The diagnostic significance of the ZNF gene family in pancreatic cancer: a bioinformatics and experimental study.

Background: Pancreatic adenocarcinoma (PAAD) is among the most devastating of all cancers with a poor survival rate. Therefore, we established a zinc finger (ZNF) protein-based prognostic prediction model for PAAD patients. Methods: The RNA-seq data for PAAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differentially expressed ZNF protein genes (DE-ZNFs) in PAAD and normal control tissues were screened using the "lemma" package in R. An optimal risk model and an independent prognostic value were established by univariate and multivariate Cox regression analyses. Survival analyses were performed to assess the prognostic ability of the model. Results: We constructed a ZNF family genes-related risk score model that is based on the 10 DE-ZNFs (ZNF185, PRKCI, RTP4, SERTAD2, DEF8, ZMAT1, SP110, U2AF1L4, CXXC1, and RMND5B). The risk score was found to be a significant independent prognostic factor for PAAD patients. Seven significantly differentially expressed immune cells were identified between the high- and low-risk patients. Then, based on the prognostic genes, we constructed a ceRNA regulatory network that includes 5 prognostic genes, 7 miRNAs and 35 lncRNAs. Expression analysis showed ZNF185, PRKCI and RTP4 were significantly upregulated, while ZMAT1 and CXXC1 were significantly downregulated in the PAAD samples in all TCGA - PAAD, GSE28735 and GSE15471 datasets. Moreover, the upregulation of RTP4, SERTAD2, and SP110 were verified by the cell experiments. Conclusion: We established and validated a novel, Zinc finger protein family - related prognostic risk model for patients with PAAD, that has the potential to inform patient management.

Twenty Years Development of Tibial Cortex Transverse Transport Surgery in PR China.

Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique. Based on the law of tension-stress, its primary function is to rebuild microcirculation which can relieve ischemic symptoms and promote wound healing. It has received more and more scholars' attention and has experienced a series of changes for 20 years since it entered PR China. The mechanisms involved have gradually become clear, such as the reconstruction of the polarization balance of macrophages, the promotion of vascular tissue regeneration, and the mobilization and regulation of bone marrow-derived stem cells. TTT technique is mainly used in the treatment of chronic ischemic diseases of the lower extremities. It has recently been successfully used in the treatment of primary lymphedema of the lower extremities. A series of improvements have been made in the external fixator's style, the size of skin incision and osteotomy, and distraction method. For example, the annular external fixator has been redesigned as a unilateral external fixator, and accordion technology has been introduced. For distraction methods after surgery, there was no uniform standard in the past. The technique can also be used in combination with other treatments to achieve better effects, such as interventional therapy, negative pressure sealed drainage, 3D printing technology, traditional Chinese medicine. Nevertheless, the surgery may bring some complications, such as secondary fracture, nail infection, skin necrosis at the surgical site, etc. Reports of complications and doubts about the technique have made the TTT technique controversial. In 2020, the relevant expert consensus was published with treatment and management principles, which might guide the better application and development of this technique.

Clinical significance of breast cancer susceptibility gene 1 expression in resected non-small cell lung cancer: A meta-analysis.

BACKGROUND: The clinical significance of breast cancer susceptibility gene 1 (BRCA1) in non-small cell lung cancer (NSCLC) patients undergoing surgery remains unclear up to now. AIM: To explore the relation of BRCA1 expression with clinicopathological characteristics and survival in patients with resected NSCLC. METHODS: EMBASE, PubMed, Web of Science, and The Cochrane Library databases were searched to identify the relevant articles. To assess the correlation between the expression of BRCA1 and clinicopathological characteristics and prognosis of patients with resected NSCLC patients, the combined relative risks or hazard ratios (HRs) with their corresponding 95% confidence intervals [CIs] were estimated. RESULTS: Totally, 11 articles involving 1041 patients were included in the meta-analysis. The results indicated that the expression of BRCA1 was significantly correlated with prognosis of resected NSCLC. Positive BRCA1 expression signified a shorter overall survival (HR = 1.60, 95%CI: 1.25-2.05; P < 0.001) and disease-free survival (HR = 1.78, 95%CI: 1.42-2.23; P < 0.001). However, no significant association of BRCA1 expression with any clinicopathological parameters was observed. CONCLUSION: BRCA1 expression indicates a poor prognosis in resected NSCLC patients. BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.

