Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [β (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (P_interaction=0.022). Compared with the Q₁ group in NDVI, WC of Q₂ and Q₃ groups in rural decreased, and the β (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (P_interaction=0.284). Compared with the Q₁ group in NDVI, the risk of central obesity in the Q₂ and Q₃ groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (P_nonlinear=0.006) and central obesity (P_nonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

Objective:To investigate the clinical features, diagnosis, treatment and prognosis of primary urethral carcinoma.Methods:The clinical and follow-up data of 12 patients with primary urethral carcinoma admitted to Beijing Hospital from July 2016 to December 2020 were retrospectively analyzed.Results:There were four males and eight females, with an average age of 66.3(53~75)years.Nine patients underwent magnetic resonance examination before operation, and eight patients presented with abnormal urethral signals.The clinical stage of female patients was generally later than those of male patients, and all patients received surgical treatment.Four male patients did not receive post-operative adjuvant treatment, and all of them attained disease-free survival.Among the eight female patients, four patients received postoperative adjuvant radiotherapy or chemotherapy, five patients had recurrence or metastasis during follow-up, and two patients died.Conclusions:The clinical stage of female urethral cancer is later than that of male.MRI examination is beneficial to the determination of local invasion of urethral cancer.For female proximal urethral cancer and male posterior urethral cancer, radical resection has a good therapeutic effect.

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

CRISP R/Cas9 is an emerging gene editing technique, which plays an important role in life science research.It is of great significance to introduce this cutting-edge scientific technique into the experimental teaching for undergraduates.Therefore, we established an undergraduate experiment system based on CRISPR/Cas9 technology.This experiment system focuses on the application of CRISPR/Cas9- mediating gene editing in mammalian cells.An engineered mouse embryonic fibroblast which genome were inserted with fluorescein mCherry gene was selected as the experimental model, and called STO-82.Firstly, sgRNAs targeting mCherry gene were designed to construct CRISPR-Cas9/sgRNA co-expression plasmids.After being confirmed by sequencing, they were transfected into STO-82 cells.Two groups of cells with mCherry negative and positive signals were detected by fluorescence-activated cell sorting.Single cells with negative fluorescence were separated and then cultivated to become monoclonal cells.The mutation status of mCherry gene in monoclonal cell lines was detected by sequence analysis.The result showed that there were mutations of insertion or deletion at target sites, indicating that the experimental system was successfully established.Therefore, this comprehensive experiment is comprised of sgRNA design, construction of CRISPR-Cas9/sgRNA co-expression plasmids, cell transfection, cell sorting, monoclonal cell cultivation and sequence analysis.This experiment system is used for experimental teaching for senior undergraduates.Teaching practice can either be decomposed into content modules or be taken as a whole program in light of actual situation.In the teaching practice at 3 classes (13 groups in total, two students every group), which adopted the model of small-class teaching (about 10 students per class), the majority completed the content modules and the expected outcomes were achieved.Through the design and teaching practice of this experiment system, the students acquire a deeper understanding for the principle and experimental procedure of CRISPR/Cas9 technology, an enhanced experimental ability and rigorous scientific thinking and also some knowledge in the risk of its medical application.

Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.
A Kinase Anchor Proteins/genetics* ; Adult ; Aged ; Biomarkers, Tumor/genetics* ; China ; Cytoskeletal Proteins/genetics* ; DNA-Binding Proteins/genetics* ; Gene Amplification ; High-Throughput Nucleotide Sequencing ; Homeodomain Proteins/genetics* ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Proteins/genetics* ; Prostatic Neoplasms/pathology* ; Proto-Oncogene Mas ; Receptors, Androgen/genetics* ; Signal Transduction/genetics* ; Zinc Finger Protein GLI1/genetics*

BACKGROUND: Repair of tendon interface is a difficulty in orthopedics and sports medicine, and the formation of new bone is conducive to its healing. Calcitonin gene-related peptide (CGRP) plays a critical role in tissue homeostasis and repair, but its effect on the bone-tendon interface repair is unknown. OBJECTIVE: To investigate the effect of CGRP on the expression of osteocalcin and to evaluate the effect of CGRP on the early healing of rotator cuff injury in a mouse model. METHODS: A mouse model of supraspinatus insertion-humerus injury was created. All model mice were then randomized into two groups, and given the injection of 5 nmol/kg CGRP (experimental group) or same volume of normal saline (control group) through the glenohumeral joint immediately after operation, thrice weekly, for 2 weeks. The mice were sacrificed at postoperative 4 and 6 weeks to remove the rotator cuff samples for hematoxylin-eosin staining and biomechanical test. The mRNA and protein expression levels of osteocalcin were surveyed by qRT-PCR, immunohistochemistry, and western blot assay. RESULTS AND CONCLUSION: At postoperative 4 and 6 weeks, the mRNA and protein expression of osteocalcin in the experimental group were significantly higher than those in the control group (P < 0.05). Compared with the control group, there were more fibrocartilages in the experimental group at 4 weeks postoperatively, and more new bone formation in the experimental group at 6 weeks postoperatively. At 4 weeks postoperatively, failure load in the experimental group increased slightly, but it was not significantly different from that in the control group (P > 0.05); at 6 weeks postoperatively, failure load in the experimental group was significantly higher than that in the control group (P<0.05). To conclude, local injection of CGRP can up-regulate the expression of osteocalcin and the formation of new bone at the injury site, which can enhance early healing the injured rotator cuff.

