Publications by authors named "Yongchun Zhou"

76 Publications

A neutral polysaccharide from restrains cisplatin-induced nephrotoxicity.

Food Sci Nutr 2021 Jul 11;9(7):3602-3616. Epub 2021 May 11.

Yunnan Provincial Key Laboratory of Panax notoginseng Faculty of Life Science and Technology Kunming University of Science and Technology Kunming China.

is an edible mushroom distributed over the south-eastern part of the Tibet Plateau, which is also recognized as an effective ethnomedicine to alleviate diseases. This study explored the effects of a kind of neutral polysaccharide (ONP) on RAW264.7 macrophages and cisplatin-induced nephrotoxicity. The results showed that ONP relieved the inflammatory response of RAW264.7 macrophages by increasing the expression level of anti-inflammatory factor IL-10. Furthermore, ONP treatment significantly prolonged the survival of the mice treated by cisplatin through decelerating pathological progress and alleviating damaged functions of the kidneys. Compared with the cisplatin group, ONP reduced the oxidative stress of the renal cells and the expression levels of pro-inflammatory factors. Apoptosis of renal cells was also weakened in the ONP treatment group. These findings indicated that ONP alleviated cisplatin nephrotoxicity mainly by inhibiting oxidative stress, inflammation, and apoptosis in the kidneys, underscoring the potential of ONP supplementation to alleviate the side effects of cisplatin chemotherapy.
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http://dx.doi.org/10.1002/fsn3.2317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269674PMC
July 2021

Molecular detection and phylogenetic analyses of Anaplasma spp. in Haemaphysalis longicornis from goats in four provinces of China.

Sci Rep 2021 Jul 8;11(1):14155. Epub 2021 Jul 8.

College of Veterinary Medicine, Longzihu Campus of Henan Agricultural University, No. 15 Longzihu University Area, Zhengdong New District, Zhengzhou, 450046, People's Republic of China.

Anaplasma species, which are distributed worldwide, are gram-negative obligate intracellular tick-borne bacteria that pose a threat to human and animal health. Haemaphysalis longicornis ticks play a vital role as vectors in the transmission of Anaplasma pathogens. However, the Anaplasma species carried by H. longicornis in China are yet to be characterized. In this study, 1074 H. longicornis specimens were collected from goats in four provinces of China from 2018 to 2019 and divided into 371 sample pools. All tick sample pools were examined for the presence of Anaplasma species via nested PCR amplification of 16S ribosomal RNA, major surface protein 4 (msp4), or citric acid synthase (gltA) genes, which were sequenced to determine the molecular and phylogenetic characteristics of the isolates. The overall Anaplasma spp-positive rate of H. longicornis was determined to be 26.68% (99/371). The percentage prevalence of A. phagocytophilum-like1, A. bovis, A. ovis, A. marginale, and A. capra were 1.08% (4/371), 13.21% (49/371), 13.21% (49/371), 1.35% (5/371), and 10.24% (38/371), respectively, and the co-infection rate of two or more types of Anaplasma was 6.47% (24/371). Phylogenetic analyses led to the classification of A. phagocytophilum into an A. phagocytophilum-like1 (Anaplasma sp. Japan) group. Anaplasma bovis sequences obtained in this study were 99.8-100% identical to those of an earlier strain isolated from a Chinese tick (GenBank accession no. KP314251). Anaplasma ovis sequences showed 99.3-99.6% identity to an A. ovis human strain identified from a Cypriot patient (GenBank accession no. FJ460443). Only one msp4 sequence of A. marginale was detected and was grouped with those of other A. marginale isolates, and these A. capra isolates obtained in this present study may be zoonotic. The detection and characterization of four Anaplasma species in H. longicornis in this study have added to the current knowledge of the parasite and provided data on multiple Anaplasma species with veterinary and medical significance from four provinces of China.
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http://dx.doi.org/10.1038/s41598-021-93629-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266805PMC
July 2021

High-resolution metabolomic biomarkers for lung cancer diagnosis and prognosis.

Sci Rep 2021 Jun 3;11(1):11805. Epub 2021 Jun 3.

Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, 650118, Yunnan, China.

Lung cancer is the leading cause of human cancer mortality due to the lack of early diagnosis technology. The low-dose computed tomography scan (LDCT) is one of the main techniques to screen cancers. However, LDCT still has a risk of radiation exposure and it is not suitable for the general public. In this study, plasma metabolic profiles of lung cancer were performed using a comprehensive metabolomic method with different liquid chromatography methods coupled with a Q-Exactive high-resolution mass spectrometer. Metabolites with different polarities (amino acids, fatty acids, and acylcarnitines) can be detected and identified as differential metabolites of lung cancer in small volumes of plasma. Logistic regression models were further developed to identify cancer stages and types using those significant biomarkers. Using the Variable Importance in Projection (VIP) and the area under the curve (AUC) scores, we have successfully identified the top 5, 10, and 20 metabolites that can be used to differentiate lung cancer stages and types. The discrimination accuracy and AUC score can be as high as 0.829 and 0.869 using the five most significant metabolites. This study demonstrated that using 5 + metabolites (Palmitic acid, Heptadecanoic acid, 4-Oxoproline, Tridecanoic acid, Ornithine, and etc.) has the potential for early lung cancer screening. This finding is useful for transferring the diagnostic technology onto a point-of-care device for lung cancer diagnosis and prognosis.
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http://dx.doi.org/10.1038/s41598-021-91276-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175557PMC
June 2021

Blood Tumor Mutational Burden as a Predictive Biomarker in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).

Front Oncol 2021 14;11:640761. Epub 2021 May 14.

Yunnan Cancer Hospital and The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Center, Kunming, China.

