Publications by authors named "Jia Ma"

195 Publications

Comparative efficacy of osteochondral autologous transplantation and microfracture in the knee: an updated meta-analysis of randomized controlled trials.

Arch Orthop Trauma Surg 2021 Jul 25. Epub 2021 Jul 25.

Department of Arthroscopy and Sports Medicine, China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, 100102, China.

Introduction: More than 19% of patients undergoing knee arthroscopies suffers from articular cartilage defects. The chondral or osteochondral lesion has negative impacts on the knee joints function and the life quality of patients. However, the treatment remains challenging as hyaline cartilage is not renewable. The purpose of this study was to systematically analyze the data of randomized controlled trials for comparing the postoperative outcomes between osteochondral autologous transplantation (OAT) and microfracture (MF) procedure. We hypothesized that the outcomes were better in OAT than MF procedure.

Materials And Methods: A systematic literature search of the EMBASE, Pubmed, and Cochrane Library databases was conducted based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The outcome measures include: the rate of excellent or good results, the rate of return to sports, the failure rate, osteoarthritis rate, International Cartilage Repair Society (ICRS) score, Lysholm Knee Score, and Tegner scale. The statistical analysis was completed using Review Manager (RevMan, version 5.3) software.

Results: The systematic search identified 7 studies with a total of 346 patients. The pooled result showed significant differences between the two groups in the rate of return to sports and failure. The following outcome scores showed significant improvement (pre- vs postoperatively): Lysholm score (p = 0.02), Tegner scale (p < 0.00001), and ICRS score (p < 0.00001). The differences were not significant in the excellent or good results and the rate of osteoarthritis.

Conclusion: The patients in OAT group may return to play quicker, even return to pre-injury level of activity compared to the MF group. OAT is better than MF procedure in accordance with Lysholm score, Tegner score, ICRS score, and the rate of failure. However, few studies have reported long-term outcomes and there has no uniform criteria for safe return to sports. Further research is needed.

Level Of Evidence: Level II, meta-analysis of randomized controlled trials.
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http://dx.doi.org/10.1007/s00402-021-04075-9DOI Listing
July 2021

Comparing the monetary value of a quality-adjusted life year from the payment card and the open-ended format.

Cost Eff Resour Alloc 2021 Jul 19;19(1):45. Epub 2021 Jul 19.

College of business administration, Shenyang Pharmaceutical University, Shenyang, 110016, China.

Background: The payment card (PC) format and the open-ended (OE) format are common methods in eliciting willingness-to-pay (WTP) of one additional quality-adjusted life year (QALY). The aim of this research is to compare these two formats in eliciting the monetary value of a QALY.

Methods: A contingent valuation survey was carried out using a pre-designed questionnaire with various hypothetical scenarios. The difference between the PC and the OE formats was evaluated by a two-sample equality test. Furthermore, generalized linear models were carried out to control observed heterogeneity and to test theoretical validity.

Results: In total, 461 individuals were involved, among whom 235 (51%) answered the PC question, while 226 (49%) answered the OE question. Excluding zero response, the mean WTP values of these two formats for different scenarios varied dramatically, which was from 13,278 to 280,177 RMB for the PC, 18,119 to 620,913 RMB for the OE. The OE format tended to elicit lower values for less serious condition and higher values for more serious condition. However, equality test of mean and median demonstrated insignificant difference of these two formats for all scenarios. For both OE and PC format, most variables were found to have significant effect on the value of WTP/QALY. Moreover, joint estimation indicated a statistically significant positive effect on the OE results. Further analysis demonstrated that the imbalanced zero response distribution caused the main difference of these two formats.

Conclusions: This research indicated insignificantly different WTP/QALY estimates of the PC format and OE format with the grouped data whereas significantly higher estimates of the OE format from the pooled data. These two formats were found to be valid. More research about the difference and the validity of various WTP eliciting methods would be recommended for a robust estimation of WTP/QALY.
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http://dx.doi.org/10.1186/s12962-021-00298-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287741PMC
July 2021

Variable Autoinhibition among Deafness-Associated Variants of Diaphanous 1 (DIAPH1).

Biochemistry 2021 Jul 19;60(29):2320-2329. Epub 2021 Jul 19.

Department of Chemistry, Barnard College, New York, New York 10027, United States.

One of the earliest mapped human deafness genes, , encodes the formin DIAPH1. To date, at least three distinct mutations in the C-terminal domains and two additional mutations in the N-terminal region are associated with autosomal dominant hearing loss. The underlying molecular mechanisms are not known, and the role of formins in the inner ear is not well understood. In this study, we use biochemical assays to test the hypotheses that autoinhibition and/or actin assembly activities are disrupted by DFNA1 mutations. Our results indicate that C-terminal mutant forms of DIAPH1 are functional and promote actin filament assembly. Similarly, N-terminal mutants are well-folded and have quaternary structures and thermal stabilities similar to those of the wild-type (WT) protein. The strength of the autoinhibitory interactions varies widely among mutants, with the , A265S, and I530S mutations having an affinity similar to that of WT and the 1213x and Δ mutations completely abolishing autoinhibition. These data indicate that, in some cases, hearing loss may be linked to weakened inhibition of actin assembly.
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http://dx.doi.org/10.1021/acs.biochem.1c00170DOI Listing
July 2021

Mesenchymal Stem Cells (MSCs) in Targeted Drug Delivery: Literature Review and Exploratory Data on Migrating and Differentiation Capacities of Bone MSCs into Hepatic Progenitor Cells.

Curr Top Med Chem 2021 Jul 7. Epub 2021 Jul 7.

Department of Surgical Oncology, Shaanxi Provincial People's Hospital (Third Hospital of Medical College of Xi'an Jiaotong University), Xi'an 710068, China.

Background And Objective: Mesenchymal stem cells (MSCs), particularly bone MSCs (BMSCs) offer great potentials for targeted therapeutic applications due to their migratory and differentiation capacities. Significant advances have been achieved in the differentiation of hepatocyte or hepatocyte-like cells both in vitro and in vivo. However, there is limited knowledge on the differentiation of BMSCs into bipotential hepatic progenitor cells or cholangiocytes. This study reviews the potentials and advances in using MSCs as vehicles for targeted drug delivery and proposes a new method for induction of differentiation in rat BMSCs into hepatic progenitor cells in vitro, and assesses the differential and migratory capacities.

