FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury.

Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.

Association between the composite dietary antioxidant index and metabolic syndrome: evidence from NHANES 2003-2018.

OBJECTIVE: A healthy and nutritional diet has been considered a promising approach to improve many adverse clinical outcomes. However, current evidence of the association of the intake of composite dietary antioxidants with metabolic syndrome (MetS) is limited. The current study was performed to explore the effect of the composite dietary antioxidant index (CDAI) on MetS and its components based on the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. MATERIALS AND METHODS: The dietary consumption was evaluated using the 24-hour diet recall method, and a previously validated approach that included six antioxidants was used to calculate CDAI. The National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) was applied to evaluate MetS. ORs and 95%CIs were computed by logistic regression. The association between CDAI and MetS was determined by subgroup analyses and restricted cubic spline (RCS) regressions. RESULTS: This study included 24,705 individuals; approximately 18,378 (74.39%) participants were determined to be without MetS and 6,327 (25.61%) with MetS. After considering all confounders, compared to individuals of the lowest quartile of CDAI, those of the highest quartile showed a 31% lower risk of MetS (OR, 0.69, 95% CI: 0.57-0.82). RCS revealed a non-linear relationship between CDAI and MetS risk. CONCLUSIONS: A non-linear association was found between CDAI and decreased MetS risk, which indicated that selective combined intake of antioxidants could be a promising and effective approach to preventing MetS for the public.

A machine-learning model based on dynamic contrast-enhanced MRI for preoperative differentiation between hepatocellular carcinoma and combined hepatocellular-cholangiocarcinoma.

AIM: To establish a machine-learning model based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to differentiate combined hepatocellular-cholangiocarcinoma (cHCC-CC) from hepatocellular carcinoma (HCC) before surgery. MATERIALS AND METHODS: Clinical and MRI data of 194 patients with histopathologically diagnosed cHCC-CC (n=52) or HCC (n=142) were analysed retrospectively. ITK-SNAP software was used to delineate three-dimensional (3D) lesions and extract high-throughput features. Feature selection was carried out based on Pearson's correlation coefficient and least absolute shrinkage and selection operator (LASSO) regression analysis. A radiomics model (radiomics features), a clinical model (i.e., clinical-image features), and a fusion model (i.e., radiomics features + clinical-image features) were established using six machine-learning classifiers. The performance of each model in distinguishing between cHCC-CC and HCC was evaluated with the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), sensitivity, and specificity. RESULTS: Significant differences in liver cirrhosis, tumour number, shape, edge, peritumoural enhancement in the arterial phase, and lipid were identified between cHCC-CC and HCC patients (p<0.05). The AUC of the fusion model based on logistic regression was 0.878 (95% CI: 0.766-0.949) in the arterial phase in the test set, and the sensitivity/specificity was 0.844/0.714; however, the AUC of the clinical and radiomics models was 0.759 (95% CI: 0.663-0.861) and 0.838 (95% CI: 0.719-0.921) in the test set, respectively. CONCLUSION: The fusion model based on DCE-MRI in the arterial phase can significantly improve the diagnostic rate of cHCC-CC and HCC as compared with conventional approaches.

[Clinical phenotypic and genotypic analysis of 5 pediatric patients with ß-ketothiolase deficiency].

Objective: To summarize the clinical and genetic characteristics of children with ß-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 µmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: ß-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of ß-ketothiolase deficiency.

Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer.

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

The Relationship between Pre-Admission Waiting Time and the Surgical Outcomes after Hip Fracture Operation in the Elderly.

