Publications by authors named "Ji Zhang"

1,357 Publications

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[Early effectiveness of robot-assisted total hip arthroplasty via direct superior approach].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Oct;35(10):1240-1245

Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Beijing, 100035, P.R.China.

Objective: To evaluate the early effectiveness of the robot-assisted total hip arthroplasty (THA) via direct superior approach (DSA).

Methods: Between March 2021 and April 2021, 11 patients (11 hips) were treated with a robot-assisted THA via DSA. There were 7 males and 4 females, with an average age of 55 years (range, 26-73 years). There were 5 patients of osteoarthritis secondary to hip dysplasia and 6 patients of osteonecrosis of femoral head. Preoperative hip Harris score was 55.8±6.3. The operation time, volume of blood loss, length of incision, postoperative blood transfusion and hospital stay, and the incidence of surgical complications were recorded. The visual analogue scale (VAS) score and Harris score were used to evaluate hip joint pain and function. The leg length discrepancy (LLD) was measured on the X-ray films. The inclination angle and anteversion angle of the acetabular component were also measured, and the difference between the planned and actual values were compared.

Results: One THA was performed via conventional posterolateral approach finally because of poor exposure. The rest of 10 THAs were performed with assistance of robotic arm via DSA. The average operation time was 89 minutes (range, 65-120 minutes); the average length of incision was 10.5 cm (range, 9-13 cm); and the average blood loss was 400 mL (range, 110-740 mL). One patient was given a blood transfusion for 2 unit. All incisions healed by first intention and no neurovascular injury, deep vein thrombosis, or fracture occurred. The length of hospital stay after operation was 2-6 days (mean, 4.4 days). The duration of follow-up was 1-3 months (mean, 2.1 months). The VAS score was 0 in 9 patients and 2 in 1 patient at the day of discharge. At last follow-up, the hip Harris score was 84.9±6.7, showing significant difference when compared with that before operation ( =-8.717, =0.000). The inclination and anteversion angles were (37.4±2.0)° and (17.1±4.5)°, respectively, and there was no significant difference when compared with the planned values [(38.2±1.6)°, (16.6±3.7)°] ( =1.809, =0.104; =-1.103, =0.299). The LLD ranged from -2 to 4 mm. No complication such as dislocation, aseptic loosening, or periprosthetic joint infection occurred.

Conclusion: The robot-assisted THA via DSA has encouraged early effectiveness.
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http://dx.doi.org/10.7507/1002-1892.202105115DOI Listing
October 2021

Whole-genome sequencing and ad hoc shared genome analysis of Staphylococcus aureus isolates from a New Zealand primary school.

Sci Rep 2021 Oct 13;11(1):20328. Epub 2021 Oct 13.

School of Veterinary Science, Massey University, Palmerston North, New Zealand.

Epidemiological studies of communicable diseases increasingly use large whole-genome sequencing (WGS) datasets to explore the transmission of pathogens. It is important to obtain an initial overview of datasets and identify closely related isolates, but this can be challenging with large numbers of isolates and imperfect sequencing. We used an ad hoc whole-genome multi locus sequence typing method to summarise data from a longitudinal study of Staphylococcus aureus in a primary school in New Zealand. Each pair of isolates was compared and the number of genes where alleles differed between isolates was tallied to produce a matrix of "allelic differences". We plotted histograms of the number of allelic differences between isolates for: all isolate pairs; pairs of isolates from different individuals; and pairs of isolates from the same individual. 340 sequenced isolates were included, and the ad hoc shared genome contained 445 genes. There were between 0 and 420 allelic differences between isolate pairs and the majority of pairs had more than 260 allelic differences. We found many genetically closely related S. aureus isolates from single individuals and a smaller number of closely-related isolates from separate individuals. Multiple S. aureus isolates from the same individual were usually very closely related or identical over the ad hoc shared genome. Siblings carried genetically similar, but not identical isolates. An ad hoc shared genome approach to WGS analysis can accommodate imperfect sequencing of the included isolates, and can provide insights into relationships between isolates in epidemiological studies with large WGS datasets containing diverse isolates.
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http://dx.doi.org/10.1038/s41598-021-99080-8DOI Listing
October 2021

Global Gender Disparities in Premature Death from Cardiovascular Disease, and Their Associations with Country Capacity for Noncommunicable Disease Prevention and Control.

Int J Environ Res Public Health 2021 Oct 2;18(19). Epub 2021 Oct 2.

Department of Global Health, School of Public Health, Peking University, Beijing 100191, China.

This study aimed to describe the prevalence of gender disparity in cardiovascular disease and explore its association with a country's capacity for controlling noncommunicable diseases. Study data were extracted from the Global Health Estimates, and the Noncommunicable Disease Country Capacity Survey. Age-standardized premature death rates from cardiovascular disease, defined as any death occurring from ages 30 to 70 years, were calculated. Univariate and multivariate general linear regression models were fitted to estimate the correlations between gender disparity and country capacity for noncommunicable disease control. Globally, the premature death rate from cardiovascular diseases was 35.6% higher among men than women in 2000, and the figure hardly changed from 2000 to 2016. The highest gender differences were observed in Europe and high-income countries. The existence of dedicated and multisectoral noncommunicable disease governance bodies and the availability of cardiovascular disease stratification in primary healthcare facilities were positively correlated with gender differences. Conclusively, gender disparities in premature death rates from cardiovascular diseases differed with economic conditions and across geographic regions, with higher relative differences observed in more developed countries. The effects of existing control measures may have plateaued in men but are ongoing among women, especially in more developed countries, widening the gender disparity.
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http://dx.doi.org/10.3390/ijerph181910389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507619PMC
October 2021

Prognostic Impact of the Symptom of New-Onset Atrial Fibrillation in Acute Myocardial Infarction: Insights From the NOAFCAMI-SH Registry.

