Publications by authors named "Song Yuan"

183 Publications

A Novel Homozygous Frameshift Mutation in ITGB3 Causes Glanzmann's Thrombasthenia.

Acta Haematol 2021 Aug 17:1-6. Epub 2021 Aug 17.

Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

The objective of this study was to elucidate the molecular characteristics of a Chinese family with Glanzmann's thrombasthenia (GT). The proband was diagnosed with GT based on clinical manifestations, platelet aggregation, and the expression of CD41 and CD61 in platelets. Whole-exome and Sanger sequencing were used to detect genetic defects related to GT in the proband and the family of the pedigree. Whole-exome sequencing showed a c.1784-1802delinsGTCACA, p. S595Cfs*70 homozygous mutation in exon 11 of the ITGB3 gene in the proband. Heterozygous mutations were found in the proband's parents, grandmother, uncle, aunt, and younger brother. This novel p. S595Cfs*70 ITGB3 gene mutation is not present in the 1000 Genomes and ExAC databases.
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http://dx.doi.org/10.1159/000517050DOI Listing
August 2021

Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3.

Histol Histopathol 2021 Jul 28:18365. Epub 2021 Jul 28.

Department of Foot and Ankle Surgery, Center for Orthopaedic Surgery, the Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Background: With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation.

Methods: A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA.

Results: We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNA-MEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects.

Conclusion: Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosis.
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http://dx.doi.org/10.14670/HH-18-365DOI Listing
July 2021

Reconstruction of Large Area of Deep Wound in the Foot and Ankle with Chimeric Anterolateral Thigh Perforator Flap.

Orthop Surg 2021 Jul 17;13(5):1609-1617. Epub 2021 Jun 17.

Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objective: To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle.

Methods: Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep-tissue injury of the soft-tissue defects. The skin flap and muscle flap were fanned out on the wound, and single- or two-staged split-thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post-operationally. Complications at both recipient site and donor site were carefully recorded.

Results: The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post-traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6-8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12-36 months post-operational follow-up.

Conclusion: The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.
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http://dx.doi.org/10.1111/os.13046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313155PMC
July 2021

[Eukaryotic expression and immunoactivity of protein A/G-horseradish peroxidase(PA/G-HRP) fusion protein as universal secondary antibody for detection of IgG originating from mice and rabbits].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jul;37(7):590-595

State Key Laboratory of Cancer Biology, Department of Immunology, Air Force Medical University, Xi'an 710032, China. *Corresponding authors, E-mail:

Objective To prepare universal secondary antibodies those can bind to the IgG from mice and rabbits, and use the antibodies in a variety of immunoassays. Methods The fusion genes of staphylococcal protein A (SPA), streptococcal protein G (SPG), and horseradish peroxidase (HRP) were synthesized, and cloned into the vector pcDNA3.1 to generate the eukaryotic expression plasmids. The plasmids were transiently transfected into HEK293F cells for expression. The fusion protein expressed in the plasmid was detected by SDS-PAGE and Western blotting, and its immunoactivity was measured by Western blotting, ELISA, and immunohistochemical staining. Results Restriction enzyme digestion and gene sequencing showed the pPA-HRP, pPG-HRP, and pPA/G-HRP plasmids were successfully created. Coomassie brilliant blue staining and Western blotting indicated that the fusion proteins PA-HRP, PG-HRP, and PA/G-HRP successfully expressed in HEK293F cells. Western blotting, ELISA, and immunohistochemical staining showed that IgGs derived from mice and rabbits could be recognized and bound by the three kinds of fusion protein, of which the fusion protein PA/G-HRP exhibited the highest affinity. Conclusion The fusion protein PA/G-HRP with high and universal IgG affinity is successfully prepared. The PA/G-HRP can replace traditional secondary antibodies against mouse and rabbit IgG in a variety of immunological assays.
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July 2021

Next‑generation sequencing of miRNAs and lncRNAs from rat femur and tibia under mechanical stress.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Orthopedics, Orthopaedic Hospital of Guangdong Province, Guangzhou, Guangdong 510610, P.R. China.