OBJECTIVES: To investigate the association between pre-admission waiting time and postoperative complications, length of stay (LOS), and costs during hospitalization. METHOD: This was a single-center, observational study. The subjects of this study were elderly hip fracture patients who were admitted to the Department of Orthopedics, West China Hospital, Sichuan University, from December 2010 to June 14, 2017, and that underwent internal fixation or joint replacement surgery. The pre-admission waiting time was treated as a categorical variable according to median and first quartile values. Outcomes included postoperative complications (pneumonia and other complications [urinary tract infection, heart failure, non-A-grade healing]), LOS, and costs during hospitalization. LOS and costs during hospitalization were converted into binary outcomes based upon median values. Binary logistic regression analyses were used to analyze correlations between pre-admission waiting time and patient outcomes. RESULTS: A total of 889 patients 60 years of age and older were enrolled in this study, of whom 65.47% were females and 34.53% were males. The proportion of patients with pre-admission waiting times less than 8 h, 8 - 24 h, and ≥ 24 h were 24.3%, 17.32%, and 58.38%, respectively. Postoperative pneumonia and other complications affected 12.04% and 6.30% of patients, respectively. Relative to patients with the pre-admission waiting times of less than 8 h, those with longer pre-admission waiting times exhibited a higher risk of postoperative pneumonia (8 - 24 h: OR = 2.72,95% CI: 1.29-5.74, p = 0.009; ≥ 24 h: OR = 2.76,95% CI: 1.48-5.14, p = 0.001). Patients with the pre-admission waiting time ≥ 24 h also exhibited a higher risk of the other complications (OR = 2.55, 95% CI: 1.53-4.26, p <0.001), a longer LOS (OR = 1.43, 95% CI:1.02-2.01, p = 0.036), and higher costs during hospitalization (OR = 1.51, 95% CI:1.05 - 2.17, p = 0.026) relative to patients with a waiting time less than 8 hours. CONCLUSION: Pre-admission waiting time was associated with postoperative complications, LOS, and hospitalization costs among older Chinese patients undergoing surgery to treat hip fractures.

[Inflammatory periodontal stem cells mediate interleukin-1ß secretion of macrophage by regulating macrophage endoplasmic reticulum stress].

Objective: To investigate the effect and mechanism of periodontal ligament stem cell (PDLSC) from inflammatory environment on the secretion of interleukin-1ß (IL-1ß) by macrophages. Methods: PDLSCs were pretreated with lipopolysaccharide (LPS) in order to simulate the inflammatory environment. Human monocyte cell line (THP-1) cells were treated with conditioned media collected from healthy and inflammatory PDLSCs respectively and divided into conditioned medium of health PDLSC (CM-H) group and conditioned medium of LPS-PDLSC (CM-LPS) group. After 24 h of co-culture, the condition media were abandoned and THP-1 cells were then cultured for another 24 h. The expression of IL-1ß in THP-1 cells supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real time-PCR (qRT-PCR) was used to detect the expression of glucose regulated protein 78 (GRP78), activating transcription factor-6 (ATF6), inositol requiring enzyme 1 (IRE1), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT enhancer binding protein homologous protein (CHOP), activating transcription factor-4 (ATF4) and X box binding protein 1 spliced (XBP1s), which were all related with endoplasmic reticulum stress (ERS), in THP-1 cells. The expressions of proteins GRP78 and CHOP were detected by Western blotting. Furthermore, THP-1 cells, which pretreated with ER inhibitor 4-phenylbutyrate (4-PBA) for intervention experiments were grouped by various concentrations of 4-PBA including groups 0 (control group), 1, 10 and 20 mmol/L and treated with condition medium of inflammatory PDLSC. ELISA was used to detect IL-1ß expression and qRT-PCR to detect expression of ERS related genes. Results: ELISA results showed that the expression of IL-1ß in THP-1 cells of group CM-LPS [(31.35±2.11) ng/L] was significantly higher than group CM-H [(8.19±1.51) ng/L] (t=12.60, P<0.01). qRT-PCR results showed that the relative expressions of GRP78, ATF6, IRE1, PERK, CHOP, ATF4 and XBP1s genes in THP-1 cells of group CM-LPS (1.782±0.070, 1.387±0.204, 1.404±0.119, 1.777±0.187, 1.325±0.156, 1.295±0.066 and 1.137±0.149, respectively) were significantly higher than those in group CM-H (P<0.05). In the 4-PBA intervention experiment, compared with group 0 mmol/L, the expressions of GRP78, IRE-1, ATF-6, PERK and CHOP were significantly lower in group 1, 10 and 20 mmol/L (P<0.05). Moreover, compared with control group [(31.23±1.98) ng/L], the expression of IL-1ß in THP-1 cells were significantly lower in group 10 mmol/L [(21.20±0.37) ng/L] and group 20 mmol/L [(23.85±1.80) ng/L] (P<0.05) with ERS inhibited. Conclusions: PDLSC from inflammatory environment could promote IL-1ß secretion of macrophages through upregulating macrophages ERS.

