The biomarkers associated with epithelial-mesenchymal transition in human keloids.

INTRODUCTION: A keloid is a type of benign fibrotic disease with similar features to malignancies, including anti-apoptosis, over-proliferation, and invasion. Epithelial-mesenchymal transition (EMT) is a crucial mechanism that regulates the metastatic behavior of tumors. Thus, identifying EMT biomarkers is paramount in comprehensively understanding keloid pathogenesis. METHODS: To identify the differentially expressed genes (DEGs) GSE92566 dataset, with 3 normal skin and 4 keloid tissues, was downloaded from GEO databases to identify the differentially expressed genes (DEGs). Further, EMT-related genes were downloaded from dbEMT 2.0 databases and intersected with GSE92566 DEGs to identify EMT-related-DEGs (ERDEGs). Subsequently, the ERDEGs were used for GO, KEGG, gene set enrichment analysis (GSEA), protein-protein interaction (PPI), and miRNAs-mRNAs network analysis. To predict small molecules for EMT inhibition, the ERDEGs were imported to cMAP databases, whereas hub genes were imported to DGidb databases. Finally, we carried out qRT-PCR and in vitro experiments to validate our findings. RESULTS: A total of 122 ERDEGs were identified, including 59 upregulated and 63 down-regulated genes. Moreover, enrichment analysis revealed that focal adhesion, AMPK signal pathway, Wnt signal pathway, and EMT biological process were significantly enriched. STRING databases and Cytoscape software were used to construct the PPI network and EMT-related hub genes. Further, 3 modules were explored from the PPI network using the Molecular Complex Detection (MCODE) plugin. In the Cytohubba plugin, 10 hub genes were explored, including FN1, EGF, SOX9, CDH2, PROM1, EPCAM, KRT19, ITGB1, CD24, and KRT18. These genes were then enriched for the focal adhesion pathway. We constructed a microRNA (miRNA)-mRNA network, which predicted hsa-miR-155-5p (8 edges), hsa-miR-124-3p (7 edges), hsa-miR-145-5p (5 edges), hsa-miR-20a-5p (5 edges) and hsa-let-7b-5p (4 edges) as the most connected miRNAs regulating EMT. Based on the ERDEGs and 10 hub genes mentioned above, ribavirin demonstrated high drug-targeting relevance. Subsequently, qRT-PCR confirmed that the expression of FN1, ITGB1, CDH2, and EPCAM corroborated with previous findings. qRT-PCR also showed that the expression levels of hsa-miR-124-3p and hsa-miR-145-5p were significantly lower in keloids and hsa-miR-155-5p was upregulated in keloids. Finally, by treating human keloid fibroblasts (HKFs) with ribavirin in vitro, we confirmed that ribavirin could inhibit HKFs proliferation and EMT. CONCLUSION: In summary, this work provides novel EMT biomarkers in keloids and predicts new small target molecules for keloid therapy. Our findings improve the understanding of keloid pathogenesis, providing new treatment options.

Comparison of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage.

OBJECTIVE: To explore the effect of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage. METHODS: The clinical data of 137 patients with primary brain stem haemorrhage (haematoma volume > 3 ml) from August 2014 to August 2022 at the First Hospital of Hebei Medical University were reviewed. Sixty-five patients were treated with stereotactic haematoma aspiration, and 72 patients were treated with conventional therapy. We followed up on patient survival after 30 days and the recovery of neurological function after 90 days. The recovery of neurological function was evaluated by the modified Rankin Scale (mRS) 90 days after treatment. The mortality and neurological recovery rates of the two treatments were compared and analysed. RESULTS: There was a significant difference in the 30-day mortality rate between the two treatment groups (p < 0.05). There was a significant difference in neurological function improvement after 90 days between the two treatment groups (P < 0.05). There was no significant difference between stereotactic aspiration and routine treatment in the prognosis of primary brainstem haemorrhage patients at 90 days after treatment (P > 0.05). CONCLUSION: Stereotactic aspiration surgery for primary brain stem haemorrhage can significantly reduce mortality and improve the neurological function of some patients.