Front Cardiovasc Med 2021 22;8:677695. Epub 2021 Sep 22.

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

New-onset atrial fibrillation (NOAF) is a common complication during acute myocardial infarction (AMI) and sometimes can be completely asymptomatic, but the clinical implications of these asymptomatic episodes require further characterization. The objective of this study was to investigate the short- and long-term prognostic impact of post-MI NOAF based on the presence of AF-related symptoms. The New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai (NOAFCAMI-SH) registry was a retrospective cohort including participants with AMI without a documented history of AF. Patients with NOAF were divided into two groups according to the AF-related symptoms. The primary endpoint was all-cause mortality. Of 2,399 patients included, 278 (11.6%) developed NOAF of whom 145 (6.0%) with asymptomatic episodes and 133 (5.5%) with symptomatic ones. During hospitalization, 148 patients died [106, 10, and 32 in the sinus rhythm (SR), asymptomatic, and symptomatic NOAF groups, respectively]. After multivariable adjustment, only symptomatic NOAF was associated with in-hospital mortality [odds ratio (OR): 2.32, 95% confidence interval (CI): 1.36-3.94] compared with SR. Over a median follow-up of 2.7 years, all-cause mortality was 3.2, 12.4, and 11.8% per year in the SR, asymptomatic, and symptomatic NOAF groups, respectively. After adjustment for confounders, it was the asymptomatic NOAF [hazard ratio (HR): 1.61, 95% CI: 1.09-2.37) rather than the symptomatic one (HR: 1.37, 95% CI: 0.88-2.12) that was significantly related to mortality. Similar results were also observed for cardiovascular mortality [HRs and 95% CI were 1.71 (1.10-2.67) and 1.25 (0.74-2.11) for asymptomatic and symptomatic NOAF, respectively]. Both asymptomatic and symptomatic NOAF episodes were associated with heart failure, whereas only those with symptomatic NOAF were at heightened risk of ischemic stroke. Our exploratory analysis further identified patients with asymptomatic high-burden NOAF as the highest-risk population (mortality: 19.6% per year). Among patients with AMI, symptomatic NOAF is related to in-hospital mortality and asymptomatic NOAF is associated with poor long-term survival. URL: https://clinicaltrials.gov/; Unique identifier: NCT03533543.
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http://dx.doi.org/10.3389/fcvm.2021.677695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492948PMC
September 2021

Corrigendum: CX3CR1 But Not CCR2 Expression Is Required for the Development of Autoimmune Peripheral Neuropathy in Mice.

Front Immunol 2021 24;12:765892. Epub 2021 Sep 24.

The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

[This corrects the article DOI: 10.3389/fimmu.2021.720733.].
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http://dx.doi.org/10.3389/fimmu.2021.765892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499671PMC
September 2021

Long non-coding RNA TTC28-AS1 attenuates high glucose-induced damage in HK-2 cells depending on the regulation of miR-320a/CD2AP axis.

Genes Genomics 2021 Oct 8. Epub 2021 Oct 8.

Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of HuBei University of Arts and Science, Xiangyang, Hubei, China.

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in DN pathogenesis.

Objective: The purpose of the present study was to explore the role and mechanism of lncRNA tetratricopeptide repeat domain 2B antisense RNA 1 (TTC28-AS1) in DN.

Methods: Cell viability and apoptosis were assessed by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of TTC28-AS1, miR-320a and CD2-associated protein (CD2AP) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-8 were gauged by enzyme-linked immunosorbent assay (ELISA). Targeted relationship between miR-320a and TTC28-AS1 or CD2AP was evaluated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

Results: Our data indicated that high glucose (HG) induced HK-2 cell damage by the repression of cell viability and autophagy and the enhancement of cell apoptosis, fibrosis and pro-inflammatory cytokines production. TTC28-AS1 was down-regulated and miR-320a was up-regulated in HG-induced HK-2 cells. TTC28-AS1 overexpression or miR-320a knockdown alleviated HG-induced damage in HK-2 cells. MiR-320 was a molecular mediator of TTC28-AS1 in regulating HG-induced HK-2 cell damage. Moreover, TTC28-AS1 functioned as a post-transcriptional regulator of CD2AP expression by miR-320a. MiR-320a knockdown relieved HG-induced damage in HK-2 cells by up-regulating CD2AP.

Conclusions: Our findings suggest that TTC28-AS1 attenuates HG-induced damage in HK-2 cells at least partially by targeting the miR-320a/CD2AP axis, highlighting its role as a promising therapeutic approach for DN treatment.
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http://dx.doi.org/10.1007/s13258-021-01167-zDOI Listing
October 2021

Molecular characteristics and risk factor analysis of Staphylococcus aureus colonization put insight into CC1 colonization in three nursing homes in Shanghai.

PLoS One 2021 7;16(10):e0253858. Epub 2021 Oct 7.