Objective To investigate the expression of 6-phosphofructo-2-kinase /fructose-2,6-bisphosphatase-3 (PFKFB3) and sphingosine 1-phosphate receptor 2 (S1 P2) in the retina of rats with type 2 diabetes mellitus (DM) and to explore the correlation of tertiary butylhydroquinone (tBHQ) with PFKFB3 and S1P2.Methods Together 60 male SD rats were divided into normal control group (NC group),diabetes mellitus group (DM group) and tBHQ group.Type 2 DM model was induced in the latter two groups.The rats in tBHQ group were given 10 g · L-1 tBHQ in high-fat and highsugar diet 1 week after successful modeling,while DM rats were fed with high-fat and high-sugar diet continuously.At 4 weeks and 12 weeks after tBHQ intervention,blood samples were taken from the hearts of rats in each group,and serum contents of fasting plasma glucose (FPG) and fasting serum insulin (FINs) were measured.Immunohistochemistry and qRT-PCR were taken to detect the distribution and expression of PFKFB3,S1 P2 and vascular endothehal growth factor (VEGF) mRNA and protein in the retina,and TUNEL methods were used to detect apoptosis index of retinal ganglion cells of rats in each group.Results There were significant difference in the FPG and FINs levels of the three groups at 4 weeks and 12 weeks (all P =0.000).Light microscopy test showed that positive expressions of PFKFB3,S1 P2 and VEGF protein were found in all groups at 4 and 12 weeks,which were mainly located in the retinal ganglion cell layer and the inner nuclear layer.Immunohistochemistry and qRT-PCR showed that the difference in relative expressions of PFKFB3,S1P2,VEGF protein and mRNA in the retina at different times after modeling were statistically significant (all P ＜ 0.05).At 4 and 12 weeks,the expression levels of PFKFB3,S1P2 and VEGF in DM group were higher than those in NC group,but their expressions in tBHQ group were significantly downregulated when compared with DM group,and all differences were statistically significant (all P ＜ 0.05).Compared with 4 weeks,PFKFB3,S1 P2 and VEGF mRNA and protein in DM group were overexpressed at 12 weeks,and the expression level of S1 P2 in tBHQ group at 12 weeks was lower than that at 4 weeks,and the differences were statistically significant (all P ＜ 0.05).TUNEL assays showed that there was significant difference in the apoptotic index (AI) of retinal ganglion cells of rats in each group at different times after modeling (all P ＜ 0.05).DM group had higher AI than NC group (P ＜ 0.05),and tBHQ group was lower than DM group (P ＜ 0.05);Compared with 4 weeks,DM group had increased AI at 12 weeks while tBHQ group had decreased AI (both P ＜ 0.05).Conclusion PFKFB3,S1P2 and VEGF are involved in the pathological process of the retina of type 2 DM rats,which may play a role through the PFKFB3 / VEGF / S1P2 signaling pathway and may be related to the apoptosis of retinal ganglion cells.And it is indicated that tBHQ has a protective effect on the retina of type 2 DM rats.

Objective To observe the effect of human immunoglobulin on elderly head and facial post herpetic neuralgia (PHN) and peripheral blood TNF-α.Methods One hundred and twenty-two inpatients with PHN aged ≥65 years old were selected and divided into the observation group (52 cases) and control group (70 cases) by the systematic sampling method.The control group was given the early conventional combined therapy,while on this basis the observation group was intravenously dripped by human immunoglobulin.The incidence rate of PHN and pain visual analog scale(VAS) score at 1,2,3 months after recovery discharge from hospital were recorded in the two groups.Other 20 healthy elderly people were selected as the healthy control group.The TNF-α level was determined in the two patients groups before and after treatment and in the healthy control group.Results The PHN occurrence rate at 1,2,3 months after discharge in the observation group was significantly lower than that in the control group(P＜0.05);the VAS score after treatment and at 1,2,3 months after discharge in the observation group was significantly lower than that in the control group (P＜0.05);serum TNF-α level after treatment in the observation group was significantly lower than that in the control group (P＜0.01),moreover which was close to the level in the healthy control group(P＞0.5).Conclusion Human immunoglobulin can reduce the PHN occurrence in the old people with head and facial herpes zoster and reduce the peripheral blood TNF-α level.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors