A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.

Intellectual disability (ID) is associated with an increased risk of developing psychiatric disorders, suggesting a common underlying genetic factor. Importantly, altered signaling and/or expression of regulator of G protein signaling 6 (RGS6) is associated with ID and numerous psychiatric disorders. RGS6 is highly conserved and undergoes complex alternative mRNA splicing producing ~36 protein isoforms with high sequence similarity historically necessitating a global approach in functional studies. However, our recent analysis in mice revealed RGS6 is most highly expressed in CNS with RGS6L(+GGL) isoforms predominating. A previously reported genetic variant in intron 17 of RGS6 (c.1369-1G>C), associated with ID, may provide further clues into RGS6L(+GGL) isoform functional delineation. This variant was predicted to alter a highly conserved canonical 3' acceptor site creating an alternative branch point within exon 18 (included in a subset of RGS6L(+GGL) transcripts) and a frameshift forming an early stop codon. We previously identified this alternative splice site and demonstrated its use generates RGS6Lζ(+GGL) isoforms. Here, we show that the c.1369-1G>C variant disrupts the canonical, preferred (>90%) intron 17 splice site and leads to the exclusive use of the alternate exon 18 splice site, inducing disproportionate expression of a subset of isoforms, particularly RGS6Lζ(+GGL). Furthermore, RGS6 global knockout mice do not exhibit ID. Thus, ID caused by the c.1369-1G>C variant likely results from altered RGS6 isoform expression, rather than RGS6 isoform loss. In summary, these studies highlight the importance of proper RGS6 splicing and identify a previously unrecognized role of G protein signaling in ID.

[The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice].

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

[Efficacy comparison between a new generation of artificial ligaments and bone-patellar tendon-bone autograft for anterior cruciate ligament revision].

Objective: To compare the clinical efficacy of a new generation of ligaments (LARS artificial ligament) and bone-patellar tendon-bone (BPTB) autograft as grafts in anterior cruciate ligament (ACL) revision. Methods: A retrospective cohort study. The clinical data of 54 patients who underwent ACL revision from January 2018 to June 2020 in the First Hospital Affiliated to Army Medical University were retrospectively analyzed. There were 44 males and 10 females with a mean age of (28.5±7.7) years (15-45 years). Among them, 24 cases underwent ACL revision with LARS artificial ligament (LARS group), the other 30 cases underwent ACL revision with BPTB (BPTB group). The subjective and objective knee joint evaluation indexes were compared between the two groups to evaluate the clinical efficacy. The subjective evaluation indexes included Tegner score, Lysholm score and the International Knee Documentation Committee (IKDC) score. The objective evaluation indexes included the Lachman test, pivot-shift test, the anterior tibial translation (ATT) measurement at the weight-bearing position and the rate of patients returned to pre-injury sports. Results: The follow-up period was (32.8±5.3) months (24-42 months). At the last follow-up, the IKDC score, Tegner score and Lysholm score in the two groups significantly increased when compared with those before surgery (all P<0.05), and there was no significant difference in those indexes between the two groups (all P>0.05). The ATT measurement in the weight-bearing position was (3.1±0.7) mm in the LARS group and it was (4.1±0.9) mm in the BPTB group, which were significantly improved when compared with those before surgery (both P<0.05), and it was better in the LARS group than in the BPTB group (P<0.05). Postoperative Lachman test and pivot-shift test results in the LARS group were better than those in the BPTB group with statistically significant difference (both P<0.05). The rate of patients returned to pre-injury sports one year after surgery was 79.2%(19/24) in the LARS group and it was 50.0%(15/30) in the BPTB group, and the difference was statistically significant (P=0.029). Conclusions: Both LARS artificial ligament and BPTB autograft can achieve good short-term clinical efficacy in ACL revision, but LARS artificial ligament group has more advantages than BPTB autograft group in knee stability and early return to sports.

Mating-Type Genes Control Sexual Reproduction, Conidial Germination, and Virulence in Cochliobolus lunatus.

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.

[A time-series study on the association of ambient temperature with daily outpatient visits of eczema in Huizhou city].

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.

Circulating miR-374b-5p negatively regulates osteoblast differentiation in the progression of osteoporosis via targeting Wnt3 AND Runx2.