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Research indicates that Staphylococcus aureus colonization in the elderly with predisposing risks is associated with subsequent infection. However, the molecular epidemiology and risk factors for S. aureus colonization among residents and staff in nursing homes (NHs) in China remain unclear. A multicenter study was conducted in three NHs in Shanghai between September 2019 and October 2019. We explored the prevalence, molecular epidemiology, and risk factors for S. aureus colonization. All S. aureus isolates were characterized based on antimicrobial resistance, virulence genes, multilocus sequence typing (MLST), staphylococcus protein A (spa) typing, and staphylococcal cassette chromosome mec (SCCmec) typing. NH records were examined for potential risk factors for S. aureus colonization. S. aureus and methicillin-resistant S. aureus (MRSA) isolates were detected in 109 (100 residents and 9 staff, 19.8%, 109/551) and 28 (24 residents and 4 staff, 5.1%, 28/551) subjects among 496 residents and 55 staff screened, respectively. Compared to methicillin-susceptible S. aureus isolates, all 30 MRSA isolates had higher resistance rates to most antibiotics except minocycline, rifampicin, linezolid, vancomycin, and teicoplanin. Sequence type (ST) 1 (21.3%) was the most common sequence type, and t127 (20.5%) was the most common spa type among 122 S. aureus isolates. SCCmec type I (70%) was the dominant clone among all MRSA isolates. CC1 (26/122, 21.3%) was the predominant complex clone (CC), followed by CC398 (25/122, 20.5%), CC5 (20/122, 16.4%) and CC188 (18/122, 14.8%). Female sex (OR, 1.70; 95% CI, 1.04-2.79; P = 0.036) and invasive devices (OR, 2.19; 95% CI, 1.26-3.81; P = 0.006) were independently associated with S. aureus colonization.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253858PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496869PMC
October 2021

Generating adversarial examples without specifying a target model.

PeerJ Comput Sci 2021 13;7:e702. Epub 2021 Sep 13.

School of Computer Science and Engineering, Anhui University of Science and Technology, Huainan, China.

Adversarial examples are regarded as a security threat to deep learning models, and there are many ways to generate them. However, most existing methods require the query authority of the target during their work. In a more practical situation, the attacker will be easily detected because of too many queries, and this problem is especially obvious under the black-box setting. To solve the problem, we propose the Attack Without a Target Model (AWTM). Our algorithm does not specify any target model in generating adversarial examples, so it does not need to query the target. Experimental results show that it achieved a maximum attack success rate of 81.78% in the MNIST data set and 87.99% in the CIFAR-10 data set. In addition, it has a low time cost because it is a GAN-based method.
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http://dx.doi.org/10.7717/peerj-cs.702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459786PMC
September 2021

Graph-Theoretic Post-Processing of Segmentation With Application to Dense Biofilms.

IEEE Trans Image Process 2021 15;30:8580-8594. Epub 2021 Oct 15.

Recent deep learning methods have provided successful initial segmentation results for generalized cell segmentation in microscopy. However, for dense arrangements of small cells with limited ground truth for training, the deep learning methods produce both over-segmentation and under-segmentation errors. Post-processing attempts to balance the trade-off between the global goal of cell counting for instance segmentation, and local fidelity to the morphology of identified cells. The need for post-processing is especially evident for segmenting 3D bacterial cells in densely-packed communities called biofilms. A graph-based recursive clustering approach, m-LCuts, is proposed to automatically detect collinearly structured clusters and applied to post-process unsolved cells in 3D bacterial biofilm segmentation. Construction of outlier-removed graphs to extract the collinearity feature in the data adds additional novelty to m-LCuts. The superiority of m-LCuts is observed by the evaluation in cell counting with over 90% of cells correctly identified, while a lower bound of 0.8 in terms of average single-cell segmentation accuracy is maintained. This proposed method does not need manual specification of the number of cells to be segmented. Furthermore, the broad adaptation for working on various applications, with the presence of data collinearity, also makes m-LCuts stand out from the other approaches.
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http://dx.doi.org/10.1109/TIP.2021.3116792DOI Listing
October 2021

MZF1 alleviates oxidative stress and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription.

J Toxicol Sci 2021 ;46(10):477-486

Department of Neurology, Jiangxi Provincial People's Hospital, China.

Objective: To investigate the protective effect of MZF1/RBM3 on rotenone-induced neuronal injury.

Methods: Rotenone (1 μM) was used to treat SH-SY5Y cells for 24 hr to simulate the cellular model of Parkinson's disease (PD), followed by detection of SH-SY5Y cell activities using MTT assay. MZF1 expression in rotenone-treated SH-SY5Y cells was detected by qRT-PCR and Western blot. MZF1 overexpression plasmid or MZF1 overexpression plasmid and RBM3 siRNA was transfected into SH-SY5Y cells, and then the expressions of MZF1 and RBM3 were detected. Oxidative stress (OS) in SH-SY5Y cells was detected using CMH2DCF-DA probes. Cell apoptosis rate was detected by flow cytometry. CHIP assay and dual-luciferase reporter assay were used to detect the binding between MZF1 and RBM3 promoter.

Results: The expression of MZF1 was significantly lower in the rotenone-induced SH-SY5Y cells. Overexpression of MZF1 significantly reduced OS and apoptosis in rotenone-induced SH-SY5Y cells. MZF1 was a transcription factor of RBM3, which promoted the transcription of RBM3, and knockdown of RBM3 inhibited the protective effect of MZF1 overexpression on SH-SY5Y cells.

Conclusion: MZF1 alleviates OS and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription.
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http://dx.doi.org/10.2131/jts.46.477DOI Listing
January 2021

The Added Value of Ga-FAPI-04 PET/CT in Patients with Head and Neck Cancer of Unknown Primary with F-FDG Negative Findings.

J Nucl Med 2021 Sep 30. Epub 2021 Sep 30.

Fudan University Shanghai Cancer Center, China.

