumors. However, persistent antigen during chronic infections or cancer leads to T cell exhaustion, suboptimal functionality, and reduced protective capacity. Despite considerable work interrogating the transcriptional regulation of exhausted CD8 T cells (TEX), the posttranscriptional control of TEX remains poorly understood. Here, we interrogated the role of microRNAs (miRs) in CD8 T cells responding to acutely resolved or chronic viral infection and identified miR-29a as a key regulator of TEX. Enforced expression of miR-29a improved CD8 T cell responses during chronic viral infection and antagonized exhaustion. miR-29a inhibited exhaustion-driving transcriptional pathways, including inflammatory and T cell receptor signaling, and regulated ribosomal biogenesis. As a result, miR-29a fostered a memory-like CD8 T cell differentiation state during chronic infection. Thus, we identify miR-29a as a key regulator of TEX and define mechanisms by which miR-29a can divert exhaustion toward a more beneficial memory-like CD8 T cell differentiation state.
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http://dx.doi.org/10.1073/pnas.2106083119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169946PMC
April 2022

Mechanically Robust and Elastic Graphene/Aramid Nanofiber/Polyaniline Nanotube Aerogels for Pressure Sensors.

ACS Appl Mater Interfaces 2022 Apr 7;14(15):17858-17868. Epub 2022 Apr 7.

College of Materials Science and Engineering, Hunan University, Changsha 410082, P. R. China.

The preparation of graphene-based aerogels with excellent mechanical strength, elasticity, and compressibility is still a challenge. Herein, we demonstrate a robust, elastic, and lightweight graphene/aramid nanofiber/polyaniline nanotube (rGO/ANF/PANIT) aerogel that is prepared by mixing graphene oxide (GO), ANF, and PANIT dispersions, followed by thermal treatment at 90 °C, freeze-drying, and a low-temperature annealing process. The PANIT bonds the graphene sheets tightly, benefitting the formation of composite gels. The ANF tightly interconnects the graphene sheets and further reinforces the composite network framework significantly, hence endowing rGO/ANF/PANIT composite aerogels with robust mechanical property. The prepared aerogels present a low density of ∼12 mg cm, high conductivity, good resilience, and high compressibility. The rGO/ANF/PANIT aerogels as pressure sensors exhibit a high sensitivity of 1.73 kPa, low detection limit (40 Pa), wide detection range, and excellent compressive cycle stability, highlighting the promising applications in pressure-sensitive electrical devices, including medical health detection, wearable electronics, and intelligent packaging fields.
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http://dx.doi.org/10.1021/acsami.2c02538DOI Listing
April 2022

Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging.

Front Immunol 2022 21;13:842008. Epub 2022 Mar 21.

Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to February 2021 using the following key words: "benign prostatic hyperplasia", "inflammation", "pathogenesis" and "disease development". Articles were obtained and reviewed to provide a systematic review of the current progress of the role of inflammation in the pathogenesis and progression of BPH. Inflammation contributes to the initiation and maintenance of unregulated cell proliferation and is closely related to the occurrence and development of BPH. Its action pathways include tissue damage and subsequent chronic healing, autoimmunity, and coaction with androgens. During the progression of inflammation, macrophages, interleukin-8 (IL-8), interleukin-1 (IL-1) and other inflammatory-related substances aggregate locally and cause BPH through various biochemical pathways. At the same time, BPH can also counteract inflammation to expand its scope and aggravate the situation. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. In the course of treatment, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.
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http://dx.doi.org/10.3389/fimmu.2022.842008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977548PMC
March 2022

Human umbilical cord-derived mesenchymal stem cells ameliorate psoriasis-like dermatitis by suppressing IL-17-producing γδ T cells.

Cell Tissue Res 2022 Jun 26;388(3):549-563. Epub 2022 Mar 26.

Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases due to their immunomodulatory capability, which has been verified in both animal experiments and clinical trials. Psoriasis is a chronic and remitting immune-related disease. Limited studies have demonstrated that MSCs might be an effective therapeutic approach for managing psoriasis, whose underlying mechanism remains to be elucidated. In our present study, human umbilical cord-derived MSCs (hUC-MSCs) were subcutaneously injected into mice with imiquimod (IMQ)-induced psoriasis-like skin inflammation to explore the feasibility of this cellular therapy. The severity of psoriasis-like dermatitis was evaluated by cumulative psoriasis area and severity index score and epidermal thickness of skin tissue sections. Flow cytometric analysis was utilized to detect T helper cells, regulatory T cells, and γδ T cells in skin-draining lymph nodes. Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the expression levels of psoriasis-related cytokines and chemokines in mouse dorsal skin lesions. We discovered that hUC-MSCs drastically diminished the severity of IMQ-induced psoriasis-like dermatitis and suppressed inflammatory cell response. Although the tail vein injection of hUC-MSCs was also effective, it was correlated with higher mortality owing to pulmonary embolism. By comparison, subcutaneous injection with two million hUC-MSCs was identified to be the optimal therapeutic strategy. Furthermore, we uncovered that hUC-MSCs might repress skin inflammation probably through inhibiting interleukin-17-producing γδ T cells. In conclusion, subcutaneous administration of hUC-MSCs might be a promising therapeutic approach for psoriasis. Our findings provide novel insights into the underpinning mechanism of hUC-MSC treatment in the management of psoriasis.
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http://dx.doi.org/10.1007/s00441-022-03616-xDOI Listing
June 2022

Signaling Through FcγRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19.

Front Immunol 2022 3;13:834988. Epub 2022 Mar 3.

Division of Pulmonary, Allergy and Critical Care Medicine, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibited higher basal levels of activation measured by P-selectin surface expression and had poor functional reserve upon stimulation. To investigate this question in more detail, we developed an assay to assess the capacity of plasma from COVID-19 patients to activate platelets from healthy donors. Platelet activation was a common feature of plasma from COVID-19 patients and correlated with key measures of clinical outcome including kidney and liver injury, and APACHEIII scores. Further, we identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with platelet activation. Mechanistically, blocking the signaling of the FcγRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect.
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http://dx.doi.org/10.3389/fimmu.2022.834988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928747PMC
March 2022

Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers.

Immunity 2022 03;55(3):557-574.e7

Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The clinical benefit of T cell immunotherapies remains limited by incomplete understanding of T cell differentiation and dysfunction. We generated an epigenetic and transcriptional atlas of T cell differentiation from healthy humans that included exhausted CD8 T cells and applied this resource in three ways. First, we identified modules of gene expression and chromatin accessibility, revealing molecular coordination of differentiation after activation and between central memory and effector memory. Second, we applied this healthy molecular framework to three settings-a neoadjuvant anti-PD1 melanoma trial, a basal cell carcinoma scATAC-seq dataset, and autoimmune disease-associated SNPs-yielding insights into disease-specific biology. Third, we predicted genome-wide cis-regulatory elements and validated this approach for key effector genes using CRISPR interference, providing functional annotation and demonstrating the ability to identify targets for non-coding cellular engineering. These studies define epigenetic and transcriptional regulation of human T cells and illustrate the utility of interrogating disease in the context of a healthy T cell atlas.
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http://dx.doi.org/10.1016/j.immuni.2022.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214622PMC
March 2022

Efficacy and Safety of Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease: An Evidence-Based Analysis.

Front Med (Lausanne) 2022 18;9:780956. Epub 2022 Feb 18.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Background: Peyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial, which propelled us to conduct the first evidence-based research on this topic.

Methods: We searched the Web of Science, PubMed, Embase, and ClinicalTrials.gov for related randomized controlled trials (RCTs). A systematic review and meta-analysis were performed to compare the penile curvature deformity (PCD), Peyronie's Disease Questionnaire peyronie's disease symptom bother (PDSB), penile pain score, total treatment-related adverse events (TAEs), and specific adverse events, including penile pain, penile edema, injection site pain, and contusion. Cochrane Collaboration's tool and Review Manager 5.3.0 version were applied, respectively, to evaluate the study quality and heterogeneity.

Results: Four articles (five RCTs) with 1,227 patients were finally included in the meta-analysis. The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: -318.77, < 0.001) and PDSB (WMD: -1.20, < 0.001) compared to the placebo group, but there was no difference in the penile pain score (WMD: -0.64, = 0.39) between the two groups. Furthermore, the incidence of TAEs in the CCH group was higher [odds ratio (OR): 12.86, < 0.001].