[Geometric model of reduction in basilar invagination with atlantoaxial dislocation and its clinical application].

Objectives: To establish a geometric model of the atlantoaxial dislocation and basilar invagination reduction,and examine its value for clinical application. Methods: A retrospective analysis of 35 patients with atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery,First Affiliated Hospital of Chongqing Medical University from May 2018 to May 2020 was conducted.There were 5 males and 30 females,aged (48±15) years(range: 19 to 69 years). The geometric model of the atlantoaxial reduction was established based on the mid-sagittal section of the cervical spine. The relevant data were calculated according to the geometric model before operation,and the fusion cage of the corresponding height was placed into C1-2 facet joint of patient for quantitative reduction. The theoretical reset value, actual reset value, postoperative symptoms and complications were collected. The paired t-test was used to compare the difference between theoretical and actual reset value to verify the reliability of the geometric model. Results: The theoretical vertical reduction distance of all patients was (5.79±2.96) mm(range:1.52 to 10.96 mm),and the actual vertical reduction distance was (7.43±2.96)mm(range: 1.40 to 12.77 mm),and there was no statistical difference between them(t=-1.96,P=0.069).The theoretical reduction angle was (10.80±2.24)°(range: 7.09 to 14.86°), the actual reduction angle was (10.64±7.00)°(range: 3.50 to 20.50°),and there was no statistical difference between them (t=0.09, P=0.933). At 6 months follow-up, 35 patients achieved satisfactory atlanto-axial joint fusion, and the symptoms were relieved. No internal fixation system displacement, fracture, wound infection and other complications occurred. Conclusion: This geometric model can estimate the vertical reduction distance and the reduction angle of the axial before operation,and provide a reference for the height of the fusion cage so as to avoid under or over-reduction.

Retrospective Planning Study of Patients with Superior Sulcus Tumours Comparing Pencil Beam Scanning Protons to Volumetric-Modulated Arc Therapy.

AIMS: Twenty per cent of patients with non-small cell lung cancer present with stage III locally advanced disease. Precision radiotherapy with pencil beam scanning (PBS) protons may improve outcomes. However, stage III is a heterogeneous group and accounting for complex tumour motion is challenging. As yet, it remains unclear as to whom will benefit. In our retrospective planning study, we explored if patients with superior sulcus tumours (SSTs) are a select cohort who might benefit from this treatment. MATERIALS AND METHODS: Patients with SSTs treated with radical radiotherapy using four-dimensional planning computed tomography between 2010 and 2015 were identified. Tumour motion was assessed and excluded if greater than 5 mm. Photon volumetric-modulated arc therapy (VMAT) and PBS proton single-field optimisation plans, with and without inhomogeneity corrections, were generated retrospectively. Robustness analysis was assessed for VMAT and PBS plans involving: (i) 5 mm geometric uncertainty, with an additional 3.5% range uncertainty for proton plans; (ii) verification plans at maximal inhalation and exhalation. Comparative dosimetric and robustness analyses were carried out. RESULTS: Ten patients were suitable. The mean clinical target volume D95 was 98.1% ± 0.4 (97.5-98.8) and 98.4% ± 0.2 (98.1-98.9) for PBS and VMAT plans, respectively. All normal tissue tolerances were achieved. The same four PBS and VMAT plans failed robustness assessment. Inhomogeneity corrections minimally impacted proton plan robustness and made it worse in one case. The most important factor affecting target coverage and robustness was the clinical target volume entering the spinal canal. Proton plans significantly reduced the mean lung dose (by 21.9%), lung V5, V10, V20 (by 47.9%, 36.4%, 12.1%, respectively), mean heart dose (by 21.4%) and thoracic vertebra dose (by 29.2%) (P < 0.05). CONCLUSIONS: In this planning study, robust PBS plans were achievable in carefully selected patients. Considerable dose reductions to the lung, heart and thoracic vertebra were possible without compromising target coverage. Sparing these lymphopenia-related organs may be particularly important in this era of immunotherapy.

