Publications by authors named "Kun Wang"

2,644 Publications

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Changes in soil prokaryotic communities and nitrogen cycling functions along a groundwater table drawdown gradient in desert wetlands.

Sci Total Environ 2022 Jun 22:156868. Epub 2022 Jun 22.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, College of Natural Resources and Environment, Northwest A & F University, Yangling, Shaanxi Province 712100, PR China; Research Center on Soil & Water Conservation, Institute of Soil and Water Conservation, Chinese Academy of Sciences Ministry of Water Resources, Yangling, Shaanxi Province 712100, PR China. Electronic address:

Desert wetlands are evolving into deserts by groundwater table (GWT) drawdown. However, the changes in microbial communities and functions during the GWT drawdown are unclear, which hinders the predictive power of biogeochemical processes across the desertification. Here, 16S rRNA gene sequencing, PICRUSt2 and qPCR were used to investigate soil prokaryotic diversity, composition and nitrogen cycling gene abundance at four vegetation types [flooded swamp (FS), drained swamp (DS), desert grassland (DG), and bare sandy land (BS)] along a GWT decline gradient in the Mu Us Desert, northern China. Results showed that prokaryotic Shannon and Chao1 indexes were significantly reduced at BS than those at FS (p < 0.05). Whereas no significant difference was observed between FS, DS and DG (p > 0.05). Distinct shifts in community composition were found along the GWT decline gradient. The dominant taxa gradually changed from obligate anaerobes and eutrophic microbes to facultative anaerobes, and finally to aerobic, oligotrophic and drought-tolerant microbes. Soil moisture was the most important factor in regulating the communities. In addition, GWT drawdown inhibited the relative abundance of genes involved in nitrogen fixation, assimilatory nitrite reduction, and nitrate oxidation, but enhanced the relative abundance of genes related to denitrification, assimilated nitrate reduction, ammonia oxidation and ammonification. Thus, GWT drawdown inhibits nitrogen input potential and exacerbates nitrogen loss potential. These results help in understanding the succession characteristics of desert wetland desertification.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156868DOI Listing
June 2022

BRAF V600E protect from cell death via inhibition of the mitochondrial permeability transition in papillary and anaplastic thyroid cancers.

J Cell Mol Med 2022 Jun 24. Epub 2022 Jun 24.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.

BRAF T1799A mutation is the most common genetic variation in thyroid cancer, resulting in the production of BRAF V600E mutant protein reported to make cells resistant to apoptosis. However, the mechanism by which BRAF V600E regulates cell death remains unknown. We constructed BRAF V600E overexpression and knockdown 8505C and BCPAP papillary and anaplastic thyroid cancer cell to investigate regulatory mechanism of BRAF V600E in cell death induced by staurosporine (STS). Induced BRAF V600E expression attenuated STS-induced papillary and anaplastic thyroid cancer death, while BRAF V600E knockdown aggravated it. TMRM and calcein-AM staining showed that opening of the mitochondrial permeability transition pore (mPTP) during STS-induced cell death could be significantly inhibited by BRAF V600E. Moreover, our study demonstrated that BRAF V600E constitutively activates mitochondrial ERK (mERK) to inhibit GSK-3-dependent CypD phosphorylation, thereby making BRAF V600E mutant tumour cells more resistant to mPTP opening. In the mitochondria of BRAF V600E mutant cells, there was an interaction between ERK1/2 and GSKa/ß, while upon BRAF V600E knockdown, interaction of GSKa/ß to ERK was decreased significantly. These results show that in thyroid cancer, BRAF V600E regulates the mitochondrial permeability transition through the pERK-pGSK-CypD pathway to resist death, providing new intervention targets for BRAF V600E mutant tumours.
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http://dx.doi.org/10.1111/jcmm.17443DOI Listing
June 2022

Targeted Sequencing Identifies the Genetic Variants Associated with High-altitude Polycythemia in the Tibetan Population.

Indian J Hematol Blood Transfus 2022 Jul 3;38(3):556-565. Epub 2021 Aug 3.

Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, Xianyang, China.

High-altitude polycythemia (HAPC) is characterized by excessive proliferation of erythrocytes, resulting from the hypobaric hypoxia condition in high altitude. The genetic variants and molecular mechanisms of HAPC remain unclear in highlanders. We recruited 141 Tibetan dwellers, including 70 HAPC patients and 71 healthy controls, to detect the possible genetic variants associated with the disease; and performed targeted sequencing on 529 genes associated with the oxygen metabolism and erythrocyte regulation, utilized unconditional logistic regression analysis and GO (gene ontology) analysis to investigate the genetic variations of HAPC. We identified 12 single nucleotide variants, harbored in 12 genes, associated with the risk of HAPC (4.7 ≤ odd ratios ≤ 13.6; 7.6E - 08 ≤ -value ≤ 1E - 04). The pathway enrichment study of these genes indicated the three pathways, the PI3K-AKT pathway, JAK-STAT pathway, and HIF-1 pathway, are essential, which -values as 3.70E - 08, 1.28 E - 07, and 3.98 E - 06, respectively. We are hopeful that our results will provide a reference for the etiology research of HAPC. However, additional genetic risk factors and functional investigations are necessary to confirm our results further.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01474-1.
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http://dx.doi.org/10.1007/s12288-021-01474-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209555PMC
July 2022

Palmitoylation Is Indispensable for Remorin to Restrict Tobacco Mosaic Virus Cell-to-Cell Movement in .

Viruses 2022 Jun 17;14(6). Epub 2022 Jun 17.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China.

