The effect of polymorphisms in FSHR gene on late follicular phase progesterone and estradiol serum levels in predicted normoresponders.

STUDY QUESTION: Does the presence of FSHR single-nucleotide polymorphisms (SNPs) affect late follicular phase progesterone and estradiol serum levels in predicted normoresponders treated with rFSH? SUMMARY ANSWER: The presence of FSHR SNPs (rs6165, rs6166, rs1394205) had no clinically significant impact on late follicular phase serum progesterone and estradiol levels in predicted normoresponders undergoing a GnRH antagonist protocol with a fixed daily dose of 150 IU rFSH. WHAT IS KNOWN ALREADY: Previous studies have shown that late follicular phase serum progesterone and estradiol levels are significantly correlated with the magnitude of ovarian response. Several authors have proposed that individual variability in the response to ovarian stimulation (OS) could be explained by variants in FSHR. However, so far, the literature is scarce on the influence of this genetic variability on late follicular phase steroidogenic response. Our aim is to determine whether genetic variants in the FSHR gene could modulate late follicular phase serum progesterone and estradiol levels. STUDY DESIGN, SIZE, DURATION: In this multicenter multinational prospective study conducted from November 2016 to June 2019, 366 patients from Vietnam, Belgium and Spain (166 from Europe and 200 from Asia) underwent OS followed by oocyte retrieval in a GnRH antagonist protocol with a fixed daily dose of 150 IU rFSH. All patients were genotyped for 3 FSHR SNPs (rs6165, rs6166, rs1394205) and had a serum progesterone and estradiol measurement on the day of trigger. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included patients were predicted normal responder women <38 years old undergoing their first or second OS cycle. The prevalence of late follicular phase progesterone elevation (PE), as well as mean serum progesterone and estradiol levels on the day of trigger were compared between the different FSHR SNPs genotypes. PE was defined as >1.50 ng/ml. MAIN RESULTS AND THE ROLE OF CHANCE: The overall prevalence of PE was 15.8% (n = 58). No significant difference was found in the prevalence of PE in Caucasian and Asian patients (17.5% versus 14.5%). Estradiol levels on the day of trigger and the number of retrieved oocytes were significantly higher in patients with PE (4779 ± 6236.2 versus 3261 ± 3974.5 pg/ml, P = 0.003, and 16.1 ± 8.02 versus 13.5 ± 6.66, P = 0.011, respectively). Genetic model analysis, adjusted for patient age, body mass index, number of retrieved oocytes and continent (Asia versus Europe), revealed a similar prevalence of PE in co-dominant, dominant and recessive models for variants FSHR rs6166, rs6165 and rs1394205. No statistically significant difference was observed in the mean late follicular phase progesterone serum levels according to the genotypes of FSHR rs6166 (P = 0.941), rs6165 (P = 0.637) and rs1394205 (P = 0.114) in the bivariate analysis. Also, no difference was found in the genetic model analysis regarding mean late follicular phase progesterone levels across the different genotypes. Genetic model analysis has also revealed no statistically significant difference regarding mean estradiol levels on the day of trigger in co-dominant, dominant and recessive models for variants FSHR rs6166, rs6165 and rs1394205. Haplotype analysis revealed a statistically significant lower estradiol level on the day of trigger for rs6166/rs6165 haplotypes GA, AA and GG when compared to AG (respectively, estimated mean difference (EMD) -441.46 pg/ml (95% CI -442.47; -440.45), EMD -673.46 pg/ml (95% CI -674.26; -672.67) and EMD -582.10 pg/ml (95% CI -584.92; -579.28)). No statistically significant differences were found regarding the prevalence of PE nor late follicular phase progesterone levels according to rs6166/rs6165 haplotypes. LIMITATIONS, REASONS FOR CAUTION: Results refer to a population of predicted normal responders treated with a normal/low fixed dose of 150 IU rFSH throughout the whole OS. Consequently, caution is needed before generalizing our results to all patient categories. WIDER IMPLICATIONS OF THE FINDINGS: Based on our results, FSHR SNPs rs6165, rs6166 and rs1394205 do not have any clinically significant impact neither on late follicular phase serum progesterone nor on estradiol levels in predicted normal responders. These findings add to the controversy in the literature regarding the impact of individual genetic susceptibility in response to OS in this population. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an unrestricted grant by Merck Sharp & Dohme (MSD, IISP56222). N.P.P. reports grants and/or personal fees from MSD, Merck Serono, Roche Diagnostics, Ferring International, Besins Healthcare, Gedeon Richter, Organon, Theramex and Institut Biochimique SA (IBSA). C.A. reports conference fees from Merck Serono, Medea and Event Planet. A.R.N., C.B., C.S., P.Q.M.M., H.T., C.B., N.L.V., M.T.H. and S.G. report no conflict of interests related to the content of this article. TRIAL REGISTRATION NUMBER: NCT03007043.

