Publications by authors named "Jue Zhang"

316 Publications

Blinking Acoustic Nanodroplets Enable Fast Super-resolution Ultrasound Imaging.

ACS Nano 2021 Oct 14. Epub 2021 Oct 14.

State Key Laboratory of Membrane Biology, National Biomedical Imaging Center, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.

The advent of localization-based super-resolution ultrasound (SRUS) imaging creates a vista for precision vasculature and hemodynamic measurements in brain science, cardiovascular diseases, and cancer. As blinking fluorophores are crucial to super-resolution optical imaging, blinking acoustic contrast agents enabling ultrasound localization microscopy have been highly sought, but only with limited success. Here we report on the discovery and characterization of a type of blinking acoustic nanodroplets (BANDs) ideal for SRUS. BANDs of 200-500 nm diameters comprise a perfluorocarbon-filled core and a shell of DSPC, Pluronic F68, and DSPE-PEG2000. When driven by clinically safe acoustic pulses (MI < 1.9) provided by a diagnostic ultrasound transducer, BANDs underwent reversible vaporization and reliquefaction, manifesting as "blinks", at rates of up to 5 kHz. By sparse activation of perfluorohexane-filled BANDs-C at high concentrations, only 100 frames of ultrasound imaging were sufficient to reconstruct super-resolution images of a no-flow tube through either cumulative localization or temporal radiality autocorrelation. Furthermore, the use of high-density BANDs-C (1 × 10/mL) with a 1:9 admixture of perfluorohexane and perfluorobutane supported the fast SRUS imaging of muscle vasculature in live animals, at 64 μm resolution requiring only 100 frames per layer. We anticipate that the BANDs developed here will greatly boost the application of SRUS in both basic science and clinical settings.
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http://dx.doi.org/10.1021/acsnano.1c07896DOI Listing
October 2021

Elevated Serum Levels of Carbohydrate Antigen 72-4 in Diabetic Kidney Disease.

Exp Clin Endocrinol Diabetes 2021 Oct 4. Epub 2021 Oct 4.

Department of Clinical Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The aim of this study was to determine whether carbohydrate antigen 72-4 (CA72-4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72-4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72-4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72-4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72-4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; for trend< 0.05). CA72-4 also showed a positive correlation with UACR (r=0.288, < 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72-4 levels ( for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72-4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72-4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.
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http://dx.doi.org/10.1055/a-1532-4576DOI Listing
October 2021

Ultrasound microvasculature imaging with entropy-based radiality super-resolution (ERSR).

Phys Med Biol 2021 Sep 30. Epub 2021 Sep 30.

Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, CHINA.

Microvasculature is highly relevant to the occurrence and development of pathologies such as cancer and diabetes. Ultrasound localization microscopy (ULM) has bypassed the diffraction limit and demonstrated its great potential to provide new imaging modality and establish new diagnostic criteria in clinical application. However, sparse microbubble distribution can be a significant bottleneck for improving temporal resolution, even for further clinical translation. Other important challenges for ULM to tackle in clinic also include high microbubble concentration and low frame rate. As part of the efforts to facilitate clinical translation, this paper focused on the low frame rate and the high microbubble distribution issue and proposed a new super-resolution imaging strategy called Entropy-based Radiality Super-resolution (ERSR). The feasibility of ERSR is validated with simulations, phantom experiment and contrast-enhanced ultrasound scan of rabbit sciatic nerve with clinical accessible ultrasound system. ERSR can achieve 10 times improvement in spatial resolution compared to conventional ultrasound imaging, higher temporal resolution (~10 times higher) and contrast-to-noise ratio under high-density microbubbles, compared with ULM under low-density microbubbles. We conclude ERSR could be a valuable imaging tool with high spatio-temporal resolution for clinical diagnosis and assessment of diseases potentially.
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http://dx.doi.org/10.1088/1361-6560/ac2bb3DOI Listing
September 2021

Nanosecond pulsed electric fields prime mesenchymal stem cells to peptide ghrelin and enhance chondrogenesis and osteochondral defect repair in vivo.

Sci China Life Sci 2021 Sep 23. Epub 2021 Sep 23.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.

Mesenchymal stem cells (MSCs) are important cell sources in cartilage tissue development and homeostasis, and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration. Here we report the effects of combining nanosecond pulsed electric fields (nsPEFs) followed by treatment with ghrelin (a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs. nsPEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs, and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined, which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats. We further found that nsPEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway. Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway, and RNA-seq results indicated 243 genes were regulated, and JAK-STAT signaling pathway was involved. Interestingly, the sequential order of applying these two stimuli is critical, with nsPEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo, but not vice versa. This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.
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http://dx.doi.org/10.1007/s11427-021-1983-yDOI Listing
September 2021

Corrigendum to "Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy Improves Survival with Acceptable Safety for Advanced Ovarian Cancer: A Clinical Study of 100 Patients".

Biomed Res Int 2021 23;2021:9789613. Epub 2021 Aug 23.

Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, China.

[This corrects the article DOI: 10.1155/2021/5533134.].
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http://dx.doi.org/10.1155/2021/9789613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421173PMC
August 2021

Hypertriglyceridemia during hospitalization independently associates with mortality in patients with COVID-19.

J Clin Lipidol 2021 Aug 10. Epub 2021 Aug 10.

Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address:

Background: Alteration in blood triglyceride levels have been found in patients with coronavirus disease 2019 (COVID-19). However, the association between hypertriglyceridemia and mortality in COVID-19 patients is unknown.

Objective: To investigate the association between alteration in triglyceride level and mortality in hospitalized COVID-19 patients.

