[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.

[Association between unhealthy lifestyles and hypertension, diabetes and dyslipidemia in old adults in China].

Objective: To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network. Methods: Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia. Results: The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension (OR=3.99, 95%CI: 1.81-8.80), diabetes (OR=4.64, 95%CI: 1.64-13.15) and dyslipidemia (OR=4.26, 95%CI: 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions: The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.

[Association between unhealthy lifestyles and hyperuricemia in occupational population and modification effect of hypertension and dyslipidemia].

Objective: To understand the relationship between unhealthy lifestyle and hyperuricemia, as well as the modification effects of hypertension and dyslipidemia in occupational population and provide a theoretical basis for the prevention of hyperuricemia. Methods: A cross-sectional survey design was adopted, based on baseline data from the Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., which included the population in 28 prefectures from Sichuan Province and Guizhou Province, and 33 districts (counties) from Chongqing Municipality between October and December 2021. This study collected the information about the demographics characteristics, lifestyles, and prevalence of chronic non-communicable diseases of the study subjects through questionnaire, physical measurement and laboratory biochemical test. The unhealthy lifestyle score was scored based on smoking, alcohol consumption, dietary patterns, physical activity, and low weight or overweight, with higher scores being associated with more unhealthy lifestyles. The multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle score, smoking, alcohol consumption, other factors and hyperuricemia, and the stratified analysis was used to explore the modification effect of hypertension and other diseases on the relationship between unhealthy lifestyle and hyperuricemia. Results: A total of 11 748 participants were included in this study, the prevalence of hyperuricemia was 34.4%. Multivariate logistic regression model showed that current/previous smoking, current/previous alcohol consumption and BMI abnormality were risk factors for hyperuricemia, and the unhealthy lifestyle score showed a "cumulative" effect on the risk for hyperuricemia, with higher score increasing the risk of hyperuricemia, and the OR increased from 1.64 (95%CI: 1.34-2.00) to 2.89 (95%CI: 2.39-3.50). Stratified analysis showed that unhealthy lifestyles had a greater impact on the risk for hyperuricemia in people with hypertension and dyslipidemia. Conclusions: The coexistence of multiple unhealthy lifestyles might increase the risk of hyperuricemia, and this effect was stronger in participants with hypertension and dyslipidemia. Timely correction of unhealthy lifestyles, and control of hypertension and dyslipidemia might reduce the risk for hyperuricemia.

[Progress in complex network theory-based studies on the associations between health-related behaviors and chronic non-communicable diseases].

In recent years, the research focus on health-related behavior and chronic non-communicable diseases has shifted from the analysis on independent effects of multiple causes on a single outcome to the evaluation the complex relationships between multiple causes and multiple effects. Complex network theory, an important branch of system science, considers the relationships among factors in a network and can reveal how health-related behaviors interact with chronic diseases through a series of complex network models and indicators. This paper summarizes the definition and development of complex network theory and its commonly used models, indicators, and case studies in the field of health-related behavior and chronic disease to promote the application of complex network theory in the field of health and provide reference and tools for future research of the relationship between health-related behavior and chronic disease.

[Association between unhealthy lifestyles and diabetic dyslipidemia in occupational population and network analysis].

Objective: To understand the influence of unhealthy lifestyle on diabetic dyslipidemia and the key influencing factors in occupational population and provided scientific evidence for the prevention of diabetic dyslipidemia. Methods: Based on baseline data and follow-up data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during 2021. Diabetic dyslipidemia was defined as diabetes plus one or more forms of dyslipidemia, and unhealthy lifestyle factors included smoking, alcohol consumption, unhealthy dietary patterns, low physical activity, and abnormal BMI. Multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle scores and diabetic dyslipidemia, network analysis was used to find and explore the key lifestyles influencing glycolipid metabolism. Results: A total of 25 631 subjects were included. People with unhealthy lifestyle score 2 and 3 were 1.93 (95%CI: 1.31-2.86) times and 2.37 (95%CI: 1.60-3.50) times more likely to have diabetes with ≥1 forms of dyslipidemia than those with scores of 0; People with unhealthy lifestyle score 1, 2 and 3 were 1.98 (95%CI: 1.08-3.61) times, 2.87 (95%CI: 1.60-5.14) times and 3.95 (95%CI: 2.22-7.06) times more likely to have diabetes with ≥2 forms of dyslipidemia than those with score 0. Network analysis found that abnormal BMI and HDL-C were the "bridge nodes" that link unhealthy lifestyles with diabetic dyslipidemia. Conclusion: The higher the score of unhealthy lifestyle, the higher the risk for diabetic dyslipidemia, abnormal BMI and HDL-C are key factors influencing the association between unhealthy lifestyle and diabetic dyslipidemia.

