Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Identification and Verification of the Ability of Cdk5 to Phosphorylate Deubiquitinating Enzyme BRCC3 In Vitro.

It is known that the expression of the deubiquitinating enzyme BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and cyclin-dependent protein kinase 5 (Cdk5) is increased in Parkinson's disease (both are involved in neuroinflammatory response). However, the regulatory mechanism of Cdk5 on the post-translational modification of BRCC3 remains unclear. Here we studied whether Cdk5 phosphorylates BRCC3. Phosphorylation of BRCC3 by Cdk5 was predicted by GPS 5.0 software. His-BRCC3 plasmid was constructed by cloning the BRCC3 gene into pGEX-6P-1 vector, and then His-BRCC3 fusion protein was induced with isopropyl ß-d-1-thiogalactopyranoside and purified using His-Tag affinity chromatography purification agarose. Phosphorylation of BRCC3 fusion protein by Cdk5 in vitro was detected by mass spectrometry and Western blotting. The results showed that multiple phosphorylation sites were predicted by GPS 5.0, and the His-BRCC3 fusion protein was successfully induced and purified. In vitro kinase assay, Western blotting, and mass spectrometry showed that Cdk5 can phosphorylate BRCC3. It has been demonstrated that protein kinase Cdk5 can phosphorylate the deubiquitinating enzyme BRCC3 in vitro, which provides new data for further study on the mechanism of neurodegeneration.

[Establishment of model to predict lateral neck recurrence of central lymph node metastasis in papillary thyroid carcinoma].

Objective: To explore the risk factors for lateral neck recurrence of central lymph node metastasis (CLMN) in papillary thyroid cancer (PTC), and to construct a model to predict the recurrence. Methods: The records of 245 consecutive PTC patients with CLMN underwent surgical treatment from 1996 to 2009 in our department were retrospectively reviewed. The threshold value of CLNM number is determined by ROC curve. The risk factors for lateral neck recurrence were determined by using Cox regression model. The identified risk factors were incorporated into a nomogram model to predict the risk of lateral neck recurrence. Results: A total of 245 patients were enrolled in the study, among them, 32 cases occurred lateral neck lymph node recurrence and 4 cases were dead of thyroid carcinoma. Multivariate analysis revealed that primary tumor size, extrathyroidal extension, the number of metastatic CLNM >3 were independent risk factors of lateral neck recurrence (P<0.05), lateral neck recurrence was a risk factor of disease-free survival(P<0.05). The nomogram model of predicting the lateral neck recurrence was further established based on the above 3 independent risk factors, the area under the receiver operating characteristic (ROC) curve of which was 0.790. Conclusions: The nomogram model based on the independent risk factors of LN recurrence can be helpful to screen the papillary thyroid carcinoma patients with high risk of lateral neck recurrence, and provide more guidance for clinical treatment.

[Prediction and investigation of the potential risk factors for the upper mediastinal metastasis of papillary thyroid carcinoma].

