SARS-Cov-2 Spike-S1 Antigen Test Strip with High Sensitivity Endowed by High-Affinity Antibodies and Brightly Fluorescent QDs/Silica Nanospheres.

The extensive research into developing novel strategies for detecting respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens, especially the sensitive point-of-care testing method, is still urgently needed to reach rapid screening of viral infections. Herein, a new lateral flow immunoassay (LFIA) platform was reported for the detection of SARS-CoV-2 spike-S1 protein antigens, in which four sensitive and specific SARS-CoV-2 mouse monoclonal antibodies (MmAbs) were tailored by using quantum dot (QD)-loaded dendritic mesoporous silica nanoparticles modified further for achieving the -COOH group surface coating (named Q/S-COOH nanospheres). Importantly, compact QD adsorption was achieved in mesoporous channels of silica nanoparticles on account of highly accessible central-radial pores and electrostatic interactions, leading to significant signal amplification. As such, a limit of detection for SARS-CoV-2 spike-S1 testing was found to be 0.03 ng/mL, which is lower compared with those of AuNPs-LFIA (traditional colloidal gold nanoparticles, Au NPs) and enzyme-linked immunosorbent assay methods. These results show that optimizing the affinity of antibody and the intensity of fluorescent nanospheres simultaneously is of great significance to improve the sensitivity of LFIA.

Therapeutic effect of low frequency electric pulse therapy on cisplatin-based chemotherapy-induced nausea and vomiting in patients with lung adenocarcinoma: A prospective controlled study.

To explore the efficacy of low-frequency electric pulse therapy (LFEPT) combined with 2 antiemetics in the prevention and treatment of cisplatin-based chemotherapy-induced nausea and vomiting (CINV) in patients with lung adenocarcinoma. A total of 82 patients with lung adenocarcinoma who received cisplatin-based chemotherapy were randomly divided into the experimental group (n=41) and control group (n=41) by random numerical table method. The experimental group was treated with LFEPT combined with 2 antiemetic drugs (tropisetron hydrochloride and dexamethasone hydrochloride), while the control group was treated with the same 2 antiemetic drugs. Revised index of nausea and vomiting and retching (R-INVR) and Functional Living Index-Emesis (FLIE) scale were used to quantitatively evaluate the symptoms of nausea and vomiting after chemotherapy, and the effect of LFEPT in the prevention and treatment of CINV was observed. The baseline characteristics had no statistical difference between the 2 groups. The degree of nausea reaction, vomiting, and dry retching were similar in 2 groups on the first day after chemotherapy. However, the degree of nausea reaction, vomiting, and dry retching were significantly improved in the experimental group than that of the control group on 2 to 5 days with all P<.05. The score of FLIE had no difference between the 2 groups on the first day after chemotherapy (84.05 vs 82.69, P=.30), and the score was significantly higher in experiment group on day 6 compared with the control group (103.71 vs 89.38, P=.02). The side effects had no difference between the 2 groups. The LFEPT can significantly ameliorate CINV in patients with lung adenocarcinoma, which is worthy of clinical application.

Safety and Immunogenicity of a Recombinant Adenovirus Type-5-Vectored Coronavirus Disease 2019 (COVID-19) Vaccine With a Homologous Prime-Boost Regimen in Healthy Participants Aged ≥6 Years: A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Trial.

BACKGROUND: We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)-vectored coronavirus disease 2019 (COVID-19) vaccine with homologous prime-boost regimens in healthy participants aged ≥6 years. METHODS: In this randomized, double-blind, placebo-controlled trial, participants received vaccine or placebo 56 days apart. Enzyme-linked immunosorbent assay (ELISA) antibodies to the receptor binding domain (RBD) and pseudovirus neutralizing antibodies were detected. Adverse events were monitored for 28 days following each vaccination. RESULTS: A total of 430 participants were enrolled in the study, with 30 participants aged 18-55 years (MID cohort), 250 aged ≥56 years (OLD cohort), and 150 aged 6-17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies that decreased with increasing age, with geometric mean titers (GMTs) of 1037.5 in the MIN cohort, 647.2 in the MID cohort, and 338.0 in the OLD cohort receiving 5 × 1010 viral particles on day 28 following boost vaccination. Pseudovirus neutralizing antibodies showed a similar pattern, with GMTs of 168.0 in the MIN cohort, 76.8 in the MID cohort, and 79.7 in the OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by 2 doses in adults, with GMTs of 1091.6 and 96.6 for ELISA antibody and neutralizing antibody, respectively. Homologous prime-boost vaccination was safe and tolerable. CONCLUSIONS: Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6-17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine.Ad5-vectored COVID-19 vaccine with a single dose was safe and tolerated, and induced robust immune responses in children and adolescents aged 6-17 years. The boosting effect on immune responses of the homologous prime-boost regime given 56 days apart was limited. CLINICAL TRIALS REGISTRATION: NCT04566770.

An update on current EPAs in graduate medical education: A scoping review.

The purpose of this scoping review is to update the recent progress of EPAs research in GME, focusing on the topical concern of EPAs effectiveness, and to provide a reference for medical researchers in countries/regions interested in introducing EPAs. Guided by Arksey and O'Malley's framework regarding scoping reviews, the researchers, in January 2021, conducted a search in five databases to ensure the comprehensiveness of the literature. After the predetermined process, 29 articles in total were included in this study. The most common areas for the implementation and evaluation of EPAs were Surgery (n = 7,24.1%), Pediatric (n = 5,17.2%) and Internal medicine (n = 4,13.8%), a result that shows a relatively large change in the research trend of EPAs in the last two years. Prior to 2018, EPAs research focused on internal medicine, psychiatry, family medicine, and primary care. The articles in the category of EPAs implementation and evaluation had four main themes: (1) validation of EPAs (n = 16,55.2%); (2) describing the experience of implementing EPAs (n = 11,37.9%); (3) examining the factors and barriers that influence the implementation and evaluation of EPAs (n = 6,20.6%); and (4) researching the experiences of faculty, interns, and other relevant personnel in using EPAs. Training programs were the most common EPAs implementation setting (n = 26,89.6%); direct observation and evaluation (n = 12,41.4%), and evaluation by scoring reports (n = 5,17.2%) were the two most common means of assessing physicians' EPA levels; 19 papers (65.5%) used faculty evaluation, and nine of these papers also used self-assessment (31.0%); the most frequently used tools in the evaluation of EPAs were mainly researcher-made instruments (n = 37.9%), assessment form (n = 7,24.1%), and mobile application (n = 6,20.7%). Although EPAs occupy an increasingly important place in international medical education, this study concludes that the implementation and diffusion of EPAs on a larger scale is still difficult.

Design and evaluation of a simulated wound management course for postgraduate year one surgery residents.

BACKGROUND: It is vital to cover wound management knowledge and operations in the early stages of resident training. With this in mind, a simulated wound management course for postgraduate year one surgery residents (PGY1s) was designed and its effectiveness was evaluated. METHODS: A retrospective quasi-experimental method was used. PGY1s in 2014 constituted the control group, and PGY1s in 2015 and 2016 constituted the intervention group. The course given to the control group comprised didactic teaching followed by deliberate practice plus immediate personalized feedback. The newly designed course given to the intervention group was reconstructed and disassembled into four components according to the simulation-based mastery learning model, which were baseline test, interactive learning, basic skills practice, and reflective learning. The same performance assessments were used in the control and intervention group, including process measurement and outcome measurement. RESULTS: The process measurement showed that the intervention group's scores were significantly higher in the "dissociation of subcutaneous tissue" and "quality of suturing and knots". The outcome measurement showed that the accuracy of debridement was greatly improved and both key and total suture numbers were significantly higher in the intervention group. CONCLUSIONS: Simulation-based mastery learning was incorporated into our proposed course framework, promoting the learning outcome of PGY1s. It has the potential to be adapted for other surgical training sites for residents in China.

Long non-coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review).

Osteogenic differentiation originating from mesenchymal stem cells (MSCs) requires tight co-ordination of transcriptional factors, signaling pathways and biomechanical cues. Dysregulation of such reciprocal networks may influence the proliferation and apoptosis of MSCs and osteoblasts, thereby impairing bone metabolism and homeostasis. An increasing number of studies have shown that long non-coding (lnc)RNAs are involved in osteogenic differentiation and thus serve an important role in the initiation, development, and progression of bone diseases such as tumors, osteoarthritis and osteoporosis. It has been reported that the lncRNA, maternally expressed gene 3 (MEG3), regulates osteogenic differentiation of multiple MSCs and also acts as a critical mediator in the development of bone formation and associated diseases. In the present review, the proposed mechanisms underlying the roles of MEG3 in osteogenic differentiation and its potential effects on bone diseases are discussed. These discussions may help elucidate the roles of MEG3 in osteogenic differentiation and highlight potential biomarkers and therapeutic targets for the treatment of bone diseases.

Copper sulfate-induced endoplasmic reticulum stress promotes hepatic apoptosis by activating CHOP, JNK and caspase-12 signaling pathways.

Copper (Cu), a transition metal, is an essential trace element in human and animal nutrition at low concentration, but Cu has toxic effects on tissues and organs at high concentration. Endoplasmic reticulum (ER) is a toxicological target in Cu poison. Thus far, no studies have focused on the relationship among copper, endoplasmic reticulum (ER) stress and apoptosis in animal and human livers. In the present study, mice treated with copper sulfate (CuSO4) were used to assess the impacts of copper on ER stress and hepatic apoptosis. A total of 240 mice were orally administered with 0 (control), 10, 20 and 40 mg/kg of CuSO4 for 42 days. The results indicated that CuSO4 at 10 mg/kg markedly induced hepatocyte apoptosis and ER stress. In addition, ER stress was characterized by the increased mRNA and protein levels of glucose-regulated protein 78 (GRP78) and 94 (GRP94). Furthermore, ER stress-triggered 3 apoptotic pathways were also activated by the increased intracellular calcium and up-regulated expression levels of genes involved in growth arrest- and DNA damage-inducible gene 153 (Gadd153/CHOP), c-Jun N-terminal kinase (JNK) and cysteine aspartate-specific protease 12 (caspase-12) signaling pathways in CuSO4-treated mice. In conclusion, CuSO4-induced ER stress can promote hepatic apoptosis in mice by activating CHOP, JNK and caspase-12 signaling pathways.

Nickel Carcinogenesis Mechanism: DNA Damage.

Nickel (Ni) is known to be a major carcinogenic heavy metal. Occupational and environmental exposure to Ni has been implicated in human lung and nasal cancers. Currently, the molecular mechanisms of Ni carcinogenicity remain unclear, but studies have shown that Ni-caused DNA damage is an important carcinogenic mechanism. Therefore, we conducted a literature search of DNA damage associated with Ni exposure and summarized known Ni-caused DNA damage effects. In vitro and vivo studies demonstrated that Ni can induce DNA damage through direct DNA binding and reactive oxygen species (ROS) stimulation. Ni can also repress the DNA damage repair systems, including direct reversal, nucleotide repair (NER), base excision repair (BER), mismatch repair (MMR), homologous-recombination repair (HR), and nonhomologous end-joining (NHEJ) repair pathways. The repression of DNA repair is through direct enzyme inhibition and the downregulation of DNA repair molecule expression. Up to now, the exact mechanisms of DNA damage caused by Ni and Ni compounds remain unclear. Revealing the mechanisms of DNA damage from Ni exposure may contribute to the development of preventive strategies in Ni carcinogenicity.

Oxidative Stability of Stripped Soybean Oil during Accelerated Oxidation: Impact of Monoglyceride and Triglyceride-Structured Lipids Using DHA as sn-2 Acyl-Site Donors.