This study was designed to investigate the impact of blood tumor mutational burden (bTMB) on advanced NSCLC in Southwest China. The relationship between the tTMB estimated by next-generation sequencing (NGS) and clinical outcome was retrospectively analyzed in tissue specimens from 21 patients with advanced NSCLC. Furthermore, the relationship between the bTMB estimated by NGS and clinical outcome was retrospectively assessed in blood specimens from 70 patients with advanced NSCLC. Finally, 13 advanced NSCLC patients were used to evaluate the utility of bTMB assessed by NGS in differentiating patients who would benefit from immunotherapy. In the tTMB group, tTMB ≥ 10 mutations/Mb was related to inferior progression-free survival (PFS) (hazard ratio [HR], 0.30; 95% CI, 0.08-1.17; log-rank = 0.03) and overall survival (OS) (HR, 0.30; 95% CI, 0.08-1.16; log-rank = 0.03). In the bTMB group, bTMB ≥ 6 mutations/Mb was associated with inferior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank < 0.01) and OS (HR, 0.31; 95% CI, 0.14-0.7; log-rank < 0.01). In the immunotherapy section, bTMB ≥ 6 mutations/Mb was related to superior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank < 0.01) and objective response rates (ORRs) (bTMB < 6: 14.2%; 95% CI, 0.03-1.19; bTMB ≥ 6: 83.3%; 95% CI, 0.91-37.08; = 0.02). These findings suggest that bTMB is a validated predictive biomarker for determining the clinical outcome of advanced NSCLC patients and may serve as a feasible predictor of the clinical benefit of immunotherapies (anti-PD-1 antibody) in the advanced NSCLC population in Yunnan Province.
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http://dx.doi.org/10.3389/fonc.2021.640761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160368PMC
May 2021

Comparison between single anterior and single posterior approaches of debridement interbody fusion and fixation for the treatment of mono-segment lumbar spine tuberculosis.

Arch Orthop Trauma Surg 2021 May 22. Epub 2021 May 22.

Department of Orthopedic, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.

Purpose: To compare the efficacy of single anterior and single posterior approach of debridement, interbody fusion, and fixation for the treatment of mono-segment lumbar spine tuberculosis (TB) patients.

Methods: Eighty-seven patients with mono-segment lumbar TB who underwent debridement, interbody fusion, and fixation through either single anterior (Group A) or single posterior approach (Group B) from January 2007 to January 2017 were enrolled in this study. The duration of the operation, blood loss, complication rate, visual analog scale (VAS), Oswestry disability index (ODI), Frankel scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kyphosis angle, correction rate, correction loss, and time taken for bone graft fusion were compared between the groups.

Results: The average period of follow-up was 34.3 ± 9.5 months (24-56 months). No significant differences were observed between patients in Group A and patients in Group B in terms of gender, age, body mass index (BMI), duration of illness and preoperative evaluative indices (P > 0.05). The mean operation time and blood loss was significantly higher in Group A (P = 0.000), along with a slightly higher rate of complications compared with Group B (P = 0.848). The VAS, ODI and Frankel scale scores showed significant improvement in both groups (P = 0.000), along with the ESR, CRP and kyphosis indices (P = 0.000), which were similar in both groups at the final follow-up.

Conclusion: Both single anterior and single posterior approaches of debridement, interbody fusion and fixation are effective for mono-segment lumbar TB patients, although the single posterior approach is of a shorter duration and results in less blood loss.
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http://dx.doi.org/10.1007/s00402-021-03955-4DOI Listing
May 2021

Unique Profile of Driver Gene Mutations in Patients With Non-Small-Cell Lung Cancer in Qujing City, Yunnan Province, Southwest China.

Front Oncol 2021 13;11:644895. Epub 2021 Apr 13.

Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China.

Objective: Qujing City, Yunnan Province, China, has a high incidence of lung cancer and related mortality. The etiology of NSCLC in Qujing area and distribution of associated molecular aberrations has not been fully elucidated. This study aimed to reveal the profile of driver gene mutations in patients with non-small-cell lung cancer (NSCLC) in Qujing and explore their relationships with clinicopathological characteristics.

Methods: In this study, the mutation profiles of NSCLC driver genes, including , and , were investigated in patients with NSCLC from Qujing and compared with those from other regions in Yunnan Province. The associations between molecular mutations and clinicopathological characteristics were further analyzed.

Results: A distinct profile of driver gene mutations was discovered in patients with NSCLC from Qujing. Interestingly, a higher proportion of compound mutations, including G719X + S768I (19.65% vs 3.38%, P < 0.0001) and G719X + L861Q (21.10% vs 2.82%, P < 0.0001), was observed in patients with NSCLC in Qujing compared with patients in non-Qujing area, besides significantly different distributions of (46.01% vs. 51.07%, = 0.0125), (3.17% vs. 6.97%, = 0.0012), (0.5% vs. 2.02%, = 0.0113), and (23.02% vs. 7.85%, < 0.0001). Further, compound mutations were more likely associated with the occupation of patients (living/working in rural areas, e.g., farmers). Moreover, G12C was the dominant subtype (51.11% vs 25.00%, = 0.0275) among patients with NSCLC having mutations in Qujing.

Conclusions: Patients with NSCLC in Qujing displayed a unique profile of driver gene mutations, especially a higher prevalence of compound mutations and dominant G12C subtype, in this study, indicating a peculiar etiology of NSCLC in Qujing. Therefore, a different paradigm of therapeutic strategy might need to be considered for patients with NSCLC in Qujing.
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http://dx.doi.org/10.3389/fonc.2021.644895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076749PMC
April 2021

The efficacy of single posterior debridement, bone grafting and instrumentation for the treatment of thoracic spinal tuberculosis.

Sci Rep 2021 Feb 11;11(1):3591. Epub 2021 Feb 11.

Department of Orthopedic, Shaanxi Provincial People's Hospital, 256# You-yi West Road, Xi'an, 710068, Shaanxi, People's Republic of China.

The aim of this study was to investigate the clinical efficacy of single posterior debridement, bone grafting and instrumentation for the treatment of thoracic spinal tuberculosis in adult patients. A retrospective analysis was conducted between June 2013 and September 2017of 88 adult patients with thoracic spinal tuberculosis. All patients were treated with single posterior debridement, bone grafting and instrumentation. The clinical manifestations and laboratory and imageological results were subsequently analysed. All patients were followed for 40.6 ± 4.1 months (range, 36-48 m). Bony fusion was achieved in all bone grafts of thoracic vertebrae. The visual analogue scale scores, erythrocyte sedimentation rate and C-reactive protein levels 6 weeks after surgery and at the final follow up were significantly lower than the preoperative levels (P < 0.05). The postoperative and final follow up kyphosis angles were both significantly smaller than the preoperative kyphosis angles (P < 0.05). The postoperative angle correction rate reached 81.5% and the postoperative angle loss reached only 4.1%. At the last follow up, American Spinal Injury Association improvement was significant, compared with the preoperative levels (P < 0.05). The single posterior approach can achieve satisfactory clinical outcomes in the treatment of thoracic spinal tuberculosis.
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http://dx.doi.org/10.1038/s41598-021-83178-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878885PMC
February 2021

Seasonal dynamics of Anaplasma spp. in goats in warm-temperate zone of China.

Ticks Tick Borne Dis 2021 05 27;12(3):101673. Epub 2021 Jan 27.