[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.

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.

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.

[The application of nasal mucosal flaps in frontal drill out procedures].

Objective: To summarize the follow-up outcomes of frontal drill out procedures (draf Ⅱb, extended draf Ⅱb and draf Ⅲ) using mucosal flaps, and discuss the surgical indications of different mucosal flaps and their potential benefits to the opening of the frontal neo-ostium. Methods: A total of 48 patients with chronic rhinosinusitis or frontal mucoceles treated by draf Ⅱb, extended draf Ⅱb and draf Ⅲ between 2013 and 2019 in Beijing TongRen Hospital were enrolled in this study. Twenty-four patients who were treated with mucosal flaps were considered as mucosal flap group (including 19 males and 5 females, aging from 19 to 71 years), and the other 24 patients who didn't have neo-ostium reconstruction were considered as control group (including 18 males and 6 females, aging from 21 to 63 years). The frontal neo-ostium crosssectional area was measured with osiriX® 7 days and 1 year postoperatively. Lund-Kennedy score (LKS) was also completed to analyze the difference of therapeutic effect between mucosal flap group and control group. SPSS 23.0 software was used for statistical analysis. Results: The postoperative follow-up time was 18 to 102 months. The postoperative epithelialization time in the mucosal flap group and the control group was (2.5±0.9) months and (3.0±0.7) months (Mean±SD), respectively, with statistically significant (t=1.97, P=0.024). At the end of follow-up, 23 cases (95.8%) had well opened frontal neo-ostium, 1 case (4.2%) was re-stenosed, and there was no revision surgery in the mucosal flap group. In the control group, 16 cases (66.7%) had well opened frontal neo-ostium, 8 cases (33.3%) were re-stenosed, 4 cases (16.7%) had revision surgery. The mucosal flap group had much fewer stenosis cases than control group (χ2=4.92, P=0.027). The neo-ostium area in the mucosal flap group and the control group was reduced by (0.87±0.58) cm2 and (1.54±1.15) cm2 1 year after operation respectively, with statistically significant (t=1.72, P=0.046). There was no case of frontal sinus atresia and no surgical complication in both groups. The two-factor repeated measurement analysis of variance after surgery showed that the average LKS of the mucosal flap group was 0.78 points lower than that of the control group. In other words, the influence of grafting technique on LKS was statistically significant (F=5.33, P=0.035). Conclusions: The application of mucosal flaps to cover the denuded bone during frontal drill out procedures can prohibit mucosal scar and new bone formation, and significantly reduce the stenosis rate of frontal neo-ostium.

[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.

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.

[High-flow nasal cannula oxygen therapy can reduce occurrence of hypoxia in elderly patients during anesthesia recovery].

