Dissociable Contributions of Basolateral Amygdala and Ventrolateral Orbitofrontal Cortex to Flexible Learning Under Uncertainty.

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

[The association between baseline TPOAb and/or TgAb positivity and thyroid immune-related adverse events in patients with malignancies following treatment with immune checkpoint inhibitors].

Objective: To investigate the association between positive anti-thyroid peroxidase antibody (TPOAb) and/or anti-thyroglobulin antibody (TgAb) and the occurrence of thyroid immune-related adverse events (irAEs) in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs). Methods: A case-control study. A total of 116 patients with malignant tumor who received ICIs treatment and underwent thyroid function evaluation at Peking Union Medical College Hospital from January 2017 to April 2023 were enrolled retrospectively, including 77 males and 39 females, with a median age of (M(Q1, Q3)) 63.0 (55.0, 70.0) years. The patients were divided into the euthyroid group (n=58) and the thyroid irAEs group (n=58) according to whether thyroid irAEs occurred after ICIs treatment. The clinical characteristics and baseline anti-thyroid antibodies associated with the occurrence of thyroid irAEs after ICIs treatment in patients with malignant tumors were evaluated. Variables with statistical significance in univariate analysis were included in multivariate logistic regression model to analyze the risk factors for thyroid irAEs in patients with malignant tumors who received ICIs treatment. Results: In irAEs group, therewore 4 (3.4%) cases of clinical thyrotoxicosis, 23(19.8%) cases of subclinical thyrotoxicosis, 23 (19.8%) cases of clinical hypothyroidism, and 8(6.9%) cases of subclinical hypothyroidism. The positive rate of anti-thyroid antibodies at baseline in the thyrioid irAEs group was higher than that in the euthyroid group［16/58（27.6%）vs 3/58（5.2%），P=0.001］. After at least one course of ICIs treatment, the incidence of thyroid irAEs in patients with positive anti-thyroid antibodies at baseline was 84.2% (16/19), whereas it was 43.3% (42/97) in patients with negative anti-thyroid antibodies(P=0.001). Univariate logistic regression analysis showed that gender (OR=2.812, 95%CI:1.257-6.293), baseline thyroid autoantibodies were positive (OR=6.984, 95%CI: 1.909-25.547), baseline TgAb positivity (OR=8.909, 95%CI: 1.923-41.280), and baseline TPOAb positivity (OR=7.304, 95%CI: 1.555-34.308) were associated with thyroid irAEs (all P<0.05). Multivariate logistic regression analysis indicated that baseline TgAb positivity (OR=7.637, 95%CI: 1.617-36.072) was a risk factor for thyroid irAEs (P=0.01). Conclusions: The incidence of thyroid irAEs is higher in patients who are positive for baseline TPOAb and/or TgAb compared to those who are negative for TPOAb and TgAb. Patients with positive TgAb at baseline are at high risk of developing thyroid irAEs.

[Correlation between serum growth differentiation factor 11 level and severity of coronary artery disease in patients with acute myocardial infarction].

Objective: To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI. Methods: This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People's Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model. Results: A total of 367 patients were enrolled, divided into control group (n=172) and STEMI group (n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) µg/L vs. 85.00 (53.93, 117.10) µg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11(OR=0.98, 95%CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI (P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score (P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95%CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95%CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95%CI: 0.72-0.81), all P<0.01. Conclusions: Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

High-Flux Neutron Generator Based on Laser-Driven Collisionless Shock Acceleration.

A novel compact high-flux neutron generator with a pitcher-catcher configuration based on laser-driven collisionless shock acceleration (CSA) is proposed and experimentally verified. Different from those that previously relied on target normal sheath acceleration (TNSA), CSA in nature favors not only acceleration of deuterons (instead of hydrogen contaminants) but also increasing of the number of deuterons in the high-energy range, therefore having great advantages for production of high-flux neutron source. The proof-of-principle experiment has observed a typical CSA plateau feature from 2 to 6 MeV in deuteron energy spectrum and measured a forward neutron flux with yield 6.6×10^{7} n/sr from the LiF catcher target, an order of magnitude higher than the compared TNSA case, where the laser intensity is 10^{19} W/cm^{2}. Self-consistent simulations have reproduced the experimental results and predicted that a high-flux forward neutron source with yield up to 5×10^{10} n/sr can be obtained when laser intensity increases to 10^{21} W/cm^{2} under the same laser energy.