College of Veterinary Medicine, Longzihu Campus of Henan Agricultural University, No. 15 Longzihu University Area, Zhengdong New District, Zhengzhou, 450046, PR China. Electronic address:

Anaplasma are tick-borne obligate intracellular bacteria that can endanger human and animal health, and until now, there have been few reports on the seasonal dynamics of Anaplasma species in China. In this study, a total of 491 goat blood samples were collected in spring (n = 124), summer (n = 135), autumn (n = 110), and winter (n = 122) from Shaanxi provinces. Single and mixed infections of Anaplasma spp. from warm-temperate regions of China were analyzed according to seasons using a nested PCR method. Positive samples were sequenced to observe the molecular and phylogenetic characteristics of the Anaplasma species, and we determined the co-infection rates of Anaplasma spp. for each season. A molecular survey of Anaplasma phagocytophilum, A. bovis, A. ovis, and A. capra in goats showed average prevalences of 71.6 % (maximum 86.7 % in summer and minimum 48.4 % in winter), 62.2 % (minimum 38.7 % in spring and maximum 94.1 % in summer), 25.5 % (minimum 0% in summer and maximum 51.6 % in spring), and 26.6 % (minimum 8.2 % in winter and maximum 55.6 % in summer), respectively. In the phylogenetic analysis, A. phagocytophilum and A. capra occupied two separate groups, Chinese A. bovis and foreign isolates appeared to be geographically isolated, and all A. ovis isolates were in the same branch as the previously described sequences. The survey indicated that goats in warm-temperate regions of China are frequently exposed to Anaplasma spp. all year round, and thus prevention and treatment efforts for anaplasmosis in the region should be strengthened.
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http://dx.doi.org/10.1016/j.ttbdis.2021.101673DOI Listing
May 2021

Effect of book-shaped acellular tendon scaffold with bone marrow mesenchymal stem cells sheets on bone-tendon interface healing.

J Orthop Translat 2021 Jan 24;26:162-170. Epub 2020 Mar 24.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

Background: Tissue engineering has exhibited great effect on treatment for bone-tendon interface (BTI) injury. The aim of this study was to evaluate the effect of a book-shaped acellular tendon scaffold (ATS) with bone marrow mesenchymal stem cells sheets (MSCS) for BTI injury repair.

Methods: ATS was designed based on the shape of "book", decellularization effect was evaluated by Hematoxylin and eosin (H&E), 4', 6-diamidino-2-phenylindole (DAPI) and scanning electron microscopy (SEM), then bone marrow mesenchymal stem cells (MSCs) were cultured on ATS to assess the differentiation inductivity of ATS. A rabbit right partial patellotomy model was established, and MSCS seeded on ATS were implanted into the lesion site. The patella-patellar tendon (PPT) at 2, 4, 8 or 16 weeks post-operation were obtained for histological, biomechanical and immunofluorescence analysis.

Results: H&E, DAPI and SEM results confirmed the efficiency of decellularization of ATS, and their in vitro tenogenic and chondrogenic ability were successfully identified. In vivo results showed increased macrophage polarization toward the M2 phenotype, IL-10 expression, regenerated bone and fibrocartilage at the patella-patellar tendon interface of animals received MSCS modified ATS implantation. In addition, the level of tensile strength was also the highest in MSCS modified ATS implantation group.

Conclusion: This study suggests that ATS combined with MSCS performed therapeutic effects on promoting the regeneration of cartilage layer and enhancing the healing quality of patella-patellar tendon interface.

The Translational Potential Of This Article: This study showed the good biocompatibility of the ATS, as well as the great efficacy of ATS with MSCS on tendon to bone healing. The results meant that the novel book-shaped ATS with MSCS may have a great potential for clinical application.
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http://dx.doi.org/10.1016/j.jot.2020.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773951PMC
January 2021

AFF4 facilitates melanoma cell progression by regulating c-Jun activity.

Exp Cell Res 2021 02 5;399(2):112445. Epub 2021 Jan 5.

Yunnan Key Laboratory of Lung Cancer Research, Kunming, China. Electronic address:

Melanoma is characterized by high mortality and poor prognosis due to metastasis. AFF4 (AF4/FMR2 family member 4), as a scaffold protein, is a component of the super elongation complex (SEC), and is involved in the progression of tumors, e.g., leukemia, head and neck squamous cell carcinoma (HNSCC). However, few studies on AFF4 have focused on melanoma. Here, AFF4 expression levels and clinicopathological features were evaluated in melanoma tissue samples. Then, we performed cell proliferation, migration and invasion assays in A375 and A2058 cells lines in vitro to evaluate the role of AFF4 in melanoma. The effects of AFF4 knockdown in vivo were characterized via a xenograft mouse model. Finally, the correlation between c-Jun and AFF4 protein levels in melanoma was analyzed by rescue assay and immunohistochemistry (IHC). We found that AFF4 expression was upregulated in melanoma tumor tissues and that AFF4 protein expression was also closely related to the prognosis of patients with cutaneous melanoma. Moreover, AFF4 could promote the invasion and migration of melanoma cells by mediating epithelial to mesenchymal transition (EMT). AFF4 might regulate c-Jun activity to promote the invasion and migration of melanoma cells. Importantly, c-Jun was regulated by the AFF4 promoted melanoma tumorigenesis in vivo. Taken together, AFF4 may be a novel oncogene that promotes melanoma progression through regulation of c-Jun activity.
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http://dx.doi.org/10.1016/j.yexcr.2020.112445DOI Listing
February 2021

ACDF plus Uncovertebrectomy versus ACDF alone for the Treatment of Cervical Spondylotic Radiculopathy: Minimum 5-Year Follow-Up.

J Neurol Surg A Cent Eur Neurosurg 2021 Mar 1;82(2):154-160. Epub 2021 Jan 1.

Department of Orthopaedic, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.

Objective:  The surgical approach for cervical spondylotic radiculopathy (CSR) is controversial. This study aims to investigate the effectiveness of the combined anterior cervical diskectomy and fusion (ACDF) and uncovertebrectomy for treatment of CSR.

Methods:  This is a retrospective case control study. One hundred and forty-six patients with CSR who underwent two different procedures (ACDF alone [group A]) and a combination of ACDF and uncovertebrectomy [group B]) from March 2008 to April 2013 were included. The operation time, blood loss, Visual Analog Scale scores of the neck (VAS-neck) and arm (VAS-arm), Neck Disability Index (NDI) score, 36-Item Short Form Health Survey (SF-36) score, fusion segment curvature, global cervical curvature, and the rate of surgical complication were evaluated.

