Publications by authors named "Jian Pan"

319 Publications

[Clinical study of age-related sensory innervation of the anterior hard palate].

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Apr;39(2):170-174

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Objectives: The present study aimed to explore the innervation of the anterior hard palatine and its relationship with individual development stage. Specifically, the effects of anesthesia on patients of different ages were observed, and neurodevelopment in the maxillofacial region was invesitgated. References that are helpful in selecting local anesthesia were provided.

Methods: A total of 182 patients with mixed dentition were randomly divided into the nasopalatine nerve block and greater palatine nerve block groups. Then, 219 patients with permanent dentition were divided into an adolescent group (13-18 years old) and adult group (over 19 years old), all of whom underwent bilateral greater palatine nerve block. Palatal mucosal pain sensation was tested pre- and post-anesthesia with Von Frey hairs.

Results: Among the children with mixed dentition, bilateral greater palatine nerve block tended to result in better anesthetic effects than nasopalatine nerve block (<0.05), except in the incisive papilla. No difference in anesthetic effect was observed between adolescents and adults (>0.05). The bilateral greater palatine nerve block was more effective in inducing an anesthestic effect in the anterior hard palatine in mixed dentition than in permanent dentition (over 13 years old; <0.05).

Conclusions: The sensation of the anterior hard palatine seems mainly dominated by the greater palatine nerve until mixed dentition and gradually shifted to the nasopalatine nerve in conjunction with maxillary development and tooth replacement. Hence, the innervation of the anterior hard palatine induce a secondary development during the development of the maxilla.
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http://dx.doi.org/10.7518/hxkq.2021.02.007DOI Listing
April 2021

Mechanism of Huayu Jianpi Fangshi decoction in urolithiasis prevention: a randomized trial.

Ann Palliat Med 2021 Mar 24. Epub 2021 Mar 24.

Department of Urology, China Academy of Chinese medical Sciences Guanganmen Hospital, Beijing, China.

Background: This study aims to explore the mechanism of the Huayu Jianpi Fangshi decoction in urolithiasis prevention.

Methods: The present study was designed as a randomized, double-blinded, placebo-controlled clinical trial. Sixty patients with the qi stagnation and blood stasis, spleen deficiency, and dampness obstruction types of urolithiasis were randomly divided into two groups: the treatment group and the control group (n=30 in both groups). Patients in the treatment group were treated with the Huayu Jianpi Fangshi decoction, while patients in the control group were treated with the Huayu Fangshi placebo decoction. Both treatments were taken orally two times per day. All patients received treatment over the course of four weeks. The main outcome indicators included the Tamm-Horsfall protein (THP) expression levels, osteopontin, and inter-αtrypsin inhibitor heavy chain 3 (ITIH3) in the patients' urine as well as changes in 24-h urinary citric acid, urinary magnesium levels, and Traditional Chinese Medicine (TCM) syndrome scores.

Results: The results of the present study revealed a significant increase in the total citric acid excretion level (244.75±59.62 vs. 297.48±57.91 mmol/L, P<0.01), significant decrease in the total urinary THP level (10.83±7.73 vs. 6.37±6.10 mg/L, P<0.05), significant decrease in the total ITIH3 level (9.51±6.32 vs. 6.14±4.46 mg/L, P<0.05) in the patients' 24-h urine, and a significant elevation of the total TCM syndrome score (5% vs. 23%, P<0.01) in the treatment group when compared with the control group.

Conclusions:
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http://dx.doi.org/10.21037/apm-20-2295DOI Listing
March 2021

High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations.

Front Oncol 2021 16;11:614420. Epub 2021 Mar 16.

Department of Hematology, Children's Hospital of Soochow University, Suzhou, China.

Background: Aberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients.

Methods: A total of 976 pediatric B-ALL, including 328 treated with CCLG-ALL-2008 protocol and 648 treated with CCCG-ALL-2015 protocol, were recruited in this retrospective study. CD123 expression was evaluated by flow cytometry. Patients with >50, 20-50, or <20% of CD123 expressing blasts were grouped into CD123, CD123, and CD123, respectively. The correlation between CD123 expression and the patients' clinical characteristics, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were studied statistically.

Results: Of 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123. In the CCLG-ALL-2008 cohort, CD123 was significantly associated with chromosome hyperdiploidy (p < 0.0001), risk stratification (p = 0.004), and high survival rate (p = 0.005). By comparing clinical outcomes, patients with CD123 displayed favorable prognosis, with a significantly better OS (p = 0.005), EFS (p = 0.017), and RFS (p = 0.045), as compared to patients with CD123 and CD123. The prognostic value of CD123 expression was subsequently confirmed in the CCCG-ALL-2015 cohort. Univariate and multivariate cox regression model analysis showed that high CD123 expression was independently associated with favorable EFS (OR: 0.528; 95% CI: 0.327 to 0.853; p = 0.009) in this cohort. In patients without prognosis-defining genomic abnormalities, high CD123 expression strongly indicated superior survival rates and was identified as an independent prognosis factor for EFS and RFS in both cohorts.

Conclusions: A group of B-ALL lacks prognosis-defining genomic aberrations, which proposes a challenge in risk stratification. Our findings revealed that high CD123 expression of leukemic blasts was associated with favorable clinical outcomes in pediatric B-ALL and CD123 could serve as a promising prognosis predictor, especially in patients without prognosis-defining genetic aberrations.
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http://dx.doi.org/10.3389/fonc.2021.614420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008053PMC
March 2021

A positive feedback loop mediated by CsERF31 initiates female cucumber flower development.

