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ObjectiveWe aimed to investigate the secular prevalence of gestational diabetes mellitus (GDM) and evaluate its adverse pregnancy outcomes among pregnant women in Hebei province, China.MethodsWe analyzed the data from the monitoring information management system for pregnant women in 22 hospitals of Hebei province, China. In this study, 366,212 individuals with singleton live births from 2014 to 2021 were included, of whom 25,995 were diagnosed with gestational diabetes. We described the incidence of common complications and further analyzed the clinical characteristics in GDM patients and the relationship between GDM and adverse pregnancy outcomes.ResultsThe top 3 pregnancy complications in Hebei province are anemia, gestational hypertension, and GDM. The average incidence of GDM was 7.10% (25,995/366,212). The incidence rate of GDM significantly increased from 2014 to 2021 (χ2trend = 7,140.663, P < 0.001). The top 3 regions with GDM incidence were Baoding (16.60%), Shijiazhuang (8.00%), and Tangshan (3.80%). The incidence of GDM in urban pregnant women (10.6%) is higher than that in rural areas (3.7%).The difference between the GDM and Non-GDM groups was statistically significant in terms of maternal age, gravidity, parity, education level, and incidence of pregnancy complications (gestational hypertension, heart diseases, and anemia) (P < 0.05). GDM individuals were at significantly increased risk of most assessed adverse pregnancy outcomes, including premature delivery, Cesarean delivery, uterine inertia, neonatal intensive care unit (NICU) admission, Apgar (activity-pulse-grimace-appearance-respiration) score at 1 min, and macrosomia (P < 0.05). The multivariate logistic regression analysis showed that GDM was an independent risk factor in terms of premature birth, Cesarean delivery, uterine inertia, placental abruption, NICU admission, and macrosomia.ConclusionThe risk of adverse pregnancy outcome in pregnant women with GDM is significantly increased. In order to reduce the occurrence of adverse pregnancy outcomes, effective interventions are needed.

sRecent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Background Tenvermectin A is a new avermectin derivative that has good insecticidal and acaricidal effects. In order to study the resistance of Plutella xylostella to tenvermectin A, a sensitive strain (SS) and a laboratory-selected tenvermectin A-resistant strain (RS, 33.57-fold) were used to evaluate cross-resistance and fitness costs as well as to determine the resistance mechanism. Results There was no cross-resistance with common pesticides except for moderate cross-resistance with cypermethrin (resistance ratio = 10.26-fold) observed in RS. The activities of metabolic enzymes were measured, and the results showed that mixed function oxidase (MFO) and carboxylate esterase (CarE) in RS increased significantly by 2.92- and 2.86-fold, respectively, compared with SS. In addition, there was no obvious difference in glutathione-S-transferase (GST), which indicated that enhanced MFO and CarE activities may be the main mechanisms of detoxification. In the four typical resistance-related genes, expression of GluCl (4.86-fold), ABCC2 (3.85-fold), and CYP6 (2.94-fold) in RS were significantly promoted, but expression of GST was not. The clone and sequence of the PxGluClα subunit displayed six mutations that could lead to changes in the amino acid residues. Conclusion High suitability related to tenvermectin A resistance was observed in RS, and it was found that the developmental stages of RS were significantly shortened and the survival rate of females was reduced. In addition, the mechanism of resistance to tenvermectin A may be regulated by the glutamate-gated chloride channel, ATP-binding cassette transporter, and MFO. In general, the study of resistance and biochemical mechanisms can provide beneficial and rational information for the management of resistance in P. xylostella. © 2021 Society of Chemical Industry.

Background Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71-4.92 mIU/L, 12.2-20.1 pmol/L, 3.9-6.0 pmol/L, 65.6-135.1 nmol/L, and 1.2-2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

Endothelial progenitor cells (EPCs) have been discovered to be relevant to the prognosis of cardiovascular diseases. Previous research has demonstrated that EPCs serve vital roles in the occurrence and development of atherosclerosis. Significant improvements have been made in MRI technology and in the experimental use of EPCs for therapeutic angiogenesis and vascular repair. Nevertheless, the migratory, adhesive, proliferative and angiogenic properties of EPCs remain unknown. The aims of the present study were to investigate the potential of using non‑invasive monitoring with ultrasmall superparamagnetic iron oxide nanoparticle (USPION)‑labeled endothelial progenitor cells (EPCs) after transplantation, and to assess the treatment outcomes in an atherosclerotic rabbit model. EPCs derived from rabbit peripheral blood samples were labeled with USPION‑poly‑l‑lysine (USPION‑PLL). The morphology, proliferation, adhesive ability and labeling efficiency of the EPCs were determined by optical and electron microscopy. Moreover, biological activity was assessed by flow cytometry. In addition, T2‑weighted image fast spin‑echo MRI was used to detect cell labeling. USPION content in the labeled EPCs was determined by Prussian blue staining and scanning electron microscopy. Rabbit atherosclerosis model was established using a high‑fat diet. USPION‑labeled EPCs were transplanted into rabbits, and in vivo MRI was performed 1 and 7 days after transplantation. It was found that EPCs cultured on Matrigel formed capillary‑like structures, and expressed the surface markers CD133, CD31, CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). The optimal USPION concentration was 32 µg/ml, as determined by adhesion and proliferation assays. It was identified that USPION‑PLL nanoparticles were 10‑20 nm in diameter. Histopathological analysis results indicated that 1 day after transplantation of the labeled EPCs, blue‑stained granules were observed in the intima of vascular lesions in rabbit models after Prussian blue staining. Therefore, the present results suggest that USPION‑labeled EPCs may play a role in repairing endothelial injury and preventing atherosclerosis in vivo.

Threadfin porgy Evynnis cardinalis is both a dominant fish species and an important fishing target in bottom trawl fisheries in the Beibu Gulf, South China Sea. It was listed as endangered (EN) in a recent International Union for Conservation of Nature (IUCN) red list. Despite its economic importance and endangered status, limited research on its biological characteristics and spatial-temporal distribution has been undertaken this last decade, creating uncertainty in current conservation and management. We analyse this species' spatial distribution characteristics using data from four seasonal bottom trawl surveys in 2014-2015, and report average catch per unit effort to vary seasonally, from 49.1 to 594.5 ind h-1 . Growth, mortality and sexual maturity are reported for four time periods based on data from bottom trawl fishery surveys over 1961-1962, 1998-1999, 2006, and 2014-2015. Length frequency distributions changed from bimodal to unimodal, and the female-to-male ratio increased. Mean body length and length at first maturity decreased, whereas the growth coefficient increased, indicating miniaturization, early sexual maturity and accelerated growth, respectively. We report sparid catch to have first exceeded maximum sustainable yield in 2001, and to have remained overfished from 2010 to 2015. Since the 1980s, low-trophic-level fishes such as E. cardinalis have replaced high-trophic-level fishes such as Crimson snapper Lutjanus erythropterus to become dominant species. As catches have increased substantially, these species have been faced with overfishing, driving the ecosystem into an unstable state.