F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in locating of primary tumor for patients with head and neck cancer of unknown primary (HNCUP). Nevertheless, it can be challenging to locate the primary malignancy in F-FDG-PET/CT scan in some cases. As Ga-radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT has promising results in detecting different tumor entities, our study aimed to evaluate the performance of Ga-FAPI-PET/CT for detecting the primary tumor in HNCUP patients with negative F-FDG findings. A total of eighteen patients (16 males and 2 females; median age, 55 years; range, 24-72 years) with negative F-FDG findings were enrolled in this study. All patients underwent F-FDG and Ga-FAPI-PET/CT within one week. Biopsy and histopathological examinations were done in the sites with positive Ga-FAPI-PET/CT findings. Ga-FAPI-PET/CT detected the primary tumor in 7 out of 18 patients (38.89%). Among the 7 patients, in respect of the primary tumor sites, 1 was in nasopharynx, 2 were in palatine tonsil, 2 were in submandibular gland, and 2 were in hypopharynx. The primary tumors showed moderate to intensive uptake of FAPI (mean SUV, 8.79; range, 2.60-16.50) and excellent tumor-to-contralateral normal tissue ratio (mean SUV ratio, 4.50; range, 2.17-8.21). In lesion-based analysis, a total of 65 lymph nodes and 17 bone metastatic lesions were identified. The mean SUV of lymph node metastases were 9.05 ± 5.29 for FDG and 9.08 ± 4.69 for FAPI ( = 0.975); as for bone metastases, the mean SUV were 8.11 ± 3.00 for FDG and 6.96 ± 5.87 for FAPI, respectively ( = 0.478). The mean tumor-to-background ratio (TBR) values of lymph node and bone metastases were 10.65 ± 6.59 vs. 12.80 ± 8.11 ( = 0.100) and 9.08 ± 3.35 vs. 9.14 ± 8.40 ( = 0.976), respectively. We presented first evidence of diagnostic role of Ga-FAPI-PET/CT in HNCUP, and our study demonstrated that Ga-FAPI-PET/CT had the potential to improve the detection rate of primary tumor in HNCUP patients with negative FDG findings. Moreover, Ga-FAPI had similar performance in assessing metastases with F-FDG.
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http://dx.doi.org/10.2967/jnumed.121.262790DOI Listing
September 2021

Bilateral lung transplantation for Castleman disease with end-stage bronchiolitis obliterans.

Clin Transplant 2021 Sep 30:e14496. Epub 2021 Sep 30.

Wuxi Lung Transplant Center, Department of Thoracic Surgery, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.

Bronchiolitis obliterans (BO) is a severe complication of Castleman disease (CD), a rare lymphoproliferative disease with unclear pathogenesis. Currently, there are no reports on the safety or outcomes of bilateral lung transplantation in patients with BO due to CD. This study aimed to characterize the clinical manifestations and features of BO and CD. We retrospectively analyzed the medical records of six consecutive patients with BO and CD who underwent bilateral lung transplantation between December 2012 and December 2020. The average age of patients at lung transplantation was 33 ± 15 years, and the age range of patients at diagnosis of CD was about 9-56 years. The body mass index was 15.2 ± 1.9 kg/m . The average time from diagnosis to lung transplantation was 4.1 ± 2.7 years. All the patients had unicentric CD (UCD); five had concomitant paraneoplastic pemphigus, and four received extracorporeal membrane oxygenation during surgery. The average hospital stay was 51 ± 53 days. Infection was the most common postoperative complication. CD did not recur in any of the patients. Thus, bilateral lung transplantation is a viable and safe treatment for selected patients with CD and BO, which can improve the quality of life and prolong survival.
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http://dx.doi.org/10.1111/ctr.14496DOI Listing
September 2021

One-step fabrication of functional carbon dots with long wavelength emission for gene delivery and bio-imaging.

J Mater Chem B 2021 Oct 20;9(40):8518-8529. Epub 2021 Oct 20.

Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu, 610064, P. R. China.

As a new-type of fluorescent material, carbon dots (CDs) are promising nanoscale reagents with the potential to integrate the functions of bio-imaging and gene/drug delivery. Most of the reported CDs for nucleic acid delivery only emitted short-wavelength (blue and green) fluorescence, making them unsuitable for application. Herein, a one-step solvothermal method was applied to prepare CDs with long wavelength emission from low molecular weight PEI and rhodamine dyes for both bio-imaging and gene delivery. The structure of the CDs was confirmed by several analytical methods including H NMR, FT-IR, TEM, and XPS. The results showed that the CDs possess excellent fluorescence properties, which enable their application in both and bio-imaging. Meanwhile, the CDs could also be used for the intracellular tracking of the gene delivery process. transfection results revealed that the CDs possessed high transfection efficiency, which was up to 162 times higher than that of the "golden standard" transfection reagent PEI 25 kDa. Besides, these CDs also exhibited better serum tolerance and lower cytotoxicity than PEI. A mechanistic study suggested that the CD/DNA complexes may release the nucleic acid cargo more effectively. This work provides a new method to prepare multi-functional CDs with non-viral gene delivery and long wavelength bio-imaging abilities.
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http://dx.doi.org/10.1039/d1tb01622aDOI Listing
October 2021

Long-Term Clinical and Immunological Impact of Severe COVID-19 on a Living Kidney Transplant Recipient - A Case Report.

Front Immunol 2021 8;12:741765. Epub 2021 Sep 8.

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, National Health Commission and Chinese Academy of Medical Sciences, Wuhan, China.

The long-term impact of COVID-19 on transplant recipients remains unknown. We describe the case of a 30-year-old male kidney transplant recipient from Wuhan, China that was treated for severe COVID-19 in February 2020. He suffered an acute lung and renal injury and required systemic treatment including adjustment of his immunosuppressant regime. He was followed up to 1-year after discharge. No chronic lung fibrosis or deterioration of his pulmonary function was observed. Despite COVID-19 mediated damage to his renal tubular cells, no transplant rejection occurred. His immunological profile demonstrated both cellular anti-SARS-CoV-2 reactivity and specific humoral immunity, indicating that it is beneficial for the transplanted patients to be immunized with SARS-CoV-2 virus vaccine. This case will help guide clinical decision making for immunocompromised individuals that become infected with SARS-CoV-2.
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http://dx.doi.org/10.3389/fimmu.2021.741765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456079PMC
October 2021

Circ_0011058 facilitates proliferation, angiogenesis and radioresistance in papillary thyroid cancer cells by positively regulating YAP1 via acting as miR-335-5p sponge.

