Estrogen-related receptor, a molecular target against lepidoptera pests.

Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests.

BmSPP is a virus resistance gene in Bombyx mori.

Introduction: Signal peptide peptidase (SPP) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although SPP is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, Bombyx mori , may be helpful in breeding virus-resistant silkworms. Methods: First, we performed RT-qPCR to analyze the expression pattern of BmSPP. Subsequently, we inhibited BmSPP using the SPP inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)2-ketone) and downregulated the expression of BmSPP using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV). Results: We observed a decreased in the expression of BmSPP during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of BmSPP in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, BmSPPKO silkworms exhibited a 12.4% reduction in mortality rate. Discussion: Collectively, this work demonstrates that BmSPP plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that BmSPP servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.

Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia / 中国药房

OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients， and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th， 2021 to Jun. 30th， 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software， and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard， the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study， among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia， with an incidence of 6.41%. After the false positive patients were excluded， 473 patients were included finally， including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR＝1.043， 95%CI （1.017， 1.070）]， estimated glomerular filtration rate （eGFR） [OR＝0.988，95%CI（0.977， 0.998）]， baseline platelet （PLT） [OR＝0.989， 95%CI（0.982， 0.996）]， nutritional risk [OR＝3.863， 95%CI（1.884， 7.921）] and cumulative defined daily doses （DDDs） [OR＝1.082， 95%CI（1.020， 1.147）] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia （P＜0.05）. The C-index values of the training set and the internal validation set were 0.824 [95%CI （0.759， 0.890）] and 0.828 [95%CI （0.749， 0.933）]， respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 （P＝0.802） and 1.804 （P＝0.406）. In the external validation set， the C-index value was 0.808 [95%CI （0.672， 0.945）]， the χ 2 value of the Hosmer-Lemeshow test was 0.899 （P＝0.638）. CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age， baseline PLT， eGFR， nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability， which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.

Comparison of gene expression profiles in healthy individuals and people with lung cancer using the meta-analysis method.

Advances in the early detection of cancer are a way for treatment to be effective. However, due to the inability of early diagnose and treatment for lung cancer, the death rate of this type of cancer is high. Usually, a high percentage of patients are diagnosed at a stage where they are not able to receive treatment. The purpose of this study was the comparison of gene expression profiles in healthy individuals and people with lung cancer. The raw data sets GSE10072 and GSE19804 were taken from the GEO online database. Differentially expressed genes (DEGs) were identified between the non-tumor and tumor tissue samples using a meta-analysis investigation. Then, gene ontology and biological pathway analysis were performed with the Enrichr online server. The protein-protein interaction network of genes obtained from the meta-analysis investigation was drawn and analyzed using the String Online database and Cytoscape Software. Meta-analysis results showed a total of 515 differentially expressed genes. The results of the functional processes and biological pathway revealed that differentially expressed genes were mainly enriched in positive regulation of cell differentiation, regulation of cell population proliferation, regulation of epithelial cell differentiation, positive regulation of epithelial cell proliferation, response to growth factor, defense response to the tumor cell, cellular response to UV, regulation of cell cycle process, cell adhesion molecules, PPAR signaling pathway, TNF signaling pathway, ECM-receptor interaction, p53 signaling pathway, PI3K-Akt signaling pathway, and Cell cycle. Finally, key genes related to lung cancer, including IL6, MMP9, VWF, PECAM1, FOS, and CAV1 were identified. In conclusion, comparisons of gene expression profiles in healthy individuals and people with lung cancer identified some key genes that can act as lung cancer markers and can be used to predict new findings on cancer. These genes can play an important role in diagnosis and early cancer treatment.

Supramolecular Adhesives with Extended Tolerance to Extreme Conditions via Water-Modulated Noncovalent Interactions.

