The prognostic value of pretreatment 18F-FDG PET-CT parameters with peripheral blood markers in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.

[Characteristics, Sources Apportionment, and Health Risks of PM2.5-bound PAHs and Their Derivatives Before and After Heating in Zibo City].

Atmospheric polycyclic aromatic hydrocarbons (PAHs) and their derivatives are a global problem that influences the environment and threatens human health. To investigate the characteristics, sources, and health risk assessment of PM2.5-bound PAHs and their derivatives, PM2.5 were collected at an urban site in Zibo from November 5 to December 26, 2020, and the concentrations of 16 conventional PAHs, nine NPAHs, and five OPAHs in PM2.5 were analyzed using gas chromatography-mass spectrometry. Source apportionment of PAHs and their derivatives was conducted using diagnostic ratios and a PMF model, and the health risks of PAHs and their derivatives to adult men and women were evaluated using the source-dependent incremental lifetime cancer risk (ILCR) model. The results showed that the average concentrations of ∑16pPAHs, ∑9NPAHs, and ∑5OPAHs in PM2.5 of Zibo City during the sampling period were (41.61 ± 13.40), (6.38 ± 5.70), and (53.20 ± 53.47) ng·m-3, respectively. The concentrations of the three PAHs increased significantly after heating, which were 1.31, 2.04, and 5.24 times larger than those before heating. During the sampling period, Chr, BaP, and BaA were the dominant components of pPAHs; 9N-Ant and 2N-Flt + 3N-Flt were the dominant components of NPAHs; and ATQ and BZO were the dominant components of OPAHs. Source apportionment results showed that motor vehicles were the main source of PAHs and their derivatives in PM2.5 before heating, whereas after heating, the main sources were the mixed source of coal and biomass combustion and secondary formation. The total BaP equivalent (TEQ) was 14.5 ng·m-3 during the sampling period, and the TEQ increased significantly after heating, which was approximately 1.2 times of that before heating. Assisted by the individual PAH source apportionment results, the ILCR of PM2.5-boundPAHs and NPAHs in Zibo City had a certain potential carcinogenic risk for adult males (1.06 × 10-5) and females (9.32 × 10-6). Among them, the health risks of PAHs from gasoline vehicles, diesel vehicles, and coal/biomass combustion were significantly higher than those from other emission sources.

Isolation and antioxidant activity of peptides from Chinese hairy tofu.

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

The clinical effect evaluation of multidisciplinary collaborative team combined with palliative care model in patients with terminal cancer: a randomised controlled study.

OBJECTIVE: To evaluate the clinical effect of a multidisciplinary collaboration team combined with a palliative care model in patients with terminal cancer. METHOD: A total of 84 patients diagnosed with terminal cancer in our hospital were included and randomly divided into an intervention group and a control group, with 42 cases in each group. Patients in the intervention group were treated by a multidisciplinary collaborative team combined with the palliative care model, and patients in the control group were treated by routine nursing intervention. The Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS) were used to evaluate negative emotions and anxiety and depression of patients before and after intervention. The Quality of Life Scale (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30) and Social Support Scale (SSRS) were used to evaluate the quality of life and social support of patients. This study has been registered in 13/01/2023 (ClinicalTrials.gov Identifier: NCT05683236). RESULT: The general data of the two groups were comparable. After intervention, the SAS (43.7 ± 7.4 vs. 54.2 ± 9.3) and SDS scores (38.4 ± 6.5 vs. 53.1 ± 8.4) of the intervention group were significantly lower than those of the control group. The total SSRS score, subjective support score, objective support score and utilisation of support of the intervention group were significantly higher than those of the control group (P < 0.05). The overall quality of life score of the intervention group was higher than that of the control group, and the difference was statistically significant (79.5 ± 4.5 vs. 73.2 ± 3.6, P < 0.05). The scores of each functional scale were significantly higher than those of the control group (P < 0.05). CONCLUSION: Compared with conventional nursing, the application of the multidisciplinary collaborative team combined with tranquilisation therapy in patients with terminal cancer can significantly reduce the anxiety and depression of patients, enable patients to obtain comprehensive social support, and effectively improve the quality of life of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05683236, 13/01/2023, Retrospectively registered.