Remorin (REM) is a plant-specific plasma membrane-associated protein regulating plasmodesmata plasticity and restricting viral cell-to-cell movement. Here, we show that palmitoylation is broadly present in group 1 remorin proteins in and is crucial for plasma membrane localization and accumulation. By screening the four members of group 1 remorin proteins, we found that only NbREM1.5 could significantly hamper tobacco mosaic virus (TMV) cell-to-cell movement. We further showed that NbREM1.5 interacts with the movement protein of TMV in vivo and interferes with its function of expanding the plasmodesmata size exclusion limit. We also demonstrated that palmitoylation is indispensable for NbREM1.5 to hamper plasmodesmata permeability and inhibit TMV cell-to-cell movement.
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http://dx.doi.org/10.3390/v14061324DOI Listing
June 2022

Analysis of the Effect of Human-Machine Co-Driving Vehicle on Pedestrian Crossing Speed at Uncontrolled Mid-Block Road Sections: A VR-Based Case Study.

Int J Environ Res Public Health 2022 Jun 12;19(12). Epub 2022 Jun 12.

School of Transportation Science and Engineering, Beihang University, Beijing 102206, China.

The current study investigates the effects of speed and time headway of human-machine co-driving vehicles on pedestrian crossing speed at uncontrolled mid-block road sections. A VR-based simulation study is conducted to study pedestrian crossing behaviour when facing human-machine co-driving vehicles. A total of 30 college students are recruited, and each participant is required to complete 5 street-crossing simulator trials facing human-machine co-driving vehicles with varying time headway levels and speeds. The correlations and differences between demographic information, time headway, vehicle speed, and pedestrian crossing speed are analyzed. The results show that gender and pedestrian's trust in human-machine co-driving vehicles are significantly correlated with pedestrian crossing speed. The pedestrian crossing speed increases with the increase in vehicle speed and decreases with the increase in vehicle time headway. In addition, the time headway has a stronger correlation with the pedestrian crossing speed than the vehicle speed. The findings will provide theoretical and methodological support for the formulation of pedestrian crossing control measures in the stage of human-machine co-driving.
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http://dx.doi.org/10.3390/ijerph19127208DOI Listing
June 2022

Distal adding-on after surgery in Lenke 5C adolescent idiopathic scoliosis: clinical and radiological outcomes.

BMC Musculoskelet Disord 2022 Jun 22;23(1):602. Epub 2022 Jun 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: To evaluate the incidence and risk factors of postoperative distal adding-on in patients with Lenke 5C adolescent idiopathic scoliosis (AIS). More accurate selection criteria for the lower instrumented vertebra (LIV) should be confirmed to prevent distal adding-on.

Methods: Forty-six patients with Lenke 5C AIS who underwent posterior fusion were enrolled in the study. Patients were allocated into adding-on and no adding-on groups. Demographic data, clinical data, and radiographic parameters were recorded and compared.

Results: Postoperative distal adding-on occurred in eight patients (17.4%) during follow-up. Demographic data, clinical data, and baseline radiographic parameters of the two groups were not significantly different. The postoperative thoracolumbar (TL) or lumbar (L) Cobb angle, LIV translation, and LIV + 1 translation were higher in the adding-on group than those in the no adding-on group, while the postoperative coronal imbalance of the adding-on group was lower than that of the no adding-on group. The level difference of last barely touched vertebra (LBTV) and last substantial touched vertebra (LSTV) with LIV were higher in the adding-on group than in the no adding-on group.

Conclusion: Postoperative TL/L curve, postoperative LIV translation, postoperative LIV + 1 translation, and postoperative coronal imbalance were determined as risk factors for postoperative distal adding-on in patients with Lenke 5C AIS. Moreover, LIV selection of LBTV-1 or LSTV-1 may cause a higher risk of postoperative distal adding-on.
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http://dx.doi.org/10.1186/s12891-022-05559-4DOI Listing
June 2022

Author Correction: WTAP-mediated mA modification of lncRNA NORAD promotes intervertebral disc degeneration.

Nat Commun 2022 Jun 22;13(1):3572. Epub 2022 Jun 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.

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http://dx.doi.org/10.1038/s41467-022-31302-7DOI Listing
June 2022

Kinetic diffusion-controlled synthesis of twinned intermetallic nanocrystals for CO-resistant catalysis.

Sci Adv 2022 Jun 22;8(25):eabo4599. Epub 2022 Jun 22.

Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.

Intermetallic catalysts are of immense interest, but how heterometals diffuse and related interface structure remain unclear when there exists a strong metal-support interaction. Here, we developed a kinetic diffusion-controlled method and synthesized intermetallic PtMo nanocrystals with twin boundaries on mesoporous carbon (PtMo/C). The formation of small-sized twinned intermetallic nanocrystals is associated with the strong Mo-C interaction-induced slow Mo diffusion and the heterogeneity of alloying, which is revealed by an in situ aberration-corrected transmission electron microscope (TEM) at high temperature. The twinned PtMo/C constitutes a promising CO-resistant catalyst for highly selective hydrogenation of nitroarenes. Theoretical calculations and environmental TEM suggest that the weakened CO adsorption over Pt sites of PtMo twin boundaries and their local region endows them with high CO resistance, selectivity, and reusability. The present strategy paves the way for tailoring the interface structure of high-melting point Mo/W-based intermetallic nanocrystals that proved to be important for the industrially viable reactions.
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http://dx.doi.org/10.1126/sciadv.abo4599DOI Listing
June 2022

Clinical Application of Shear Wave Elastography With Shear Wave Dispersion Imaging in the Preoperative Evaluation of Hepatic Parenchyma in Patients With Liver Tumors.

J Ultrasound Med 2022 Jun 22. Epub 2022 Jun 22.

Department of Ultrasound, North China Medical Treatment Health Group, Fengfeng General Hospital, Handan, China.

Objectives: This study aimed to compare the diagnostic accuracy of shear wave elastography (SWE) with that of shear wave dispersion (SWD) in evaluation of hepatic parenchyma in patients with liver tumors before resection.

Methods: A total of 174 patients with liver tumors were prospectively enrolled. SWE and SWD examinations were performed. Fibrosis stage and necroinflammatory activity were determined histopathologically according to the Scheuer standard. We compared the diagnostic accuracy of SWE and SWD.