Osteoporosis is defined as an aging-related skeletal disorder involving deterioration of bone mass and bone structure, and consequently, increased risk of fractures. Emerging evidence indicates the dysregulation of microRNAs (miRNAs) in the progression of osteoporosis. However, whether such associated miRNAs control osteoblast differentiation or constitute therapeutic targets remains elusive. In the present study, we found elevated circulating miR-374b-5p level associated with postmenopausal osteoporosis. miR-374b-5p served as a critical suppressor of osteoblast differentiation. We further identified that miR-374b-5p directly targeted Wnt family member 3 (Wnt3) and Runt-related transcription factor 2 (Runx2) through its 3'-untranslated regions (3'UTRs). Moreover, the antagonist of miR-374b-5p could promote bone formation in ovariectomy (OVX)-induced mice. Together, our results revealed that miR-374b-5p directly targeted Wnt3 and Runx2, negatively regulating osteoblast differentiation and bone formation. Collectively, circulating miR-374b-5p in the serum might serve as a potential diagnostic and therapeutic strategy for osteoporosis.

Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids.

PURPOSE: To evaluate high-dose intravenous glucocorticoid treatment on tear inflammatory cytokines and ocular surface parameters in patients with active TED. Correlations between tear inflammatory cytokines and clinical parameters were also investigated. METHODS: This prospective pilot study included 15 moderate-to-severe and active TED patients. Control group consist of 15 sex and age-matched healthy subjects. All TED patients were treated with high-dose intravenous methylprednisolone with cumulative dose of 4.5 g during the therapy subdivided into 12 weekly infusions. Tear concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) were measured by multiplex bead analysis in TED patients at baseline and 12 weeks after treatment. Ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescent staining, and Schirmer's test were obtained from TED and controls. RESULTS: All baseline cytokine levels except for IL-17A were significantly elevated in active TED patients compared with controls. Concentrations of IL-1ß, IL-6, IL-8, TNF-α, and VEGF were significantly decreased at 12 weeks compared with baseline. OSDI and TBUT showed significant improvement at 6 and 12 weeks. There were significant positive correlations between IL-6, IL-8, and CAS, and negative correlation was found between IL-6 level and TED duration before methylprednisolone treatment. The reduction of IL-6, IL-8, and VEGF were positive correlated with the reduction in CAS at 12 weeks. CONCLUSIONS: High-dose glucocorticoids treatment improved ocular surface symptom, increased the tear film stability, and decreased tear inflammatory cytokines in active TED. The reduction of the inflammatory cytokines is consistent with the improvement of clinical parameters.

Identification of genetic loci associated with growth traits at weaning in yak through a genome-wide association study.

A multilocus GWAS was performed to explore the genetic architecture of four growth traits in yak. In total, 354 female yaks for which measurements of body weight (BW), withers height (WH), body length (BL) and chest girth (CG) at weaning were available underwent genotyping with the Illumina BovineHD BeadChip (770K). After quality control, we retained 98 688 SNPs and 354 animals for GWAS analysis. We identified seven, 18, seven and nine SNPs (corresponding to seven, 17, seven and eight candidate genes) associated with BW, WH, BL and CG at weaning respectively. Interestingly, most of these candidate genes were reported to be involved in growth-related processes such as muscle formation, lipid deposition, feed efficiency, carcass composition and development of the central and peripheral nervous system. Our results offer novel insight into the molecular architecture underpinning yak growth traits. Further functional analyses are thus warranted to explore the molecular mechanisms whereby these genes affect these traits of interest.

Anomalous relaxation kinetics and charge-density-wave correlations in underdoped BaPb1-x Bi x O3.