Plant Physiol 2021 Mar 21. Epub 2021 Mar 21.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Sex determination is a crucially important developmental event that is pervasive throughout nature and enhances the adaptation of species. Among plants, cucumber (Cucumis sativus L.) can generate both unisexual and bisexual flowers, and the sex type is mainly controlled by several 1-aminocyclopropane-1-carboxylic acid synthases (CsACSs). However, the regulatory mechanism of these synthases remains elusive. Here, we used gene expression analysis, protein-DNA interaction assays, and transgenic plants to study the function of a gynoecium-specific gene, ETHYLENE RESPONSE FACTOR31 (CsERF31), in female flower differentiation. We found that in a predetermined female flower, ethylene signaling activates CsERF31 by CsEIN3, and then CsERF31 stimulates CsACS2, which triggers a positive feedback loop to ensure female rather than bisexual flower development. A similar interplay is functionally conserved in melon (Cucumis melo L.). Knockdown of CsERF31 by RNAi causes defective bisexual flowers to replace female flowers. Ectopic expression of CsERF31 suppresses stamen development and promotes pistil development in male flowers, demonstrating that CsERF31 functions as a sex switch. Taken together, our data confirm that CsERF31 represents the molecular link between female-male determination and female-bisexual determination, and provide mechanistic insight into how ethylene promotes female flowers, rather than bisexual flowers, in cucumber sex determination.
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http://dx.doi.org/10.1093/plphys/kiab141DOI Listing
March 2021

Minimally myelosuppressive regimen for remission induction in pediatric AML: long-term results of an observational study.

Blood Adv 2021 Apr;5(7):1837-1847

Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.

Treatment refusal and death as a result of toxicity account for most treatment failures among children with acute myeloid leukemia (AML) in resource-constrained settings. We recently reported the results of treating children with AML with a combination of low-dose cytarabine and mitoxantrone or omacetaxine mepesuccinate with concurrent granulocyte colony-stimulating factor (G-CSF) (low-dose chemotherapy [LDC]) for remission induction followed by standard postremission strategies. We have now expanded the initial cohort and have provided long-term follow-up. Eighty-three patients with AML were treated with the LDC regimen. During the study period, another 100 children with AML received a standard-dose chemotherapy (SDC) regimen. Complete remission was attained in 88.8% and 86.4% of patients after induction in the LDC and SDC groups, respectively (P = .436). Twenty-two patients in the LDC group received SDC for the second induction course. Significantly more high-risk AML patients were treated with the SDC regimen (P = .035). There were no significant differences between the LDC and SDC groups in 5-year event-free survival (61.4% ± 8.7% vs 65.2% ± 7.4%, respectively; P = .462), overall survival (72.7% ± 6.9% vs 72.5% ± 6.2%, respectively; P = .933), and incidence of relapse (20.5% ± 4.5% vs 17.6% ± 3.9%, respectively; P = .484). Clearance of mutations based on the average variant allele frequency at complete remission in the LDC and SDC groups was 1.9% vs 0.6% (P < .001) after induction I and 0.17% vs 0.078% (P = .052) after induction II. In conclusion, our study corroborated the high remission rate reported for children with AML who received at least 1 course of LDC. The results, although preliminary, also suggest that long-term survival of these children is comparable to that of children who receive SDC regimens.
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http://dx.doi.org/10.1182/bloodadvances.2020003453DOI Listing
April 2021

Wnt Signaling Regulates the Lymphatic Endothelial Transdifferentiation of Adipose-Derived Stromal Cells .

Cell Reprogram 2021 Mar 29. Epub 2021 Mar 29.

State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Lymphedema is a chronic, progressive disease that causes pain as well as heavy economic burdens to patients. Reconstruction of the impaired lymphatic system is the key to treat lymphedema. Currently, there is no cure, but mesenchymal stromal cells show promising potential for lymphatic endothelial regeneration. Adipose-derived stromal cells (ADSCs) have been proved to support lymphangiogenesis both and . However, the mechanism in vascular endothelial growth factor C-induced (VEGF-C-induced) lymphatic endothelial transdifferentiation of ADSCs remains unknown. In this study, we show a novel link between the Wingless and int-1 (Wnt) pathway and the lymphatic endothelial differentiation process. We used LiCl to activate Wnt and DKK-1 to inhibit Wnt. Compared with the Wnt inhibition group and the control groups, the Wnt activation group produced more lymphatic endothelial cell (LEC)-related mRNA and proteins. Besides, Wnt-activated ADSCs formed longer tubes in two-dimensional culture and promoted the growth of lymphatic vessels in a three-dimensional transwell ADSC-LEC co-culture system. Our results demonstrated that activation of Wnt during the lymphatic endothelial transdifferentiation of ADSCs would enhance the efficacy of VEGF-C treatment. We anticipate our assay to expand our knowledge of Wnt in cell transdifferentiation and lay a foundation for future efforts to explore a novel and effective ADSC-based therapy for lymphedema.
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http://dx.doi.org/10.1089/cell.2020.0058DOI Listing
March 2021

A Positive Feedback Loop Mediated by CsERF31 Initiates Female Cucumber Flower Development: ETHYLENE RESPONSE FACTOR31 mediates a positive feedback loop that initiates female cucumber flower development.

Plant Physiol 2021 Mar 21. Epub 2021 Mar 21.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Sex determination is a crucially important developmental event that is pervasive throughout nature and enhances the adaptation of species. Among plants, cucumber (Cucumis sativus L.) can generate both unisexual and bisexual flowers, and the sex type is mainly controlled by several 1-aminocyclopropane-1-carboxylic acid (ACC) synthases. However, the regulatory mechanism of these synthases remains elusive. Here, we used gene expression analysis, protein-DNA interaction assays and transgenic plants to study the function of a gynoecium-specific gene, ETHYLENE RESPONSE FACTOR31 (CsERF31), in female flower differentiation. We found that in a predetermined female flower, ethylene signalling activates CsERF31 by CsEIN3, and then CsERF31 stimulates CsACS2, which triggers a positive feedback loop to ensure female rather than bisexual flower development. A similar interplay is functionally conserved in melon (Cucumis melo L.). Knockdown of CsERF31 by RNAi causes defective bisexual flowers to replace female flowers. Ectopic expression of CsERF31 suppresses stamen development and promotes pistil development in male flowers, demonstrating that CsERF31 functions as a sex switch. Taken together, our data confirm that CsERF31 represents the molecular link between female-male determination and female-bisexual determination, and provide mechanistic insight into how ethylene promotes female flowers, rather than bisexual flowers, in cucumber sex determination.
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http://dx.doi.org/10.1093/plphys/kiab141DOI Listing
March 2021

CsUFO is involved in the formation of flowers and tendrils in cucumber.