Objective. To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren’s syndrome (pSS). Methods. Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher’s exact analysis, Mann–Whitney U-test, and Kruskal-Wallis test compared differences among groups. Independent risk factors of pSS were determined by multiple logistic regression analysis. Receiver-operator characteristic curves (ROC) were carried out to estimate the diagnostic value. Results. Compared to non-SS controls, loss of membranous EpEX and EpICD expression was observed in LSGB of pSS patients, which occurred in parallel with increased accumulation of cytoplastic and nuclear EpICD. The subcellular EpEX/EpICD expressions were associated with various features of pSS patients, especially histopathological grade of LSGB. Furthermore, high IHC scores of membranous EpEX were independent risk factors for pSS, even for the pSS patients at early stage. The IHC scores of subcellular EpEX/EpICD were of great diagnostic value for pSS with high sensitivity (70-80%) and specificity (85-95%). Conclusion. This study first found the aberrant expression pattern of EpCAM in LSG of pSS patients. The IHC scores of subcellular EpEX/EpICD were demonstrated to have the potential to act as diagnostic biomarkers for pSS.

Background The prevalence of anxiety and depression in pregnant women has significantly increased after the spread of COVID-19 throughout the world. We carried out this meta-analysis to reveal the information about risk factors for depression and anxiety in pregnant women during the COVID-19 pandemic. Methods We searched the PubMed, Embase and CNKI (China National Knowledge Infrastructure) databases for all articles. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the risk factors for mental health. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Results We collected 17 studies including 15,050 pregnant women during the COVID-19 pandemic. Our results found that factors including decrease in the perception of general support and difficulties in household finances have damage effects on anxiety, and factors including undereducated, unemployed during pregnancy, with a chronic physical illness before pregnancy, decrease in the perception of general support, difficulties in household finances, disobey the isolation rules, and smoking during pregnancy have increased risk of depression. Conclusion Our meta-analysis revealed some risk factors for mental health in pregnant women during COVID-19 pandemic. Mental health interventions in pregnant women may involve targeted methods individually.

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 patients with rheumatic diseases were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet's disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p

ObjectivesHip involvement is an important cause of disability and poor prognosis in patients with spondyloarthritis (SpA). Tumor necrosis factor (TNF)-α inhibitor treatment has been demonstrated to be effective in SpA patients with hip arthritis; however, quantitative assessment using MRI in long-term follow-up needs further application and observation.MethodsA total of 239 patients were involved in this study. Methotrexate and sulfasalazine were given as basic treatment. In total, 165 patients received TNF-α inhibitors plus basic treatment, and 74 received basic treatment only, as controls. Clinical symptoms were assessed at baseline and at weeks 12, 24, and 52. MRI performances of hip arthritis, including bone marrow edema (BME) and synovitis, were quantitatively assessed using the Hip Inflammation MRI Scoring System (HIMRISS).ResultsThe clinical values of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Harris hip score, and Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR in both groups showed significant clinical remission at week 52 (p < 0.001). However, the change in disease activity levels at week 52 in the control group was significantly worse than in the TNF-α inhibitor group. At week 52, MRI showed a significant remission trend in the TNF-α inhibitor group versus baseline, and total HIMRISS scores were significantly decreased (26.49 ± 10.37 vs. 20.59 ± 9.41, p < 0.001); the control group only had slight improvement (p < 0.05).ConclusionsTNF-α inhibitors could significantly improve clinical and MRI manifestations of hip involvement in patients with SpA. Quantitative MRI assessment combined with clinical assessment can be used to accurately evaluate the treatment effect of TNF-α in SpA patients with hip involvement to help guide targeted treatment.

ObjectiveInjections of proteoglycan aggrecan (PGA) have been reported to induce axial spondyloarthritis (ax-SpA) in BALB/c mice. It is considered to be a model for radiographic ax-SpA. However, evaluation of the extent of axial disease by histopathological assessment of every intervertebral space is labor-intensive. The objective of our paper is to test the feasibility of Micro Computed Tomography (Micro-CT) in rapidly enumerating the number of intervertebral spaces affected in each mouse.MethodsArthritis was induced in BALB/c mice by intraperitoneal injections of PGA. Involvement of several spinal segments, and selected sacroiliac and hip joints were evaluated by histopathology. The involvement of all intervertebral spaces, sacroiliac and hip joints was evaluated by Micro-CT.ResultsBALB/c mice injected with PGA developed histopathology of SpA-like axial lesions, including spondylitis, sacroiliac joint arthritis and hip joint arthritis. Micro-CT allowed us to clearly enumerate the number of lesions in each mouse.ConclusionMicro-CT allows quantitative assessment of the extent of axial involvement in PGA-induced mouse spondylitis. This can be a useful tool in assessing therapeutic interventions.

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As an important methyltransferase, G9a has been reported to be abnormally expressed in various human cancers and plays essential roles in tumorigenesis. However, the biologic functions and molecular mechanisms of G9a in gastric cancer (GC) remain unclear. GC is the fifth most frequent cancer around the world and seriously threatens human health, especially in developing countries. Here, our results showed that high expression of G9a was intensively correlated with poor prognosis and more advanced stages of GCs. Knockdown of G9a or treatment with its inhibitor, BIX01294, significantly reduced cell growth by cell cycle arrest and autophagy. In addition, the mechanistic target of rapamycin (mTOR) was evidently decreased after G9a silencing or inhibition, and mTOR activation partially rescued the effects of cell proliferation inhibition and autophagy induced by G9a knockdown or inhibition. Down-regulation of G9a effectively inhibited mTOR expression and tumor growth in the xenograft tumor model of GC cells. We also showed that G9a regulates mTOR and cell proliferation and autophagy depending on its histone methylase activity. Using chromatin immunoprecipitation analysis, we found that mTOR expression was associated with promoter methylation and an enrichment for mono- and dimethylated histone 3 lys 9 (H3K9). G9a knockdown revealed an apparent decrease in H3K9 monomethylation levels, but no apparent change in H3K9 dimethylation levels at the mTOR promoter. These results indicate that G9a is a novel and promising therapeutic target for GC treatment.-Yin, C., Ke, X., Zhang, R., Hou, J., Dong, Z., Wang, F., Zhang, K., Zhong, X., Yang, L., Cui, H. G9a promotes cell proliferation and suppresses autophagy in gastric cancer by directly activating mTOR.

Anti-nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome-wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 × 10-22 ; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 (P = 5.78 × 10-28 ; OR, 3.89; 95% CI, 3.05-4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti-sp100-positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA-DRβ1-Asn77/Arg74, DRβ1-Ser37, and DPβ1-Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10-9 ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.