Role of HIF-1α in pathogenic mechanisms of keloids.

BACKGROUDS AND OBJECTIVE: Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids. METHODS: We reviewed and summarized the relevant published studies. RESULTS: Hypoxia results in the accumulation of hypoxia-inducible factor 1α (HIF-1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial-mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance. CONCLUSION: It is, therefore, essential to understand the role of HIF-1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.

A comparison of proliferation levels in normal skin, physiological scar and keloid tissue.

Proliferation is an important characteristic of life, and many signaling pathways participate in this complicated process. The MAPK/Erk pathway is a classic pathway in cell proliferation. In this study, expression levels of key factors in the MAPK/Erk pathway were measured to assess the proliferation level among normal skin, physiological scar, and keloid tissue. Thirty patients were selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January 2019 to December 2020. Histological appearance and fiber tissue content were observed by Hematoxylin and eosin staining and Masson staining. Expression levels of key factors in the MAPK/Erk pathway (ATF2, c-Jun, c-Myc, p38 and STAT1) and relative proteins (HIF-1α and PCNA) in tissues were detected by immunohistochemistry and analyzed as the percentage of positively stained cells in both the tissue epidermis and dermis. Western blot was used for quantitative analysis of the above factors. In results, keloid tissue showed a significantly higher fiber and less cell content. In the immunohistochemical result, higher expression of key factors was observed in the epidermis than in the dermal layer, and the expression of all factors was increased remarkably in keloid tissue. In western blot analysis, all factors (except STAT1) showed higher expression in keloid tissue. In our former research, keloid showed similar apoptosis level as physiological scar and normal skin. On combining our former conclusion and results in this study, an imbalance condition between the high proliferation level and normal apoptosis level may lead to the growth characteristics of keloid.

A new photodynamic therapy photosensitizer (p1) promotes apoptosis of keloid fibroblasts by targeting caspase-8.

Photodynamic therapy (PDT) is a new therapy for treating cancer with less toxicity, high selectivity, good cooperativity, and repetitive usability. However, keloid treatment by PDT is mainly focused on clinical appearance, and few studies have been conducted on the mechanisms of PDT. In this study, key factors of the classical mitochondrial apoptosis signaling pathway were measured to assess the effect of a new PDT photosensitizer (p1). A specific inhibitor of caspase-8 (Z-IETD-FMK) was also used to verify the possible mechanisms. Twelve samples were obtained from 12 patients (six with keloids and six without) selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January to December 2020. After cell culture, fibroblasts were divided into 13 groups. The morphology of fibroblasts in each group was observed by microscopy. Cell activity was measured by cell counting kit-8, and cell apoptotic morphology was observed by TUNEL staining. The reactive oxygen species (ROS) relative value was measured by a ROS test kit. The expression levels of key mitochondrial factors (caspase-3, caspase-8, cytochrome-c, Bax, and Bcl-2) were assessed by western blot, and mRNA expression of caspase-3 and caspase-8 was measured by RT-qPCR. We showed that p1 had a satisfactory proapoptotic effect on keloid fibroblasts by increasing the expression of ROS, caspase-3, caspase-8, and cytochrome-c, and decreasing the Bcl-2/Bax ratio; however, this effect was partially inhibited by Z-IETD-FMK, indicating that caspase-8 may be one of the p1's targets to achieve the proapoptotic effect.

Simultaneous detection of 9 respiratory pathogens using a newly developed multiplex real-time PCR panel based on an automatic molecular detection and analysis system.