Correction: The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT).

Correction for 'The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT)' by Pengyuan Qi et al., Biomater. Sci., 2020, 8, 2778-2785, DOI: .

Internal Fixation versus Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fractures in the Elderly: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the clinical efficacy of internal fixation versus hemiarthroplasty in the treatment of unstable intertrochanteric fractures in the elderly. METHODS: A search was conducted in PubMed, Web of Science, Embase, and Cochrane Library databases up to April 2020. The present study compared internal fixation and hemiarthroplasty in the treatment of unstable intertrochanteric fractures in the elderly. RevMan5.3 software provided by the International Cochrane Group was used for the meta-analysis. To compare the differences in the operation time, intraoperative bleeding, length of hospital stay, superficial infection, Harris hip score, mortality within 1 year, mortality within 2 years, reoperation, incidence of deep venous thrombosis (DVT), partial weight-bearing time, non-union, and implant-related complications between an internal fixation group and an hemiarthroplasty group. RESULTS: A total of 1300 patients were included in nine studies. The results showed that the operation time (MD = -18.09, 95% CI: -27.85--8.34, P = 0.0003), intraoperative bleeding (MD = -195.31, 95% CI: -244.8--147.74, P < 0.0001), implant-related complications (MD = 3.83, 95% CI: 1.74-8.45, P = 0.0008), and partial weight-bearing time (MD = 17.21, 95% CI: 1.63-32.79, P = 0.03) have statistical significance. However, there is not statistical significance for the Harris hip joint function scale (HHS) (MD = 5.60, 95% CI: -1.13-12.33, P = 0.10), DVT (MD = 1.02, 95% CI: 0.45-2.27, P = 0.97), length of hospital stay (MD = -1.08, 95% CI: -2.82-0.66, P = 0.22), superficial Infection (OR = 0.92, 95% CI: 0.43-1.98, P = 0.89), mortality within 1 year (OR = 0.95, 95% CI: 0.61-1.48, P = 0.81), mortality within 2 years (OR = 0.93, 95% CI: 0.61-1.43, P = 0.75), reoperation (MD = 1.80, 95% CI: 0.64-5.04, P = 0.26), and non-union (OR = 1.20, 95% CI: 0.48-3.03, P = 0.70). The result of the subgroup analysis showed no significant differences between the less than 2 years follow-up and the 2 years or more follow-up group. The only difference was for the Harris hip score: the internal fixation group was superior to the hemiarthroplasty group in the less than 2 years subgroup analysis, while there was no difference between the internal fixation group hemiarthroplasty group in the 2 years or more subgroup analysis. CONCLUSION: Compared with the internal fixation group, those in the hemiarthroplasty group could carry out weight-bearing training early and implant-related complications were reduced, but it requires longer operation time and there is greater intraoperative blood loss. There is no difference in mortality, the incidence of DVT, non-union, HHS, reoperation, length of hospital stay, and superficial infection. Hemiarthroplasty may be a better choice for unstable intertrochanteric fractures in the elderly.

CEACAM1 Inhibited IκB-α/NF-κB Signal Pathway Via Targeting MMP-9/TIMP-1 Axis in Diabetic Atherosclerosis.