Results: Both SWE and SWD values of the liver were highly correlated with liver fibrosis stage (P < .05, respectively). Both SWE and SWD values of the liver were moderately correlated with necroinflammatory activity (P < .05, respectively). Both SWE and SWD values of the liver were not correlated with steatosis (P > .05, respectively). Both SWE and SWD values were significantly different among the patients with different stages of liver fibrosis (P < .001, respectively). The area under the receiver operating characteristic (ROC) curve of SWE value was 0.982, 0.977, 0.969, and 0.984 for predicting S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively. The optimal cutoff SWE values were 6.9, 7.9, 8.7, and 10.6 kPa for S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively. The area under the ROC curve of SWD value was 0.967, 0.960, 0.925, and 0.954 for predicting S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively. The optimal cutoff SWD values were 11.2, 12.0, 13.2, and 16.0 m/s/kHz for S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively.

Conclusions: SWE and SWD could be noninvasive and accurate for predicting the stage of liver fibrosis in patients with liver tumors before surgery. SWE was more accurate than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4).
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http://dx.doi.org/10.1002/jum.16029DOI Listing
June 2022

PDZK1 interacting protein 1 (PDZK1IP1) promotes the progression of papillary thyroid cancer.

J Clin Endocrinol Metab 2022 Jun 21. Epub 2022 Jun 21.

Department of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province 430030, China.

Background: The incidence of papillary thyroid cancer (PTC) has increased rapidly in recent decades, and tumor progression events are common in PTC. The purpose of our study is to identify the differentially expressed genes (DEGs) correlated with PTC progression and investigate the function of PDZK1IP1 in PTC.

Methods: We first analyzed DEGs associated with PTC progression between paired PTC and normal thyroid tissues in three GEO datasets (GSE29265, GSE33630 and GSE60542) and TCGA database. Data from TCGA database and our institution were utilized to explore the relationship between PDZK1IP1 expression and clinicopathological characteristics of PTC. The CCK8 cell proliferation assay, clone formation assay, flow cytometry assay and the xenograft model were used to investigate the function of PDZK1IP1 in PTC.

Results: 39 DEGs associated with PTC progression were identified, in which only PDZK1IP1 was upregulated in PTC tissue at both mRNA and protein levels. Besides, we found that high expression of PDZK1IP1 in TCGA database was associated with poor progression-free survival, extrathyroidal extension, high stage, tall cell variant and BRAF V600E mutation of the PTC (P<0.001). In our collected samples, high expression of PDZK1IP1 was only related to lymph node metastasis (P<0.05). Overexpression of PDZK1IP1 significantly promoted proliferation and inhibited apoptosis of PTC cells. Knockdown of PDZK1IP1 significantly inhibited proliferation, promoted apoptosis, and prevented xenograft formation of PTC cells.

Conclusion: PDZK1IP1 is an oncogene for tumorigenesis and development of PTC and might be a potential therapeutic target.
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http://dx.doi.org/10.1210/clinem/dgac376DOI Listing
June 2022

Prevention of taxane-associated acute pain syndrome with etoricoxib for patients with breast cancer: A phase II randomised trial.

Eur J Cancer 2022 Jun 16;171:150-160. Epub 2022 Jun 16.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; Shantou University Medical College, Shantou, Guangdong, 515041, China. Electronic address:

Background: For patients with breast cancer who receive docetaxel chemotherapy, taxane-associated acute pain syndrome (T-APS), considered a form of neural pathology, is a significant clinical problem. We evaluated the effect of prophylactic etoricoxib on T-APS in patients with breast cancer.

Materials And Methods: We conducted a phase II randomised trial including 144 patients with breast cancer receiving four cycles of docetaxel-based chemotherapy. Patients were randomised in the ratio 1:1 to receive prophylactic etoricoxib (60 mg, Day 1 to Day 8) or no prophylactic treatment. The primary end-point was the overall incidence of T-APS across all cycles. Secondary end-points included the incidence of severe pain (greater than 5 on a scale 0-10); severity and duration of T-APS; Functional Assessment of Cancer Therapy-Breast subscale; chronic sensory and motor neurotoxicity and adverse events.

Results: The overall incidence of T-APS across all cycles of chemotherapy in the etoricoxib group was 57.1%, while that in the control group was 91.5% (P < 0.001). The incidences of severe T-APS were 11.4% and 54.9% for the etoricoxib and control groups, respectively (P < 0.001). The mean Functional Assessment of Cancer Therapy-Breast subscale score of the etoricoxib group (103.79-107.24) was significantly higher than that of the control group (93.88-96.71) (P = 0.001 at cycle 1 and P < 0.001 at cycles 2-4). After four cycles of docetaxel chemotherapy, the etoricoxib group demonstrated a significantly higher mean Functional Assessment of Cancer Treatment Neurotoxicity subscale score than the control group (38.46, 95% CI: 37.63-39.29; 34.59, 95% CI: 33.73-35.45, respectively; P < 0.001). Electromyography showed that most peripheral sensory nerves in the etoricoxib group had significantly improved action potential amplitudes and conduction velocities compared with those in the control group.

Conclusion: Prophylactic use of etoricoxib could significantly reduce the incidence and severity of docetaxel-induced acute pain syndrome and potentially decrease docetaxel-induced peripheral neuropathy.

Trial Registration: ClinicalTrials.gov, NCT04565600.
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http://dx.doi.org/10.1016/j.ejca.2022.05.019DOI Listing
June 2022

Clinical application of two dimensional shear wave elastography with a propagation map in evaluating liver fibrosis in patients with liver tumors.

Clin Hemorheol Microcirc 2022 Jun 17. Epub 2022 Jun 17.

Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China.

Objective: This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection.

Methods And Materials: From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis.

Results: The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0 kPa vs. 9.4 kPa, p <  0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6 kPa vs. 6.0 kPa, p <  0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (r = 0.834, p <  0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0-S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6 kPa, respectively. The areas under the ROC curve of S≥1, S≥2, S≥3, and S = 4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S≥1, S≥2, S≥3, and S = 4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa.