Research on CRISPR/system in major cancers and its potential in cancer treatments.

Cancer is a serious public health problem in the world and the prevention and control of cancer has become one of the health strategies of governments around the world. According to the data of the International Agency for Research on Cancer (IARC), about 8 million people die of cancer every year in the world. With the continuous progress of medical technology, there are many methods to treat cancer at present. However, many treatment methods have achieved different therapeutic effects, some of them have obvious toxic and side effects. Therefore, it is necessary to study simpler and more effective new therapies for alleviating pain and prolonging lifetime of patients. In this view, we focus on the application progress of CRISPR system in some major cancers and its potential in cancer treatments.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

Ethanol combined with coil embolisation for the treatment of arteriovenous malformations in a patient with Parkes Weber syndrome.

Parkes Weber syndrome is a rare congenital condition of the vascular system with severe symptoms and life-threatening complications. The challenge is to manage the arteriovenous malformations, and there is no consensus on optimal treatment. We report the case of an 18-year-old woman with Parkes Weber syndrome who was treated with ethanol combined with coil embolisation at an early stage. After two sessions of embolisation, a significant devascularisation was achieved. No sign of recurrence was observed two years after the initial procedure. The patient's symptoms and signs were greatly relieved during the follow-up period. This case raises awareness of Parkes Weber syndrome and highlights the importance of timely intervention, as well as offering a promising therapeutic option for this condition.

[Targeted therapy for malignant peripheral nerve sheath tumor: translational research and clinical application].

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.

Oncogene miR-934 promotes ovarian cancer cell proliferation and inhibits cell apoptosis through targeting BRMS1L.

OBJECTIVE: Ovarian cancer is a common malignant cancer among women. Increasing studies have demonstrated that microRNAs function as important regulation factors in the progression of ovarian cancer. MATERIALS AND METHODS: Human ovarian cancer cell lines HO8910 and OVCAR-3 were transfected with miR-934 inhibitor and corresponding negative control (inhibitor control). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) and TUNEL assay, respectively. The expression levels of proliferation/apoptosis-related genes and BRMS1L were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting. Furthermore, the association between miR-934 and BRMS1L was investigated through luciferase reporter assays. RESULTS: MiR-934 was significantly increased in ovarian cancer cell lines, whereas BRMS1L was significantly decreased. Downregulated miR-934 remarkably inhibited cell proliferation and induced cell apoptosis. Meanwhile, miR-934 could influence the expression levels of Ki67, Cyclin D1, Caspase3, and Bcl-2. In addition, BRMS1L was identified as a target gene of miR-934. CONCLUSIONS: Oncogene miR-934 promotes ovarian cancer cell proliferation and inhibits cell apoptosis through targeting BRMS1L. MiR-934 and BRMS1L may be novel biomarkers or therapeutic targets for ovarian cancer in the future.

A novel method for assessing proximal tibiofibular joint on MR images in patients with knee osteoarthritis.

OBJECTIVES: To validate a method to measure the morphological parameters of the proximal tibiofibular joint (PTFJ) in patients with knee osteoarthritis (OA). METHODS: 408 participants were examined in this cross-sectional subject-based study. We calculated the fibular contacting area of PTFJ (S) and its projection areas onto the horizontal plane (load-bearing area, Sτ), the sagittal plane (lateral stress-bolstering area, Sφ) and the coronal plane (posterior stress-bolstering area, Sυ). Joint space narrowing (JSN) and osteophyte was measured using radiographs. Cartilage defects, bone marrow lesions (BMLs) and cartilage volume were evaluated using magnetic resonance imaging (MRI). RESULTS: The average PTFJ fibular contacting area was 2.4 cm2 (SD, ±0.7 cm2). Intra-observer and inter-observer reliabilities of measures of PTFJ morphological parameters were excellent (≥0.90). S, Sτ and Sφ were significantly associated with JSN in the medial tibiofemoral compartment (PR: 1.40, 95% CI 1.10-1.78; PR: 1.65, 95% CI 1.25-2.18 and PR: 0.53, 95% CI 0.29-0.97, respectively). There was a significantly positive association between S, Sτ and medial and/or femoral tibial cartilage defects. S, Sτ and Sυ were significantly and positively associated with medial and/or femoral tibial BMLs (PR: 1.36, 95% CI 1.12-1.64; PR: 1.47, 95% CI 1.17-1.83; and PR: 1.39, 95% CI 1.06-1.82, respectively) after adjustment. S and Sτ were significantly and negatively associated with medial tibial cartilage volume. CONCLUSIONS: This novel method to assess the morphological parameters of PTFJ in MRI is reproducible. These parameters are associated with knee radiographic and MRI-based OA-related structural abnormalities, suggesting clinical construct validity. Its predictive validity needs to be examined in future longitudinal studies.