Development of supramolecular adhesives with strong tolerance to extreme conditions has emerged as an important research area. In this study, by balancing supramolecular interactions such as hydrogen bonding interactions, electrostatic interactions, π-π stacking interactions, and cation-π interactions, we designed and prepared a series of two-component supramolecular adhesives derived from small organic molecules. Highly efficient interfacial adhesion with maximum adhesion strength of ≈10.0 MPa was realized on various surfaces in air, organic solvents, or liquid nitrogen. Owing to balanced supramolecular interactions, water participation prolonged and increased the tolerance of the adhesives in extreme environments. We demonstrate that the combination of imidazole-based ionic liquids and phenols can be applied for various interfacial adhesions, thereby aiding the development of next-generation adhesives capable of adapting to various extreme conditions in a controlled manner.

The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial.

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative agent commonly used in general anesthesia, procedural sedation, and intensive care unit (ICU) sedation. This study aimed to explore the efficacy and safety of remimazolam versus propofol for the induction and maintenance of general anesthesia in preschool-age children undergoing elective surgery. Methods and analysis: In this multicenter, randomized, single-blind, positive-controlled non-inferior clinical trial, one hundred ninety-two children aged 3-6 years will be randomly allocated as a 3:1 ratio into two groups: Group R with an intravenous dose of remimazolam 0.3 mg/kg for the induction of anesthesia followed by a constant infusion rate of remimazolam 1-3 mg/kg/h to maintain anesthesia, and Group P with an intravenous dose of propofol 2.5 mg/kg for the induction of anesthesia followed by a constant infusion rate of propofol 4-12 mg/kg/h to maintain anesthesia. The primary outcome will be the rate of the successful induction and maintenance of anesthesia. The secondary outcomes will include the time to LoC, the Bispectral Index (BIS) value, awakening time, extubation time, post-anesthesia care unit (PACU) discharge time, usage of additional sedative drugs during the induction period, usage of remedial drugs in PACU, emergence delirium, pain in PACU, behavior scores at day 3 after surgery, parental and anesthesiologists' satisfaction, and adverse events. Ethics and dissemination: This study has been approved by the ethics review boards at all participating hospitals. The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Reference No. LCKY 2020-380, November 13, 2020) is the central ethics committee.

Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice / 中国天然药物

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.

Small molecules targeting protein-protein interactions for cancer therapy

Protein-protein interactions (PPIs) are fundamental to many biological processes that play an important role in the occurrence and development of a variety of diseases. Targeting the interaction between tumour-related proteins with emerging small molecule drugs has become an attractive approach for treatment of human diseases, especially tumours. Encouragingly, selective PPI-based therapeutic agents have been rapidly advancing over the past decade, providing promising perspectives for novel therapies for patients with cancer. In this review we comprehensively clarify the discovery and development of small molecule modulators of PPIs from multiple aspects, focusing on PPIs in disease, drug design and discovery strategies, structure-activity relationships, inherent dilemmas, and future directions.

Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy.

Objectives: Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. Materials and methods: We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Results: Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Conclusion: Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

Strong Dynamic Interfacial Adhesion by Polymeric Ionic Liquids under Extreme Conditions.

Interfacial adhesion under extreme conditions has attracted increasing attention owing to its potential application of stopping leakages of oil or natural gas. However, interfacial adhesion is rarely stable at ultralow temperatures and in organic solvents, necessitating the elucidation of the molecular-level processes. Herein, we used the intermolecular force-control strategy to prepare four linear polymers by tuning the proportion of hydrogen bonding and the number of electrostatic sites. The obtained polymeric ion liquids displayed strong dynamic adhesion at various interfaces. They also efficiently tolerated organic solvents and ultracold temperatures. Highly reversible rheological behaviors are observed within a thermal cycle between high and ultracold temperatures. Temperature-dependent infrared spectra and theoretical calculation reveal thermal reversibility and interfacial adhesion/debonding processes at the molecular level, respectively. This intermolecular force-control strategy may be applied to produce environmentally adaptive functional materials for real applications.