Observation of a Strongly Isospin-Mixed Doublet in

ß decay of proton-rich nuclei plays an important role in exploring isospin mixing. The ß decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through ß-delayed two-proton emission (ß2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P ß decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in ß-decay experiments.

The effect of polymorphisms in FSHR and FSHB genes on ovarian response: a prospective multicenter multinational study in Europe and Asia.

STUDY QUESTION: Does the presence of single nucleotide polymorphisms (SNPs) in the FSH receptor gene (FSHR) and/or FSH beta subunit-encoding gene (FSHB) influence ovarian response in predicted normal responders treated with rFSH? SUMMARY ANSWER: The presence of FSHR SNPs (rs6165, rs6166, rs1394205) has a statistically significant impact in ovarian response, although this effect is of minimal clinical relevance in predicted normal responders treated with a fixed dose of 150 IU rFSH. WHAT IS KNOWN ALREADY: Ovarian reserve markers have been a breakthrough in response prediction following ovarian stimulation. However, a significant percentage of patients show a disproportionate lower ovarian response, as compared with their actual ovarian reserve. Studies on pharmacogenetics have demonstrated a relationship between FSHR or FSHB genotyping and drug response, suggesting a potential effect of individual genetic variability on ovarian stimulation. However, evidence from these studies is inconsistent, due to the inclusion of patients with variable ovarian reserve, use of different starting gonadotropin doses, and allowance for dose adjustments during treatment. This highlights the necessity of a well-controlled prospective study in a homogenous population treated with the same fixed protocol. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium, and Spain (168 from Europe and 200 from Asia), from November 2016 until June 2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonist protocol with a fixed daily dose of 150 IU rFSH until triggering. Blood sampling and DNA extraction was performed prior to oocyte retrieval, followed by genotyping of four SNPs from FSHR (rs6165, rs6166, rs1394205) and FSHB (rs10835638). PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible were predicted normal responder women <38 years old undergoing their first or second ovarian stimulation cycle. Laboratory staff and clinicians were blinded to the clinical results and genotyping, respectively. The prevalence of hypo-responders, the number of oocytes retrieved, the follicular output rate (FORT), and the follicle to oocyte index (FOI) were compared between different FSHR and FSHB SNPs genotypes. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of derived allele homozygous SNPs in the FSHR was rs6166 (genotype G/G) 15.8%, rs6165 (genotype G/G) 34.8%, and rs1394205 (genotype A/A) 14.1%, with significant differences between Caucasian and Asian women (P < 0.001). FSHB variant rs10835638 (c.-211 G>T) was very rare (0.5%). Genetic model analysis revealed that the presence of the G allele in FSHR variant rs6166 resulted in less oocytes retrieved when compared to the AA genotype (13.54 ± 0.46 vs 14.81 ± 0.61, estimated mean difference (EMD) -1.47 (95% CI -2.82 to -0.11)). In FSHR variant rs1394205, a significantly lower number of oocytes was retrieved in patients with an A allele when compared to G/G (13.33 ± 0.41 vs 15.06 ± 0.68, EMD -1.69 (95% CI -3.06 to -0.31)). A significantly higher prevalence of hypo-responders was found in patients with the genotype A/G for FSHR variant rs6166 (55.9%, n = 57) when compared to A/A (28.4%, n = 29), ORadj 1.87 (95% CI 1.08-3.24). No significant differences were found regarding the FORT across the genotypes for FSHR variants rs6166, rs6165, or rs1394205. Regarding the FOI, the presence of the G allele for FSHR variant rs6166 resulted in a lower FOI when compared to the A/A genotype, EMD -13.47 (95% CI -22.69 to -4.24). Regarding FSHR variant rs6165, a lower FOI was reported for genotype A/G (79.75 ± 3.35) when compared to genotype A/A (92.08 ± 6.23), EMD -13.81 (95% CI -25.41 to -2.21). LIMITATIONS, REASONS FOR CAUTION: The study was performed in relatively young women with normal ovarian reserve to eliminate biases related to age-related fertility decline; thus, caution is needed when extrapolating results to older populations. In addition, no analysis was performed for FSHB variant rs10835638 due to the very low prevalence of the genotype T/T (n = 2). WIDER IMPLICATIONS OF THE FINDINGS: Based on our results, genotyping FSHR SNPs rs6165, rs6166, rs1394205, and FSHB SNP rs10835638 prior to initiating an ovarian stimulation with rFSH in predicted normal responders should not be recommended, taking into account the minimal clinical impact of such information in this population. Future research may focus on other populations and other genes related to folliculogenesis or steroidogenesis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an unrestricted grant by Merck Sharp & Dohme (MSD). N.P.P. reports grants and/or personal fees from MSD, Merck Serono, Roche Diagnostics, Ferring International, Besins Healthcare, Gedeon Richter, Theramex, and Institut Biochimique SA (IBSA). N.L.V. and M.T.H. report consultancy and conference fees from Merck, Ferring, and MSD, outside the submitted work. P.D. has received honoraria for lecturing and/or research grants from MSD, Ferring International, and Merck. D.S. reports grants and/or personal fees from MSD, Ferring International, Merck Serono, Cook, and Gedeon Richter. A.R.N., B.A.M., C.S., J.M., L.H.L., P.Q.M.M., H.T., and S.G. report no conflict of interests. TRIAL REGISTRATION NUMBER: NCT03007043.