Methods: We conducted a retrospective study of 600 hospitalized patients with COVID-19 diagnosis (ICD10CM:U07.1) and/or SARS-CoV-2 positive testing results between March 1, 2020 and December 21, 2020 at a tertiary academic medical center in Milwaukee, Wisconsin. De-identified data, including demographics, medical history, and blood triglyceride levels were collected and analyzed. Of the 600 patients, 109 patients died. The triglyceride value on admission was considered the baseline and the peak was defined as the highest level reported during the entire period of hospitalization. Hypertriglyceridemia was defined as greater than 150 mg/dl. Logistic regression analyses were performed to evaluate the association between hypertriglyceridemia and mortality.

Results: There was no significant difference in baseline triglyceride levels between non-survivors (n = 109) and survivors (n = 491) [Median 127 vs. 113 mg/dl, p = 0.213]. However, the non-survivors had significantly higher peak triglyceride levels during hospitalization [Median 179 vs. 134 mg/dl, p < 0.001]. Importantly, hypertriglyceridemia independently associated with mortality [odds ratio=2.3 (95% CI: 1.4-3.7, p = 0.001)], after adjusting for age, gender, obesity, history of hypertension and diabetes, high CRP, high leukocyte count and glucocorticoid treatment in a multivariable logistic regression model.

Conclusions: Hypertriglyceridemia during hospitalization is independently associated with 2.3 times higher mortality in COVID-19 patients. Prospective studies are needed to independently validate this retrospective analysis.
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http://dx.doi.org/10.1016/j.jacl.2021.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353976PMC
August 2021

Comprehensive meta-analysis of anti-BCMA chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma.

Ann Med 2021 12;53(1):1547-1559

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.

Background: Chimeric antigen receptor (CAR) T-cell therapy shows impressive results in clinical trials. We conducted a meta-analysis based on the most recent data to systematically describe the efficacy and safety of anti-BCMA CAR T therapy for patients with relapsed or refractory multiple myeloma (R/R MM).

Methods: PubMed, Embase, Web of Science, Cochrane library, ClinicalTrials.gov, China Biology Medicine disc (CBM disc) and Wanfang Data were searched on 8 November 2020. Registration number of PROSPERO was CRD42020219127.

Results: From 763 articles, we identified 22 appropriate studies with 681 patients. The pooled overall response rate (ORR) was 85.2% (95%CI 0.797-0.910), complete response rate (CRR) was 47.0% (95%CI 0.378-0.583), and minimal residual disease (MRD) negativity rate was 97.8% (95%CI 0.935-1.022). The pooled incidence of grade 3-4 cytokine release syndrome was 6.6% (95%CI 0.036-0.096) and neurotoxicity was 2.2% (95%CI 0.006-0.038). The median progression-free survival (PFS) was 14.0 months and median overall survival (OS) was 24.0 months. Subgroup analysis showed dual epitope-binding CAR T cells achieved the best therapy outcomes and humanized CAR T cells had the best safety profile. Patients who were older, heavily pre-treated or received lower dose of CAR T cells had worse ORR. There was no significant difference in ORR, CRR and PFS between patients with and without high-risk cytogenetic features. The PFS and CRR of non-extramedullary disease (EMD) group was superior to those of EMD group.

Conclusion: Anti-BCMA CAR T therapy is effective and safe for patients with R/R MM. It can improve the prognosis of patients with high-risk cytogenetic features while the prognosis of patients with EMD remains poor. Moreover, patients are likely to benefit from an earlier use of CAR T therapy and human-derived CAR T cells have obvious advantages based on the existing data.
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http://dx.doi.org/10.1080/07853890.2021.1970218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409966PMC
December 2021

Sex Differences in Biopsy-Confirmed Diabetic Kidney Disease.

Front Endocrinol (Lausanne) 2021 29;12:670674. Epub 2021 Jul 29.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Background: To investigate the association between sex differences and end-stage kidney disease (ESKD) in patients with biopsy-confirmed diabetic kidney disease (DKD).

Method: We performed a retrospective cohort study. A total of 336 patients with biopsy-confirmed DKD who were followed up for at least 12 months were enrolled. Baseline clinical and pathological data at the time of biopsy were collected. ESKD was defined by an estimated glomerular filtration rate of <15 ml/min/1.73 m or initiation of renal replacement therapy. The association between sex differences and ESKD was assessed using the log-rank test and Cox regression.

Result: There were 239 (71%) male and 97 (29%) female patients in our cohort. Female patients had higher systolic blood pressure, total cholesterol and low-density lipoprotein cholesterol levels compared with male. There were a lower proportion of female patients in the very high risk grade according to the chronic kidney disease categories (37% of female vs. 44% of male). During a median follow-up time of 20 months, 101 (57.7%) male and 43 (44.3%) female entered into ESKD, with no significant difference by the log-rank test (0.05). Univariate [male: hazard ratio (HR) [95% confidence interval (CI)], 1.005, (0.702-1.439)] and multivariable ([male: HR (95%CI), 1.164, (0.675-2.007)]. Cox regression further showed that sex difference was not significantly associated with ESKD.

Conclusion: Female patients had the higher systolic blood pressure, total cholesterol, LDL-C, compared with male patients. However, there was no significant association observed between sex difference and ESKD in our study.
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http://dx.doi.org/10.3389/fendo.2021.670674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360678PMC
July 2021

NREM Sleep EEG Characteristics Correlate to the Mild Cognitive Impairment in Patients with Parkinsonism.