Novel cross-locking intramedullary nails for olecranon: a finite element analysis and specimen experiments / 中华创伤骨科杂志

Objective:To determine the mechanical properties of our self-designed novel cross-locking intramedullary nails and the impact of number of conical locking nails on the fixation through a finite element analysis and specimen experiments.Methods:Mimics 19.0 and SolidWorks 2014 were used to create transverse fracture models of the olecranon which were subjected to fixation with respectively K-wire tension band (KTB) and our self-designed novel cross-locking intramedullary nails (NIN). The strengths of KTB and NIN fixation were analyzed by Ansys. Fifteen human ulna specimens were used to construct a transverse fracture model of the olecranon; an Instron E10000 mechanical testing machine was used to determine mechanical properties in fixation respectively with KTB, one NIN (NIN-1) and 3 NINs (NIN-3).Results:In the finite element analysis, in simulation of the forearm flexed at 45° under a 100 N load, the deformation of the fracture surface of the olecranon in fixation with KTB, NIN-1 and NIN-3 was respectively 0.131 mm, 0.123 mm and 0.121 mm. In the specimen experiments, in simulation of the forearm flexed at 45°, the maximum failure loads for fixation with KTB, NIN-1 and NIN-3 were (313.38±27.68) N, (528.56±53.58) N and (871.04±94.95) N, respectively, showing significant differences among the 3 groups ( P<0.05). The maximum failure load for NIN-3 fixation was significantly greater than that for KTB or NIN-1 fixation, and the maximum failure load for NIN-1 fixation was significantly greater than that for KTB fixation ( P<0.05). Conclusions:Compared with KTB fixation, NIN fixation is more convenient in operation and has better mechanical properties. NIN-3 fixation has the best mechanical properties.

Clinical efficacy of pancreaticoduodenectomy with TRIANGLE operation in the treatment of pancreatic head cancer / 中华消化外科杂志

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy with TRIANGLE operation in the treatment of pancreatic head cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 51 patients with pancreatic head cancer who were admitted to the Sichuan Provincial People′s Hospital, Affiliated Hospital of School of Medicine of University of Electronic Science and Technology of China from January 2017 to July 2018 were collected. There were 33 males and 18 females, aged from 42 to 74 years, with a median age of 56 years. Of the 51 patients, 24 cases undergoing standard pancreaticoduodenectomy, in which No.12, 13 and 17 lymph nodes were dissected, combined with transcatheter arterial infusion chemo-therapy (TAI) were allocated into the standard group, and 27 cases undergoing pancreaticoduo-denectomy with TRIANGLE operation, in which No.7, 8, 9, 12, 13, 16, 17 lymph nodes were dissected, combined with TAI were allocated into the TRIANGLE group, respectively. Observation indicators: (1) intraoperative conditions of the two groups; (2) postoperative conditions of the two groups; (3) follow-up and survival. Follow-up was conducted using outpatient examination and telephone interview once three months to detect tumor recurrence and metastasis and survival of patients up to July 2021 or the death of patient. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the chi-square test or the Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan‐Meier method was used to calculate the survival rate and median survival time and draw survival curve. Log‐Rank test was used for survival analysis. Results:(1) Comparison of intraoperative conditions between the two groups. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion were (501±61)minutes, (563±278)mL, 4 in the standard group, versus (556±46)minutes, (489±234)mL, 6 in the TRIANGLE group, respectively. There was a significant difference in the operation time between the two groups ( t=3.62, P<0.05) but there was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups ( t=1.03, χ2=0.25, P>0.05). (2) Comparison of postoperative conditions between the two groups. Of the 51 patients, 30 had 50 times of postoperative complications, including 18 times of grade Ⅰ complications of Clavien-Dindo classification, 29 times of grade Ⅱ complications of Clavien-Dindo classification, 2 times of grade Ⅲa complications of Clavien-Dindo classification, 1 time of grade Ⅲb complications of Clavien-Dindo classification, respectively. Cases with postoperative complications, cases with delayed gastric emptying, cases without or with pancreatic fistula as class A or class B, cases with biliary fistula, cases with bleeding, cases with diarrhea were 15, 4, 13, 7, 4, 4, 2, 2 in the standard group, versus 15, 6, 14, 10, 3, 4, 1, 3 in the TRIANGLE group, respectively. There was no significant difference in cases with postoperative complications, cases with delayed gastric emptying, cases with pancreatic fistula between the two groups ( χ2=0.16, 0.02, Z=-0.04, P>0.05) and there was no significant difference in cases with biliary fistula, cases with bleeding, cases with diarrhea between the two groups ( P>0.05). Cases with complications as Clavien-Dindo grade Ⅰ, grade Ⅱ, grade Ⅲ were 10, 11, 2 in the standard group, versus 8, 18, 1 in the TRIANGLE group, showing no significant difference between the two groups ( Z=-0.67, P>0.05). The duration of postoperative hospital stay was (23±8)days in both of the standard group and the TRIANGLE group, showing no significant difference between the two groups ( t=0.31, P>0.05). (3) Follow-up and survival. All the 51 patients were followed-up for 6 to 54 months, with a median follow-up time of 17 months. The postoperative 1-year overall survival rate was 75.0% and 81.5% in the standard group and the TRIANGLE group, respectively. The postoperative 3-year overall survival rate was 12.5% and 22.2% in the standard group and the TRIANGLE group, respectively. The median postoperative survival time was 15.00 months (95% confidence interval as 12.63 to 17.37 months) and 21.00 months (95% confidence interval as 15.91 to 19.62 months) in the standard group and the TRIANGLE group, respectively. There was a significant difference in survival of patients between the two groups ( χ2=4.30, P<0.05). Cases with tumor recurrence during post-operative 1 year and 3 year were 9 and 20 in the standard group, versus 6 and 15 in the TRIANGLE group, respectively. There was no significant difference in cases with tumor recurrence during postoperative 1 year between the two groups ( P>0.05) and there was a significant difference in cases with tumor recurrence during postoperative 3 year between the two groups ( P<0.05). Conclusion:Compared with standard pancreaticoduodenectomy, pancreaticoduodenectomy with TRIANGLE operation can prolong the median survival time of patients with pancreatic head cancer without increasing surgical related complications.

Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

Construction of evaluation indicator system for promoting common prosperity of health care in Zhejiang province / 中华医院管理杂志

Objective:To establish a set of scientific and reasonable indicator system of common prosperity in the field of health, so as to promote the construction and evaluation of the demonstration area of common prosperity with high quality of health.Methods:According to the requirements of promoting common prosperity demonstration area with high quality of health in Zhejiang province, the initial indicator pool was established through literature research and theoretical analysis in July 2021, and experts were convened to carry out expert brainstorming to determine indicator system in the form of meetings. Delphi method was used to conduct two rounds of expert consultation on the indicator system.Finally, the analytic hierarchy process and percentage weight method were used to calculate the indicator weight value.Results:The final indicator system included 4 first-level indicators and 30 second-level indicators. Among the first-level indicators, the weight values of the development, equilibrium, inclusiveness, and sustainability were 0.326 4, 0.242 8, 0.245 8, and 0.185 0. There were 8 second-level indicators in developmental indicator dimension, of which the indicator with the highest weight was the per capita health expectancy. The balance indicator dimension included 6 second-level indicators, of which the indicator with the highest weight was the per capita financing difference of basic medical insurance between the urban workers with the urban-rural residents. The inclusive indicator dimension included 6 second-level indicators, and the proportion of personal health expenditure to total health expenditure had the highest weight. The sustainability indicator dimension included 10 second-level indicators, and the proportion of government health expenditure in fiscal expenditure had the highest weight.Conclusions:The indicator system constructed in this research could provide certain guidance and reference for promoting the construction of common prosperity in health, and provide some reference for follow-up research in this field.

Erratum: Author correction to "Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers" Acta Pharmaceutica Sinica B 11 (2021) 355-372

[This corrects the article DOI: 10.1016/j.apsb.2020.05.004.].

Layer-specific speckle tracking echocardiography in evaluating alterations of myocardial mechanics in mice models of physiological aging / 中华老年医学杂志