Association of MICA gene polymorphisms with thionamide-induced agranulocytosis.

BACKGROUND: Thionamide-induced agranulocytosis (TIA), namely antithyroid drug (ATD)-induced agranulocytosis, is one of the most feared adverse effect of ATDs. It is defined as a granulocyte count of less than 0.5 × 109/L after ATD administration. Several studies reported that TIA is associated with human leukocyte antigen (HLA) and nearby genes. Our previous study found that the susceptibility genes of TIA are similar in north China and European populations. METHODS: We evaluated the associations of 23 candidate single nucleotide polymorphisms (SNPs) in 37 patients with TIA and 254 patients with Graves' disease (GD) as controls by iPLEX MassARRAY system. RESULTS: Five SNPs in the MHC class I polypeptide-related sequence A(MICA) genes [rs4349859 (p = 1.43E-7); rs145575084 (p = 5.79E-6); rs116135464 (p = 3.70E-5); rs148015908 (p = 3.79E-5) and rs189600525 (p = 2.15E-4)] were found to be significantly associated with TIA after Bonferroni correction. After combining with previous data of rs4349859 and HLA-B*27:05, the haplotype analysis showed that patients carrying P-A-C-A-T-T-A haplotype have a higher risk of TIA (p = 9.76E-7; OR = 14.85, 95% CI 3.63-60.77). CONCLUSION: Our findings suggest that five high linked SNPs of MICA gene are significantly associated with susceptibility to TIA.

Positive selection signatures in Anqing six-end-white pig population based on reduced-representation genome sequencing data.

Anqing six-end-white (AQ) pig performs well on resistance to coarse fodder and disease, reproduction and meat quality, offering high potential for exploitation. Environmental conditions and strict selections from local farmers have cultivated the AQ pig to be an outstanding and unique local pig breed. Thus we aim to detect genetic positive selection signatures within the AQ pig population to explore underlying genetic mechanisms. A relative extended haplotype homozygosity (REHH) test was performed in the population of 79 AQ pigs to seek evidence demonstrating that selective actions have left an imprint on the whole genome. In total, 430 500 REHH tests were performed on 53 067 core regions with average REHH tests of 8.11, average lengths of 11.50 kb and an overall length of 610.38 Mb which accounted for 26.94% of the whole genome. Finally, a total of 1819 core haplotypes (P < 0.01) and 586 candidate genes were obtained. These genes were mainly related to meat quality (MYOG, SNX19), resistance to disease (CRISPLD2, CD14) and reproduction traits (ERBB2, NRP2). A panel of genes within the 30 top significant REHH tests was mainly categorized to traits of meat quality and disease resistance. Among 13 KEGG pathways, MAPK, GnRH and Oxytocin signaling pathways, associated with the biological processes of crucial economic traits, were noteworthy. The excellent characteristics of the AQ pig benefited from the combination of natural and human factors. We provide a sketch map that shows the distribution of selection footprints on the whole genome of AQ pig and found potential genes for future studies.

Identification of genes related to intramuscular fat independent of backfat thickness in Duroc pigs using single-step genome-wide association.