[Tumor-secreted vascular endothelial growth factor A increases the pulmonary metastasis from nasopharyngeal carcinoma].

Objective: Vascular endothelial growth factor A (VEGFA) was investigated as the key protein which might promote the specific metastasis progress of nasopharyngeal carcinoma. Methods: Sixteen specimens of pulmonary metastasis carcinoma and counterparts in primary nasopharyngeal carcinoma tissue were collected from patients. The expression of VEGFA through immunohistochemistry was investigated.VEGFA was knocked down by siRNA in two cell lines of nasopharyngeal carcinoma (CNE-1 and 5-8F), MTT and Transwell test were used to explore the role of VEGFA in praxiology. Then shRNA was used to cultivate the stable CNE-1 cell line with down-regulated-expression of VEGFA. The nude mice models were built through tail vein injection of specific nasopharyngeal carcinoma cells, and lungs were collected to perform further metastasis analysis. Results: Previous genetic studies showed that VEGFA had higher expression in metastasis tissue, and the result was validated in the present study using immunohistochemistry. The percentage of positive cells was 84.8% in pulmonary metastasis group, 51.5% in primary tissue group (t=8.639, P<0.05), average optical density was 0.154 in pulmonary metastasis group, 0.061 in primary tissue group (t=18.791, P<0.05). Low expression of VEGFA inhibited cell viability of optical density value of CNE-1 in siRNA gourp was 0.715, 0.902 in control group (t=7.274, P<0.05); 5-8F in siRNA group was 0.715, 0.935 in control group (t=7.751, P<0.05). Number counting suppressed migration of CNE-1 in siRNA group was 52 per high-power lens, 124 per high-power lens in control group (t=29.380, P<0.05), 5-8F in siRNA group was 65 per high-power lens, 155 per high-power lens in control group (t=18.181, P<0.05). Number counting invasion of CNE-1 in siRNA gourp was 38 per high-power lens, 86 per high-power lens in control group (t=27.665, P<0.05), 5-8F in siRNA group was 52 per high-power lens, 116 per high-power lens in control group (t=40.972, P<0.05) in vitro. Furthermore, knock-down of VEGFA in nasopharyngeal carcinoma reduced the pulmonary metastasis in vivo. Number counting of tumor volumes in shRNA group was 2.4, and 11.0 in control group (t=6.143, P<0.05); average optical density of immunohistochemistry in shRNA group was 0.033, and 0.176 in control group (t=15.734, P<0.05). Conclusions: Results above reveal the overexpression of VEGFA in nasopharyngeal carcinoma can facilitate the pulmonary metastasis. Targeting VEGFA may provide a new biomarker of clinical study.

[Effect of nasal glucocorticoid combined with loratadine or montelukast on allergic rhinitis].