Cell Signal 2021 Sep 22;88:110155. Epub 2021 Sep 22.

Department of Nephrology, Henan Provincial People's Hospital, Zhengzhou City, Henan Province, China.

Background: Circular RNAs (circRNAs) are reported to be associated with multiple biological processes in human cancers. However, there are still numerous circRNAs whose functions remain unclear. The aim of this study was to investigate the role of circ_0011058 in papillary thyroid cancer (PTC).

Methods: Quantitative real-time PCR (qPCR) was utilized to detect the expression of circ_0011058, microRNA-335-5p (miR-335-5p) and Yes-associated Protein 1 (YAP1). Cell proliferation was detected using cell counting kit-8 (CCK-8) assay and EdU assay. Cell apoptosis was detected by flow cytometry assay. Angiogenesis ability was assessed using tube formation assay. The expression of angiogenesis-related proteins and YAP1 protein was detected by western blot. Radioresistance was examined using colony formation assay. The binding relationship between miR-335-5p and circ_0011058 or YAP1 was verified by dual-luciferase reporter assay, pull-down assay and RIP assay. Xenograft models were constructed to ensure the role of circ_0011058.

Results: Circ_0011058 expression was aberrantly elevated in PTC tissues and cells. The downregulation of circ_0011058 suppressed proliferation, angiogenesis and radioresistance in PTC cells. MiR-335-5p was defined as a target of circ_0011058, and miR-335-5p inhibition reversed the effects of circ_0011058 downregulation. In addition, YAP1 was a target of miR-335-5p, and circ_0011058 positively regulated YAP1 expression by targeting miR-335-5p. MiR-335-5p restoration inhibited proliferation, angiogenesis and radioresistance in PTC cells, while YAP1 overexpression abolished these effects. Animal study showed that circ_0011058 knockdown inhibited tumor growth in vivo.

Conclusion: Circ_0011058 promoted PTC cell proliferation, angiogenesis and radioresistance by upregulating YAP1 via acting as miR-335-5p sponge.
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http://dx.doi.org/10.1016/j.cellsig.2021.110155DOI Listing
September 2021

Electroacupuncture inhibits the corneal ROS/TXNIP/NLRP3 signaling pathway in a rat model of dry eye syndrome.

Acupunct Med 2021 Sep 23:9645284211039235. Epub 2021 Sep 23.

Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, China.

Background: Electroacupuncture (EA) treatment has been found to ameliorate clinical symptoms in patients with dry eye, but its mechanisms are still not entirely clear.

Objective: To study the regulation of EA on ocular surface function and the corneal reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/Nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in dry eye syndrome (DES) model rats.

Methods: Male Sprague-Dawley (SD) rats were randomly divided into five groups: Normal, Model, Model + EA, Model + NAC (N-actetylcysteine) and Model + NS (normal saline). The DES model was developed by subcutaneous injection of scopolamine hydrobromide with exposure to an air draft in the latter four groups. After intervention, the Schirmer I test (SIT), tear film break-up time (BUT) and ROS content were measured, the histopathological changes of corneal tissues were observed, and the mRNA and protein expression levels of TXNIP, NLRP3, apoptosis-associated Speck-like protein containing CARD (ASC), caspase-1, interleukin (IL)-1β and IL-18 were detected.

Results: Compared with the Model group, the SIT and BUT increased significantly in the Model + EA group after intervention (p < 0.05), and the corneal injury was improved. Corneal ROS content declined in both Model + EA and Model + NAC groups (p < 0.05), and mRNA expression of TXNIP, NLRP3, ASC and caspase-1 also decreased (p < 0.01). Corneal protein expression of TXNIP, NLRP3, IL-1β and IL-18 decreased significantly in the Model + EA group (p < 0.01).

Conclusion: Inhibiting the ROS/TXNIP/NLRP3 signaling pathway may be the mechanism underlying the role of EA in improving corneal injury in DES model rats.
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http://dx.doi.org/10.1177/09645284211039235DOI Listing
September 2021

Quantitative Electrophysiological Evaluation of the Analgesic Efficacy of Two Lappaconitine Derivatives: A Window into Antinociceptive Drug Mechanisms.

Neurosci Bull 2021 Sep 22. Epub 2021 Sep 22.

College of Life Science, Northwest Normal University, Lanzhou, 730070, China.

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
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http://dx.doi.org/10.1007/s12264-021-00774-wDOI Listing
September 2021

Economic burden of comorbid chronic conditions among survivors of stroke in China: 10-year longitudinal study.

BMC Health Serv Res 2021 Sep 17;21(1):978. Epub 2021 Sep 17.

Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China.

Background: The coexistence of chronic diseases among people with stroke is common. However, little is known about the extent of incremental healthcare expenditures associated with having physically and psychologically chronic conditions among stroke survivors.

Methods: We used the nationally representative data from the China Health and Nutrition Survey, including 36,076 participants enrolled as our analytic cohort of ten years of follow-up visits (2006, 2009, 2011, 2015). Chronic conditions include hypertension, diabetes, obesity, and impaired cognitive function. Two-part models were used to estimate the effect of comorbid chronic conditions on total annual healthcare expenditure, out-of-pocket (OOP) healthcare expenditure, and incidence of catastrophic healthcare expenditure (CHE).