Exercise intervention has become one of the most effective methods to prevent and treat osteoporosis, which is a common age‑related disease and seriously affects the health and quality of life of the elderly. However, the molecular mechanism remains to be elucidated. The present study demonstrated the exercise‑induced promotion of osteogenic differentiation and inhibition of adipogenic differentiation in femur and tibia by establishing an animal exercise model using a treadmill exercise system. MicroRNA (miRNA/miR) and long non‑coding (lnc)RNA sequencing analyses identified 16 upregulated and two downregulated miRNAs in the exercise group, as well as 44 upregulated lncRNAs and 39 downregulated lncRNAs in the exercise group. There was increased expression of miR‑9942 and miR‑7704 in both the femur and tibia and an upregulation of miR‑30d, miR‑5100 and miR‑1260 in the femur of animals from the exercise group. In addition, four of the five most downregulated lncRNAs, including lncRNA MSTRG.2625, lncRNA MSTRG.1557, lncRNA MSTRG.691 and lncRNA MSTRG.7497, were demonstrated to be suppressed in both the femur and tibia after treadmill exercise. The results of the present study provided a valuable resource for further exploring the molecular mechanisms underlying the regulation of osteoporosis by exercise.
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http://dx.doi.org/10.3892/mmr.2021.12200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201655PMC
August 2021

Free flap transplantation combined with Ilizarov bone transport for the treatment of severe composite tibial and soft tissue defects.

J Int Med Res 2021 May;49(5):3000605211017618

Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objective: To evaluate the clinical efficacy of free flap transplantation combined with Ilizarov bone transport in the treatment of severe composite tibial and soft tissue defects.

Methods: We retrospectively analyzed the clinical data of 40 patients with severe composite tibial and soft tissue defects who underwent free flap transplantation combined with Ilizarov bone transport. The clinical efficacy was evaluated according to the following criteria: success rate of wound repair by free flap transplantation, incidence or recurrence rate of deep infection, healing rate of bone defects and external fixation index, incidence of complications, and functional score of affected extremities.

Results: All infections were generally well controlled by radical debridement and negative-pressure therapy, and all 40 patients' wounds healed after repair and reconstruction of the tibia and soft tissues. Postoperative complications were alleviated by active treatment. The mean external fixation time was 12.83 ± 2.85 months, and the external fixation index was 1.55 m/cm. According to the Association for the Study and Application of Methods of Ilizarov (ASAMI) score, an excellent or good functional outcome was attained in 85% of patients.

Conclusion: Free flap transplantation combined with Ilizarov bone transport is an effective treatment for severe composite tibial and soft tissue defects.
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http://dx.doi.org/10.1177/03000605211017618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168033PMC
May 2021

Senescence-associated secretory phenotype and activation of NF-κB in splenocytes of old mice exposed to irradiation at a young age.

Dev Comp Immunol 2021 Sep 8;122:104124. Epub 2021 May 8.

Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. Electronic address:

DNA damage-induced cellular senescence is involved in aging. We reported previously that p53 mice subjected to irradiation at a young age exhibited an increased number of splenic lymphocytes in the S and G2/M phases. However, the detailed nature of splenic disorders in these mice is not fully understood. In this study, we investigated the effects on molecules in splenocytes, especially on senescence factors after early exposure of mice to radiation. Mice, 8- (young) or 17-, 30-, and 41-week-old (old) p53 were subjected to 3-Gy whole-body irradiation. Splenocytes were prepared at 56 weeks of age. Immunoblot showed that irradiation at 8 weeks enhanced the expression and phosphorylation of p53, cyclin-dependent kinase 2, cell division cycle 6, and the MDM2 proto-oncogene in splenocytes. However, these molecules were not affected by irradiation at 17, 30, and 41 weeks of age. Similarly, irradiation at 8, but not 17, 30, or 41 weeks, induced phosphorylation of IKKα, NF-κB inhibitor alpha, and p65. Electrophoretic mobility shift assay demonstrated that active forms of NF-κB were increased. In addition, enzyme-linked immunosorbent assay showed that lipopolysaccharide-induced IL-6 production was enhanced in splenocytes of mice irradiated at 8 weeks. ATP levels were increased in splenocytes of mice irradiated at 8, but not 17, 30, or 41 weeks. CDK2 expression and p65 phosphorylation were induced in CD45R/B220 cells from irradiated mice. Overall, irradiation induced a NF-κB-related immune response in the spleen with an increase in senescence marker proteins, such as CDKs and IL-6, which are known to be typical senescence-associated secretory phenotype factors related to stresses, such as DNA damage.
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http://dx.doi.org/10.1016/j.dci.2021.104124DOI Listing
September 2021

Emergency amputation necessitated within 24 hours by a human bite: a case report.