Theor Appl Genet 2021 Mar 19. Epub 2021 Mar 19.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Key Message: An unusual flower and tendril (uft) mutant in cucumber was caused by a mutation in Csa1G056950 encoding an F-box protein. Flowers and tendrils are important agronomic and yield traits of cucumber (Cucumis sativus L.). In this study, we identified an unusual flower and tendril (uft) mutant from an ethyl methanesulfonate (EMS) mutagenesis population. Genetic analysis revealed that the phenotype of the uft mutant was regulated by a single recessive nuclear gene. Map-based cloning and MutMap results demonstrated that Csa1G056950 (CsUFO), encoding an F-box protein, was the causal gene for the uft mutant phenotype of cucumber. A single nucleotide polymorphism (SNP) mutation (C to T) in the second exon of CsUFO resulted in premature translation termination. The expression level of CsUFO was significantly decreased in apical buds of the uft mutant compared with the wild-type (WT) WD1. Transcriptome analysis indicated that many genes for organ development were down-regulated in uft plants, suggesting CsUFO-associated networks that regulate flower and tendril development. These findings provide a new insight into understanding the molecular mechanisms of flower organogenesis in cucumber.
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http://dx.doi.org/10.1007/s00122-021-03811-4DOI Listing
March 2021

Semisynthesis and Biological Evaluation of Platencin Thioether Derivatives: Dual FabF and FabH Inhibitors against MRSA.

ACS Med Chem Lett 2021 Mar 15;12(3):433-442. Epub 2021 Feb 15.

Xiangya International Academy of Translational Medicine at Central South University, Changsha, Hunan 410013, China.

The discovery and clinical use of multitarget monotherapeutic antibiotics is regarded as a promising approach to reduce the development of antibiotic resistance. Platencin (PTN), a potent natural antibiotic initially isolated from a soil actinomycete, targets both FabH and FabF, the initiation and elongation condensing enzymes for bacterial fatty acid biosynthesis. However, its further clinical development has been hampered by poor pharmacokinetics. Herein we report the semisynthesis and biological evaluation of platencin derivatives - with potent antibacterial activity against methicillin-resistant in vitro. Some of these PTN analogues showed similar yet distinct interactions with FabH and FabF, as shown by molecular docking, differential scanning fluorometry, and isothermal titration calorimetry. Compounds , , , and were further evaluated in a mouse peritonitis model, among which showed in vivo antibacterial activity comparable to that of PTN. Our results suggest that semisynthetic modification of PTN is a rapid route to obtain active PTN derivatives that might be further developed as promising antibiotics against drug-resistant major pathogens.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957939PMC
March 2021

COCH predicts survival and adjuvant TACE response in patients with HCC.

Oncol Lett 2021 Apr 10;21(4):275. Epub 2021 Feb 10.

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China.

The aim of the present study was to measure the expression of Cochlin (COCH) and analyze its association with survival, recurrence and the benefits from adjuvant transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) following hepatectomy. Patients with high COCH expression levels had a poorer prognosis in terms of overall and disease-free survival rate compared with those with low COCH expression levels. Further analysis revealed that patients with low COCH expression who received TACE experienced markedly lower early recurrence rates compared with those who did not receive TACE. However, patients with high COCH expression with and without adjuvant TACE after resection experienced no difference in disease recurrence rates. The expression of COCH was found to be associated with hepatitis B virus infection, portal vein tumor thrombosis and Barcelona Clinic Liver Cancer stage in HCC. Therefore, the findings of the present study indicated that clinical detection of COCH expression may help estimate the prognosis of patients with HCC, as well as determine whether to administer TACE after surgery to prevent recurrence.
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http://dx.doi.org/10.3892/ol.2021.12536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905559PMC
April 2021

Epidemiology and genomics of prostate cancer in Asian men.

Nat Rev Urol 2021 Mar 10. Epub 2021 Mar 10.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Prostate cancer is a global health problem, but incidence varies considerably across different continents. Asia is traditionally considered a low-incidence area, but the incidence and mortality of prostate cancer have rapidly increased across the continent. Substantial differences in epidemiological features have been observed among different Asian regions, and incidence, as well as mortality-to-incidence ratio, is associated with the human development index. Prostate cancer mortality decreased in Japan and Israel from 2007 to 2016, but mortality has increased in Thailand, Kyrgyzstan and Uzbekistan over the same period. Genomic analyses have shown a low prevalence of ERG oncoprotein in the East Asian population, alongside a low rate of PTEN loss, high CHD1 enrichments and high FOXA1 alterations. Contributions from single-nucleotide polymorphisms to prostate cancer risk vary with ethnicity, but germline mutation rates of DNA damage repair genes in metastatic prostate cancer are comparable in Chinese and white patients from the USA and UK. Pharmacogenomic features of testosterone metabolism might contribute to disparities seen in the response to androgen deprivation between East Asian men and white American and European men. Overall, considerable diversity in epidemiology and genomics of prostate cancer across Asia defines disease characteristics in these populations, but studies in this area are under-represented in the literature. Taking into account this intracontinental and intercontinental heterogeneity, translational studies are required in order to develop ethnicity-specific treatment strategies.
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http://dx.doi.org/10.1038/s41585-021-00442-8DOI Listing
March 2021

International Recommendations on Re-irradiation by Intensity-modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma.

Int J Radiat Oncol Biol Phys 2021 Feb 2. Epub 2021 Feb 2.

Department of Clinical Oncology, University of Hong Kong Shenzhen Hospital and University of Hong Kong, HONG KONG, CHINA. Electronic address:

Purpose: Re-irradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging as prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking as available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions.

Methods And Materials: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was re-circulated to the whole panel for review and reconsideration. The current guideline was based on majority voting following repeated iteration for final agreement.