Objective:To explore alterations of myocardial mechanics in mice models of physiological aging.Methods:Mice aged from 3 weeks to 24 months were chosen(n=50). Conventional echocardiography and layer speckle tracking echocardiography(LS-STE)were applied to evaluate alterations of myocardial mechanics in different ages(each for 10 mise). Pathological myocardial alterations in the aging process were detected using HE and Masson's trichrome staining.Results:Clear age-dependent changes in mice of different ages were observed when assessed using parameters of conventional echocardiography( P<0.05 for all). Values from parameters of LS-STE also showed that longitudinal, circumferential and radial strain in both the endocardium and the epicardium gradually decreased during physiological aging( P<0.05 for all). Compared with the 3-weeks old group, longitudinal strain in the endocardium was significantly reduced in the 14-months old group[(-23.49±2.32) vs.(-17.19±2.28), P<0.05]; Compared with the 3-weeks old group, radial strain, longitudinal strain in the endocardium, longitudinal strain in the epicardium, circumferential strain in the endocardium and circumferential strain in the epicardium were significantly reduced in the 24-months old group[(32.90±5.01) vs.(21.80±5.54), (-23.49±2.32) vs.(-15.44±2.27), (-13.23±3.19) vs.(-7.59±2.21), (-25.93±4.09) vs.(-20.31±4.08), (-9.30±1.92) vs.(-6.01±1.04), P<0.05)]; HE and Masson's trichrome staining of the myocardium indicated increases in the cross-sectional area of cardiomyocytes and fibrosis during the aging process. Conclusions:LS-STE can accurately detect early cardiac dysfunction and pathological myocardial alterations associated with aging in mice and may serve as an effective tool in evaluating anti-myocardial aging.

Mechanical Properties of Novel Interlocking Intramedullary Nail for Fixing Transverse Olecranon Fractures / 医用生物力学

Objective To study the effect of interlocking intramedullary nail on fixing transverse olecranon fracture. Methods Nine pairs of fresh ulna specimens were collected and the transverse fracture model of olecranon was established. Kirschner wire tension band and interlocking intramedullary nail were used to repair the fracture. Cyclic dynamic tension loads with amplitude of 25 N, mean value of 45 N and frequency of 05 Hz were applied to the triceps tendon under simulated elbow flexion conditions of 30°, 45° and 60°, respectively. The fracture displacements of specimens within 300 cycles were recorded in three groups. ResultsAt 30° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.831±0.333) mm and (3.723±2.390) mm, respectively. At 45° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.167±0.374) mm and (2.455±0.609) mm, respectively. At 60° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.407±0.342) mm and (3.112±1.025) mm, respectively. The fracture displacement of interlocking intramedullary nail was smaller. Conclusions The mechanical properties of interlocking intramedullary nail are better than those of Kirschner wire tension band, and the interlocking intramedullary nail is more stable and firmer for fixing transverse olecranon fracture. Moreover, the interlocking intramedullary nail is installed with the operating tool, thus the operation is more accurate and faster, and the operation efficiency is greatly improved.

Mechanics Analysis on Novel Micro-Movement Elastic Implant of Distal Tibiofibular Syndesmosis in Dorsiflexion Position / 医用生物力学

Objective To study mechanical properties of the novel micro-movement elastic implant of distal tibiofibular syndesmosis in dorsiflexion position.Methods A combination of simulation and experiment was used. The normal ankle dorsiflexion model, the bone nail repaired model and the micro-movement elastic implant repaired model were established by using Mimics and CT data. Besides, ANSYS Workbench was used for finite element analysis. Mechanical experiments on lower limb specimens were conducted on Instron E10000 mechanical test instrument, and five sets of experimental data were measured and analyzed.Results Mechanical properties of the micro-movement elastic implant repaired model were closer to those of the normal ankle dorsiflexion model, but stress of the micro-movement elastic implant repaired mode was greater than that of the bone nail repaired model. The results of two-sample heteroscedasticity t test indicated that there was no significant difference in resistance torque between the micro-movement elastic implant repaired model and the normal ankle dorsiflexion model.Conclusions For dorsiflexion position, repairing mechanical properties of the novel micro-movement elastic implant are much better than those of the bone nail, and there is still room for optimizing the micro-movement elastic implant.

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease

Parkinson's disease (PD), known as one of the most universal neurodegenerative diseases, is a serious threat to the health of the elderly. The current treatment has been demonstrated to relieve symptoms, and the discovery of new small-molecule compounds has been regarded as a promising strategy. Of note, the homeostasis of the autolysosome pathway (ALP) is closely associated with PD, and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD. Thus, pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far. In this review, we focus on summarizing several autophagy-associated targets, such as AMPK, mTORC1, ULK1, IMPase, LRRK2, beclin-1, TFEB, GCase, ERR