Methods: The BMSCs of Sprague Dawley (SD) rats were harvested from the femur and the tibiae of the rats. After isolation and culturing, BMSCs from Passage 1 were used for the study. The in vitro differentiation of the hepatic progenitor cells was performed using a 2-step induction approach after 5-day serum deprivation from the BMSCs and culturing in Dulbecco's modified eagle medium. Spontaneous in vitro differentiation of BMSCs was examined in the absence of growth factors for 15 days as a control treatment. Hepatocytes differentiation was achieved by exposing the culture to collagen type I-coated plates. Cholangiocytes differentiation was achieved by replating the BMC-HepPCs on a layer of Matrigel. Immunofluorescence was conducted on twelve-well plates to determine cell differentiation. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to determine the total RNA extracted using the Trizol LS reagent. In the hepatocyte differentiation group, after periodic acid-schiff (PAS) staining for glycogen, the inverted microscope was used to determine differentiation and undifferentiated BMC-HepPCs served as controls. The amount of low-density lipoprotein (LDL) uptake by the BMSCs-derived hepatocytes were assessed using fluorescence microscopy. The secretion of rat albumin was quantified using a quantitative ELISA kit.

Results: Differentiation induction is indicative of the sequential supplementation of sodium butyrate and cytokines, which are involved in the embryonic development of the mammalian liver. Hepatic progenitor cells, derived from bone marrow, can be differentiated bidirectionally in vitro into both hepatocyte and cholangiocyte cell lines. The differentiated cells, including hepatic progenitor cells, hepatocytes, and bile duct-like cells, were identified and analyzed at mRNA and protein levels.

Conclusion: Our findings show that BMSCs can be utilized as novel bipotential hepatic progenitor cells and thereby for hepatobiliary disease treatment or hepatobiliary tissue engineering.
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http://dx.doi.org/10.2174/1568026621666210708092728DOI Listing
July 2021

PDS5B inhibits cell proliferation, migration, and invasion via upregulation of LATS1 in lung cancer cells.

Cell Death Discov 2021 Jun 21;7(1):168. Epub 2021 Jun 21.

Department of Laboratory Medicine, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, China.

PDS5B (precocious dissociation of sisters 5B) plays a pivotal role in carcinogenesis and progression. However, the biological functions of PDS5B in lung cancer and its underlying mechanisms are not fully elucidated. In the present study, we used MTT assays, wound-healing assays, and transwell migration and invasion approach to examine the cell viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells after PDS5B modulation. Moreover, we investigated the function of PDS5B overexpression in vivo. Furthermore, we detected the expression of PDS5B in tissue samples of lung cancer patients by immunohistochemical study. We found that upregulation of PDS5B repressed cell viability, migration, and invasion in NSCLC cells, whereas downregulation of PDS5B had the opposite effects. We also observed that PDS5B overexpression retarded tumor growth in nude mice. Notably, PDS5B positively regulated LATS1 expression in NSCLC cells. Strikingly, low expression of PDS5B was associated with lymph node metastasis in lung cancer patients. Our findings suggest that PDS5B might be a therapeutic target for lung cancer.
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http://dx.doi.org/10.1038/s41420-021-00537-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257726PMC
June 2021

[Comparison of the efficacy between open and arthroscopic Latarjet procedure in the treatment of anterior shoulder instability:a Meta-analysis].

Zhongguo Gu Shang 2021 Jun;34(6):573-83

The Forth Department of Joint, Wangjing Hospital of China Academy of Chinese Medical Science, Beijing 100102, China.

Objective: To compare the clinical efficacy between open and arthroscopic Latarjet procedure in the treatment of anterior shoulder instability by using Meta-analysis.

Methods: Search PubMed, Medline, Embase, Cochrane, China National Knowledge Infrastructure(CNKI), Wanfang database, China Biological Literature system(CBM) and VIP database. Review all retrospective or prospective cohort studies and randomized controlled trials on open and arthroscopic Latarjet procedure for anterior shoulder instability. Binary variables (postoperative recurrence rate, incidence of intraoperative and postoperative complications) and continuousvariables [shoulder external rotation range of motion, Walch-Duplay score, Rowe score, WOSI score, postoperative visual analogue scale (VAS), postoperative anxiety degree and operation time] were selected for analysis. NOS bias risk assessment criteria (recommended by Cochrane collaboration Network) were used to evaluate the literature quality of retrospective or prospective cohort studies, and modified Jadad scale was used to evaluate the quality of randomized controlled trials. Literature screening, literature quality evaluation and data extraction were carried out independently by two observers. RevMan 5.3 software was used for Meta analysis.

Results: (1)A total of 9 studies were included, including 8 retrospective cohort studies and 1 prospective cohort study. A total of 956 patients were included in this study, including open Latarjet procedure(=436) and arthroscopic Latarjet procedure(=520). (2)The postoperative WOSI score in the open group was better than that of arthroscopic group (=93.74, 95%:26.00 to 161.49, =0.007), and the α angle was smaller than arthroscopic group(=-6.44, 95%:-12.08 to 0.81, =0.02). (3)The recurrence rate of open Latarjet group was lower than that of arthroscopic Latarjet group, but there was no significant difference between the two groups (=0.84, 95%:0.23 to 3.05, =0.79). (4)There were no significant difference in shoulder external rotation, Walch-Duplay score, Rowe score, postoperative visual analogue score, postoperative anxiety degree and operation time between open and arthroscopic Latarjet group.

Conclusion: The arthroscopic Latarjet stabilisation shows satisfactory and comparable results to open procedure, and the postoperative recurrence and complication rates are low in both group. Both open and arthroscopic Latarjet procedure are reliable surgical procedures in the treatment of anteriorly shoulder instability. Arthroscopic procedure has longer learning curve than open procedure, the doctors may either choose arthroscopic or open Latarjet procedure based on personal skills and preference, as well as the patient's condition. However, all the literatures included in this study are cohort studies with low level of evidence. The research lack randomized controlled trials, and small sample size is small. In the future, randomized controlled studies with large sample size and high level of evidence are still needed to determine the efficacy difference between the two.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.06.019DOI Listing
June 2021

A Bacteriophage DNA Mimic Protein Employs a Non-specific Strategy to Inhibit the Bacterial RNA Polymerase.

Front Microbiol 2021 2;12:692512. Epub 2021 Jun 2.

BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

DNA mimicry by proteins is a strategy that employed by some proteins to occupy the binding sites of the DNA-binding proteins and deny further access to these sites by DNA. Such proteins have been found in bacteriophage, eukaryotic virus, prokaryotic, and eukaryotic cells to imitate non-coding functions of DNA. Here, we report another phage protein Gp44 from bacteriophage SPO1 of , employing mimicry as part of unusual strategy to inhibit host RNA polymerase. Consisting of three simple domains, Gp44 contains a DNA binding motif, a flexible DNA mimic domain and a random-coiled domain. Gp44 is able to anchor to host genome and interact bacterial RNA polymerase the β and β' subunit, resulting in bacterial growth inhibition. Our findings represent a non-specific strategy that SPO1 phage uses to target different bacterial transcription machinery regardless of the structural variations of RNA polymerases. This feature may have potential applications like generation of genetic engineered phages with Gp44 gene incorporated used in phage therapy to target a range of bacterial hosts.
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http://dx.doi.org/10.3389/fmicb.2021.692512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208478PMC
June 2021

Orlistat induces ferroptosis-like cell death of lung cancer cells.

Front Med 2021 Jun 4. Epub 2021 Jun 4.

Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, 233030, China.

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
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http://dx.doi.org/10.1007/s11684-020-0804-7DOI Listing
June 2021

Kinetic and structural parameters governing Fic-mediated adenylylation/AMPylation of the Hsp70 chaperone, BiP/GRP78.

Cell Stress Chaperones 2021 Jul 3;26(4):639-656. Epub 2021 May 3.

From the Department of Biological Sciences, Purdue University, 915 W. State St., LILY G-227, West Lafayette, IN, 47907, USA.

Fic (filamentation induced by cAMP) proteins regulate diverse cell signaling events by post-translationally modifying their protein targets, predominantly by the addition of an AMP (adenosine monophosphate). This modification is called Fic-mediated adenylylation or AMPylation. We previously reported that the human Fic protein, HYPE/FicD, is a novel regulator of the unfolded protein response (UPR) that maintains homeostasis in the endoplasmic reticulum (ER) in response to stress from misfolded proteins. Specifically, HYPE regulates UPR by adenylylating the ER chaperone, BiP/GRP78, which serves as a sentinel for UPR activation. Maintaining ER homeostasis is critical for determining cell fate, thus highlighting the importance of the HYPE-BiP interaction. Here, we study the kinetic and structural parameters that determine the HYPE-BiP interaction. By measuring the binding and kinetic efficiencies of HYPE in its activated (Adenylylation-competent) and wild type (de-AMPylation-competent) forms for BiP in its wild type and ATP-bound conformations, we determine that HYPE displays a nearly identical preference for the wild type and ATP-bound forms of BiP in vitro and preferentially de-AMPylates the wild type form of adenylylated BiP. We also show that AMPylation at BiP's Thr366 versus Thr518 sites differentially affect its ATPase activity, and that HYPE does not adenylylate UPR accessory proteins like J-protein ERdJ6. Using molecular docking models, we explain how HYPE is able to adenylylate Thr366 and Thr518 sites in vitro. While a physiological role for AMPylation at both the Thr366 and Thr518 sites has been reported, our molecular docking model supports Thr518 as the structurally preferred modification site. This is the first such analysis of the HYPE-BiP interaction and offers critical insights into substrate specificity and target recognition.
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http://dx.doi.org/10.1007/s12192-021-01208-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275707PMC
July 2021

L-Se-methylselenocysteine sensitizes lung carcinoma to chemotherapy.

Cell Prolif 2021 May 1;54(5):e13038. Epub 2021 Apr 1.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: Organic Selenium (Se) compounds such as L-Se-methylselenocysteine (L-SeMC/SeMC) have been employed as a class of anti-oxidant to protect normal tissues and organs from chemotherapy-induced systemic toxicity. However, their comprehensive effects on cancer cell proliferation and tumour progression remain elusive.

Materials And Methods: CCK-8 assays were conducted to determine the viabilities of cancer cells after exposure to SeMC, chemotherapeutics or combined treatment. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation levels were assessed via fluorescence staining. The efficacy of free drugs or drug-loaded hydrogel against tumour growth was evaluated in a xenograft mouse model.

Results: Among tested cancer cells and normal cells, the A549 lung adenocarcinoma cells showed higher sensitivity to SeMC exposure. In addition, combined treatments with several types of chemotherapeutics induced synergistic lethality. SeMC promoted lipid peroxidation in A549 cells and thereby increased ROS generation. Significantly, the in vivo efficacy of combination therapy was largely potentiated by hydrogel-mediate drug delivery.

Conclusions: Our study reveals the selectivity of SeMC in the inhibition of cancer cell proliferation and develops an efficient strategy for local combination therapy.
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http://dx.doi.org/10.1111/cpr.13038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088472PMC
May 2021

Epigenetic Remodeling Hydrogel Patches for Multidrug-Resistant Triple-Negative Breast Cancer.

Adv Mater 2021 May 1;33(18):e2100949. Epub 2021 Apr 1.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

The induced expansion of tumor-initiating cells (T-ICs) upon repeated exposure of tumors to chemotherapeutic drugs forms a major cause for chemoresistance and cancer metastasis. Here, a tumor-microenvironment-responsive hydrogel patch is designed to modulate the plasticity of T-ICs in triple-negative breast cancer (TNBC), which is insensitive to hormone- and HER2-targeting. The on-site formation of the hydrogel network patches tumors in a chemoresistant TNBC murine model and senses intratumoral reactive oxygen species for linker cleavage and payload release. Patch-mediated inhibition of the histone demethylase lysine-specific demethylase 1 (LSD1) epigenetically regulates the switch of T-ICs from self-renewal to differentiation, rehabilitating their chemosensitivity. Moreover, the hydrogel patch enhances tumor immunogenicity and increases T-cell infiltration via epigenetic activation of innate immunity. A single-dose of the hydrogel patch harboring LSD1 inhibitor and chemotherapy agent efficiently suppresses tumor growth, postsurgical relapse, and metastasis. The superior efficacy against multidrug resistance further reveals the broad applicability of epigenetic remodeling hydrogel patches.
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http://dx.doi.org/10.1002/adma.202100949DOI Listing
May 2021

[Tibialis anterior allograft versus hamstring tendon autograft for anterior cruciate ligament reconstruction:long-term clinical outcomes].

Zhongguo Gu Shang 2021 Mar;34(3):269-74

Forth Department of Joint, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China.

Objective: To compare the clinical outcomes of arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) with a tibialis anterior allograft (TAA)versus hamstring tendon autograft (HTA) after 10 years follow-up.

