The protective effect of LCZ696 in coxsackievirus B3-induced acute viral myocarditis mice.

AIMS: Acute viral myocarditis (AVMC) is the aetiology of heart failure (HF) with few specific treatments. The improvement of left ventricular ejection fraction (LVEF) is a critical predictor for the prognosis of AVMC. LCZ696 is a drug used in HF to improve LVEF, with a few research on AVMC. In this research, we evaluated the effects and mechanism of LCZ696 in improving LVEF in AVMC. METHODS: Eighty 4-week-old male BALB/c mice were randomly divided into four groups of 20: Sham; Sham + LCZ696 (60 mg/kg/d); AVMC; AVMC + LCZ696. The above experiments were repeated by CVB3-infected HL-1 and Mdivi-1 to down-regulated dynamin-related protein 1(Drp1). Adeno-associated virus 9 (AAV9) with enhanced green fluorescent proteins (GFP) was injected to produce Drp1-overexpression mice and set up four groups: AVMC group, AVMC + AAV group, AVMC + LCZ696 group, and AVMC + LCZ696 + AAV group (n = 20 in each group). LVEF was evaluated by echocardiography at a similar heart rate (HR) at d7, Drp1 (p-Drp1), inflammation and apoptosis by histology and Western blot (WB), and mitochondrial by electron microscopy. RESULTS: Cardiac function were injured in AVMC that LCZ696 reversed (LVEF, %: Sham: 68.99 ± 9.67; Sham + LCZ696: 71.96 ± 6.20; AVMC: 30.95 ± 6.40*; AVMC + LCZ696: 68.99 ± 9.67*#, *P < 0.05 vs. Sham, #P < 0.05 vs. AVMC). LCZ696 attenuated p-Drp1 expression, inflammation, apoptosis, and mitochondrial fission (p-Drp1/Drp1: Sham: 1; Sham + LCZ696: 1.37 ± 0.22; AVMC: 2.29 ± 0.36*; AVMC+LCZ696: 1.43 ± 0.08*#, *P < 0.05 vs. Sham, #P < 0.05 vs. AVMC). Some of the above results were repeated in CVB3-infected HL-1 cells and Mdivi-1. AAV increased Drp1 expression and mitochondrial fission, inflammatory, and apoptosis. Compared with the AVMC + AAV group, the LVEF increased from 24.44 ± 0.03% to 32.33 ± 0.05% in the AVMC + LCZ696 + AAV group(P < 0.05), p-Drp1/Drp1 decreased from 0.54 ± 0.12 to 0.42 ± 0.09*, and IL-6, c-IL-1ß, and c-caspase-3/caspase-3 decreased from 1.07 ± 0.22 to 0.72 ± 0.08*, from 1.03 ± 0.14 to 0.79 ± 0.09*, and from 4.69 ± 0.29 to 0.92 ± 0.13*, respectively (*P < 0.05). CONCLUSIONS: LCZ696 has a protective effect on AVMC by improving LVEF and reducing inflammation and apoptosis, which may be due to the inhibition of Drp1-mediated mitochondrial fission.

Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability.

In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD+-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.

[3D mirror printing combined with minimally invasive percutaneous plate osteosynthesis in the treatment of adult median clavicle fracture].

OBJECTIVE: To retrospectively analyze clinical effect of 3D mirror printing combining with minimally invasive percutaneous plate osteosynthesis(MIPPO) technology in the treatment of adult clavicle fracture. METHODS: The clinical data of 32 adult patients with collarbone AllmanⅠdisplacement of fracture who had undergone the combination of 3D mirror printing with MIPPO technology treatment were collected from October 2019 to October 2020. There were 19 males and 13 females, aged from 19 to 55 years old with an average of(34.12±16.42) years old. According to Allman classification, there were 14 cases of AllmanⅠb and 18 cases of AllmanⅠc. Fracture occurred on the left in 17 cases and on the right in 15 cases. Postoperative complications, operation time, incision length, intraoperative blood loss, the number of fluoroscopies, fracture healing time of all patients were retrospectively analyzed, and the curative effect was evaluated by Constant-Murley shoulder joint score before operation, 1 and 6 months after operation. RESULTS: All the 32 patients were followed up for 6 to 8 months, with an average of (6.67±2.13) months. All the patients did not have postoperative complications such as incision infection and skin numbness in the operating area. The operation time was (35.37±4.28) min. The incision length was (3.78±0.45) cm. Intraoperative blood loss was(37.23±4.76) ml. The number of fluoroscopies was(3.12±0.47) times. Fracture healing time was (8.18±2.58) weeks. Constant-Murley shoulder joint score of the affected side at 1 and 6 months after operation was 81.08±3.92 and 98.03±1.05 respectively, which had a significant difference compared with 54.62±5.25 before operation(P<0.05). According to Constant-Murley shoulder function score at 6 months after operation, 30 cases were excellent and 2 cases were good. CONCLUSION: 3D mirror printing can effectively assist MIPPO technique in the treatment of adult clavicle AllmanⅠdisplaced fracture. It not only has the advantages of less trauma and fewer complications of the MIPPO technique, but also can further shorten the operation time and improve the operation maneuverability. It is a better method in the treatment of adult clavicle AllmanⅠdisplaced fracture.

Related factors influencing Chinese psychiatric nurses' turnover: A cross-sectional study.

WHAT IS KNOWN ON THE SUBJECT: Because of increasingly stressful, dangerous and unpredictable psychiatric nursing work, psychiatric nurses have experienced higher job stress than general ward nurses. Little is known about the factors that affect the turnover intention of Chinese psychiatric nurses. Understanding the influencing factors of nurses' turnover intention will help to formulate targeted measures to stabilize psychiatric nursing teams. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE: The results showed that 70.2% of psychiatric nurses had higher turnover intention. The strong turnover intention of Chinese psychiatric nurses is a problem that needs to be considered by managers. The results showed that having more children, between 31 and 39 years old, and having a part-time job were strongly associated with turnover intention. In addition, "job stress" was also an important factor, psychiatric nurses' turnover intention decreased as their job stress level decreased. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Nursing managers should pay attention to nurses who have more children, between 31 and 39 years old, and take on part-time jobs. Additionally, nursing managers should reduce job stress and implement targeted programmes to prevent psychiatric nurses' turnover. Experience-sharing meetings and mindfulness-based stress reduction training are also useful to improve the mental health status of psychiatric nurses with great job stress. Nursing managers should arrange human resources and shifts appropriately to give nurses with more children more time with their families. Provide more development opportunities for psychiatric nurses between 31 and 39 years old. Managers explore the reasons why nurses take on part-time jobs and take targeted interventions (such as increasing income) to reduce the behaviour that happens. ABSTRACT: Introduction Nurses' turnover is the main cause of nursing shortages, greatly affected by nurses' intention to leave. Nurses' turnover rate is particularly high in psychiatric wards. Several factors influencing the turnover intention of psychiatric nurses have not been well identified in China, and the association between job stress and turnover intention is still limited. Aims To examine the relationship between job stress and turnover intention and identify the influencing factors of psychiatric nurses' turnover intention. Methods Data were collected from 2355 psychiatric Chinese nurses using a cross-sectional design with an online questionnaire investigation. Results Psychiatric nurses had higher turnover intention. Significant factors influencing their turnover intention were job stress, having more children, age between 31 and 39 years old, part-time jobs, education, income and patient-to-nurse ratio. Discussion Demographics and job-related factors should be considered when developing strategies to reduce the turnover intention of psychiatric nurses. Implications for practice Nursing managers should pay attention to nurses with higher job stress levels and different demographic characteristics. Effective measures should be taken to reduce psychiatric nurses' job stress and turnover intention, such as arranging reasonable shifts, implementing targeted family-friendly policies, increasing their occupational possibilities and promoting mental health.

Long noncoding RNA Gas5 induces cell apoptosis and inhibits tumor growth via activating the CHOP-dependent endoplasmic reticulum stress pathway in human hepatoblastoma HepG2 cells.

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor-associated regulatory factors. LncRNA growth arrest-specific transcript 5 (Gas5) acts as an anti-oncogene in most cancers. Whether Gas5 acts as an oncogene or anti-oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription-polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull-down experiments and analyzed by mass spectrometry. A series of novel Gas5-interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose-regulated protein (GRP78) was identified as a direct target of Gas5 by Rip-qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5-mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.

Effect of pH on the In Vitro Biocompatibility of Surfactant-Assisted Synthesis and Hydrothermal Precipitation of Rod-Shaped Nano-Hydroxyapatite.