Conclusion: 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection.
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http://dx.doi.org/10.3233/CH-221511DOI Listing
June 2022

Rapid, Simple, and Highly Specific Detection of With Visualized Recombinase Polymerase Amplification.

Front Cell Infect Microbiol 2022 2;12:878881. Epub 2022 Jun 2.

Department of Central Laboratory, The Second People's Hospital of Lianyungang City (Cancer Hospital of Lianyungang), Affiliated to Jiangsu University, Lianyungang, China.

is a major pathogen that causes microbiological illness in humans. The introduction of polyvalent vaccines has resulted in a significant decrease in pneumococcal-related mortality. However, pneumococcal infections continue to be a leading cause of death in children under the age of 5 and adults over the age of 65 worldwide. A speedy and highly sensitive diagnostic tool is necessary for routine adoption to adequately manage patients and control the spread of infection. In this study, we investigated a new nucleic acid amplification technique, isothermal recombinase polymerase amplification (RPA), which amplifies DNA at 37°C under isothermal conditions with high specificity, efficiency, and rapidity. Using the autolysin gene as the molecular diagnostic target, an RPA primer-probe combination was designed and optimized for the detection of . This RPA reaction produced amplification products labeled with specific chemical markers, to be detected with gold-nanoparticle-based lateral flow strips (LFS), reducing the reliance on equipment and trained personnel. The high specificity of the RPA-LFS technique was demonstrated with the specific detection of 22 strains of but not 25 closely related pathogenic bacteria. The assay showed good sensitivity, and detected down to 3.32 colony-forming units/μL. When used on clinical samples, the assay provided accurate and consistent results compared with PCR. The compliance with the culture-biochemistry method was 98.18% and the kappa index was 0.977. These results reveal that the RPA-LFS test significantly improved identification, particularly in resource-limited areas.
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http://dx.doi.org/10.3389/fcimb.2022.878881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201913PMC
June 2022

Sensitive naked-eye detection of telomerase activity based on exponential amplification reaction and lateral flow assay.

Anal Bioanal Chem 2022 Jun 17. Epub 2022 Jun 17.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 1 Ningde Road, Qingdao, 266073, China.

Telomerase is a promising diagnostic and prognostic biomarker for cancers. Sensitive, simple, and reliable telomerase activity detection is vital for cancer diagnosis. Herein, we developed an ultrasensitive visualized assay for telomerase activity that combined the exponential amplification reaction (EXPAR) and lateral flow assay for easy and quick signal readout, which we termed as a lateral flow readout-EXPAR (LFR-EXPAR) assay. In the LFR-EXPAR assay, telomerase elongation products initiate the exponential amplification reaction, the generated trigger hybridizes with the reporter to form the recognition site of the nicking enzyme, and the nicking enzyme cuts the reporter strand. The degradation of the reporter can be detected with a universal lateral flow dipstick and read out with the naked eye. After conducting a series of proof-of-concept investigations, the LFR-EXPAR assay was found to achieve a sensitivity comparable to that of a TRAP (telomere repeat amplification protocol) assay. The LFR-EXPAR assay can be used to realize ultrasensitive and point-of-care detection of telomerase without requiring specialized instruments, holding great promise for early cancer diagnosis.
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http://dx.doi.org/10.1007/s00216-022-04179-0DOI Listing
June 2022

Integrated analysis reveals the pivotal interactions between immune cells in the melanoma tumor microenvironment.

Sci Rep 2022 Jun 16;12(1):10040. Epub 2022 Jun 16.

Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Melanoma is the most lethal type of skin cancer. Despite the breakthroughs in the clinical treatment of melanoma using tumor immunotherapy, many patients do not benefit from these immunotherapies because of multiple immunosuppressive mechanisms. Therefore, there is an urgent need to determine the mechanisms of tumor-immune system interactions and their molecular determinants to improve cancer immunotherapy. In this study, combined analysis of microarray data and single-cell RNA sequencing data revealed the key interactions between immune cells in the melanoma microenvironment. First, differentially expressed genes (DEGs) between normal and malignant tissues were obtained using GEO2R. The DEGs were then subjected to downstream analyses, including enrichment analysis and protein-protein interaction analysis, indicating that these genes were associated with the immune response of melanoma. Then, the GEPIA and TIMER databases were used to verify the differential expression and prognostic significance of hub genes, and the relationship between the hub genes and immune infiltration. In addition, we combined single cell analysis from GSE123139 to identify immune cell types, and validated the expression of the hub genes in these immune cells. Finally, cell-to-cell communication analysis of the proteins encoded by the hub genes and their interactions was performed using CellChat. We found that the CCL5-CCR1, SELPLG-SELL, CXCL10-CXCR3, and CXCL9-CXCR3 pathways might play important roles in the communication between the immune cells in tumor microenvironment. This discovery may reveal the communication basis of immune cells in the tumor microenvironment and provide a new idea for melanoma immunotherapy.
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http://dx.doi.org/10.1038/s41598-022-14319-2DOI Listing
June 2022

[Retracted] Filamin A regulates EGFR/ERK/Akt signaling and affects colorectal cancer cell growth and migration.

Mol Med Rep 2022 Aug 15;26(2). Epub 2022 Jun 15.

Department of Immunology, Hebei Medical University, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, P.R. China.

Following the publication of this article, an interested reader drew to the authors' attention that various panels in the scratch-wound assays shown in Fig. 1C appeared to contain overlapping sections, such that the data may have been derived from a more limited selection of original sources where the data were intended to show the data from discrete experiments. Furthermore, the results shown in the Kaplan-Meier overall survival analysis plots in Fig. 4C appeared to be inconsistent with the date of publication of this article. Independently, the Editorial Office also investigated the issues of concern in this article, and although the authors attenpted to explain these issues and requested the publication of a corrigendum, the Editor of has declined this request and determined that this article should be retracted from the journal on the basis of an overall lack of confidence in the presented data. Upon receiving this decision from the Editor, the authors were not in agreement that the article should be retracted. The Editor apologizes to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 20: 3671-3678, 2019; DOI: 10.3892/mmr.2019.10622].
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http://dx.doi.org/10.3892/mmr.2022.12770DOI Listing
August 2022

The intra-arterial selective cooling infusion system: A mathematical temperature analysis and in vitro experiments for acute ischemic stroke therapy.