Timely identification of respiratory pathogens guides specific treatment, reduces hospital costs and minimizes the excessive use of antibiotics. A new multiplex real-time PCR panel was developed based on an automatic molecular detection and analysis system (AutoMolec system), consisting of three separate internally controlled assays. Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, human metapneumovirus, influenza B virus, respiratory syncytial virus and human parainfluenza virus 1-3 may be directly detected in original samples. The system's clinical performance was evaluated by comparison with an approved commercial kit, using 517 clinical samples. The limit of detection of the AutoMolec mRT-PCR panel ranged from 4 × 10-4 ∼3.3 TCID50/mL and no cross-reaction with common respiratory pathogens was observed. The AutoMolec mRT-PCR panel had 99.09% sensitivity and 100.0% specificity and overall detection consistency was 99.61%, making it comparable to that of the commercial kit. Therefore, the AutoMolec mRT-PCR panel has great potential for routine screening of respiratory infection in China.

The optimal extent of lymph node dissection in N1b papillary thyroid microcarcinoma based on clinicopathological factors and preoperative ultrasonography.

Background: The optimal extent of lymph node (LN) dissection in the management of N1b papillary thyroid microcarcinoma (PTMC) is still under debate in clinical practice, so we aimed to identify the risk factors associated with multilevel lateral lymph node metastasis (LLNM) with regard to the extent of LN dissection. Methods: The clinical data of 182 N1b PTMC patients between January 2019 and June 2021 at Tianjin Medical University Cancer Institute and Hospital were retrospectively reviewed. The frequency pattern and distribution of LLNM were analyzed for risk factors. We assessed the diagnostic value of preoperative ultrasonography (USG) for identifying levels II-V metastasis in PTMC patients. Results: The proportion of multilevel LLNM in N1b PTMC was 72.1%, and the most common pattern was metastasis at two levels (41.2%). Capsule invasion [odds ratio (OR) =6.861, 95% confidence interval (CI): 1.462-32.190, P=0.015], upper pole [OR =2.125, 95% CI: 1.010-4.473, P=0.047], central LN ratio [OR =7.315, 95% CI: 1.309-40.877, P=0.023], thyroid-stimulating hormone (TSH) >1.5 mIU/mL [OR =2.773, 95% CI: 1.269-6.060, P=0.011], and extranodal extension (ENE) [OR =2.632, 95% CI: 1.207-5.739, P=0.015] were independent risk factors for multilevel metastasis. In addition, unltrasonography had high sensitivity and specificity in the diagnosis of metastasis at level V (75.0%, 78.4%) and multilevel LLNM (67.2%, 64.8%). Conclusions: Modified radical neck dissection (MRND) in N1b PTMC patients may be reserved for patients with simultaneous 3-level LLNM or clinically evident metastasis at level V. Preoperative USG may have certain suggestive significance in the diagnosis of multilevel LLNM in primary PTMC.

Effects of moisture content on the enolization products formation in glucose-proline Maillard reaction models.

BACKGROUND: 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d-glucose and l-proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times. RESULTS: DDMP was predominantly generated in dry or low water-content heating models along with n increased 1-deoxyglucosone (1-DG) generation via 2,3-enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1-DG, and DDMP due to a change in the reaction mechanism from 2,3-enolization to 1,2-enolization, which facilitated 3-deoxyglucosone (3-DG) and HMF formation. CONCLUSION: Increased moisture content in glucose-proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3-enolization to 1,2-enolization to generate more 3-DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2-enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry.

Safety of early surgery for geriatric hip fracture patients taking clopidogrel: a retrospective case-control study of 120 patients in China.