Methods: A clinical data of 107 patients who underwent arthroscopic ACLR with a single bundle tendon between March 2007 and March 2010 was retrospectively analyzed. Among the patients, 48 patients were reconstructed with a tibialis anterior allograft (TAA group), including 26 males and 22 females, ranging in age from 16 to 38 years, with a mean of 27.2±6.2 years;59 patients were reconstructed with a hamstring tendon autograft (HTA group), including 31 males and 28 females, ranging in age from 16 to 40 years, with a mean of 28.0±7.6 years. The preoperative tibial anterior displacement and knee joint function, as well as knee joint stability, tibial anterior displacement and knee joint function at 10 years after operation were observed. Lachman test was used to evaluate the forward joint stability and pivot shift test to evaluate the rotational stability of the knee;KT-2000 side-to-side difference (SSD) was used to measure tibial anterior displacement;International Knee Documentation Committee(IKDC) score and Lysholm score were used to evaluate knee function.

Results: The incisions of both groups were healed by first intention, and no early complications occurred after operation. All patients were followed-up 10 to 13 years, the mean time was 11.7 years. There was no graft failure were found during the follow up period. The KT-2000 SSD of the TAA group and the HTA group at ten years after operation were 1.9±0.7 and 1.8±0.6 respectively, which were significantly improved than 8.8±0.9 and 8.6±1.0 preoperatively(<0.05), but there were no significant difference between the two groups(>0.05). The total Lysholm score of the TAA group and the HTA group at ten years after operation were 90.4±4.4 and 90.7±3.4 respectively, which were significantly improved than 51.4±13.3 and 51.2±14.6 preoperatively(<0.05), but there were no significant difference between the two groups(>0.05). The total IKDC score of the TAA group and the HTA group at ten years after operation were 91.5±4.1 and 90.9±3.2 respectively, which were significantly improved than 45.8±12.2 and 47.0±14.5 preoperatively(<0.05), but there were no significant difference between the two groups(>0.05). No significant difference were found between the two groups in Lachman test and pivot shift test at 10 years after operation (>0.05).

Conclusion: The TAA and HTA have equal long term effect in ACL reconstruction, doctors and patients can choose the graft according to the actual situation.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.03.016DOI Listing
March 2021

The Combined Contribution of Vascular Endothelial Cell Migration and Adhesion to Stent Re-endothelialization.

Front Cell Dev Biol 2021 4;9:641382. Epub 2021 Mar 4.

West China School of Basic Medical Sciences and Forensic Medicine, Institute of Biomedical Engineering, Sichuan University, Chengdu, China.

Coronary stent placement inevitably causes mechanical damage to the endothelium, leading to endothelial denudation and in-stent restenosis (ISR). Re-endothelialization depends mainly on the migration of vascular endothelial cells (VECs) adjacent to the damaged intima, as well as the mobilization and adhesion of circulating VECs. To evaluate the combined contribution of VEC migration and adhesion to re-endothelialization under flow and the influence of stent, models were constructed to simulate various endothelial denudation scales (2 mm/5 mm/10 mm) and stent deployment depths (flat/groove/bulge). Our results showed that (1) in 2 mm flat/groove/bulge models, both VEC migration and adhesion combined completed the percentage of endothelial recovery about 27, 16, and 12%, and migration accounted for about 21, 15, and 7%, respectively. It was suggested that the flat and groove models were in favor of VEC migration. (2) With the augmentation of the injury scales (5 and 10 mm), the contribution of circulating VEC adhesion on endothelial repair increased. Taken together, endothelial restoration mainly depended on the migration of adjacent VECs when the injury scale was 2 mm. The adhered cells contributed to re-endothelialization in an injury scale-dependent way. This study is helpful to provide new enlightenment for surface modification of cardiovascular implants.
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http://dx.doi.org/10.3389/fcell.2021.641382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969796PMC
March 2021

BMP4 overexpression induces the upregulation of APP/Tau and memory deficits in Alzheimer's disease.

Cell Death Discov 2021 Mar 15;7(1):51. Epub 2021 Mar 15.

Department of Laboratory Medicine, School of Laboratory Medicine, Bengbu Medical College, 233030, Bengbu, Anhui, China.

Alzheimer's disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex and is related to the abnormal expression of the amyloid β (Aβ), APP, and Tau proteins. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD and that endogenous levels of BMP4 mainly affect hippocampal function. To determine whether BMP4 participates in AD development, transgenic mice were constructed that overexpress BMP4 under the control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, transfection, TUNEL, and Western blotting assays to define the role of BMP4 in cells. We found that middle-aged BMP4 transgenic mice exhibited impaired memory via the Morris water maze experiment. Moreover, their hippocampal tissues exhibited high expression levels of AD-related proteins, including APP, Aβ, PSEN-1, Tau, P-Tau (Thr181), and P-Tau (Thr231). Furthermore, in multiple cell lines, the overexpression of BMP4 increased the expression of AD-related proteins, whereas the downregulation of BMP4 demonstrated opposing effects. Consistent with these results, BMP4 modulation affected cell apoptosis via the regulation of BAX and Bcl-2 expression in cells. Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.
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http://dx.doi.org/10.1038/s41420-021-00435-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961014PMC
March 2021

[Anatomical reconstruction of lateral ligament complex with singletunnel pullout stutrue fixation for chronic lateral ankle instability].

Zhongguo Gu Shang 2021 Feb;34(2):143-7

Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.

Objective: To explore clinical effects of single-tunnel pullout structure fixation and anatomical reconstruction of lateral ligament complex in treating chronic lateral ankle instability.

Methods: From January 2016 to December 2018, clinical data of 23 patients with chronic lateral malleolus instability who underwent anatomical reconstruction of lateral malleolus ligament complex with single-tunnel pullout structure fixation, were retrospectively studied. Among them, including 7 males and 16 females, aged from 17 to 33 years old with an avergae of (26.0±4.3) years old;16 patients classified to grage 0, and 7 patients classified to gradeⅠaccording to Kellgren-Lawrence(K-L) grading;the time of sprain ranged form 2 to 15 with an average of (5.7±2.9) times;the time from injury to operation ranged to 4 to 18 months with an average of (9.0±3.3) months. The range of movement of operative and uninjured ankle joints were measured at 24 months after opertaion, visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) were used to evaluate ankle joint function and improvement of pain, K-L grading and MRI scoring of osteoarthritis of ankle (MSOA) were used to evaluate degree of cartilage degeneration of ankle joint.

Results: All patients were followed up from 24 to 48 months with an average of (33.4±6.7) months. All the anterior talofibular ligaments and calcaneofibular ligaments were dissected and reconstructed by single-tunnel pullout structure fixation. The range of motion of dorsiflexion, plantarflexion, varus, and valgus on the operative side of ankle joint were smaller than those on the healthy side. There were no statistically differences in dorsiflexion and eversion between operative side and healthy side of ankle joint (>0.05), while there were statistically differences in plantarflexion and varus (<0.05). AOFAS score improved from 55.19±6.94 before surgery to 93.77±3.42 at 24 months after operation (<0.05), and 23 patients were all excellent. VAS score reduced from 5.30±1.12 before opertaion to 1.10±0.81 at 24 months after operation (<0.05). Forteen patients were grade 0, 8 patients were gradeⅠand 1 patient were gradeⅡaccording to K-L grading, and there were no differences between before and after operation (>0.05). MSOA score increased from 3.74±2.54 before operation to 7.04±2.51 at 24 months after opertaion (<0.05).