Superconductivity often emerges in proximity of other symmetry-breaking ground states, such as antiferromagnetism or charge-density-wave (CDW) order. However, the subtle interrelation of these phases remains poorly understood, and in some cases even the existence of short-range correlations for superconducting compositions is uncertain. In such circumstances, ultrafast experiments can provide new insights by tracking the relaxation kinetics following excitation at frequencies related to the broken-symmetry state. Here, we investigate the transient terahertz conductivity of BaPb1-x Bi x O3--a material for which superconductivity is "adjacent" to a competing CDW phase--after optical excitation tuned to the CDW absorption band. In insulating BaBiO3 we observed an increase in conductivity and a subsequent relaxation, which are consistent with quasiparticles injection across a rigid semiconducting gap. In the doped compound BaPb0.72Bi0.28O3 (superconducting below TC = 7 K), a similar response was also found immediately above TC This observation evidences the presence of a robust gap up to T [Formula: see text] 40 K, which is presumably associated with short-range CDW correlations. A qualitatively different behavior was observed in the same material for [Formula: see text] 40 K. Here, the photoconductivity was dominated by an enhancement in carrier mobility at constant density, suggestive of melting of the CDW correlations rather than excitation across an optical gap. The relaxation displayed a temperature-dependent, Arrhenius-like kinetics, suggestive of the crossing of a free-energy barrier between two phases. These results support the existence of short-range CDW correlations above TC in underdoped BaPb1-x Bi x O3, and provide information on the dynamical interplay between superconductivity and charge order.

Optical limiting, nonlinear refraction and nonlinear absorption of the associates of Cd0.5Zn0.5S quantum dots and dyes.

The optical limiting properties of alloyed Cd0.5Zn0.5S quantum dots associated with erythrosine dye are analyzed using 532 nm, 40 ps pulses. We show that joint influence of saturable absorption, reverse saturable absorption and two-photon absorption cause the optical limiting of 532 nm radiation at the pulse energies exceeding 1 mJ. The nonlinear refraction and nonlinear absorption of these quantum dots associated with different organic dyes were studied using 1064 nm and 532 nm radiation. The nonlinear refraction index and nonlinear absorption coefficient of Cd0.5Zn0.5S quantum dots were measured at λ = 1064 nm to be 2 × 10-13 cm2 W-1 and 1.2 × 10-8 cm W-1, while the reverse saturable absorption of Cd0.5Zn0.5S quantum dots and erythrosine at λ = 532 nm was almost two orders larger. The potential applications of these quantum dots for high-order harmonic generation are discussed.

Magnetic-Field Tuning of Light-Induced Superconductivity in Striped La_{2-x}Ba_{x}CuO_{4}.

Optical excitation of stripe-ordered La_{2-x}Ba_{x}CuO_{4} has been shown to transiently enhance superconducting tunneling between the CuO_{2} planes. This effect was revealed by a blueshift, or by the appearance of a Josephson plasma resonance in the terahertz-frequency optical properties. Here, we show that this photoinduced state can be strengthened by the application of high external magnetic fields oriented along the c axis. For a 7 T field, we observe up to a tenfold enhancement in the transient interlayer phase correlation length, accompanied by a twofold increase in the relaxation time of the photoinduced state. These observations are highly surprising, since static magnetic fields suppress interlayer Josephson tunneling and stabilize stripe order at equilibrium. We interpret our data as an indication that optically enhanced interlayer coupling in La_{2-x}Ba_{x}CuO_{4} does not originate from a simple optical melting of stripes, as previously hypothesized. Rather, we speculate that the photoinduced state may emerge from activated tunneling between optically excited stripes in adjacent planes.

[Effect of positive end-expiratory pressure on the cross-sectional area of the internal jugular vein and anatomic relationship between the internal jugular vein and the carotid artery in general anaesthesia of laryngeal mask airway].