Results: Among survivors of stroke during 2006 to 2015, the prevalence rates of hypertension, diabetes, obesity and impaired cognitive function were 75.5, 9.8, 12.7 and 65.1%, significantly higher than those among adults without stroke history (27.9, 2.7, 10.0 and 41.2%). Having hypertension ($794.5, p = 0.004), diabetes ($3978.5, p < 0.001) were associated with the largest incremental total healthcare expenditures. Stroke survivors with diagnosed hypertension and diabetes had additional 5.7 (p < 0.001) and 10.4 (p < 0.001) percentage point of CHE rate, respectively. Total healthcare expenditures were $2413.0 (P < 0.001) and $5151.7 (P < 0.001) higher among patients with 2, and ≥ 3 chronic conditions, respectively, than those individuals with no chronic conditions.

Conclusions: Excess expenditures associated with chronic diseases were substantial among stroke survivors. These results highlight the needs for both prevention and better management of multimorbidity among stroke survivors, which in turn may lower the financial burden of treating these concurrent comorbidities.
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http://dx.doi.org/10.1186/s12913-021-07010-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447672PMC
September 2021

Seroprevalence of IgM and IgG Antibodies against SARS-CoV-2 in Asymptomatic People in Wuhan: Data from a General Hospital Near South China Seafood Wholesale Market during March to April in 2020.

Biomed Environ Sci 2021 Sep;34(9):743-749

National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test, -test, and Mann-Whitney test were used to compare the standardized seroprevalence of IgG and IgM for age and gender between different groups. The results indicated the standardized seroprevalence of IgG and IgM showed a downward trend and was significantly higher among females than males. Besides, different geographic areas and workplaces had different seroprevalence of IgG among asymptomatic people, and the number of abnormalities in CT imaging were higher in IgG antibody-positive cases than IgG-negative cases. We hope these findings can provide references for herd immunity investigation and provide basis for vaccine development.
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http://dx.doi.org/10.3967/bes2021.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485512PMC
September 2021

Microstructure and Mechanical Properties of Carbides Reinforced Nickel Matrix Alloy Prepared by Selective Laser Melting.

Materials (Basel) 2021 Aug 24;14(17). Epub 2021 Aug 24.

High-Temperature Materials Department, Central Iron & Steel Research Institute, Beijing 100081, China.

Selective laser melting was used to prepare the ceramic particles reinforced nickel alloy owing to its high designability, high working flexibility and high efficiency. In this paper, a carbides particles reinforced Haynes 230 alloy was prepared using SLM technology to further strengthen the alloy. Microstructures of the carbide particles reinforced Haynes 230 alloy were investigated using electron microscopy (SEM), electron probe microanalysis (EPMA) and transmission electron microscopy (TEM). Meanwhile, the tensile tests were carried out to determine the strengths of the composite. The results show that the microstructure of the composite consisted of uniformly distributed MC and MC type carbides and the strengths of the alloy were higher than the matrix alloy Haynes 230. The increased strengths of the carbide reinforced Haynes 230 alloy (room temperature yield strength 113 MPa increased, ~ 33.2%) can be attributed to the synergy strengthening including refined grain strengthening, Orowan strengthening and dislocation strengthening.
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http://dx.doi.org/10.3390/ma14174792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432457PMC
August 2021

CX3CR1 But Not CCR2 Expression Is Required for the Development of Autoimmune Peripheral Neuropathy in Mice.

Front Immunol 2021 16;12:720733. Epub 2021 Aug 16.

The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

One hallmark of Guillain-Barre syndrome (GBS), a prototypic autoimmune peripheral neuropathy (APN) is infiltration of leukocytes (macrophages and T cells) into peripheral nerves, where chemokines and their receptors play major roles. In this study, we aimed to understand the potential contribution of chemokine receptors CCR2 and CX3CR1 in APN by using a well-established mouse model, B7.2 transgenic (L31) mice, which possesses a predisposed inflammatory background. We crossbred respectively CCR2KO and CX3CR1KO mice with L31 mice. The disease was initiated by partial ligation on one of the sciatic nerves. APN pathology and neurological function were evaluated on the other non-ligated sciatic nerve/limb. Our results revealed that L31/CX3CR1KO but not L31/CCR2KO mice were resistant to APN. CX3CR1 is needed for maintaining circulating monocyte and CD8 T cell survival. While migration of a significant number of activated CD8 T cells to peripheral nerves is essential in autoimmune response in nerve, recruitment of monocytes into PNS seems optional. Disease onset is independent of CCR2 mediated blood-derived macrophage recruitment, which can be replaced by compensatory proliferation of resident macrophages in peripheral nerve. CX3CR1 could also contribute to APN its critical involvement in maintaining nerve macrophage phagocytic ability. We conclude that blockade of CX3CR1 signaling may represent an interesting anti-inflammatory strategy to improve therapeutic management for GBS patients.
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http://dx.doi.org/10.3389/fimmu.2021.720733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415420PMC
August 2021

Streamflow prediction using an integrated methodology based on convolutional neural network and long short-term memory networks.

Sci Rep 2021 09 1;11(1):17497. Epub 2021 Sep 1.

School of Sciences, University of Southern Queensland, Toowoomba, QLD, 4350, Australia.

