[Rethinking kidney disease surveillance in the era of big data].

Chronic kidney disease is increasingly recognized as an important global public health problem, posing a heavy burden to the health system. It is necessary to monitor the status of kidney diseases and promote early intervention and management. Due to the large regional differences in the characteristics of kidney diseases and the uneven distribution of medical resources in China, traditional monitoring methods have several limitations in comprehensively exploring the burden and trends of kidney diseases. On the premise of ensuring data security and personal privacy, a cost-effective kidney disease surveillance system could be developed by integrating big data, artificial intelligence, and surveillance systems and utilizing health care data from different sources, thereby overcoming major disadvantages of traditional monitoring methods and providing reference for the prevention and control of kidney diseases in China.

[Effect of modification of antihypertensive medications on the association of nitrogen dioxide long-term exposure and chronic kidney disease].

OBJECTIVE: To investigate the potential effect of modification of antihypertensive medications on the association of nitrogen dioxide (NO2) long-term exposure and chronic kidney disease (CKD). METHODS: Data of the national representative sample of adult population from the China National Survey of Chronic Kidney Disease (2007-2010) were included in the analyses, and exposure data of NO2 were collected and matched. Generalized mixed-effects models were used to analyze the associations between NO2 and CKD, stratified by the presence of hypertension and taking antihypertensive medications. The stratified exposure-response curves of NO2 and CKD were fitted using the natural spine smoothing function. The modifying effects of antihypertensive medications on the association and the exposure-response curve of NO2 and CKD were analyzed. RESULTS: Data of 45 136 participants were included, with an average age of (49.5±15.3) years. The annual average exposure concentration of NO2 was (7.2±6.4) µg/m3. Altogether 6 517 (14.4%) participants were taking antihypertensive medications, and 4 833 (10.7%) participants were identified as having CKD. After adjustment for potential confounders, in the hypertension population not using antihypertensive medications, long-term exposure to NO2 was associated with a significant increase risk of CKD (OR: 1.38, 95%CI: 1.24-1.54, P < 0.001); while in the hypertension population using antihypertensive medications, no significant association between long-term exposure to NO2 and CKD (OR: 0.96, 95%CI: 0.86-1.07, P=0.431) was observed. The exposure-response curve of NO2 and CKD suggested that there was a non-linear trend in the association between NO2 and CKD. The antihypertension medications showed significant modifying effects both on the association and the exposure-response curve of NO2 and CKD (interaction P < 0.001). CONCLUSION: The association between long-term exposure to NO2 and CKD was modified by antihypertensive medications. Taking antihypertensive medications may mitigate the effect of long-term exposure to NO2 on CKD.

[Effect of phacoemulsification on the Berger space].

Objective: To investigate the effect of phacoemulsification on the Berger space (BS). Methods: A prospective cohort study. Patients with cataract who underwent phacoemulsification and intraocular lens implantation in the Department of Ophthalmology, Affiliated Hospital of Nantong University from May 2021 to October 2021 were enrolled. The BS was observed by slit-lamp microscopy and anterior segment optical coherence tomography (AS-OCT) before and 1 month after operation. Intraoperative optical coherence tomography with a 25G optical fiber was performed to observe the BS. The number of eyes with the BS and materials in the BS (MIB) detected perioperatively was counted, and the width of the BS was measured. Statistical analysis was carried out by the Chi-square test, generalized estimating equations, Mann-Whitney U test and binary logistic regression analysis. Results: A total of 119 patients (119 eyes) were included [44 males, 75 females; mean age, (65±12) years]. Preoperatively, the BS was identified in only 4 eyes (3.4%), and no MIB was found. Intraoperatively, the BS was identified in 47 eyes (39.5%), and the MIB was observed in 20 eyes (16.8%). At one month postoperatively, the BS was identified in 33 eyes (27.7%), of which 16 eyes (13.4%) still had MIB. There were significant differences in the detection rates of the BS and MIB between intraoperative and preoperative groups (both P<0.001). The difference in the detection rate of the BS postoperatively compared to intraoperatively was statistically significant (P=0.001), while the difference in the detection rate of MIB was not statistically significant (P>0.05). The intraoperative and postoperative width of the BS [M (Q1, Q3)] was 160.3 (61.6, 273.1) µm and 106.8 (0, 259.4) µm, respectively, and the difference was statistically significant (Z=-2.28, P=0.023). In addition, the detection rate of the BS and MIB in patients with a high risk of zonular fiber weakness [60.7% (17/28) and 42.9% (12/28)] was significantly higher than that in patients without this risk factor [33.0% (30/91) and 8.8% (8/91)] (χ²=6.90, P=0.009; P<0.001). In the multivariable model, weakness of zonular fibers (OR=0.214, 95%CI: 0.081 to 0.561) and higher cumulative dissipated energy (OR=1.255, 95%CI: 1.047 to 1.504) were the main risk factors for structural changes of the BS intraoperatively. Conclusion: Phacoemulsification can damage the normal anatomical structure of the BS, resulting in intraoperative entrance of fluid and particulates to the BS.