Biomed Res Int 2021 24;2021:5561974. Epub 2021 Jul 24.

Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

Early identification and diagnosis of mild cognitive impairment (MCI) in patients with parkinsonism (PDS) are critical. The aim of this study was to identify biomarkers of MCI in PDS using conventional electroencephalogram (EEG) power spectral analysis and detrended fluctuation analysis (DFA). In this retrospective study, patients with PDS who underwent an overnight polysomnography (PSG) study in our hospital from 2019 to 2020 were enrolled. Patients with PDS assessed by clinical examination and questionnaires were divided into two groups: the PDS with normal cognitive function (PDS-NC) group and the PDS with MCI (PDS-MCI) group. Sleep EEG signals were extracted and purified from the PSG and subjected to a conventional power spectral analysis, as well as detrended fluctuation analysis (DFA) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Forty patients with PDS were enrolled, including 25 with PDS-NC and 15 with PDS-MCI. Results revealed that compared with PDS-NC patients, patients with PDS-MCI had a reduced fast ratio ((alpha + beta)/(delta + theta)) and increased DFA during NREM sleep. DFA during NREM was diagnostic of PDS-MCI, with an area under the receiver operating characteristic curve of 0.753 (95% CI: 0.592-0.914) ( < 0.05). Mild cognitive dysfunction was positively correlated with NREM-DFA ( = 0.426, = 0.007) and negatively correlated with an NREM-fast ratio ( = -0.524, = 0.001). This suggested that altered EEG activity during NREM sleep is associated with MCI in patients with PDS. NREM sleep EEG characteristics of the power spectral analysis and DFA correlate to MCI. Slowing of EEG activity during NREM sleep may reflect contribution to the decline in NREM physiological function and is therefore a marker in patients with PDS-MCI.
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http://dx.doi.org/10.1155/2021/5561974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328717PMC
September 2021

Victimization and depressive symptoms among Chinese adolescents: A moderated mediation model.

J Affect Disord 2021 Nov 20;294:375-381. Epub 2021 Jul 20.

School of Humanities and Social Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Baohe District, Hefei 230022, PR China. Electronic address:

Background: Victimization as an inducing factor of depressive symptoms has been confirmed in previous studies. However, little is known about how and when it induces depressive symptoms in adolescents.

Methods: In total, 1174 Chinese adolescents were recruited to complete the Juvenile Victimization Questionnaire, Security Questionnaire, Positive Psychological Capital Questionnaire, and the Chinese version of the Center for Epidemiologic Studies Depression Scale.

Results: After controlling for gender and school type, the sense of security partially mediated the association between victimization and depressive symptoms. Moreover, direct association and the mediating effect of the sense of security were moderated by psychological capital. The moderating effect occurred in the second half of the mediating effect.

Limitations: Causal conclusions cannot be drawn based on cross-sectional research design. All measures were based on participant self-report.

Conclusions: The mediating model constructed in this study emphasized the important influence of stress, emotion, and psychological diathesis on adolescent depressive symptoms.
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http://dx.doi.org/10.1016/j.jad.2021.07.022DOI Listing
November 2021

Resistance Phenotype and Molecular Epidemiology of Carbapenem-Resistant Isolates in Shanghai.

Microb Drug Resist 2021 Jul 23. Epub 2021 Jul 23.

Department of Clinical Laboratory, Shanghai Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The emergence and wide global spread of carbapenem-resistant (CRKP) isolates are of great concern, and the aim of this study was to investigate drug resistance, molecular epidemiology, and genetic relationship of CRKP isolates from patients in Shanghai, China. A retrospective study was conducted from April 2018 to July 2019, and a total of 133 CRKP isolates were collected. Antimicrobial susceptibility was determined by VITEK-2 automated microbiology analyzer platform (bioMérieux, France) and the broth microdilution method. Polymerase chain reaction assays were used to investigate the presence of drug resistance genes. A modified carbapenem inactivation method was performed to detect carbapenemases. Multilocus sequence typing and pulsed-field gel electrophoresis (PFGE) were conducted for genetic relatedness of 50 CRKP isolates selected. Among 670 isolates of , 133 (19.9%) strains were identified as CRKP, of which, 76.7% (102/133) strains were isolated from intensive care units (ICUs). All the 133 CRKP isolates were found to be carbapenemase-producers and harbor bla gene. No other carbapenemase genes of , , , and were detected. Furthermore, β-lactamase genes of , , and were the most common resistance-associated genes among these producing isolates. All the 133 CRKP strains displayed >95% of resistance to cephalosporins and carbapenems, except for gentamicin, trimethoprim-sulfamethoxazole, amikacin, tigecycline and colistin, and ceftazidime-avibactam. The most common sequence type was ST11, accounting for 90.0% of the 50 CRKP selected, followed by ST15 (10.0%). PFGE analysis clustered the 50 producing isolates into seven (A-G) distinct clonal clusters at 85% cutoff. Of which, A and G were the two major clusters, accounting for the majority of the strains collected in emergency ICU and neurosurgical ICU. And all the strains of clusters D and E were collected in cardiothoracic surgery ICU, except for one strain collected in one outpatient. The -producing belonged to ST11 was widely disseminated in ICUs, and active and effective surveillance of infection control strategies was initiated to limit the spread of CRKP strains.
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http://dx.doi.org/10.1089/mdr.2020.0390DOI Listing
July 2021

A Training Simulator for Fractional Dilation and Curettage With Visualized Force-Position Feedback and Quantitative Evaluation.

Obstet Gynecol 2021 07;138(1):100-105

Academy for Advanced Interdisciplinary Studies and the College of Engineering, Peking University, and the Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China.