Knee Scores of Patients with Non-Lateral Compartmental Knee Osteoarthritis Undergoing Mobile, Fixed-Bearing Unicompartmental Knee and Total Knee Arthroplasties: A Randomized Controlled Trial.

OBJECTIVE: To evaluate knee scores and clinical efficacies of patients with non-lateral unicompartmental knee osteoarthritis (OA) who randomly underwent mobile-bearing (MB) unicompartmental knee arthroplasty (UKA), fixed-bearing (FB) UKA, and total knee arthroplasty (TKA). METHODS: From September 2015 to February 2017, a prospective, randomized, parallel, single-center trial of 180 patients (78 males and 102 females; 63.3 ± 6.9 years) with non-lateral compartmental knee OA was performed in the first author-affiliated hospital. The patients were randomly divided into three groups (each group included 60 patients) and received medial cemented Oxford phase 3 MB UKA, medial cemented Link FB UKA, or cemented DePuy Sigma PFC TKA, respectively. A similar perioperative management and fast-track surgery program was carried out for all patients. The knee scores at 3-year follow-up after operation and clinical efficacies of these three groups of patients were recorded, investigated, and compared. RESULTS: Primarily, compared to the TKA group, the UKA groups (MB UKA and FB UKA) had shorter operative time (median 63.2 < 67.1 min), less bleeding (8.6 < 30.0 mL), earlier resumption of walking without crutches (3.0 < 8.0 days) and walking up and down the stairs (5.0 < 10.0 days) (P < 0.001), higher FJS scores (78.0 > 74.5) (P = 0.007), better results in all knee scores (except VAS and KSS function scores) (P < 0.05), and a larger maximum flexion angle of the knee at the 3-year follow-up (123.0° > 96.0°) (P = 0.001). Secondarily, compared to the TKA group, the MB UKA group showed better results in the Western Ontario and McMaster Universities index (WOMAC) stiffness (83.6 > 79.6), WOMAC total (86.3 > 83.2), Oxford knee score (OKS) (20.0 < 23.0), Forgotten Joint Score (FJS) (78.5 > 74.5), and a larger maximum flexion angle of the knee (123.0 > 96.0) (P < 0.05). Moreover, the FB UKA group showed higher Hospital for Special Surgery Knee Score (HSS) (91.0 > 88.5), WOMAC stiffness (84.3 > 79.6), WOMAC function (85.2 > 81.7), WOMAC total scores (87.6 > 83.2), and a larger maximum flexion angle of the knee (119.0° > 96.0°) than the TKA group (P < 0.05). Overall, there was no significant difference in all knee scores and maximum flexion angles of the knee for the MB UKA and FB UKA groups (P > 0.05). There was one case with original bearing dislocation in MB UKA group. One patient with displacement of the femoral component caused by a fall injury, and another patient, who lost his life in a car accident, were involved in the FB UKA group. There was an infection case and an intermuscular vein thrombosis case in TKA group. CONCLUSION: UKA showed more advantages than TKA; however, there was no significant difference between the MB UKA and FB UKA groups for treatment of non-lateral compartmental knee OA.

LncRNA LINC00337 sponges mir-1285-3p to promote proliferation and metastasis of lung adenocarcinoma cells by upregulating YTHDF1.

BACKGROUND: Emerging studies have shown that long noncoding RNAs (lncRNAs) predominantly function in the carcinogenesis of multiple developing human tumors. The current study aimed to investigate the underlying mechanisms of LINC00337 in lung adenocarcinoma. METHODS: We analyzed TCGA and GTEx datasets and chose LINC00337 as the research object. Cell proliferation, cell apoptosis, cell cycle, migration, and invasion were detected in the gain and loss experiments of LINC00337 both in vitro and in vivo. Moreover, RNA pull-down, luciferase reporter assays, western blotting analysis, and rescue experiments were performed to investigate the underlying molecular mechanisms of LINC00337 function. RESULTS: LINC00337 expression was remarkably upregulated in lung adenocarcinoma. In addition, LINC00337 knockdown was shown to repress cell migration, invasion, and proliferation, as well as the cell cycle, and gear up apoptosis in lung adenocarcinoma in vitro and in vivo. With respect to the mechanism, LINC00337 knockdown boosted miR-1285-3p expression and then restrained YTHDF1 expression post-transcriptionally. Crucially, both miR-1285-3p decrement and YTHDF1 overexpression successfully reversed the influence on cell proliferation, migration, invasion, and apoptosis caused by LINC00337 shRNA. CONCLUSIONS: These results suggest that LINC00337 acts as an oncogenic lncRNA, targeting miR-1285-3p and regulating YTHDF1 expression, to promote the progression of lung adenocarcinoma.

A New Three-Dimensional Classification of Proximal Tibiofibular Fractures: A Multicenter Study.

OBJECTIVES: To propose an updated definition of proximal tibia and fibula fracture (PTFF) and establish a three-dimensional (3D) structure-based classification of PTFF. METHODS: In total, 1358 adult patients (837 males and 521 females; 43.61 ± 15.13 years， 1364 affected knees) who were diagnosed with PTFF at the departments of orthopaedic surgery of four hospitals from January 2010 to December 2019 were enrolled. The new classification of PTFF, termed Wu classification, included three parts: classification of columns in the horizontal plane, regions in the frontal plane, and segments in the sagittal plane. All PTFFs were classified according to Schatzker, Luo, and Wu classification systems. Additionally, the incidence and characteristics of PTFFs were analyzed. RESULTS: The major internal structural fractures of PTFF were tibial plateau fracture (TPF) only (725, 53.15%), TPF and proximal fibular fracture (274, 20.09%), and isolated avulsion fracture of the posterior cruciate ligament (PCL) (189, 13.86%). Approximately a quarter of PTFF cases could not be classified using Schatzker or Luo classifications, but all PTFF cases could be classified using Wu classification. The most frequent PTFFs included all four columns in region IV, segment 2 (235, 17.23%); the posterolateral and posteromedial columns in region II, segment 2 (191, 14.00%); and the lateral and posterolateral columns in region IV, segment 2 (136, 9.97%). Isolated avulsion fracture of the anterior cruciate ligament (ACL) was categorized as three injury types, most of which involved the lateral and medial columns in region II, segment 1 (40/63, 64%). More than 97% of cases of isolated fractures of the PCL involved the posterolateral and posteromedial columns in region II, segment 2. The most frequent combined avulsion fracture of the ACL and PCL included all four columns in region II, segment 2 (18/24, 75%). All of the isolated avulsion fractures of the ACL were located in segment 1, and all those of the PCL in segment 2. The most common type of isolated proximal fibular fracture involved the posterolateral column in region III, segment 2 (23/26, 88%). The most frequent combined TPF and proximal fibular fracture involved all four columns in region IV, segment 2 (107/274, 39.05%). CONCLUSIONS: All cases of PTFF could be classified by the new 3D Wu classification which should be beneficial for clinical diagnosis, guidance of treatment, statistical analysis, academic communication, and prognosis, and the most frequent PTFF involved all four columns in region IV, segment 2.

LncRNA AC079630.4 expression associated with the progression and prognosis in lung cancer.