J Int Med Res 2021 May;49(5):3000605211012201

Department of Foot and Ankle Surgery, Center for Orthopaedic Surgery, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510610, China.

We herein review and analyze the diagnosis, treatment, and outcome of a severe infection caused by a human bite. A 68-year-old man was bitten on the forearm by a 3-year-old child. Rapid progression of infection, severe local and systemic poisoning, and diverse clinical manifestations were observed at presentation. Based on the medical history, physical signs, imaging examinations (X-ray films, color Doppler ultrasound, and computed tomography), laboratory examinations, and multidisciplinary consultation, the patient was diagnosed with gas gangrene or gas gangrene-like changes. Twenty-four hours after the injury, an emergency amputation was performed (open amputation with wound closure after 1 week). After the operation, the patient was sent to the intensive care unit for isolation and further anti-infection and anti-shock treatments. His condition gradually improved after treatment and he was discharged without further complications. Bacteriological and pathological examinations indicated infection leading to extensive necrotizing fasciitis of the limb and severe systemic poisoning. In addition, pre-existing myelodysplastic syndrome progressing to acute myeloid leukemia was identified as a possible predisposing factor. Human bites can cause serious infections requiring timely treatment, particularly in patients with predisposing comorbidities.
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http://dx.doi.org/10.1177/03000605211012201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113944PMC
May 2021

A Clinical Risk Score to Predict In-hospital Mortality from COVID-19 in South Korea.

J Korean Med Sci 2021 Apr 19;36(15):e108. Epub 2021 Apr 19.

Division of Cardiology, Department of Internal Medicine, Ulsan Medical Center, Ulsan, Korea.

Background: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19.

Methods: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score). The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves.

Results: The incidence of mortality was 4.3% in both the development and validation set. A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85-0.91) and 0.97 (95% CI, 0.84-0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com).

Conclusion: This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.
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http://dx.doi.org/10.3346/jkms.2021.36.e108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055508PMC
April 2021

Reconstruction of coronoid process of the ulna: a literature review.

J Int Med Res 2021 Apr;49(4):3000605211008323

Department of Foot and Ankle Surgery, Center for Orthopaedic Surgery, the Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

As a pivotal part of the elbow joint structure, the coronoid process of the ulna plays a vital role in maintaining elbow joint stability. Loss of coronoid process height causes instability of the elbow joint depending on the fracture characteristics and size. The diagnosis and treatment of coronoid process fractures has gained widespread attention from orthopedic surgeons. Nevertheless, few reports have described reconstruction of coronoid process fractures and defects that affect elbow joint stability. Treatment of elbow joint instability induced by coronoid process defects is challenging because most cases are complicated by other elbow joint injuries. Moreover, the clinical efficacy remains unclear. The present narrative review was performed to examine the research progress on reconstruction of the coronoid process. The findings of this review provide evidence for clinical repair and reconstruction of coronoid process defects and contribute to the published literature on this topic.
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http://dx.doi.org/10.1177/03000605211008323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053771PMC
April 2021

A transgene-encoded truncated human epidermal growth factor receptor for depletion of anti- B-cell maturation antigen CAR-T cells.

Cell Immunol 2021 05 14;363:104342. Epub 2021 Mar 14.

Department of Oncology, Xinqiao Hospital, The Army Medical Unviersity, Chongqing, China. Electronic address:

Background: Chimeric antigen receptor T cells (CAR-T) against B-cell maturation antigen (BCMA) has been used to treat multiple myeloma (MM). CAR-T cells co-expressing a truncated human EGFR (tEGFR) has been proposed for in vivo cell ablation.

Methods: We designed and tested a novel anti-BCMA CAR. We transduced T cells with retroviral vectors encoding CAR and tEGFR. The anti-BCMA-CAR-transduced T cells were evaluated for the functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication of BCMA. Cetuximab was used for in vivo cell ablation.

Results: The CAR-T cells could specifically recognize BCMA, and anti-BCMA CAR-T cells could exhibit interferon-γ and cytotoxicity specifically produced by BCMA and eradicate tumor in vivo. Cetuximab could mediate antibody-dependent cellular cytotoxicity and in vivo elimination.

Conclusions: We confirm that BCMA is a suitable target for CAR- T cells and tEGFR is a effective tool for cellular ablation.
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http://dx.doi.org/10.1016/j.cellimm.2021.104342DOI Listing
May 2021

Urinary SARS-CoV-2 RNA is An Indicator For The Progression and Prognosis of COVID-19 Disease.