BACKGROUND: Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal. METHODS: Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued <5 days before surgery constituted the clopidogrel group. The control group constituted 60 patients not taking antiplatelet or anticoagulant drugs and matched 1:1 with the clopidogrel group for sex, fracture type, operative procedure, and time from injury to operation (±10 h). The primary outcome was perioperative blood loss and the secondary outcomes were transfusion requirement, complications, and mortality. The Student's t test or Wilcoxon signed rank sum test was used for continuous variables and the Chi-square test was used for categorical variables. RESULTS: Age, body mass index, American Society of Anesthesiologists score, and percentage undergoing general anesthesia were comparable between the groups (P > 0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P < 0.001) and cerebrovascular disease (45.0% vs. 15.0%; P < 0.010) were significantly higher in the clopidogrel vs. control groups, respectively. The median clopidogrel discontinuation time before operation was 73.0 (range: 3.0-120.0) h. There was no significant difference in the estimated perioperative blood loss between the clopidogrel group (median: 745 mL) and control group (median: 772 mL) (P = 0.866). The intra-operative transfusion rate was higher in the clopidogrel group (22/60, 36.7%) than that in the control group (12/60, 20.0%) (P < 0.050). However, there was no significant difference in the blood transfusion rate during the entire perioperative period (26/60, 43.3% vs. 20/60, 33.3%; clopidogrel group vs. control group, respectively; P > 0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups. CONCLUSIONS: Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.

Efficacy of proprioceptive training on the recovery of total joint arthroplasty patients: a meta-analysis.

BACKGROUND: Optimal balance control is of paramount importance for function recovery after total joint arthroplasty (TJA). The study objective of this meta-analysis was to assess the short- and mid-term effects of proprioceptive and balance training for patients undergoing TJA. METHODS: Electronic searches were conducted from PubMed, Cochrane library, and Embase databases to identify eligible RCTs through May 2020. Standard mean difference (SMD) with 95% confidence interval (95%CI) was applied to calculate pooled effect estimates between proprioceptive and balance training and control group. Main outcomes were self-reported functionality, balance, pain, quality of life, and function (range of motion). RESULTS: Seven randomized controlled trials were finally included in this meta-analysis. Pooled results found that balance and proprioceptive trainings have a positive role in improving self-reported functionality at short-term after TJA. Moreover, balance and proprioceptive trainings were associated with an increase of the balance at short- and mid-term after TJA. These results were further confirmed by subgroup analysis between preoperative and postoperative administration of balance and proprioceptive trainings. CONCLUSION: Our meta-analysis suggests that balance and proprioceptive trainings after TJA improved self-reported functionality and balance. These improvements were maintained at mid-terms. More research is needed to confirm balance and proprioceptive trainings for pain and quality of life for TJA.

Repair of cutaneous and mucosal upper lip defects using double V-Y advancement flaps.

BACKGROUND: The repair and reconstruction of the upper lip defects should focus on the important anatomical landmarks of the upper lip. In this investigation, double V-Y advancement flaps were used to simultaneously repair the cutaneous and mucosal defects of the upper lip. It was especially suitable for young patients with tight skin and high-risk scar hyperplasia in the donor sites. OBJECTIVE: The objective was to examine the surgical outcomes following the simultaneous repairation of upper lip mucocutaneous defects using double V-Y advancement flaps. METHODS: A retrospective review of all patients with defects near the vermilion border who underwent double V-Y flaps repair from July 2014 to November 2018 was performed. Transverse V-Y advancement flaps were used to repair the cutaneous defects and longitudinal V-Y advancement flaps to repair the mucosal defects. RESULTS: Fifteen patients (six males, nine females) were retrospectively reviewed. Defects spanning the vermilion border ranged from 0.8 × 0.5 to 2.5 × 1.5 cm2 . Follow-up was for 3 months or longer. There were no perioperative complications or visible postoperative scars, and major anatomic landmarks were preserved and reconstructed. All patients were satisfied with the aesthetic outcome. CONCLUSION: Double V-Y advancement flaps are suitable for the repair of superficial mucocutaneous defects smaller than 50% of the lateral upper lip, especially for younger patients with tight skin.

Refinements of the application of paramedian forehead flap in nasal defects repair in Asian patients.