Background: Dilation and curettage (D&C) is a basic, but important procedure with many applications in obstetrics and gynecology. Fractional D&C provides comprehensive sampling of the endocervix and subsequently the uterus. This study designs and validates a novel fractional D&C training simulator visualizing the intrauterine operation in real time and quantitatively assessing technical skills.

Method: The fractional D&C training simulator, consisting of measurement hardware and visual software, can display the curette tip's trajectory and force in the uterus in real time. The simulator also presents assessment indices (the cervical coverage index, cervical overlap index, uterine coverage index, uterine overlap index) to indicate the completion degree and quality of surgical performance.

Experience: Seventy-five participants with three levels of D&C experience, including 26 novices, 24 intermediates, and 25 experts, were recruited to perform fractional D&C using the training simulator and asked to fill in a postprocedure questionnaire. All assessment indices of the novices were significantly lower than those of experienced surgeons (experts and intermediates) (P<.05). The simulator was highly regarded as a teaching tool and identified frequent areas of incomplete curettage even by experienced surgeons.

Conclusion: The fractional D&C training simulator provides valuable visualized force-position feedback and quantitative evaluation and may be beneficial for surgical training.
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http://dx.doi.org/10.1097/AOG.0000000000004443DOI Listing
July 2021

Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy Improves Survival with Acceptable Safety for Advanced Ovarian Cancer: A Clinical Study of 100 Patients.

Biomed Res Int 2021 22;2021:5533134. Epub 2021 Jun 22.

Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, China.

Background: The mainstay of treatment for advanced ovarian cancer is debulking surgery followed by chemotherapy that includes carboplatin and paclitaxel, but the prognosis is poor. This study is aimed at evaluating the efficacy and safety of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) as first-line surgical treatment in patients with advanced ovarian cancer (AOC).

Methods: FIGO stage III/IV AOC patients underwent CRS+HIPEC as first-line surgical treatment at our center from December 2007 to January 2020. The primary endpoint was survival, and the secondary endpoint was safety.

Results: Among 100 patients, the median Karnofsky performance status (KPS) score was 80 (50-100), median peritoneal cancer index (PCI) was 19 (1-39), median completeness of cytoreduction (CC) score was 1 (0-3), number of organ regions removed was 4 (3-9), number of peritoneal regions removed was 4 (1-9), and number of anastomoses was 1 (0-4). The median follow-up was 36.8 months; 75 (75.0%) patients were still alive, and 25 (25.0%) had died. The median overall survival (mOS) was 87.6 (95% CI: 72.1-103.0) months, and the 1-, 2-, 3-, 4-, and 5-year survival rates were 94.1%, 77.2%, 68.2%, 64.2%, and 64.2%, respectively. Univariate analysis showed that better mOS correlated with an age ≤, KPS ≥ 80, ascites ≤ 1000 ml, PCI < 19, and CC score 0-1. Multivariate Cox analysis showed that CC was an independent factor for OS; patients who underwent CRS with a CC score 0-1 had a mPFS of 67.8 (95% CI: 48.3-87.4) months. The perioperative serious adverse event and morbidity rates were 4.0% and 2.0%, respectively.

Conclusions: CRS+HIPEC improves survival for AOC patients with acceptable safety at experienced high-volume centers. Stringent patient selection and complete CRS are key factors for better survival.
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http://dx.doi.org/10.1155/2021/5533134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245244PMC
September 2021

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis.

Nanomicro Lett 2021 Mar 8;13(1):88. Epub 2021 Mar 8.

Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.

Sepsis, a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection, is a leading contributor to mortality in intensive care units. Sepsis-related deaths have been reported to account for 19.7% of all global deaths. However, no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis. Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis. Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry, targeting infection and/or imbalanced immune responses, have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment. Nanoplatforms can overcome the barriers faced by clinical strategies, including delayed diagnosis, drug resistance and incapacity to manage immune disorders. Here, we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts, summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies. Based on these state-of-the-art studies, this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.
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http://dx.doi.org/10.1007/s40820-021-00598-3DOI Listing
March 2021

The CNOT4 Subunit of the CCR4-NOT Complex is Involved in mRNA Degradation, Efficient DNA Damage Repair, and XY Chromosome Crossover during Male Germ Cell Meiosis.

Adv Sci (Weinh) 2021 05 16;8(10):2003636. Epub 2021 Mar 16.

MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University Hangzhou 310058 China.

The CCR4-NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6/6L and CNOT7/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. knockout male mice have been reported to be infertile. In this study, viable / double knockout mice are constructed, and the males are fertile. These results indicate that CNOT7 has CNOT6/6L-independent functions in vivo. It is also demonstrated that CNOT4 is required for post-implantation embryo development and meiosis progression during spermatogenesis. Conditional knockout of in male germ cells leads to defective DNA damage repair and homologous crossover between X and Y chromosomes. CNOT4 functions as a previously unrecognized mRNA adaptor of CCR4-NOT by targeting mRNAs to CNOT7 for deadenylation of poly(A) tails, thereby mediating the degradation of a subset of transcripts from the zygotene to pachytene stage. The mRNA removal promoted by the CNOT4-regulated CCR4-NOT complex during the zygotene-to-pachytene transition is crucial for the appropriate expression of genes involved in the subsequent events of spermatogenesis, normal DNA double-strand break repair during meiosis, efficient crossover between X and Y chromosomes, and ultimately, male fertility.
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http://dx.doi.org/10.1002/advs.202003636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132151PMC
May 2021

An automatic framework for evaluating the vascular permeability of bone metastases from prostate cancer.