Conclusion: Treatment of chronic lateral ankle instability with reconstruction of lateral ligament complex with single-tunnel pullout structure fixation could provide better tendon and bone healing conditions, improve surgical safety and could achieve satisfactory clinical outcomes.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.02.009DOI Listing
February 2021

[Anatomical reconstruction of lateral ligament complex with singletunnel pullout stutrue fixation for chronic lateral ankle instability].

Zhongguo Gu Shang 2021 Feb;34(2):143-7

Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.

Objective: To explore clinical effects of single-tunnel pullout structure fixation and anatomical reconstruction of lateral ligament complex in treating chronic lateral ankle instability.

Methods: From January 2016 to December 2018, clinical data of 23 patients with chronic lateral malleolus instability who underwent anatomical reconstruction of lateral malleolus ligament complex with single-tunnel pullout structure fixation, were retrospectively studied. Among them, including 7 males and 16 females, aged from 17 to 33 years old with an avergae of (26.0±4.3) years old;16 patients classified to grage 0, and 7 patients classified to gradeⅠaccording to Kellgren-Lawrence(K-L) grading;the time of sprain ranged form 2 to 15 with an average of (5.7±2.9) times;the time from injury to operation ranged to 4 to 18 months with an average of (9.0±3.3) months. The range of movement of operative and uninjured ankle joints were measured at 24 months after opertaion, visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) were used to evaluate ankle joint function and improvement of pain, K-L grading and MRI scoring of osteoarthritis of ankle (MSOA) were used to evaluate degree of cartilage degeneration of ankle joint.

Results: All patients were followed up from 24 to 48 months with an average of (33.4±6.7) months. All the anterior talofibular ligaments and calcaneofibular ligaments were dissected and reconstructed by single-tunnel pullout structure fixation. The range of motion of dorsiflexion, plantarflexion, varus, and valgus on the operative side of ankle joint were smaller than those on the healthy side. There were no statistically differences in dorsiflexion and eversion between operative side and healthy side of ankle joint (>0.05), while there were statistically differences in plantarflexion and varus (<0.05). AOFAS score improved from 55.19±6.94 before surgery to 93.77±3.42 at 24 months after operation (<0.05), and 23 patients were all excellent. VAS score reduced from 5.30±1.12 before opertaion to 1.10±0.81 at 24 months after operation (<0.05). Forteen patients were grade 0, 8 patients were gradeⅠand 1 patient were gradeⅡaccording to K-L grading, and there were no differences between before and after operation (>0.05). MSOA score increased from 3.74±2.54 before operation to 7.04±2.51 at 24 months after opertaion (<0.05).

Conclusion: Treatment of chronic lateral ankle instability with reconstruction of lateral ligament complex with single-tunnel pullout structure fixation could provide better tendon and bone healing conditions, improve surgical safety and could achieve satisfactory clinical outcomes.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.02.009DOI Listing
February 2021

[Inhibition of Wnt/β-catenin signal and NOX4 impairs repair of silica-induced lung epithelial cell injury].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Feb;37(2):132-139

Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public health, Ningxia Medical University, Yinchuan 750004, China. *Corresponding authors, E-mail:

Objective To investigate the effects of the interaction between Wnt/β-catenin signal and NADPH oxidase 4 (NOX4) on the proliferation of pulmonary epithelial cells in response to silica exposure. Methods The airway instillation of silica to C57BL/6 mice was used to produce mouse silicosis models. Immunohistochemistry was used to determine NOX4 expression in the lungs of silicosis mice. Human lung epithelial cells (BEAS-2B) were exposed to silica to generate an oxidative injury epithelial cell model in vitro. Wnt signal conditioned medium (Wnt3a-CM) and Wnt signal inhibitor XAV939 were used to alter the activity of Wnt signal. An infection adenoviral vector expressing short hairpin RNA to NOX4 (NOX4 shRNA) was used to knock down NOX4 expression in BEAS-2B cells. Western blotting was performed to access the expression of Wnt3a, active-β-catenin (ABC), transcription factor 4 (TCF4), cyclin D1 and NOX4 proteins in lung tissues and human lung epithelial cells. CCK-8 assay was used to determine the effects of silica of different concentrations on cell viability as well as the effects of NOX4 expression knockdown on cell proliferation in human lung epithelial cells. CellROX fluorescent probe loading assay was used to detect the release of reactive oxygen species (ROS). Results Mouse silicosis model and BEAS-2B cell model of oxidative damage were successfully generated. The stimulation of silica significantly activated Wnt/β-catenin signal and induced NOX4 expression, sequentially resulting in ROS production. While ROS scavenger N-acetyl-L-cysteine (NAC) inhibited the silica-induced release of ROS, and then inhibited the expression of ABC protein and Wnt/β-catenin signal activity. An activation of Wnt signaling induced by Wnt3a-conditioned medium (Wnt3a-CM) increased the expression of NOX4, whereas the Wnt signal inhibitor XAV939 inhibited the expression of NOX4. The expression of Wnt/β-catenin signal ABC and cyclin D1 and cell proliferation were significantly inhibited by the shRNA-mediated suppression of NOX4 expression. Conclusion Blocking Wnt/-catenin signal and down-regulating NOX4 expression inhibit the proliferation of lung epithelial cells and the damage repair of lung epithelial cells induced by the silica exposure.
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February 2021

A systematic review and meta-regression of studies eliciting willingness-to-pay per quality-adjusted life year in the general population.

Expert Rev Pharmacoecon Outcomes Res 2021 Feb 1:1-9. Epub 2021 Feb 1.

School of business administration, Shenyang Pharmaceutical University, Shenyang, China.

Objectives: From the demand-side perspective, the monetary value of one additional quality-adjusted life year (QALY) is estimated as willingness-to-pay per QALY (WTPQ). This study aims to summarize the methods and contexts of elicitation of willingness-to-pay per quality-adjusted life year (WTPQ) in the general population and to investigate the heterogeneity of WTPQ estimates.

Methods: Meta-regression analysis was conducted using Comprehensive Meta-Analysis Software. Sensitivity analyses were undertaken by replacing the lowest and highest 5% and 2.5% of WTPQ by percentiles.

Results: 33 studies with 102 WTPQ estimates were included. The overall mean and median WTPQ estimates are $1,280,002 and $44,072, respectively. The meta-regressions demonstrated that types of health gain (quality of life or life length) and certainty of health outcomes are statistically significant factors. Furthermore, compared with online interviews, face-to-face interviews tend to yield lower WTPQ. Moreover, the declining trend of QALY gains and positive effect with statistical significance of the sample age were also noticed.

Conclusion: For valid and representative values of WTPQ, future researchers should therefore take into consideration various scenarios and investigate both health gain with certainty and uncertainty, health gain from both life length and quality of life, and different size of QALY gains.
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http://dx.doi.org/10.1080/14737167.2021.1878881DOI Listing
February 2021

Adult Body Height and Cardiometabolic Disease Risk: The China National Health Survey in Shaanxi.

Front Endocrinol (Lausanne) 2020 21;11:587616. Epub 2020 Dec 21.

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.

Objectives: Based on data from the China National Health Survey, we aimed to examine the association between body height and cardiometabolic disease (CMD) in a large adult population from Shaanxi province, and further to test whether this association was hinged upon other population characteristics.

Methods: This population-based study was conducted in 2014 in Shaanxi Province, China. Utilizing a multi-stage stratified cluster sampling method, total 5,905 adults with complete data were eligible for analysis, and 1,151 (19.5%) of them had CMD. Of 1,151 CMD patients, 895 (15.1%) had one disorder and 256 (4.4%) had ≥2 disorders.

Results: Using the bi-directional stepwise method and all-subsets regression, five factors-age, body mass index, family histories of CMD, exercise, and height-constituted the optimal model when predicting CMD risk. Restricted cubic spline regression showed a reduced tendency towards CMD with the increase of body height, with per 10 cm increment in body height corresponding to 14% reduced risk. Ordinal Logistic regression supported the contribution of body height on both continuous and categorical scales to CMD risk before and after adjustment, yet this contribution was significantly confounded by exercise and education, especially by exercise, which can explain 65.4% of total impact. For example, short stature was associated with an increased risk of CMD after multivariable adjustment not including exercise and education (odds ratio, 95% confidence interval, P: 1.42, 1.21 to 1.66, <0.001), and tall stature was associated with a reduced risk (0.77, 0.64 to 0.92, 0.003).

Conclusions: Our findings indicate short stature was a risk factor, yet tall stature was a protective factor for CMD in Chinese. Notably, the prediction of short and tall stature for CMD may be mediate in part by exercise.
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http://dx.doi.org/10.3389/fendo.2020.587616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780292PMC
May 2021

Prevalence of mild cognitive impairment in community-dwelling Chinese populations aged over 55 years: a meta-analysis and systematic review.

BMC Geriatr 2021 01 6;21(1):10. Epub 2021 Jan 6.

Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shangha, China.

Background: Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and overt dementia, with amnesic MCI (aMCI) being the dominant subtype. This study aims to synthesise the prevalence results of MCI and aMCI in community-dwelling populations in China through a meta-analysis and systematic review.

Methods: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol. English and Chinese studies published before 1 March 2020 were searched from ten electronic bibliographic databases. Two reviewers screened for relevance of the studies against the pre-defined inclusion and exclusion criteria and assessed the quality of the included studies using the Risk of Bias Tool independently. A random-effect model was adopted to estimate the prevalence of MCI and aMCI, followed by sub-group analyses and meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analyses.

Results: A total of 41 studies with 112,632 participants were included in the meta-analyses. The Chinese community-dwelling populations over 55 years old had a pooled prevalence of 12.2% [95% confidence interval (CI): 10.6, 14.2%] for MCI and 10.9% [95% CI, 7.7, 15.4%] for aMCI, respectively. The prevalence of MCI increased with age. The American Psychiatric Association's Diagnostic tool (DSM-IV) generated the highest MCI prevalence (13.5%), followed by the Petersen criteria (12.9%), and the National Institute on Aging Alzheimer's Association (NIA-AA) criteria (10.3%). Women, rural residents, and those who lived alone and had low levels of education had higher MCI prevalence than others.

Conclusion: Higher MCI prevalence was identified in community-dwelling older adult populations in China compared with some other countries, possibly due to more broadened criteria being adopted for confirming the diagnosis. The study shows that aMCI accounts for 66.5% of MCI, which is consistent with findings of studies undertaken elsewhere.

Systematic Review Registration Number: PROSPERO CRD42019134686.
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http://dx.doi.org/10.1186/s12877-020-01948-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789349PMC
January 2021

A Positive Feed Forward Loop between Wnt/-Catenin and NOX4 Promotes Silicon Dioxide-Induced Epithelial-Mesenchymal Transition of Lung Epithelial Cells.

Oxid Med Cell Longev 2020 8;2020:3404168. Epub 2020 Dec 8.

Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China.

Silicosis is a chronic fibrotic lung disease caused by the accumulation of silica dust in the distal lung. Canonical Wnt signaling and NADPH oxidase 4 (NOX4) have been demonstrated to play a crucial role in the pathogenesis of pulmonary fibrosis including silicosis. However, the underlying mechanisms of crosstalk between these two signalings are not fully understood. In the present study, we aimed to explore the interaction of Wnt/-catenin and NOX4 of human epithelial cells in response to an exposure of silica dust. Results demonstrated an elevated expression of key components of Wnt/-catenin signaling and NOX4 in the lungs of silicon dioxide- (SiO-) induced silicosis mice. Furthermore, the activated Wnt/-catenin and NOX4 signaling are accompanied by an inhibition of cell proliferation, an increase of ROS production and cell apoptosis, and an upregulation of profibrogenic factors in BEAS-2B human lung epithelial cells exposed to SiO. A mechanistic study further demonstrated that the Wnt3a-mediated activation of canonical Wnt signaling could augment the SiO-induced NOX4 expression and reactive oxygen species (ROS) production but reduced glutathione (GSH), while Wnt inhibitor DKK1 exhibited an opposite effect to Wnt3a. , an overexpression of NOX4 further activated SiO-induced Wnt/-catenin signaling and NFE2-related factor 2 (Nrf2) antioxidant response along with a reduction of GSH, whereas the shRNA-mediated knockdown of NOX4 showed an opposite effect to NOX4 overexpression. These results imply a positive feed forward loop between Wnt/-catenin and NOX4 signaling that may promote epithelial-mesenchymal transition (EMT) of lung epithelial cells in response to an exposure of silica dust, which may thus provide an insight into the profibrogenic role of Wnt/-catenin and NOX4 crosstalk in lung epithelial cell injury and pathogenesis of silicosis.
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http://dx.doi.org/10.1155/2020/3404168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744200PMC
December 2020

Nitidine chloride suppresses NEDD4 expression in lung cancer cells.