Results: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of re-irradiation (including patient selection, targets contouring, dose prescription and constraints).

Conclusion: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of re-irradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's conditions, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.041DOI Listing
February 2021

Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs.

Front Genet 2020 25;11:590672. Epub 2021 Jan 25.

School of Medical Informatics, Harbin Medical University, Daqing, China.

Circular RNAs (circRNAs) are evolutionarily conserved and abundant non-coding RNAs whose functions and regulatory mechanisms remain largely unknown. Here, we identify and characterize an epigenomically distinct group of circRNAs (TAH-circRNAs), which are transcribed to a higher level than their host genes. By integrative analysis of cistromic and transcriptomic data, we find that compared with other circRNAs, TAH-circRNAs are expressed more abundantly and have more transcription factors (TFs) binding sites and lower DNA methylation levels. Concordantly, TAH-circRNAs are enriched in open and active chromatin regions. Importantly, ChIA-PET results showed that 23-52% of transcription start sites (TSSs) of TAH-circRNAs have direct interactions with cis-regulatory regions, strongly suggesting their independent transcriptional regulation from host genes. In addition, we characterize molecular features of super-enhancer-driven circRNAs in cancer biology. Together, this study comprehensively analyzes epigenomic characteristics of circRNAs and identifies a distinct group of TAH-circRNAs that are independently transcribed via enhancers and super-enhancers by TFs. These findings substantially advance our understanding of the regulatory mechanism of circRNAs and may have important implications for future investigations of this class of non-coding RNAs.
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http://dx.doi.org/10.3389/fgene.2020.590672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868561PMC
January 2021

Feasibility of Atlas Pedicle Screw Fixation Perpendicular to the Coronal Plane-A 3D Anatomic Analysis.

Global Spine J 2021 Feb 2:2192568220980715. Epub 2021 Feb 2.

Department of Orthopedics, Affiliated Zigong Fourth People's Hospital, Zigong, China.

Study Design: An anatomic analysis.

Objective: To investigate the feasibility of the ideal atlas pedicle screw trajectory perpendicular to the coronal plane via atlas digital 3D reconstruction.

Methods: One hundred adult atlases were evaluated in this study. The projection of the corridor for atlas pedicle screw fixation perpendicular to the coronal plane was quickly obtained using the perspective model of 3D reconstruction, and the area, long axis, short axis and width of the pedicle corridor were measured. The inner trajectory was near the lateral wall of the pedicle, and the center of the corridor was point A. The lateral trajectory was near the lateral wall of the transverse foramen, and the center of the trajectory was point C. The midpoint of A and C was B. The length of the inner, middle and lateral trajectorys were measured. The distances from points A, B and C to the posterior tubercle of the atlas and safety swing angle were measured.

Results: From the dorsal view, the pedicle corridor was fitted into an ellipse with an average long axis of 13.6 mm, an average short axis of 5.2 mm, and an average area of 56.3 mm. From the axial view, the pedicle corridor had an average width of 9.4 mm. The average lengths of the inner trajectory, middle trajectory and lateral trajectory were 31.7 mm, 28.7 mm and 25.1 mm, respectively; The average distances from the posterior tubercle to points A, B and C were 17.1 mm, 20.8 mm and 24.5 mm, respectively. The average swing angles from points A, B and C were 16.1°, 25.5°, and 28.1°, respectively.

Conclusion: Atlas pedicle screw fixation perpendicular to the coronal plane is feasible for almost all the volunteers. Pedicle screws close to the pedicle lateral wall of the atlas posterior arch perpendicular to the coronal plane is an advanced technique that is easy to master.
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http://dx.doi.org/10.1177/2192568220980715DOI Listing
February 2021

Study of micro-trichome (mict) reveals novel connections between transcriptional regulation of multicellular trichome development and specific metabolism in cucumber.

Hortic Res 2021 Feb 1;8(1):21. Epub 2021 Feb 1.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Trichomes that cover the epidermis of aerial plant organs play multiple roles in plant protection. Compared with a unicellular trichome in model plants, the development mechanism of the multicellular trichome is largely unclear. Notably, variations in trichome development are often accompanied by defects in the biosynthesis of cuticle and secondary metabolites; however, major questions about the interactions between developmental differences in trichomes and defects in metabolic pathways remain unanswered. Here, we characterized the glabrous mutant mict/csgl1/cstbh via combined metabolomic and transcriptomic analyses to extend our limited knowledge regarding multicellular trichome development and metabolism in cucumber. Mict was found to be explicitly expressed within trichome cells. Transcriptomic analysis indicated that genes involved in flavonoid and cuticle metabolism are significantly downregulated in mict mutants. Further metabolomic analysis confirmed that flavonoids, lipids, and cuticle compositions are dramatically altered in mict mutants. Additional studies revealed that Mict regulates flavonoid, lipid, and cuticle biosynthesis by likely directly binding to downstream functional genes, such as CsTT4, CsFLS1, CsCER26, and CsMYB36. These findings suggest that specific metabolic pathways (e.g., flavonoids and cuticle components) are co-regulated by Mict and provide insights into transcriptional regulation mechanisms of multicellular trichome development and its specific metabolism in cucumber.
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http://dx.doi.org/10.1038/s41438-020-00456-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848009PMC
February 2021

Motivating role of type H vessels in bone regeneration.