Results:  There were no significant differences in the basic demographic and clinical characteristics between the two groups ( > 0.05). No significant differences were noticed in the fusion segment curvature and global cervical curvature between the two groups ( > 0.05). Whereas the operation time and blood loss in group B were greater than those in group A ( < 0.05), the VAS-neck, VAS-arm, NDI, and SF-36 scores were better in group B ( < 0.05). The surgical complication rate between the two groups was not significantly different ( > 0.05).

Conclusions:  Clinical efficacy of ACDF plus uncovertebrectomy for the treatment of patients with CSR may be better than that of ACDF alone, but at the expense of more operation time and blood loss.
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http://dx.doi.org/10.1055/s-0040-1720992DOI Listing
March 2021

Oncogenic Genetic Alterations in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

Cancer Manag Res 2020 29;12:10861-10874. Epub 2020 Oct 29.

Yunnan Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People's Republic of China.

Purpose: To investigate the impact of oncogenic genetic alterations (GAs) on non-small-cell lung cancer (NSCLC) in southwestern China.

Patients And Methods: We first collected 579 pathologically confirmed NSCLC specimens and then used next-generation sequencing (NGS) to evaluate the DNA samples for GAs. Both the tissue and plasma samples were provided by 28 patients. Furthermore, subgroup analyses based on sample type, concordance, and GA type were carried out.

Results: GAs were detected by NGS in 61.8% (358/579) of patients. Two hundred and twenty-nine patients (39.6%) harbored EGFR mutations, 63 (10.9%) harbored KRAS mutations, 13 (2.2%) harbored BRAF mutations, 30 (5.18%) harbored ALK fusions, and 13 (2.2%) had ROS1 fusions. We found that females ( < 0.01), nonsmokers ( < 0.001), adenocarcinoma ( < 0.001), and tissue ( = 0.03) had a relatively high EGFR mutation rate. Notably, NSCLC patients from Xuanwei had a significantly different mutational pattern for EGFR in comparison with that of non-Xuanwei patients (higher G719X + S768I mutations and multiple gene alterations, but fewer exon 19 deletion mutations and single gene alterations). We found that adenocarcinoma ( = 0.02), family history of malignancy ( = 0.03), Xuanwei origin ( < 0.001), and tissue ( = 0.04) were associated with a higher number of KRAS mutations. Subgroup analysis showed that ALK ( < 0.001) and ROS1 ( < 0.05) fusions and rare EGFR mutations ( < 0.001) were associated with non-Han ethnic patients.

Conclusion: Yunnan NSCLC patients from Xuanwei and non-Han ethnic patients had an obviously unique prevalence of GAs.
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http://dx.doi.org/10.2147/CMAR.S266069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605593PMC
October 2020

Comparison of conventional fenestration discectomy with Transforaminal endoscopic lumbar discectomy for treating lumbar disc herniation:minimum 2-year long-term follow-up in 1100 patients.

BMC Musculoskelet Disord 2020 Sep 23;21(1):628. Epub 2020 Sep 23.

Department of Orthopedic, Shaanxi Provincial People's Hospital, 256# You-yi West Road, Xi'an, 710068, Shaanxi, People's Republic of China.

Purpose: To compare the efficacy of conventional interlaminar fenestration discectomy (IFD) with transforaminal endoscopic lumbar discectomy (TELD) for treating lumbar disc herniation (LDH).

Methods: The clinical data of 1100 patients who had been diagnosed with LDH between January 2012 and December 2017 were retrospectively analysed. IFD was performed on 605 patients in Group A, whereas TELD was performed on 505 patients in Group B. The Oswestry Disability Index, Visual Analogue Scale for pain and modified MacNab criteria were used to evaluate the outcomes. The surgery duration, intraoperative blood loss, postoperative off-bed activity and postoperative length of hospital stay were recorded.

Results: The follow-up period ranged from 24 to 60 months, with an average of 43 months. The excellent and good outcome rates were 93.5% in Group A and 92.6% in Group B. There was no significant difference in efficacy between the groups (P > 0.05). However, Group B had significantly less intraoperative blood loss and shorter bed rest duration and postoperative length of hospital stay than Group A (P < 0.05). There were two cases of postoperative recurrence in Group A and three in Group B.

Conclusions: Although conventional IFD and TELD had similar levels of efficacy in treating LDH, TELD had several advantages. There was less intraoperative bleeding, shorter length of hospital stay and shorter bed rest duration. It can be considered a safe and effective surgical option for treating LDH.
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http://dx.doi.org/10.1186/s12891-020-03652-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513495PMC
September 2020

[Cancer Screening Program in Urban Kunming of Yunnan: Evaluation of Lung Cancer Risk Assessment and Screening].

Zhongguo Fei Ai Za Zhi 2020 Jul;23(7):541-546

Department of Yunnan Cancer Center, Yunnan Cancer Center/Yunnan Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.

Background: Lung cancer is the most common neoplasmas with a poor prognosis and a low 5-year survival rate. Early screening is an important measure for the prevention and treatment of lung cancer. At present, different countries have issued corresponding lung cancer screening guidelines, but China still lacks guidelines based on Chinese population research. Therefore, the National Cancer Center launched a Multi-center Cancer Screening Program in Urban China. This study analyzed the evaluation of lung cancer risk assessment model and screening effect in urban China of Yunnan, so as to explore the evaluation model of high-risk lung cancer population suitable for China's national conditions and develop lung cancer screening guidelines for Chinese.

Methods: A questionnaire survey and lung cancer risk assessment were conducted on 165,337 people in 36 street offices in 4 main urban areas of Kunming, Yunnan Province, using cluster sampling method from January 2015 to December 2019. People with high-risk of lung cancer conducted low-dose computed tomography (LDCT) screening of chest. What's more, all participants were followed up by active or passive follow-up.

Results: There were 264 patients were diagnosed lung cancer by pathology, and the overall incidence of lung cancer was 0.16% (264/165,337). The high-risk group (0.31%, 116/37,914) was higher than the non-high-risk group (0.12%, 148/127,423), and the difference was statistically significant (P<0.001). The incidence of lung cancer in the high-risk group was higher than the non-high-risk group among the male, female, and lower 50-year-old or more than 50-year-old subgroups, with statistical differences (P<0.001), but there was no statistical difference in the group without LDCT screening (P=0.73). The sensitivity of the lung cancer high-risk population assessment model was 43.94% (116/264) and the specificity was 77.10% (127,275/165,073). The early diagnosis rate of the screening group was 72.97% (54/74), which was significantly higher than that of the non-screening group [28.48% (43/151)].

Conclusions: The lung cancer high-risk population assessment model of National Key Public Health Program: Cancer Screening Program in Urban China can detect high-risk populations and improve the early diagnosis rate of lung cancer effectively.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.101.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406440PMC
July 2020

Tumor Mutational Burden and PD-L1 Expression in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

Onco Targets Ther 2020 8;13:5191-5198. Epub 2020 Jun 8.