Enhanced sequestration of molybdenum(VI) using composite constructed wetlands and responses of microbial communities.

The molybdenum (Mo) non-point source pollution in the mining area has an irreversible impact on the surrounding water and soil ecosystems. Herein, three integrated vertical subsurface flow constructed wetlands (CWs) were constructed to assess the effects of combination substrates and plant on the removal of Mo(VI). Results showed that CW1 with combination substrates and cattail exhibited a favorable removal performance for Mo(VI) at 80.90%. Moreover, most Mo(VI) retained in the CWs was retained in the substrate (58.13-88.04%), and the largest fraction of Mo(VI) retained was the water-soluble fraction on the surface of the combination substrates. Mo(VI) removal was also influenced by the microbial community composition in substrate, especially their co-occurrence networks. The species that showed significant positive correlation with Mo(VI) removal were Planctomycetes, Latescibacteria, Armatimonadetes, and Gemmatimonadetes. Moreover, CWs added plants showed that more co-occurrences interaction between taxa occurs, which means that the wetlands efficiently select recruitment of potential microbial consortia and change the co-occurrences to remove pollution in the substrate. These results could be useful in providing an ecology-based solution for the treatment of Mo(VI) in wastewater, especially in adjusting the microbial communities for Mo(VI) removal at the genetic level.

[Current status and prospects of anti-angiogenic small-molecule tyrosine kinase inhibitors in the therapy of soft tissue sarcoma].

Chemotherapy is the main systemic treatment for patients with advanced soft tissue sarcoma, and immunotherapy is only effective for some special subtypes. Anti-angiogenic small molecule tyrosine kinase inhibitors represented by pazopanib and anlotinib are the main drugs of targeted therapy. They have been clearly recommended as the second-line treatment of non-specific soft tissue sarcoma in guidelines. In recent years, in addition to second-line monotherapy in patients with advanced sarcoma, some studies have been carried out in second-line combination therapy, maintenance therapy, first-line therapy and neoadjuvant therapy. This article briefly reviews the application status and prospect of anti-angiogenic small molecule tyrosine kinase inhibitors in advanced soft tissue sarcoma.

[Retrospective study on the efficacy and safety of low dose apatinib in reversing chemotherapy resistance in sarcoma].

Objective: To explore whether apatinib can reverse the chemotherapy resistance of patients with advanced sarcoma. Methods: The clinical data of advanced sarcoma patients after chemotherapy who received the original chemotherapy regimen combined with low-dose apatinib in Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2018 to November 2021 were collected retrospectively to evaluate the efficacy and safety of this regimen. The primary end point was progression-free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AE). The patients were grouped according to the diagnosis: osteosarcoma, soft tissue sarcoma and undifferentiated small round cell sarcoma. And the benefits of combination treatment was investigated with the stratified analysis of best outcome of combined therapy, lines of chemotherapy received, best response and PFS of original chemotherapy. Results: A total of 30 patients were included in this study, including 20 males and 10 females. The mean age was (25.6±14.7) years. There were 9 cases of osteosarcoma, 11 cases of soft tissue sarcoma and 10 cases of undifferentiated small round cell sarcoma. No patient achieved complete response, 8 patients (26.7%) achieved partial response, 19 patients (63.3%) achieved disease stability, the ORR was 26.7%(8/30), and the DCR was 90.0%(27/30). The median PFS and OS were 4.1 and 13.1 months respectively. Among the three different subtypes of sarcoma, the ORR of osteosarcoma was 44.4% (4/9), the median PFS was 4.1 months, and the median OS was not yet achieved; the ORR of undifferentiated small round cell sarcoma was 40% (4/10), the median PFS was 6.4 months, and the median OS was 10.9 months; No response was observed in soft tissue sarcoma, and the median PFS and median OS was 3.5 and 7.3 months respectively. Patients who achieved objective response had better PFS than patients with stable disease (12.8 vs 3.8 months, P=0.015), and patients with PFS≥ 6 months of original chemotherapy had better PFS benefits (12.7 vs 2.7 months, P<0.001). However, the number of original chemotherapy lines and the best response of original chemotherapy had no significant effect on the PFS of this combination regimen. In terms of safety, the related toxicity of apatinib was no more than grade 2, and the grade 4 chemotherapy-related adverse reactions was mainly hematological toxicity, of which 2 patients interrupted treatment because of febrile neutropenia. Conclusion: Low dose apatinib is effective in reversing chemotherapy resistance of osteosarcoma and undifferentiated small round cell sarcoma with acceptable adverse reactions.