Conclusions: The current evidence suggests that CCH has a significant effect on treating PD. Considering that all these adverse events are acceptable and curable, CCH could slow the disease progression in the acute phase or act as a substitute for patients unable or unwilling to undergo surgery. However, the conclusion could not be certainly drawn until RCTs with a larger scale proved it.
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http://dx.doi.org/10.3389/fmed.2022.780956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896480PMC
February 2022

Establishment of an Individualized Predictive Model to Reduce the Core Number for Systematic Prostate Biopsy: A Dual Center Study Based on Stratification of the Disease Risk Score.

Front Oncol 2021 14;11:831603. Epub 2022 Feb 14.

Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.

Purpose: To establish an individualized prostate biopsy model that reduces unnecessary biopsy cores based on multiparameter MRI (mpMRI).

Materials And Methods: This retrospective, non-inferiority dual-center study retrospectively included 609 patients from the Changhai Hospital from June 2017 to November 2020 and 431 patients from the Fujian Union Hospital between 2014 and 2019. Clinical, radiological, and pathological data were analyzed. Data from the Changhai Hospital were used for modeling by calculating the patients' disease risk scores. Data from the Fujian Union Hospital were used for external verification.

Results: Based on the data of 609 patients from the Changhai Hospital, we divided the patients evenly into five layers according to the disease risk score. The area under the receiver operating characteristic (ROC) curve (AUC) with 95% confidence intervals (CI) was analyzed. Twelve-core systemic biopsy (12-SBx) was used as the reference standard. The SBx cores from each layer were reduced to 9, 6, 5, 4, and 4. The data of 279 patients with benign pathological results from the Fujian Union Hospital were incorporated into the model. No patients were in the first layer. The accuracies of the models for the other layers were 88, 96.43, 94.87, and 94.59%. The accuracy of each layer would be increased to 96, 100, 100, and 97.30% if the diagnosis of non-clinically significant prostate cancer was excluded.

Conclusions: In this study, we established an individualized biopsy model using data from a dual center. The results showed great accuracy of the model, indicating its future clinical application.
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http://dx.doi.org/10.3389/fonc.2021.831603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882832PMC
February 2022

Zinc Intakes and Health Outcomes: An Umbrella Review.

Front Nutr 2022 8;9:798078. Epub 2022 Feb 8.

Department of Urology, Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

It is widely accepted that the zinc element is crucial in human beings. Zinc has gained more attention during the COVID-19 pandemic due to its utilization for the treatment and prevention of respiratory tract infections. However, some studies also pointed out that zinc intake might cause unwanted side effects and even be dangerous when overdosed. To reveal the relationship between zinc intake and health outcomes, we performed an umbrella review from human studies. In total, the umbrella review included 43 articles and identified 11 outcomes for dietary zinc intake and 86 outcomes for supplementary zinc intake. Dietary zinc intake in the highest dose would decrease the risk of overall and specific digestive tract cancers, depression, and type 2 diabetes mellitus (T2DM) in adults. Supplementary zinc consumption in adults was linked to an improvement of depression, antioxidant capacity and sperm quality, higher serum zinc concentration, and lower concentration of inflammatory markers. Zinc supplementation in children would reduce the incidence of diarrhea and pneumonia, improve zinc deficiency and boost growth. However, zinc might not decrease all-cause mortality in adults or the in-hospital mortality of COVID-19. And better maternal and neonatal outcomes may not derive from pregnant women who consumed higher or lower doses of zinc supplementation (>20 mg/day and <20 mg/day, respectively). Dose-response analyses revealed that a daily 5 mg increment of zinc would lower the risk of colorectal and esophageal cancer, whereas a large dose of zinc supplementation (daily 100 mg) showed no benefit in reducing prostate cancer risk.
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http://dx.doi.org/10.3389/fnut.2022.798078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861317PMC
February 2022

Dysregulated Peripheral Invariant Natural Killer T Cells in Plaque Psoriasis Patients.

Front Cell Dev Biol 2021 3;9:799560. Epub 2022 Feb 3.

Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.