Mounting evidence has demonstrated the important role of long non-coding RNAs (lncRNAs) in the development and progression of lung cancer. In this study, we combined the methods of bioinformatics analysis and experimental validation, and aim to investigate the clinical significance and underlying mechanism of the novel lncRNA AC079630.4 in lung cancer. Finally, we found that AC079630.4 was significantly down-regulated in lung cancer tissues, including in its subtypes. Samples with low AC079630.4 expression had a more advanced pathological stage and a worse prognosis than those with high expression. In functional prediction, the KEGG pathway of apoptosis and the TRAIL signaling pathway were enriched in the samples with high AC079630.4 expression. In experimental validation, AC079630.4 over-expression could significantly inhibit the proliferation and clonality, and up-regulated the receptors of TRAIL (TRAIL-R1 and TRAIL-R2) in lung cancer cells. In conclusion, we adopted the methods of bioinformatics analysis and experimental validation, and identified a novel lncRNA of AC079630.4 as a tumor suppressor in lung cancer.

A Promising Mouse Model of Graves' Orbitopathy Induced by Adenovirus Expressing Thyrotropin Receptor A Subunit.

Background: Graves' orbitopathy (GO) is the most common and serious manifestation of Graves' disease (GD). It is characterized by orbital inflammation and tissue remodeling. Although several GO models have been reported, most lack a full assessment or mechanistic evaluation. Here, we established a promising mouse model mimicking many aspects of human GO with a frequency of 70% and characterized the key role of T cells in the progression of GO. Methods: An adenovirus expressing the human thyrotropin (TSH) receptor A subunit (Ad-TSHRA) was injected in the muscles of female BALB/C mice nine times to induce GO. At predetermined time points, histological examinations of retrobulbar tissues and thyroid glands were performed to dynamically monitor changes; serum autoantibodies and total thyroxine levels were examined to evaluate thyroid function. Flow cytometry of CD4+ T cell subgroups and RNA sequencing (RNA-Seq) of splenocytes were also performed to explore the underlying mechanism. Results: After nine injections, 7 of 10 mice challenged with Ad-TSHRA developed the orbital changes associated with GO. Seven mice manifested retrobulbar fibrosis, and four mice showed adipogenesis. Exophthalmia, conjunctival redness, and orbital lymphocyte infiltration were also observed in a subset of mice. The orbitopathy was first detected after seven injections and followed the hyperplastic change observed in thyroids after four injections. Flow cytometry revealed increased proportions of Th1 cells and decreased proportions of Th2 cells and regulatory T (Treg) cells in the splenocytes of GO mice. This change in CD4+ T cell subgroups was confirmed by orbital immunohistochemical staining. Genes involved in T cell receptor signaling, proliferation, adhesion, inflammation, and cytotoxicity were upregulated in GO mice according to the RNA-Seq; a trend of upregulation of these GO-specific genes was observed in mice with hyperthyroidism without orbitopathy after four injections. Conclusions: A GO mouse model was successfully established by administering nine injections of Ad-TSHRA. The model was achieved with a frequency of 70% and revealed the importance of T cell immunity. A potential time window from Graves' hyperthyroidism to GO was presented for the first time. Therefore, this model could be used to study the pathogenesis and novel treatments for GO.

Effect of Dihydrotestosterone on CostimulatoryMolecules in a Mouse Model of Graves' Disease.

Objective Graves' disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males. Costimulatory molecules play an essential role in regulating autoimmune responses. The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone (DHT) in an in vivo BALB/c mouse model of experimental autoimmune Graves' disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves' disease model. Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization. Four weeks after the third immunization, the mice were euthanatized, and then the spleen and thymus were removed. Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit. Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus. Flow cytometry was used to analyze the percentage of CD4+ T cells in splenic lymphocytes. Quantitative data were compared with unpaired t-tests. Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels. Higher expression of programmed death-1 was found in the spleen of Graves' disease mice receiving 5 mg of DHT treatment (0.635±0.296 vs. 0.327±0.212; t=2.714, P=0.014), similarly, T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in both the spleen (1.004±0.338 vs. 0.646±0.314; t=2.205, P=0.022) and the thymus (0.263±0.127 vs. 0.120±0.076; t=3.221, P=0.004) also increased after 5 mg of DHT treatment compared with the parallel placebo model mice. Moreover, the percentage of CD4+ T cells declined in the splenic lymphocytes of Graves' disease mice treated with 5 mg of DHT (19.90%±3.985% vs. 24.05%±2.587%; t=2.804, P=0.012). A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine (r=-0.7106, P=0.014) as well as free thyroxine (r=-0.6542, P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves' disease, which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4+ T cells.

C-kit signaling promotes human pre-implantation 3PN embryonic development and blastocyst formation.

BACKGROUND: Although in vitro culture system has been optimized in the past few decades, the problem of few or no high quality embryos has been still not completely solved. Accordingly, fully understanding the regulatory mechanism of pre-implantation embryonic development would be beneficial to further optimize the in vitro embryo culture system. Recent studies have found the expression of c-kit in mouse embryo and its promotion effects on mouse embryonic development. However, it is unclear the expression, the role and the related molecular regulatory mechanism of c-kit in human pre-implantation embryo development. Therefore, the present study is to determine whether c-kit is expressed in human pre-implantation embryos, and to investigate the possible regulatory mechanism of c-kit signaling in the process of embryonic development. METHODS: The present study includes human immature oocytes and three pronucleus (3PN) embryos collected from 768 women (28-32 ages) undergoing IVF, and normal 2PN embryos collected from ICR mice. Samples were distributed randomly into three different experimental groups: SCF group: G-1™ (medium for culture of embryos from the pro-nucleate stage to day 3) or G-2™ (medium for culture of embryos from day3 to blastocyst stage) + HSA (Human serum album) solution + rhSCF; SCF + imanitib (c-kit inhibitor) group: G-1™ or G-2™ + HSA solution + rhSCF + imanitib; SCF + U0126 (MEK/ERK inhibitor) group: G-1™ or G-2™ + HSA solution + rhSCF + U0126; Control group: G-1™ or G-2™ + HSA solution + PBS; The rate of good quality embryos at day 3, blastulation at day 6 and good quality blastulation at day 6 were analysis. RT-PCR, western blot and immunofluorescence staining were applied to detect the target genes and proteins in samples collected from human or mice, respectively. RESULTS: c-kit was expressed ubiquitously in all human immature oocytes, 3PN embryos and 3PN blastocysts. In the experiment of human 3PN embryos, compared with other groups, SCF group showed obviously higher rate of good quality at day 3, better rate of blastocyst formation at day 6 and higher rate of good quality blastocyst formation at day 6. Furthermore, we observed a higher ETV5 expression in SCF group than that in other groups. Similar results were also found in animal experiment. Interestingly, we also found a higher phosphorylation level of MEK/ERK signal molecule in mice embryos from SCF group than those from other groups. Moreover, inhibition of MEK/ERK signaling would remarkably impeded the mice embryonic development, which might be due to the reduced ETV5 expression. CONCLUSIONS: The present study firstly revealed that c-kit signaling might promote the human pre-implantation embryonic development and blastocyst formation by up-regulating the expression of ETV5 via MEK/ERK pathway. Our findings provide a new idea for optimizing the in vitro embryo culture condition during ART program, which is beneficial to obtain high quality embryos for infertile patients.

Acute Massive Gastrointestinal Bleeding in the Elderly.

An 82-year patient presented with nausea, coffee-ground emesis, melena and hematochezia on July 10, 2011. The patient received blood transfusion on July 11, and continued to bleed from July 12 to 17. The patient underwent upper gastrointestinal endoscopy on July 16. There were no abnormalities in the esophagus, stomach and duodenum. Then the patient presented with shortness of breath, extreme fear, fatigue, hypotension, sweating, and cold limbs. Dopamine, as well as pressurised infusion of packed red blood cells and fresh frozen plasma were given to the patient to maintain blood pressure. CT angiography (CTA) revealed no aortic fistula, and enteroscopy revealed active bleeding in the vicinity of the ligament of Treitz. The retrograde exploration of gastroscopy revealed a 5×4 cm diverticulum on the posterior wall of the duodenum under the ligament of Treitz. Active bleeding of the small artery in the diverticulum was observed via incision of the duodenal wall, and the diverticulum was isolated. Hemostasis was achieved after ligation of blood vessels, and diverticulectomy was performed. Enteroscopy is important for the diagnosis of duodenal and upper small intestinal diseases. Repeated endoscopic exploration of multiple sites in the small intestine revealed the cause of the bleeding. The multidisciplinary team finally found the cause of the bleeding and its proper management.

Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion.

BACKGROUND: Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. METHODS AND RESULTS: In this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind-limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate-treated mice. Likewise, there were fewer capillaries in the ischemic hind-limb tissue of cyanate-exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube-formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3-kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. CONCLUSIONS: Impaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.

Cod skin peptide reduces chemotherapy-induced toxicity in gastric cancer patients.

BACKGROUND AND OBJECTIVES: The present study was conducted to evaluate the effect of cod skin peptide (CSPE) on chemotherapy-induced toxicity in gastric cancer patients. METHODS AND STUDY DESIGN: A cohort of 60 gastric cancer patients for chemotherapy was randomly divided into two groups (n=30 per group), who were orally treated with either supplemental CSPE or placebo apart from chemotherapy. The hematologic and gastrointestinal toxicities experienced by the patients, as well as their Karnofsky Performance Status (KPS) as an index of quality of life was evaluated. RESULTS: Leukocyte counts and haemoglobin levels were significantly reduced in the group treated with peptide (p<0.05), while gastrointestinal toxicity was not affected (p>0.05). KPS consists of 11 categories of quality of life, and the score denoted in deciles ranges from 100 (asymptomatic, normal function) to 0 (death). The KPS score is used to evaluate a cancer patient's ability to function at work and home, the severity of symptoms, and the patient's need for personal and medical care. Treatment with CSPE significantly improved the quality of life of patients, as indicated by increased KPS scores (p<0.05). CONCLUSIONS: CSPE can potentially be considered as a food supplement that can be used to improve the quality of life of cancer patients.

The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis.

OBJECTIVES: Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. METHODS: One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. RESULTS: The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=-0.348, P=0.013 and r=-0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=-0.490, P=0.028 and r=-0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (ß=0.403, P=0.006). CONCLUSION: CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSwNP patients, PBEC is independent predictor of FEV1 change ratio.

Overoxidized polypyrrole/graphene nanocomposite with good electrochemical performance as novel electrode material for the detection of adenine and guanine.

Most conducting polymer/graphene composites have excellent electrical conductivity. However, the background currents of these composites modified electrodes are much larger. In order to improve the sensitivities of these methods, it is necessary to decrease the background signal. In this paper, porous structure films of overoxidized polypyrrole/graphene (PPyox/GR) have been electrochemically coated onto glassy carbon electrode (GCE) and successfully utilized as an efficient electrode material for the quantitive detection of adenine and guanine, two of the most important components of DNA and RNA. The permselective polymer coatings with low background current could improve the selectivity and sensitivity of microelectrodes for the electropositive purine bases. The GRs into these polymers would further improve sensitivity by increasing the electroactive surface area. The electrochemical sensor can be applied to the quantification of adenine and guanine with a linear range covering 0.06-100 µM and 0.04-100 µM, and a low detection limit of 0.02 µM and 0.01 µM, respectively. More importantly, the proposed method was applied to quantify adenine and guanine in calf thymus DNA with satisfactory results.

[Influence of recombinant lentiviral vector encoding miR-15a/16-1 in biological features of human nasopharyngeal carcinoma CNE-2Z cells].