Objective: To predict and investigate the potential risk factors for the upper mediastinal metastasis of papillary thyroid carcinoma (PTC). Methods: This study was a prospective cohort study. The admission criteria were patients with untreated thyroid cancer diagnosed in Cancer Hospital, Chinese Academy of Medical Sciences from December 2013 to December 2015, and positive lymph node (cN1, including cN1a and cN1b) was diagnosed by ultrasound. All patients underwent neck to thorax enhanced Computed Tomography (CT) examination preoperatively. All patients with suspected upper mediastinal lymph node metastasis experienced suspicious regional dissection, and those who had not undergone surgery and whose postoperative pathology was non-papillary thyroid carcinoma were excluded. Kaplan-Meier method was selected for survival analysis and all the factors were analyzed by multivariate Logistic regression. Results: Of the 248 patients, 54 were prompted by postoperative pathology for upper mediastinal lymph node metastasis, 86 cases were phase T1, 94 cases were phase T2, 17 cases were phase T3 and 51 cases were phase T4, 21 cases were N1a phase and 227cases were N1b phase. There was a statistically significant difference in the T-phase and N-phase between the upper mediastinal lymph node metastasis group and no upper mediastinal lymph node metastasis group(P<0.05). Univariate analysis showed that among the preoperative relevant factors, ultrasound tumor length> 2 cm, ultrasound tumor bilaterally, CT double neck lymph node metastasis, increased thyroglobulin (Tg), and increased anti-thyroglobulin antibody (ATG) were all risk factors for upper mediastinal lymph node metastasis(all P<0.05). Among the postoperative factors, bilateral tumor, double neck lymph node metastasis, tumor invasion of the recurrent laryngeal nerve, trachea, esophagus or larynx, T3 staging, T4 staging, total number of metastatic lymph nodes>10, the number of metastatic lymph nodes in level Ⅵ>3 and >6, the proportion of metastatic lymph nodes in level Ⅵ>1/2, the number of metastatic lymph nodes in level Ⅳ> 5 and metastatic proportion >1/3 are risk factors for metastasis of upper mediastinal lymph node(all P<0.05). Multivariate analysis showed that CT indicated double neck lymph node metastasis, increased Tg, increased ATG, the proportion of metastatic lymph nodes in level Ⅵ >1/2, and in level Ⅳ>1/3 are independent risk factors for upper mediastinum lymph node metastasis(all P<0.05). The 5-year recurrence-free survival rates of the upper mediastinal lymph node metastasis group and the no upper mediastinal lymph node metastasis group were 92.3% and 94.8% respectively, and the difference was not statistically significant(P=0.307). Conclusions: For preoperative ultrasound considering the presence of lymph node metastases, enhanced neck to thorax CT should be performed routinely. When bilateral cervical lymph node metastasis is determined by CT, or endocrine tests suggest abnormally increased antibodies, attention should be paid to the upper mediastinal lymph nodes metastasis. In the course of neck dissection, if more lymph node metastases in level Ⅵ and level Ⅳ were detected, surgeons should be vigilant of the upper mediastinal metastasis. The prognosis of patients underwent complete mediastinal dissection is not significantly different from that of patients without mediastinal metastasis.

[A retrospective safety study on screening of the samples in the clinical biobank of Beijing Hospital].

To investigate whether the laboratory specimens preserved in Beijing Hospital Biobank during a specific period had been contaminated by SARS-Cov-2 through a cross-sectional study, and to establish a retrospective biobank safety screening system. Laboratory specimens were collected from the Department of Respiratory and Critical Care Medicine and the Fever Clinic of Beijing Hospital from November 1, 2019 to January 22, 2020, nucleic acid and serological antibody testing were performed for SARS-CoV-2 in these specimens (including 79 serum, 20 urine, 42 feces and 21 bronchoalveolar lavage fluid specimens). The safety of the stored samples during this period was defined by negative and positive results. Both the nucleic acid test and serological antibody test showed negative for SARS-CoV-2, indicating that these specimens were safely stored in the biobank. High-risk specimens collected in our hospital during the early stage of the COVID-19 outbreak are free of SARS-CoV-2, and a safety screening strategy for the clinical biobank is established to ensure the biosafety of these samples.

[Protective effect of vitamin D in mice with acute liver failure].

Objective: To explore the protective effect of vitamin D in acute liver failure through a mouse model. Methods: Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1ß, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test. Results: Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1ß, and NLRP-3 mRNA expression (P < 0.05), and increased macrophages quantitation (P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury (P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise (P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues (P < 0.05). Conclusion: Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.

Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China.

BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0-70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086-15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498-19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.

[Correlation between serum bilirubin and cardiovascular autonomic neuropathy in patients with type 2 diabetes].