Streamflow (Q) prediction is one of the essential steps for the reliable and robust water resources planning and management. It is highly vital for hydropower operation, agricultural planning, and flood control. In this study, the convolution neural network (CNN) and Long-Short-term Memory network (LSTM) are combined to make a new integrated model called CNN-LSTM to predict the hourly Q (short-term) at Brisbane River and Teewah Creek, Australia. The CNN layers were used to extract the features of Q time-series, while the LSTM networks use these features from CNN for Q time series prediction. The proposed CNN-LSTM model is benchmarked against the standalone model CNN, LSTM, and Deep Neural Network models and several conventional artificial intelligence (AI) models. Q prediction is conducted for different time intervals with the length of 1-Week, 2-Weeks, 4-Weeks, and 9-Months, respectively. With the help of different performance metrics and graphical analysis visualization, the experimental results reveal that with small residual error between the actual and predicted Q, the CNN-LSTM model outperforms all the benchmarked conventional AI models as well as ensemble models for all the time intervals. With 84% of Q prediction error below the range of 0.05 m s, CNN-LSTM demonstrates a better performance compared to 80% and 66% for LSTM and DNN, respectively. In summary, the results reveal that the proposed CNN-LSTM model based on the novel framework yields more accurate predictions. Thus, CNN-LSTM has significant practical value in Q prediction.
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http://dx.doi.org/10.1038/s41598-021-96751-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410863PMC
September 2021

A potential method for sex estimation of human skeletons using deep learning and three-dimensional surface scanning.

Int J Legal Med 2021 Nov 30;135(6):2409-2421. Epub 2021 Aug 30.

Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, People's Republic of China.

Deep learning based on radiological methods has attracted considerable attention in forensic anthropology because of its superior classification capacities over human experts. However, radiological instruments are limited in their nature of high cost and immobility. Here, we integrated a deep learning algorithm and three-dimensional (3D) surface scanning technique into a portable system for pelvic sex estimation. Briefly, the images of the ventral pubis (VP), dorsal pubis (DP), and greater sciatic notch (GSN) were cropped from virtual pelvic samples reconstructed from CT scans of 1000 individuals; 80% of them were used to train and internally evaluate convolutional neural networks (CNNs) that were then evaluated externally with the remaining samples. An additional 105 real pelvises were documented virtually with a handheld 3D surface scanner, and the corresponding snapshots of the VP, DP, and GSN were predicted by the trained CNN models. The CNN models achieved excellent performance in the external testing using CT-based images, with accuracies of 98.0%, 98.5%, and 94.0% for VP, DP, and GSN, respectively. When the CT-based models were applied to 3D scanning images, they obtained satisfactory accuracies above 95% on the VP and DP images compared to the GSN with 73.3%. In a single-blind trial, a multiple design that combined the three CNN models yielded a superior accuracy of 97.1% with 3D surface scanning images over two anthropologists. Our study demonstrates the great potential of deep learning and 3D surface scanning for rapid and accurate sex estimation of skeletal remains.
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http://dx.doi.org/10.1007/s00414-021-02675-zDOI Listing
November 2021

Protective function of interleukin-22 in pulmonary fibrosis.

Clin Transl Med 2021 Aug;11(8):e509

Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor-beta (TGF-β) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin-22 (IL-22) in the pathogenesis of IPF by regulating the TGF-β pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL-22R knock out (IL-22RA1 ) and IL-22 supplementation mouse models were used to determine if IL-22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL-22 and/or TGF-β1. In a clinical cohort, the expression level of IL-22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL-22 expression was associated with poorer pulmonary function. IL-22R mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL-22 augmentation by intranasal instillation of recombinant IL-22 repressed inflammation and fibrotic phenotype. In vitro, IL-22 treatment repressed TGF-β1 induced gene markers representing epithelial-mesenchymal-transition and fibroblast-myofibroblast-transition, likely via the inhibition of TGF-β receptor expression and subsequent Smad2/3 activation. IL-22 appears to be protective against pulmonary fibrosis by inhibiting TGF-β1 signaling, and IL-22 augmentation may be a promising approach to treat IPF.
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http://dx.doi.org/10.1002/ctm2.509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387792PMC
August 2021

Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1.

Redox Biol 2021 Oct 24;46:102114. Epub 2021 Aug 24.

Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, Henan, 450001, PR China. Electronic address:

Neddylation is essential for cardiomyocyte survival in the presence of oxidative stress, and it participates in autophagy regulation. However, whether MLN4924-an inhibitor of neddylation-exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) remains unknown. In the present study, MLN4924 exerted strong cardioprotective effects, demonstrated by significantly elevated cell viability, a decreased LDH leakage rate, and improved cell morphology following HO-induced injury in vitro. MLN4924 also markedly decreased the serum myocardial zymogram level, ameliorated cardiac histopathological alterations, and alleviated left ventricular contractile dysfunction, thus limiting the cardiac infarct size in vivo compared with those in MI/R mice. Amazingly, such action of MLN4924 was abrogated by a combined treatment with the autophagic flux inhibitor, chloroquine. The mRFP-GFP-LC3 assay illustrated that MLN4924 restored the defective autophagic flux via enhancing the autolysosome formation. Notably, the expression levels of Rab7 and Atg5 were markedly up-regulated in MLN4924 treated cells and mice subjected to HO or MI/R, respectively, while knockdown of Sirt1 in cells and heart tissue largely blocked such effect and induced autophagosome accumulation by inhibiting its fusion with lysosomes. Transmission electron microscopic analysis, histopathological assay and TUNEL detection of the heart tissues showed that the absence of Sirt1 blocked the cardioprotective effect of MLN4924 by further exacerbating the impaired autophagic flux during MI/R injury in vivo. Taken together, MLN4924 exhibited the strong cardioprotective action via restoring the impaired autophagic flux in HO-induced injury in vitro and in MI/R mice. Our work implicated that Sirt1 played a critical role in autophagosome clearance, likely through up-regulating Rab7 in MI/R.
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http://dx.doi.org/10.1016/j.redox.2021.102114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406034PMC
October 2021

Protection of the enhanced Nrf2 deacetylation and its downstream transcriptional activity by SIRT1 in myocardial ischemia/reperfusion injury.

Int J Cardiol 2021 Nov 14;342:82-93. Epub 2021 Aug 14.

