Objective: To investigate the expression of transient receptor polycystic protein 2(TRPP2) in oral squamous epithelial cell and its effect on the invasion and migration of oral squamous cell carcinoma(OSCC), and to explore the potential signaling pathway of TRPP2 affecting OSCC metastasis. Methods: The OSCC model with TRPP2 knockdown was constructed by CRISPR-Cas9 lentivirus plasmid transfection technique. The effect of TRPP2 protein knockdown was verified by Western blot. The effect of TRPP2 on OSCC proliferation was detected by CCK-8 assay and clone formation assay. RT-qPCR was used to detect the target genes associated with TRPP2 metastasis to OSCC. Western blot and RT-qPCR were used to detect the expression of EpCAM and its transcription factors associated with unfolded protein response(UPR). The effects of TRPP2 on the invasion and migration of OSCC were examined by invasion test and scratch test. Results: Compared with HOK in oral epithelial cells, the expression of TRPP2 in OSCC was significantly higher. When TRPP2 was knocked down, OSCC proliferation and clonalformation were significantly enhanced. Compared with the control group, a total of 494 differential genes were significantly expressed in TRPP2 knockdown transcription profile, among which 234 genes were up-regulated and 260 genes were down-regulated. The expression of EpCAM gene, which is related to cell adhesion, was up-regulated. In addition, UPR related genes PERK, ATF6, GRP78 were up-regulated, while ATF6 and EpCAM were down-regulated in OSCC compared to HOK cells. The expression of ATF6 and EpCAM in oral squamous cell carcinoma cells was up-regulated by TRPP2 knockdown, and the cell migration and invasion ability decreased. The ATF6 inhibitor ceapin-A7(5 μmol/L) restored the OSCC migration and invasion ability of TRPP2 knockdown. Conclusion TRPP2 is highly expressed in OSCC. When TRPP2 is knocked down, OSCC proliferation ability is enhanced, migration and invasion ability are inhibited. TRPP2 mediates the expression of EpCAM through activation of UPR, thus affecting the invasion and migration of oral squamous cell carcinoma.

Breast cancer is the most diagnosed cancer in women worldwide and the leading cause of most cancer-related deaths,posing a serious threat to women′s health worldwide.At present,although the prognosis of some patients with breast cancer has improved,the emergence of drug resistance and the metastasis and recurrence of breast cancer are still the main reasons for poor prognosis.CD36 is a multiligand transmembrane glycoprotein expressed on various cell types.In recent years,studies have confirmed that CD36 can reshape the lipid metabolism of cancer cells;promote the differentiation of tumor-related macrophages into M2 type and recruitment into tumor tissues;regulate the function of Treg cells,CD8+T cells,DCs,and other immune cells,and thus promote tumor development.In addition,CD36 is also associated with breast cancer stem cells,metastasis-initiating cells,and breast drug resistant cells.Therefore,CD36 could be an important potential therapeutic target for breast cancer.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

Objective To analyze the biomechanical feasibility of two-point fixation by distal radius plate for the treatment of SandersⅢ calcaneal fractures. Methods The three-dimensional (3D) finite element musculoskeletal foot model was established based on CT and MRI images, which comprised bones, muscles, plantar fascia, ligaments and soft tissues. After validation, the SandersⅢ calcaneal fracture models fixed by distal radial plate (two-point fixation) and calcaneal plate (three-point fixation) were established, so as to compare the biomechanical characteristics of two calcaneal models. Results The maximum stress of the two-point fixation and three-point fixation model was 324.70 and 407.90 MPa, respectively. The maximum displacements of the two models were 2.498 and 2.541 mm, respectively. There was no significant difference in the posterior articular surface displacement between the two models. In both models, the Bohler’s angle and Gissane’s angle were within the normal range. Conclusions The two-point fixation by distal radial plate can satisfy the biomechanical stability of calcaneal fracture treatment. Compared with traditional steel plate, the two-point fixation shows the advantage of smaller surgical trauma, more uniform overall stress distribution, early weight-bearing rehabilitation after surgery, which is a novel treatment recommended for treating calcaneal fractures.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

