The role of serum cystatin C (Scys) for the detection of acute kidney injury (AKI) has not been fully discussed. This meta-analysis was aimed to investigate the overall diagnostic accuracy of Scys ...for AKI in adults, and further identify factors affecting its performance. Studies before Sept. 2016 were retrieved from PubMed, Embase, Web of Science and the Cochrane Library. A total of 30 prospective cohort studies (involving 4247 adults from 15 countries, 982 patients occurring AKI) were included. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools demonstrated no significant bias had influenced the methodological quality of the included studies. Scys showed a high predictive power for all-cause AKI, that the area under the receiver operating characteristic curve was 0.89. The detailed assessment parameters, such as sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for Scys were 0.82, 0.82, 4.6, 0.22 and 21, respectively. Although Scys could be slightly influenced by the following factors: settings, AKI diagnostic criteria, ethnicity, determination method, age and gender, these factors above did not reach statistically significance. In conclusion, Scys could be a vital promising marker to screen out AKI.
Trichomonas vaginitis (TV) is the most common non-viral sexually transmitted infection (STI) worldwide. The high prevalence of TV combined with mild or asymptomatic early symptoms leads to clinical ...vulnerability from delayed diagnosis. Latent infection can increase the incidence of pelvic infections, infertility, and adverse pregnancy complications. Data from 898 women who underwent vaginal flora testing from June 2014 to December 2014 were used to create a nomogram to assess the risk of TV in women in order to guide TV prevention and clinical intervention. The prediction model was evaluated in terms of identification, calibration, and clinical utility using the C-index, calibration plots, decision curve analysis, and internal validation. Predictors in the TV nomogram included age, occupation, yearly income, tea drinking, bathing frequency, menopause, spontaneous abortion, use of contraceptives, history of gynecological surgery, and HPV infection. The C-index of the TV risk prediction model was 0.732 (95% confidence interval: 0.695-0.768). It showed good discriminatory and predictive power. Decision curve analysis indicated that the nomogram had a good net benefit when the threshold probability of TV in women was 2-80%. The established TV prediction model easily, accurately, and quickly predicts the risk of TV onset.
This trial aims to assess whether dexmedetomidine can reduce the incidence of postoperative cognitive dysfunction in elderly orthopaedic patients and explore the specific mechanism.
Postoperative ...cognitive dysfunction is a common complication after orthopaedic surgery that results in poor prognosis and increases the length of hospital stays and costs. Dexmedetomidine has been confirmed as a drug that can improve postoperative cognitive dysfunction in some studies. However, to date, the specific mechanism by which dexmedetomidine improves postoperative cognitive dysfunction is still elusive.
A single-centre, prospective, double-blinded, randomized controlled trial will be conducted at Hebei General Hospital. Ninety-six elderly patients who undergo total hip or knee replacement will be studied in this trial and randomly divided into two groups. Patients in the experimental group will receive a loading dose of 0.5 μg/kg dexmedetomidine for 10 min and then a maintenance dose of 0.5 μg/kg/h dexmedetomidine until 30 min before the end of the operation, and patients in the control group will be infused with an equal volume of normal saline. The incidence of postoperative cognitive dysfunction will be the primary outcome. Changes in the balance of T helper 17 cell and regulatory T cell; the levels of matrix metalloproteinase 9, S-100β, IL-17A, and IL-10; perioperative complications; hospitalization duration; and intraoperative blood loss will be the secondary outcomes.
The consequences of this trial will show that dexmedetomidine can improve postoperative cognitive dysfunction in elderly orthopaedic patients, which may be related to the balance of T helper 17/regulatory T cells.
Chinese Clinical Trial Registry ChiCTR2200055802 . Registered on 20 January 2022.
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily, which has been implicated in the pathophysiology of the nervous system. Recently, several studies have suggested ...that BDNF and/or its receptor, tropomyosin related kinase B (TrkB), are involved in tumor growth and metastasis in several cancers, including prostate cancer, neuroblastoma, pancreatic ductal carcinoma, hepatocellular carcinoma, and lung cancer. Despite the increasing emphasis on BDNF/TrkB signaling in human tumors, how it participates in primary tumors has not yet been determined. Additionally, little is known about the molecular mechanisms that elicit signaling downstream of TrkB in the progression of non-small-cell lung cancer (NSCLC). In this study, we report the significant expression of BDNF in NSCLC samples and show that BDNF stimulation increases the synthesis of BDNF itself through activation of STAT3 in lung cancer cells. The release of BDNF can in turn activate TrkB signaling. The activation of both TrkB and STAT3 contribute to downstream signaling and promote human non-small-cell lung cancer proliferation.
5-aminolevulinic acid through a needle-free, plum-blossom needle or conventional needle followed by photodynamic therapy are available options for non-melanoma skin cancer treatment.
To compare these ...three techniques of injection of 5-aminolevulinic, regarding treatment response and adverse effects in patients with non-melanoma skin cancer.
Non-melanoma skin cancer patients have received six cycles of 0.5 mL intralesional 20% w/v 5-aminolevulinic acid through a conventional needle (CPT cohort, n = 158), or plum-blossom needle (BPT cohort, n = 118), or needle-free injection (NPT cohort, n = 105) followed by irradiation with a red light. Data regarding treatment response and adverse effects were collected and analyzed.
The treatment response was higher among patients of NPT cohort than those of CPT (p = .012, q = 3.981) and BPT (p = .012, q = 3.472) cohorts. Conventional and plum-blossom needle injections therapies were reported scar, local redness, and worse cosmetic appearance in the follow-up period.
Needle-free injection of intralesional 5-aminolevulinic acid followed by irradiation with red light therapy were reported high treatment response with manageable adverse effects for non-melanoma skin cancer patients than that of conventional and plum-blossom needle injections.
III.
Aims
Micro‐vesicles (MVs) from bone mesenchymal stem cells (MSCs) have been shown to contribute to the recovery of damaged kidney. The aims of the present study are to investigate the biological ...effects and repair mechanisms of MVs.
Methods
Micro‐vesicles were obtained from MSC supernatants. In vitro, the proximal tubular epithelial cells (HK‐2) were treated with transforming growth factor (TGF‐β1). The expressions of E‐cadherin and α‐smooth muscle actin (α‐SMA) were evaluated. In vitro, the mice were divided into: control, unilateral ureteral obstruction (UUO), UUO+MSC, and UUO+MV group. MVs and MSCs were injected after surgery. The mice were killed 7/14 days after surgery and handled for further tests. The micro‐RNA expressions were labeled using the miRCURY Hy3/Hy5 Power labeling kit and hybridized on the miRCURY LNA Array.
Results
In vitro, MV reversed transforming growth factor‐β1 (TGF‐β1)‐induced morphological changes, and firmed the expression of E‐cadherin and reduced the secretion of α‐SMA in HK2 cells. In vivo, the level of blood urea nitrogen (BUN) in the MV and MSC group was lower than the UUO (P < 0.01). The Scr level decreased after 7 days of MV treatment (P < 0.05). Administration of MSC and MV reduced Scr level at day 14 (P < 0.05). The level of serum UA decreased with MV administration (day 7,14, P < 0.01). Herein, a total of 503 expressed miRNAs were detected, of which, 266 were in MSC, including 237 in MVs.
Conclusion
Micro‐vesicles (MVs) protect kidneys both in vivo and vitro, and MVs are superior to MSCs in some respects. MVs can be a potential therapy in treatment of kidney diseases.
Summary at a Glance
This paper has had three reviews with mixed recommendations. The topic is novel – use of mesenchymal stem cells to deliver miRNA via endosome vesicles. The English may require some editorial proofing, but otherwise suitable for publication.
Background Hypoxia is one of most typical features in the tumor microenvironment of solid tumor and an inducer of endoplasmic reticulum (ER) stress, and HIF-1alpha functions as a key transcription ...factor regulator to promote tumor angiogenesis in the adaptive response to hypoxia. Increasing evidence has suggested that hypoxia plays an important regulatory role of ER homeostasis. We previously identified TMTC3 as an ER stress mediator under nutrient-deficiency condition in esophageal squamous cell carcinoma (ESCC), but the molecular mechanism in hypoxia is still unclear. Methods RNA sequencing data of TMTC3 knockdown cells and TCGA database were analyzed to determine the association of TMTC3 and hypoxia. Moreover, ChIP assay and dual-luciferase reporter assay were performed to detect the interaction of HIF-1alpha and TMTC3 promoter. In vitro and in vivo assays were used to investigate the function of TMTC3 in tumor angiogenesis. The molecular mechanism was determined using co-immunoprecipitation assays, immunofluorescence assays and western blot. The TMTC3 inhibitor was identified by high-throughput screening of FDA-approved drugs. The combination of TMTC3 inhibitor and cisplatin was conducted to confirm the efficiency in vitro and in vivo. Results The expression of TMTC3 was remarkably increased under hypoxia and regulated by HIF-1alpha. Knockdown of TMTC3 inhibited the capability of tumor angiogenesis and ROS production in ESCC. Mechanistically, TMTC3 promoted the production of GTP through interacting with IMPDH2 Bateman domain. The activity of Rho GTPase/STAT3, regulated by cellular GTP levels, decreased in TMTC3 knockdown cells, whereas reversed by IMPDH2 overexpression. Additionally, TMTC3 regulated the expression of VEGFA through Rho GTPase/STAT3 pathway. Allopurinol inhibited the expression of TMTC3 and further reduced the phosphorylation and activation of STAT3 signaling pathway in a dose-dependent manner in ESCC. Additionally, the combination of allopurinol and cisplatin significantly inhibited the cell viability in vitro and tumor growth in vivo, comparing with single drug treatment, respectively. Conclusions Collectively, our study clarified the molecular mechanism of TMTC3 in regulating tumor angiogenesis and highlighted the potential therapeutic combination of TMTC3 inhibitor and cisplatin, which proposed a promising strategy for the treatment of ESCC. Keywords: Hypoxia, Tumor angiogenesis, TMTC3, IMPDH2, Rho GTPase/STAT3
Klotho, as a new anti-aging gene, can shed into circulation and act as a multi-functional humoral factor that influences multiple biological processes. Recently, published studies suggest that klotho ...can also serve as a potential tumor suppressor. The aim of this study is to investigate the effects and possible mechanisms of action of klotho in human lung cancer cell line A549.