Objective:To evaluate the effect of nasal glucocorticoid combined with second-generation antihistamines or leukotriene receptor antagonists on the treatment of moderate severe allergic rhinitis, and explore the optimal scheme of personalized treatment for AR patients.Method:Fiftyseven patients with persistent moderatesevere allergic rhinitis were randomly divided into three groups and treated by mometasone furoate aqueous nasal spray (group MOM), mometasone furoate aqueous nasal spray combined with loratadine (group MOM+L), mometasone furoate aqueous nasal spray combined with montelukast (group MOM+M) for 4 weeks. Four major clinical symptoms of allergic rhinitis: nasal congestion, nose itching, sneezing and runny nose were evaluated by "symptom rating score" before treatment and after treatment for 4 weeks.Result:After treatment, the total nasal symptom scores of each group showed a decreasing tendency, and the differences between various time points were statistically significant (P< 0.05). For the symptom of nasal congestion, the symptom score of MOM+M group was significantly lower than that of MOM group and MOM+L group at the 2nd and 4th week after treatment. For the symptoms of sneezing and nasal itching, MOM+L group had the lowest score at each time point after treatment and the difference was statistically significant compared with MOM group (P< 0.05), but there was no significant difference between MOM group and MOM+M group (P> 0.05). For the symptom of runny nose, the score of MOM+L group was significantly lower than MOM group (P< 0.05) at the 1st and 2nd week, MOM+M group was significantly lower than MOM group (P< 0.05) at the 2nd and 4th week, while there was no significant difference between MOM+L group and MOM+M group (P> 0.05).Conclusion:Nasal glucocorticoid alone or combined with secondgeneration antihistamines or leukotriene receptor antagonists can effectively control nasal symptoms of moderatesevere allergic rhinitis, yet the effect of combination therapy is better. For nasal congestion, nasal glucocorticoid combined with leukotriene receptor antagonists have a better effect. For nasal itching and sneezing, the choice of nasal glucocorticoid combined with second-generation antihistamines may be more sensible. For runny nose, nasal glucocorticoid combined with second-generation antihistamines or leukotriene receptor antagonists have similar efficacy.

Risk of second malignant neoplasms in women and girls with germ cell tumors.

Background: While an elevated risk of second malignant neoplasms (SMNs) has been observed in men treated for germ cell tumors (GCTs), risk of SMNs have not been quantified in adult women or in girls treated for GCTs. Patients and methods: One-year survivors of primary GCTs diagnosed between January 1980 and December 2012 were identified from Surveillance, Epidemiology, and End Results (SEER 9) registries. Risk of SMNs was calculated using SEER*Stat. Results: Among 1507 patients, a total of 47 SMNs were identified. The overall risk of SMNs was not elevated in females overall or in females treated for GCT during adulthood although SMN sites (pancreas, soft tissue, bladder, kidney, and thyroid) and trends were comparable with those in men. There were too few childhood GCT cases with SMNs for further analysis. Conclusions: Unlike men, women treated for GCTs did not have a statistically significant elevated risk of SMNs [standardized incidence ratio = 1.11; 95% confidence interval (CI) = 0.81-1.47]. The fact that SMNs in women occur in sites similar to those observed in men indicate that long-term follow-up of a larger cohort of females treated for GCT is warranted.

[Detection and screen of pulmonary metastasis-related signature genes in nasopharyngeal carcinoma].

Objective: To establish an animal model of pulmonary metastasis from nasopharyngeal carcinoma (NPC) and to investigate differential genes associated with pulmonary metastasis. Methods: CNE cell line was used to construct the stable metastasis CNE/Luc cell line which steadily expresses the fluorescent enzyme genes. The CNE/Luc cells were injected into immunodeficiency mice through tail vein, and with the in vivo imaging technology, the mice with pulmonary metastasis were filtered out. The pulmonary metastasis cells, were separated and injected into the tail vein of other nude mice to obtain the tissue-specificity metastasis cells confirmed by fluorescent imaging system. Based on the gene chip, the differential genes associated with pulmonary metastasis for NPC were found. Results: The gene expression profiles of nasopharyngeal carcinoma cell line CNE/Luc and their lung metastasis-associated subpopulation CNE/Luc-2 were constructed by gene chip technology. Ten metastasis-related genes were screened by software analysis, namely as TP53, PIK3CA, MET, KRAS, VEGFA, EDNRB, GSK3B, FOXO3, SOD2, and BIRC3. Conclusions: Some genes including TP53, PIK3CA, MET, KRAS, VEGFA, EDNRB, GSK3B, FOXO3, SOD2, and BIRC3 are indicated to have important roles in the lung metastasis of nasopharyngeal carcinoma.

[Phase â £ clinical trial for external use of recombinant human granulocyte-macrophage colony-stimulating factor gel in treating deep partial-thickness burn wounds].