BACKGROUND: Due to the relatively higher tendency of postsurgery scars, insufficient cartilage support, and low surgical acceptability, nasal defect repair with forehead flap in Asian patients needs further study. OBJECTIVE: We aim to determine the necessity of tissue expansion, timing of pedicle division, and the importance of cartilage scaffold reinforcement and scar prevention at the donor site during nasal reconstruction in Asian patients with paramedian forehead flap. METHODS: A retrospective analysis was performed on patients who underwent nasal reconstruction with forehead flap at our hospital from January 2013 to January 2018. The demographical information, surgery details, and postoperative complications of all patients were recorded. The reconstructed nose, scars, and eyebrow deformities were evaluated by digital photographs, and the overall satisfaction of the patients was documented. RESULTS: The study included 15 patients (7 males and 8 females). All nasal defects involved at least two aesthetic units and included seven full-thickness defects. Only one patient underwent two revision operations. Complications like hematoma, infection, and necrosis were not detected, except in one patient with partial necrosis of the flap. All patients were satisfied with the reconstructed nose and did not report any respiratory dysfunction. No obvious scars or eyebrow deformities were observed. CONCLUSION: Three-stage full-thickness forehead flap should be used to repair nasal defects in Asian patients, with immediate cartilage scaffold reconstruction at stage one and reinforcement at stage two. Botox injection into the forehead can refine the scar.

Adipose-Derived Stromal Cells Attenuate Adipose Inflammation in Obesity through Adipocyte Browning and Polarization of M2 Macrophages.

Obesity is a metabolic condition associated with multiple health problems such as endocrine and metabolic dysfunction and chronic inflammation in adipose tissues. In this study, the ADSCs could be stimulated to differentiate into brown adipocyte with rosiglitazone treatment based on the Oil-Red-O staining trial. Furthermore, the multilocular lipid droplets located in the center was increased in differentiated brown adipocytes, and brown fat-associated proteins, UCP1, PPAR-γ, and LPL were highly expressed in brown adipocytes differentiated from ADSCs. Additionally, the results of animal experiments showed that both weight and amount of VLDL and LDL were decreased in the serum of obese mice after transplantation of rosiglitazone-induced brown adipocytes, while the level of HDL increased. Moreover, the proteins associated with lipid metabolism, LPA and UCP1, were downregulated, and the inflammatory response was suppressed through inhibition of the ITGAM/NF-κB-mediated proinflammatory responses and polarization of M2 macrophages. Similarly, the amounts of proinflammatory cytokines, TNF-α, IL-6, and IL-1ß were decreased after rosiglitazone-induced brown adipocyte transplantation. On the contrary, anti-inflammatory cytokine IL-10 was significantly increased in both groups of obese mice, with or without brown adipocyte transplantation. Therefore, the adipose-derived stromal cells with induced browning could promote lipid consumption and alternative polarization of M2 macrophages to attenuate adipose inflammation in obesity mouse models, which thus provides a potential therapy for obesity.

Systematic profiling of alternative splicing signature reveals prognostic predictor for cervical cancer.

AIM: Cervical cancer is a common malignant carcinoma of the gynecological tract with high morbidity and mortality. Therefore, it is crucial to elucidate the pathogenesis, prevention, diagnosis and prognosis of cervical cancer by searching for the involved key genes. METHOD: In this study, the alternative splicing (AS) events of 253 patients with cervical cancer were analyzed, and 41,766 AS events were detected in 9961 genes. Univariate analysis was performed to screen prognostic AS events. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to identify the pathways in which these AS events were involved. RESULTS: We found that exon skip (ES) is the main AS event in patients with cervical cancer. There was pronounced consistency between the genes involved in overall survival and those involved in recurrence. At the same time, we found that a gene may exhibit several different types of AS events, and these different AS events may be related to prognosis. Four characteristic genes, HSPA14, SDHAF2, CAMKK2 and TM9SF1, that can be used as prognostic markers for cervical cancer were selected. CONCLUSION: The importance of AS events in the development of cervical cancer and prediction of prognosis was revealed by a large amount of data at the whole genome level, which may provide a potential target for cervical cancer treatment. We also provide a new method for exploring the pathogenesis of cervical cancer to determine clinical treatment and prognosis more accurately.