Given their wide range of biomedical applications, hydroxyapatite (HA) nanoparticles are an attractive material widely used in many fields. Therefore, a simple, inexpensive, and stable process for the synthesis of HA nanoparticles is necessary to meet current needs. Herein, we studied HA synthesis assisted by four surfactants, namely cation, anion, non-ionic, and zwitterion templates, to verify the synthesis phase, aspect ratio, morphology, and biocompatibility under different environments (i.e., pH 4 and 9) before and after calcination. Results showed that before calcination, the surfactant-free groups could not produce HA but showed an abundant dicalcium phosphate anhydrous (DCPA) phase at pH 4. Except for the anionic group containing a small amount of DCPA, all surfactant-assistant groups presented single-phase HA in acidic and alkaline environments. The diameter of HA synthesized at pH 4 was significantly larger than that of HA synthesized at pH 9, and the effect of aspect ratio changes after calcination was more significant than that before calcination. The uncalcined rod-shaped HA synthesized with a non-ionic template at pH 4 demonstrated excellent cell viability, whereas anionic, cationic, and non-ionic surfactants exhibited biocompatibility only after calcination. At pH 9, non-ionic and uncalcined zwitterion-assisted rod-shaped HA showed excellent biocompatibility. In conclusion, the uncalcined HA rod-shaped nanoparticles synthesized from the non-ionic template at pH 4 and 9 and the zwitterion template at pH 9, as well as all surfactant-assisted HA after calcination, had no cytotoxicity. These tailor-made non-toxic HA types can meet the different requirements of apatite composite materials in biomedical applications.

[Influence of Precipitation Change on Soil Respiration in Desert Grassland].

Global climate change has significantly changed precipitation patterns. Soil respiration (SR), as an important pathway through which CO2 is released from the soil carbon pool into the atmosphere, may affect the carbon cycle process of terrestrial ecosystems and have a feedback effect on global climate change in response to precipitation change. However, at present there is limited understanding of how SR is affected by precipitation change. Field precipitation control experiments were conducted (with -40%, -20%, natural, 20%, and 40% precipitation) on desert grassland in the west of the Loess Plateau, to investigate the influence of precipitation change on SR dynamics and its relationship with soil water content, soil temperature, aboveground biomass, soil organic carbon, microbial biomass carbon, carbon-nitrogen ratio, and other factors. The results show that the diurnal variations of SR under different precipitation treatments were consistent in unimodal and bimodal models over three years. SR showed an increasing trend with added precipitation, relative to the control, and significant differences were observed between the second year (wetter) and the third year (drier) of the precipitation-manipulation experiment, indicating that precipitation changes had a legacy effect on SR. At the same time, SR was lowest under the -40% treatment and highest under the 40% treatment during the wetter year. The negative response of SR to precipitation exclusion treatments was stronger than the positive response to precipitation addition treatments. SR in drier years was significantly higher under precipitation addition treatments than the control, and the positive response of SR to increased precipitation treatment was significantly stronger than that under decreased precipitation treatment. In addition, soil water content, aboveground biomass, soil organic carbon, and carbon-nitrogen ratio were the environmental factors that obviously affected SR and increased with additional precipitation. SR increased with increases in soil water content, aboveground biomass, soil organic carbon, and carbon-nitrogen ratio, but decreased with increases in microbial biomass carbon. Among these factors, soil water content had the highest interpretation rate for SR, indicating that soil water content was the main environmental factor controlling SR in desert grassland. In both wetter and drier years, the amplitude of plant biomass input was lower than the amplitude of SR output under precipitation change, indicating that precipitation change may be unfavorable to soil carbon sequestration, especially in drier years, when precipitation change has a stronger influence on carbon pool output. Therefore, precipitation changes on SR in desert grassland in various dry and wet years may have different influences on the carbon cycle process of ecosystems, thus providing a reference for regional carbon budget assessment.

A specific tRNA half, 5'tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2.

BACKGROUND: Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear. METHODS: Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5'tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5'tiRNA-His-GTG. The regulation of 5'tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments. RESULTS: Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5'tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5'tiRNA-His-GTG in CRC and found that targeting 5'tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5'tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5'tiRNA-His-GTG, which renders 5'tiRNA-His-GTG to "turn off" hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes. CONCLUSIONS: In summary, the findings revealed a specific 5'tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.

Anxiety, depression and cognitive emotion regulation strategies in Chinese nurses during the COVID-19 outbreak.