MicroRNA-223 negatively regulates LPS-induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts.

AIM: To investigate the effect of miR-223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1ß and IL-18 in human dental pulp fibroblasts (HDPFs). METHODOLOGY: Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR-223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR-223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase-1, IL-1ß and IL-18 was determined by qRT-PCR and Western blotting, respectively. The release of IL-1ß and IL-18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one-way analysis of variance; P < 0.05 indicated statistical significance. RESULTS: A decrease in miR-223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (P < 0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR-223 in HDPFs. The miR-223 inhibitor further promoted ATP plus LPS-induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS-induced group (P < 0.05). In contrast, the miR-223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS-induced group (P < 0.05). CONCLUSION: MiR-223 served as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.

[Influence of female age on the fresh cycle live birth rate of different controlled ovarian hyperstimulation protocols in poor ovarian response patients].

Objective: To investigate the influence of age on the fresh cycle live birth rate in patients with poor ovarian response in different controlled ovarian hyperstimulation groups. Methods: The clinical data of 3 342 patients in The First Affiliated Hospital of Zhengzhou University from February 2014 to November 2018 were retrospectively collected, including early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol group (1 375 cases), mid-luteal phase short-acting GnRH agonist long protocol group (1 161 cases) and GnRH antagonist protocol group (806 cases); each group was divided into 4 subgroups according to age: ≤30 years, 31－35 years, 36－40 years and >40 years, the pregnancy outcomes in each age subgroup were analyzed under different controlled ovarian hyperstimulation protocols. Results: In early-follicular phase long-acting GnRH agonist long protocol group, the final live birth rates of each age subgroup were 39.4% (228/579), 36.1% (135/374), 16.6% (48/290) and 3.0% (4/132); in mid-luteal phase short-acting GnRH agonist long protocol group, live birth rates of each age subgroup were 32.1% (99/308), 20.8% (55/264), 13.0% (45/346) and 7.0% (17/243); in GnRH antagonist protocol group, live birth rates of each age subgroup were 22.8% (26/114), 16.3% (25/153), 11.2% (31/278), and 3.8% (10/261); the live birth rate of each group decreased significantly with the increase of age (all P<0.01). When the age≤35 years old, the fresh cycle live birth rate of the early-follicular phase long-acting GnRH agonist long protocol group was significantly better than those of the other two groups (all P<0.01). The multivariate logistic regression analysis of age and live birth rate of the three controlled ovarian hyperstimulation groups showed age was the independent influence factor (OR=0.898, 95%CI: 0.873-0.916, P<0.01; OR=0.926, 95%CI: 0.890-0.996, P<0.01; OR=0.901, 95%CI: 0.863-0.960, P<0.01). Conclusions: Age is an independent influencing factor for the prediction of fresh cycle live birth rate in low ovarian response patients. No matter which controlled ovarian hyperstimulation protocol is adopted, the final live birth rate decreases significantly with the increase of women's age. In addition, the early-follicular phase long-acting GnRH agonist long protocol has the highest fresh cycle live birth rate among all controlled ovarian hyperstimulation groups.

Three-field versus two-field lymphadenectomy in transthoracic oesophagectomy for oesophageal squamous cell carcinoma: short-term outcomes of a randomized clinical trial.