CNS Neurosci Ther 2022 Jun 15. Epub 2022 Jun 15.

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

Introduction: The neuroprotection of acute ischemic stroke patients can be achieved by intra-arterial selective cooling infusion using cold saline, which can decrease brain temperature without influencing the body core temperature. This approach can lead to high burdens on the heart and decreased hematocrit in the scenario of loading a high amount of liquid for longtime usage. Therefore, autologous blood is utilized as perfusate to circumvent those side effects.

Methods: In this study, a prototype instrument with an autologous blood cooling system was developed and further evaluated by a mathematical model for brain temperature estimation.

Results: Hypothermia could be achieved due to the adequate cooling capacity of the prototype system, which could provide the lowest cooling temperature into the blood vessel of 10.5°C at 25 rpm (209.7 ± 0.8 ml/min). And, the core body temperature did not alter significantly (-0.7 ~ -0.2°C) after 1-h perfusion. The cooling rate and temperature distributions of the brain were analyzed, which showed a 2°C decrease within the initial 5 min infusion by 44 ml/min and 13.7°C perfusate.

Conclusion: This prototype instrument system could safely cool simulated blood in vitro and reperfuse it to the target cerebral blood vessel. This technique could promote the clinical application of an autologous blood perfusion system for stroke therapy.
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http://dx.doi.org/10.1111/cns.13883DOI Listing
June 2022

Mechanism of ferroptosis in hypertensive nephropathy.

Transl Androl Urol 2022 May;11(5):617-626

School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

Background: In recent years, it has been demonstrated that ferroptosis can be involved in a variety of kidney injury processes, but the role played by ferroptosis in hypertensive kidney injury is still unclear. The aim was to explore the mechanism of ferroptosis playing a role in hypertensive kidney disease and related signalling pathways.

Methods: GSE37455 microarray data was downloaded from the Gene Expression Omnibus (GEO) database and preprocessed. Batch correction and differential analysis were performed on the normal population and the hypertensive nephropathy samples using the "sva" and "limma" packages in R software. Ferroptosis-related genes were obtained from the FerrDb database and normalized and processed using UniProt. Ferroptosis-related differentially expressed genes were obtained using Venny 2.1. and imported into the Search Tool for the Retrieval of Interacting Genes (STRING) to obtain protein-protein interactions (PPIs). The data were imported into Cytoscape 3.7.2 for processing to identify the core differential genes of ferroptosis based on nodes. Gene set enrichment analysis (GSEA) was performed on the core differential genes of ferroptosis to infer the pathway of ferroptosis action in hypertensive nephropathy.

Results: The R software processing yielded 37 differential genes, including 13 upregulated genes and 24 downregulated genes. 202 ferroptosis-related genes were obtained by screening, and 3 ferroptosis-related differentially expressed genes were obtained after taking the intersection. The ferroptosis-related core differentially expressed gene albumin () was obtained by PPI network analysis and Cytoscape processing. GSEA analysis revealed that ferroptosis may act in hypertensive nephropathy through pathways such as drug metabolism-cytochrome P450, branched-chain amino acid (BCAA) metabolism, retinol metabolism, and biological processes (BPs) such as organic and amino acid metabolism and humoral immunity.

Conclusions: Ferroptosis may act in the development of hypertensive nephropathy through pathways such as BCAA metabolism and retinol metabolism and BPs such as organic and amino acid metabolism and humoral immunity.
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http://dx.doi.org/10.21037/tau-22-276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177265PMC
May 2022

AI in spotting high-risk characteristics of medical imaging and molecular pathology.

Precis Clin Med 2021 Dec 4;4(4):271-286. Epub 2021 Dec 4.

CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.

Medical imaging provides a comprehensive perspective and rich information for disease diagnosis. Combined with artificial intelligence technology, medical imaging can be further mined for detailed pathological information. Many studies have shown that the macroscopic imaging characteristics of tumors are closely related to microscopic gene, protein and molecular changes. In order to explore the function of artificial intelligence algorithms in in-depth analysis of medical imaging information, this paper reviews the articles published in recent years from three perspectives: medical imaging analysis method, clinical applications and the development of medical imaging in the direction of pathological molecular prediction. We believe that AI-aided medical imaging analysis will be extensively contributing to precise and efficient clinical decision.
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http://dx.doi.org/10.1093/pcmedi/pbab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982528PMC
December 2021

Research on Improving the Partial Discharge Initial Voltage of SiC/EP Composites by Utilizing Filler Surface Modification and Nanointerface Interaction.

Polymers (Basel) 2022 Jun 5;14(11). Epub 2022 Jun 5.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, School of Electrical and Electronic Engineering, North China Electric Power University, Beijing 102206, China.

SiC/EP composites are promising insulating materials due to their high thermal conductivity, stable chemical properties, and nonlinear electrical conductivity. However, the compatibility of micron-sized SiC particles with the organic polymer matrix is poor, and defects such as air gaps may be introduced at the interface, which reduces the partial discharge resistance of the composite materials. In order to improve the partial discharge initial voltage (PDIV) of SiC/EP composites, in this paper, SiC/EP composites with different proportions were prepared by surface modification of filler and compound of micro/nano particles. Firstly, a method of secondary modification of SiC particles was proposed, which was first modified by alkali washing and then silane coupling agent KH560, and the effectiveness of the modification was verified. Therefore, the interface bonding ability between the filler and the matrix was improved, the air gap defects at the interface were reduced, and the PDIV of the composite material was improved. When the filling ratio is 10 wt%, the PDIV was enhanced by 13.75%, and when the filling ratio was further increased, the improvement was reduced. In contrast, the introduction of nanoparticles into the composites can effectively improve the PDIV of composite materials. In this study, nanoparticles were used to form a shell-core structure in epoxy resins to exert their huge specific surface area and active surface properties, thereby changing the overall crosslinking properties of the composites. Through experimental research, the optimal micro-nano particle compounding ratio was explored. Under the optimal mixing ratio, the PDIV of the composite material can be increased by more than 90%.
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http://dx.doi.org/10.3390/polym14112297DOI Listing
June 2022

Expression Profiles and Characteristics of Apple lncRNAs in Roots, Phloem, Leaves, Flowers, and Fruit.