OBJECTIVE: To evaluate the clinical efficacy and safety of external use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel on deep partial-thickness burn wounds. METHODS: Sixty-eight hospitals in our country including our unit performed a phase Ⅳ clinical trial for rhGM-CSF gel in patients (conforming to the study criteria) with deep partial-thickness burn wounds from November 2010 to July 2012. Multicenter, randomized, positive-homogenous-controlled, and open trial method was used in the trial, and patients from 10 hospitals were grouped into the positive-homogenous-controlled trial, while patients from the other 58 hospitals were grouped into open trial. (1) Controlled trial. Patients were divided into rhGM-CSF group and conventional treatment group (CT) with the ratio of 1∶1 according to the stratified randomization method. Wounds of patients in rhGM-CSF group were coated with rhGM-CSF gel, and wounds of patients in group CT were covered by gauze with iodophor. Scores of wound exudate and wound edge response before treatment and on treatment day (TD) 2, 4, 8, 10, 14, 20, and 28 were conventionally evaluated. Wound healing rates on TD 8, 10, 14, 20, and 28 were calculated. Complete wound healing time and overall efficiency including cure, excellence, progress, and invalid situation on TD 28 were recorded. Safety indexes including vital signs and laboratory test indexes before and during treatment, and adverse reactions during treatment were observed. (2) Open trial. Wounds of patients in this trail were all coated with rhGM-CSF gel. Complete wound healing time, overall efficiency, and safety indexes of patients were recorded as in controlled trial. Data were processed with CMH-χ(2) test, Fisher's exact test, signed rank sum test, paired t test, Log-Rank test, and Wilcoxon rank sum test. RESULTS: (1) Controlled trail. A total of 366 patients from 10 hospitals were included in this trial, and 358 cases with 177 cases in rhGM-CSF group and 181 cases in group CT finished the trial. There were no statistically significant differences in gender, age, injury characteristics, and combined medication situation between patients in two groups (χ(2)=1.510, with t values from 0.458 to 0.820, P values above 0.05). Scores of wound exudate of patients in two groups were similar before treatment and on TD 2, 20, and 28 (t=0.420, with Z values from 0.735 to 1.939, P values above 0.05). Scores of wound exudate of patients in rhGM-CSF group were significantly lower than those in group CT on TD 4, 8, 10, and 14 (with Z values from 2.054 to 2.580, P values below 0.05). Scores of wound edge response of patients in two groups were similar before treatment and on each TD (t=0.340, with Z values from -1.147 to 1.874, P values above 0.05). Wound healing rate of patients in rhGM-CSF group was significantly higher than that in group CT on each TD (with Z values from 2.630 to 5.235, P values below 0.01). The complete wound healing time of patients in rhGM-CSF group was (16.93±0.40) d, which was significantly shorter than that in group CT[(19.88±0.41) d, χ(2)=26.732, P<0.001]. At last, 171 (96.61%) patients were completely cured in rhGM-CSF group, while excellence, progress, and invalid results were achieved in 3 (1.69%), 1 (0.56%), and 2 (1.13%) patients, respectively. Whereas, 161 (88.95%) patients were completely cured in group CT, while excellence, progress, and invalid results were achieved in 11 (6.08%), 5 (2.76%), and 4 (2.12%) patients, respectively. Total efficacy of patients in rhGM-CSF group was significantly higher than that in group CT (χ(2)=5.784, P<0.05). Levels of vital signs and laboratory test indexes of patients in two groups before and during treatment were similar. There were no statistically significant differences in adverse reaction or drug-related adverse reaction between patients in two groups during treatment (with P values above 0.05). (2) Open trial. A total of 2 380 patients were enrolled in, and 2 329 patients finished the trial. The complete wound healing time of patients was (16.28±0.10)d. At last, 2 257 (96.91%) patients were totally cured, while excellence, progress, and invalid results were achieved in 36 (1.55%), 16 (0.69%), and 20 (0.86%) patients, respectively. Vital signs and laboratory test indexes of patients before and during treatment were similar. The drug-related adverse reaction was observed in 44 patients (1.89%). CONCLUSIONS: External use of rhGM-CSF gel on deep partial-thickness burn wounds can promote wound healing and is safe for clinical use.