The objective of the present study was to generate multiple regression models for stature estimation on the basis the combination of the clavicle, scapula and sternum derived from 3D-VRT images in Chinese population. The study sample comprised 363 individuals from China, including 159 females and 204 males, with documented ages between 19 and 82 years. Separate multiple linear regression equations for estimating stature on the basis of the measurements from the clavicle, scapula and sternum were then devised for males and females. For assessing the correlation between the stature and measurements of the clavicle, scapula and sternum, the Pearson's correlation coefficient was calculated and its significance was tested by Students t test. Finally, the multiple regression equations calculated from the measurements of the clavicle, scapula and sternum in relation to stature for each sex were established in the present study. The accuracy of stature prediction ranged from 4.777 to 5.313 cm for male and from 4.388 to 4.658 cm for female. In conclusion, the present results provide indications that the combination of the clavicle, scapula and sternum should be used as alternatives for stature estimation, and the multiple equations presented for stature estimation seem to be a more accurate than the equations from single bone.

BackgroundDehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed ofMyristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated.MethodsIn this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo.ResultsOur findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models.ConclusionsCollectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

Purpose To investigate risk factors of bone cement leakage in percutaneous vertebroplasty(PVP)for osteoporotic vertebral compression fracture (OVCF). Methods A total of 236 patients (344 vertebrae) who underwent PVP between November 2016 and June 2020 were enrolled in the study. Clinical and radiological characteristics, including age, gender, course of disease, trauma, type of vertebral fracture, cortical continuity of vertebral body, intervertebral vacuum cleft (IVC), fracture severity, fracture level, basivertebral foramen, bone cement dispersion types, the cement injection volume, the type of cement leakage, puncture approach, and intrusion of the posterior wall, were considered as potential risk factors. Three types of leakage (type-B, type-C, and type-S) were defined and risk factors for each type were analyzed. Logistic analysis was used to study the relationship between each factor and the type of cement leakage. Results The incidences of the three types of leakage were 28.5%, 24.4%, and 34.3%. The multinomial logistic analysis revealed that the factors of type-B leakage were the shape of cement and basivertebral foramen. One significant factor related to type-C leakage was cortical disruption, and the factors of type-S leakage were bone cement dispersion types, basivertebral foramen, cleft, fracture severity, an intrusion of the posterior wall, and gender. Conclusion Different types of cement leakage have their own risk factors, and the analysis of risk factors of these might be helpful in reducing the rate of cement leakage.

To investigate specific technique and clinical effects of closed folding top consolidation maneuver combined with splint fixation maneuver for consolidation and cedar bark external fixation splint for the treatment of double fractures of distal ulna and radius in children.From January 2017 to December 2019, 17 children with double fractures of distal ulna and radius were treated with closed folded apex consolidation maneuver, including 13 males and 4 females, aged from 4 to 11 years old with an average of (7.29±2.34) years old. The fractures were fixed with cedar bark splint and followed up for 6 months, and alignment of fracture was evaluated according to the latest X-rays by follow up, and function of the affected limbs was evaluated by Anderson forearm function evaluation criteria.Fifteen of 17 children were successfully reset immediately, and 2 children were successfully reset again. The average fixed time was (25.00±3.35) days. At 6 months of follow up, 12 patients got excellent results, 3 good, 2 fair, and 0 poor according to Anderson forearm function evaluation criteria. The position of all children were larger than 3/4, and 10 children were received anatomical reduction, alignment of 4 children was less than 10°, 3 children was less than 15°. No complications such as fracture displacement, nonunion, compartment syndrome, and forearm rotation dysfunction occurred.Restoration of distal radius double fracture in children with the combination of the closed folding and top fixation maneuver and splint fixation maneuver has advantages of higher success rate, lower complications, which could reduce operating difficultyand pain of patients.

Ankylosing spondylitis (AS) is most common in adolescents and the ultimate result is disability, which places a huge burden on patients and society. Therefore, the key to improve the prognosis of AS is the early diagnosis of hip injury. To examine if AS patients whose hip pain is either absent or minimal might already have observable MRI and X-ray hip changes. Clinical and imaging hip data were systematically analyzed in 200 healthy controls (HC) and 300 AS with varying degrees of hip pain. Forty-four patients with early hip osteoarthritis (OA) served as positive imaging controls. In MRI images, BME lesions in the STIR sequence were much more frequent in AS (62%) compared to HC (2%) (p < 0.0001). Most importantly, 42% of AS with no or minimal hip pain had one or more MRI lesions. This was much more frequent compared to the 2% in HC (p < 0.05). These lesions in AS were observed singly or in combination in the trochanters (8%), femoral heads (12%), and acetabula (13%). Parallel finding that X-ray changes were present in patients with minimal or no hip pain was also observed with X-ray. Based on the normal hip width of HC, joint space narrowing was observed in 94.3% of the entire AS cohort, and importantly 56.7% of AS patients with no or mild hip pain. In these latter patients, functional activities of the hips such as walking were normal. At least 40% of AS patients with minimal or no hip pain might already show MRI and X-ray changes.

Forensic identification of human remains is crucial for legal, humanitarian, and civil reasons. Wide heterogeneity in sphenoid sinus morphology can be used for personal identification. This study aimed to propose a new protocol for personal identification based on three-dimensional (3D) reconstruction of sphenoid sinus CT images using Iterative Closest Point (ICP) algorithm. Seven hundred thirty-two patients which consisted of 348 females and 384 males were retrospectively included. The study sample includes 732 previous images as a source point set and 743 later ones as a scene target set. The sphenoid sinus computed tomography (CT) images were processed on a workstation (Dolphin imaging) to obtain 3D images and stored as a file format of Stereo lithography (.STL). Then, a Python library vtkplotter was used to transform the STL format to PLY format, which was adapted to Point Cloud Library (PCL). The ICP algorithm was used for point clouds matching. The metric Rank-N recognition rate was used for evaluation. The scene target set of 743 individuals was compared with the source point set of 732 individual models and achieved Rank-1 accuracy of 96.24%, Rank-2 accuracy of 99.73%, and Rank-3 accuracy of 100%. Our results indicated that the 3D point cloud registration of sphenoid sinuses was useful for assessing personal identification in forensic contexts.