Psoriasis is a common immune-mediated skin disease that involves T-cell-mediated immunity. Invariant natural killer T (NKT) cells are a unique lymphocyte subpopulation that share properties and express surface markers of both NK cells and T cells. Previous reports indicate that NKT cells regulate the development of various inflammatory diseases. IL-17 is a key cytokine in the pathogenesis of psoriasis and a key therapeutic target. Secukinumab is a fully human IgG1κ antibody that targets IL-17A, thereby antagonizing the biological effects of IL-17. To explore the expression of NKT cells in psoriasis patients and the effect of secukinumab on them. We examined the frequencies of NKT cells, Tregs, naïve and memory CD4and CD8T cells in the PBMCs as well as their cytokine production in a cohort of 40 patients with moderate-to-severe plaque psoriasis and 40 gender- and age-matched healthy controls. We further collected peripheral blood of another 15 moderate-to-severe plaque psoriasis patients who were treated with secukinumab and evaluated the proportion of NKT cells in the PBMCs at baseline and week 12. The frequencies of conventional CD4 T cells, CD8 T cells, and Tregs in the PBMCs were comparable between psoriasis patients and healthy controls, but the frequencies of Th17 cells, Tc1 cells and Tc17 cells were increased in psoriasis patients. The frequency of peripheral NKT cells and CD69 NKT cells was significantly decreased in psoriasis patients. Both NKT2 cells and NKT17 cells were increased in psoriasis patients, but the ratio of NKT2 cells vs NKT17 cells was significantly reduced in psoriasis patients. After receiving secukinumab, the proportion of NKT cells in the PBMCs of patients was increased, while the proportion of NKT17 cells was decreased. Dysregulated NKT cells may be involved in the pathogenesis of psoriasis and secukinumab may play a regulatory role on NKT cells.
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http://dx.doi.org/10.3389/fcell.2021.799560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850372PMC
February 2022

Vitamin C Intake and Cancers: An Umbrella Review.

Front Nutr 2021 20;8:812394. Epub 2022 Jan 20.

Department of Urology, Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Based on the existing systematic reviews and meta-analyses, we conducted this umbrella review aiming at evaluating the quality of evidence, validity and biases of the relationship between vitamin C (VC) intake and incidence and outcomes of multiple cancers. We identified 22 cancer outcomes within 3,562 articles. VC consumption was associated with lower incidence of bladder cancer, breast cancer, cervical tumors, endometrial cancer, esophageal cancer, gastric cancer, glioma, lung cancer, pancreatic cancer, prostate cancer, renal cell cancer, and total cancer occurrence. VC intake was also related to decreased risk of breast cancer prognosis (recurrence, cancer-specific mortality, and all-cause mortality).
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http://dx.doi.org/10.3389/fnut.2021.812394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812486PMC
January 2022

Non-coding small nucleolar RNA SNORD17 promotes the progression of hepatocellular carcinoma through a positive feedback loop upon p53 inactivation.

Cell Death Differ 2022 May 15;29(5):988-1003. Epub 2022 Jan 15.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Recent evidence suggests that small nucleolar RNAs (snoRNAs) are involved in the progression of various cancers, but their precise roles in hepatocellular carcinoma (HCC) remain largely unclear. Here, we report that SNORD17 promotes the progression of HCC through a positive feedback loop with p53. HCC-related microarray datasets from the Gene Expression Omnibus (GEO) database and clinical HCC samples were used to identify clinically relevant snoRNAs in HCC. SNORD17 was found upregulated in HCC tissues compared with normal liver tissues, and the higher expression of SNORD17 predicted poor outcomes in patients with HCC, especially in those with wild-type p53. SNORD17 promoted the growth and tumorigenicity of HCC cells in vitro and in vivo by inhibiting p53-mediated cell cycle arrest and apoptosis. Mechanistically, SNORD17 anchored nucleophosmin 1 (NPM1) and MYB binding protein 1a (MYBBP1A) in the nucleolus by binding them simultaneously. Loss of SNORD17 promoted the translocation of NPM1 and MYBBP1A into the nucleoplasm, leading to NPM1/MDM2-mediated stability and MYBBP1A/p300-mediated activation of p53. Interestingly, p300-mediated acetylation of p53 inhibited SNORD17 expression by binding to the promoter of SNORD17 in turn, forming a positive feedback loop between SNORD17 and p53. Administration of SNORD17 antisense oligonucleotides (ASOs) significantly suppressed the growth of xenograft tumors in mice. In summary, this study suggests that SNORD17 drives cancer progression by constitutively inhibiting p53 signaling in HCC and may represent a potential therapeutic target for HCC.
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http://dx.doi.org/10.1038/s41418-022-00929-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090725PMC
May 2022

Ultrawide Bandwidth High-Frequency Ultrasonic Transducers With Gradient Acoustic Impedance Matching Layer for Biomedical Imaging.