Intramuscular fat (IMF) is an important meat-quality trait of pigs, which influences pork's shearing force, hydraulics, tenderness and juicy flavor. However, to achieve a higher percentage of lean meat, pigs with lower backfat thickness (BF) are intensively selected for, which may lead to a reduction in pork quality. Therefore, the objective of this study was to locate loci that affect IMF without changing BF. A single-step GWAS was performed on 950 Duroc pigs genotyped by a 50K SNP chip in order to detect genomic variants relevant to IMF and BF. The significant SNPs detected were afterwards divided into a BF subset (seven SNPs), an IMF subset (11 SNPs) and a subset of both traits (12 SNPs), according to their P-value and LD. After SNP and QTL annotation, our results indicated that SSC1: 167938652, 166363826, 164829874 and 167171587 might be associated with IMF without changing BF. In the subset of both traits, we found that the combined effect of ALGA0006602 (SSC1: 159538854) and 12784636 (SSC1: 160773437) might improve the IMF without changing BF. Our gene annotation result showed that TLE3, ITGA11, SMAD6, PAQR5 and [RNF152A/G × MC4RA/A ] genes might affect IMF independently of BF. We believe that the SNPs and genes identified in this study will be valuable for the future molecular breeding of IMF in Duroc pigs.

[Selection of neck dissection operation for head neck cancer].

As the primary surgical procedure of treating and preventing cervical lymph node metastasis in head and neck cancers, neck dissection (ND) have increasingly becoming standardized and reasonable since the past hundred years. However, the preoperative uncertainty of cervical lymph node metastasis for patient with head neck cancer, whether perform ND and the dissection region often confuse the surgeons. Provide a currently standardized ND operation manner according to the metastatic characteristics and operative wound degree as a reference to surgeons may facilitate the therapeutic and prevent effects on patients with head and neck cancer.

[mRNA level of N-methyl-D-aspartic acid receptor NR1 subunit in patients with major depressive disorder and its relationship with clinical features].

Objective: To investigate the characteristics of glutamatergic neurotransmitter and neurotransmission dysfunction in patients with major depressive disorder (MDD) and its relationship with clinical characteristics. Methods: Fifty-two patients with MDD and 51 healthy controls were selected. Hamilton Depression scale-17 (HAMD-17) and Hamilton Anxiety Scale (HAMA) were used to evaluate the symptoms of depression and anxiety. The serum glutamate level was measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA level of NR1 subunit of NMDA receptor. Results: There was no significant difference in gender and age between MDD group and healthy control group. Compared with the control group, the level of serum glutamate [(35±6) mg/L vs (29±6) mg/L, P = 0.021] and mRNA level of NR1 (1.5±0.8 vs 0.8±0.6, P = 0.001) in MDD group were significantly higher. In MDD group, serum glutamate level was positively correlated with depression core symptom score (r = 0.52, P = 0.028), and mRNA level of NR1 subunit was positively correlated with the total course of disease (r = 0.42, P = 0.024). Conclusion: MDD patients may have disorder of glutamatergic neurotransmitter and abnormal expression of NR1 subunit.

[The value of spleen density in predicting prognosis of patients with gastric cancer after curative gastrectomy].

Objective: To investigate the value of spleen density in predicting the prognosis of patients with gastric cancer after radical gastrectomy. Methods: A total of 415 patients with gastric cancer who underwent radical resection in the Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from January 2012 to December 2015 were retrospectively analyzed. Of the patients, there were 295 males and 120 femles with a median age of 59 years (range 28-83 years). The patients were divided into diffuse decreased spleen density group (DROSD) (spleen density≤43.0 HU, n=118) and non-diffuse decreased spleen density group (N-DROSD) (spleen density>43.0 HU, n=297) according to the density of spleen detected by computed tomography (CT). The receiver operating characteristic (ROC) curve was used to identify the checkpoint of spleen density in predicting the recurrence of the gastric cancer in those patients. The relationship with clinicopathological factors and prognosis in the two groups were further analyzed. Results: The optimal critical value of spleen density for predicting postoperative recurrence of gastric cancer was 43.0 HU, the area under the curve of ROC was 0.608, and the sensitivity and specificity was 84.9% and 40.4%, respectively. Spleen density was related to albumin, hemoglobin, neutrophil lymphocyte ratio (NLR) and tumor diameter in patients with gastric cancer (all P<0.05). The 5-year disease-free survival rate and 5-year disease-specific survival rate of all the patients was 45.5% and 50.1%, respectively. Univariate survival analysis showed that age, NLR, PLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-free survival rate (all P<0.05); Age, NLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-specific survival rate (all P<0.05). Multivariate survival analysis showed that high NLR level (HR=1.501, 95%CI: 1.136-1.984), late TNM stage (HR=2.559, 95%CI: 1.850-3.539), DROSD (HR=2.093, 95%CI: 1.571-2.788) and no adjuvant chemotherapy (HR=1.583, 95%CI: 1.204-2.083) were independent risk factor for the 5-year disease-free survival rate (all P<0.05). Late TNM stage (HR=1.938, 95%CI: 1.395-2.692), DROSD (HR=1.566, 95%CI: 1.180-2.078) and no adjuvant chemotherapy (HR=1.336, 95%CI: 1.016-1.758) were independent risk factors for the 5-year disease-free survival rate (all P<0.05). For stage Ⅰ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 78.6% and 83.7%, respectively; and the 5-year disease-specific survival rates was 85.7% and 89.8%, respectively (both P>0.05). For stage Ⅱ and Ⅲ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 15.4% and 48.8%, respectively, and the 5-year disease-specific survival rates was 17.3% and 54.0%, respectively (all P<0.001). Conclusion: As an imaging evaluation method, spleen density is a new tool, which can be used as a prognostic indicator for gastric cancer patients.