Objective: To investigate the effect of positive end-expiratory pressure(PEEP) on the cross-sectional area (CSA) of the internal jugular vein (IJV) and anatomic relationship between the IJV and the common carotid artery (CCA) in general anaesthesia of laryngeal mask airway(LMA). Methods: Sixty American Society of Anesthesiologists (ASA) Ⅰ or Ⅱ grade patients undergoing elective operation received general anaesthesia using LMA from May to November 2017, aged 20-65, were included in this study and randomly divided into 4 groups: group P0 (PEEP: 0 cmH(2)O), group P5 (PEEP: 5 cmH(2)O), group P10 (PEEP: 10 cmH(2)O), group P15 (PEEP: 15 cmH(2)O). Following the induction of anesthesia, LMA was inserted, and mechanical ventilation was started while the right cervical vessels was imaged by ultrasonography after applying 4 different PEEPs in random order. Measurements were made after 1 min in each PEEP. The CSA, transverse diameter (TD), anteroposterior diameters (AD) of the IJV and the diameter, overlap distance and overlap index of CCA was measured. The arterial blood pressure, heart rate, and vasoactive drugs used were also recorded. Results: The CSA of group P0, P10 and P15 was (1.36±0.55), (1.80±0.54), (2.02±0.58) cm(2). The TD was (1.31±0.33), (1.61±0.49), (1.74±0.53) cm. The AD was (1.12±0.20), (1.33±0.30), (1.46±0.32) cm. Compared to group P0, the CSA, TD and AD of IJV in group P10 and P15 were significantly increased (P0/P10: t=7.81, 3.81, 4.30, all P<0.01; P0/P15: t=11.68, 5.40, 6.96, all P<0.01). There was no significant difference in the AD and TD of IJV between group P10 and P15 (all P>0.05), while the CSA of group P15 was bigger than that of group P10 (t=2.17, P<0.05). The overlap distance of group P0, P10 and P15 was (0.51±0.12), (0.62±0.16), (0.66±0.15) cm. The overlap index was (76.80±20.03)%, (91.10±26.13)%, (96.21±25.36)%. Compared to group P0, the overlap distance and overlap index in group P10 and P15 were significantly increased (P0/P10: t=4.49, 3.41, both P<0.01; P0/P15: t=5.91, 4.63, both P<0.01). There was no significant changes in the overlap distance and overlap index between group P10 and P15 (all P>0.05). The MAP of group P15 was lower than that of group P10 [(73.35±9.73 )vs (67.58±12.58) mmHg, t=2.745, P<0.05]. No patients were given atropine or norepinephrine. Conclusions: The application of PEEP effectively increases the CSA of IJV in general anaesthesia of LMA. At the same time, it also lead to higher overlap index between the IJV and CCA.Ten cmH(2)O PEEP provides the best balance between the increase of CSA and the stability of haemodynamics.

[Diagnosis and treatment experience of 161 cases of pancreatic serous cystic neoplasm in single center and analysis of cause of preoperation misjudgement].

Objective: To analyze the causes of preoperative miscarriage of pancreatic serous cystadenoma (SCN) and find the ways to improve it. Methods: Clinical data of 425 pancreatic cystic neoplasm patients who underwent surgical resection from January 2006 to December 2016 in Department of Pancreatic Surgery in Huashan Hospital were retrospectively analyzed.Excel database was created which covered 128 fields of 7 fields: general information of patients, preoperative blood biochemical indexes, tumor markers, surgical related data, postoperative complications, imaging findings and pathology.One hundred and sixty-one cases of SCN were analyzed in depth, mainly in three aspects: surgical benefit, preoperative imaging diagnostic value and interference factors in preoperative judgement.The classification data were analyzed by χ(2) test and the quantitative data were analyzed by t test.The Logistic regression model was used for multiple factor analysis. Results: Of the 425 PCN cases surgically removed, 161 cases (37.9%) were SCN, the incidence of operative complications was 40.4%(65/161), the hospitalization days was (20.7±12.1)days and the medical cost was (75 267±37 866) yuan.Only 3 of 161 cases of SCN were accurately diagnosed by preoperative imaging methods, 61 cases were diagnosed as "cystic lesions of pancreas" (37.9%) and 52 cases were diagnosed as "pancreatic cystadenoma" (32.3%). SCN was misdiagnosed as MCN(32.3%) and IPMN(28%) before operation.25.5% of them were diagnosed as SCN before operation, but still underwent radical operation.The rate of preoperative imaging diagnosis for identifying SCN was 62.8%.The lack of preoperative endoscopy and the lack of understanding of the image characteristics and biological behavior of SCN were the most important factors affecting the accuracy of preoperative judgment.Statistics found that gender, age, CA125 and tumor location can be used as independent factors contribute to the clinical identification(χ(2)=8.995, P=0.003; χ(2)=10.019, P=0.007; t=3.157, P=0.002; χ(2)=6.790, P=0.009). Logistic analysis showed that women, older than 60 years old, the tumors located in the pancreatic body and tail were the independent factors of SCN classification and diagnosis (OR=0.481, 0.376, 0.577, 0.666, 95% CI: 0.305-0.759, 0.199-0.710, 0.361-0.924, 0.433-1.024, P=0.002, 0.003, 0.022, 0.064). Conclusions: SCN has more benign biological behavior.Although surgical excision is acceptable for clinical safety, the corresponding benefit is very limited.It is possible to improve the rationality of SCN clinical operation decisions to some extent by performing endoscopic examination, imaging doctors to improve the SCN feature recognition and surgeons to enhance the awareness of SCN.