Phys Med Biol 2021 Jun 8;66(12). Epub 2021 Jun 8.

College of Engineering, Peking University, Beijing, People's Republic of China.

Vascular permeability can reflect tumorigenesis and metastasis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess microvascular permeability by pharmacokinetic parameter estimation. Most estimation methods require manually selected arterial input function (AIF) or reference regions. However, the result will be unstable due to the annotation, which relies on personal experience. In this study, we propose an automatic framework for evaluating vascular permeability of bone metastases from prostate cancer without selecting AIF.This retrospective study comprised of 15 prostate cancer patients with bone metastases. Based on clinical consensus for three typical DCE-MRI curve patterns, three characteristic curves as regularization constraints were introduced to the extended Tofts model (ETM) using clustering strategy, and the clustering-based blind identification of multichannel (CBM) framework was then proposed for pharmacokinetic parameter estimation. With automatic segmentation of the whole bone area, we obtained the estimation of the pharmacokinetic parameters in the bone area and quantified for bone metastases. Two experienced radiologists compared the CBM estimations with the diagnostic results and we compared the estimations with those of the ETM in bone metastasis regions to evaluate the feasibility of the CBM framework.The higher signal regions ofandindicated the metastasis of prostate cancer, which is consistent with the cancer area marked by the radiologists. In addition, theandin bone metastasis regions were significantly higher than in normal bone regions ( < 0.001, < 0.001). The consistency of estimation by using the CBM framework and conventional ETM method was confirmed by Bland-Altman analysis.The proposed CBM framework can provide a fully automatic and reliable quantitative estimation of vascular permeability for bone metastases in prostate cancer patients.
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http://dx.doi.org/10.1088/1361-6560/ac02d3DOI Listing
June 2021

Effects of Continuous Positive Airway Pressure on Sleep EEG Characteristics in Patients with Primary Central Sleep Apnea Syndrome.

Can Respir J 2021 22;2021:6657724. Epub 2021 Apr 22.

Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China.

This study aimed to investigate the effects of continuous positive airway pressure (CPAP) on the electroencephalographic (EEG) characteristics of patients with primary central sleep apnea syndrome (CSAS). Nine patients with primary CSAS were enrolled in this study. The raw sleep EEG data were analyzed based on two main factors: fractal dimension (FD) and zero-crossing rate of detrended FD. Additionally, conventional EEG spectral analysis in the delta, theta, alpha, and beta bands was conducted using a fast Fourier transform. The FD in patients with primary CSAS who underwent CPAP treatment was significantly decreased during nonrapid eye movement (NREM) sleep but increased during rapid eye movement (REM) sleep ( < 0.05). Regarding the EEG spectral analysis, the alpha power increased, while the delta/alpha ratio decreased during REM sleep in patients with CSAS ( < 0.05). In conclusion, CPAP treatment can reduce FD in NREM sleep and increase FD during REM sleep in patients with primary CSAS. FD may be used as a new biomarker of EEG stability and improvement in brain function after CPAP treatment for primary CSAS.
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http://dx.doi.org/10.1155/2021/6657724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084662PMC
April 2021

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis.

Nanomicro Lett 2021 Dec 8;13:88. Epub 2021 Mar 8.

Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 People's Republic of China.

Sepsis, a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection, is a leading contributor to mortality in intensive care units. Sepsis-related deaths have been reported to account for 19.7% of all global deaths. However, no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis. Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis. Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry, targeting infection and/or imbalanced immune responses, have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment. Nanoplatforms can overcome the barriers faced by clinical strategies, including delayed diagnosis, drug resistance and incapacity to manage immune disorders. Here, we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts, summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies. Based on these state-of-the-art studies, this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.
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http://dx.doi.org/10.1007/s40820-021-00598-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938387PMC
December 2021

Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy.

Theranostics 2021 26;11(8):3642-3660. Epub 2021 Jan 26.

Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Host defense peptides (HDPs) have emerged as a novel therapeutic paradigm for wound management; however, their clinical applications remain a challenge owing to their poor pharmacological properties and lack of suitable pharmaceutical formulations. Nanodefensin (ND), a nanoengineered human α-defensin 5 (HD5), has shown improved pharmacological properties relative to the parent compound. In this study, we engineered a nanodefensin-encased hydrogel (NDEFgel), investigated the effects of NDEFgel on wound healing, and elucidated underlying mechanisms. ND was chemically synthesized and tested functions by antimicrobial and scratch assays and western blotting. Different NDEFgels were evaluated by characterizations including degradation, drug release and antimicrobial activity. In full-thickness excisional murine models, the optimal NDEFgel was directly applied onto wound sites, and the efficacy was assessed. Moreover, the underlying mechanisms of pro-regenerative effect developed by NDEFgel were also explored. Apart from bactericidal effects, ND modulated fibroblast behaviors by promoting migration and differentiation. Among the tested hydrogels, the Pluronic F127 (Plu) hydrogel represented the most desirable carrier for ND delivery owing to its favorable controlled release and compatibility with ND. Local treatment of NDEFgel on the wound bed resulted in accelerated wound regeneration and attenuated bacterial burden. We further demonstrated that NDEFgel therapy significantly upregulated genes related to collagen deposition and fibroblasts, and increased the expression of myofibroblasts and Rac1. We therefore found that Rac1 is a critical factor in the ND-induced modulation of fibroblast behaviors through a Rac1-dependent cytoskeletal rearrangement. Our results indicate that NDEFgel may be a promising dual-action therapeutic option for advanced wound management in the future.
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http://dx.doi.org/10.7150/thno.53089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914350PMC
July 2021

Ouabain Exhibited Strong Anticancer Effects in Melanoma Cells via Induction of Apoptosis, G2/M Phase Arrest, and Migration Inhibition.