Yunnan Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People's Republic of China.

Purpose: To explore the impact between the tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression on NSCLC in the Yunnan region of southwestern China.

Patients And Methods: Seventy-one NSCLC specimens that were pathologically confirmed were collected at first. The TMB and driver genetic alterations were evaluated accordingly by next-generation sequencing (NGS). Afterwards, clinical parameters and tumor PD-L1 expressions were collected. Finally, the relationship between TMB, PD-L1 expression and clinical outcome was evaluated.

Results: The median TMB was 5 (0.6-49) mutations/Mb by our NGS panel and the majority of patients (63/71, 88.7%) did not receive immunotherapy. The progression-free survival (PFS) was longer in TMB-low patients versus TMB-high ones (median 18.0 vs. 9.0 months, hazard ratio = 0.34, 95% confidence interval 0.14 to 0.84, = 0.02) and the cut-off value was 10 mutations/Mb. The overall survival (OS) was longer in TMB-low patients vs. TMB-high ones (median 21.0 vs. 10.0 months, HR = 0.32, 95% CI 0.12 to 0.82, = 0.02). Notably, our study also found that, excluding the eight patients with immunotherapy, the PFS was longer in patients with TMB-low vs. TMB-high (median 19.0 vs. 8.0 months, HR = 0.11, 95% CI 0.03 to 0.39, < 0.01) and the OS was longer in TMB-low patients vs. TMB-high (median 21.0 vs 10.0 months, HR = 0.12, 95% CI 0.03 to 0.42, < 0.01).

Conclusion: TMB was a valid and independent prognostic biomarker for NSCLC patients' clinical outcome and comprehensive screening of TMB based on NGS is recommended for individualized treatment strategies in Yunnan population.
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http://dx.doi.org/10.2147/OTT.S255947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292484PMC
June 2020

Factors associated with the burden of family caregivers of elderly patients with femoral neck fracture: a cross-sectional study.

J Orthop Surg Res 2020 Jun 23;15(1):234. Epub 2020 Jun 23.

Department of Orthopedics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, People's Republic of China.

Background: This study aimed to study the factors associated with caregiver burden among caregivers of elderly patients with femoral neck fracture.

Methods: This cross-sectional study was based on a non-probabilistic sampling of 183 elderly postoperative patients (aged 65 years or older) with femoral neck fracture who were hospitalized in the orthopedic center in our hospital and their family caregivers. Data were collected from January 2016 to June 2019. Patients and family caregivers completed the sociodemographic questionnaire. The Social Support Rating Scale (SSRS), the General Self-Efficacy Scale (GSE), and the Chinese version of the Zarit Burden Interview (ZBI) were used to evaluate social support, self-efficacy, and caregiver burden, respectively. By analyzing the clinical data of patients and family caregivers and combining the factors that affect the caregiver burden in parallel studies, we selected the factors that affected the caregiver burden in this study and conducted a multivariate analysis of these factors. P < 0.05 was considered statistically significant.

Results: We observed 176 caregivers aged 69.28 ± 7.19 years old, among whom 52.3% were male, 58.0% lived in the city, 84.0% were spouses of the patients, and 67.0% had a primary school educational background. The ZBI score of the family caregivers was 37.8 ± 8.9, and 82.7% of the caregivers were under a moderate to severe burden. The patient's functional status, Harris score, and pain score and the caregiver's SSRS scores, GSE scores, and the ratio of medical expenses to monthly income per capita were factors that affected the caregiver burden.

Conclusions: Most family caregivers of elderly patients with femoral neck fracture are subject to a considerable care burden, and social support and self-efficacy intervention are conducive to reducing the caregiver burden.
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http://dx.doi.org/10.1186/s13018-020-01749-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310331PMC
June 2020

miR-107 inhibited malignant biological behavior of non-small cell lung cancer cells by regulating the STK33/ERK signaling pathway and .

J Thorac Dis 2020 Apr;12(4):1540-1551

Department of Thoracic Surgery Ι, the Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Yunnan Cancer Center, The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Kunming 650118, China.

Background: The role of miRNAs in non-small cell lung cancer (NSCLC) has been broadly studied and confirmed, and miR-107 has attracted an ever-growing level of attention. This study set out to research the mechanism of the effect of miR-107 on the malignant biological behavior of NSCLC and .

Methods: The expression of miRNAs related to the development of NSCLC was detected by RT-qPCR. Western blotting was carried out to detect expression levels of serine/threonine kinase 33 (STK33) and proteins related to the extracellular regulated protein kinases (ERK) signaling pathway, while cell proliferation was detected using cell counting kit-8 (CCK-8). The cell apoptosis rate was measured using flow cytometry. The invasion ability was detected by Transwell assay. In vivo tumor growth assays were performed on mice. The expression ERK signaling pathway-related proteins was evaluated by immunohistochemistry staining. The targeted relationship between miR-107 and STK33 was confirmed by the dual luciferase reporter gene.

Results: In NSCLC cell lines and tissues, miR-107 was downregulated. Overexpression of miR-107 inhibited malignant biological behavior of NSCLC cell lines, and suppressed tumor growth . In addition, STK33 is one of the target genes of miR-107. Therefore, miR-107 suppressed cell proliferation and invasion and promoted tumor growth and cell apoptosis of NSCLC . The mechanism was found to be miR-107 targeting STK33, and a lack of STK33 led to the activation of ERK signaling pathway.

Conclusions: miR-107 inhibited malignant biological behavior of NSCLC through regulation of the STK33/ERK signaling pathway.
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http://dx.doi.org/10.21037/jtd.2020.03.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212150PMC
April 2020

Mechanistic study on the inhibition of biofilm by agrC-specific binding polypeptide.

Ann Transl Med 2020 Mar;8(6):337

Department of Thoracic Surgery I, the Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Yunnan Cancer Center, The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Kunming 650118, China.

Background: Considering the wide-spread misuse of antibiotics, the development of new antibacterial drugs may effectively prevent the emergence of antibiotic resistance in bacteria. The understanding of the mechanism underlying the agrC-specific binding polypeptide-mediated inhibition of biofilm formation may supply ideas for the development of new antibacterial drugs.