AIMS: To explore the association between cognitive emotion regulation strategies and anxiety and depression among nurses during the COVID-19 outbreak. BACKGROUND: Nurses play a vital role in responding to the COVID-19 outbreak, but many of them suffer from psychological problems due to the excessive workload and stress. Understanding the correlation between cognitive emotion regulation strategies and anxiety and depression will promote targeted psychosocial interventions for these affected nurses. METHODS: This cross-sectional study of 586 nurses was conducted in Eastern China. Participants completed online questionnaires that investigated anxiety, depression and cognitive emotion regulation strategies. RESULTS: The prevalence of nurses' anxiety and depression was 27.6% and 32.8%, respectively. Lower self-blame, rumination and catastrophizing, as well as greater acceptance and positive refocusing, were related to fewer symptoms of anxiety or depression. CONCLUSION: The cognitive emotion regulation strategies of acceptance and positive refocusing contribute to reducing anxiety or depression. These strategies should be considered when implementing psychotherapeutic interventions to improve nurses' adverse emotional symptoms. IMPLICATIONS FOR NURSING MANAGEMENT: This study highlights the need to assess cognitive emotion regulation strategies use in screening for anxiety and depression. Nurse managers should develop psychosocial interventions including appropriate strategies to help nurses with adverse emotions during a pandemic.

Long non­coding RNA MEG3 suppresses epithelial­to­mesenchymal transition by inhibiting the PSAT1­dependent GSK­3ß/Snail signaling pathway in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer in China, and the prognosis of patients remains poor mainly due to the occurrence of lymph node and distant metastasis. The long non­coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to have tumor­suppressive properties and to play an important role in epithelial­to­mesenchymal transition (EMT) in some solid tumors. However, whether MEG3 is involved in EMT in ESCC remains unclear. In the present study, the MEG3 expression level and its association with tumorigenesis were determined in 43 tumor tissues of patients with ESCC and in ESCC cells using reverse transcription­quantitative PCR analysis. Gene microarray analysis was performed to detect differentially expressed genes (DEGs). Based on the functional annotation results, the effects of ectopic expression of MEG3 on cell growth, migration, invasion and EMT were assessed. MEG3 expression level was found to be markedly lower in tumor tissues and cells. Statistical analysis revealed that MEG3 expression was significantly negatively associated with lymph node metastasis and TNM stage in ESCC. Fluorescence in situ hybridization assay demonstrated that MEG3 was expressed mainly in the nucleus. Ectopic expression of MEG3 inhibited cell proliferation, migration, invasion and cell cycle progression in EC109 cells. Gene microarray results demonstrated that 177 genes were differentially expressed ≥2.0 fold in MEG3­overexpressing cells, including 23 upregulated and 154 downregulated genes. Functional annotation revealed that the DEGs were mainly involved in amino acid biosynthetic process, mitogen­activated protein kinase signaling, and serine and glycine metabolism. Further experiments indicated that the ectopic expression of MEG3 significantly suppressed cell proliferation, migration, invasion and EMT by downregulating phosphoserine aminotransferase 1 (PSAT1). In pathological tissues, PSAT1 and MEG3 were significantly negatively correlated, and high expression of PSAT1 predicted poor survival. Taken together, these results suggest that MEG3 may be a useful prognostic biomarker and may suppress EMT by inhibiting the PSAT1­dependent glycogen synthase kinase­3ß/Snail signaling pathway in ESCC.

Enterotoxigenic Bacteroides fragilis induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B.

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.

JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy.

Rationale: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods: Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results: Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B-knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B. Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B (P < 0.001) in 60 human CRC tissues. Conclusion: These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B, thus driving the malignancy of CRC.

[Finite element analysis of InterTan for the treatment of femoral intertrochanteric fractures].

OBJECTIVE: To study the biomechanical characteristics of InterTan for the treatment of femoral intertrochanteric fracture of Evans-Jensen IV. METHODS: Scanning the femur and internal plant of volunteers with spiral CT to obtain DICOM format data. Three-dimensional models of left femur and InterTan were reconstructed by Mimics software. On this basis, a three-dimensional finite element model of internal fixation for Evans-Jensen IV intertrochanteric fracture of femur was established. The stress and microstrain distribution of Von Mses in different models were studied. The biomechanical stability after internal fixation of the Evans Jensen IV femoral intertrochanteric fracture was analyzed. RESULTS: The stress pattern of the femur of InterTan model was the same as that of the normal femur, which was mainly located on the medial side of the proximal femur and the lower third of the femur. However, the stress of femur in InterTan model was lower than that in the same part of normal femur. The peak stress of the femur in the model was 13.92 MPa, located at the end of the inner plant in contact with the femur. The stress peak of the plant in the model was 146.5 MPa at the lower contact point between the tension nail and the main nail. CONCLUSIONS: InterTan fixation has obvious biomechanical advantages and is not easy to cause stress fractures in the middle femur in patients with osteopenic Evans-Jensen IV intertrochanteric fractures. In particular, for patients with greater activity in the intertrochanteric fracture of the Evans-Jensen IV femur, InterTan fixation has better stability and provides a theoretical basis for the choice of internal fixation.

Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner.

Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.

Effect of adenosine on autophagy and proliferation of hepatocellular carcinoma cells / 中国药理学通报

Aim To investigate the effect of adenosine on the autophagy and proliferation of hepatocellular carcinoma cells, and improve the curative effect of a-denosine on hepatocellular carcinoma. Methods HepG2 cells were incubated with adenosine, CCK-8 method was used to study the changes of cell prolifera-tion,Western blot was used to study the expression of LC3-Ⅱ and LC3-Ⅰ, and MDC staining was used to observe the number of autophagosomes. Results HepG2 cells were incubated with adenosine(1.0~4.0 mmol·L-1) for 48 h,the proliferation of HepG2 cells were detected at the different time points (12,24,48 h),and the result showed the proliferation was signifi-cantly inhibited by adenosine (P < 0.01). HepG2 cells were incubated with adenosine (0.2,0.5,1.0, 2.0,4.0 mmol·L-1) for 24 h,the ratio of LC3-Ⅱ/LC3-Ⅰ decreased significantly in low concentration of adenosine group (0.2, 0.5 mmol·L-1, P <0.05;1.0 mmol·L-1,P<0.01),and the ratio of LC3-Ⅱ/LC3-Ⅰ increased significantly in higher concentration of adenosine group (4.0 mmol·L-1, P <0.05). HepG2 cells were incubated with adenosine(1.0 mmol·L-1) for 24 h, the ratio of LC3-Ⅱ/LC3-Ⅰ de-creased significantly at 6,12 and 24 h detecting point, the number of autophagosomes were reduced, the low-est ratio of LC3-Ⅱ/LC3-Ⅰ and autophagosomes were observed at 12 h detecting point(P<0.01). Conclu-sions Adenosine inhibits the proliferation of hepato-cellular carcinoma cells,the low concentration of aden-osine inhibits the autophagy,while the high concentra-tion of adenosine increases the autophagy, which is of great significance to reduce multi-drug resistance and improve the therapeutic effect of anti-hepatoma drugs.

Long non-coding RNA MEG3 induces cell apoptosis in esophageal cancer through endoplasmic reticulum stress.

Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as cell growth, apoptosis and migration. Although downregulation of lncRNA MEG3 has been identified in several cancers, little is known about its role in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to detect MEG3 expression in clinical ESCC tissues, investigate its biological functions and the endoplasmic reticulum (ER) stress-relative mechanism. MEG3 expression levels were detected by qRT-PCR in both tumor tissues and adjacent non-tumor tissues from 28 ESCC patients. PcDNA3.1-MEG3 recombinant plasmids were constructed and transfected to EC109 cells. Cell growth was analyzed by CCK-8 assay. Cell apoptosis was analyzed by fluorescence microscope and Annexin V/PI assay. The protein expression was determined by western blot analysis. The results showed that MEG3 decreased significantly in ESCC tissues relative to adjacent normal tissues. PcDNA3.1-MEG3 plasmids were successfully constructed and the expression level of MEG3 significantly increased after MEG3 transfection to EC109 cells. Ectopic expression of MEG3 inhibited EC109 cell proliferation and induced apoptosis in vitro. MEG3 overexpression increased the expression of ER stress­related proteins (GRP78, IRE1, PERK, ATF6, CHOP and cleaved­caspase-3). Our results first demonstrate that MEG3 is downregulated in ESCC tissues. MEG3 was able to inhibit cell growth and induced apoptosis in EC109 cells, most probably via activation of the ER stress pathway.

Comparative analysis of the expression patterns of eight suppressors of cytokine signaling in tongue sole, Cynoglossus semilaevis.