Objective: To investigate the correlation between serum bilirubin and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes mellitus patients. Methods: A total of 369 patients with type 2 diabetes mellitus who were hospitalized at the Department of Endocrinology, Nanjing Jinling Hospital from April 2017 to October 2018 were enrolled, including 226 males and 143 females, with an average age of (54.6±12.1) years. According to cardiovascular reflex tests (CARTs), all the patients were divided into Non CAN group(149 patients without CAN) and CAN group (220 patients complicated with CAN). The difference of serum bilirubin levels between the two groups was compared. The differences of CARTs and the incidence of CAN were compared by tertiles of serum bilirubin levels. The binary logistic regression was used to analyze the risk factors for diabetic cardiovascular autonomic neuropathy. Results: The serum total bilirubin [(9.28±2.74) µmol/L vs (11.08±2.98) µmol/L, P<0.001], direct bilirubin [(3.17±1.20) µmol/L vs (3.71±1.24) µmol/L, P<0.001] and indirect bilirubin levels [(6.11±1.89) µmol/L vs (7.37±2.10) µmol/L, P<0.001] in CAN group were significantly lower than that in Non CAN group. With the increase of serum bilirubin, the incidence of CAN decreased (P<0.01). Multivariate Logistic regression analysis showed that serum total bilirubin (OR=0.819, 95%CI: 0.744-0.901, P<0.001), direct bilirubin (OR=0.739, 95%CI: 0.601-0.908, P=0.004) and indirect bilirubin (OR=0.749, 95%CI: 0.653-0.860, P<0.001) were inversely correlated with the incidence of CAN. Conclusions: Within the physiological range, lower level of serum bilirubin is inversely correlated with the incidence of CAN. It is noteworthy to screen diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus who had a lower serum bilirubin level.

[The optimal cutoff value of waist-to-height ratio in Chinese: based on cardiovascular risk and metabolic disease].

Objective: Waist-to-height ratio (WHtR), a measurement of the distribution of body fat, correlated with abdominal obesity indicating that it might be a better predictor of cardiovascular risk and metabolic disease. We, therefore, evaluated optimal WHtR cutoff points according to the risk of framingham risk score (FRS) and metabolic syndrome (MS) in Chinese. Methods: The subjects were from China National Diabetes and Metabolic Disorders Survey during 2007-2008. Receiver operating characteristic analysis was used to examine the optimal cutoff values of WHtR according to the risk of FRS and MS. Results: A total of 27 820 women and 18 419 men were included in the evaluation. The average age was (45.0±13.7) years. The proportions of FRS ≥10% and MS increased with WHtR both in men and women. The cutoff points of WHtR for the risk of FRS ≥10% and MS were 0.51, 0.52 in men, and 0.52, 0.53 in women, respectively. When FRS ≥10% and MS were taken into consideration with a certain weights, the pooled cutoffs of WHtR were 0.51 in men, and 0.53 in women, respectively. By using the similar method, the optimized cutoff points were 0.52, 0.51, 0.50 for men and 0.51, 0.53, 0.54 for women in age group 20-39, 40-59 and ≥60 years, respectively. Conclusions: The optimal cutoffs of WHtR are 0.51 in men, and 0.53 in women for FRS≥10% in combination with MS indicating that this WHtR cutoff points might be used as indexes to evaluate obesity and risk of obesity-related diseases.

Effects of Inulin Supplementation in Low- or High-Fat Diets on Reproductive Performance of Sows and Antioxidant Defence Capacity in Sows and Offspring.

This experiment was conducted to investigate the effects of inulin supplementation in low- or high-fat diets on both the reproductive performance of sow and the antioxidant defence capacity in sows and offspring. Sixty Landrace × Yorkshire sows were randomly allocated to four treatments with low-fat diet (L), low-fat diet containing 1.5% inulin (LI), high-fat diet (H) and high-fat diet containing 1.5% inulin (HI). Inulin-rich diets lowered the within-litter birth weight coefficient of variation (CV, p = 0.05) of piglets, increased the proportion of piglets weighing 1.0-1.5 kg at farrowing (p < 0.01), reduced the loss of body weight (BW) and backfat thickness (BF) during lactation (p < 0.05) and decreased the duration of farrowing as well as improved sow constipation (p < 0.05). Sows fed fat-rich diets gained more BW during gestation (p < 0.01), farrowed a greater number of total (+1.65 pigs, p < 0.05) and alive (+1.52 pigs p < 0.05) piglets and had a heavier (+2.06 kg, p < 0.05) litter weight at birth as well as a decreased weaning-to-oestrous interval (WEI, p < 0.01) compared with sows fed low-fat diets. However, it is worth noting that the H diet significantly decreased the serum activities of superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) and increased the serum malondialdehyde (MDA) levels in sows and piglets (p < 0.05). In contrast, HI diet enhanced the activities of T-SOD and GSH-Px and decreased the serum MDA concentrations (p < 0.05) in sows and piglets. In summary, the fat-rich diets fed to sows during gestation had beneficial effects on reproductive performance, but aggravated the oxidative stress in sow and piglets. Inulin-rich diets fed to sow during gestation had beneficial effects on within-litter uniformity of piglet birthweight and enhanced the antioxidant defence capacity of sows and piglets.

Effects of Dietary Supplementation of ß-hydroxy-ß-methylbutyrate on Sow Performance and mRNA Expression of Myogenic Markers in Skeletal Muscle of Neonatal Piglets.

The effects of dietary ß-hydroxy-ß-methylbutyrate (HMB) supplementation during gestation on reproductive performance of sows and the mRNA expression of myogenic markers in skeletal muscle of neonatal pigs were determined. At day 35 of gestation, a total of 20 sows (Landrace × Yorkshire, at third parity) were randomly assigned to two groups, with each group receiving either a basal diet or the same diet supplemented with 4 g/day ß-hydroxy-ß-methylbutyrate calcium (HMB-Ca) until parturition. At parturition, the total and live litter size were not markedly different between treatments, however, the sows fed HMB diet had a decreased rate of stillborn piglets compared with the sows fed the control (CON) diets (p < 0.05). In addition, piglets from the sows fed HMB diet tended to have an increased birth weight (p = 0.08), and a reduced rate of low birth weight piglets (p = 0.05) compared with piglets from the CON sows. Nevertheless, lower feed intake during lactation was observed in the sows fed the HMB diet compared with those on the CON diet (p < 0.01). The relative weights of the longissimus dorsi (LD) and semitendinosus (ST) muscle were higher (p < 0.05) in neonatal pigs from the HMB than the CON sows. Furthermore, maternal HMB treatment increased the mRNA levels of the myogenic genes, including muscle regulatory factor-4 (MRF4, p < 0.05), myogenic differentiation factor (MyoD) and insulin-like growth factor-1 (IGF-1, p < 0.01). In conclusion, dietary HMB supplementation to sows at 4 g/day from day 35 of gestation to term significantly improves pregnancy outcomes and increases the expression of myogenic genes in skeletal muscle of neonatal piglets, but reduces feed intake of sows during lactation.

3D Modelling on Biodegradable Nanoparticle-Enhanced Cryoablation of Liver Tumor Based on Real Anatomical Model.

BACKGROUND: Nanoparticle-enhanced freezing is of great importance for developing a conformal targeted cryoablation for liver tumor with complex shape. However, the safety and biocompatibility of nanoparticles should also be of major concerns. OBJECTIVE: This study is to investigate the enhanced cryoablation mediated by the MgO nanoparticles which are nontoxic, biodegradable, and have few side-effects on the human body. MATERIALS AND METHODS: A three-dimensional numerical model has been developed based on a real geometrical anatomical structure to characterize such nanocryosurgical freezing of liver tumor. The evolutions of temperature field and ablation volume were investigated subject to different concentrations and scopes of the loaded nanoparticles, respectively. Additionally, the results of different probe numbers were also taken into consideration. RESULTS: It was found that the lesion growth was evidently affected by the configurations of both the nanoparticles and cryoprobes. Both ablation and frozen regions were enlarged with the increase of the loading ratio and scope of MgO nanoparticles. It was worth mentioning that thermal-physiological behavior of the adjacent large blood vessels also played an important role in affecting the target temperature field distribution. CONCLUSION: The present study established a feasible way for verisimilarly simulating the physiological manifestation of human liver in the process of nano-freezing modality, which would provide a valuable guidance for future clinical practice of conformal nano-cryoablation on liver tumor.

[Understanding the risk factors for infectious diseases, their prevention, and control, among residents of Zhejiang Province].