Aging (Albany NY) 2020 12 3;13(1):782-793. Epub 2020 Dec 3.

Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, Anhui, China.

Nitidine chloride (NC) possesses anticancer properties in various types of human malignancies. However, the effects of NC on lung cancer cells have not been elucidated. Moreover, the molecular mechanism of NC-involved antitumor activity is unclear. Therefore, we aimed to determine the biological effect of NC and the underlying molecular insights in lung cancer cells. The antineoplastic function of NC was assessed by MTT assays, Annexin V-FITC/PI apoptosis assay, wound healing analysis, and Transwell chamber migration and invasion assay in lung cancer cells. NEDD4 modulation was evaluated by western blotting assays of lung cancer cells after NC treatments. NEDD4 overexpression and downregulation were employed to validate the critical role of NEDD4 in the NC-mediated tumor suppressive effects. We found that NC suppressed cell viability, migration and invasion, but induced apoptosis in lung cancer cells. Mechanistic exploration revealed that NC exhibited its antitumor effects by reducing NEDD4 expression. Furthermore, our rescue experiments dissected that overexpression of NEDD4 abrogated the NC-mediated antineoplastic effects in lung cancer cells. Consistently, downregulation of NEDD4 enhanced the NC-induced anticancer effects. Thus, NC is a promising antitumor agent in lung cancer, indicating that NC might have potential therapeutic applications in the treatment of lung cancer.
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http://dx.doi.org/10.18632/aging.202185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834991PMC
December 2020

Psychometric evaluation of the DAILY EATS questionnaire in individuals living with obesity.

J Patient Rep Outcomes 2020 Nov 23;4(1):99. Epub 2020 Nov 23.

RTI Health Solutions, 3040 East Cornwallis Road, Post Office Box 12194, Research Triangle Park, NC, 27709-2194, USA.

Background: Physiological and behavioral factors including hunger, satiety, food intake, and cravings are health determinants contributing to obesity. Patient-reported outcome (PRO) measures focused on eating-related factors provide insight into the relationships between food choice and quantity, weight change, and weight-loss treatment for individuals living with obesity. The DAILY EATS is a novel 5-item, patient-reported measure evaluating key eating-related factors (Worst and Average Hunger, Appetite, Cravings, and Satiety).

Methods: Psychometric analyses, consistent with regulatory standards, were conducted to evaluate the DAILY EATS using data from two randomized trials that included individuals with severe obesity without diabetes (NCT03486392) and with severe obesity and type 2 diabetes (NCT03586830). Additional measures included Patient Global Impression of Status (PGIS) and Patient Global Impression of Change items, Impact of Weight on Quality of Life-Lite, Ease of Weight Management, and Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8b and 10a. The reliability, validity, and responsiveness of the DAILY EATS were assessed, and a scoring algorithm and thresholds to interpret meaningful score changes were developed.

Results: Item-level analyses of the DAILY EATS supported computation of an Eating Drivers Index (EDI), comprising the related items Worst Hunger, Appetite, and Cravings. Internal consistency (Cronbach's coefficient alphas ≥0.80) and test-retest reliability (coefficients > 0.7) of the EDI were robust. Construct validity correlation patterns with other PRO measures were as hypothesized, with moderate to strong significant correlations between the EDI and PGIS-Hunger (0.30 ≤ r ≤ 0.68), PGIS-Cravings (0.33 ≤ r ≤ 0.77) and PGIS-Appetite (0.52 ≤ r ≤ 0.77). Anchor- and distribution-based analyses support reductions ranging from 1.6 to 2.1 as responder thresholds for the EDI, representing meaningful within-person improvement.

Conclusions: The DAILY EATS individual items and the composite EDI are reliable, sensitive, and valid in evaluating the concepts of hunger, appetite, and cravings for use in individuals with severe obesity with or without type 2 diabetes.
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http://dx.doi.org/10.1186/s41687-020-00259-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683653PMC
November 2020

Further discussion on the association between desmoglein 2 and tumor size of non-small cell lung cancer.

J Cancer Res Clin Oncol 2021 Feb 22;147(2):633-635. Epub 2020 Nov 22.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No 14th, 3rd section, Renmin South Road, Chengdu, 610041, China.

We have read the article by Cai et al. and find there is a discrepancy between their data and conclusion. Their statement, "Specifically, DSG2 expression was associated with tumor size", is not supported by their own clinicopathological data and analysis. After reviewing some similar articles, we also found no available evidence showed a statistically significant association between them. Therefore, we would like to suggest Cai et al. to rectify the results they published.
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http://dx.doi.org/10.1007/s00432-020-03465-7DOI Listing
February 2021

Streptomyces sp. strain TOR3209: a rhizosphere bacterium promoting growth of tomato by affecting the rhizosphere microbial community.

Sci Rep 2020 11 18;10(1):20132. Epub 2020 Nov 18.

Key Laboratory of Plants Genetic Engineering Center, Institute of Genetics and Physiology (Hebei Agricultural Products Quality and Safety Research Center), Hebei Academy of Agriculture and Forestry Sciences, Shijiazhuang, Hebei, 050000, People's Republic of China.

Aiming at revealing the possible mechanism of its growth promoting effect on tomato, the correlations among Streptomyces sp. TOR3209 inoculation, rhizobacteriome, and tomato growth/production traits were investigated in this study. By analyses of Illumina sequencing and plate coating, differences in rhizosphere microbial communities were found in different growth stages and distinct inoculation treatments. The plant biomass/fruit yields and relative abundances of families Flavobacteriaceae, Sphingobacteriaceae, Polyangiaceae and Enterobacteriaceae in treatments T (tomato inoculated with TOR3209) and TF (tomato inoculated with TOR3209 + organic fertilizer) were higher than that in the controls (CK and CK+ organic fertilizer), respectively. The analysis of Metastats and LEfSe revealed that the genera Flavobacterium and Sorangium in seedling stage, Klebsiella in flowering stage, Collimonas in early fruit setting stage, and genera Micrococcaceae, Pontibacte and Adhaeribacter in late fruit setting stage were the most representative rhizobacteria that positively responded to TOR3209 inoculation. By cultivation method, five bacterial strains positively correlated to TOR3209 inoculation were isolated from rhizosphere and root endosphere, which were identified as tomato growth promoters affiliated to Enterobacter sp., Arthrobacter sp., Bacillus subtilis, Rhizobium sp. and Bacillus velezensis. In pot experiment, TOR3209 and B. velezensis WSW007 showed joint promotion to tomato production, while the abundance of inoculated TOR3209 was dramatically decreased in rhizosphere along the growth of tomato. Conclusively, TOR3209 might promote the tomato production via changing of microbial community in rhizosphere. These findings provide a better understanding of the interactions among PGPR in plant promotion.
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http://dx.doi.org/10.1038/s41598-020-76887-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675979PMC
November 2020

Concurrent Apatinib and Brain Radiotherapy in Patients With Brain Metastases From Driver Mutation-negative Non-small-cell Lung Cancer: Study Protocol for an Open-label Randomized Controlled Trial.