Upregulated microRNA-301a in osteosarcoma promotes tumor progression by targeting CDC14A.

MicroRNAs (miRs) are associated with tumor progression in various cancers, such as gastric and hepatic carcinomas, and lung cancer. miR-301a is overexpressed and displays oncogenic activity in cancers. We investigated the biological involvement of miR-301a in osteosarcoma (OS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze expression levels of miR-301a in 24 OS and matched adjacent non-tumor tissues. A miR-301a mimic was transferred into OS cell lines U-2 OS and MG-63 to upregulate miR-301a. The effects of miR-301a were investigated by examining cell proliferation, migration, and the cell cycle. The miR-301 target was predicted by TargetScan and confirmed by western blotting and qRT-PCR. The expression of miR-301a was significantly higher in OS tissues compared with the matched adjacent non-tumor tissues (0.959 ± 0.39 vs 3.9516 ± 1.18). Upregulated miR-301a significantly increased proliferation at 48 and 72 h compared to the negative control (U-2 OS: 2.11 ± 0.21 vs 2.88 ± 0.24; 2.70 ± 0.26 vs 3.71 ± 0.24; MG-63: 2.19 ± 0.20 vs 3.19 ± 0.22; 3.1 ± 0.25 vs 4.01 ± 0.27) and migration capability (U-2 OS: 100 ± 20.19 vs 150.68 ± 32.83; MG-63: 100 ± 17.20 vs 133.35 ± 26.26), and decreased apoptosis in both U-2 OS (10.87 ± 2.53 vs 4.01 ± 2.23) and MG-63 (15.26 ± 2.15 vs 8.25 ± 3.07). The cell cycle studies revealed that miR-301a caused an increase of the G2 population in U-2 OS (38.6 ± 6.58 vs 47.2 ± 7.27) and MG-63 (44.01 ± 5.28 vs 57.9 ± 4.25). Additional experiments indicated that CDC14A was upregulated by miR-301a (0.63 ± 0.06 vs 0.98 ± 0.06; 1.49 ± 0.25 vs 2.99 ± 0.14). Overexpressed miR-301a may increase CDC14A expression and promote cell proliferation and migration in OS cells. Therefore, miR- 301a may be useful for osteosarcoma diagnosis and therapy.

Relationship between estrogen receptor 1 gene polymorphisms and postmenopausal osteoporosis of the spine in Chinese women.

The purpose of this study was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor 1 gene (ESR1) at rs2234693 and rs9340799, as well as to investigate the relationship between ESR gene polymorphisms and postmenopausal osteoporosis (OP) of the spine in Chinese women. We recruited 198 postmenopausal women with OP and 276 healthy women between May 2012 and September 2015 in Zhongshan Hospital. Dual energy x-ray absorptiometry was used to measure the bone mineral density (BMD) of the lumbar vertebrae in all subjects. In addition, PCR-restriction fragment length polymorphism based analysis was conducted to identify the genotypes of ESR1. The distribution of ESR1 in the osteoporosis group and the control group was determined; the relationship between ESR polymorphisms and BMD was analyzed. The distributions of BMD were: TT < TC < CC, GG < AG < AA. The TT, TTGG, and TCGG genotypes were found to be lower as compared to the other genotypes. Stratified analysis suggested that the TT genotype and the combined genotypes TTGG and TCGG were significantly higher in the OP group as compared to the control group (P < 0.01). Therefore, ESR1 polymorphisms at rs2234693 and rs9340799 may be associated with OP, and could be used as markers to screen those with high risks to postmenopausal OP in Chinese women.

Prevalence of Helicobacter pylori infection and its association with lipid profiles.