OBJECTIVE: To study the influence of recombinant lentiviral vector encoding miR-15a/16-1 on biological features of human nasopharyngeal carcinoma CNE-2Z cells and underlying mechanisms. METHODS: GFP-positive CNE-2Z cells transfected with recombinant lentiviral vector were selected. The experiment was divided into control group, transfected group, radiotherapy group, transfected-radiotherapy group. Cell proliferation was analyzed by MTT. Apoptosis was detected by flow cytometry. Radiotherapy sensitivity of the cells in control group and transfected group was evaluated by colony forming experiment. The expressions of miR-15a, miR-16-1 and bcl-2 mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of bcl-2 protein was detected by Western blot. The activation of Caspase-2 and Caspase-3 was evaluated by spectrophotometry. RESULTS: Relative expression quantities of miR-15a and miR-16-1 in infected group were 524.80 ± 40.79 (t = 494.611, P = 0.000) and 466.11 ± 40.96 (t = 386.8, P = 0.000), respectively. The proliferation of the cells in transfected-radiotherapy group was the most obvious, followed by the cells in radiotherapy group and transfected group (F = 424.3, P = 0.000). The apoptosis rates of control group, transfected group, radiotherapy group and transfected-radiotherapy group were (2.2 ± 1.4)%, (9.6 ± 0.8)%, (2.9 ± 1.1)%, and (18.6 ± 0.7)% respectively(F = 158.5, P = 0.000). Clonogenic assay showed that the values of SF2, Do (1.473) and Dq (1.581) in transfected group were lower than those in control group. The relative expression levels of bcl-2 mRNA in transfected group, radiotherapy group, and transfected-radiotherapy group had no significant difference (P > 0.05). Decrease in the expression of bcl-2 protein in transfected-radiotherapy group was most significantly, followed by that in transfected group. The percentages of activated Caspase-2 in control group, radiotherapy group, transfected group and transfected -radiotherapy group were 0.12 ± 0.01, 0.24 ± 0.04, 0.35 ± 0.02, and 0.44 ± 0.04, respectively (F = 115.500, P = 0.000). The percentages of activated Caspase-3 in the groups were 0.13 ± 0.01, 0.27 ± 0.01, 0.43 ± 0.02, and 0.83 ± 0.06, respectively (F = 439.921, P = 0.000). CONCLUSIONS: Recombinant lentiviral vector LV-miR15a/16-1 could improve the expression of miR-15a and miR-16-1 in CNE-2Z cells, inhibit the proliferation of CNE-2Z cells, promote apoptosis and enhance the sensitivity of the cells to radiotherapy probably by inhibiting bcl-2 expression, activating Caspase-2 and Caspase-3.

[An exploration of induction methodology and experimental duration of Graves disease animal model].

OBJECTIVE: To compare the efficacy of Graves disease animal models induced by thyroid stimulating hormone receptor (TSHR) plasmid DNA (pcDNA3.1-TSHR) and by TSHR A subunit recombinant adenovirus (Ad-TSHR289), and to investigate the influence of duration for preparing animal model induced by Ad-TSHR289 on Graves hyperthyroidism and its related indices. METHODS: The plasmid group and the adenovirus group were set up respectively. The plasmid group: 21 female BALB/c mice were randomly divided into model group (n = 12) and control group (n = 9). The model group were injected intradermally with pcDNA3.1-TSHR 50 µg, once every 3 weeks, totally 3 times. Then 4 weeks after the last immunization, the mice were euthanized to obtain blood for testing TSHR antibody (TRAb), total T(4), and thyroid tissue for histological examination. The controls were injected with the same dose of pcDNA3.1 in the same way. The adenovirus group: 52 female BALB/c mice were divided into 10-week model group (n = 8), 14-week model group (n = 10) and 18-week model group (n = 8), and the respective controls (n = 8, n = 10, n = 8) were set up. All model groups were injected intramuscularly with Ad-TSHR289, three times at three weekly intervals. Then the mice were euthanized at 4, 8 and 12 weeks to test TRAb, total T(4) level and to observe the change of thyroid histology. The controls were treated with the same dose of Ad-lacz in the same way. Another 8 mice were scheduled to test the dynamic variation of TRAb before and after the 3 times immunization. RESULTS: In the plasmid model group, only two of 12 mice developed weak antibody responses against TSHR, and no elevated total T(4) level and no hyperplasia changes of thyroid were observed. In the 10-week model group, all mice had high level TRAb [(807.65 ± 136.33) U/L], Six-eighths mice had hyperthyroidism exhibited hyperplasia changes. In the 14-week model group, the TRAb level [(650.12 ± 192.88) U/L] and the incidence of hyperthyroidism (3/10) were lower than those in 10-week group. Histologically, the degree of thyroid hyperplasia lightened to a small extent, but its positive rate did not decline. In the 18-week model group, only 2 of 8 mice displayed slightly elevated TRAb level, and no mice showed increased total T(4) level. Additionally, thyroid tissues of 2 mice were mildly abnormal. Compared with the model groups at different time, the change of antibody levels of the mice for TRAb dynamic observation exhibited the similar trend. CONCLUSIONS: Being good at repeatability and high incidence of hyperthyroidism, the animal model of Graves disease induced by Ad-TSHR289 is still an ideal research tool presently. The duration of model can be maintained 18 weeks, and 10 weeks is the best period to sustain characteristic of Graves disease.