[A multicenter randomized controlled study of bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang in the treatment of patients newly diagnosed with Helicobacter pylori infection and dyspepsia].

Objective: To investigate the Helicobacter pylori (H. pylori) eradication rate and improvement of dyspepsia in patients who were newly diagnosed with H. pylori infection and dyspepsia and treated by bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang(JHWK). Methods: Patients who were newly diagnosed with dyspepsia and H. pylori infection and treated in 16 medical centers in China between December 1, 2017 and September 30, 2019 were randomly divided into two groups. The experimental group received bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days), followed by JHWK (30 days), and the course of treatment was 44 days in total. In the control group, the administration regimen was bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days). The main outcome measure was H. pylori eradication rate, while the secondary outcome measures were dyspepsia symptom changes and adverse events during the treatment and the 1st month after treatment. Results: A total of 1 054 patients were included in the study. There were 522 cases enrolled in the experimental group, including 224(42.91%) men and 298(57.09%) women, and the age was 53(26, 73) years old; 532 cases enrolled in the control group, including 221(41.54%) men and 311(58.46%) women, and the age was 46(22, 71) years old. Based on PP analysis, it was found that the H. pylori eradication rate in the experimental group was significantly higher than those in the control group (93.85% vs 87.88%, P=0.001). In the group of all enrolled patients, the symptom dyspepsia after H. pylori eradication was significantly improved compared with that before treatment [4(4, 7) vs 15(10, 22), P<0.001], so was the superior and middle abdominal pain [1(1, 4) vs 4(1, 8), P<0.001], the postprandial fullness [1(1, 4) vs 4(4, 9), P<0.001], the early satiety [1(1, 1) vs 4(1, 4), P<0.001], and the heartburn [1(1, 1) vs 1(1, 4), P<0.001]. The symptom dyspepsia after treatment was significantly improved compared with that before treatment in the experimental, the control groups, the successful and the unsuccessful H. pylori eradication groups. The superior and middle abdominal pain after treatment was signifcantly improved than that before treatment [1(1, 2) vs 1(1, 4), P<0.001], so were the postprandial fullness [1(1, 3) vs 1(1, 4), P=0.002] and the dyspepsia[4(4, 7) VS 7(4, 10), P<0.001]. There was no statistically significant difference in the incidence of adverse events between the experimental group and the control group (1.34% vs 0.38%, P=0.09). Conclusions: Compared with bismuth-containing quadruple therapy, bismuth-containing quadruple therapy followed by JHWK significantly improves the H. pylori eradication rate without increasing the incidence of adverse events. H. pylori eradication therapy can improve symptoms of patients with H. pylori infection and dyspepsia.

[Association between healthy lifestyle and risk of rehospitalization in male or female patients with chronic heart failure].