The current work aimed to clarify the effects of four structured lipids, including monoglycerides with docosahexaenoic acid (2D-MAG), diacylglycerols with caprylic acid (1,3C-DAG), triglyceride with caprylic acid at sn-1,3 and DHA at sn-2 position (1,3C-2D-TAG) and caprylic triglyceride on the oxidative stability of stripped soybean oil (SSO). The results revealed that compared to the blank group of SSO, the oxidation induction period of the sample with 2 wt% 2D-MAG and that with 1,3C-DAG were delayed by 2-3 days under accelerated oxidation conditions (50 °C), indicating that 2D-MAG and 1,3C-DAG prolonged the oxidation induction period of SSO. However, the inhibitory effect of α-tocopherol on SSO oxidation was reduced by 2D-MAG after addition of 2D-MAG to SSO containing α-tocopherol. 2D-MAG exhibited different antioxidative/pro-oxidative effects in the added/non-added antioxidants system. Compared to caprylic triglyceride, DHA at the sn-2 acyl site induced oxidation of structured lipids, thus further promoting the oxidation of SSO. The antioxidant was able to inhibit not only the oxidation of DHA in the SSO, but also the transesterification of sn-2 DHA to sn-1/sn-3 DHA in the structured lipid.

Analysis of volatile compounds in pork from four different pig breeds using headspace solid-phase micro-extraction/gas chromatography-mass spectrometry.

PURPOSE: The volatile compounds that contribute to the flavor of pork are unknown. Therefore, the present study aimed to determine the differences in volatile compounds from pork meats of four different pig breeds using headspace solid-phase micro-extraction (HS-SPME)/gas chromatography-mass spectrometry (GC-MS). METHODS: Piglets from four breeds (8/breed) (crossbred Ziwuling Sus scrofa [SUS] and purebreds Bamei pig [BAM], American Yorkshire pig [YOK], and Hezuo pig [HZP]) were selected. Characteristics of meat were measured. HS-SPME/GC-MS were used to analyze the volatile compounds of the meats. RESULTS: The tenderness, taste, succulence, and broth flavor of the BAM and HZP were good. One hundred and eight volatile compounds with known molecular formulas were identified in BAM, 106 in SUS, 98 in YOK, and 98 in HZP. Sixty-four common volatile compounds were found in all four breeds. The highest relative amount of volatile compounds was found in the BAM. The compounds which may contribute to the flavor of pork were 3-methyl-1-butanol, 1-nonanal, octanal, hexanal, 2-pentyl-furan, 1-penten-3-one, N-morpholinomethyl-isopropyl-sulfide, methyl butyrate, and (E,E)-2, 4-decadienal. CONCLUSION: The volatile compounds in pork belong to several classes, and the highest relative amount of volatile compounds was found in BAM.

Manipulate Micrometer Surface and Nanometer Bulk Phase Separation Structures in the Active Layer of Organic Solar Cells via Synergy of Ultrasonic and High-Pressure Gas Spraying.

For organic solar cells, the vertical and lateral micro-/nanometer-scale structure in the active layer largely determines the device performance. In this work, the surface and bulk domain size of the photoactive layer are successfully manipulated with a facile two-step spraying method, that is, an ultrathin active layer by high-pressure spraying is deliberately stacked on top of the thick active layer by ultrasonic spraying. Thus, the morphology is effectively optimized with the comprehensive study of optical and electrical characteristics, such as photon absorption, exciton dissociation efficiency, and bimolecular recombination. Moreover, the novel method can be used not only in the fullerene system but also in the nonfullerene system, demonstrating the remarkable universality through this synergy method. This work provides an easy and reliable strategy to improve photovoltaic device performance in the industrial large-area spray-coating process.

Involvement of H19/miR-326 axis in hepatocellular carcinoma development through modulating TWIST1.