Res Sq 2021 Feb 18. Epub 2021 Feb 18.

We aimed to analyse clinical characteristics and find potential factors predicting poor prognosis in patients with coronavirus disease 2019 (COVID-19). We analyzed the demographic and clinical data of COVID-19 patients and detected SARS-CoV-2 RNA in urine sediments collected from 53 COVID-19 patients enrolled in Renmin Hospital of Wuhan University from January 31, 2020 to February 18, 2020 with qRT-PCR analysis, and then classified those patients based on clinical conditions (severe or non-severe syndrome) and urinary SARS-CoV-2 RNA (U or U ). We found that COVID-19 patients with severe syndrome (severe patients) showed significantly higher positive rate (11 of 23, 47.8%) of urinary SARS-CoV-2 RNA than non-severe patients (4 of 30, 13.3%, p = 0.006). U patients or severe U subgroup exhibited higher prevalence of inflammation and immune discord, cardiovascular diseases, liver damage and renal disfunction, and higher risk of death than U patients. To understand the potential mechanisms underlying the viral urine shedding, we performed renal histopathological analysis on postmortems of patients with COVID-19 and found that severe renal vascular endothelium lesion characterized by increase of the expression of thrombomodulin and von Willebrand factor, markers to assess the endothelium dysfunction. We proposed a theoretical and mathematic model to depict the potential factors determining the urine shedding of SARS-CoV-2. This study indicated that urinary SARS-CoV-2 RNA detected in urine specimens can be used to predict the progression and prognosis of COVID-19 severity.
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http://dx.doi.org/10.21203/rs.3.rs-203728/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899468PMC
February 2021

LncRNA PVT1 promotes the malignant progression of acute myeloid leukaemia via sponging miR-29 family to increase WAVE1 expression.

Pathology 2021 Aug 6;53(5):613-622. Epub 2021 Feb 6.

Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China. Electronic address:

LncRNA PVT1 has been demonstrated to be upregulated in acute myeloid leukaemia (AML) patients and indicates a poor prognosis. Nevertheless, its role in AML remains obscure. This study investigated the regulatory role and potential mechanisms of PVT1 in the progression of AML. Expression of PVT1, miR-29 family and WAVE1 was detected by quantitative real-time polymerase chain reaction. CCK8 and EdU assays were performed to assess the proliferation of AML cells. Cell cycle and apoptosis were determined by propidium iodide (PI) staining and Annexin V/PI staining on a flow cytometer. Transwell assay was carried out to evaluate the migration and invasion abilities. The interaction between miR-29 family and PVT1/WAVE1 was confirmed by dual luciferase reporter assay and RNA immunoprecipitation assay. The protein levels of WAVE1, Bcl-2, Bax, cleaved Caspase 3, cyclin D1, and p21 were detected by western blotting. Xenograft transplantation was performed to determine the tumourigenicity of AML cell in vivo. PVT1 expression was significantly increased in AML patient samples and cells, which positively correlated with WAVE1 expression. Silencing of PVT1 restrained growth, migration and invasion, while inducing apoptosis of AML cells. Moreover, PVT1 acted as a sponge for miR-29 family to increase WAVE1 expression in AML cells. Overexpression of WAVE1 partly counteracted PVT1 knockdown-induced anti-tumour effects on AML cells in vitro and xenograft tumour in vivo. PVT1 facilitated the progression of AML via regulating miR-29 family/WAVE1 axis, which supported the conclusion that PVT1 may be a promising therapeutic target for AML.
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http://dx.doi.org/10.1016/j.pathol.2020.11.003DOI Listing
August 2021

Predicting the Water Rebound Effect in China under the Shared Socioeconomic Pathways.

Int J Environ Res Public Health 2021 02 1;18(3). Epub 2021 Feb 1.

Gansu Meteorological Information and Technical Equipment Support Center, Lanzhou 730020, China.