IEEE Trans Ultrason Ferroelectr Freq Control 2022 06 26;69(6):1952-1959. Epub 2022 May 26.

The high-frequency ultrasonic transducers with larger bandwidths yield excellent imaging performance in the biomedical field. However, achieving perfect acoustic impedance matching from the piezo-element to the target medium in the operating frequency spectrum is still a challenge. Conventional matching layers are mostly fabricated by only one or two uniform materials which are limited by their acoustic property. We propose a novel composite matching layer with gradient acoustic impedance based on a 1-3 gradient composite structure and multilevel matching theory. The proposed gradient-composite matching layer applied for ultrasonic transducer provides efficient impedance matching and ultrawide bandwidth which can significantly improve the quality of biomedical imaging. The active aperture size of the matching layer is 5× 5 mm, and the overall thickness for five equivalent layers is 115 [Formula: see text]. The -6-dB bandwidth and the center frequency obtained by the ultrasonic transducer equipped with the 1-3 gradient composite matching layer are 141.7% and 22.3 MHz, respectively. The exceedingly good imaging performance of the fabricated ultrasonic transducer was demonstrated by the tungsten wire phantom and study on the biological tissues of a zebrafish and porcine eyeball. The theoretical and experimental results provide a novel train of thought for improving the quality of biomedical ultrasonic imaging.
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http://dx.doi.org/10.1109/TUFFC.2022.3141203DOI Listing
June 2022

Association of urinary organophosphate esters level with sex steroid hormones levels in adult males: A nationwide study, NHANES 2013-2014.

Andrology 2022 03;10(3):567-575

Department of Urology and Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Background: Exposure to environmental pollution via different mechanisms is associated with multiple endocrine dysfunctions. Organophosphate esters (OPEs) are endocrine-disrupting chemicals that affect sex steroid hormones.

Purpose: We aimed to study the effect of OPEs and their metabolites, such as diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP), on sex steroid hormones in males.

Design, Setting, Participants, And Intervention: This cross-sectional analytical study analyzed data from the 2013-2014 National Health and Nutrition Examination Survey among 763 male participants aged ≥20 years.

Main Outcome Measures: The relationships between the metabolites of OPEs and total testosterone, estradiol, sex hormone-binding globulin, and the ratio of total testosterone to estradiol (a parameter derived from total testosterone and estradiol) were evaluated using multivariate linear regression models that were adjusted for potential confounders.

Results: A total of 763 participants, with a mean age of 44.59 (±15.59) years, were enrolled. Of these, 65.7% participants had non-Hispanic white ancestry, 9.83% had non-Hispanic black ancestry, and 15.97% had Hispanic ancestry. Participants with higher urinary level of DPHP had a lower level of total testosterone and estradiol. Moreover, higher urinary levels of BDCPP were associated with higher estradiol.

Conclusion: According to our study, which is based on a representative population of US adults, exposure to OPEs was significantly associated with altered sex hormone levels (total testosterone and estradiol). Further studies focused on the underlying mechanisms regarding the association between each metabolite and sex steroid hormones are required.
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http://dx.doi.org/10.1111/andr.13149DOI Listing
March 2022

Broadband High-Frequency Ultrasonic Transducer Based Functional Photoacoustic Mesoscopy for Psoriasis Progression.

IEEE Trans Ultrason Ferroelectr Freq Control 2022 06 26;69(6):1926-1931. Epub 2022 May 26.

In vivo imaging of skin is commonly used to investigate dynamic processes in the progression and treatment of psoriasis. Photoacoustic mesoscopy is a new non-invasive imaging modality widely used in bio-imaging, and has recently been applied to imaging skin in vivo. However, photoacoustic imaging has shortcomings. Although high-frequency ultrasonic transducers enable high-resolution photoacoustic imaging, the images may be bandwidth-limited. To overcome this limitation, we designed and fabricated a broadband ultrasonic transducer for photoacoustic mesoscopy. The center frequency of the transducer was 32 MHz (88% bandwidth at -6 dB). The transducer was used to visualize mouse and human skin morphology. Colocalization of high- and low-frequency components revealed information about both the skin surface and dermis. To explore dynamic structural changes in mouse back skin during psoriasis progression, we measured blood oxygen saturation and total hemoglobin in a mouse model using multiwavelength imaging without contrast agents. The results indicate that functional photoacoustic mesoscopy using a broadband high-frequency transducer has great potential for clinical imaging of skin disease.
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http://dx.doi.org/10.1109/TUFFC.2021.3136870DOI Listing
June 2022

Evolvable Acoustic Field Generated by a Transducer with 3D-Printed Fresnel Lens.