Onco Targets Ther 2021 25;14:1261-1273. Epub 2021 Feb 25.

Burn and Plastic Surgery, Zhongda Hospital Affiliated Southeast University, Nanjing, 210009, People's Republic of China.

Background: Malignant melanoma was characterized by insensitive chemotherapy, drug resistance, and high metastatic ability, which resulted in the main reason for the mortality among skin-related cancers. The current agents were not sufficient to improve the treatment status of melanoma patients, and it was still needed to develop new chemotherapeutic drugs for melanoma. Our study aimed to study the anticancer effects and potential mechanisms of ouabain on melanoma cells.

Methods: The inhibitory effects of ouabain were determined by CCK8 and colony formation assays, and the morphological changes of melanoma cells were observed by inverted microscope. The apoptosis induction and cell cycle distribution were detected by annexin V/PI double staining and PI staining, respectively. The expression of the biomarker proteins in apoptosis and G2/M phase were determined by Western blotting analysis. The effects of ouabain on the migration of melanoma cells were measured by transwell migration assay and wound closure analysis. The potential mechanisms of ouabain in melanoma cells were analyzed by transcriptome sequencing.

Results: Our present study demonstrated that ouabain exhibited strong inhibitory effects on cell proliferation and triggered dramatical morphological changes of melanoma cells. Moreover, ouabain induced significant apoptosis in A375 rather than SK-Mel-28 cells via upregulation of bax expression and downregulation of bcl-2 expression. Consistently, ouabain treatment induced cell cycle arrest at G2/M phase in both A375 and SK-Mel-28 cells via upregulation of cyclin B1 and downregulation of cdc2 and cdc25c. Importantly, ouabain suppressed the migration of A375 and SK-Mel-28 cells. Furthermore, the transcriptome sequencing demonstrated that p53 and MAPK signaling pathway might play important roles in the inhibitory effects of ouabain.

Conclusion: Our study revealed that ouabain exhibited dramatical anticancer effects, which provided a novel application for cardiac glycoside drugs in the clinical treatment of melanoma.
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http://dx.doi.org/10.2147/OTT.S283548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920615PMC
February 2021

p300/CBP inhibitor A-485 inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss.

Int Immunopharmacol 2021 May 21;94:107458. Epub 2021 Feb 21.

Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China. Electronic address:

Osteoporosis is one of the most common metabolic bone diseases among pre- and post-menopausal women. Despite numerous advances in the treatment of osteoporosis in recent years, the outcomes remain poor due to severe side effects. In this study, we investigated whether A-485, a highly selective catalytic p300/CBP inhibitor, could attenuate RANKL-induced osteoclast differentiation and explored the underlying molecular mechanisms. The protective role of A-485 in osteoporosis was verified using a mouse model of ovariectomy (OVX)-induced bone loss and micro-CT scanning. A-485 inhibited RANKL-induced osteoclast differentiation in vitro by reducing the number of tartrate-resistant acid phosphatase-positive osteoclasts without inducing significant cytotoxicity. In particular, A-485 dose-dependently disrupted F-actin ring formation and downregulated the expression of genes associated with osteoclast differentiation, such as CTSK, c-Fos, TRAF6, VATPs-d2, DC-STAMP, and NFATc1, in a time- and dose-dependent manner. Moreover, A-485 inhibited the RANKL-induced phosphorylation of MAPK pathways and attenuated OVX-induced bone loss in the mouse model while rescuing the loss of bone mineral density. Our in vitro and in vivo findings suggest for the first time that A-485 has the potential to prevent postmenopausal osteoporosis and could therefore be considered as a therapeutic molecule against osteoporosis.
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http://dx.doi.org/10.1016/j.intimp.2021.107458DOI Listing
May 2021

Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice.

Am J Hum Genet 2021 03 23;108(3):469-481. Epub 2021 Feb 23.

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha 410078, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha 410078, China; Laboratory of Reproductive and Stem Cell Engineering, National Health and Family Planning Commission, Changsha 410078, China. Electronic address:

Total fertilization failure (TFF) can occur during in vitro fertilization (IVF) treatments, even following intracytoplasmic sperm injection (ICSI). Various male or female factors could contribute to TFF. Increasing evidence suggested that genetic variations in PLCZ1, which encodes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 (PLCζ), is involved in oocyte activation and is a key male factor in TFF. In the present study, we explored the genetic variants in male individuals that led to TFF. A total of 54 couples with TFF or poor fertilization (fertilization rate < 20%) were screened, and 21 couples were determined to have a male infertility factor by the mouse oocyte activation test. Whole-exome sequencing of these 21 male individuals identified three homozygous pathogenic variants in ACTL9 (actin like 9) in three individuals. ACTL9 variations led to abnormal ultrastructure of the perinuclear theca (PT), and PLCζ was absent in the head and present in the neck of the mutant sperm, which contributed to failed normal calcium oscillations in oocytes and subsequent TFF. The key roles of ACTL9 in the PT structure and TFF after ICSI were further confirmed in an Actl9-mutated mouse model. Furthermore, assisted oocyte activation by calcium ionophore exposure successfully overcame TFF and achieved live births in a couple with an ACTL9 variant. These findings identified the role of ACTL9 in the PT structure and the correct localization of PLCζ. The results also provide a genetic marker and a therapeutic option for individuals who have undergone ICSI without successful fertilization.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008497PMC
March 2021

TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis.