A Prospective Study to Compare Analgesia from Femoral Obturator Nerve Block with Fascia Iliaca Compartment Block for Acute Preoperative Pain in Elderly Patients with Hip Fracture.

BACKGROUND This study aimed to compare femoral obturator nerve block (FONB) with fascia iliaca compartment block (FICB) in the management of acute preoperative pain in elderly patients with hip fracture. MATERIAL AND METHODS Patients ≥65 years (n=154) diagnosed with hip fracture who had surgery within 48 hours of hospital admission included two groups who received ultrasound-guided nerve block, the FONB group (n=77), and the FICB group (n=77). The visual analog scale (VAS) score for pain, requirement for analgesic drugs, nursing care requirements after hospitalization, post-operative complications, and rehabilitation were compared between the FONB and FICB patient groups. RESULTS The VAS scores after both nerve block procedures were significantly reduced compared with those before both nerve block procedures (P<0.05), but there were no differences on the second day after nerve block. The VAS scores at rest and on exercise in the FONB group were significantly lower than those in the FICB group at 30 min and one day after nerve block (P<0.05). The requirement for postoperative analgesic drugs in the FONB group was significantly lower than that in the FICB group (P=0.048). The incidence of nausea and vertigo in the FICB group were significantly higher than in the FONB group (P=0.031 and P=0.034, respectively). Patients in the FONB group experienced significantly improved quality of postoperative function (P=0.029). CONCLUSIONS Both FONB and FICB provided pain control for elderly patients with hip fracture. However, compared with FICB, FONB resulted in significantly improved analgesia with a reduced requirement for analgesic drugs.

Screening of prognostic biomarkers for endometrial carcinoma based on a ceRNA network.

OBJECTIVE: This study aims to reveal the regulation network of lncRNAs-miRNAs-mRNA in endometrial carcinoma (EC), to investigate the underlying mechanisms of EC occurrence and progression, to screen prognostic biomarkers. METHODS: RNA-seq and miRNA-seq data of endometrial carcinoma were downloaded from the TCGA database. Edge.R package was used to screen differentially expressed genes. A database was searched to determine differentially expressed lncRNA-miRNA and miRNA-mRNA pairs, to construct the topological network of ceRNA, and to elucidate the key RNAs that are for a prognosis of survival. RESULTS: We screened out 2632 mRNAs, 1178 lncRNAs and 189 miRNAs that were differentially expressed. The constructed ceRNA network included 97 lncRNAs, 20 miRNAs and 73 mRNAs. Analyzing network genes for associations with prognosies revealed 169 prognosis-associated RNAs, including 92 lncRNAs, 16miRNAs and 61 mRNAs. CONCLUSION: Our results reveal new potential mechanisms underlying the carcinogenesis and progression of endometrial carcinoma.

Decreased expression of peroxiredoxin1 inhibits proliferation, invasion, and metastasis of ovarian cancer cell.

AIM: The aim of this study was to explore the expression of peroxiredoxin1 (PRDX1) in epithelial ovarian cancer, analyze the relationship between PRDX1 and clinicopathologic parameters of patients with ovarian cancer, including their prognosis, and describe changes and the mechanisms involved in malignant biologic behavior of ovarian cancer cells when PRDX1 expression is inhibited. METHODS: The expression of PRDX1 was detected immunohistochemically in 15 samples of normal ovarian tissue, 21 benign, 11 borderline, and 101 malignant epithelial ovarian tumors. Changes in ovarian cancer cell proliferation, invasion, and metastasis before and after inhibiting PRDX1 expression were assessed by cell function assay. Additionally, gene set enrichment analysis (GSEA) of PRDX1 was performed by the Cancer Genome Atlas database. A protein- protein interaction network was then constructed and a pathway function analysis of the genes in the network was conducted. RESULTS: PRDX1 expression was mainly localized to the cytoplasm, as well as the nucleus of cells. The expression rate of PRDX1 in epithelial ovarian malignant tissues (96.04%) was significantly higher than that in borderline (72.72%) and benign (57.14%) epithelial ovarian tumors, and normal ovarian tissue (20%; all P<0.05). Cox multivariate regression analysis indicated that advanced clinical stage, low tissue differentiation, and high expression of PRDX1 were independent risk factors affecting the prognosis of epithelial ovarian cancer (all P<0.05). Cell function assay verified that the decreased expression of PRDX1 inhibited ovarian cancer cell proliferation, invasion, and metastasis. GSEA analysis indicated that PRDX1 was significantly related to the Wnt signaling pathway. Western blot analysis confirmed that PRDX1 could regulate the expression of ß-catenin in the Wnt pathway. CONCLUSION: Decreased expression of PRDX1 can attenuate cell proliferation, invasion, and metastasis of ovarian cancer cells. The expression of PRDX1 is related to the prognosis of patients with ovarian cancer and can therefore be used as a biomarker.