Objective: To investigate the understanding of infectious diseases, their prevention, and control, and the factors influencing this literacy among urban and rural residents of Zhejiang Province. Methods: In November- December 2014, a multistage stratified cluster sampling questionnaire was administered at study sites in eight districts of Zhejiang province: Hangzhou city Gongshu district, Hangzhou city Chun'an county, Wenzhou city Cangnan county, Dongyang city, Jiaxing city Jiashan county, Zhoushan city Putuo district, Linhai city, Lishui city Jinyun county. The inclusion criteria were: 15-60 years old, living locally for more than six continuous months, and no mental illness. The exclusion criteria were: foreigner residing locally, resident of Hong Kong, Macau, or Taiwan, or unable to communicate through speech or writing. In this study, 4 091 questionnaires were distributed, and 4 020 valid questionnaires were returned(98.26%). Health literacy regarding infectious diseases was measured at five levels: knowledge, skills, behaviors, access to information, and understanding of the prevention of infectious diseases. A total score was calculated for each questionnaire, and a total score of ≥80 was deemed to indicate an understanding of the prevention of infectious diseases. A χ2 test was used to compare the levels of health literacy in different populations with single-factor analyses, and a multivariate unconditional logistic regression model was used to analyze the factors affecting infectious diseases prevention and treatment literacy levels. Results: Of the 4 020 respondents(aged(43.84 ± 10.28)years), 1 964 were male(48.86%)and 2 056 were female(51.14%). In the total surveyed population, 15.17%(n=610)understood the prevention of infectious diseases, 294 were male(14.97%)and 316 were female(15.37%)(χ2=2.48, P=0.115). When the participants in the different age groups were analyzed, 23.11%, 20.29%, 13.27%, and 11.04% of those aged 18- 29(n=116), 30- 39(n= 166), 40- 49(n=178), and ≥50 years(n=150), respectively, understood infectious disease prevention(χ2= 63.16, P<0.001). When the participants were analyzed according to education, 46.01%, 24.86%, 12.03%, 5.27%, or 2.39% of those educated at university(n=167), at high school/vocational school/college(n=175), at middle school(n=215), at elementary school(n=46), or who were illiterate/slightly literate(n=7), respectively, understood infectious disease prevention(χ2=436.67, P<0.001). Among the urban(n=336)and rural participants(n=274), 18.98% and 12.18% understood infectious disease prevention, respectively(χ2= 35.57, P<0.001), so the urban residents had better health literacy than rural residents(OR=1.28, 95% CI= 1.06- 1.54), and those aged 18- 29 or 30- 39 years had even better health literacy than the rural residents(OR=1.39, 95%CI=1.01-1.91). When the health literacy levels of migrant workers were compared with those of agency/institutional personnel, business people, unemployed, and retirees, the OR(95% CI)values were 2.52(1.82-3.49), 1.69(1.24-2.30), 2.99(1.65-5.39), and 2.43(1.59-3.72), respectively. When the illiterate/slightly literate were compared with those educated at university, high school/vocational school/secondary school, and junior high school, the OR(95%CI)values were 35.11(15.73-78.36), 13.31(6.11-28.99), and 5.37(2.48-11.62), respectively. Conclusion: Limited levels of health literacy are common among the residents of Zhejiang Province. Lower education level, older age, and rural residence were predictors of low health literacy in this study.

Asporin and osteoarthritis.

OBJECTIVE: To provide an overview of the literature describing the role of asporin, a small leucine-rich proteoglycan (SLRP), in osteoarthritis (OA). METHOD: A literature search was performed and reviewed using the narrative approach. RESULTS: As a class I SLRP member, asporin, is distinct from other SLRPs. Accumulating evidence demonstrates the involvement of asporin in OA pathogenesis. Many human studies have been conducted to explore the association between the D-repeat polymorphisms and OA susceptibility, but these yield inconsistent results. Possible mechanisms for the involvement of asporin in OA pathology include its influence on TGF-ß (transforming growth factor-ß) signaling pathways and collagen mineralization. To date, no studies were found to use an asporin-deficient animal model that would help to understand disease mechanisms. Many issues must be addressed to clarify the link between asporin and OA to provide a novel therapeutic strategy for OA, perhaps through controlling and modifying the TGF-ß-ECM system. CONCLUSIONS: Studies examined demonstrate the involvement of asporin in OA pathogenesis, and possible mechanisms by which asporin may be involved in this process have been proposed. However, large-scale interracial studies should be conducted to investigate the association between asporin and OA, and further investigations are needed to obtain a better understanding of the disease mechanism, develop novel therapeutic strategies, and explore new approaches for diagnosis of OA.