MicroRNA (miRNA) is a type of highly conserved nucleotide sequence composed of 18 to 25 nucleotides, which can specifically bind to the 3'-noncoding regions of mRNA, and then play a negative regulatory role in degrading mRNA or inhibiting translation. Long non-coding RNA (lncRNA) is a type of nucleotide sequence that exceeds 200 nucleotides in length and cannot encode proteins or can only encode protein peptides. It regulates gene expression at the levels of epigenetic, transcriptional and post-transcriptional. As an important energy storage organ, fat plays an important role in regulating the energy balance of animals, and is closely related to meat production traits such as meat production and meat quality. And the disorder of fat function can lead to hyperlipidemia, type 2 diabetes and a series of cardiovascular diseases, so the molecular regulation mechanism of animal fat deposition has attracted more attention. In recent years, more and more studies have found that miRNA and lncRNA play a crucial role in animal fat deposition. We review here the current research progresses in the role of miRNA and lncRNA in animal fat deposition, to provide theoretical guidance and new ideas for further revealing the molecular regulation mechanism of animal fat deposition.

Objective To investigate the mechanism of occurrence and rehabilitation of heel pain, so as to provide a theoretical basis for the effectiveness of heel pain treatment. Methods The CT and MRI data acquired from feet and knees of patients with heel pain were reconstructed to establish the bone-muscle composite finite element model. Based on the established model, the effect of calf muscle contracture on biomechanical properties of the foot and ankle was simulated by using the finite element method . Results When the calf muscles produce upward lifting power, plantar pressure was transferred from the heel area to the forefoot area, and there was no significant difference in pressure distribution by different combination schemes of muscle forces. The strain of the plantar fascia was increased, with stress concentration on the calcaneus surface. Under 240 N force, the peak stress at the Achilles tendon attachment position and the calcaneus nodules was up to 10.82 MPa and 11.2 MPa, respectively. Conclusions The stress concentration in calf muscles and Achilles led to the changes in biomechanics of the ankle, which resulted in heel pain. The method of improving the overall biomechanical environment by releasing concentrated stress to restore the position of the bones and joints of the ankle joint is the mechanism for rehabilitation of heel pain.

Objective To ascertain the frequency distribution of CT examinations in children.Method A wide range of information was collected through the radiology information system (RIS),including ID,sex,birth date,examination time,the examined part of body and other relevant ones related to children who underwent CT examinations between Jan 1,2012 and Dec 31,2012.The SAS software was used for data processing and statistical analysis.Results A total of 1 542 children underwent 1 670 examinations,of which 67％ were male.Head CT examination was the most frequent,accounting for 71.9％ of all CT examinations,and followed by the abdomen/pelvis examinations.The number of examinations of children undergoing the repetitive examination accounted for 6.4％; 51.7％ of the examinations was for trauma.The positive rate of CT examination was 51％,dependent upon the age and examined body parts to some extent.The younger patients had lower positive rate,and the positive rate of head CT examination was lower than those in other parts.Conclusions To reduce the possible cancer risk to be induced by the ionizing radiation from CT,justification of CT examination should be considered for children.

Objective To provide the dose information from the epidemiological cohort established in 1980 in Jiangsu province using normalized workload method,and to estimate cumulative skin dose to medical diagnostic X-ray workers based on personal dosimeter were worn as members of the epidemiologicat cohort.Methods Data for fixed cohort members of X-ray exposure history from 1950 to June 2011 were collected.According to correction factors such as examination types and protection conditions,exposure doses from 1950s to June of 2011 were estimated through a Visual Basic language program.Results Average annual doses vary significantly between during different time periods:10.1 (6.1-12.3) mGy/year during 1950-1965,3.5 (2.1-5.4) mGy/year for 1966-1984 and 1.3 (0.9-1.9) mGy/year during 1985-2011,respectively.Conclusions Average annual doses received by 3 961 medical diagnostic X-ray workers during different time periods in this investigation are nearly consistent with the results reported previously and show a roughly similar trend.