In this study, plasmids encoding klotho or klotho specific shRNAs were constructed to overexpress or knockdown klotho in vitro. A549 cells were respectively treated with pCMV6-MYC-KL or klotho specific shRNAs. The MTT assay was used to evaluate the cytotoxic effects of klotho and flow cytometry was utilized to observe and detect the apoptosis of A549 cells induced by klotho. The activation of IGF-1/insulin signal pathways in A549 cells treated by pCMV6-MYC-KL or shRNAs were evaluated by western blotting. The expression levels of bcl-2 and bax transcripts were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
Overexpression of klotho reduced the proliferation of lung cancer A549 cells, whereas klotho silencing in A549 cells enhanced proliferation. Klotho did not show any effects on HEK-293 cells. Klotho overexpression in A549 cells was associated with reduced IGF-1/insulin-induced phosphorylation of IGF-1R (IGF-1 receptor)/IR (insulin receptor) (P < 0.01). Overexpression of klotho can promote the apoptosis of A549 cells (P < 0.01). Overexpression of klotho, a bcl family gene bax, was found up-regulated and bcl-2, an anti-apoptosis gene, was found down-regulated (P < 0.01). In contrast, bax and bcl-2 were found down-regulated (P < 0.05) and up-regulated (P < 0.01), respectively when silencing klotho using shRNAs.
Klotho can inhibit proliferation and increase apoptosis of A549 cells, this may be partly due to the inhibition of IGF-1/insulin pathways and involving regulating the expression of the apoptosis-related genes bax/bcl-2. Thus, klotho can serve as a potential tumor suppressor in A549 cells.
Lung cancer has one of the highest morbidity and mortality rates in the world. Frailty is common in many countries and is a major cause of premature functional decline and premature death in older ...adults, and may affect the treatment and prognosis of lung cancer patients. To investigate the predictive value of frailty at diagnosis on all-cause mortality in lung cancer patients, this study retrospectively collected and analysed clinical information on lung cancer patients from 2015-2018. A total of 1667 patients with primary lung cancer were finally included in this study. The median follow-up time of patients was 650 (493, 1001.5) days. A total of 297(17.8%) patients had FI-LAB(the frailty index based on laboratory test) status of frail at the moment of diagnosis and the all-cause mortality rate for all patients was 61.1% (1018/1667). In a univariate model, we found a higher total all-cause mortality risk in frail patients (frail vs. robust, HR(hazard ratio) = 1.616, 95% CI(confidence interval) = 1.349,1.936), after balancing other variables combined into model 1 to model 6. The results were analyzed visually using ROC(Receiver operating characteristic) curves with nomogram and the AUC values ranged from 0.866-0.874. The final inclusion of age, TNM stage, CCI(Charlson comorbidity index) score, surgery history and chemotherapy into a multifactorial model balanced the predictive power of frailty grading on all-cause mortality. The study showed that for lung cancer patients, the higher the level of frailty at diagnosis, the higher the risk of all-cause mortality. In the context of widespread electronic medical records in hospitals, it is convenient and feasible to use FI-LAB to assess the prognosis of lung cancer patients.
Abrasive flow polishing plays an important part in modern ultra-precision machining. Ultrafine particles suspended in the medium of abrasive flow removes the material in nanoscale. In this paper, ...three-dimensional molecular dynamics (MD) simulations are performed to investigate the effect of impacting direction on abrasive cutting process during abrasive flow polishing. The molecular dynamics simulation software Lammps was used to simulate the cutting of single crystal copper with SiC abrasive grains at different cutting angles (0
o
–45
o
). At a constant friction coefficient, we found a direct relation between cutting angle and cutting force, which ultimately increases the number of dislocation during abrasive flow machining. Our theoretical study reveal that a small cutting angle is beneficial for improving surface quality and reducing internal defects in the workpiece. However, there is no obvious relationship between cutting angle and friction coefficient.
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