Methods: cells were cultured with different concentrations (0, 100, 200, 400, 800, and 1,600 µg/mL) of agrC-specific binding polypeptide (N1) and blank (N0). Crystal violet staining was performed to test the formation of biofilms and to determine the best concentration of agrC-specific binding polypeptides, and the bacterial inhibitory concentration was also determined. At different time points (6, 12, 18, 24, and 30 h), XTT assay was used to measure bacterial viability, and the real-time quantitative polymerase chain reaction was performed to measure the expression of , , , and genes. The sulfuric acid-phenol method was used to determine polysaccharide intercellular adhesin (PIA) levels.

Results: The biofilm formation ability of was the lowest after treatment with 800 µg/mL agrC-specific binding polypeptide. After 6 h of culture, agrC-specific binding polypeptide upregulated the expression of , , , and and increased the bacterial viability. However, the polypeptide downregulated the expression of , , , and and inhibited growth and PIA formation after 12 h of culture. Although agrC-specific binding polypeptide upregulated the expression of , , , and after 18 h, they inhibited bacterial growth and PIA formation.

Conclusions: Thus, agrC-specific binding polypeptide could downregulate the expression of , , , and and inhibit PIA formation by after 12 h, demonstrating its transient inhibitory effects on the biofilm formation ability of . Its effective concentration was 800 µg/mL.
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http://dx.doi.org/10.21037/atm.2020.02.84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186710PMC
March 2020

A Multiplex PCR Detection Assay for the Identification of Clinically Relevant Species in Field Blood Samples.

Front Microbiol 2020 7;11:606. Epub 2020 Apr 7.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.

The genus (Rickettsiales: Anaplasmataceae), which includes the species , , , and , is responsible for a wide variety of infections in both human and veterinary health worldwide. Multiple infections with these four pathogens have been reported in many cases. We introduce a novel multiplex PCR for the simultaneous detection of , , , and , based on species-specific primers against the ( and ), (), and 16S rRNA () genes. To verify the specificity of the PCR reactions, we evaluated four sets of primers to analyze samples containing different blood pathogens. The sensitivity of the multiplex PCR was evaluated by amplifying 10-fold dilutions of total genomic DNA extracted from sheep blood infected with , , , or . The reproducibility of the assay was evaluated by testing 10-fold dilutions of total genomic DNA extracted from sheep blood infected with these pathogens from 10 to 10 ng/μL per reaction in triplicate on three different days. A total of 175 field blood DNA samples were used to evaluate the reproducibility of multiplex PCR compared with the simplex PCRs. PCR primers used in this study were confirmed to be 100% species-specific using blood pathogens previously identified by other methods. The lower limit of detection of the multiplex PCR with good repeatability enabled the detection of , , and at concentrations of 3 × 10, 5 × 10, 2 × 10, and 7 × 10 ng/μL, respectively. There was no significant difference between conventional and multiplex PCR protocols used to detect the four species ( > 0.05). The results of the multiplex PCR revealed that the gene, the gene, the gene, and the 16S rRNA gene were reliable target genes for species identification in clinical isolates, being specific for each of the four target species. Our study provides an effective, sensitive, specific, and accurate tool for the rapid differential clinical diagnosis and epidemiological surveillance of pathogens in sheep and goats.
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http://dx.doi.org/10.3389/fmicb.2020.00606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154085PMC
April 2020

Identification of a potential tumor suppressor gene, , in non-small cell lung cancer.

Cancer Biol Med 2020 02;17(1):76-87

State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Oncogenes have been shown to be drivers of non-small cell lung cancer (NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to identify tumor suppressing ubiquitin pathway genes (UPGs) that were critical to lung tumorigenesis. The 696 UPGs were silenced by an siRNA screening in NSCLC cells; the potential tumor suppressing UPGs were analyzed, and their clinical significance was investigated. We reported that silencing of 11 UPGs resulted in enhanced proliferation of NSCLC cells, and four UPGs (, , , and ) were significantly downregulated in tumor samples compared to that in normal lung tissues and their expression levels were positively associated with overall survival (OS) of NSCLC patients. Among these genes, was the most significant one. expression was decreased in tumor samples compared to that in paired normal lung tissues in 59/86 (68.6%) NSCLCs, was correlated with TNM stage and sex of NSCLC patients, and was significantly higher in non-smoking patients than in smoking patients. Silencing UBL3 accelerated cell proliferation and ectopic expression of UBL3 suppressed NSCLC and . These results showed that UBL3 represented a tumor suppressor in NSCLC and may have potential for use in therapeutics and for the prediction of clinical outcome of patients.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142850PMC
February 2020

Ophiocordyceps lanpingensis polysaccharides attenuate pulmonary fibrosis in mice.

Biomed Pharmacother 2020 Jun 4;126:110058. Epub 2020 Mar 4.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with growing prevalence. Currently available therapies for treating IPF are not desirable due to the limited efficacy and multiple side effects. Ophiocordyceps lanpingensis is one strain of entomogenous fungi, which has been collected from the eastern part of the Himalayas. This study revealed that O. lanpingensis polysaccharides (OLP) could attenuate bleomycin (BLM) induced lung fibrosis in mice. Results showed that OLP treatments significantly reduced BLM-induced collagen deposition and decreased the accumulation of macrophages. The oxidative stress of the lung was alleviated by OLP. The expression levels of pro-inflammatory and pro-fibrogenic factors in OLP groups were also decreased compared with those in the BLM group, which might explain the improved alveolar integrity and function in the OLP treated groups. Our findings indicated that OLP treatment could alleviate pulmonary fibrosis progression mainly through reducing the recruitment of macrophages to the lungs.
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http://dx.doi.org/10.1016/j.biopha.2020.110058DOI Listing
June 2020

Factors related to the burden of family caregivers of elderly patients with spinal Tumours in Northwest China.

BMC Neurol 2020 Feb 28;20(1):69. Epub 2020 Feb 28.

Department of Nursing Administration, Honghui Hospital, Xi'an Jiaotong University College of Medicine, 555# You-yi East Road, Xi'an, 710054, Shaanxi, People's Republic of China.

Background: Family caregivers of elderly patients with spinal tumours experience considerable pain and burden during the care process. This study aims to investigate the factors associated with caregiver burden in family caregivers of elderly patients with spinal tumours.

Methods: A total of 220 elderly patients with spinal tumours (age ≥ 65 years) hospitalized at the spine centre of our hospital from January 2015 to December 2017 and their family caregivers were recruited for this cross-sectional study. All participants completed a sociodemographic questionnaire. Caregiver burden, social support and self-efficacy were assessed by the Chinese version of the Zarit Burden Interview (ZBI), the Social Support Rating Scale (SSRS) and the General Self-Efficacy Scale (GSE), respectively. The factors related to caregiver burden were analysed by multivariate analysis. P < 0.05 was considered statistically significant.