Int J Mol Sci 2022 May 25;23(11). Epub 2022 May 25.

Research Institute of Pomology, Chinese Academy of Agricultural Sciences (CAAS), Key Laboratory of Horticulture Crops Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Xingcheng 125100, China.

LncRNAs impart crucial effects on various biological processes, including biotic stress responses, abiotic stress responses, fertility and development. The apple tree is one of the four major fruit trees in the world. However, lncRNAs's roles in different tissues of apple are unknown. We identified the lncRNAs in five tissues of apples including the roots, phloem, leaves, flowers, and fruit, and predicted the intricate regulatory networks. A total of 9440 lncRNAs were obtained. LncRNA target prediction revealed 10,628 potential lncRNA-messenger RNA (mRNA) pairs, 9410 pairs functioning in a cis-acting fashion, and 1218 acting in a trans-acting fashion. Functional enrichment analysis showed that the targets were significantly enriched in molecular functions related to photosynthesis-antenna proteins, single-organism metabolic process and glutathione metabolism. Additionally, a total of 88 lncRNAs have various functions related to microRNAs (miRNAs) as miRNA precursors. Interactions between lncRNAs and miRNAs were predicted, 1341 possible interrelations between 187 mdm-miRNAs and 174 lncRNAs (1.84%) were identified. MSTRG.121644.5, MSTRG.121644.8, MSTRG.2929.2, MSTRG.3953.2, MSTRG.63448.2, MSTRG.9870.2, and MSTRG.9870.3 could participate in the functions in roots as competing endogenous RNAs (ceRNAs). MSTRG.11457.2, MSTRG.138614.2, and MSTRG.60895.2 could adopt special functions in the fruit by working with miRNAs. A further analysis showed that different tissues formed special lncRNA-miRNA-mRNA networks. MSTRG.60895.2-mdm-miR393-MD17G1009000 may participate in the anthocyanin metabolism in the fruit. These findings provide a comprehensive view of potential functions for lncRNAs, corresponding target genes, and related lncRNA-miRNA-mRNA networks, which will increase our knowledge of the underlying development mechanism in apple.
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http://dx.doi.org/10.3390/ijms23115931DOI Listing
May 2022

Speckle Reduction in Ultrasound Images of the Common Carotid Artery Based on Integer and Fractional-Order Total Variation.

Ultrason Imaging 2022 Jun 8:1617346221096840. Epub 2022 Jun 8.

Department of Electronic Engineering, School of Information Science and Engineering, Yunnan University, Kunming, Yunnan, China.

Designing a technique with higher speckle noise suppressing capability, better edge preserving performance, and lower time complexity is a research objective for the common carotid artery (CCA) ultrasound despeckling. Total variation based techniques have been widely used in the image denoising and have good performance in preserving the edges in the images. However, the total variation based filters can produce the staircase artifacts. To address this issue, second-order total variation based techniques have been proposed for the image denoising. However, the previous study has been proved that the fractional differential model has better performance in reducing the speckles in ultrasound despeckling compared with the second-order model. Thus, to improve the performance of ultrasound despeckling and edge preserving, a novel despeckling model based on integer and fractional-order total variation (IFOTV) is proposed for CCA ultrasound images. Moreover, the minimization problems in our despeckling model are solved by the alternating direction method of multiplier (ADMM). In results with synthetic images, the edge preservation index (EPI) values of proposed method are 0.9524, 0.8797, and 0.7351 as well as 0.9137, 0.8253, and 0.6847 under three different levels of noise, which are the highest among four advanced methods. In results with simulated CCA ultrasound images, the speckle suppression and mean preservation indices of proposed method are 0.5596, 0.6571, and 0.8106 under three different levels of noise, which are the best among four advanced methods. In results with clinical images, the average absolute error of intima-media thickness measurements of proposed method is 0.0660 ± 0.0679 (mean ± std in mm), which is the lowest among four advanced methods. In conclusion, the IFOTV method has improved performance in suppressing the speckle noise and preserving the edge, and is thus a potential alternative to the current filters for the CCA ultrasound despeckling.
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http://dx.doi.org/10.1177/01617346221096840DOI Listing
June 2022

3D printed hydrogel scaffolds combining glutathione depletion-induced ferroptosis and photothermia-augmented chemodynamic therapy for efficiently inhibiting postoperative tumor recurrence.

J Nanobiotechnology 2022 Jun 7;20(1):266. Epub 2022 Jun 7.

Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.

Surgical resection to achieve tumor-free margins represents a difficult clinical scenario for patients with hepatocellular carcinoma. While post-surgical treatments such as chemotherapy and radiotherapy can decrease the risk of cancer recurrence and metastasis, growing concerns about the complications and side effects have promoted the development of implantable systems for locoregional treatment. Herein, 3D printed hydrogel scaffolds (designed as Gel-SA-CuO) were developed by incorporating one agent with multifunctional performance into implantable devices to simplify the fabrication process for efficiently inhibiting postoperative tumor recurrence. CuO nanoparticles can be effectively controlled and sustained released during the biodegradation of hydrogel scaffolds. Notably, the released CuO nanoparticles not only function as the reservoir for releasing Cu to produce intracellular reactive oxygen species (ROS) but also serve as photothermal agent to generate heat. Remarkably, the heat generated by photothermal conversion of CuO nanoparticles further promotes the efficiency of Fenton-like reaction. Additionally, ferroptosis can be induced through Cu-mediated GSH depletion via the inactivation of GPX4. By implanting hydrogel scaffolds in the resection site, efficient inhibition of tumor recurrence after primary resection can be achieved in vivo. Therefore, this study may pave the way for the development of advanced multifunctional implantable platform for eliminating postoperative relapsable cancers.
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http://dx.doi.org/10.1186/s12951-022-01454-1DOI Listing
June 2022

Study on the structure and physicochemical properties of fenugreek galactomannan modified via octenyl succinic anhydride.