Micromachines (Basel) 2021 Oct 26;12(11). Epub 2021 Oct 26.

Interdisciplinary Division of Biomedical Engineering, The Hong Kong Ploytechnic University, Hong Kong 999077, China.

Evolvable acoustic fields are considered an effective method for solving technical problems related to fields such as biological imaging, particle manipulation, drug therapy and intervention. However, because of technical difficulties and the limited technology available for realizing flexible adjustments of sound fields, few studies have reported on this aspect in recent years. Herein, we propose a novel solution, using a Fresnel lens-focused ultrasonic transducer for generating excited-signal-dependent acoustic pressure patterns. Finite element analysis (FEA) is used to predict the performance of a transducer with a Fresnel lens. The Fresnel lens is printed using 3D additive manufacturing. Normalized intensity maps of the acoustic pressure fields are characterized from the Fresnel lens-focused transducer under various numbers of excited-signal cycles. The results demonstrate that under different cycle excitations, a temporal evolution acoustic intensity can be generated and regulated by an ultrasound transducer with a 3D Fresnel lens. This acoustical pattern control method is not only simple to realize but also has considerable application prospects.
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http://dx.doi.org/10.3390/mi12111315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617849PMC
October 2021

Stack-Layer Dual-Element Ultrasonic Transducer for Broadband Functional Photoacoustic Tomography.

Front Bioeng Biotechnol 2021 28;9:786376. Epub 2021 Oct 28.

Department of Biomedical Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Current Photoacoustic tomography (PAT) approaches are based on a single-element transducer that exhibits compromised performance in clinical imaging applications. For example, vascular, tumors are likely to have complicated shapes and optical absorptions, covering relatively wide spectra in acoustic signals. The wide ultrasonic spectra make it difficult to set the detection bandwidth optimally in advance. In this work, we propose a stack-layer dual-element ultrasonic transducer for PAT. The central frequencies of the two piezoelectric elements are 3.06 MHz (99.3% bandwidth at -6 dB) and 11.07 MHz (85.2% bandwidth at -6 dB), respectively. This transducer bridges the sensitivity capability of ultrasound and the high contrast of optical methods in functional photoacoustic tomography. The dual-element transducer enabled multiscale analysis of the vascular network in rat brains. Using a multi-wavelength imaging scheme, the blood oxygen saturation was also detected. The preliminary results showed the great potential of broad-bandwidth functional PAT on vascular network visualization. The method can also be extended to whole-body imaging of small animals, breast cancer detection, and finger joint imaging.
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http://dx.doi.org/10.3389/fbioe.2021.786376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581210PMC
October 2021

3D Printed Integrated Multi-Layer Microfluidic Chips for Ultra-High Volumetric Throughput Nanoliposome Preparation.

Front Bioeng Biotechnol 2021 11;9:773705. Epub 2021 Oct 11.

School of Mechanical and Electrical Engineering, Central South University, Changsha, China.

Although microfluidic approaches for liposomes preparation have been developed, fabricating microfluidic devices remains expensive and time-consuming. Also, owing to the traditional layout of microchannels, the volumetric throughput of microfluidics has been greatly limited. Herein an ultra-high volumetric throughput nanoliposome preparation method using 3D printed microfluidic chips is presented. A high-resolution projection micro stereolithography (PμSL) 3D printer is applied to produce microfluidic chips with critical dimensions of 400 µm. The microchannels of the microfluidic chip adopt a three-layer layout, achieving the total flow rate (TFR) up to 474 ml min, which is remarkably higher than those in the reported literature. The liposome size can be as small as 80 nm. The state of flows in microchannels and the effect of turbulence on liposome formation are explored. The experimental results demonstrate that the 3D printed integrated microfluidic chip enables ultra-high volumetric throughput nanoliposome preparation and can control size efficiently, which has great potential in targeting drug delivery systems.
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http://dx.doi.org/10.3389/fbioe.2021.773705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542840PMC
October 2021

Surgical management of tuberculous epididymo-orchitis: a retrospective study of 81 cases with long-term follow-up.