Results: The 216 elderly patients with spinal tumours were 71.59 ± 8.49 years old, and their caregivers were 70.46 ± 9.13 years old. A total of 170 patients were cared for by their spouses, who accounted for 78.7% of all caregivers. The ZBI score for the family caregivers was 35.5 ± 7.5, and most caregivers (84.5%) reported a moderate or heavy burden. The factors related to caregiver burden included patient paralysis, the primary cancer site, chemotherapy and/or radiation, cognitive dysfunction, functional status, monthly income, pain score, caregivers' SSRS score, and GSE score.

Conclusions: Most family caregivers of elderly patients with spinal tumours have a considerable caregiver burden. Interventions based on social support and self-efficacy can help reduce caregiver burden.
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http://dx.doi.org/10.1186/s12883-020-01652-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047359PMC
February 2020

[Trend Analysis of Clinical Epidemiological Characteristics of Lung Cancer in Yunnan Cancer Hospital from 2005 to 2014].

Zhongguo Fei Ai Za Zhi 2020 Mar 27;23(3):142-149. Epub 2020 Feb 27.

Department of Yunnan Cancer Center, Yunnan Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Center, Kunming 650118, China.

Background: Yunnan is a country with a high incidence of lung cancer in China and all over the world, and its morbidity and mortality are still rising. With changes in lifestyle and environment, the clinical epidemiological characteristics of lung cancer are converting. However, the trend of clinical characteristics of lung cancer in Yunnan has not been reported in the past 10 years, and we should start further research. The aim of this study was to explore the clinical characteristics and changes of lung cancer in Yunnan from 2005 to 2014, and to provide a theoretical basis for lung cancer prevention and treatment in this region.

Methods: A retrospective survey was used to extract the cases of lung cancer patients who were treated in our hospital from 2005 to 2014 by simple random sampling. The sociodemographic and clinicopathological characteristics of the patients were extracted by using a unified and standardized questionnaire. And the statistical analysis of the data was performed.

Results: A total of 1,000 patients with lung cancer were enrolled, with an average age of (58.1±10.1) years, and the ratio of male to female was 3.08/1.00. The proportion of male patients decreased from 75.0% in 2005 to 66.0% in 2014, while female patients increased from 25.0% to 34.0% (P=0.007). The proportion of patients aged ≥60 years increased from 30.0% in 2005 to 39.0% in 2014, and the proportion of patients under 60 years of age decreased, but there was no statistical difference (P=0.532). The proportion of patients with lower levels of education (primary or junior high school) increased from 36.0% to 66.0% (P<0.001). The proportion of smokers decreased from 71.0% to 47.0%, and the number of non-smokers increased from 29.0% to 52.0% (P=0.003). The patients with advanced lung cancer (IIIb-IV) increased from 20.0% to 54.0%, while the proportion of stage II-IIIa decreased from 62.0% to 24.0% (P=0.002). The proportion of adenocarcinoma increased from 36.0% to 61.0%, while squamous cell carcinoma decreased from 32.0% to 27.0% (P<0.001). Chest X-ray applications decreased from 91.0% to 58.0% (P<0.001), while chest computed tomography (CT) usage increased from 46.0% to 89.0% (P<0.001). Head magnetic resonance imaging (MRI) usage increased from 1.0% to 15.0% (P<0.001). The bone scan increased from 35.0% to 78.0% (P<0.001). The positron emission tomography-CT (PET-CT) inspection technique increased significantly from 0.0% to 17.0%. Chemotherapy (P=0.67) and surgery (P=0.78) were the most common treatments and the treatments were unchanged over the past 10 years.

Conclusions: The proportion of female patients increased, the clinical stage was late, and the pathological type transformation was a major challenge in the prevention and treatment of lung cancer in Yunnan. Despite major changes in sociodemographic and clinicopathological features, the choice of primary treatment modalities has not changed, and further research is needed.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.03.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118330PMC
March 2020

Dogs as New Hosts for the Emerging Zoonotic Pathogen in China.

Front Cell Infect Microbiol 2019 26;9:394. Epub 2019 Nov 26.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.

is an emerging zoonotic tick-borne pathogen with a broad host range, including many mammals. Dogs have close physical interactions with humans and regular contact with the external environment. Moreover, they have been previously reported to be hosts of , and . To confirm whether dogs are also hosts of , pathogen DNA was extracted from blood samples of 521 dogs, followed by PCR amplification of the citrate synthase () gene, heat shock protein () gene, and major surface protein 4 () gene of the . A total of 12.1% (63/521) of blood samples were shown to be -positive by PCR screening. No significant differences were observed between genders ( = 0.578) or types ( = 0.154) of dogs with infections. However, significantly higher infections occurred in dogs with regular contact with vegetation ( = 0.002), those aged over 10 years ( = 0.040), and during the summer season ( = 0.006). Phylogenetic analysis based on , and sequences demonstrated that the isolates obtained in this study were clustered within the clade, and were distinct from other species. In conclusion, dogs were shown to be a host of the human pathogenic . Considering the affinity between dogs and humans and the zoonotic tick-borne nature of , dogs should be carefully monitored for the presence of .
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http://dx.doi.org/10.3389/fcimb.2019.00394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901931PMC
August 2020

Study on the Effects of Estradiol in Staphylococcus epidermidis Device-Related Capsule Formation.

Aesthetic Plast Surg 2020 04 12;44(2):558-569. Epub 2019 Dec 12.

First Department of Mammary Surgery, Yunnan Cancer Hospital and The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan Province, China.

Background: Capsular contracture, mainly caused by Staphylococcus epidermidis (S. epidermidis) biofilm formation, is a complex problem for breast cancer patients who undergo surgical prosthetic breast reconstruction. Estradiol has been reported to be involved in the formation of bacterial biofilms. Thus, the underlying mechanism of estradiol in capsular contracture needs to be investigated.

Methods: Biofilm-related gene expressions were measured by qRT-PCR after sterilizing the silicone with bacterial suspension and E2 treatment in vitro. Rat models were established with bilateral ovariectomy operations and estradiol subcutaneous injections. The effects of estradiol on capsular contracture were detected by monitoring serum estradiol levels, bacterial infection rate in organs, biofilm formation and capsular contracture in vivo; inflammatory factors in vivo were examined as well. Biofilm on the silicone implants was observed under a scanning electron microscope.

Results: Both positive regulatory genes and negative regulatory genes were increased by the high concentration of estradiol, suggesting that estradiol can promote the formation of biofilm by not only positive but also negative regulations. High estradiol levels increased bacterial infection rate in organs, biofilm formation and capsular contracture. Further, high estradiol caused a large number of inflammatory cells to infiltrate and caused serious inflammatory reactions that aggravate the immune imbalances of the host.