Overexpression of long noncoding RNA (lncRNA) H19 has been observed in various cancers, which indicates that H19 exert important roles in the progression of carcinogenesis. MiR-326 has been reported to play tumor suppressive roles in multiple tumors. Recently, the competing endogenous RNA (ceRNA) hypothesis has implied that lncRNAs might function as molecular sponges for microRNAs in various cancers. However, the roles of H19/miR-326 in human hepatocellular carcinoma (HCC) still remain unclear. The aim of our study was to determine H19/miR-326 expression in HCC cells and investigate their roles in HCC development. We found that H19 was significantly elevated and miR-326 was decreased in HCC cells including Hep3B, HepG2, MHCC-97L, SK-hep1, Hun7, SMCC-7721 compared with LO2 cells, respectively. In the subsequent experiments, we observed that inhibition of H19 can repress HCC cell growth, migration, and invasion in vitro. H19 downregulation can increase miR-326 expression in HCC cells. Meanwhile, miR-326 mimics can also inhibit HCC progression, whereas miR-326 inhibitors exhibited a reverse phenomenon by modulating H19 expression. In addition, a negative association between H19 and miR-326 was predicted and confirmed. Furthermore, the transcription factor TWIST1 has been recognized as a significant regulator in tumor progression. Here, by performing bioinformatics analysis, TWIST1 was identified as a downstream target of miR-326. The findings of our study implied that lncRNA H19 can serve as a ceRNA to sponge miR-326 and modulate TWIST1 levels in HCC pathogenesis. Taken these together, these findings indicated that H19/miR-326/TWIST1 axis was involved in HCC development and can indicate a novel HCC target.

Evaluating risk factors of radiation pneumonitis after stereotactic body radiation therapy in lung tumor: Meta-analysis of 9 observational studies.

BACKGROUND: In this study, we assessed the association of SBRT (stereotactic body radiotherapy) dose and volume with radiation pneumonitis (RP) risk in lung tumor. METHODS: Relevant articles were identified up to April 2018, using following databases; Medline, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The pooled OR (odds ratio) with 95% CI (confidence interval) data [mean ± SD (standard deviation)] obtained from different studies was analyzed by statistical analysis using a fixed-effects model or a random-effects model when appropriate. RESULTS: The analysis was based on nine observational studies, which were identified based on the study selection criteria. Between RP and non-RP patients, no difference was observed based on age, but significant differences were observed based on planning target volume (PTV), mean ipsilateral lung dose (MLD), total MLD, and V5, V10, V20 and V40 (the percentage of lung volume exceeding 5, 10, 20 and 40 Gy). In addition, PTV >145 cm3, total MLD ≥4.7 Gy, V5 ≥26.8%, V10 >12% and V20 ≥5.8 were associated with RP risk. Overall, the grade assessments of V5 and V20 revealed moderate quality evidence. CONCLUSION: The present study indicated V5 and V20 as major risk factors for RP after SBRT treatment in lung tumor. In addition, it was observed that lung DVH (Dose Volume Histogram) patterns should be assessed more carefully, while predicting RP incidence after SBRT.

miR-140-5p-mediated regulation of the proliferation and differentiation of human dental pulp stem cells occurs through the lipopolysaccharide/toll-like receptor 4 signaling pathway.

Human dental pulp stem cells (DPSCs) are oral mesenchymal stem cells with potential to differentiate into various cell types. Recent studies of DPSCs have focused on microRNAs (miRNAs), a class of small noncoding RNAs that play crucial roles in regulating DPSC phenotypes. In the current study, the expression of miR-140-5p was significantly decreased during lipopolysaccharide (LPS)-mediated differentiation of DPSCs in vitro. Overexpression of miR-140-5p enhanced proliferation of DPSCs and inhibited DPSC differentiation, whereas suppression of miR-140-5p produced the opposite effect. Moreover, the expression of toll-like receptor 4 (TLR-4), a critical regulator of DPSCs, was negatively correlated with the levels of miR-140-5p. A luciferase reporter analysis confirmed that miR-140-5p could regulate TLR-4 by directly binding to the 3'-untranslated region (3'-UTR) of the TLR4 mRNA. Additionally, we suppressed TLR-4 expression by treating cells with a TLR-4 inhibitor, CLI-095, and demonstrated that the effect of the miR-140-5p inhibitor on DPSC proliferation and differentiation could be partially reversed by blocking TLR-4. Taken together, our data suggest that miR-140-5p is a novel miRNA that regulates DPSC proliferation and differentiation.

Jian Pi Li Qi Decoction Alleviated Postembolization Syndrome Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of Jian Pi Li Qi (JPLQ) decoction in improving quality of life of patients with hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE). METHODS: A randomized, double-blind, placebo-controlled trial was conducted. A total of 150 patients with HCC were randomly assigned into 3 groups. Groups were designed as follows: neither herbal medicine nor placebo administration (group A), placebo treatment (group B), and JPLQ decoction treatment (group C). The measurement methods of the observed outcomes include MD Anderson Symptom Inventory-Gastrointestinal module, armpit temperature, and laboratory tests. RESULTS: Among the 140 patients studied, the 12 symptoms rated as most severe, which characterize postembolization syndrome (PES), were fever, pain, fatigue, nausea, disturbed sleep, distress, lack of appetite, drowsiness, dry mouth, vomiting, constipation, and feeling bloated. All these increased significantly (all P < .05) after TACE; 7 symptoms, including fever, pain, fatigue, lack of appetite, drowsiness, dry mouth, and constipation (all P < .05), were found to be relieved significantly by JPLQ. JPLQ also improved the liver function damage caused by TACE. CONCLUSION: JPLQ decoction may be an effective modality to relieve PES and protect liver function in patients with HCC after TACE.

Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.

AIM: To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment. MATERIALS AND METHODS: A total of 883 patients with stage II-III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS), local recurrence (LR) and distant metastases (DM). Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients. RESULTS: The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73]) and 0.68 (95% CI = [0.64, 0.72]) on the original dataset, and 0.76 (95% CI = [0.67, 0.86]) and 0.73 (95% CI = [0.63, 0.83]) on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category. CONCLUSIONS: The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.

Is adjuvant radiotherapy warranted in resected pT1-2 node-positive rectal cancer?

BACKGROUND: Stage T1-2 rectal cancers are unlikely to have lymph node metastases and neoadjuvant therapy is not routinely administered. Postoperative management is controversial if lymph node metastases are detected in the resected specimen. We studied the outcomes of patients with pT1-2 node-positive rectal cancer in order to determine whether adjuvant radiotherapy was beneficial. METHODS: We conducted a retrospective analysis of 284 patients with pathological T1-2 node-positive rectal cancer from a single institution. Outcomes, including local recurrence (LR), distant metastasis (DM), disease free survival (DFS) and overall survival (OS), were studied in patients with detailed TN staging and different adjuvant treatment modalities. RESULTS: The overall 5-year LR, DM, DFS and OS rates for all patients were 12.5%, 32.9%, 36.4% and 76.8%, respectively. Local control was inferior among patients who received no adjuvant therapy. Patients could be divided into three risk subsets: Low-risk, T1N1; Intermediate-risk, T2N1 and T1N2; and High-risk, T2N2. The 5-year LR rates were 5.3%, 9.8% and 26.4%, respectively (p = 0.005). In High-risk patients, addition of radiotherapy achieved a 5-year LR rate of 9.1%, compared 34.8% without radiotherapy. CONCLUSIONS: In our study, we provide the detailed outcomes and preliminary survival analysis in a relatively infrequent subset of rectal cancer. Three risk subsets could be identified based on local control for pT1-2 node positive rectal cancer. Postoperative treatment needs to be individualized for patients with pT1-2 node-positive rectal cancer.

Different responses to mechanical injury in neonatal and adult ovine articular cartilage.