The rebound effect exists widely in the fields of energy, irrigation, and other resource utilizations. Previous studies have predicted the evolution of different resource utilizations under the shared socioeconomic pathways (SSPs), but it is still unclear whether total water use has a rebound effect. This study uses the SSPs as the basic prediction framework and evaluates the water resources and economic status of the provinces in China using the hydro-economic (HE) classification method. Then, combined with the SSPs scenario setting parameters, the conditional convergence model and the method recommended by the Food and Agriculture Organization of the United Nations (FAO) are used to simulate the changes in water use efficiency of the different provinces in China under different scenarios. Based on the future GDP forecast data of China's provinces, combined with the forecast of water use efficiency changes, the total water use changes in China's 31 provinces under different pathways from 2016 to 2030 are calculated. Among them, the future GDP data is predicted based on the Cobb-Douglas production function and SSPs scenario settings. Using a comprehensive evaluation of the evolution of the efficiency and the total amount, this study reveals whether there is a rebound effect. The results showed that with the continuous growth in the water use efficiency, the total water use had a "U" type trend, which indicated that there was a rebound effect in the total water use of China under the different SSPs. Based on this information, this study proposes some suggestions for irrigation water-saving technologies and policies.
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http://dx.doi.org/10.3390/ijerph18031326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908152PMC
February 2021

Drug-coated balloon treatment for nonsmall de-novo coronary artery disease: angiographic and clinical outcomes.

Coron Artery Dis 2021 Sep;32(6):534-540

Department of Cardiology, Ulsan Medical Center, Ulsan.

Objectives: Although drug-coated balloons (DCBs) are established for de-novo lesions in small coronary arteries, the impact of DCB treatment according to the reference vessel diameter (RVD) remains poorly defined. This study aimed to evaluate the angiographic and long-term clinical outcomes of DCB treatment for de-novo coronary lesions according to RVD.

Methods And Results: A total of 227 patients were retrospectively enrolled and stratified according to an RVD >2.5 mm [nonsmall vessel disease (NSVD) group, n = 100] and ≤2.5 mm [small vessel disease (SVD) group, n = 127]. The primary endpoint was late lumen loss (LLL) at a 6-month follow-up, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization and target vessel thrombosis). The LLL among the 206 patients (90.8%) returning for scheduled angiography at 6 month was similar (NSVD, 0.03 ± 0.22 mm vs. SVD, 0.06 ± 0.25 mm; P = 0.384). TVF was also comparable in both groups at a median follow-up of 3.4 years (NSVD, 7.0 vs. SVD, 7.9 %; P = 0.596). At baseline, there were numerically more dissections in the SVD group compared to the NSVD group (47.2 vs. 35.0 %; P = 0.064); however, most of these had disappeared in both groups at a 6-month follow-up. In a multivariable analysis, the presence of dissection was not associated with LLL or TVF in either group.

Conclusions: The safety and efficacy of DCB treatment for de-novo coronary lesions, in terms of LLL and TVF, was unrelated to RVD.
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http://dx.doi.org/10.1097/MCA.0000000000001006DOI Listing
September 2021

Roles of DNA Methylation in Cold Priming in Tartary Buckwheat.

Front Plant Sci 2020 7;11:608540. Epub 2020 Dec 7.

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, China.

Plants experience a wide array of environmental stimuli, some of which are frequent occurrences of cold weather, which have priming effects on agricultural production and agronomic traits. DNA methylation may act as an epigenetic regulator for the cold response of Tartary buckwheat (). Combined with long-term field observation and laboratory experiments, comparative phenome, methylome, and transcriptome analyses were performed to investigate the potential epigenetic contributions for the cold priming of Tartary buckwheat variety Dingku1. Tartary buckwheat cv. Dingku1 exhibited low-temperature resistance. Single-base resolution maps of the DNA methylome were generated, and a global loss of DNA methylation was observed during cold responding in Dingku1. These sites with differential methylation levels were predominant in the intergenic regions. Several hundred genes had different DNA methylation patterns and expressions in different cold treatments (cold memory and cold shock), such as , , and . The application of a DNA methylation inhibitor caused a change of the free lysine content, suggesting that DNA methylation can affect metabolite accumulation for Tartary buckwheat cold responses. The results of the present study suggest important roles of DNA methylation in regulating cold response and forming agronomic traits in Tartary buckwheat.
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http://dx.doi.org/10.3389/fpls.2020.608540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750358PMC
December 2020

IL-Y Aggravates Murine Chronic Graft--Host Disease by Enhancing T and B Cell Responses.

Front Immunol 2020 23;11:559740. Epub 2020 Nov 23.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Suzhou, China.

IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft--host disease (cGVHD) remains unknown. Here, using murine models of scleroderma-like and lupus-like cGVHD, we examined the function of IL-Y in the pathogenesis of cGVHD by hydrodynamically injecting minicircle-IL-Y expressing plasmids (MC IL-Y). In contrast with the reported immune suppressive function of IL-Y, administration of MC IL-Y enhanced cGVHD severity reflected by deteriorated multi-organ pathologic damages. In lupus-like cGVHD model, urine protein and the serum anti-dsDNA antibody (IgG) were significantly upregulated by IL-Y treatment. Further study demonstrated that IL-Y impacts both donor T and B cell response. In T cells, IL-Y inhibited the generation of CD4Foxp3 regulator T (Treg) cells during the development of cGVHD. IL-Y may also increase the infiltration of pathogenic TNF-α producing CD4 and CD8 T cells through IL-27R in recipient spleens, as this effect was diminished in IL-27R deficient T cells. Moreover, IL-Y enhanced the differentiation of ICOS T follicular helper (Tfh) cells. In B cells, the percentage of germinal center (GC) B cells in recipient spleens was significantly upregulated by MC IL-Y plasmid administration. The levels of co-stimulatory molecules, MHC-II and CD86, on B cells were also enhanced by IL-Y expression. Taken together, our data indicated that IL-Y promoted the process of cGVHD by activating pathogenic T and B cells.
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http://dx.doi.org/10.3389/fimmu.2020.559740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719702PMC
May 2021

LncRNA SNHG5 upregulation induced by YY1 contributes to angiogenesis via miR-26b/CTGF/VEGFA axis in acute myelogenous leukemia.

Lab Invest 2021 03 14;101(3):341-352. Epub 2020 Dec 14.

Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, P.R. China.

Acute myelogenous leukemia (AML) is the most common acute leukemia in adults. Despite great progress has been made in this field, the pathogenesis of AML is still not fully understood. We report here the biological role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in the pathogenesis of AML and the underlying mechanisms. The results showed that lncRNA SNHG5 was highly expressed in AML cancer cell lines. In vitro studies displayed that inhibition of SNHG5 with shRNA resulted in suppression of survival, cell cycle progression, migration/invasion of AML and capacity of adhesion and angiogenesis in human umbilical vein endothelial cells. Mechanistic studies revealed a SNHG5/miR-26b/connective tissue growth factor (CTGF)/vascular endothelial growth factor A (VEGFA) axis in the regulation of AML angiogenesis. Finally, Yin Yang 1 (YY1) was found to transactivate and interact with SNHG5 promoter, leading to the upregulation of SNHG5 in AML. Collectively, upregulation of lncRNA SNHG5 mediated by YY1, activates CTGF/VEGFA via targeting miR-26b to regulate angiogenesis of AML. Our work provides new insights into the molecular mechanisms of AML.
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http://dx.doi.org/10.1038/s41374-020-00519-9DOI Listing
March 2021

Water-in-Oil Pickering Emulsions Stabilized Solely by Water-Dispersible Phytosterol Particles.

Langmuir 2020 12 30;36(49):14991-14998. Epub 2020 Nov 30.

Department of Food Science and Engineering, Jinan University, Guangzhou 510632, PR China.

Water-in-oil (W/O) Pickering emulsions were successfully synthesized by water-dispersible phytosterol (PS) particles formed through simple antisolvent precipitation. The effects of the organic/aqueous ratio on the particle morphology, crystallinity, and contact angle were investigated. Sheet-like PS particles with reduced crystallinity were further used as W/O Pickering emulsion stabilizers. The properties of the formed W/O emulsions could be transformed by changing the oil type, water-phase fraction, or particle contents. Results showed that emulsions with 80% water fraction could be stabilized by 3% particles in the aqueous phase, where dodecane was used as the oil phase. W/O Pickering emulsions stabilized by PS particles showed temperature responsiveness. When dried, PS particles could be well dispersed either in the water or oil phase to stabilize W/O Pickering emulsions. Therefore, this kind of PS particles could not only enrich the family of food-grade Pickering stabilizers, especially the W/O type, but also provide a smart Pickering stabilizer to fabricate environmental-responsive emulsion products.
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http://dx.doi.org/10.1021/acs.langmuir.0c02301DOI Listing
December 2020

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes.

Yonsei Med J 2020 Dec;61(12):1004-1012

Department of Cardiology, Peking University Shougang Hospital, Shijingshan District, Beijig, China.

Purpose: Dissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.

Materials And Methods: A total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).

Results: The cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, =0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, =0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.

Conclusion: The presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).
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http://dx.doi.org/10.3349/ymj.2020.61.12.1004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700881PMC
December 2020

Feruloylated oligosaccharides and ferulic acid alter gut microbiome to alleviate diabetic syndrome.

Food Res Int 2020 11 8;137:109410. Epub 2020 Jun 8.

Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, PR China. Electronic address:

Gut microbiome has been proven to be involved in the development of type 2 diabetes (T2D). Additionally, increasing evidence showed that the composition of gut microbiome is highly associated with the outcome of T2D therapy. Previously we demonstrated that feruloylated oligosaccharides (FOs) and ferulic acid (FA) alleviated diabetic syndrome in rats, but the detailed mechanism has not been explored yet. In this study we strived to characterize how FOs and FA altered the gut microbiome and related metabolome in diabetic rats by using high-throughput sequencing of 16S rRNA and gas chromatography (GC). Our results showed that FOs reduced the abundance of Lactobacillus, Ruminococcus, Oscillibacter, and Desulfovibrio, but increased the abundance of Akkermansia, Phascolarctobacterium and Turicibacter. The structure of gut microbiome in FOs treated rats was similar with healthy rats rather than diabetic rats. Likewise, FA decreased the portion of Lactobacillus, Ruminococcus, but promoted the growth of Bacteroides, Blautia, Faecalibacterium, Parabacteroides and Phascolarctobacterium. Additionally, the short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), the main bacterial lipid metabolites in gut mediating host glucose metabolism, was dramatically elevated along with FOs and FA treatment. Our findings indicated that FOs and FA attenuated diabetic syndrome in rats most likely by modulating the composition and metabolism of gut microbiome. The study gives new insight into the mechanism underlying the anti-diabetes effect of functional foods as well as facilitates the development of dietary supplements for diabetic patients.
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http://dx.doi.org/10.1016/j.foodres.2020.109410DOI Listing
November 2020

Donor γδT Cells Promote GVL Effect and Mitigate aGVHD in Allogeneic Hematopoietic Stem Cell Transplantation.

Front Immunol 2020 16;11:558143. Epub 2020 Oct 16.

Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Disease relapse and graft-versus-host disease (GVHD) are the major complications affecting the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). While the functions of αβT cells are extensively studied, the role of donor γδT cells in allo-HSCT is less well defined. Using TCRδ donors lacking γδT cells, we demonstrated that donor γδT cells were critical in mediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absence of donor γδT cells, IFN-γ production by CD8 T cells was severely impaired. Vγ4 subset was the major γδT cell subset mediating the GVL effect , which was partially dependent on IL-17A. Meanwhile, donor γδT cells could mitigate acute GVHD in a murine allo-HSCT model by suppressing CD4 T cell activation and the major γδT cell subset that exerted this protective function was also Vγ4 γδT cells. Therefore, our findings provide evidence that donor γδT cells, especially Vγ4 subset, can enhance GVL effect and mitigate aGVHD during allo-HSCT.
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http://dx.doi.org/10.3389/fimmu.2020.558143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596318PMC
May 2021

Upregulation of miR-223 abrogates NLRP3 inflammasome-mediated pyroptosis to attenuate oxidized low-density lipoprotein (ox-LDL)-induced cell death in human vascular endothelial cells (ECs).

In Vitro Cell Dev Biol Anim 2020 Sep 10;56(8):670-679. Epub 2020 Sep 10.

Department of Function Examination, Affiliated Sixth Hospital of Xinjiang Medical University, Wuxing South Road 39, Urumqi, 830000, Xinjiang, China.

MiR-223 is closely associated with pathogenesis of coronary artery disease (CAD); however, the molecular mechanisms are unclear. In the present study, the human vascular endothelial cells (ECs) were isolated from patients undergoing coronary artery bypass graft and treated with oxidized low-density lipoprotein (ox-LDL) to induce cellular CAD models in vitro. We found that ox-LDL inhibited cell proliferation and viability, and promoted cell apoptosis in ECs. Of note, ox-LDL promoted cell pyroptosis, and both the pyroptosis inhibitor necrosulfonamide (NSA) and NLRP3 ablation restored cell viability in ECs treated with ox-LDL, indicating that ox-LDL induced EC death by triggering cell pyroptosis. In addition, miR-223 was downregulated by ox-LDL in ECs, and miR-223 overexpression rescued cell viability in ECs treated with ox-LDL. Interestingly, there existed targeting sites in miR-223 and 3' untranslated regions (3' UTRs) of NLRP3 mRNA, and further experiments validated that miR-223 negatively regulated NLRP3 expressions in ECs at both transcriptional and translational levels. Finally, we verified that upregulation of NLRP3 abrogated the protective effects of miR-223 overexpression on ox-LDL-treated ECs. Collectively, this in vitro study proved that overexpression of miR-223 protected ox-LDL-stimulated ECs from death through inactivating NLRP3 inflammasome-mediated pyroptotic cell death.
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http://dx.doi.org/10.1007/s11626-020-00496-9DOI Listing
September 2020

immune activation of splenocytes following exposure to tar from Asian sand dust.

J Toxicol Environ Health A 2020 10 20;83(19-20):649-658. Epub 2020 Aug 20.

Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health , Kitakyushu, Japan.

Air pollution, especially that initiated by particulate matter (PM), has been implicated as a risk factor for several inflammatory diseases. Previously, it was reported that PM enhances immune responses. PM includes the tar fraction that contains polycyclic aromatic hydrocarbons (PAHs), which produce adverse health effects in exposed individuals. However, the influence of the tar fraction (as a component of PM) on splenocytes is not fully understood. The aim of this study was to determine the effects of the tar fraction extracted from PM collected from the atmosphere in Fukuoka, Japan, on mouse splenocytes. ICR mice were administered tar (1 or 5 μg/mouse) intratracheally 4 times at 2-week intervals, and splenocytes from the tar-treated mice were extracted and examined. The parameters determined were proliferation, cytokine concentrations and transcription factors activation. Following tar treatment, splenocyte proliferation increased relative to controls. Concanavalin A (ConA)-induced interleukin (IL)-2 formation and ConA- or lipopolysaccharide (LPS)-induced interferon-γ production were elevated in splenocytes from tar-exposed mice. However, the production of tumor necrosis factor-α and IL-6 induced by LPS was not markedly changed following tar treatment. Further, nuclear factor of activated T cells, but not nuclear factor-κB, was enhanced in splenocytes of tar-exposed mice. Data indicate that tar-activated splenocytes and PM-bound PAHs might contribute to T cell activation in the spleen.
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http://dx.doi.org/10.1080/15287394.2020.1806160DOI Listing
October 2020

Manganese enhances the antitumor function of CD8 T cells by inducing type I interferon production.

Cell Mol Immunol 2021 Jun 17;18(6):1571-1574. Epub 2020 Aug 17.

Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456, Singapore.

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http://dx.doi.org/10.1038/s41423-020-00524-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166851PMC
June 2021

LncRNA-MALAT1 regulates proliferation and apoptosis of acute lymphoblastic leukemia cells via miR-205-PTK7 pathway.

Pathol Int 2020 Oct 4;70(10):724-732. Epub 2020 Aug 4.

Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Long non-coding RNA (lncRNA) MALAT1 has been confirmed to function as an oncogene in various solid tumors. MALAT1 level has been shown to be upregulated in relapsed acute lymphoblastic leukemia (ALL) patients, but the mechanism is unclear. This study aims to investigate the functional roles and underlying mechanisms of MALAT1 in ALL. MALAT1 and miR-205 expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). MTT assay and flow cytometry were performed to evaluate cell proliferation and apoptosis, respectively. Protein level of protein tyrosine kinase-7 (PTK7) was detected by Western blot assay. Dual luciferase reporter assay was conducted to confirm the binding of MALAT1 and miR-205, as well as miR-205 and PTK7. The levels of MALAT1 and PTK7 were upregulated in ALL samples. In contrast, miR-205 level was downregulated in ALL in ALL samples. Moreover, MALAT1 silencing or miR-205 overexpression restrained proliferation and promoted apoptosis of ALL cells. Mechanistically, MALAT1 sponged miR-205 to regulate PTK7 expression. In summary, MALAT1 affected ALL cell proliferation and apoptosis via regulating miR-205-PTK7 axis. Our results suggest that MALAT1-miR-205-PTK7 axis participates in the proliferation and apoptosis of ALL, which may provide a potential treatment target for ALL.
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http://dx.doi.org/10.1111/pin.12993DOI Listing
October 2020
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