BACKGROUND: The benefit and harm of three-field lymphadenectomy for oesophageal cancer are still unknown. The aim of this study was to compare overall survival and morbidity and mortality between three- and two-field lymphadenectomy in patients with oesophageal squamous cell carcinoma. METHODS: Between March 2013 and November 2016, patients with squamous cell carcinoma of the middle or distal oesophagus were assigned randomly to open oesophagectomy with three-field (cervical-thoracic-abdominal) or two-field (thoracic-abdominal) lymphadenectomy. No chemo(radio) therapy was given before surgery. This paper reports on the secondary outcomes of the study: pathology and surgical complications. RESULTS: Some 400 patients were randomized, 200 in each group. A median of 37 (i.q.r. 30-49) lymph nodes were dissected in the three-field group, compared with 24 (18-30) in the two-field group (P < 0·001). Some 43 of 200 patients (21·5 per cent) in the three-field group had cervical lymph node metastasis. More patients in the three-field group had pN3 disease: 21 of 200 (10·5 per cent) versus 10 of 200 (5·0 per cent) (P = 0·040). The rate and severity of postoperative complications were comparable between the two groups, except that six patients in the three-field arm needed reintubation compared with none in the two-field group (3·0 versus 0 per cent; P = 0·030). The 90-day mortality rate was 0 per cent in the three-field group and 0·5 per cent (1 patient) in the two-field group (P = 1·000). CONCLUSION: Oesophagectomy with three-field lymphadenectomy increased the number of lymph nodes dissected and led to stage migration owing to a 21·5 per cent rate of cervical lymph node metastasis. Postoperative complications were largely comparable between two- and three-field lymphadenectomy. Registration number: NCT01807936 ( https://www.clinicaltrials.gov).

ANTECEDENTES: El beneficio y los daños potenciales de la linfadenectomía en tres campos (three-field, 3-FLD) en el cáncer de esófago aún se desconoce. El objetivo de este estudio fue comparar la supervivencia global y la morbilidad y mortalidad entre la linfadenectomía en tres campos (3-FLD) y la linfadenectomía en dos campos (two-field lymphadenectomy, 2-FLD) en pacientes con carcinoma escamoso de esófago. MÉTODOS: Entre marzo de 2013 y noviembre de 2016, pacientes con carcinoma escamoso del tercio medio y distal del esófago fueron asignados de forma aleatoria a esofaguectomía abierta con linfadenectomía 3-FLD (cervical-torácica-abdominal) o 2-FLD (torácica-abdominal). No se administró quimioterapia o quimiorradioterapia antes de la cirugía. Este estudio describe los resultados secundarios: datos de la anatomía patología y complicaciones quirúrgicas. RESULTADOS: Se aleatorizaron un total de 400 pacientes a linfadenectomía 3-FLD y 2-FLD (200 pacientes en cada grupo). En el grupo de 3-FLD se disecaron una mediana (rango) de 37 (30-49) ganglios linfáticos en comparación con 24 (18-30) en el grupo de 2-FLD (P < 0,001). Un total de 43 de 200 (21,5%) pacientes en el grupo 3-FLD presentaron metástasis en los ganglios linfáticos (lymph node metastasis, LNM) cervicales. Más pacientes en el grupo 3-FLD presentaron un estadio de la enfermedad pN3 en comparación con el grupo 2-FLD: 21 de 200 (10,5%) versus 10 de 200 (5,0%), P = 0,040). La tasa y gravedad de las complicaciones postoperatorias fue comparable en ambos grupos, aparte de 6 pacientes en la rama 3-FLD que necesitaron reintubación (3,0%) en comparación con ninguno en el grupo 2-FLD (P = 0,030). La mortalidad a los 90 días fue del 0% en 3-FLD y del 0,5% (1 paciente en el grupo 2-FLD (P = 1,000). CONCLUSIÓN: La esofaguectomía con 3-FLD aumenta el número de ganglios linfáticos y conduce a una migración del estadio debido a la tasa de LNM cervicales del 21,5%. Las complicaciones postoperatorias fueron similares entre las linfadenectomías 3-FLD y 2-FLD.

Deep RNA-Seq reveals miRNome differences in mammary tissue of lactating Holstein and Montbéliarde cows.