J Clin Invest 2021 02;131(4)

Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials.
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http://dx.doi.org/10.1172/JCI135197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880419PMC
February 2021

[Clinical and laboratory characteristics of 215 cases of coronavirus disease 2019 with different prognosis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Dec;32(12):1428-1433

State Key Laboratory of Virology Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, China. Corresponding author: Zhu Ya, Email:

Objective: To analyze the clinical and laboratory characteristics of coronavirus disease 2019 (COVID-19) patients with different prognosis, and to provide evidence for the diagnosis and treatment of COVID-19.

Methods: The clinical and laboratory characteristics of 215 cases of confirmed COVID-19 patients admitted in the First People's Hospital of Tianmen City from January 18 to March 10, 2020 were retrospectively analyzed, including blood cell indexes, inflammatory indexes [C-reactive protein (CRP) and procalcitonin (PCT)], liver function, cardiac function, renal function, blood coagulation function, electrolyte, chest CT scan, and 2019 novel coronavirus (2019-nCoV) nucleic acid tests. The differences of above indexes in the two groups were compared and analyzed. In addition, 55 patients with other viral pneumonia were selected as the control group who admitted to the hospital from August 1 to November 30, 2019. The changes of laboratory indexes of COVID-19 group and control group were observed.

Results: In the 215 patients, 206 patients survived and 9 patients died. The average age of survival group was significantly lower than that in the death group, and the average length of hospital stay was significantly longer than the death group. (1) Clinical features: the proportion of underlying diseases in the death group was significantly higher than that in the survival group, such as dyspnea, sore throat, shiver, hypertension, diabetes, coronary heart disease, renal disease, and surgical history. There were no significant differences in other symptoms, signs and underlying diseases between the two group. (2) Laboratory test indexes of the two groups: in death group, white blood cell count [WBC (×10/L): 10.6 (4.0, 13.4) vs. 4.90 (3.92, 6.26)], neutrophils count [NEU (×10/L): 9.7 (3.4, 12.2) vs. 2.9 (2.1, 4.2)]; ratio of neutrophils to lymphocytes [NLR: 14.66 (5.19, 18.48) vs. 2.34 (1.47, 3.34)], CRP [mg/L: 130.21 (35.74, 210.86) vs. 17.90 (3.11, 50.23)], PCT [mg/L: 1.46 (0.45, 13.12) vs. 0.04 (0.02, 0.07)], lactate dehydrogenase [LDH (μmol×s×L): 4.80 (3.34, 7.37) vs. 3.77 (2.99, 5.12)], creatinine [Cr (μmol/L): 72.9 (69.6, 627.5) vs. 68.4 (55.5, 81.9)], D-dimer [mg/L: 0.86 (0.56, 3.32) vs. 0.39 (0.33, 0.58)], the area of ground glass opacity of chest CT scan [77.8% (7/9) vs. 35.0% (72/206)], the area of local patchy shadows [55.6% (5/9) vs. 17.5% (36/206)], the area of bilateral patchy shadows [100.0% (9/9) vs. 49.5% (102/206)] were significantly higher than those in survival group (all P < 0.01), lymphocyte count [LYM (×10/L): 0.6 (0.5, 0.8) vs. 1.3 (1.0, 1.6)], Na [mmol/L: 136.1 (131.0, 136.8) vs. 138.8 (136.5, 140.4)], Cl [mmol/L: 97.7 (92.7, 100.9) vs. 102.7 (100.2, 104.3)], and carbon dioxide [CO (mmol/L): 23.0 (20.6, 28.5) vs. 29.2 (27.7, 30.9)] were significantly lower than those in survival group (all P < 0.05). (3) Laboratory test indicators in COVID-19 and control groups: in COVID-19 group, WBC, NEU, LYM, platelet count (PLT), coefficient of variation of red blood cell distribution width (RDW-CV), standard deviation of red blood cell distribution width (RDW-SD) and Cl were significantly lower than those in control group, NLR, CRP, K and CO were significantly higher than those in control group.

Conclusions: The major early symptoms of COVID-19 are fever, cough, chest tightness and fatigue. Age and underlying disease may be the risk factors which affect the prognosis of patients with COVID-19. The laboratory indexes such as WBC, NEU, LYM, CRP, PCT, LDH and Cr between death group and survival group were significantly abnormal in the early stages of COVID-19, which would have important implications for the prognosis of patients with COVID-19. Meanwhile, laboratory test indexes, including WBC, NEU, LYM, PLT, RDW-CV, RDW-SD, CRP, Cl, K and CO, also have important value in the differential diagnosis between COVID-19 and other viral pneumonia.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200824-00590DOI Listing
December 2020

Publisher Correction: Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging.

Nat Methods 2021 Feb;18(2):220

State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, College of Future Technology, Peking University, Beijing, China.

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http://dx.doi.org/10.1038/s41592-021-01066-xDOI Listing
February 2021

Establishment and histopathological study of patient-derived xenograft models and primary cell lines of epithelioid malignant peritoneal mesothelioma.

Exp Anim 2021 May 21;70(2):225-235. Epub 2021 Jan 21.

Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China.