BMC Infect Dis 2021 Oct 15;21(1):1068. Epub 2021 Oct 15.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Guoxue Alley, No. 37, Chengdu, 610041, Sichuan, People's Republic of China.

Background: Nowadays, most studies of tuberculous epididymo-orchitis (TBEO) are case reports or small sample cohort series. Our study is aimed to present the largest series of TBEO with our management experiences and long-term follow-up outcomes.

Methods: Patients diagnosed with TBEO after surgical procedures at Department of Urology, West China Hospital from 2008 to 2019 were included. All clinical features, auxiliary examination results, treatment and histopathological findings were extracted if available.

Results: Eighty-one patients (mean age 50.77 ± 16.1 years) were included. Scrotal swelling (N = 47, 58.0%) and pain (N = 29, 35.8%) were the most common presenting complaint. Pyuria and microscopic hematuria were observed in twenty-two (27.2%) and eight patients (9.9%), respectively. Urine acid fast bacilli cultures were available in 16 patients and all were negative. The mean duration between the onset of symptoms and the definite diagnosis was 6.42 ± 7.0 months. TBEO was considered in 30 (37.0%), tumors in 28 (34.6%) and nonspecific bacterial epididymo-orchitis in 23 (28.4%) patients. All patients received triple therapy of chemotherapy-surgery-pharmacotherapy and definite diagnosis was confirmed through histopathology of surgical specimens. Fifty-five patients were followed up regularly (mean follow-up 82.35 ± 36.6 months). One patient (1.2%) died from liver cirrhosis and no recurrence was observed. Postoperative complications included erectile dysfunction in 4 patients (4.9%), premature ejaculation in 5 patients (6.2%) and sterility in 7 patients (8.6%).

Conclusions: We recommend patients with advanced TBEO to receive triple therapy of chemotherapy-surgery-pharmacotherapy. Physicians should pay more attention to patients' sexual function and fertility during follow up after treatment completed.
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http://dx.doi.org/10.1186/s12879-021-06753-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520285PMC
October 2021

Comparison of Perioperative, Renal Functional, and Oncological Outcomes Between Off-Clamp and On-Clamp Robot-Assisted Partial Nephrectomy for Renal Tumors: An Updated Evidence-Based Analysis.

Front Oncol 2021 21;11:730662. Epub 2021 Sep 21.

Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Objectives: We aimed to report the latest and largest pooled analysis and evidence update to compare the perioperative, renal functional, and oncological outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN) for renal tumors.

Patients And Methods: We performed a systematic literature search using PubMed, Embase, and Web of Science up to August 2021 for studies that compared the efficacy and/or safety between off-clamp and on-clamp RAPN for renal tumors. Outcomes measured were operating time, estimated blood loss (EBL), conversion rate, length of stay (LOS), complication rate, transfusion rate, long-term % decrease in estimated glomerular filtration rate (eGFR), positive surgical margin rate, and recurrence rate.

Results: A total of 21 eligible articles involving 4,493 patients (1,274 off-clamp 3,219 on-clamp) were included for the evidence synthesis. Baseline characteristics of the two groups were similar in all outcomes except that lower R.E.N.A.L. score and smaller tumor size were observed in the off-clamp group. Pooled analysis showed shorter operative time, higher EBL, and lower complication rate in the off-clamp group. No significant difference was observed in the conversion rate, LOS, and transfusion rate. The recurrence rates were similar in the two groups, while a lower positive surgical margin rate was observed in the off-clamp group. Finally, the off-clamp group had a superior postoperative renal functional outcome.

Conclusions: Given the presence of heterogeneity and potential bias, urologists should select the clamp strategy based on their experience and patient-specific factors.
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http://dx.doi.org/10.3389/fonc.2021.730662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490928PMC
September 2021

Mechanically strong multifunctional three-dimensional crosslinked aramid nanofiber/reduced holey graphene oxide and aramid nanofiber/reduced holey graphene oxide/polyaniline hydrogels and derived films.

Nanoscale 2021 Oct 14;13(39):16734-16747. Epub 2021 Oct 14.

College of Materials Science and Engineering, Hunan University, Changsha 410082, P. R. China.

To endow high mechanical strength and thermal stability aramid nanofibers (ANF) with novel functionality will lead to great applications. Herein, a strategy to generate covalent bonds among components towards obtaining uniform ANF/reduced holey graphene oxide (ANF/rHGO) and ANF/rHGO/polyaniline (ANF/rHGO/PANI) hydrogels with high mechanical properties is proposed through solvent exchange gelation and subsequent hydrothermal treatment. The as-prepared ANF/rHGO and ANF/rHGO/PANI hydrogels demonstrate excellent recoverability at high compressive strength of 20.2 and 13.8 kPa with a strain of 34.4% and 30.6%, respectively, compared to a recoverability of 92.5% at a strain of ∼20% for ANF hydrogels. Moreover, ANF/rHGO and ANF/rHGO/PANI aerogels possess fast and high oil absorption capacity of 38.9-64.1 g g and 24.5-44.0 g g, respectively. ANF/rHGO and ANF/rHGO/PANI films obtained after vacuum-drying exhibit a high tensile strength of 121.4 and 95.5 MPa, respectively. Additionally, ANF/rHGO/PANI thin films present good selective absorption of visible light by controlling the doping level of PANI. ANF/rHGO/PANI aerogel films prepared by freeze-drying are assembled into flexible solid-state symmetric supercapacitors and deliver a favorable specific capacitance of 200 F g, a desirable capacitance retention of 98.9% after 2500 mechanical bending cycles and an approximately 100% capacitance retention even after keeping tensile force for 15 h. The as-prepared hydrogels, aerogels and derived films with such excellent performances are promising for applications in oil pollution removal, optical filters and flexible load-bearing energy storage devices.
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http://dx.doi.org/10.1039/d1nr03826eDOI Listing
October 2021

Iron intake and multiple health outcomes: Umbrella review.

Crit Rev Food Sci Nutr 2021 Sep 29:1-18. Epub 2021 Sep 29.

Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Iron is an essential trace element, while excess iron can lead to different levels of physical abnormalities or diseases. This umbrella review aimed to conduct a systematic evaluation of the possible relationships between iron intake and various health outcomes. We retrieved PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews from inception through May 2021. A total of 34 meta-analyses with 46 unique health outcomes were identified. Heme iron intake was positively associated with nine outcomes, including colorectal cancer, type 2 diabetes mellitus, and cardiovascular disease mortality, while dietary total iron intake could decrease the risk of colorectal adenoma, esophageal cancer, coronary heart disease, and depression. Iron supplementation was a protective factor against eight outcomes. However, it was associated with decreased length and weight gain. The quality of evidence for most outcomes was "low" or "very low" with the remaining eleven as "high" or "moderate". All outcomes were categorized as class III, IV, or NS based on evidence classification. Although high iron intake has been identified to be significantly associated with a range of outcomes, firm universal conclusions about its beneficial or negative effects cannot be drawn given the low quality of evidence for most outcomes.
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http://dx.doi.org/10.1080/10408398.2021.1982861DOI Listing
September 2021

The associations between organophosphate esters and urinary incontinence in the general US population.

Environ Sci Pollut Res Int 2022 Feb 14;29(7):10400-10407. Epub 2021 Sep 14.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Organophosphate esters (OPEs) impact health in many ways. Since its relationship with urinary incontinence remains unknown, we aimed to explore their associations in the US general population. We combined the results of urine specimens test and self-reported urinary incontinence conditions from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 among 2666 participants and then conducted linear regression and logistic regression to analyse associations between log2-transformed OPE concentrations and urinary incontinence. We found that 0.92% of men and 15.74% of women complained of mixed urinary incontinence (MUI). The concentrations of diphenyl phosphate (DPHP) were significantly correlated to MUI among women when treated as a continuous variable (adjusted odds ratio (OR) = 1.15; 95% confidence interval (CI), 1.01-1.31; p = 0.0369) and as a categorical variable (adjusted OR = 1.24; 95% CI, 1.03-1.49; p for trend = 0.0245), whereas no positive correlation was found in males. There were no significant associations between the other three OPEs: bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and dibutyl phosphate (DBUP). The association of DPHP with an increased prevalence OR of MUI in women is a public health concern; future prospective studies are needed to explore its potential mechanism.
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http://dx.doi.org/10.1007/s11356-021-14153-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783883PMC
February 2022
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