Objective: To explore the association between healthy lifestyle and risk of rehospitalization in male or female patients with chronic heart failure (CHF). Methods: Discharged patients with CHF of Henan Provincial People's Hospital Collaboration Hospital were recruited in our study from January 1,2017 to December 31, 2018. The basic information of patients were collected through the electronic medical record system,the questionnaires were used to collect the related influencing factors. Healthy lifestyle includes 4 items, namely non-smoking, moderate exercise, healthy body mass index (BMI) and reasonable diet.Multivariate logistic regression was used to analyze the association between healthy lifestyle and the risk of rehospitalization of CHF patients of different genders. Results: A total of 2 697 patients with CHF were enrolled in this study, including 1 308 male patients(621 rehospitalizations,687 controls)and 1 389 female patients(684 rehospitalizations,705 controls).Among male patients, there was no significant difference in age, residence, marital status, education level, average monthly income, and medical insurance between the rehospitalization group and the control group (all P>0.05). Among female patients, there was no significant difference in age, residence, marital status, education level, average monthly income, and medical insurance between the rehospitalization group and the control group (all P>0.05). Whether in male or female patients with CHF, we found that patients with 4 healthy lifestyles were associated with reduced risk of rehospitalization: male patients OR=0.34, 95%CI 0.11-0.99, P=0.002,female patients OR=0.27, 95%CI 0.13-0.79, P=0.012. A combination of non-smoking and any other 2 healthy lifestyles was associated with reduced risk of rehospitalization: male patients with no smoking, moderate exercise, healthy BMI, OR=0.32, 95%CI 0.11-0.99, P=0.043; female patients OR=0.28, 95%CI 0.12-0.93, P=0.032;male patients with no smoking, moderate exercise, reasonable diet OR=0.42, 95%CI 0.24-0.98, P=0.044,female patients OR=0.40, 95%CI 0.12-0.94, P=0.031;male patients with no smoking, healthy BMI, reasonable diet OR=0.31, 95%CI 0.21-0.92, P=0.039,female patients OR=0.27,95%CI 0.11-0.87, P=0.014. In female patients with CHF, the combination of non-smoking and moderate sports was associated with reduced risk of hospitalization (OR=0.23, 95%CI 0.19-0.97, P=0.038), while no similar results were seen in male patients (OR=0.65, 95%CI 0.33-1.84, P=0.315). Conclusion: Healthy lifestyle is associated with reduced risk of rehospitalization in patients with CHF, and the related healthy lifestyle and its combination may differ between male and female patients.

Positive-Parity Linear-Chain Molecular Band in

An inelastic excitation and cluster-decay experiment ^{2}H(^{16}C,^{4}He+^{12}Be or ^{6}He+^{10}Be)^{2}H was carried out to investigate the linear-chain clustering structure in neutron-rich ^{16}C. For the first time, decay paths from the ^{16}C resonances to various states of the final nuclei were determined, thanks to the well-resolved Q-value spectra obtained from the threefold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the J^{π}=0^{+} band head of the predicted positive-parity linear-chain molecular band with (3/2_{π}^{-})^{2}(1/2_{σ}^{-})^{2} configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to ^{6}He+^{10}Be(∼6 MeV) final channel, corresponding well to another predicted linear-chain structure with the pure σ-bond configuration.

Large Isospin Asymmetry in

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

Knockdown of lncRNA HCP5 protects against cerebral ischemia/reperfusion injury by regulating miR-652-3p.

Previous studies have shown that lncRNAs play crucial roles in cerebral ischemia/reperfusion injury. In this study, the function and possible mechanism of lncRNA HCP5 in cerebral ischemia/reperfusion injury was investigated. An oxygen glucose deprivation (OGD) model in N2a cells was used to simulate cerebral ischemia/reperfusion injury in vitro. The functional mechanism of lncRNA HCP5 was detected using Trypan blue staining, JC-1, MTT and dual luciferase reporter assays. The expression of apoptosis-related proteins (Bcl-2 and Bax) was measured by Western blot analysis. We found that lncRNA HCP5 was upregulated in N2a cells treated with OGD/R, and knockdown of lncRNA HCP5 enhanced cell viability and reduced cell death. In addition, miR-652-3p was found to act as a sponge for lncRNA HCP5. The overexpression of miR- 652-3p can prevent cerebral ischemic reperfusion injury, however, lncRNA HCP5 attenuated the protective effect of miR-652-3p in cerebral ischemic reperfusion injury. In conclusion, upregulation of lncRNA HCP5 may exacerbate cerebral ischemic reperfusion injury by sponging miR-652-3p.

[Application of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy].