Int J Biol Macromol 2022 Jun 3;214:91-99. Epub 2022 Jun 3.

MOE Engineering Research Center of Forestry Biomass Materials and Bioenergy, Beijing Forestry University, Beijing 100083, PR China. Electronic address:

To improve the mechanical strength of borax-crosslinked fenugreek galactomannan hydrogels and broaden the application field of galactomannan-based hydrogels, fenugreek galactomannan (FG) was esterified via octenyl succinic anhydride (OSA), and the parameters affecting the esterification reaction were systematically studied. The optimum process for OSA-modified FG (OFG) was as follows: FG concentration 1.5 wt%, n (OSA): n (FG) = 2, n (4-dimethylamino-pyridine, DMAP): n (FG) = 4, and reaction time 12 h. Under this condition, the degree of substitution (DS) was 0.31, and the product yield was 115.05 %. Characterization of FT-IR, H NMR, and HPLC confirmed that the OSA group was successfully introduced into the FG skeleton. The mechanical strength of borax crosslinked OFG hydrogel (OFGH) is 18 times higher than that of FG hydrogel. OFGH shows excellent self-healing, injectable properties and electrical conductivity. This will further expand the application of borax crosslinked galactomannan-based hydrogels in the fields of sensors, drug delivery, and wound dressing.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.05.196DOI Listing
June 2022

The same genetic regulation strategy produces inconsistent effects in different Saccharomyces cerevisiae strains for 2-phenylethanol production.

Appl Microbiol Biotechnol 2022 Jun 6;106(11):4041-4052. Epub 2022 Jun 6.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China.

A CRISPR/Cas9 system with gene editing efficiency of 100% in the industrial diploid Saccharomyces cerevisiae CWY-132 strain for 2-phenylethanol (2-PE) production was constructed. The effect of deletion of acetyltransferase gene ATF1 in the Ehrlich pathway on 2-PE synthesis was studied for the first time in S. cerevisiae. Laboratory and industrial strains were compared for the deletion effect of ATF1 and acetaldehyde dehydrogenase genes ALD2 and ALD3 involved in competing branches of the Ehrlich pathway on the 2-PE titer. The results showed that in 2-PE low-yielding haploid strain PK-2C, the ATF1∆ mutant produced 2-PE of 0.45 g/L, an increase of 114%, whereas in CWY-132, the 2-PE yield of ATF1∆ decreased significantly from 3.50 to 0.83 g/L. In PK-2C, the 2-PE yield of ALD2∆ increased from 0.21 to 1.20 g/L, whereas in CWY-132, it decreased from 3.50 to 3.02 and 2.93 g/L in ALD2∆ and ALD3∆ mutants, respectively, and to 1.65 g/L in ALD2∆ALD3∆. These results indicate that the same genetic manipulation strategy used for strains with different 2-PE yield backgrounds produces significantly different or even opposite effects. Moreover, we found that a supply of NADH or GSH increased the 2-PE production in S. cerevisiae. The correlation between the synthesis of 2-PE and ethanol was also revealed, and the tolerance of cells to 2-PE and ethanol was suggested to be a key limiting factor for further increase of 2-PE production in high-yielding strains. KEY POINTS: • Deletion of genes competing for 2-PE synthesis produces different effects in S. cerevisiae strains. • The ATF1∆, ALD2∆, or ALD3∆ increased 2-PE production in laboratory strains but not industrial strains. • The supply of NADH or GSH increased the titer of 2-PE in S. cerevisiae.
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http://dx.doi.org/10.1007/s00253-022-11993-0DOI Listing
June 2022

The lncRNA Punisher Regulates Apoptosis and Mitochondrial Homeostasis of Vascular Smooth Muscle Cells via Targeting miR-664a-5p and OPA1.

Oxid Med Cell Longev 2022 25;2022:5477024. Epub 2022 May 25.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, 266021, China.

Long noncoding RNAs (lncRNAs) are important regulators of various cellular functions. Recent studies have shown that a novel lncRNA termed Punisher is highly expressed in cardiovascular progenitors and has potential role in cardiovascular diseases. However, its role, especially in molecular mechanism, is unclear. In our present study, we observed that Punisher was obviously downregulated in atherosclerotic plaques. Further research proved that it can suppress the apoptosis of VSMCs potentially contributing to the progression of atherosclerosis. Intriguingly, Punisher revealed to regulate mitochondria fission as well as mitochondrial functions induced by hydrogen peroxide (HO) in VSMCs. Mechanistically, Punisher was further proved to serve as a ceRNA which directly binds to miR-664a-5p and consequently regulates its target OPA1, and finally contributes to the biological function of VSMCs. Particularly, Punisher overexpression distinctly suppressed neointima formation and VSMC apoptosis in vivo. Encouragingly, these results were in accordance with findings obtained with the clinical evaluation of patients with atherosclerosis. Our data provides the significant relationship among OPA1, mitochondrial homeostasis, VSMC apoptosis, and atherosclerosis. And lncRNA Punisher and miR-664a-5p could serve as the novel and potential targets in the diagnosis and treatment of cardiovascular diseases.
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http://dx.doi.org/10.1155/2022/5477024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159832PMC
June 2022

Efficacy and Safety of Prostatic Artery Embolization in the Treatment of High Risk Benign Prostatic Hyperplasia and its Influence on Postoperative Life Quality of Patients.