BACKGROUND: Genetic polymorphisms are known to influence milk production and composition. However, the genomic mechanisms involved in the genetic regulation of milk component synthesis are not completely understood. MicroRNAs (miRNAs) regulate gene expression. Previous research suggests that the high developmental potential of the mammary gland may depend in part on a specific miRNA expression pattern. The objective of the present study was to compare the mammary gland miRNomes of two dairy cow breeds, Holstein and Montbéliarde, which have different mammogenic potentials that are related to differences in dairy performance. RESULTS: Milk, fat, protein, and lactose yields were lower in Montbéliarde cows than in Holstein cows. We detected 754 distinct miRNAs in the mammary glands of Holstein (n = 5) and Montbéliarde (n = 6) midlactating cows using RNA-Seq technology, among which 738 were known and 16 were predicted miRNAs. The 25 most abundant miRNAs accounted for 90.6% of the total reads. The comparison of their abundances in the mammary glands of Holstein versus Montbéliarde cows identified 22 differentially expressed miRNAs (Padj ≤ 0.05). Among them, 11 presented a fold change ≥2, and 2 (miR-100 and miR-146b) were highly expressed. Among the most abundant miRNAs, miR-186 is known to inhibit cell proliferation and epithelial-to-mesenchymal transition. Data mining showed that 17 differentially expressed miRNAs with more than 20 reads were involved in the regulation of mammary gland plasticity. Several of them may potentially target mRNAs involved in signaling pathways (such as mTOR) and lipid metabolism, thereby indicating that they could influence milk composition. CONCLUSION: We found differences in the mammary gland miRNomes of two dairy cattle breeds. These differences suggest a potential role for miRNAs in mammary gland plasticity and milk component synthesis, both of which are related to milk production and composition. Further research is warranted on the genetic regulation of miRNAs and their role in milk synthesis.

Systematic analyses for candidate genes of milk production traits in water buffalo (Bubalus Bubalis).

Water buffalo (Bubalus bubalis) is of great economic importance as a provider of milk and meat in many countries. However, the milk yield of buffalo is much lower than that of Holstein cows. Selection of candidate genes related to milk production traits can be applied to improve buffalo milk performance. A systematic review of studies of these candidate genes will be greatly beneficial for researchers to timely and efficiently understand the research development of molecular markers for buffalo milk production traits. Here, we identified and classified the candidate genes associated with buffalo milk production traits. A total of 517 candidate genes have been identified as being associated with milk performance in different buffalo breeds. Nineteen candidate genes containing 47 mutation sites have been identified using the candidate gene approach. In addition, 499 candidate genes have been identified in six genome-wide association studies (GWASes) including two studies performed with the bovine SNP chip and four studies with the buffalo SNP chip. Genes CTNND2 (catenin delta 2), APOB (apolipoprotein B), FHIT (fragile histidine triad) and ESRRG (estrogen related receptor gamma) were identified in at least two GWASes. These four genes, especially APOB, deserve further study to explore regulatory roles in buffalo milk production. With growth in the number of buffalo genomic studies, more candidate genes associated with buffalo milk production traits will be identified. Therefore, future studies, such as those investigating gene location and functional analyses, are necessary to facilitate the exploitation of genetic potential and the improvement of buffalo milk performance.

[Prevalence and risk factors of aortic valve calcification among the elderly residents of Wuxi city, Jiangsu province].

Objective: To evaluate the prevalence and risk factors of aortic valve calcification among the elderly (≥65 years old) resident of Wuxi city, Jiangsu province. Methods: The household registration population aged ≥65 years old in Wuxi city was selected as the research subject by stratified sampling method from August 2017 to December 2018. Echocardiography was performed to assess the aortic valve calcification, and the participants were divided into calcification group and non-calcification group. Multivariate logistic regression analysis was used to explore the related risk factors of aortic valve calcification. Results: The age of the respondents was (73.6±7.1) years old, of which 48.8% (461 cases) were males.The prevalence rate of aortic valve calcification was 22.0% (208/944) in the elderly (≥ 65 years old) residents in Wuxi city. The prevalence rate in 65-69 years old, 70-74 years old, 75-79 years old, 80-84 years old and ≥85 years old was 16.7% (58/347),16.7% (41/245),16.2% (26/161),23.3% (24/103), and 67.0% (59/88),respectively. There were significant differences in age, weight, abdominal circumference, hip circumference, high-salt diets, exercise, hypertension, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, and carotid atherosclerosis between the non-calcified group (736 cases) and the calcified group (208 cases) (P<0.01 or 0.05).Multivariate logistic regression analysis showed that age (OR=1.077, 95%CI 1.053-1.101, P<0.001), diabetes mellitus (OR=1.697, 95%CI 1.174-2.453, P=0.005), and coronary heart disease (OR=1.964, 95%CI 1.378-2.799, P<0.001) were the risk factors of aortic valve calcification. Conclusions: The prevalence of aortic valve calcification in the elderly (≥65 years old) residents in Wuxi city of Jiangsu province increases with aging. Age, diabetes mellitus and coronary heart disease are the risk factors of aortic valve calcification in this population cohort.