The CRISPR/Cas system inhibited the pro-oncogenic effects of alternatively spliced fibronectin extra domain A via editing the genome in salivary adenoid cystic carcinoma cells.

OBJECTIVES: To identify the association of fibronectin (FN) extra domain A (EDA) with the progression of salivary adenoid cystic carcinoma (SACC). Accordingly, the exclusion of EDA exon through the CRISPR/Cas9 system was investigated as the rescue for such pro-oncogenic splicing. MATERIALS AND METHODS: SACC-83 cells were transiently transfected with plasmids containing recombinant EDA, and the cellular growth and motility were then accessed in vitro. Epithelial-mesenchymal transition (EMT) was investigated with immunohistochemistry, Western blot, and real-time PCR analysis. SACC tissues from 81 patients were used to access the associations between EDA+FN and clinical-pathological parameters. CRISPR/Cas9 plasmids containing sgRNA were designed and co-transfected into SACC-83 cells; the effects of EDA knockout on cellular growth and motility were then accessed. RESULTS: The recombinant EDA exhibited little effect on the proliferation of SACC cells, but significantly promoted the migration and invasion of the cells (P < 0.05), accompanied with upregulated EMT (P < 0.05); consistently, the expression of EDA+FN was positively associated with the metastasis, nerve invasion and recurrence of SACC (P < 0.05). Furthermore, the EDA knockout from the FN gene in most SACC cells resulted in a decrease in cell motility and invasion, as well as prolonged population doubling time, compared with untreated SACC-83 cells (P < 0.05). CONCLUSION: The EDA domain significantly promoted the motility of SACC cells, and positively associated with the tumor progression in patients with SACC. Thus, it is a potential risk factor and also a therapeutic target for SACC. The CRISPR/Cas9 system may control a pro-oncogenic splicing process through the exclusion of EDA exon from the FN gene, leading to inhibition of motility, invasion and proliferation of cancer cells.

Novel Y-chromosome polymorphisms in Chinese domestic yak.

Y-chromosome-specific haplotypes (Y-haplotypes) constructed using single nucleotide polymorphisms (Y-SNPs) in the MSY (male-specific region of the Y-chromosome) are valuable in population genetic studies. But sequence variants in the yak MSY region have been poorly characterized so far. In this study, we screened a total of 16 Y-chromosome-specific gene segments from the ZFY, SRY, UTY, USP9Y, AMELY and OFD1Y genes to identify Y-SNPs in domestic yaks. Six novel Y-SNPs distributed in the USP9Y (g.223C>T), UTY19 (g.158A>C and g.169C>T), AMELY2 (g.261C>T), OFD1Y9 (g.165A>G) and SRY4 (g.104G>A) loci, which can define three Y-haplotypes (YH1, YH2 and YH3) in yaks, were discovered. YH1 was the dominant and presumably most ancient haplotype based on the comparison of UTY19 locus with other bovid species. Interestingly, we found informative UTY19 markers (g.158A>C and g.169C>T) that can effectively distinguish the three yak Y-haplotypes. The nucleotide diversity was 1.7 × 10(-4) ± 0.3 × 10(-4) , indicating rich Y-chromosome diversity in yaks. We identified two highly divergent lineages (YH1 and YH2 vs. YH3) that share similar frequencies (YH1 + YH2: 0.82-0.89, YH3: 0.11-0.18) among all three populations. In agreement with previous mtDNA studies, we supported the hypothesis that the two highly divergent lineages (YH1 and YH2 vs. YH3) derived from a single gene pool, which can be explained by the reunion of at least two paternal populations with the divergent lineages already accumulated before domestication. We estimated a divergence time of 408 110 years between the two divergent lineages, which is consistent with the data from mitochondrial DNA in yaks.

Effect of dietary N-carbamylglutamate levels on reproductive performance of gilts.