Cell Prolif 2020 Sep 19;53(9):e12874. Epub 2020 Jul 19.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Coupling between angiogenesis and osteogenesis has an important role in both normal bone injury repair and successful application of tissue-engineered bone for bone defect repair. Type H blood vessels are specialized microvascular components that are closely related to the speed of bone healing. Interactions between type H endothelial cells and osteoblasts, and high expression of CD31 and EMCN render the environment surrounding these blood vessels rich in factors conducive to osteogenesis and promote the coupling of angiogenesis and osteogenesis. Type H vessels are mainly distributed in the metaphysis of bone and densely surrounded by Runx2 and Osterix osteoprogenitors. Several other factors, including hypoxia-inducible factor-1α, Notch, platelet-derived growth factor type BB, and slit guidance ligand 3 are involved in the coupling of type H vessel formation and osteogenesis. In this review, we summarize the identification and distribution of type H vessels and describe the mechanism for type H vessel-mediated modulation of osteogenesis. Type H vessels provide new insights for detection of the molecular and cellular mechanisms that underlie the crosstalk between angiogenesis and osteogenesis. As a result, more feasible therapeutic approaches for treatment of bone defects by targeting type H vessels may be applied in the future.
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http://dx.doi.org/10.1111/cpr.12874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507571PMC
September 2020

The application of bone marrow mesenchymal stem cells and biomaterials in skeletal muscle regeneration.

Regen Ther 2020 Dec 28;15:285-294. Epub 2020 Nov 28.

State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.

Skeletal muscle injuries have bothered doctors and caused great burdens to the public medical insurance system for a long time. Once injured, skeletal muscles usually go through the processes of inflammation, repairing and remodeling. If repairing and remodeling stages are out of balance, scars will be formed to replace injured skeletal muscles. At present, clinicians usually use conventional methods to restore the injured skeletal muscles, such as flap transplantation. However, flap transplantation sometimes needs to sacrifice healthy autologous tissues and will bring extra harm to patients. In recent years, stem cells-based tissue engineering provides us new treatment ideas for skeletal muscle injuries. Stem cells are cells with multiple differentiation potential and have ability to differentiate into adult cells under special condition. Skeletal muscle tissues also have stem cells, called satellite cells, but they are in small amount and new muscle fibers that derived from them may not be enough to replace injured fibers. Bone marrow mesenchymal stem cells (BM-MSCs) could promote musculoskeletal tissue regeneration and activate the myogenic differentiation of satellite cells. Biomaterial is another important factor to promote tissue regeneration and greatly enhance physiological activities of stem cells . The combined use of stem cells and biomaterials will gradually become a mainstream to restore injured skeletal muscles in the future. This review article mainly focuses on the review of research about the application of BM-MSCs and several major biomaterials in skeletal muscle regeneration over the past decades.
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http://dx.doi.org/10.1016/j.reth.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770413PMC
December 2020

A Transcriptional Regulatory Loop of Master Regulator Transcription Factors, PPARG, and Fatty Acid Synthesis Promotes Esophageal Adenocarcinoma.

Cancer Res 2021 Mar 5;81(5):1216-1229. Epub 2021 Jan 5.

Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Although obesity is one of the strongest risk factors for esophageal adenocarcinoma, the molecular mechanisms underlying this association remain unclear. We recently identified four esophageal adenocarcinoma-specific master regulator transcription factors (MRTF) ELF3, KLF5, GATA6, and EHF. In this study, gene-set enrichment analysis of both esophageal adenocarcinoma patient samples and cell line models unbiasedly underscores fatty acid synthesis as the central pathway downstream of three MRTFs (ELF3, KLF5, GATA6). Further characterizations unexpectedly identified a transcriptional feedback loop between MRTF and fatty acid synthesis, which mutually activated each other through the nuclear receptor, PPARG. MRTFs cooperatively promoted PPARG transcription by directly regulating its promoter and a distal esophageal adenocarcinoma-specific enhancer, leading to PPARG overexpression in esophageal adenocarcinoma. PPARG was also elevated in Barrett's esophagus, a recognized precursor to esophageal adenocarcinoma, implying that PPARG might play a role in the intestinal metaplasia of esophageal squamous epithelium. Upregulation of PPARG increased synthesis of fatty acids, phospholipids, and sphingolipids as revealed by mass spectrometry-based lipidomics. Moreover, ChIP-seq, 4C-seq, and a high-fat diet murine model together characterized a novel, noncanonical, and cancer-specific function of PPARG in esophageal adenocarcinoma. PPARG directly regulated the ELF3 super-enhancer, subsequently activating the transcription of other MRTFs through an interconnected regulatory circuitry. Together, elucidation of this novel transcriptional feedback loop of MRTF/PPARG/fatty acid synthesis advances our understanding of the mechanistic foundation for epigenomic dysregulation and metabolic alterations in esophageal adenocarcinoma. More importantly, this work identifies a potential avenue for prevention and early intervention of esophageal adenocarcinoma by blocking this feedback loop. SIGNIFICANCE: These findings elucidate a transcriptional feedback loop linking epigenomic dysregulation and metabolic alterations in esophageal adenocarcinoma, indicating that blocking this feedback loop could be a potential therapeutic strategy in high-risk individuals.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026506PMC
March 2021

Changes in nutritional status and serum proteins in children with acute lymphoblastic leukemia during induction therapy: a single-centre report from China.

Leuk Lymphoma 2020 Dec 28:1-6. Epub 2020 Dec 28.

Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

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http://dx.doi.org/10.1080/10428194.2020.1864361DOI Listing
December 2020

MBD2 Mediates Septic AKI through Activation of PKCη/p38MAPK and the ERK1/2 Axis.

Mol Ther Nucleic Acids 2021 Mar 28;23:76-88. Epub 2020 Sep 28.

Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Our previous study demonstrated that the methyl-CpG-binding domain protein 2 (MBD2) mediates vancomycin (VAN)-induced acute kidney injury (AKI). However, the role and regulation of MBD2 in septic AKI are unknown. Herein, MBD2 was induced by lipopolysaccharide (LPS) in Boston University mouse proximal tubules (BUMPTs) and mice. For both and experiments, we showed that inhibition of MBD2 by MBD2 small interfering RNA (siRNA) and MBD2-knockout (KO) substantially improved the survival rate and attenuated both LPS and cecal ligation and puncture (CLP)-induced AKI, renal cell apoptosis, and inflammatory factor production. Global genetic expression analyses and experiments suggest that the expression of protein kinase C eta (PKCη), caused by LPS, is markedly suppressed in MBD2-KO mice and MBD2 siRNA, respectively. Mechanistically, chromatin immunoprecipitation (ChIP) analysis indicates that MBD2 directly binds to promoter region CpG islands of PKCη via suppression of promoter methylation. Furthermore, PKCη siRNA improves the survival rate and attenuates LPS-induced BUMPT cell apoptosis and inflammatory factor production via inactivation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)1/2, which were further verified by PKCη siRNA treatment in CLP-induced AKI. Finally, MBD2-KO mice exhibited CLP-induced renal cell apoptosis and inflammatory factor production by inactivation of PKCη/p38MAPK and ERK1/2 signaling. Taken together, the data indicate that MBD2 mediates septic-induced AKI through the activation of PKCη/p38MAPK and the ERK1/2 axis. MBD2 represents a potential target for treatment of septic AKI.
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http://dx.doi.org/10.1016/j.omtn.2020.09.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723772PMC
March 2021

PROTAC Bromodomain Inhibitor ARV-825 Displays Anti-Tumor Activity in Neuroblastoma by Repressing Expression of or .

Front Oncol 2020 26;10:574525. Epub 2020 Nov 26.

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.

Neuroblastoma (NB) is one of the most common solid tumors in childhood. To date, targeting , a well-established driver gene in high-risk neuroblastoma, is still challenging. In recent years, inhibition of bromodomain and extra terminal (BET) proteins shows great potential in multiple of -driven tumors. ARV-825 is a novel BET inhibitor using proteolysis-targeting chimera (PROTAC) technology which degrades target proteins by the proteasome. In this study, we investigated the effect of ARV-825 in neuroblastoma and . Our results showed that ARV-825 treatment robustly induced proliferative suppression, cell cycle arrest, and apoptosis in NB cells. Moreover, ARV-825 efficiently depleted BET protein expression, subsequently repressing the expression of or . In the NB xenograft model, ARV-825 profoundly reduced tumor growth and led to the downregulation of BRD4 and expression in mice. Taken together, these findings provide evidence that PROTAC BET inhibitor is an efficient way to achieve / manipulation, and ARV-825 can be used as a potential therapeutic strategy for the treatment of neuroblastoma.
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http://dx.doi.org/10.3389/fonc.2020.574525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726414PMC
November 2020

Controlled Delivery of Growth Factor by Hierarchical Nanostructured Core-Shell Nanofibers for the Efficient Repair of Critical-Sized Rat Calvarial Defect.

ACS Biomater Sci Eng 2020 10 10;6(10):5758-5770. Epub 2020 Sep 10.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China.

Electrospun nanofibers have received much attention as bone tissue-engineered scaffolds for their capacity to mimic the structure of natural extracellular matrix (ECM). Most studies have reproduced nanofibers with smooth surface for tissue engineering. This is quite different from the triple-helical nanotopography of natural collagen nanofibrils. In this study, hierarchical nanostructures were coated on the surface of drug-loaded core-shell nanofibers to mimic natural collagen nanofibrils. The nanoshish-kebab (SK) structure was decorated regularly on the surface of the nanofibers, and the inner-loaded bone morphogenetic protein 2 (BMP2) exhibited a gentle release pattern, similar to a zero-order release pattern in kinetics. The in vitro study also showed that the SK structure could accelerate cell proliferation, attachment, and osteogenic differentiation. Four groups of scaffolds were implanted in vivo to repair critical-sized rat calvarial defects: (1) PCL/PVA (control); (2) SK-PCL/PVA; (3) PCL/PVA-BMP2; and (4) SK-PCL/PVA-BMP2. Much more bone was formed in the SK-PCL/PVA group (24.57 ± 3.81%) than in the control group (1.21 ± 0.23%). The BMP2-loaded core-shell nanofibers with nanopatterned structure (SK-PCL/PVA-BMP2) displayed the best repair efficacy (76.38 ± 4.13%), followed by the PCL/PVA-BMP2 group (39.86 ± 5.74%). It was believed that the hierarchical nanostructured core-shell nanofibers could promote osteogeneration and that the SK structure showed synergistic ability with nanofiber-loaded BMP2 in vivo for bone regeneration. Thus, this BMP2-loaded core-shell nanofiber scaffold with hierarchical nanostructure holds great potential for bone tissue engineering applications.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00837DOI Listing
October 2020

Morphological changes in and quantitative analysis of macular retinal microvasculature by optical coherence tomography angiography in hypertensive retinopathy.

Hypertens Res 2021 Mar 14;44(3):325-336. Epub 2020 Dec 14.

Department of Ophthalmology, the First Hospital Affiliated of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.

Hypertension is a serious global health problem. Hypertensive retinopathy is generally considered to be a predictor of vascular disease elsewhere in the human body. In the past few decades, a variety of grading systems have been proposed for hypertensive retinopathy. However, these grading systems have some limitations. This study utilized optical coherence tomography angiography (OCTA) to investigate the morphological changes and macular retinal microvasculature in depth among 100 patients with hypertensive retinopathy and 66 healthy participants. Five main pathological changes were discovered in hypertensive retinopathy, as follows: focal capillary sparsity, scattered microangioma, focal macular arch ring defects, focal capillary disorder, and focal capillary nonperfusion at the levels of the superficial and deep vascular networks. In addition, we have found that the number of various pathological changes shows an increasing trend as hypertensive retinopathy progresses and may be related to renal damage. Finally, deep vessel density tended to decrease with progressive stages of hypertensive retinopathy and could be the best indicator to predict the risk of hypertensive retinopathy. Our study, therefore, proposes 3 stages of hypertensive retinopathy without macular edema according to the pathophysiology found by OCTA: stage 1 (only focal capillary sparsity), taking the place of KWB grade I; stage 2 (focal capillary sparsity and scattered microangioma), taking the place of KWB grade II; and stage 3 (focal capillary sparsity, scattered microangioma, focal capillary disorder, and nonperfusion), taking the place of KWB grade III. Hence, OCTA may be a potentially useful tool for evaluating the pathophysiology and staging of hypertensive retinopathy. Further longitudinal prospective studies are needed to confirm our findings.
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http://dx.doi.org/10.1038/s41440-020-00583-0DOI Listing
March 2021

Excision margin of T3 basal cell carcinoma in maxillofacial area: A retrospective cohort study of Asians.