Serum CTRP3 Level is Associated with Osteoporosis in Postmenopausal Women.

BACKGROUND: As a novel adipokine, CTRP3 involves in various functions of energy metabolism. Recent advance reveals a complex interaction between bone and adipose tissue via the secretion of adipokines. AIMS: A hospital-based case-control study was conducted to investigate the role of serum CTRP3 in osteoporosis among postmenopausal women. METHODS: Serum levels of CTRP3 and osteocalcin were measured. Bone mineral density (BMD) was obtained on femoral neck and lumbar spines by dual energy X-ray absorptiometry. RESULTS: Serum CTRP3 level was lower in subjects with osteoporosis (76.7±22.1 ng/ml) than it in controls (89.4±22.5 ng/ml) (P<0.001). Meanwhile, the frequency of osteoporosis presented a significant decrease (66.4%, 53.9% and 35.9%, P<0.001), in the tertiles of serum CTRP3. Furthermore, serum CTRP3 witnessed an association with a lower risk of osteoporosis (adjusted odds ratio=0.973, 95% confidence interval [0.963-0.983], P<0.001). Lastly, serum CTRP3 level was positively correlated with femoral BMD (r=0.403, P<0.001), lumbar BMD (r=0.368, P<0.001), and HDL-C (r=0.118, P=0.022), among all participants after adjustment. Meanwhile, CTRP3 presented negative correlations with HOMA-IR (r=-0.136, P=0.008) and insulin (r=-0.192, P <0.001). CONCLUSIONS: It shows that a decreased serum level of CTRP3 was independently associated with osteoporosis.

Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma.

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.

A Comparison of Different Training Methods in the Successful Learning of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

BACKGROUND: Standardized training of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS- TBNA) is available only in highly developed countries. OBJECTIVE: To compare the skill differences in the performance of EBUS-TBNA by pulmonologists trained under different learning methods. METHODS: We performed a retrospective study of 145 EBUS-TBNA cases. We set up 3 comparative training groups: a standardized training group, a teaching group, and a self-study group. The main clinical outcomes were sensitivity, specificity and accuracy of EBUS-TBNA. Cumulative sum analysis was used to track EBUS-TBNA proficiency of the 3 groups. RESULTS: The sensitivities of EBUS-TBNA in the different groups were 90, 88, and 67%, respectively. The accuracies of the different groups were 91, 90, and 71%, respectively. With respect to the sensitivity and accuracy, there was no significant difference between the standardized training group and teaching group. However, the self-study group was inferior to the other 2 groups. By comparing the learning curve among the groups, we found that the minimum number of operations needed to reach a 90% accuracy for the standardized training group, the teaching group and the self-study group was 17, 32 and 40 cases, respectively. CONCLUSION: Compared with the teaching and self-study groups, the standardized training group resulted in practitioners achieving high skill levels following the performance of a lower number of cases. Pulmonologists trained in the teaching group achieved a similar level of skills, but required more experience to reach this level. Practitioners in the self-study group did not achieve a satisfactory level of skills, despite performing a high number of cases.