Clin Lung Cancer 2021 03 21;22(2):e211-e214. Epub 2020 Oct 21.

Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Brain radiotherapy (BR) is a well-recognized approach for multiple brain metastases (BMs) from non-small-cell lung cancer (NSCLC). However, the prognosis for these patients remains poor. Apatinib, an antiangiogenic agent targeting vascular endothelial growth factor receptor-2, has shown excellent efficacy in multiple solid tumors. This phase II (WWW. ClinicalTrials.gov Identifier: VEGFR-2 NCT03801200) randomized trial aims to evaluate the efficacy and safety of this combined modality paradigm in patients with BMs from driver mutation-negative NSCLC. This is a multicenter, open-label, randomized controlled clinical trial. A total of 90 eligible patients will be allocated in a 1:1 ratio, to either the experimental group (concurrent apatinib and BR) or the control group (BR alone). The primary endpoint is intracranial progression-free survival. The secondary endpoints include intracranial objective response rate, intracranial disease control rate, intracranial time to progression, overall survival, and occurrence of peritumoral brain edema using standardized measurement. Quality of life and adverse events will also be evaluated. Assessments will be carried out before enrollment (baseline) along with 4 and 12 weeks after radiotherapy, followed by every 12 weeks thereafter and up to 24 months. In summary, the aim of this trial is to demonstrate the clinical efficacy and safety of concurrent BR and apatinib in patients with driver mutation-negative NSCLC with multiple BMs, in efforts to expand management options for this population with poor prognosis.
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http://dx.doi.org/10.1016/j.cllc.2020.10.007DOI Listing
March 2021

Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway.

Cell Death Discov 2020 19;6:91. Epub 2020 Sep 19.

Department of Laboratory Medicine, School of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui 233030 China.

Nitidine chloride (NC) has significant anti-tumor properties; however, the precise mechanism related to NC still needs further investigation. This study intends to investigate the anti-tumor functions and the feasible molecular basis of NC in NSCLC cells. Therefore, we determined the mechanism of NC-mediated anti-tumor function through various methods. Cell proliferation ability and migration and invasion were detected by CCK-8, colony formation assay and Transwell assay, respectively. Furthermore, flow cytometry was used to detect apoptosis, cell cycle and ROS. Moreover, protein expression level was measured by western blot. Our results showed that NC can inhibit the growth, motility of NSCLC cells, induce apoptosis and arrest cell cycle. Meanwhile, NC increased the level of ROS in NSCLC cells. Moreover, western blot data showed that NC suppressed the expression of Lats1, Mob1, and YAP, and enhanced the expression of p-Lats1, p-Mob1, p-YAP1 (ser127). Overall, our research reveals that NC exerts anticancer activity by activating and modulating the Hippo signaling pathway.
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http://dx.doi.org/10.1038/s41420-020-00326-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502074PMC
September 2020

Endoscopic Esophageal Submucosal Tunnel Dissection for Cystic Lesions Originating from the Muscularis Propria of the Gastric Cardia.

J Oncol 2020 20;2020:5259717. Epub 2020 Aug 20.

Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China.

Objective: To analyze the types and properties of cystic lesions originating from the muscularis propria of the gastric cardia (CLMPGC), explore the growth pattern and anatomical characteristics, and evaluate the safety, feasibility, and clinical efficacy of endoscopic esophageal submucosal tunnel dissection (ESTD).

Methods: From September 2013 to July 2018, we treated 6 patients with CLMPGC whom we had diagnosed using endoscopy, endoscopic ultrasound (EUS), and Computed Tomography (CT) before the operations. ESTD was the best option for treatment for all these patients. Postoperative observation and follow-ups were performed, and the operational, clinical data, and treatment results are analyzed.

Results: The mean age of the patients was 50.67 ± 11.59 years (male : female = 1 : 1). The only clinical manifestations the patients exhibited were upper abdominal discomfort. The diameter of the masses was 2.05 ± 0.73 (1.1-3.0) cm. The duration of the ESTD operation was 93.5 (82-256) mins, and the length of hospital stay was 7.50 ± 1.38 days. Postoperative pathology showed 4 cases of an epithelioid cyst, and 2 cases of mucocele with xanthogranuloma. There were no complications, such as hemorrhage, pneumothorax, and pleural effusion during and after the operation. No recurrence during the follow-ups was observed.

Conclusion: The CLMPGC were mainly mucocele and epidermoid cyst, in an expansive growth pattern, and these lesions had no distinct borders with the muscularis propria. The muscularis propria formed a complete wall of the lesion. There was no direct blood supply to the lesions from big blood vessels. Endoscopic esophageal submucosal tunnel dissection was a safe, feasible, and effective treatment for CLMPGC.
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http://dx.doi.org/10.1155/2020/5259717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455822PMC
August 2020

A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19).

J Med Virol 2021 02 28;93(2):1057-1069. Epub 2020 Sep 28.

Department of Neurosurgery, Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, PR China.

To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I  = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I  = 95.6%) mild and 51% (95% CI: 42%-61%; I  = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I  = 78.9%) and cough 41% (95% CI: 35%-47%, I  = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I  = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I  = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I  = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I  = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I  = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I  = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I  = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.
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http://dx.doi.org/10.1002/jmv.26398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436402PMC
February 2021

Arsenic trioxide encapsulated liposomes prepared via copper acetate gradient loading method and its antitumor efficiency.

Asian J Pharm Sci 2020 May 19;15(3):365-373. Epub 2018 Dec 19.

School of Pharmacy, Shenyang Pharmaceutical University, China.

In this study, arsenic trioxide (ATO) was encapsulated in liposomes via copper acetate (Cu(OAc)) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and -21.97 ± 0.6 mV, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATO-Cu complex. The drug release of ATO-Cu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the pH of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased and T, and improved tumor distribution of As compared to administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%, meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc) gradients; the co-administration of ATO and Cu(II) via liposomal formulation may find wide applications in the treatment of various tumors.
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http://dx.doi.org/10.1016/j.ajps.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327756PMC
May 2020
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