[Resynchronization Therapy for Chronic Heart Failure: Diagnostic and Therapeutic Approaches].

Chronic heart failure (CHF) remains one of the most important problems of modern cardiology. One of the effective treatment methods is resynchronization therapy (RT). The article presents an analysis of literature data on the effectiveness of RT in improving the quality of life, reducing the number of hospitalizations and mortality in patients with heart failure with severe left ventricular systolic dysfunction and expanding QRS complex, and also discusses key methods for optimizing RT.

[The Rice OsDUF810 Family: OsDUF810.7 May be Involved in the Tolerance to Salt and Drought].

With the advance of sequencing technology, the number of sequenced plant genomes has been rapidly increasing. However, understanding of the gene function in these sequenced genomes lags far behind; as a result, many coding plant sequences in public databases are annotated as proteins with domains of unknown function (DUF). Function of a protein family DUF810 in rice is not known. In this study, we analysed seven members of OsDU810 (OsDUF810.1-OsDUF810.7) family with three distinct motifs in rice Nipponbare. By phylogenetic analysis, OsDUF810 proteins fall into three major groups (I, II, III). Expression patterns of the seven corresponding OsDUF810 protein-encoding genes in 15 different rice tissues vary. Under drought, salt, cold and heat stress conditions and ABA treatment, the expression of OsDUF810.7 significantly increases. Overexpression of this protein in E. coli lead to a significant enhancement of catalase (CAT) and peroxidase (POD) activities, and improved bacterial resistance to salt and drought.

[Voxel-based morphometry (VBM) MRI analysis of gray matter in patients with occupational noise-induced hearing loss].

Objective: To investigate the changes of brain gray matter volume in patients with occupational noise-induced hearing loss by voxel based morphometry (VBM) . Methods: 16 age-and education-matched healthy controls and 42 patients with occupational noise induced hearing loss, including 27 in mild group and 15 in severe group, received MRI 3D-FSPGR sequence T1WI sagittal scan, and then underwent VBM of brain gray matter volume data analysis. Results: The brain gray matter volume of the left occipitotemporal lateral gyrus, the anterior cingulate gyrus, the bilateral angular gyrus, the precuneus and the near midline area of cerebellum differed between experimental group and control group (P<0.01) . Conclusion: The volume of gray matter in specific brain areas of patients with occupational noise-induced hearing loss was changed, and the effect of noise on brain structure was revealed from the perspective of imaging.

miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4.

Radiotherapy is one of the most important treatments for esophageal cancer, but radioresistance remains a major challenge. Previous studies have shown that microRNAs (miRNAs or miRs) are involved in human cancers. miR-124 has been widely reported in various cancers and it is intimately involved in proliferation, cell cycle regulation, apoptosis, migration, and invasion of cancer cells. The aim of this study was to explore the relationship between the miR-124/cyclin-dependent kinase 4 (CDK4) axis and the radiosensitivity of esophageal cancer cells. In this study, we identified the reduced expression of miR-124 in 18 paired esophageal cancer tissues compared to their matched normal tissues. In order to investigate the physiological role of miR-124 in esophageal cancer, the cell counting kit-8 (CCK-8) assay and wound healing assay were performed, and the results suggest that miR-124 overexpression decreases tumor growth and aggression. Next, we detected the effects of ectopic miR-124 expression on the apoptosis of an esophageal cancer cell line (TE-1) following radiotherapy. Using the CCK-8 assay and Hoechst 332528 stain, we found that ectopic expression of miR-124 led to a higher percentage of apoptotic cells. Finally, we identified that CDK4 is a direct target of miR-124 in TE-1 cells using target prediction algorithms and a luciferase reporter assay. Moreover, western blot assay confirmed that CDK4 was downregulated during miR-124 transfection. Taken together, we illustrate that the miR-124/CDK4 axis plays an important role in radiation sensitivity of human esophageal cancer cells by targeting CDK4.

The necessity of strength evaluation in assessment of clinical outcome after shoulder surgery : follow-up data from patients with complex proximal humerus fractures treated by locking plate fixation.