OBJECTIVE: To explore the effect of high-flow nasal cannula (HFNC) oxygen therapy in elderly patients during anesthesia recovery. METHOD: A total of 178 elderly patients undergoing elective non-cardiac surgeries were randomly assigned into HFNC oxygen therapy group (group H) or nasal cannula oxygen therapy group (group N), with 89 patients in each group.All the patients were admitted in postanesthesia care unit (PACU) after the surgery for recovery following the routine procedure.After trachea extubation, the patients in group H received HFNC oxygen therapy and those in group N had nasal cannula oxygen therapy.In both groups, arterial blood gas analysis was performed at 10 min after oxygen inhalation and the respiratory parameters were recorded.During oxygen inhalation, the occurrence and frequency of hypoxia (oxygen saturation < 90%), trachea reintubation and adverse events (unplanned admission to ICU, vomiting, aspiration, etc.) were recorded. RESULTS: All the patients recovered safely from anesthesia in the PACU and subsequently received routine care, and only 1 patient in group N required trachea reintubation.Compared with those in group N, that patients in group H had a significantly lower incidence of hypoxia (3.4% vs 11.2%, P=0.044), a higher arterial partial pressure of oxygen (161.96±51.21 vs 114.35±43.60 mmHg, P < 0.001), and a higher oxygenation index(398.76±231.86 vs 324.10±194.16, P=0.021).The mean respiratory rate, arterial partial pressure of carbon dioxide and blood oxygen saturation were all comparable between the two groups. CONCLUSION: HFNC oxygen therapy during anesthesia recovery is safe and effective in elderly patients and can reduce the occurrence of hypoxia after tracheal extubation and improve arterial partial pressure of oxygen and oxygenation.

[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.

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.

Whale Optimization Algorithm for Multiconstraint Second-Order Stochastic Dominance Portfolio Optimization.

In the field of asset allocation, how to balance the returns of an investment portfolio and its fluctuations is the core issue. Capital asset pricing model, arbitrage pricing theory, and Fama-French three-factor model were used to quantify the price of individual stocks and portfolios. Based on the second-order stochastic dominance rule, the higher moments of return series, the Shannon entropy, and some other actual investment constraints, we construct a multiconstraint portfolio optimization model, aiming at comprehensively weighting the returns and risk of portfolios rather than blindly maximizing its returns. Furthermore, the whale optimization algorithm based on FTSE100 index data is used to optimize the above multiconstraint portfolio optimization model, which significantly improves the rate of return of the simple diversified buy-and-hold strategy or the FTSE100 index. Furthermore, extensive experiments validate the superiority of the whale optimization algorithm over the other four swarm intelligence optimization algorithms (gray wolf optimizer, fruit fly optimization algorithm, particle swarm optimization, and firefly algorithm) through various indicators of the results, especially under harsh constraints.

The antifibrotic effect and mechanism of a novel tyrosine kinase inhibitor, ZSP1603, in preclinical models of pulmonary fibrosis.

OBJECTIVE: This study aimed to investigate the efficacy and molecular mechanisms of ZSP1603 as a novel anti-fibrotic compound. MATERIALS AND METHODS: The unilateral left pulmonary fibrosis model was established in the Sprague Dawley (SD) rats. The bilateral pulmonary fibrosis model was established in the C57BL/6J mice. The therapeutic treatment regimen began after the induction of pulmonary fibrosis. The preventive treatment regimen began on the first day of bleomycin administration. Animals were randomly divided into the sham, model, Nintedanib, and ZSP1603 treatment groups. Haematoxylin and eosin (H&E) and Masson's trichrome staining were performed to evaluate pulmonary injury, inflammation, and fibrosis. Cell Counting Kit-8 (CCK-8) assay and Western blot were used to investigate the effects and mechanisms of ZSP1603 on the proliferation of primary human pulmonary fibroblasts (pHPFs). The messenger ribonucleic acid (mRNA) expression of transforming growth factor (TGF)-ß1, tissue inhibitor of metalloproteinase 1 (TIMP-1), and collagen 1A1 (COL1A1) in pHPFs was detected by quantitative Real Time-Polymerase Chain Reaction (PCR). RESULTS: ZSP1603 inhibited the proliferation of pHPFs in vitro by blocking the platelet-derived growth factor receptor-ß (PDGF-Rß) and extracellular signal-regulated kinase (ERK) signalling pathway. ZSP1603 also inhibited the differentiation of pHPFs by reducing the expression of TGF-ß1, TIMP-1, and COL1A1. ZSP1603 significantly attenuated pulmonary injury, inflammation, and fibrosis in vivo in four independent animal studies of pulmonary fibrosis. CONCLUSIONS: ZSP1603 is an effective anti-fibrotic compound with clear mechanisms.

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.