BACKGROUND: Articular cartilage injury remains a major challenge in orthopedic surgery. This study aimed to identify differences in gene expression and molecular responses between neonatal and adult articular cartilage during the healing of an injury. METHODS: An established in vitro model was used to compare the transcriptional response to cartilage injury in neonatal and adult sheep by microarray analysis of gene expression. Total RNA was isolated from tissue samples, linearly amplified, and 15,208 ovine probes were applied to cDNA microarray. Validation for selected genes was obtained by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We found 1,075 (11.6%) differentially expressed probe sets in adult injured cartilage relative to normal cartilage. A total of 1,016 (11.0%) probe sets were differentially expressed in neonatal injured cartilage relative to normal cartilage. A total of 1,492 (16.1%) probe sets were differentially expressed in adult normal cartilage relative to neonatal normal cartilage. A total of 1,411 (15.3%) probe sets were differentially expressed in adult injured cartilage relative to neonatal injured cartilage. Significant functional clusters included genes associated with wound healing, articular protection, inflammation, and energy metabolism. Selected genes (PPARG, LDH, TOM, HIF1A, SMAD7, and NF-κB) were also found and validated by RT-qPCR. CONCLUSIONS: There are significant differences in gene expression between neonatal and adult ovine articular cartilage following acute injury. They are partly due to intrinsic differences in the process of development, and partly to different biological responses to mechanical trauma between neonatal and adult articular cartilage.

Tolerability and outcomes of radiotherapy or chemoradiotherapy for rectal cancer in elderly patients aged 70 years and older.

PURPOSE: To assess the safety and outcomes of radiotherapy (RT) or chemoradiotherapy (CRT) in elderly patients (≥70) with rectal cancer. METHODS: Elderly patients aged 70 and older with rectal cancer, who were treated with RT or CRT at a single institution, were retrospectively analyzed. Performance status (KPS and ECOG score) and comorbidity (Charlson comorbidity index) were calculated, and their correlation with treatment toxicity and overall survival were studied. Risk factors for overall survival were investigated using univariate and multivariate survival analysis. RESULTS: A total of 126 patients with locally advanced disease, local recurrence or synchronous metastasis were included, with a 3-year OS rate of 48.1%. Scheduled dosage of radiation was delivered to 69% of patients. Grade 3 toxicities occurred more often in patients treated with CRT versus RT. The occurrence of grade 3 toxicities was not related to KPS score, ECOG score, number of comorbidities, and Charlson score. Multivariate analysis found that only age and Charlson score were independent prognostic factors for predicting patients' 3-year OS. The 3-year OS rate was significantly higher in patients with Charlson score <4 vs Charlson score ≥4 (71.1% vs. 26.4%, P=0.0003). CONCLUSIONS: Although toxicities may be significant, elderly patients with rectal cancer of varied stages can be safely treated with RT or CRT with careful monitoring and frequent modification of treatment. Except for patients' age, Charlson comorbidity index may be helpful in assessing patients' outcomes in elderly patients with rectal cancer.

Rapamycin increases pCREB, Bcl-2, and VEGF-A through ERK under normoxia.

Rapamycin may serve as a new anti-osteosarcoma (OSA) agent due to its ability to inhibit the metastatic behavior of OSA. However, only limited benefit is observed in rodent studies and clinical trials using rapamycin as a single agent in the treatment of OSA. The target of rapamycin, mammalian target of rapamycin has multiple biological functions and may be linked with the kinases that mediate the phosphorylation of cyclic AMP-responsive element-binding (CREB) protein, an import factor in tumor progression. By employing an OSA cell line MG-63, we investigated how rapamycin regulates the phosphorylation of CREB (pCREB) at Ser133 and the expressions of two putative CREB targets, B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor-A (VEGF-A). Under normoxia, we found that rapamycin (100 nM) induced an increase of pCREB that was prevented by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 or cAMP-dependent protein kinase (PKA) inhibitor H89. However, H89 enhanced Akt phosphorylation and did not decrease the cell viability upon rapamycin treatment. In contrast, U0126 did not enhance Akt phosphorylation and decreased the cell viability upon rapamycin treatment. Moreover, U0126 prevented the rapamycin-induced increase of Bcl-2 and VEGF-A levels. Under hypoxia, rapamycin effectively prevented the hypoxia-induced increase of pCREB, Bcl-2, and VEGF-A. Our study demonstrated that rapamycin might be less effective in treating OSA cells under normoxia and provided the rationale for a combination of rapamycin and MEK/ERK inhibitor in the treatment of OSA.