State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China. Electronic address:

Nrf2, the master gene transcriptor of antioxidant proteins, and SIRT1, the unique Class III histone deacetylase of sirtuins, have been involved in protecting myocardial ischemia/reperfusion (MI/R) injury. However, whether the protective effect of SIRT1 is directly related to the deacetylation of Nrf2 in the pathology of MI/R remains to be investigated. The current study was designed to evaluate the regulation of Nrf2 deacetylation and transcriptional activity by SIRT1 in MI/R. Hypoxia/reoxygenation (H/R) cardiomyocytes and MI/R mice were used to assess the role of SIRT1 in Nrf2 activation. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also evaluated. We found that Nrf2 physically interacted with SIRT1 not only in normal and H/R cardiomyocytes in vitro, but also in Sham or I/R hearts in vivo. Adenovirus induced SIRT1 overexpression resulted in protected H/R induced cell death, accompanied by declined LDH release. Through MI/R in vivo, cardiac overexpression of SIRT1 led to ameliorated cardiac function and infarct size, as well as the decreased cardiac oxidative stress. Notably, such beneficial actions of SIRT1 were blocked by the Nrf2 silence. Mechanically, acetylation of Nrf2 was significantly decreased by SIRT1 overexpression in cardiomyocytes or in whole hearts, which upregulated the downstream signaling pathway of Nrf2. Taken together, we uncovered a clue, for the first time that SIRT1 physically interacts with Nrf2. The cardioprotective effect of SIRT1 overexpression against MI/R is associated with the increased Nrf2 deacetylation and activity. These findings have offered a direct proof and new perspective of post-translational modification in the understanding of oxidative stress and MI/R treatment.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.007DOI Listing
November 2021

Efficacy and Safety of a Nanoparticle Therapeutic Vaccine in Patients with Chronic Hepatitis B: A Randomized Clinical Trial.

Hepatology 2021 Aug 15. Epub 2021 Aug 15.

Institute of Immunology, PLA, Army Medical University, Chongqing, China.

Background & Aim: HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, εPA-44, for CHB.

Approach & Results: A two-stage phase II trial, which included a 76-week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68-week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov number, NCT00869778). In stage 1, 360 HLA-A2-positive and HBeAg-positive patients were randomly and equally distributed to receive six subcutaneous injections of 600 µg or 900 µg εPA-44 or placebo at week 0, 4, 8, 12, 20, and 28. In stage 2, 183 patients received extended 900 µg εPA-44 and 26 patients were observed for relapse without further treatment. The primary endpoint was the percentage of patients with HBeAg seroconversion at week 76. At week 76, patients receiving 900 µg εPA-44 achieved significantly higher HBeAg seroconversion rate (38.8%) vs. placebo (20.2%) (95% CI, 6.9-29.6%; P=0.002). With a combined endpoint of HBeAg seroconversion, ALT normalization and HBV DNA <2000 IU/mL, both 900 µg (18.1%) and 600 µg (14.3%) resulted in significantly higher rate vs. placebo (5.0%) (P=0.002 and P=0.02, respectively) at week 76. In stage 2, none (0/20) of 900 µg εPA-44 treated patients experienced serologic relapse. The safety profile of εPA-44 was comparable to that of placebo.

Conclusions: Among progressive CHB patients with HLA-A2-positive, a finite duration of 900 µg εPA-44 monotherapy resulted in significantly higher HBeAg seroconversion rate than placebo and sustained off-treatment effect. A phase III trial is ongoing (ChiCTR2100043708).
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http://dx.doi.org/10.1002/hep.32109DOI Listing
August 2021

Albendazole inhibits NF-κB signaling pathway to overcome tumor stemness and bortezomib resistance in multiple myeloma.

Cancer Lett 2021 Nov 12;520:307-320. Epub 2021 Aug 12.

Department of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, Center for Medical Genetics, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, 110# Xiangya Road, Changsha, 410011, China. Electronic address:

Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1 MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma.
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http://dx.doi.org/10.1016/j.canlet.2021.08.009DOI Listing
November 2021

Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma.

NPJ Genom Med 2021 Aug 11;6(1):65. Epub 2021 Aug 11.

School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Trimethylation of histone H3 lysine 27 trimethylation (H3K27me3) may be recruited by repressive Polycomb complexes to mediate gene silencing, which is critical for maintaining embryonic stem cell pluripotency and differentiation. However, the roles of aberrant H3K27me3 patterns in tumorigenesis are not fully understood. Here, we discovered that grand silencer domains (breadth > 50 kb) for H3K27me3 were significantly associated with epithelial cell differentiation and exhibited high gene essentiality and conservation in human esophageal epithelial cells. These grand H3K27me3 domains exhibited high modification signals involved in gene silencing, and preferentially occupied the entirety of topologically associating domains and interact with each other. We found that widespread loss of the grand H3K27me3 domains in of esophageal squamous cell carcinomas (ESCCs) were enriched in genes involved in epithelium and endothelium differentiation, which were significantly associated with overexpression with increase of active modifications of H3K4me3, H3K4me1, and H3K27ac marks, as well as DNA hypermethylation in the gene bodies. A total of 208 activated genes with loss of grand H3K27me3 domains in ESCC were identified, where the higher expression and mutation of T-box transcription factor 20 (TBX20) were associated with worse patients' outcomes. Our results showed that knockdown of TBX20 may have led to a striking defect in esophageal cancer cell growth and carcinogenesis-related pathway, including cell cycle and homologous recombination. Together, our results reveal that loss of grand H3K27me3 domains represent a catalog of remarkable activating regulators involved in carcinogenesis.
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http://dx.doi.org/10.1038/s41525-021-00232-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358006PMC
August 2021
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