Front Surg 2022 17;9:905394. Epub 2022 May 17.

Department of Internal Medicine, Changde Geriatric Hospital, Changde City, China.

Objective: To evaluate the efficacy, safety and postoperative quality of life of high risk benign prostatic hyperplasia (BPH) patients treated with prostatic artery embolization.

Methods: 34 patients with high-risk BPH were selectedfrom January 2020 to June 2021 in our hospital. All patients were treated with prostatic artery embolization. The changes of international prostate symptom score (IPSS), prostate volume (PV), remaining urine (RU), maximum urine flow rate (Qmax), quality of life scale -74(GQOLI-74), time to sleep without disturbance (HUS) judgment, self-rating anxiety scale (SAS) score and self-rating depression scale (SDS) were compared before operation, 1 month and 6 months after operation.

Results: Prostatic artery embolization was successful in all 34 patients, including unilateral embolization in 15 patients and bilateral embolization in 19 patients. No severe complications occurred in the postoperative patients. The IPSS, PV and RU levels of the patient one month and six months after surgery were lower than those before surgery, while the Qmax level was higher than that before surgery. Besides, the IPSS, PV and RU levels six months after surgery were significantly lower than those one month after surgery, and the Qmax level was significantly higher than that one month after surgery (< 0.05). The GQOLI-74 score six months after surgery was significantly higher than that before surgery (< 0.05). The HUS of the patient six months after surgery was significantly increased, and the SAS and SDS scores were significantly decreased as compared with those before surgery (< 0.05).

Conclusion: For high-risk patients with BPH, prostate embolization is an effective and safe method, which can significantly improve the quality of life of patients after surgery and has good application prospects.
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http://dx.doi.org/10.3389/fsurg.2022.905394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152163PMC
May 2022

Case Report: Clinical and Procedural Implications of Ommaya Reservoir Implantation in Cystic Brain Metastases Followed by Radiosurgery Treatment.

Front Surg 2022 16;9:901674. Epub 2022 May 16.

Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: Therapy for large or deep cystic brain metastases is a troublesome procedure in clinical departments. Stereotactic cyst aspiration, combined with Gamma Knife radiosurgery, can be an effective treatment for cystic brain metastases. However, there is still a possibility that a reaccumulation of cystic fluid may lead to poor efficacy or even reoperation.

Case Presentation: We present a case of a 67-year-old man who was diagnosed with lung cancer brain metastasis. The intracranial lesion seen on imaging appeared to be cystic and located deep inside the brain with associated limb dysfunction. The patient did not respond well to chemotherapy and underwent cyst aspiration with Ommaya reservoir implantation under neuronavigation. Repeated cystic fluid reaccumulation and exacerbation of symptoms occurred during treatment. We performed repeated aspiration via the Ommaya reservoir to control the symptoms and combined it with radiotherapy. During the follow-up period of 14 months, the intracranial tumor was effectively and satisfactorily controlled.

Conclusions: We highlight that Ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reaccumulation, thereby avoiding the need for a second surgical procedure.
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http://dx.doi.org/10.3389/fsurg.2022.901674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149303PMC
May 2022

Higher efficacy of resveratrol against advanced breast cancer organoids: A comparison with that of clinically relevant drugs.

Phytother Res 2022 Jun 1. Epub 2022 Jun 1.

Breast Cancer Department, Cancer Center, Guangdong Provincial People's Hospital Affiliated to South China University of Technology School of Medicine, Guangzhou, China.

The lack of reliable drugs is a therapeutic challenge of advanced breast cancers (ABCs). Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy against individual breast cancer cases remains unknown. This study aims to use ABC-derived organoids (ABCOs) as the ex vivo therapeutic platform to clarify the effectiveness of resveratrol against different ABC subtypes. Immunohistochemical staining confirmed that the ABCOs maintained their original tumors' ER, PR, HER2, and Ki67 expression patterns. ABCO proliferation and viability tests showed >50% cell death rates in 79.2% (19/24) of Res-treated, 28.6% (2/7) fulvestrant-treated, 66.7% (4/6) paclitaxel-treated, and 66.7% (6/9) gemcitabine-treated ABCOs. pSTAT3 nuclear translocation was more frequent in Res-sensitive (17/19; 89.47%) than that (1/5; 20%) of Res-insensitive ABCOs, which were suppressed upon Res treatment. Statistical analysis revealed a close correlation of STAT3 activation with the efficacy of Res, but not related to tumor receptor expression patterns (ER, PR, HER2) and pathological classification. We demonstrate for the first time the higher efficacy and broader spectrum of Res against different subtypes of ABCOs in comparison with that of conventional antibreast cancer drugs, providing an alternative approach for better management of ABCs.
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http://dx.doi.org/10.1002/ptr.7515DOI Listing
June 2022

Pyroptosis: Role and Mechanisms in Cardiovascular Disease.

Front Cardiovasc Med 2022 11;9:897815. Epub 2022 May 11.

Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.

Cardiovascular disease (CVD) is a common disease that poses a huge threat to human health. Irreversible cardiac damage due to cardiomyocyte death and lack of regenerative capacity under stressful conditions, ultimately leading to impaired cardiac function, is the leading cause of death worldwide. The regulation of cardiomyocyte death plays a crucial role in CVD. Previous studies have shown that the modes of cardiomyocyte death include apoptosis and necrosis. However, another new form of death, pyroptosis, plays an important role in CVD pathogenesis. Pyroptosis induces the amplification of inflammatory response, increases myocardial infarct size, and accelerates the occurrence of cardiovascular disease, and the control of cardiomyocyte pyroptosis holds great promise for the treatment of cardiovascular disease. In this paper, we summarized the characteristics, occurrence and regulation mechanism of pyroptosis are reviewed, and also discussed its role and mechanisms in CVD, such as atherosclerosis (AS), myocardial infarction (MI), arrhythmia and cardiac hypertrophy.
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http://dx.doi.org/10.3389/fcvm.2022.897815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130572PMC
May 2022
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