Suppressor of cytokine signaling (SOCS) family members are inhibitors of cytokine signaling pathways and key regulators of immunological homeostasis. They have been extensively studied in mammalian models, but systematic analyses of SOCS in fish are limited. In the current study, a total of eight SOCS genes from tongue sole (Cynoglossus semilaevis) were characterized. All eight CsSOCS exhibit conserved structures of SOCS and were phylogenetically grouped together with the respective SCOS members known in mammalian and teleost species. Under normal physiological conditions, the expressions of the eight CsSOCS genes were detected at varied levels in nine major tissues, with most CsSOCS highly expressed in kidney. Following challenge with intracellular and extracellular bacterial pathogens, the majority of CsSOCS genes exhibited distinctly different expression profiles in a time-, tissue-, and pathogen-dependent manner. In general, intracellular pathogen caused wider and higher levels of CsSOCS expressions than extracellular pathogen. These results suggest that different members of SOCSs in teleost may play different roles in the infection processes of different bacterial pathogens.

Molecular characterization and expression analysis of nine CC chemokines in half-smooth tongue sole, Cynoglossus semilaevis.

Chemokines are a large, diverse group of small cytokines that can be classified into several families, including the CC chemokine family, which plays a pivotal role in host defense by inducing leukocyte chemotaxis under physiological and inflammatory conditions. Here we studied 9 CC chemokines from half-smooth tongue sole (Cynoglossus semilaevis). Phylogenetic analysis divided these chemokines into four groups. The tissue specific expression patterns of the 9 chemokines under normal physiological conditions varied much, with most chemokines highly expressed in immune organs, while some other chemokines showing high expression levels in non-immune organs. In addition, the 9 chemokines exhibited similar or distinctly different expression profiles in response to the challenge of virus and intracellular and extracellular bacterial pathogens. These results indicate that in tongue sole, CC chemokines may be involved in different immune responses as homeostatic or inflammatory chemokines.

The effectiveness of prenatal serum biomarker screening for neural tube defects in second trimester pregnant women: a meta-analysis.

BACKGROUND: Neural tube defects (NTDs) are common and serious birth defects all over the world. Prenatal screening for NTDs using maternal serum alpha-fetoprotein (MSAFP) during the second trimester of pregnancy has been widely used, but its effectiveness remains unclear. METHODS: We evaluated the studies published in the English and Chinese on MSAFP screening for NTDs. The homogeneity of the studies was evaluated by the forest graph. Meta-analysis was applied to calculate the combined effect values and their 95% confidence intervals. RESULTS: As many as 22 articles were selected according to the criteria and were included in the meta-analysis, for a total of 684,140 pregnant women screened during the second trimester. All the studies selected were homogenous according to the forest graph (chi(2) = 25.17, P > 0.10). The combined relative risk estimate was 0.25 and its 95% confidence interval was 0.21 to 0.29. The combined protective rate was 75%. The sensitivity and specificity of MSAFP screening were 75.1 and 97.7%, respectively. CONCLUSION: Use of MSAFP during the second trimester in pregnant women is an effective measure for the screening of NTDs.

[Infection of tupaia hepatocytes with hepatitis C virus in vitro].

OBJECTIVE: Tupaia belangeri (tree shrew) has a close phylogenetic relationship with primates and has been shown to be susceptible to a variety of human viruses. This study was conducted to investigate whether or not hepatitis C virus (HCV) could infect primary tupaia hepatocytes (PTHs) in vitro. METHODS: Serum-derived HCV was cultivated with PTHs, and then positive and negative strand HCV RNA in PTHs, as well as the encapsidated HCV RNA in the culture medium were detected to evaluate the infection. Virus from the culture medium of the infected PTHs was passed to naïve PTHs, and the quasispecies of HCV were compared among the inoculum and PTHs after infection and passage. RESULTS: Both positive and negative strand HCV RNA were detected in PTHs after infection. The negative strand RNA was detectable from day 5 to day 10 after infection, while the positive strand RNA was positive up to day 14. HCV RNA, which was RNase resistant, could be detected from the culture medium of the infected PTHs from day 3 to day 14. Production of infectious virons of PTH were demonstrated by passage HCV to naïve PTHs. Compared analysis of HCV quasispecies after infection and passage showed that PTHs were selectively infected with defined HCV quasispecies, and new quasispecies emerged in PTHs after passage. CONCLUSION: The present study strongly indicates that PTHs could be infected by HCV and support HCV replication in vitro. Our results would be helpful for the establishment of a tupaia model of HCV infection.