The effect of dietary N-carbamylglutamate (NCG) supplementation during the entire gestation on reproductive performance of gilts was determined. At the initial day of gestation, forty-five cross-bred (Landrace × Large white) gilts were randomly assigned to five groups receiving a basal diet (control group) and basal diet supplemented with 0.05%, 0.10%, 0.15% and 0.20% NCG until parturition, respectively. At parturition, total litter size, live litter size and rate of stillbirth were not markedly affected by NCG supplementation. However, gilts in 0.05% NCG-supplemented group had more pigs born alive than gilts in control group (+1.11 pigs, p = 0.12), and live litter weight was increased (+12.13-19.17%, p < 0.05) in 0.05%, 0.10% and 0.15% NCG-supplemented groups relative to control group. And also, average birthweight of piglets born alive was higher (+6.57%, p < 0.05) in 0.05% NCG-supplemented group than in control group. Furthermore, on days 30, 60, 90 and 110 of gestation, concentrations of arginine and ornithine in plasma were higher (p < 0.05) in 0.05%, 0.10%, 0.15% and 0.20% NCG-supplemented groups than in control group, respectively. In addition, the chorioallantois gene expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor A (VEGF-A), placental growth factor (PLGF) and angiopoietin-2 (ANG-2) was all increased (p < 0.05) in 0.05%, 0.10% and 0.15% NCG-supplemented groups than in control group. In conclusion, dietary supplementation with 500 mg/kg NCG during the entire gestation significantly improves pregnancy outcomes in gilts, which may be associated with the improved concentrations of arginine in plasma and placental angiogenic factors gene expression of gilts.

Identification of CYP2C19 inhibitors from phytochemicals using the recombinant human enzyme model.

The aim of the present study was to develop the recombinant insect cell-expressed protein as an in vitro model for inhibitors screening for human cytochrome P450 2C19 (CYP2C19), and to use the model to investigate the inhibition effect of three phytochemicals on CYP2C19 in vitro. Omeprazole was applied as the probe substrate. The estimated inhibitory constant (K(i)) of ticlopidine and fluvoxamine were 0.64 +/- 0.025 microM and 0.29 +/- 0.090 microM, respectively. After co-incubation with ticlopidine or fluvoxamine, the mean omeprazole Michaelis-Menten constant (K(m)) increased from 4.99 +/- 0.22 microM to 16.25 +/- 1.22 microM or 19.20 +/- 1.73 microM, respectively, while omeprazole's mean V(max) did not vary much. Both ticlopidine and fluvoxamine were competitive inhibitors of CYP2C19. The IC50 of three phytochemicals, isoalantolactone, curcumol and schisandrin A was determined as 38.91 microM, 121.0 microM and 86.41 microM, and the K(i) as 5.02 +/- 1.04 microM, 35.84 +/- 8.95 microM, and 4.46 +/- 0.017 microM, respectively. The in vitro model for inhibitor screening established using recombinant CYP2C19 could be used to assess the inhibition potential of drug candidates. Isoalantolactone and schisandrin A are potent inhibitors of CYP2C19, while curcumol is a moderate potent inhibitor of CYP2C19.

Relationship between eNOS gene polymorphism and cerebral infarction of young and middle-aged Chinese Han population.

PURPOSE: To discuss the relationship between the acute cerebral infarction of differently aged population and the variable number tandem repeat polymorphism of endothelial nitric oxide synthase (eNOS) gene. METHODS: The genotypes of 129 acute cerebral infarction patients and 100 healthy control subjects were determined by PCR and polyacrylamide gel electrophoresis (PAGE). RESULTS: In the patient group, the frequency of allelic gene a was higher than that in the control group (13.56 % vs 3 %, p < 0.01), and the frequencies of the patients followed the descending order from young through middle-aged to elderly (42.31 % vs 17.2 % vs 5.8 %). The frequencies of the young, middle-aged and elderly population in the control group differed significantly (5.55 % vs 2.94 % vs 2.63 %), and those of the young and middle-aged population in the two groups also differed statistically significantly. CONCLUSION: The ab genotype of eNOS 4th intron is correlated with the acute cerebral infarction of young and middle-aged Chinese Han population that may involve allelic gene a as an independent risk factor (Tab. 3, Fig. 3, Ref. 13).