Oral Dis 2020 Dec 3. Epub 2020 Dec 3.

Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: Basal cell carcinoma is the most common skin cancer worldwide. Surgical excision is considered as the mainstay of treatment, while the evidence of excision margin in advanced stage is lacking, especially in maxillofacial area.

Materials And Methods: We conducted a 2-center retrospective cohort study. Disease-free survival rate was estimated for 116 Asian patients with T3 basal cell carcinoma in maxillofacial area who received stand surgical excision with margin of 3-5 mm (Group A), 6-9 mm (Group B), and 10-15 mm (Group C).

Results: For the entire cohort, five-year disease-free survival rates of Groups A, B, and C were 82.1%, 93.5%, and 92.4%, respectively. When compared with Group B, Group A was correlated with lower disease-free survival rate (HR 5.48, p = .04), and Group C was not associated with different disease-free survival rate (HR 0.85, p = .62). Perineural invasion (p = .006) and pathologic subtypes of infiltrative basal cell carcinoma (p = .01) were independent prognosticator for disease-free survival rate.

Conclusions: This multicenter cohort study validated that T3 basal cell carcinoma Asian patients of maxillofacial area treated with excision margin of 6-9 mm had a substantial benefit of disease-free survival rate and skin conservation.
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http://dx.doi.org/10.1111/odi.13742DOI Listing
December 2020

Identification of novel CEBPA double mutations capable of promoting familial AML via the suppression of myeloid differentiation.

Am J Transl Res 2020 15;12(10):6965-6972. Epub 2020 Oct 15.

Department of Hematology, Children's Hospital of Soochow University Soochow 215025, Jiangsu, China.

CCAAT-enhancer-binding protein α (CEBPA) gene carrying two mutations (CEBPA double mutations) is known to promote familial acute myeloid leukemia (AML). However, the underlying mechanism by which CEBPA double mutations promote AML remains poorly understood. Here we report that a family with three generations suffering from familial AML carries novel double mutations of CEBPA. Seven bases of GCGCGGG were inserted into the N-terminal c.113-114 of CEBPA as germline mutations and three bases of AAG were inserted into the C-terminal c.939-940 as a somatic mutation. To test the functional impact of this double mutation, we constructed plasmid encoding the double mutants of CEBPA and transfected it into the myeloid precursor 32Dcl3 cells. Lentiviral induced overexpression of CEBPA with these double mutations inhibited myeloid differentiation of these 32Dcl3 cells, and led to approximately 4-fold fewer frequency of CD11b expression. Our results confirm that the double mutations of CEBPA at both N- and C-terminals are potentially to induce leukemogenesis of AML.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653564PMC
October 2020

Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury.

World J Stem Cells 2020 Oct;12(10):1196-1213

State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.

Background: Nerve diseases and injuries, which are usually accompanied by motor or sensory dysfunction and disorder, impose a heavy burden upon patients and greatly reduce their quality of life. Dental pulp stem cells (DPSCs), derived from the neural crest, have many characteristics that are similar to those of neural cells, indicating that they can be an ideal source for neural repair.

Aim: To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery.

Methods: DPSCs were isolated, cultured, and identified by multilineage differentiation and flow cytometry. Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction. Then, we collected the secretions of DPSCs. We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays. Finally, we generated a sciatic nerve crush injury model and used the sciatic function index, walking track analysis, muscle weight, and hematoxylin & eosin (H&E) staining to further evaluate the nerve repair ability of DPSCs.

Results: DPSCs highly expressed several specific neural markers, including GFAP, S100, Nestin, P75, and NF200, and were inclined toward neural differentiation. Furthermore, neural-induced DPSCs (N-DPSCs) could express neurotrophic factors, including NGF, BDNF, and GDNF. The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells. , both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy. However, in terms of anatomy and motor function, as shown by H&E staining, immunofluorescent staining, and walking track analyses, the repair effects of N-DPSCs were more sustained, potent, and effective than those of DPSCs and the controls.

Conclusion: In summary, this study demonstrated that DPSCs are inclined to differentiate into neural cells. N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs. Furthermore, our results suggested that N-DPSCs could help crushed nerves with functional recovery and anatomical repair . Thus, DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.
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http://dx.doi.org/10.4252/wjsc.v12.i10.1196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596440PMC
October 2020

Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

J Cell Mol Med 2020 12 22;24(23):13763-13774. Epub 2020 Oct 22.

Department of Respiratory and Critical Care Medicine, The Third People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

Type 2 diabetes mellitus (T2DM) is a risk factor for pulmonary tuberculosis (PTB) and increased mortality. This work focused on the functions of phosphorylated STAT3 in lung injury in mouse with T2DM-associated PTB and the molecules involved. A mouse model with T2DM-PTB was induced by administrations of streptozotocin, nicotinamide and mycobacterium tuberculosis (Mtb). A pSTAT3-specific inhibitor AG-490 was given into mice and then the lung injury in mice was observed. The molecules involved in AG-490-mediated events were screened out. Altered expression of miR-19b, miR-1281 and NFAT5 was introduced to identify their involvements and roles in lung injury and PTB severity in the mouse model. Consequently, pSTAT3 expression in mice with T2DM-associated PTB was increased. Down-regulation of pSTAT3 by AG-490 prolonged the lifetime of mice and improved the histopathologic conditions, and inhibited the fibrosis, inflammation, Mtb content and number of apoptotic epithelial cells in mouse lung tissues. pSTAT3 transcriptionally suppressed miR-19b/1281 expression to up-regulate NFAT5. Inhibition of miR-19b/1281 or up-regulation of NFAT5 blocked the protective roles of AG-490 in mouse lung tissues. To conclude, this study evidenced that pSTAT3 promotes NFAT5 expression by suppressing miR-19b/1281 transcription, leading to lung injury aggravation and severity in mice with T2DM-associated PTB.
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http://dx.doi.org/10.1111/jcmm.15954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754065PMC
December 2020

[Expression and Clinical Significance of Long Non-coding RNA AC002454.1 in Children with Acute Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Oct;28(5):1433-1439

Department of Hematology-Oncology; Children's Hospital of Soochow University, Suzhou 215025, Jiangsu Province, China,E-mail:

Objective: To study the difference of long non coding RNA (lncRNA) expression profile in bone marrow specimens of children with acute leukemia (AL) and other hematological disease children with normal bone marrows as controls, to screen the lncRNA related with childhood hematological diseases, and to explore the expression of lncRNA AC002454.1 and its clinical significance in AL children.

Methods: The microarray gene chip technology was used to statistically analyze the lncRNA in bone marrow cells of newly diagnose AL children and control children. Ninty-seren differentially expressed lncRNAs were selected. The bone marrow specimens of ALL children (21 cases), AML children (22 cases) and control children (21 cases) were verified and compared by using qRT-PCR; then the lncRNA with maximum differential expression-lncRNA AC002454.1 was selected and used to analyze the relation of relative expression level with clinical indicators.

Results: The microarray gene chip detection showed that 1 884 differentially expressed lncRNA were found in ALL children, and 4 289 differentically expressed lncRNA were found in AML children. The results confirming these differentically expressed lncRNA by qRT-PCR showed that 9 lncRNA expression were significantly up-regulated in ALL children, and 12 lncRNA expression were significantly up-regulated in AML children. Among these up-regulated lncRNA, the difference of AC002454.1 expression was most significant in ALL and AML children (P<0.05, P<0.01). The detection showed that there was a significant difference, in AC002454.1 relative expression level of newly diagnosed T-ALL and B-ALL children (P<0.01), moreover, this difference also was found in ALL and AML children (P<0.05). The detection analysis showed that there was no statistical difference in AC002454.1 relative expression level among the different sex, age, WBC count at initial diagnosis, chromosome, fusion gene, and risk stratification (P>0.05 for all).

Conclusion: The lncRNA expression profile of AL children has been gained by using the lncRNA microarray gene chip technicology. AC002454.1 the significantly high expression exist in AL children, which relates with immunotyping and prognosis of AL children in a certain degree.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.05.001DOI Listing
October 2020

Prevalence of comprehensive DNA damage repair gene germline mutations in Chinese prostate cancer patients.

Int J Cancer 2021 Feb 16;148(3):673-681. Epub 2020 Oct 16.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Germline DNA damage repair (DDR) deficiency has been associated with increased cancer risk, poor prognosis and therapeutic opportunity for prostate cancer (PCa) patients. However, the landscape of germline mutations in PCa covering comprehensive DDR genes has not been reported. We performed whole-exome sequencing in 246 patients who meet the National Cancer Center Network guidelines for genetic testing and analyzed variants in 276 DDR genes, which was from the Cancer Genome Atlas. A total of 79 deleterious germline alterations in 60 DDR genes were identified in 31% (76/246) patients. Mutations were found in nine DDR pathways, including 11.8% men in homologous recombination repair (HR) pathways, 2.4% men in mismatch repair (MMR) pathway and 16.7% (41/246) patients in non-HR/MMR pathways. In HRR and MMR pathways, mutations were mostly identified in BRCA2 (5.3%), HFM1 (0.8%), ZSWIM7 (0.8%), MSH2 (0.8%) and MSH3 (0.8%). When compared with the cancer-free cohort, POLN and POLG conferred high risk to PCa with odds ratio 6.9 and 20.5, respectively. We provided a comprehensive view of germline DDR gene mutations in PCa patients. We also identified two potential PCa predisposition genes: POLN and POLG, which have not been reported in the Western population, confirming the necessity of customizing a multigene panel for Chinese PCa patients.
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http://dx.doi.org/10.1002/ijc.33324DOI Listing
February 2021

Interleukin-4-loaded hydrogel scaffold regulates macrophages polarization to promote bone mesenchymal stem cells osteogenic differentiation via TGF-β1/Smad pathway for repair of bone defect.

Cell Prolif 2020 Oct 19;53(10):e12907. Epub 2020 Sep 19.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: Tissue engineering is a promising strategy for repair of large bone defect. However, the immune system reactions to biological scaffold are increasingly being recognized as a crucial factor influencing regeneration efficacy. In this study, a bone-bioactive hydrogel bead loaded with interleukin-4 (IL-4) was used to regulate macrophages polarization and accelerate bone regeneration.

Methods: IL-4-loaded calcium-enriched gellan gum (Ca-GG + IL-4) hydrogel beads were synthesised. And the effect on cell behaviour was detected. Furthermore, the effect of the Ca-GG + IL-4 hydrogel bead on macrophage polarization and the effect of macrophage polarization on bone mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation were evaluated in vitro and in vivo.

Results: BMSCs were able to survive in the hydrogel regardless of whether IL-4 was incorporated. Immunofluorescence staining and qPCR results revealed that Ca-GG + IL-4 hydrogel bead could promote M2 macrophage polarization and increase transforming growth factor (TGF)-β1 expression level, which activates the TGF-β1/Smad signalling pathway in BMSCs and promotes osteogenic differentiation. Moreover, immunohistochemical analysis demonstrated Ca-GG + IL-4 hydrogel bead could promote M2 macrophage polarization and reduce cell apoptosis in vivo. In addition, micro-CT and immunohistochemical analysis at 12 weeks post-surgery showed that Ca-GG + IL-4 hydrogel bead could achieve superior bone defect repair efficacy in vivo.

Conclusions: The Ca-GG + IL-4 hydrogel bead effectively promoted bone defect regeneration via regulating macrophage polarization, reducing cell apoptosis and promoting BMSCs osteogenesis through TGF-β1/Smad pathway. Therefore, it is a promising strategy for repair of bone defect.
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http://dx.doi.org/10.1111/cpr.12907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574882PMC
October 2020