OBJECTIVE: To evaluate the prevalence of Helicobacter pylori (H. pylori, HP) infection in subjects receiving routine physical examination and its associations with age, sex, body mass index (BMI) and lipid profiles. MATERIALS AND METHODS: Clinical information of 22,103 individuals who took routine physical examinations, including that on age, gender, height, weight, triglyceride, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and data of HP infection were collected and analyzed. RESULTS: H. pylori infection rate in 22,103 subjects taking routine physical examination was 44.5 %. More men tended to be infected with H. pylori than women (45.9 % vs 42.8 %; p < 0.01). The highest positive rate group was in the age group of 30-39 years (46.8 %) and the lowest rate was in the age group younger than 30 years (40.5 %). The obese had higher infection rate than the non-obese (p < 0.01). Mann-Whitney U test was used to explore the relationships between lipid profiles and H. pylori infection. There were significant associations among HDL, triglyceride and HP infection (p < 0.01). However, significant differences were not confirmed between cholesterol, LDL and H. pylori infection. CONCLUSION: H. pylori infection was common among subjects receiving physical examination in Shanghai and it was most significantly associated with HDL and triglyceride, indicating that H. pylori might be a new cardiovascular risk factor (Tab. 3, Ref. 23).

Evaluation of common variants in CNR2 gene for bone mineral density and osteoporosis susceptibility in postmenopausal women of Han Chinese.

UNLABELLED: Postmenopausal osteoporosis is a major health problem with important genetic factors in postmenopausal women. We thoroughly evaluated the relationship of CNR2 polymorphisms with osteoporosis in a cohort of 1032 osteoporosis patients and 2089 healthy controls from Han Chinese postmenopausal women. Statistically significant differences, depending on different genotypes, were presented. INTRODUCTION: Osteoporosis is a major health problem in postmenopausal women, which is a multifactorial disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetic polymorphism in susceptibility genes. The aim of our study was to investigate whether CNR2 gene, which attributes to osteoporosis susceptibility in some populations, is associated with bone mineral density (BMD) or osteoporosis in Han Chinese postmenopausal women. METHODS: We examine 39 SNPs covering the region of CNR2 gene in 3121 Han Chinese postmenopausal women, consisting of 1032 osteoporosis patients and 2089 healthy controls, to evaluate the association with BMD and osteoporosis. RESULTS: We found that rs4237 and rs2501431 were significantly associated with BMD and osteoporosis (corrected p = 0.020085 and 0.017199) in our sample, and the TT genotype of rs2501431 and the AA genotype of rs4237 had lower lumbar spine BMD and femoral neck BMD compared with the other genotypes. Additionally, analyses by haplotypes indicated that two haplotype blocks, containing rs4237 and rs2501431 respectively, in the CNR2 gene significantly associated with BMD and osteoporosis (both global permutation p < 0.001), and a risk haplotype (ATTT) in the block of rs3003336-rs2501431-rs2502992-rs2501432 had almost 4-fold increase in the cases. CONCLUSIONS: Our results provide further supportive evidence for an important role of CNR2 gene in the etiology of osteoporosis and suggest that it may be a genetic risk factor for BMD and osteoporosis in Han Chinese postmenopausal women.

Influence of adenosine on preservation of porcine pancreas in islet transplantation.

Ischemia time during transplantation has greatly restricted the quality and utilization of grafts. To improve the quality of islet transplantation, adenosine was added into the University of Wisconsin (UW) pancreas perfusate to assess its effect on islet yield and function in porcine pancreas. Ten pancreata from donation after cardiac death pigs were obtained and randomly divided into two groups: control group (N = 5) with UW perfusion solution, and experimental group (N = 5) with adenosine-enriched UW perfusion solution. The yield and purity of the islet cells were counted after they were collected, purified, and stained with dithizone. Acridine orange/propidium iodide staining was applied to determine islet cell viability. Islet function was assessed by glucose stimulated insulin secretion assays, and released insulin was quantified by enzyme-linked immunosorbent assay. The metabolic substrates of the pancreas were analyzed by trace dialysis technology. We found that the addition of adenosine in UW perfusion solution significantly increased the yield, purity and viability of islet cells, as well as enhanced their insulin release. In addition, the levels of metabolic substrates, pyruvate and lactate, were significantly reduced. The addition of adenosine could effectively increase islet cell viability during mechanical perfusions, which may improve islet transplantation. This perfusion protocol may be clinically feasible, and should be considered in the clinical setting.