Malignant peritoneal mesothelioma (MPM) is a rare malignancy with few experimental models. This study used the human surgical specimen to establish MPM patient-derived xenograft (PDX) models and primary cell lines to provide a study platform for MPM in vitro and in vivo, and conducted histopathological analysis. Our study used the experimental peritoneal cancer index (ePCI) score to evaluate gross pathology, and the results showed that the ePCI score of the female and male nude mice were 8.80 ± 1.75 and 9.20 ± 1.81 (P=0.6219), respectively. The Hematoxylin and eosin (HE) staining of animal models showed that the tumor was epithelioid mesothelioma and invaded multiple organs. Immunohistochemistry (IHC) staining showed that Calretinin, Cytokeratin 5/6, WT-1 and Ki-67 were all positive. The Swiss-Giemsa and Immunofluorescence (IF) staining of primary cell lines were also consistent with the pathological characteristics of mesothelioma. We also performed the whole-exome sequencing (WES) to identify the mutant genes between models and the patient. And the results showed that 21 mutant genes were shared between the two groups, and the genes related to tumorigenesis and development including BAP1, NF2, MTBP, NECTIN2, CDC23, LRPPRC, TRIM25, and DHRS2. In conclusion, the PDX models and primary cell lines of MPM were successfully established with the epithelioid mesothelioma identity confirmed by histopathological evidence. Moreover, our study has also illustrated the shared genomic profile between models and the patient.
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http://dx.doi.org/10.1538/expanim.20-0119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150237PMC
May 2021

[Consistency of two commercial secondary antibodies for immunohistochemistry].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jan;37(1):47-53

Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038; Department of Peritoneal Cancer Surgery, Capital Medical University (Beijing Technical Training Base of Tumor Deep Hyperthermia and Whole-body Hyperthermia), Beijing 100038, China. *Corresponding author, E-mail:

Objective To compare the consistency of immunohistochemical staining between the two commercial secondary antibodies. Methods Eighteen common immunohistochemical primary antibodies were selected and positive and negative controls were set up according to the recommendations from the AD Hoc Committee of International Experts. Under the same experimental conditions, the DAKO automatic immunohistochemical staining platform was used to test two different secondary antibodies for immunohistochemical staining. The standard group for the secondary antibody was provided by the DAKO polymer system (DAKO EnVision FLEX, High pH), and the experimental group for the secondary antibody was provided by the Power-Stain kit (Power-Stain 1.0 Poly HRP DAB Kit for Mouse+Rabbit). Subsequently, the images were captured. A single-blind, positioning, qualitative and semi-quantitative scoring criterion was used for describing the positive stains by the experienced pathologist. Absorbance corrected values, measured area values and positive integral absorbance were detected by the digital pathology quantitative measurement in the same areas from the two groups. Then, the mean absorbance was calculated. Results The stains of all the samples from the two groups showed accurate location and consistent qualitative evaluation. No significant differences were found between the two groups in all the semi-quantitative scoring, including stain intensity, positive stain percentages and mean absorbance. Conclusion The two commercial secondary antibodies have strong consistency in the immunohistochemical staining.
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January 2021

A deep learning model for diagnosing dystrophinopathies on thigh muscle MRI images.

BMC Neurol 2021 Jan 11;21(1):13. Epub 2021 Jan 11.

Department of Neurology, Peking University First Hospital, Beijing, China.

Background: Dystrophinopathies are the most common type of inherited muscular diseases. Muscle biopsy and genetic tests are effective to diagnose the disease but cost much more than primary hospitals can reach. The more available muscle MRI is promising but its diagnostic results highly depends on doctors' experiences. This study intends to explore a way of deploying a deep learning model for muscle MRI images to diagnose dystrophinopathies.

Methods: This study collected 2536 T1WI images from 432 cases who had been diagnosed by genetic analysis and/or muscle biopsy, including 148 cases with dystrophinopathies and 284 cases with other diseases. The data was randomly divided into three sets: the data from 233 cases were used to train the CNN model, the data from 97 cases for the validation experiments, and the data from 102 cases for the test experiments. We also validated our models expertise at diagnosing by comparing the model's results on the 102 cases with those of three skilled radiologists.

Results: The proposed model achieved 91% (95% CI: 0.88, 0.93) accuracy on the test set, higher than the best accuracy of 84% in radiologists. It also performed better than the skilled radiologists in sensitivity : sensitivities of the models and the doctors were 0.89 (95% CI: 0.85 0.93) versus 0.79 (95% CI:0.73, 0.84; p = 0.190).

Conclusions: The deep model achieved excellent accuracy and sensitivity in identifying cases with dystrophinopathies. The comparable performance of the model and skilled radiologists demonstrates the potential application of the model in diagnosing dystrophinopathies through MRI images.
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http://dx.doi.org/10.1186/s12883-020-02036-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798322PMC
January 2021

Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging.

Nat Methods 2021 01 6;18(1):46-49. Epub 2021 Jan 6.

State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, College of Future Technology, Peking University, Beijing, China.

We have developed a miniature two-photon microscope equipped with an axial scanning mechanism and a long-working-distance miniature objective to enable multi-plane imaging over a volume of 420 × 420 × 180 μm at a lateral resolution of ~1 μm. Together with the detachable design that permits long-term recurring imaging, our miniature two-photon microscope can help decipher neuronal mechanisms in freely behaving animals.
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http://dx.doi.org/10.1038/s41592-020-01024-zDOI Listing
January 2021

Corrigendum: Glucose-Regulated Protein 78 Signaling Regulates Hypoxia-Induced Epithelial-Mesenchymal Transition in A549 Cells.

Front Oncol 2020 15;10:615415. Epub 2020 Dec 15.

Integrative Cancer Centre, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

[This corrects the article .].
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http://dx.doi.org/10.3389/fonc.2020.615415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771355PMC
December 2020
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