Objective: To explore the application value of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy. Methods: The retrospective cohort study was conducted. The clinicopathological data of 82 patients with gastric cancer who were admitted to Henan Tumor Hospital from April 2016 to April 2019 were collected. 38 patients who used carbon nanoparticles labeled node staining were in the observation group, while other 44 patients were in the control group. Data analysis including the operation and results of harvested of lymph nodes. Results: All patients successfully completed the operation.Thirty-eight patients successfully completed the injection of carbon nanoparticles. Surgery: observation group operating time was (150±28) min, intraoperative blood loss was (207±121) ml, group operating time was (140±23) min, intraoperative blood loss was (256±182) ml. There was no statistically significant difference between the two groups. Detection of Lymph node: A total of 1 260 lymph nodes were detected in the observation group and 981 in the control group. In the observation group, the mean lymph node sorting time was (17.2±3.3) min, the average number of harvested lymph node was 33.2±10.4, the number of the first station of lymph node was 19.8±5.3, the second station of lymph node was 13.4±6.4, the number of harvested small node(<5 mm) was 673, the positive lymph nodes was 13(range,1-31). They were all higher than those in the control group, which were (20.6±4.4)min,22.3±6.6, 12.6±4.1, 9.7±3.2,432,6 (range,1-13) , respectively. The difference between the two groups was statistically significant (P<0.05). The metastasis rate was 19.1% (241/1 260) in observation group and 16.5%(162/981) in the control group. The difference was no statistical(P>0.05). The rate of black -dyed harvested lymph node was 54.4%(686/1 260) in carbon nanoparticles group. Conclusions: The application of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy is feasible and safe. It can increase the number of lymph nodes detected, which is beneficial to the evaluation of chemotherapy effect and prognosis of patients.

[Comparative analysis of serum glutamate and gamma-aminobutyric acid levels in patients with bipolar depressive disorder and major depression disorder].

Objective: To investigate the difference of serum glutamate (Glu) and gamma- aminobutyric acid (GABA) levels between depressive patients and bipolar disorder patients with depressive episodes. Methods: From May 2018 to March 2019, forty-seven patients with depression (depression group) and 45 patients with bipolar depressive episode (bipolar depression group) were selected from the department of psychiatry, the First Affiliated Hospital of Jinan University, and 41 healthy controls (healthy control group) were simultaneously recruited from the community. The subjects' depression and anxiety were assessed by 17 items of Hamilton depression scale (HAMD-17) and Hamilton Anxiety Scale (HAMA). The serum levels of Glu, GABA and Glu decarboxylase (GAD) were detected by enzyme-linked immunosorbent assay (ELISA) . Results: The serum Glu level ( (36±7) mg/L, (37±7) mg/L vs (28±4) mg/L, F=10.97, P<0.01) and Glu/GABA ratio (5.77±0.35, 8.18±0.24 vs 3.35±0.33, F=37.68, P<0.01) in depression and bipolar depression groups were higher than those of healthy control group, while the GABA level ((6.1±0.7) µmol/L,(4.1±0.8) µmol/L vs (8.1±1.2) µmol/L, F=21.61, P<0.01) and GAD ((31±6) U/L, (31±6) U/L vs (35±6) U/L, F=5.61, P<0.01) were lower than those of healthy control group. The level of serum GABA in bipolar depression group was lower than that in depression group. However, Glu/GABA was higher in bipolar depression group than that in depression group (P<0.01). The level of serum GABA in depression group was negatively correlated with HAMD sleep disorder factor (r=-0.46, P=0.01). Conclusions: Both depression and bipolar depression have abnormal levels of Glu, GABA neurotransmitters and imbalance between Glu and GABA in peripheral blood circulation. Moreover, these abnormalities are more obvious in patients with bipolar depression.

[Diagnostic value of non-invasive model for hepatic steatosis in patients infected with human immunodeficiency virus].

Objective: Hepatic steatosis has a high incidence in human immunodeficiency virus (HIV) infected people, and there is no effective non-invasive method to evaluate it. This study aims to evaluate the diagnostic value of non-invasive models for hepatic steatosis in this population. Methods: A single-center retrospective study was applied to evaluate: (1) the diagnostic value of controlled attenuation parameters (CAP) and hepatic steatosis index (HSI) in HIV-infected patients with hepatic steatosis; (2) the ability of the non-invasive model to distinguish hepatic steatosis caused by abnormal glucose and lipid metabolism and hepatic steatosis caused by hepatitis C virus infection; (3) the diagnostic value of the above models for hepatic steatosis in patients co-infected with HIV/hepatitis C virus. The diagnostic value of the model was analyzed and evaluated by diagnostic test and receiver operating characteristic curve. Results: (1) the diagnostic value of hepatic steatosis for HIV-infected patients: when CAP = 232 dB/m, the sensitivity and specificity were 89.2% and 78.1%, respectively; when HSI = 34, the sensitivity and specificity were 79.1% and 83.2%, respectively. (2) The ability to identify the causes of hepatic steatosis in HIV-infected patients: when CAP = 258dB/m, the sensitivity and specificity were 81.5% and 88.2%, respectively; when HSI = 37, the sensitivity and specificity were 70.7% and 92.4%, respectively. (3) The diagnostic value of hepatic steatosis in patients co-infected with HIV/hepatitis C virus: when CAP = 241 dB/m, the sensitivity and specificity were 80% and 71.4%, respectively; when HSI = 32, the sensitivity and specificity were 73% and 68.9%, respectively. Conclusion: CAP and HSI have superior diagnostic value for hepatic steatosis in patients infected with HIV.