Background Lycorine hydrochloride (LH), an alkaloid extracted from the bulb of the Lycoris radiata, is considered to have anti-viral, anti-malarial, and anti-tumorous effects. At present, the underlying mechanisms of LH in gastric cancer remain unclear. MCL1, an anti-apoptotic protein of BCL2 family, is closely related to drug resistance of tumor. Therefore, MCL1 is considered as a potential target for cancer treatment. Methods The effect of LH on gastric cancer was assessed in vitro (by MTT, BrdU, western blotting…) and in vivo (by immunohistochemistry). Results In this study, we showed that LH has an anti-tumorous effect by down-regulating MCL1 in gastric cancer. Besides, we unveiled that LH reduced the protein stability of MCL1 by up-regulating ubiquitin E3 ligase FBXW7, arrested cell cycle at S phase and triggered apoptosis of gastric cancer cells. Meanwhile, we also demonstrated that LH could induce apoptosis of the BCL2-drug-resistant-cell-lines. Moreover, PDX (Patient-Derived tumor xenograft) model experiment proved that LH combined with HA14–1 (inhibitor of BCL2), had a more significant therapeutic effect on gastric cancer. Conclusions The efficacy showed in our data suggests that lycorine hydrochloride is a promising anti-tumor compound for gastric cancer.

Background Preventive intra-aortic balloon pump (IABP) for high-risk patients with stable hemodynamics is controversial, and its definition of high-risk is still unclear. This study aimed to investigate the effect of prophylactic IABP on the early outcome of left main disease (LMD) patients receiving off-pump coronary artery bypass grafting (OPCABG) with stable hemodynamics. Methods From January 2013 to April 2020, 257 consecutive patients who underwent OPCABG through sternotomy were enrolled in this study. All LMD patients (greater than 70%) had stable hemodynamics (BP>100 mmHg without vasoconstrictor substance infusion). Early outcomes of 125 patients with prophylactic IABP (IABP group) and 132 patients without IABP (Control group) were compared in this study. Results IABP did not show favorable effect on the conversion to CPB (RR 0.63, 95%CI 0.05–7.89, P = 0.7211), perioperative MI (RR 0.69, 95%CI 0.22–2.12, P = 0.5163), mortality (RR 0.65, 95%CI 0.04–10.25, P = 0.7608) or the composite end of the conversion, MI and mortality (RR 0.63, 95%CI 0.23–1.74, P = 0.3747). There was greater incidence of prolonged ventilation in IABP after adjustment (RR2.16, 95%CI 1.12–4.18, P = 0.0221). There was no IABP-related mortality or limb ischemia. Conclusion No significant difference in early outcomes was observed in hemodynamically stable patients with LMD between prophylactic IABP group and control group. Prophylactic IABP may be unnecessary in patients with LMD undergoing OPCABG.

The anatomic stage groups (ASG) have been arguably the most powerful in predicting breast cancer (BC) outcomes. Recognizing the prognostic influence of histologic grade and receptor status, the 8th AJCC mandates their incorporation into the newly established prognostic stage groups (PSG). This staging scheme was subsequently revised to provide pathological and clinical prognostic stage tables (PPSG/CPSG) due to its incapability to categorize a significant subset of BCs, with the former only used for patients having surgical resection as the initial treatment, and the latter for all patients. Given the increasingly used neoadjuvant therapy, PPSG cannot be assigned in a significant proportion of higher staged BCs. In this study, we validated the CPSG in a cohort of 5321 BCs. Compared to ASG, the application of CPSG resulted in assigning 16.1% and 27.2% of cases to a higher or a lower stage group in non-stage IV BCs, respectively. The changes were seen mostly frequently in ASG IB, followed by IIIC, IIB, IIA, IIIA, IIIB, and IA. In 7.9% of cases, the assigned CPSG changed more than one stage group from the ASG. CPSG provided an improved overall discriminating power in predicting BC-specific survival when compared to ASG. Pairwise comparison using the Cox proportional hazard model demonstrated further advantages for CPSG as the latter showed a significant difference in all categories when compared to their proximate groups, except IIA vs. IB and IIIA vs. IIIB. In contrast, a significantly different hazard was only seen when comparing IIB vs. IIA, IIIA vs. IIB, and IV vs. IIIC for ASG. Thus, the revised 8th AJCC CPSG provided a superior overall staging scheme for predicting prognostic outcomes in BC patients receiving standard of care treatment. Further validation using the available data with larger populations and longer follow-up may be needed to refine and improve this table.

Background The COVID-19 pandemic has become a great threat to public health, which has greatly impacted the study and life of undergraduate students in China. This study aims to perform a survey of their knowledge, attitude and practice (KAP) associated with COVID-19. Methods A cross-sectional survey was designed to gather information regarding the COVID-19 related KAP among undergraduates during the home isolation in the outbreak. Subjects were recruited from 10 universities in Shaanxi Province, China. Enrollees voluntarily submitted their answers to a pre-designed questionnaire online. Results A total of 872 subjects (female, 534; male, 338) were enrolled with ages from 17 to 25 years old. This cohort included 430 medical and 442 non-medical students, 580 freshmen and 292 higher school year students. There were 453 from public schools and 442 from private school, residing in 28 regions and provinces at the time of study. Results showed that appropriate knowledge was acquired by 82.34% subjects; the levels were significantly higher in undergraduates from public universities and medical majors than those from private schools and non-medical majors (ppp Conclusions Most undergraduates acquired necessary knowledge, positive attitude and proactive practice in response to COVID-19 outbreak; but their KAP scores significantly varied by gender, major and school types.

At present, the clinical detection method of human papillomavirus (HPV) is mainly based on the PCR method. However, this method can only be used to detect HPV DNA and HPV types, and cannot be used to accurately predict cervical cancer. HPV16 E7 is an oncoprotein selectively expressed in cervical cancers. In this study, we prepared an HPV16 E7-histidine (HIS) fusion oncoprotein by using a prokaryotic expression and gained several mouse anti-HPV16 E7-HIS fusion oncoprotein monoclonal antibodies (mAbs) by using hybridoma technology. Two mAbs, 69E2 (IgG2a) and 79A11 (IgM), were identified. Immunocytochemistry, immunofluorescence, immunohistochemistry, and Western blot were used to characterize the specificity of these mAbs. The sequences of the nucleotide bases and predicted amino acids of the 69E2 and 79A11 antibodies showed that they were novel antibodies. Indirect enzyme-linked immunosorbent assay (ELISA) with overlapping peptides, indirect competitive ELISA, and 3D structural modeling showed that mAbs 69E2 and 79A11 specifically bound to the three exposed peptides of the HPV16 E7 (HPV16 E749&ndash, 66, HPV16 E773&ndash, 85, and HPV16 E791&ndash, 97). We used these two antibodies (79A11 as a capture antibody and 69E2 as a detection antibody) to establish a double-antibody sandwich ELISA based on a horseradish peroxidase (HRP)-labeled mAb and tetramethylbenzidine (TMB) detection system for quantitative detection of the HPV16 E7-HIS fusion oncoprotein, however, it was not ideal. Then we established a chemiluminescence immunoassay based on a labeled streptavidin-biotin (LSAB)-ELISA method and luminol detection system&mdash, this was sufficient for quantitative detection of the HPV16 E7-HIS fusion oncogenic protein in ng levels and was suitable for the detection of HPV16-positive cervical carcinoma tissues. Collectively, we obtained two novel mouse anti-HPV16 E7 oncoprotein mAbs and established an LSAB-lumino-dual-antibody sandwich ELISA method for the detection of the HPV16 E7-HIS fusion oncogenic protein, which might be a promising method for the diagnosis of HPV16-type cervical cancers in the early stage.