Atherosclerosis (AS) is the most common and serious complication in type 2 diabetes mellitus (T2DM). Recent studies have emphasized that inflammation is the main cause of atherosclerosis. Studies have shown that carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) regulates the expression of matrix metallopeptidase 9 (MMP-9) after ischemic stroke to reduce inflammation. The aim of this study was to elucidate potential molecular mechanism of CEACAM1 on the inflammatory response in atherosclerosis. The serum levels of CEACAM1, MMP-9, and tissue inhibitors of metalloproteinase 1 (TIMP-1) in T2DM patients and healthy control was detected. The results showed that the levels of CEACAM1 and TIMP-1 were significantly decreased, and the levels of MMP-9 were significantly higher than those in the control group. Moreover, we also observed the effect of CEACAM1 on atherosclerosis in T2DM rats. Hematoxylin & eosin (HE) staining and oil red staining showed that CEACAM1 recombinant protein reduced intima-media thickness and the area of atherosclerotic plaques. To further explore the molecular mechanism of CEACAM1 regulating MMP-9/TIMP-1, we conducted experiments in rat aorta vascular endothelial cells and rat aorta smooth muscle cells. The result showed that CEACAM1 inhibits inflammatory response via MMP-9/TIMP-1 axis. Taken together, CEACAM1 attenuates diabetic atherosclerosis by inhibition of IκB/NF-κB signal pathway via MMP-9/TIMP-1 axis, which indicate that CEACAM1 is potentially amenable to therapeutic manipulation for clinical application in atherosclerosis in T2DM.

Conservative Treatment or Surgical Treatment: A Case Report and Literature Review of Multiple Fractures of the Lower Extremities in a Child with Insensitivity to Pain.

Congenital pain insensitivity is a rare genetic disease and its clinical manifestations are many. In orthopaedics, common complications of this disease include painless fracture and Charcot's arthropathy. We followed up a case of multiple fractures of the lower extremity in two years, during which time he came to the clinic for five painless fractures of the lower extremity in a total of six parts. A mutation was found on the NTKRI gene (chr1:156813923(hg19), NM_001007792.1: c.1221938C > T). We have developed a combination of surgery and conservative treatments for his condition, focusing on the mental state of the child and considering comprehensive treatment to be the best option for this type of patient. Occult fractures caused by pain insensitivity are often treated only as fractures, however their complications require routine examination and cleaning, suitable protective shoes, splint fixation, stretching, guided exercise planning, and early treatment of injuries. Due to the risk of fracture in the future, it is important that parents pay attention to the behavior and psychology of the child, such as not letting the child participate in exercise with a risk of injury, protective measures while playing, engaging in psychological counseling, and inducing interest in mental activity. These interventions will play a very important role in preventing the recurrence of fracture.

The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT).

The potential role of borophene as a radiosensitizer in PT and BNCT was investigated. Our study focused on two aspects: (1) the synthesis and characterization of borophene nanomaterials; and (2) biocompatibility and dose enhancement. To overcome the limitation of vapor-based technology, we successfully deployed the liquid-phase exfoliation (LPE) method to produce borophene targeting for biomedical applications. Bringing together spatial distribution and dose deposition, the in vitro microdosimetry study was carried out in the presence of borophene. A quantitative study of the dose enhancement ratio (DER) was performed with Monte-Carlo simulation. The synthesized borophene showed good biocompatibility with less than 10% cell death at a concentration of up to 0.2 mg ml-1. The uptake of borophene within individual cells penetrated through cell membranes but outside the nucleus. For proton PT, no significant change in the DER is found. For carbon PT, the DER increases by about 5% as the concentration of 10B reaches 1 mg g-1. For BNCT, a DER of more than 2 can be obtained for a concentration as low as 100 µg g-1. This study lays a foundation for utilizing novel borophene-based nanomaterials as radiosensitizers as well as imaging probes in cancer treatment.

Reversible and Irreversible Inhibition of Cytochrome P450 Enzymes by Methylophiopogonanone A.