Genetic parameter estimates for body conformation traits using composite index, principal component, and factor analysis.

Information about genetic parameters is population specific and it is crucial for designing animal breeding programs and predicting response to selection. This study was carried out to estimate the genetic parameters for 23 body conformation traits of 45,517 Chinese Holstein reared in Eastern China from 1995 to 2017 with the Bayesian inference method using a linear animal mixed model. The methods to integrate these traits included (1) using the composite index from the Dairy Association of China and (2) applying principal component analysis and factor analysis to explore the relationship between the conformation traits. Estimates of heritability using the composite index were low (0.04; feet and legs) to moderate (0.23; body capacity). Strong genetic correlations were observed between the individual body conformation traits. Both principal components (1 to 7; eigenvalues ≥ 1) and latent factors (1 to 7; eigenvalues ≥ 1) explained 60.37% of total variability. Principal component 1 and factor 1 accounted for the traits that are usually associated with milk production. Moderate to low heritability were estimated through multi-trait analysis for principal components (from 0.07 to 0.21) and latent factors (from 0.07 to 0.23). Genetic correlations among the 2 multivariate techniques are typically lower compared with the one existing among the measured traits. Results from these analyses suggest the possibility of using both principal component analysis and factor analysis in morphological evaluation, simplifying the information given by the body conformation traits into new variables that could be useful for the genetic improvement of the Chinese Holstein population. This information could also be used to avoid analyzing large number of correlated traits, thereby improving precision and reducing computation burdens to analyze large and complex data.

[Treatment and analysis of prognostic factors of stage â ¡ and â ¢ undifferentiated high-grade pleomorphic sarcoma in extremities and trunk].

Objective: To evaluate the efficacy and prognostic factors of comprehensive treatment of undifferentiated high grade pleomorphic sarcoma (UHGPS) in extremities and trunk, including surgery, radiotherapy and chemotherapy. Methods: A retrospective analysis and follow-up of 131 UHGPS cases with clinical stage Ⅱ or Ⅲ in extremities and trunk soft tissue was performed to analyze the prognostic factors. Survival data were collected through follow-up. The survival rate was calculated with life table method and Kaplan-Meier survival curves were drawn. Survival rate between the two groups was compared using Log rank test. The multivariate analysis was performed using Cox regression model. Results: The median survival time of 131 patients was 41.6 months. The 1-year, 3-year and 5-year survival rates were 95.0%, 82.0%, and 77.0%, respectively. The 5-year recurrence-free survival rate was 81.0%, and the 5-year metastasis-free survival rate was 72.0%. Univariate analysis showed that the tumor size, initial or recurrence, surgical margin, AJCC stage, and with/without standard treatment were associated with overall survival (all P<0.05). Stratification analysis according to the American Joint Committee of Cancer (AJCC) stage showed that 5-year survival rate of stage Ⅱ patients with radiotherapy was 100.0%, which was higher than that of patients without radiotherapy (79.6%) and the difference was statistically significant (P=0.010); but no statistical significance of radiotherapy for stage Ⅲ and chemotherapy for stage Ⅱ or Ⅲ patients (all P>0.05). The multivariate analysis showed surgical margin (HR=4.220, P=0.002), with/without standard treatment (HR=4.040, P=0.030) were independent risk factors associated with prognosis of UHGPS patients. Conclusions: For UHGPS with stage Ⅱ or stage Ⅲ in extremities and trunk soft tissue, patients with complete resection and standard treatment have improved prognosis. Therefore, standard treatment, including extensive resection for the first surgery, should be performed according to expert consensus in order to increase the long-term survival rate. Adjuvant radiotherapy should be performed for stage Ⅱ patients.