Highlights • COVID-19 belongs to yi bing in traditional Chinese medicine(TCM), and its pathogenesis is characterized by "dampness, heat, poison, stasis, closure and prostration". • Experiences in TCM are well worth learning for the management of patients with COVID-19. • Health care systems should have both Chinese medicine practitioners and Western medical doctors to work together to give optimal care for this COVID-19 crisis., Objective Presentation of a case illustrating the benefits of traditional Chinese medicine (TCM) for treatment of Coronavirus disease 2019 (COVID-19) in critically ill patients. Clinical features and outcome A 58-year-old woman presented with cough, fever, dizziness, chest tightness, polypnea and poor appetite. She was admitted to Guizhou Provincial People’s hospital, and diagnosed with critically ill type of COVID-19 in February, 2020. According to the patient's symptoms and signs, the TCM syndrome differentiation was qi deficiency, dampness-stasis and toxin accumulation. Then she received the combined therapy of a modified Chinese herbal formula and Western medicine. During a twelve-day period of treatment, her respiratory distress and appetite quickly improved. Abnormal laboratory indicators were resumed in time and lung lesions in CT scan largely absorbed. no side effects associated with this Chinese herbal formula were found. Before discharge, two consecutive nasopharyngeal swabs were shown to be negative for severe acute respiratory coronavirus 2 (SARS-CoV-2). Conclusions Our case report suggests that collaborative treatments with traditional Chinese medicine prove beneficial in the management of COVID-19 in critically ill patients. In order to give optimal care for this COVID-19 crisis for the whole world, Chinese medicine practitioners and Western medical doctors should work together in frontline.

Objectives This study aimed to determine the sensitivity of a first-trimester routine scan in detecting spina bifida (SB) and evaluating the first-trimester intracranial signs. Methods This retrospective study was a review of a prospectively collected database. All cases of SB diagnosed in a tertiary center from 2008 to 2015 were identified. The ultrasound images and medical records were reviewed. All cases of SB diagnosed prenatally were confirmed at birth or autopsy. Results A total of 24 cases of SB were diagnosed from 53,349 pregnancy cases. Except for 10 cases with a body stalk anomaly, craniorachischisis, or iniencephaly, 7 cases with open spina bifida (OSB) and 7 cases with closed spina bifida (CSB) were analyzed. The first-trimester detection rates were 100% (7 of 7) for OSB and 28.5% (2 of 7) for CSB. Eight cases were highly suspected of SB in the first trimester because of an abnormal appearance of the posterior brain; 3 were false-positive cases. Two isolated cases of OSB had first-trimester intracranial signs. An obliterated cisterna magna (CM) showed the highest sensitivity for OSB but low specificity. Two cases of OSB had no discernible landmark of intracranial translucency and the CM, and 4 showed normal intracranial translucency with an obliterated CM. All CSB cases were coupled with a normal hind brain except for 2 cases. Conclusions A first-trimester routine scan has high sensitivity in screening for OSB. The CM may be the most sensitive intracranial sign.

Age estimation is an important topic of human identification in forensic practice, especially coming to biological samples in crime scene, such as blood, saliva, semen. As rate-limiting enzyme in Nucleotide excision repair (NER) that was associated with aging, Excision repair cross-complementation group 5 (ERCC5) was considered to be a candidate biomarker for individual age estimation. The ERCC5 mRNA and protein expression levels association with age have been demonstrated in our previous study. However, very little is known about relationship DNA-based quantification of ERCC5 with age. In this study, we detected ERCC5 level in peripheral blood from a Chinese Han population by SYBR qPCR assay to gain better insight into the quantitative relationship with age. The results showed ERCC5 level declined with individual age with a negative correlation(r = -0.8, R2 = 0.63, P

Background: Circular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD. Methods and Results: Using RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs. Conclusion: Collectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.

Invasive fungal infection (IFI) is one of the leading causes of early death after renal transplantation. Voriconazole (VRC) is the first-line drug of IFI. Because of the large inter- and intra-individual variability in VRC plasma concentrations and the narrow therapeutic window for treating patients with IFIs, it is crucial to study the factors which could influence pharmacokinetic variability. We performed a population pharmacokinetics (PPK) study of VRC for personalized medicine. A total of 125 trough concentrations (Cmin) from 56 patients were evaluated retrospectively. Nonlinear mixed effect model (NONMEM) was used to describe a PPK model that was internally validated by Bootstrap method. Potential covariates included demographic characteristics, physiological and pathological data, concomitant medications, and CYP2C19 genotype. A one-compartment model with first-order absorption and elimination was fit to characterize the VRC pharmacokinetics in renal transplant recipients (RTRs). Aspartate aminotransferase (AST) had a significant influence on clearance (CL) while CYP2C19 genotype had a major impact on the volume of distribution (V). The parameters of CL and V were 4.76 L·h-1 and 22.47 L, respectively. The final model was V (L) = 22.47 × [1 + 2.21 × (EM = 1)] × [1+ 4.67 × (IM = 1)] × [1 + 3.30 × (PM = 1)] × exp (0.96); CL (Lh-1) = 4.76 × (AST / 33)^(−0.23) × exp (0.14). VRC Cmin in intermediate metabolizers was significantly higher than in extensive metabolizers. Liver function and CYP2C19 polymorphism are major determinants of VRC pharmacokinetic variability in RTRs. Genotypes and clinical biomarkers can determine the initial scheme. Subsequently, therapeutic drug monitoring can optimize clinical efficacy and minimize toxicity. Hence, this is a feasible way to facilitate personalized medicine in RTRs. In addition, it is the first report about PPK of VRC in RTRs. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy., Highlights • DN, DP cells were reprogrammed into innate NK-like cells after thymic CD147 deleted • Loss of CD147 results in impaired Bcl11b expression and T-lineages development, which can be rescued by Wnt3a stimulation. • CD147 is an vital target for immune modulation via NK-like cells in tumor therapy. Tumor therapy is a difficult task and many methods have been used. Among them, tumor immunotherapy is a focus in the field and has made great progress. In this study, we found CD147 is an vital target for immune modulation via NK-like cells in tumor therapy, which means CD147 antibody may be through regulating immune cells to achieve tumor therapy. Although CD147 antibody has been used for liver cancer, making clear the mechanism of CD147 antibody mediated tumor therapy may be benefit for guiding clinical treatment.