Conclusion: High estradiol levels contribute to increasing capsular contracture caused by S. epidermidis biofilm formation.

No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-019-01567-3DOI Listing
April 2020

Comparative study on the mutational profile of adenocarcinoma and squamous cell carcinoma predominant histologic subtypes in Chinese non-small cell lung cancer patients.

Thorac Cancer 2020 01 6;11(1):103-112. Epub 2019 Nov 6.

Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Distinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well-established. However, comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive.

Methods: We analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture-based ultra-deep sequencing of 68 lung cancer-related genes.

Results: Of the 318 NSCLC patients, 215 were diagnosed with LUAD and 103 with LUSC. Adenocarcinoma in situ and acinar adenocarcinoma were the most predominant subtypes of LUAD. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. Among the LUAD subtypes, EGFR sensitizing mutations were most prevalent in the invasive lepidic subtype. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were also EGFR-mutants. Patients with colloidal, invasive mucinous, and fetal subtypes had the least number of EGFR mutations. Moreover, KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. A total of 90% of the LUSC patients harbor mutations in TP53, wherein all patients except five with nonkeratinizing were TP53 mutants. PIK3CA amplifications were most prevalent in keratinizing, followed by basaloid and nonkeratinizing subtypes.

Conclusion: These data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions.
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http://dx.doi.org/10.1111/1759-7714.13208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938761PMC
January 2020

YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.

Nat Commun 2019 10 25;10(1):4892. Epub 2019 Oct 25.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.

Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan domestic mammals compared to reciprocal lowlanders. Furthermore, mA modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.
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http://dx.doi.org/10.1038/s41467-019-12801-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814821PMC
October 2019

Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer.

Front Med 2020 Jun 28;14(3):318-326. Epub 2019 Sep 28.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

In order to unveil ubiquitin pathway genes (UPGs) that are essential for non-small cell lung cancer (NSCLC) cell proliferation, we recently conducted a siRNA screening experiment to knockdown the expression of 696 UPGs found in the human genome in A549 and H1975 NSCLC cells. We found that silencing of one of the candidates, RFWD3 that encodes an E3 ubiquitin ligase essential for the repair of DNA interstrand cross-links in response to DNA damage, led to dramatic inhibition of NSCLC cell proliferation with significant Z-scores. Knockdown of RFWD3 suppressed colony forming activity of NSCLC cells.We further evaluated the significance of RFWD3 in NSCLCs and found that this gene was more elevated in tumor samples than in paired normal lung tissues and was inversely associated with the clinical outcome of patients with NSCLC. Moreover, RFWD3 expression was significantly higher in smokers than in non-smokers. These results show for the first time that RFWD3 is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.
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http://dx.doi.org/10.1007/s11684-019-0708-6DOI Listing
June 2020

lncRNA DLEU2 modulates cell proliferation and invasion of non-small cell lung cancer by regulating miR-30c-5p/SOX9 axis.

Aging (Albany NY) 2019 09 20;11(18):7386-7401. Epub 2019 Sep 20.

Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.

Increasing evidence indicated that long noncoding RNAs (lncRNA) play critical roles in the progression of multiple cancers and that dysregulation of lncRNA promotes tumor progression. However, the function and underlying mechanism of lncRNA DLEU2 in biological behaviors of NSCLC cells are still largely unknown. Our studies confirmed that lncRNA DLEU2 was highly expressed in NSCLC tissues and cell lines, which was correlated with shorter overall survival in NSCLC patients. , knockdown of lncRNA DLEU2 inhibited proliferation, invasion, migration and induced apoptosis of both A549 and LLC cells; , it suppressed tumor growth and metastasis. lncRNA DLEU2 directly interacted with miR-30c-5p, which further targeted SOX9 and exerted oncogenic functions in NSCLC. Mechanistically, overexpression of lncRNA DLEU2 exhibits tumorigenic effects through downregulating the inhibitory effect of miR-30c-5p on SOX9 expression. In conclusion, Our finding confirmed that lncRNA DLEU2 as a novel oncogenic in NSCLC, which provide a potential novel diagnostic and therapeutic target for NSCLC.
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http://dx.doi.org/10.18632/aging.102226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781974PMC
September 2019

GLT8D1 overexpression as a novel prognostic biomarker in human cutaneous melanoma.

Melanoma Res 2019 12;29(6):612-620

Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming medical University (Yunnan Cancer Center).

Aberrant glycosylation plays a major role in the progression of melanoma, but little is known about glycosyltransferases. Glycosyltransferase 8 domain containing 1 (GLT8D1) is located in the Golgi apparatus and is related to transferase activity in mammals. However, its role in cancer remains unclear. The aim of this study was to investigate the expression of GLT8D1 in human melanoma and explore the relationship between GLT8D1 expression and the clinicopathological characteristics of melanoma patients via GEO data analysis combined with clinical patient data. The analysis of 45 malignant melanoma samples and 18 benign nevus samples from the GEO database was performed. Moreover, 67 patients with cutaneous melanoma and 38 patients with mucosal melanoma as well as 40 benign nevus samples were collected for our study. Immunohistochemistry analyses were implemented to evaluate GLT8D1 expression at protein level. The GEO data analysis exhibited that the GLT8D1 mRNA expression was upregulated in the melanoma samples compared with the benign nevus samples. Likewise, GLT8D1 protein expression in the cutaneous melanoma and mucosal melanoma samples was significantly higher than that in the benign nevus tissue samples (P = 0.001 and 0.046, respectively). Furthermore, the GLT8D1 protein expression in cutaneous melanoma was higher than that in mucosal melanoma (P = 0.001). The high GLT8D1 protein expression was remarkably correlated with Clark level (P = 0.027), AJCC stage (P = 0.003), ulceration status (P = 0.041), Ki-67 expression (P = 0.030) and especially with histopathological type (P = 0.001). The results of the Kaplan-Meier survival and Cox regression analyses revealed that cutaneous melanoma patients with high GLT8D1 expression (P = 0.036), Clark level (P = 0.018) and advanced AJCC stage (P = 0.003) encountered poor overall survival. Overall survival (P = 0.040) and progression-free survival (P = 0.019) were worse for the patients with high GLT8D1 expression than for the patients with low expression. These data implied that GLT8D1 could be an independent prognostic factor for an unfavorable prognosis in cutaneous malignant melanoma patients and that GLT8D1 overexpression might serve as a novel prognostic biomarker.
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http://dx.doi.org/10.1097/CMR.0000000000000631DOI Listing
December 2019
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