In order to minimize the bias of Constant score we modified the allocation of strength subscore. One hundred and two patients with 3- and 4-part proximal humerus fractures were treated using locking plate fixation and followed up for > 1 year. The clinical outcomes were assessed by DASH score abbreviated Constant score (AbbCS strength item excluded) modified Constant score (ModCS with 12-pound strength) and original Constant score (CS with 25-pound strength). The satisfaction rate was determined for each scoring instrument. Compared to CS the satisfaction rate was significantly higher in DASH score AbbCS and ModCS (all p < 0.001) but the latter 3 groups did not show significant difference. ROC analysis showed that a > 7-pound shoulder strength was present in patients with satisfied outcome assessed by DASH score. In conclusion strength evaluation is necessary for the assessment of shoulder function but the over-allocated strength should be modified in Constant score.

[Upregulated Notch1 expression promotes bone morphogenetic protein-2/4 expression of calcified human heart valve interstitial cells].

OBJECTIVE: To observe the protein expression of Notch1 in the cultured calcified human heart valve interstitial cells (hVICs) in vitro and related mechanisms. METHODS: hVICs were divided into two groups: control hVICs were cultured in conventional media for 14 days and calcified hVICs were cultured with calcification inducers: ß-glycerophosphate (500 µl), ascorbic acid (200 µl), dexamethasone(100 µl) for 7 days. The calcified hVICs were further divided into calcified hVICs group and inhibited calcified hVICs by adding specific Notch1 inhibitor DAPT (50 µmol/L(4 µl/hole))groups and cultured for another 7 days. Inflammatory response of all groups were induced by lipopolysaccharide (LPS) for 8 to 12 hours. Western blot was used to detect the protein expression of Notch1, phosphorylation nuclear transcription factor κB (p-NF-κB), bone morphogenetic protein-2/4(BMP-2/4). ELISA was applied to detect the content of BMP-2 secretion of the groups. Von Kossa staining was used to observe of cellular calcification. RESULTS: (1)Von Kossa staining is positive in the induced calcification group, the expression of Notch1, p-NF-κB, BMP-2 and BMP-4 is significantly higher in the induced calcification group than in the control group (all P<0.05). The expression of BMP-2 is significantly higher in the induced calcification group than in control group ((88.23±3.28) pg/ml vs. (25.41±3.68) pg/ml, P=0.02). (2) After treatment with DAPT, the calcification and the expression of Notch1, p-NF-κB, BMP-2 and BMP-4 were significantly decreased compared to calcification group (all P<0.05). The expression of BMP-2 is (26.74±4.62) pg/ml in the calcification inhibition group and (80.41±2.96) pg/ml in calcified control group (P=0.02). CONCLUSIONS: Upregulated Notch 1 expression promotes BMP-2/4 secretion in LPS stimulated hVICs, and contributes to osteogenic changes in hVICs. Inhibiting Notch1 can decrease the BMP-2/4 secretion and calcification in hVICs, which may serve as a novel therapeutic option for treating calcific valve disease.

Revisiting DARPP-32 in postmortem human brain: changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression.

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32 or PPP1R1B) has been of interest in schizophrenia owing to its critical function in integrating dopaminergic and glutaminergic signaling. In a previous study, we identified single-nucleotide polymorphisms (SNPs) and a frequent haplotype associated with cognitive and imaging phenotypes that have been linked with schizophrenia, as well as with expression of prefrontal cortical DARPP-32 messenger RNA (mRNA) in a relatively small sample of postmortem brains. In this study, we examined the association of expression of two major DARPP-32 transcripts, full-length (FL-DARPP-32) and truncated (t-DARPP-32), with genetic variants of DARPP-32 in three brain regions receiving dopaminergic input and implicated in schizophrenia (the dorsolateral prefrontal cortex (DLPFC), hippocampus and caudate) in a much larger set of postmortem samples from patients with schizophrenia, bipolar disorder, major depression and normal controls (>700 subjects). We found that the expression of t-DARPP-32 was increased in the DLPFC of patients with schizophrenia and bipolar disorder, and was strongly associated with genotypes at SNPs (rs879606, rs90974 and rs3764352), as well as the previously identified 7-SNP haplotype related to cognitive functioning. The genetic variants that predicted worse cognitive performance were associated with higher t-DARPP-32 expression. Our results suggest that variation in PPP1R1B affects the abundance of the splice variant t-DARPP-32 mRNA and may reflect potential molecular mechanisms implicated in schizophrenia and affective disorders.