Grading of pancreatic neuroendocrine tumors (pNETs) is currently based on mitotic rate and Ki67 proliferation index. Phosphohistone-H3 (PHH3) is an effective marker for mitosis that has been proposed to use in grading various NETs. It remains unclear which method more accurately predicts grade and clinical outcome. Cases of pNET were evaluated using immunohistochemical stains for Ki67 and PHH3. In addition, each case was evaluated for necrosis, lymphovascular invasion, and perineural invasion and compared with stage. R project statistical analysis was used for comparisons. Sixty-three cases were included in the study including 29 males and 34 females (M:F 0.9) with a median age of 59 years (ranging 34–84). There was not a significant discrepancy in the stratification of tumor grades for Ki67 and PHH3. PHH3 significantly predicted lymph node metastasis ( p=0.041). Necrosis correlated with overall survival ( p=0.017). The results suggest that PHH3 is an effective marker for determining mitotic activity and can be used alternative to Ki67. In addition, necrosis may be included in the reporting of pNET as it may play a prognostic role. Larger scale studies are warranted to understand the biology and behavior of these tumors.

Background As one of the endoplasmic reticulum proteins, calreticulin (CRT) plays a significant role in the body, and it has been used by many researchers as a target for anti-tumor therapy. Objective The main purpose of the present study was to study expression of CRT of human osteosarcoma, and analyze the distinctions between normal and tumor tissues, pre- and post-chemotherapy patients, and metastatic and non-metastatic tumors in respect to this expression. Methods Immunofluorescent staining was used in order to investigate expression of CRT in diverse tissues. The whole RNA and proteins were extracted from the crushed tissues and used in the reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis. Results The present study detected expression of CRT in patients with osteosarcoma and revealed a higher expression level in normal tissues surrounding tumors compared with tumor tissues, in the non-metastasis group compared with the metastasis group, and in the chemotherapy group compared with the non-chemotherapy group. Conclusions These results could indicate a brand-new biological marker which may be applied to estimate the features and prognosis of osteosarcoma.

To expand the database on magnetic resonance imaging (MRI) analysis of distal tibial and calcaneal epiphyses as proposed by Saint-Martin et al. and investigate a more elaborate staging technique to establish regression models for age estimation in a modern Chinese Han population. T1-weighted ankle MRIs were retrospectively collected from April 2008 to July 2019, and data from 590 individuals (372 males and 218 females; aged from 8 to 25 years old) were obtained. One-sided sagittal images were assessed because data from both sides were considered coincidental, as no significant differences were found (P > 0.05). Three-stage and six-stage staging techniques were applied separately and subsequently compared. A subset was re-assessed a second time and by a different observer. Regression models were established accordingly. Our results showed very good repeatability and consistency of two staging techniques (all Cohen’s kappa values were more than 0.8). By comparison, the values of the coefficient of determination (R2) of the six-stage technique were generally higher than those of the three-stage technique. Compared with the distal tibia and two ankle bones combined, the calcaneus decreased the mean absolute deviation (MAD) with the six-stage technique. In males, incorporating only the calcaneus resulted in a MAD of 2.15 years, with correct classification rates of 87.5% adults and 50.0% among minors. In females, the corresponding results were 1.67 years, 100.0%, and 44.4%, respectively. The six-stage technique may outperform the three-stage technique in MRI analysis of ankle bones for age estimation, while age estimation based on the calcaneus may perform better than that based on the distal tibia or both ankle bones in a modern Chinese Han population.

BACKGROUND The current study aims to investigate the expression of antisense noncoding RNA in the INK4 locus (ANRIL) in serum of patients with ischemic stroke and its correlation with high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). METHODS Real time PCR analysis was carried out to evaluate the level of ANRIL. The levels of hs-CRP and MMP-9 were evaluated using ELISA. ROC analysis was carried out to evaluate the diagnostic value of ANRIL, hs-CRP and MMP-9. Pearson's correlation analysis was carried out to evaluate the expression of ANRIL in serum of hs-CRP and MMP-9. RESULTS Our data showed that the expression levels of ANRIL, hs-CRP, and MMP-9 in serum of the patients were significantly higher than those of the control group (p < 0.05). Pearson's correlation analysis showed that there was a positive correlation between the expression of ANRIL and hs-CRP and MMP-9. Meanwhile, serum levels of ANRIL, hs-CRP, and MMP-9 in patients with severe neurological deficits were significantly higher than those in patients with moderate and mild neurological deficits (p < 0.05). Moreover, the expression levels of ANRIL, hs-CRP, and MMP-9 in serum of patients with different degrees of neurological impairment have different correlations. More importantly, ROC analysis demonstrated that the combined use of ANRIL, hs-CRP, and MMP-9 demonstrated higher diagnostic value for stroke patients. CONCLUSIONS Serum ANRIL may be used as a molecular marker in the diagnosis of ischemic stroke and may play an important role in the pathogenesis and development of ischemic stroke in cooperation with hs-CRP and MMP-9.

Injectable gels as a new avenue have demonstrated profound promise for the treatment of cancers. However, the long-lasting but far-reaching challenge of in situ treatment of cancers is how to construct an injectable gel only with original chemotherapeutic agents. In this work, we reported injectable gels with a high and quantitative drug loading based on the self-assembly of paclitaxel (PTX) itself. Non-covalent forces, hydrogen bond interactions and π-π stacking, play a crucial role in the formation of PTX gels. In vivo gel retention experiment illustrates that PTX gel remains in situ post injection for more than 40 days. Compared with saline and PTX (intravenous and in situ administration), subcutaneous injection of PTX gel not only reduces the toxicity of the drug in normal organs, resulting in the increase of mouse body, but also maintains sustained release of PTX in the tumor vicinity and thereby displays excellent antitumor activity. The results of histopathological analysis indicate that PTX gel shows less side effects or systemic toxicity to the normal organs, and more importantly, effectively inhibits tumor metastasis. This novel injectable PTX gel has great potential as an effective self-assembly system in situ treatment of cancers.

The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct.Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations.Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P0.001 and0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P0.0001 and 0.0009, and P0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF-1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022).The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.