Methylophiopogonanone A (MOA), an abundant homoisoflavonoid bearing a methylenedioxyphenyl moiety, is one of the major constituents in the Chinese herb Ophiopogon japonicas This work aims to assess the inhibitory potentials of MOA against cytochrome P450 enzymes and to decipher the molecular mechanisms for P450 inhibition by MOA. The results showed that MOA concentration-dependently inhibited CYP1A, 2C8, 2C9, 2C19, and 3A in human liver microsomes (HLMs) in a reversible way, with IC50 values varying from 1.06 to 3.43 µM. By contrast, MOA time-, concentration-, and NADPH-dependently inhibited CYP2D6 and CYP2E1, along with KI and kinact values of 207 µM and 0.07 minute-1 for CYP2D6, as well as 20.9 µM and 0.03 minutes-1 for CYP2E1. Further investigations demonstrated that a quinone metabolite of MOA could be trapped by glutathione in an HLM incubation system, and CYP2D6, 1A2, and 2E1 were the major contributors to catalyze the metabolic activation of MOA to the corresponding O-quinone intermediate. Additionally, the potential risks of herb-drug interactions triggered by MOA or MOA-related products were also predicted. Collectively, our findings verify that MOA is a reversible inhibitor of CYP1A, 2C8, 2C9, 2C19, and 3A but acts as an inactivator of CYP2D6 and CYP2E1. SIGNIFICANCE STATEMENT: Methylophiopogonanone A (MOA), an abundant homoisoflavonoid isolated from the Chinese herb Ophiopogon japonicas, is a reversible inhibitor of CYP1A, 2C8, 2C9, 2C19, and 3A but acts as an inactivator of CYP2D6 and CYP2E1. Further investigations demonstrated that a quinone metabolite of MOA could be trapped by glutathione in a human liver microsome incubation system, and CYP2D6, 1A2, and 2E1 were the major contributors to catalyze the metabolic activation of MOA to the corresponding O-quinone intermediate.

[Inhibitory effect of flavonoids from Scutellariae Radix on human cytochrome P450 1A].

This study investigated the inhibitory effect of eight natural flavonoids in Chinese herb Scutellariae Radix on huamn cytochrome P450 1 A(CYP1 A), a key cancer chemo-preventive target. In this study, phenacetin was used as a probe substrate for CYP1 A, while human liver microsomes and recombinant human CYP1 A enzymes were used as enzyme sources. Liquid chromatography-tandem mass spectrometry was used to monitor the formation rates of acetaminophen, the O-deethylated metabolite of phenacetin. The dose-dependent inhibition curves were depicted based on the changes of the formation rates of acetaminophen, while the IC_(50) were determined. Inhibition kinetic analyses and docking simulations were used to investigate the inhibition modes and mechanism of wogonin(the most potent CYP1 A inhibitor in this herb), while the inhibition constants(K_i) of wogonin against both CYP1 A1 and CYP1 A2 were determined. Among all tested flavonoids, wogonin, 7-methoxyflavanone and oroxylin A displayed a strong inhibitory effect on CYP1 A(IC_(50)<1 µmol·L~(-1)), baicalein exhibited a moderate inhibitory effect on CYP1 A(IC_(50) between 1-10 µmol·L~(-1)), and baicalin, scutellarein and wogonoside displayed a very weak inhibitory effect on CYP1 A(IC_(50) between 10-25 µmol·L~(-1)), but scutellarin displayed a negligible inhibitory effect on CYP1 A(IC_(50)>100 µmol·L~(-1)). Further investigations demonstrated that wogonin had a weak inhibitory effect on other human CYP enzymes, suggesting that it could be used as a lead compound for the development of specific inhibitors of CYP1 A. Furthermore, the inhibition kinetic analyses clearly demonstrated that wogonin could strongly inhibit phenacetin O-deethylation in both CYP1 A1 and CYP1 A2 in a competitive manner, with K_i values at 0.118 and 0.262 µmol·L~(-1), respectively. Molecular docking demonstrated that wogonin could strongly interact with CYP1 A1 and CYP1 A2 via hydrophobic and π-π interactions, as well as Ser120 and Ser116 in CYP1 A1 via hydrogen-bonding. In conclusion, this study found that some flavonoids in Scutellariae Radix displayed a strong inhibitory effect on CYP1 A, while wogonin is the most potent CYP1 A inhibitor with a relatively high selectivity towards CYP1 A over other human CYPs.