DNA Methylation Differences in Peripheral Blood of Patients with Anaphylaxis.

ABSTRACT: Objective To study the DNA methylation of nucleated cells in peripheral blood of patients died from anaphylactic shock caused by cephalosporin drugs and to provide a new research direction and basis for the forensic diagnosis of shock caused by drug hypersensitiveness. Methods Methylation microarray was used to detect DNA methylation of nucleated cells in peripheral blood of patients died from anaphylactic shock caused by cephalosporin drugs and normal subjects. Sequencing data and chip data were analyzed for differences in DNA methylation using R language methylkit, ChAMP package. Random forest algorithm was used to evaluate the importance of the DNA methylation differential sites. Results Differential sites of DNA methylation highly associated with anaphylaxis caused by cephalosporin drugs were obtained at loci such as ETS1, PRR23B and GNAS. Conclusion Cephalosporin allergy is associated with DNA methylation, and DNA methylation may be a new strategy for forensic identification of anaphylactic shock and death.

[Characteristics and clinical significance of pulmonary function test and KL-6 in ASSD-ILD and IPF].

Objective: To study the characteristics and clinical significance of pulmonary function test and kerbs von den lungen 6 (KL-6) in anti-synthetase syndrome related interstitial lung disease (ASSD-ILD) and idiopathic pulmonary fibrosis (IPF). Methods: The clinical data of 43 patients with ASSD-ILD (ASSD-ILD group) from May 2015 to May 2017 were collected retrospectively, including 12 males and 31 females, and 34 patients with IPF (IPF group) treated in the First Affiliated Hospital of Zhengzhou University during the same period, including 28 males and 6 females, were also included. The basic information, and the value of pulmonary function test [pulmonary function parameters included the forced vital capacity expressed as percent predicted (FVC%pred), the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred), the ratio of FVC to FEV(1) (FVC/FEV(1)), the peak expiratory flow expressed as percent predicted (PEF%pred), the forced expiratory flow at 25%, 50%, 75% of FVC as percent predicted (FEF(25)%pred, FEF(50)%pred, and FEF(75)%pred), the maximum mid-expiratory flow as percent predicted (MMEF% pred), and the diffusing capacity for carbon monoxide as percent predicted (DLCO% pred)], and serum KL-6 level in ASSD-ILD and IPF were compared. Results: The FEV(1)%pred, FEF(50)%pred, FEF(75)%pred, and MMEF%pred values in ASSD-ILD group were significantly lower than those in IPF group (all P<0.05), while the FVC% pred, FVC/FEV(1), PEF% pred, FEF(25)%pred, and DLCO% pred values in ASSD-ILD group had no significant difference compared with IPF group (all P>0.05). There was no significant difference in serum KL-6 level between ASSD-ILD group and IPF group [(1 169±911) vs (1 210±908) U/ml, t=0.62, P=0.463]. Follow-up analysis showed that the serum KL-6 level of ASSD-ILD patients who died within two years was significantly higher than that of survivors [(2 060±1 168) vs (1 042±858) U/ml, t=2.93, P=0.041]. The serum KL-6 level of patients who died within two years of IPF patients was also significantly higher than that of patients who survived [(1 767±865) vs (1 089±894) U/ml, t=2.53, P=0.026]. The serum KL-6 level in ASSD-ILD group was negatively correlated with FVC%pred (r=-0.43, P=0.004), FEV(1)%pred (r=-0.39, P=0.010) and DLCO% pred (r=-0.41, P=0.006). There was no correlation between serum KL-6 level and pulmonary function test indexes in IPF group (all P>0.05). Conclusions: There is difference in pulmonary function test between ASSD-ILD patients and IPF patients. High serum KL-6 level will be predictive of poor prognosis.

[Short-term effect of Isobar dynamic stabilization system fixation combined with lumbar discectomy in patients with lumbar disc herniation].