The incidence of bilateral breast cancer (BBC) reportedly ranges from 1.4 to 11.8%. Women with a first primary breast cancer are at a 2- to 6-fold increased risk of developing contralateral BC. However, there have been limited studies analyzing the clinicopathologic features of BBC and conflicting data exist on the prognostic significance of BBC. In this study, we sought to analyze the incidence of BBC in the era of modern medicine and assess the clinicopathologic characteristics and prognostic outcomes compared to unilateral BC (UBC). Of the 5941 patients with stage I-III BC diagnosed between 1998 and 2013 at our institution, 110 developed BBC, including 58 synchronous BBC (SBBC, interval between the first and the contralateral BC ≤3 months) and 52 metachronous BBC (MBBC, interval >3 months). The median time to the second tumor was 67.9 months among patients with MBBC. BBC was associated with a significantly lower rate of having a ductal type, high grade, HER2-positive or node-positive disease when compared to UBC, while no difference was found for age, race, ER/PR status, or pathologic tumor stage. When compared to MBBC, SBBC was strongly associated with a lobular phenotype, non-high grade, and ER/PR-positive disease; and further demonstrated a significantly higher concordant rate for ER, PR, and HER2 status. Patients with BBC had a significantly worse distant relapse-free survival (RFS) but a similar disease-specific survival (DSS) when compared to those with UBC. Being African American, having a high histologic grade and higher pathologic tumor or node stage was significantly associated with a worse prognosis, while SBBC was associated with a favorable RFS by multivariate analysis. Nodal status was the only independent prognosticator for DSS in patients with BBC. Further investigation into the complex biologic and clinical behavior of BBC may provide novel insights into the therapeutic strategies in the pursuit of precision medicine in this unique subset of patients.

The present study is an attempt to estimation of stature and sex from skull measurements by multidetector computed tomography (MDCT) in contemporary Chinese. In the present study, fifteen measurements for every skull were taken from CT image of 382 Chinese. The sample was composed of 200 males and 182 females with an average age of 47 and 46 years, respectively. Discriminant function was used in sex determination and regression analysis was used in stature estimation from skull measurements. The stepwise analysis of all measurements yielded a sex classification accuracy rate of 89.3%. The classification accuracy rates of the univariate discriminant function analyses were from 50.5% to 84.8%. For stature estimation, the standard error of estimate (SEE) ranged from 5.072 to 6.355 cm for male, from 5.090 to 5.829 cm for female, respectively. This study is the first to provide a metric and statistical characterization of the skull in contemporary Chinese, and indicates that it is feasible to sex estimation by skull measurement. Furthermore, the equations presented for stature estimation in this study may be used as alternatives in forensic cases, particularly in cases where better predictors such as the long bones are not available.

This study aimed to investigate factors that influence antenatal care utilization and their association with adverse pregnancy outcomes (defined as low birth weight, stillbirth, preterm delivery or small for gestational age) among pregnant women in Kumasi. A quantitative cross-sectional study was conducted of 643 women aged 19–48 years who presented for delivery at selected public hospitals and private traditional birth attendants from July–November 2011. Participants’ information and factors influencing antenatal attendance were collected using a structured questionnaire and antenatal records. Associations between these factors and adverse pregnancy outcomes were assessed using chi-square and logistic regression. Nineteen percent of the women experienced an adverse pregnancy outcome. For 49% of the women, cost influenced their antenatal attendance. Cost was associated with increased likelihood of a woman experiencing an adverse outcome (adjusted OR = 2.15; 95% CI = 1.16–3.99; p = 0.016). Also, women with >5 births had an increased likelihood of an adverse outcome compared with women with single deliveries (adjusted OR = 3.77; 95% CI = 1.50–9.53; p = 0.005). The prevalence of adverse outcomes was lower than previously reported (44.6 versus 19%). Cost and distance were associated with adverse outcomes after adjusting for confounders. Cost and distance could be minimized through a wider application of the Ghana National Health Insurance Scheme.

To study the effect of matrine on tumor growth, inflammatory factors and immune function in Wistar rat with breast cancer.Sixty female Wistar rats were randomly divided into control group (The mean tumor weight of matrine low-dose, medium-dose, high-dose groups and lentinan group were (4.99±0.93) g, (4.52±0.92) g, (4.22±1.18) g and (4.52±0.92) g respectively, which were significantly lower than that in model group. There was no statistical difference on the mean tumor weight among matrine groups and lentinan group (Matrine has an obvious antitumor action which is related to its ability to enhance cellular and humoral immunity, reduce inflammatory reaction.

To develop population - specific stature prediction equations from measurements of the lower limb bone in a contemporary Chinese. 303 individuals of Han group in Western China, including 201 females and 102 males were collected. The study sample was randomly divided into two subgroups. A calibration sample, which consisted of 171 females and 87 males, was used to develop the regression formula. A validation sample comprising the remaining 30 female and 15 male individuals was then used to test the predictive accuracy of the established formula. The regression equations were developed from intact bones and fragments of the femur, tibia and fibula, the maximum lengths of femur, tibia, and fibula were highly correlated with the stature. The maximum length of femur provide the most accurate result with the prediction accuracy of 3.84 cm for unknown sex, 4.00 cm in the male group, 3.45 cm in the female group, 3.61 cm in the group with age no more than 45, 3.45 cm in the group with age above 45. Moreover, the multiple regression equations were developed, and they portray a more accurate stature in instances in which the femur, tibia and fibula are available. This paper provides indications that the femur, tibia and fibula are important bones for stature estimation and they could be effectively used in forensic cases.

Aim To detect the potential regulation pathway of microRNA-455-5p (miR-455-5p) and RAB18, member RAS oncogene family (RAB18) in gastric cancer (GC) cells and tissues and discuss the clinical significance of miR-455-5p in GC genesis and progression. Methods Real-time PCR was used to measure mRNA level of miR-455-5p in GC, TargetScan and dual luciferase assay were used to predict and demonstrate the candidate target gene of miR-455-5p, Western blot were utilized to detect the protein level of RAB18. Cell function assays were also performed to determine the function of miR-455-5p in GC. Results miR-455-5p was reduced significantly in gastric cancer cells and tissues compared with the corresponding normal control, the lower expression of miR-455-5p was related to advanced clinical stage in gastric cancer, re-expression of miR-455-5p could inhibit human GC cell proliferation and invasion, overexpression of miR-455-5p could also promote GC cell apoptosis. Furthermore, we found that RAB18 was a candidate target of miR-455-5p. Re-expression of miR-455-5p could inhibit the protein level of RAB18. Conclusion MiR-455-5p might serve as a novel biomarker in gastric cancer by targeting RAB18.

To perform a study to clarify how strong the chronological age relates to ossification of the knee in Chinese on X-rays and the MRI when a similar four-stage grading system was used. 322 individuals with conventional radiographs and MRI were collected from routine medical investigations and evaluated retrospectively. Bland Altman plots were performed to reveal the agreement of grading of MRI and radiograph. Regression analysis was conducted to establish a mathematical model for age estimation. The ossification process of the knee occurs earlier in females than in males for about 1-2 years. The process on X-ray grading is consistently higher than that of MRI. The chronological age is well correlated with both grading of MRI and radiograph (all p values were less than 0.001). By comparison, the R-square of grading of MRI were relatively higher than that of radiograph. Finally, the chronological age is well correlated with the ossification of the knee when both grading of MRI and radiograph were used, with the R-square for MRI were relatively higher than that of radiograph. Furthermore, the use of MRI will reduce exposure to X-ray radiation as much as possible.