[Detecting phospho-signaling protein of bone marrow leukemia cells by phospho-signaling flow cytometry].

The purpose of this study was to establish the phospho-specific flow cytometry (phospho-flow) to detect the phosphorylated signaling proteins of leukemia cells and to evaluate its useful value in leukemia study. The bone marrow of leukemia children was collected, and treated by phospho-flow of extracted mononuclear cells (MNC) and phospho-flow of directly fixed bone marrow (BM) respectively. In phospho-flow of extracted MNC, the MNC extracted from BM were fixed and permeabilized, then were cultured with P-AKT and P-ERK1/2, finally were analyzed by flow cytometry. In phospho-flow of directly fixed BM, the BM was treated with fixation/lysis buffer and 90% methanol, then were incubated with the surface CD antibody, P-AKT and P-ERK1/2, finally the treated BM cells were analyzed by flow cytometry. The results showed that the positive rates of P-AKT and P-ERK1/2 in MNC treated by phospho-flow of extracted MNC of 26 leukemia children were 46.2% and 30.8% respectively, while the positive rates of P-AKT and P-ERK1/2 in BM treated by phospho-flow of directly fixed BM were 50.0% and 38.5% respectively. The comparison of positive rates of P-AKT and P-ERK1/2 between the 2 treatment protocol showed no difference (p > 0.05). It is concluded that the phospho-flow of directly fixed BM established by our laboratory can be used to analyze the signaling proteins of leukemia cells.

Association of insulin-like growth factor-1 with thyroid nodules.

The aim of the present study was to investigate the relationship between insulin-like growth factor-1 (IGF-1) and thyroid nodules. A total of 56 patients with thyroid nodules confirmed by physical examination and ultrasound screening were randomly selected. The patients were divided into three groups by radionuclide scan: the hot nodule group (group 1, n=18); the cold and solid nodule group (group 2, n=18); and the cold and cystic nodule group (group 3, n=20). Cystic fluid samples from patients with cystic cold thyroid nodules were defined as group 4. A control group of 18 healthy adults matched for age, gender and body mass index (group 0) was also included. For all participants, levels of the thyroid hormones, TT3, TT4, TSH and IGF-1, were determined by radioimmunoassay. The measurement data were expressed as the mean ± standard deviation (SD). The analysis of variance was performed by the t-test and the correlation analysis was performed by linear regression. The serum levels of IGF-1 in the solid cold nodule group were significantly higher than those in the hot nodule group (P<0.05). Serum levels of IGF-1 in the cystic cold nodule group were significantly lower than those in the control group (P<0.05). The serum IGF-1 levels in the cystic fluid were significantly lower than those in the cystic cold nodule (P<0.05) and the control groups (P<0.05). Additionally, the mean serum IGF-1 level in patients with thyroid adenoma was significantly higher than that in the control group (P<0.05). The serum IGF-1 level may not be involved in the pathogenesis of hot thyroid nodules and cold and cystic thyroid nodules; however, it may play a significant role in the pathogenesis of certain solid cold thyroid nodules.