Occurrence and Characterization Microstructure of Iron Impurities in Halloysite.

The quality of the clays and over all halloysite are mostly associated with minor amounts of ferruginous impurities content, since this element gives an undesirable reddish color to the halloysite mineral. Hence, finding out the modes of occurrence of iron in halloysite is of prime importance in the value addition and optimum utilization of halloysite. In order to analyze the occurrence of iron impurities in halloysite, Transmission Electron Microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were combined with wet chemical analysis methods to study the low-grade halloysite. The results indicated that the mineral phases of iron impurities in the concentrates are mainly composed of amounts of magnetite, goethite and hematite. Two types of occurrences for iron impurities have been found. One is single crystalline mineral consist in the halloysite, which contains three different phases of Goethite FeO(OH) (44.75%), Magnetite Fe3O4 (27.43%) and Hematite Fe2O3 (31.96%). The other is amorphous Fe-Al-Si glial materials. This study is of significance in the theoretical research on the halloysite mineralogy and in the developmental practice of halloysite in coal measures.

[Influence of perioperative hypertension on postoperative cardiovascular complications in chest cancer patients].

BACKGROUND & OBJECTIVE: The incidence of perioperative hypertension is increasing in recent decades. Hypertension increases the risk of anaesthesia and surgical operation, and also affects the prognosis of patients apparently. This study was to investigate the influence of perioperative hypertension on postoperative cardiovascular complications in chest cancer patients. METHODS: Clinical data of 464 chest cancer patients, received thoracotomy in Cancer Center of Sun Yat-sen University between Aug. 2005 and Dec. 2005, were analyzed. Of the 464 patients, 152 had perioperative hypertension, and 312 did not. Postoperative cardiovascular complications of the 2 groups were compared with Chi-square test. RESULTS: The 2 groups had no significant differences in age, sex, tumor type, preoperative chronic disease, and preoperative cardiovascular disease (P>0.05). Postoperative cardiovascular complications were developed in 54 patients in perioperative hypertension group (including 41 cases of arrhythmia, 8 cases of hypotension, 3 cases of heart failure, and 2 cases of cardiac ischemia) and in 53 patients in perioperative non-hypertension group (including 41 cases of arrhythmia, 9 cases of hypotension, 2 cases of heart failure, and 1 case of cardiac ischemia). The occurrence rate of postoperative cardiovascular complications was significantly higher in perioperative hypertension group than in perioperative non-hypertension group (35.53% vs. 16.99%, P<0.05). CONCLUSION: Perioperative hypertension obviously increases the incidence of postoperative cardiovascular complications in chest cancer patients after thoracotomy.

Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15).

PURPOSE: This multi-institutional Phase III randomized study compared 10 Gy single-fraction radiotherapy (RT) with 20 Gy in five fractions in the palliation of thoracic symptoms from lung cancer. METHODS AND MATERIALS: The primary end point was palliation of thoracic symptoms at 1 month after RT, evaluated by a patient-completed daily diary card. Secondary end points included quality of life, toxicity, and survival. RESULTS: Most (69%) of 230 patients randomized had locally advanced disease unsuitable for curative treatment. The treatment arms were well balanced with respect to the known prognostic factors. At 1 month after RT, no difference was found in symptom control between the two arms, as judged by the daily diary scores. The changes in the scores on the Lung Cancer Symptom Scale indicated that the fractionated RT (five fractions) group had greater improvement in symptoms related to lung cancer (p = 0.009), pain (p = 0.0008), ability to carry out normal activities (p = 0.037), and better global quality of life (p = 0.039). The European Organization for Research and Treatment of Cancer QLQ-C30 scores showed that patients receiving five fractions had a greater improvement in scores with respect to pain (p = 0.04). No significant difference was found in treatment-related toxicity. Patients who received five fractions survived on average 2 months longer (p = 0.0305) than patients who received one fraction. CONCLUSION: Although the two treatment strategies provided a similar degree of palliation of thoracic symptoms, the difference in survival between the two study arms was of a clinically relevant magnitude.