Objective: To investigate the short-term effect of Isobar dynamic stabilization system fixation combined with lumbar discectomy in patients with lumbar disc herniation. Methods: From June 2015 to June 2017, 62 patients with lumbar disc herniation treated in the First Affiliated Hospital of Zhengzhou University were divided into control group and observation group according to the therapy. The 31 patients in the control group were treated with simple excision of nucleus pulposus and the 31 patients in the observation group were treated with Isobar dynamic stabilization system fixation combined with lumbar discectomy. The score of Oswestry disability index (ODI) and Japanese Orthopedic Association (JOA) score of low back pain, lumbar and adjacent stage activity, inflammatory factor levels[C reaction protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α)] were compared between the two groups before and after the operation and 6 months after the operation. The data were compared between the two groups with t test. Results: After the operation and 6 months after, the ODI scores of the two groups decreased and the JOA scores increased significantly (25.5±3.0, 27.5±3.2 vs 15.3±2.2 and 18.6±2.3, 23.3±2.9 vs 15.3±2.0), the ODI scores of the observation group was significantly lower than those in the control group; the JOA scores were significantly higher than those in the control group (t=0.04-10.19, all P<0.05). The operative time, hospital stay, intraoperative blood lose and complications rate in the observation group were all significantly lower than those in the control group. The total activity of lumbar vertebrae in the observation group was significantly higher than that in the control group after operation and 6 months after (t=37.67, 36.60, both P<0.05); the activity of adjacent segments in the observation group was significantly lower than that of the control group (t=9.28, 3.79, both P<0.05); the Pfirrmann grade was significantly lower than that in the control group (t=3.11, 5.05, both P<0.05). The levels of CRP, IL-6 and TNF-α in the two groups were lower than those before operation, and those were also significantly lower in the observation than the corresponding indexes in the control group (t=0.52-10.99, all P<0.05). Conclusion: Isobar dynamic stable system fixation combined with lumbar intervertebral disc resection can effectively improve the lumbar function and lumbar activity in patients with lumbar intervertebral disc herniation, and reduce the level of inflammation and relapse.

MicroRNA-31 inhibits osteosarcoma cell proliferation, migration and invasion by targeting PIK3C2A.

OBJECTIVE: To elucidate the role of microRNA-31 (miR-31) in osteosarcoma and the molecular mechanism of miR-31 in the proliferation, migration, and invasion of osteosarcoma. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to examine the expression of microRNA-31 in human osteosarcoma tissues. Pearson's chi-squared test was used to analyze the correlation between microRNA-31 and clinicopathological features. Proliferation, migration, invasion, and PI3K3C2A protein in treated osteosarcoma cells were detected by Cell Counting Kit-8 (CCK-8) assay, transwell assay without Matrigel, transwell assay with Matrigel, and Western blot analysis, respectively. RESULTS: qRT-PCR showed that miR-31 was down-regulated in osteosarcoma tissues compared with paired para-tumor bone tissues. The lower level of miR-31 was closely associated with high-grade osteosarcoma, metastasis, and poor overall survival. CCK-8 and transwell assay showed that miR-31 inhibited osteosarcoma cells proliferation, migration, and invasion. According to luciferase assay, miR-31 inhibits osteosarcoma cell proliferation, migration, and invasion through inhibiting PIK3C2A. Reversely, overexpression of PIK3C2A inhibited partial effect of miR-31 on proliferation, migration, and invasion in vitro. CONCLUSIONS: MiR-31 inhibits osteosarcoma cell proliferation, migration, and invasion by targeting PICK3C2A. MiR-31 can thus be used as a therapeutic target in osteosarcoma treatment.

Establishment and characterization of a brain-cell line from kelp grouper Epinephelus moara.

A new brain-cell line, EMB, was developed from kelp grouper Epinephelus moara, a cultured marine fish. The EMB cells were subcultured for more than 60 passages. The cells were cultured in Leibovitz's L-15 medium (L15) supplemented with antibiotics, foetal bovine serum (FBS), 2-mercaptoethanol (2-ME) and basic fibroblast growth factor (bFGF). The cells could grow at 18-30° C, with the maximum growth between 24 and 30° C. The optimum FBS concentration for the cells growth ranged between 15 and 20%. Chromosome analysis indicated that the modal chromosome number was 48 in the cells at passage 45. After being transfected with pEGFP-N3 plasmid, the cells could successfully express green fluorescence protein (GFP), implying that this cell line can be used for transgenic studies. A significant cytopathic effect (CPE) was observed in the cells after infection with Singapore grouper iridovirus (SGIV) or red spotted grouper nervous necrosis virus (RGNNV) and the viral replication was confirmed by quantitative real-time PCR (qrt-PCR) assay, which suggested EMB's application potential for studies of SGIV and RGNNV.

Rapid Communication: Period2 gene silencing increases the synthesis of αs-casein protein in bovine mammary epithelial cells.