Objectives: To analyze the expression of E-cadherin and β-catenin in triple-negative breast cancer (TNBC) to assess their prognostic significance. Methods: The expression of E-cadherin and β-catenin was examined semiquantitatively and correlated with other pathologic factors and survival outcomes. Results: Of 72 consecutive TNBCs, 56% showed reduced membranous expression of E-cadherin or β-catenin, with a strong correlation to each other. Of the clinicopathologic factors analyzed, tumor size and nodal status were significantly associated with overall survival and disease-specific survival, while the latter remained an independent factor by multivariate analysis. Reduced E-cadherin and β-catenin were both significantly associated with a poor overall survival and disease-specific survival by univariate and multivariate analyses. Conclusions: E-cadherin and β-catenin expression provides discriminative prognostic power independent of conventional pathologic factors, thus further reinforcing the important role of cell adhesion molecules in the process of tumor metastasis, especially in TNBC.

Ovarian cancer continues to be the most lethal gynecologic malignancy worldwide. IL-27 is a novel member of the IL-12 cytokine family. The aim of this study was to investigate the effects of IL-27 on the ovarian cystadenocarcinoma cell line SKOV3 and determine possible mechanisms underlying its effect. We stably transfected an IL-27 plasmid, empty vector, IL-27 shRNA or negative control into SKOV3 cells. Cell proliferative activity was evaluated using a WST-1 cell proliferation assay kit. Cell viability was quantified by measurements of lactate dehydrogenase release. The mRNA levels of nine genes were tested by q-PCR. Western blotting was used to verify apoptosis and signal pathways. We found that the IL-27 plasmid significantly enhanced cytotoxicity and inhibited the proliferation of SKOV3 cells. Caspase-3 protein was augmented by IL-27 plasmid and abated by IL-27 shRNA. The incremental expression of IL-27 activated the STAT3 pathway and attenuated the Akt pathway. The over-expression of IL-27 could significantly upregulate a series of antitumor cytokines including IL-6, IL-12 and interferon-γ and down-regulate protumor factors such as TLR4 and NF-κB1. Our data show that IL-27 has direct antitumor capacity in ovarian cancer cells via enhancing apoptosis by inducing the STAT3 pathway and restraining the Akt pathway. Precis: IL-27 enhanced the cytotoxicity and suppressed the proliferation of ovarian cancer cells by activating STAT3 and inhibiting the Akt signal pathway. IL-27 plays an important role in antitumor activity against epithelial ovarian cancer.

The associations between Type D personality and poor quality of life, overall survival, and mental health in gastric cancer survivors.The aim of this research was to explore quality of life (QoL), mental health status, Type D personality, symptom duration, and emergency admissions of Chinese gastric cancer patients, as well as the relationship between these factors.Eight hundred thirty eligible Chinese patients newly diagnosed with gastric cancer between July 2009 and July 2011 were enrolled in this prospective study. Type D personality was measured with the 14-item Type D Personality Scale (DS14). Mental health status was measured with the Hospital Anxiety and Depression Scale. The QoL outcomes were assessed longitudinally using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Quality of Life Questionnaire-STO22 at baseline and six months after diagnosis.The proportion of patients with symptom duration of more than one month and who were diagnosed after emergency admissions in the Type D group was significantly higher than that in the non-Type D personality group. At both of the time points, Type D patients reported statistically significant lower scores on role, emotional, cognitive, and social functioning (all Ps 0.001) functional scales, global health status/QoL scales (P 0.001), and worse symptom scores compared to patients without a Type D personality. During the six-month time frame, a higher percentage of patients in the Type D group demonstrated a considerable QoL deterioration. Clinically elevated levels of anxiety and depression were more prevalent in Type D than in non-Type D survivors (both Ps 0.001). There was a statistically significant difference in three-year overall survival between the patients in the Type D group and the non-Type D personality group.Type D personality is associated with poor QoL, three-year overall survival and mental health status among survivors of gastric cancer, even after adjustment of confounding background variables. The Type D personality group experienced increased levels of pain and fatigue compared to non-Type D patients. Type D personality might be a general vulnerability factor to screen for subgroups at risk of longer symptom duration and emergency admissions in clinical practice.

In order to develop population – specific discriminant function equations and stature prediction equations for predicting sex and stature from measurements of the scapula in a contemporary Chinese, 414 individual 3D CT images were collected from participants undergoing routine examination. Sex differences for the variables were tested by Student’s t-test. Fisher’s method has been followed for discriminant analysis. Regression analysis was applied to match the six linear parameters against stature. The stepwise analysis of all measurements yielded a sex classification accuracy rate of 86.7% and a sex bias of 3.1%. All the classification accuracy rates of the univariate discriminant function analyses are of more than 80%. For stature estimation, the accuracy of stature prediction ranged from 5.252 to 7.210 cm for male, from 4.630 to 6.484 cm for female, respectively. This paper provides indications that the scapula is an important bone for sex diagnosis and it could be effectively used as alternatives in forensic cases. Furthermore, the equations presented for stature estimation in this study should be used as alternatives in forensic cases when long bones were unavailable for stature estimation.

Receptor activator of NF-κB (RANK) and its ligand, RANKL, are essential for osteoclastogenesis and modulate osteolytic bone metastasis. The RANKL/RANK system is also fundamental for mammary gland development and plays a potential role in breast carcinogenesis. c-Src, a nonreceptor tyrosine kinase downstream of RANK, is overexpressed in most breast cancers and plays a key role in several transduction pathways. The aim of the study was to examine the expression of these molecules in tissue microarrays constructed from 62 advanced breast cancers and 10 breast cancers controls (no metastasis after follow-up). Significantly higher levels of RANK and lower levels of RANKL were found in triple-negative (ER-/PR-/HER2-) tumors when compared with luminal subtypes, whereas their levels in the HER2 subtype were quantitatively in between. RANK expression was significantly associated with tumor grade/differentiation by multivariate analysis. Despite their high expression in bone, neither molecule in primary tumors seemed to be related to a bone-seeking phenotype. Rather, they were significantly correlated with a brain-metastatic phenotype. RANKL and RANK were significantly associated with survival outcomes. Further, Src expression showed a significantly positive linear relationship with RANK, suggesting a potential mechanism of the RANKL-RANK axis in regulating breast cancer cell differentiation and antiapoptosis. Thus, these molecules may be potential therapeutic targets, especially in triple-negative tumors, for which the only systemic treatment option is cytotoxic chemotherapy.