(), a core clock gene, encodes a circadian rhythm protein which has been shown to control mammary metabolism in rodents. Whether regulates milk component synthesis such as α-casein protein in bovine mammary cells is unknown. Thus, we used gene silencing technology to determine if silencing could affect α-casein synthesis and cell growth in cultured primary bovine mammary epithelial cells (BMEC). The BMEC were established by enzymatic digestion of mammary tissue from mid-lactation cows. A transient-transfection technique was used to insert a small interfering RNA (siRNA) oligonucleotide specific for to inhibit transcription. Control and siRNA-transfected cells were cultured for 48 h. qRT-PCR and ELISA analysis showed that silencing enhanced the synthesis of 2 kinds of α-casein ( < 0.05) through upregulating the mRNA level of and ( < 0.01). Furthermore, the 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) results demonstrated that cell proliferation was not affected ( > 0.05). These data led us to hypothesize that PER2 protein may potentially play an important role in the control of milk protein synthesis and, hence, represents a target that can be used to regulate protein synthesis rate during lactation.

[The levels of neuropeptide S in the brain of asthmatic mice with anxiety and the relationship with the inflammatory mediators].

Objective: To investigate the levels of neuropeptide S in the brain of asthmatic mice with anxiety and the effects of inflammatory mediatores on changes of neuropeptide S in in vitro experiments. Methods: According to the random number table method, 40 BALB/C mice were randomly divided into 4 groups: the control group, the asthma group, the anxiety group and the asthma and anxiety group. The relative expressions of neuropeptide S mRNA in the brain tissue of each group were detected by quantitative real-time polymerase chain reaction(QRT-PCR). Rat cortex neurons obtained by primary culture were divided into 4 groups: the PBS control group, the interleukin-1 beta group, the interleukin-6 group and the tumor necrosis factor-alpha group. After stimulation with inflammatory cytokines the mRNA expressions of neuropeptide S were measured by QRT-PCR and neuropeptide S levels in the cell culture supernatants were measured by emzyme linked immunosorbent assay(ELISA). Results: The relative expressions of neuropeptide S mRNA were decreased in the anxiety group(0.87±0.05) and the asthma and anxiety group(0.79±0.03)compared with the control group(1.00±0.05)and the asthma group(0.96±0.06), most notably in the asthma and anxiety group (all P<0.05). Compared to the PBS control group[(1.00±0.06), (50.6±1. 8)ng/L] and the interleukin-1 beta group[(0.94±0.08), (49.5±1.0)ng/L], the levels of neuropeptide S mRNA and neuropeptide S were decreased in the interleukin-6 group[(0.88±0.07), (45.4±1.2)ng/L] and the tumor necrosis factor-alpha group[(0.86±0.07), (46.0±1.0)ng/L](all P<0.05). There were no significant differences between the interleukin-1 beta group and the PBS control group(all P>0.05). Conclusions: Up-regulated interleukin-6 and tumor necrosis factor-alpha in asthma can inhibit the secretion of neuropeptide S in neuronal cells. The decline of brain neuropeptide S, which has anti-anxiety effect, may lead to the occurrence of anxiety, which may be a potential mechanism of comorbidity of asthma and anxiety.

The Power of Serum Uric Acid in Predicting Metabolic Syndrome Diminishes With Age in an Elderly Chinese Population.

OBJECTIVES: Although serum uric acid (sUA) is not a criterion for diagnosing metabolic syndrome (MetS), many studies have identified a positive association between sUA and MetS in patients of various ages and ethnicities. This association has not been fully established in the very elderly. DESIGN: Cross-sectional and longitudinal study. SETTING AND PARTICIPANTS: A total of 18,906 Chinese elderly aged 65 and older undergoing routine health checkups in Taiwan were enrolled. MEASUREMENTS: Modified Adult Treatment Panel III criteria were used to define MetS. All participants were further divided into nine groups with gender specification according to age (the young-old, 65 to 74; old-old, 75 to 84; and oldest-old, 85 and over) and sUA concentration tertile (males: sUAG1, <5.7 mg/dL; sUAG2, 5.7-6.7 mg/dL; and sUAG3, > 6.7 mg/dL; females: sUAG1, <4.9 mg/dL; sUAG2, 4.9-5.9 mg/dL; and sUAG3, > 5.9 mg/dL). A cross-sectional study was first performed to determine the correlation between sUA and MetS and its components. A longitudinal study then excluded subjects with MetS at baseline to explore the risk of MetS according to sUA levels in 3 age groups. RESULTS: In the cross-sectional study, we observed a graded, positive association between sUA and MetS components that diminished after age 75. Subjects with higher sUA levels had higher odds ratios (OR) for the occurrence of MetS in the young-old and old-old groups of both sexes (P<0.001) except sUAG2 males in the old-old group. However, the association diminished with age and only a higher OR was observed in sUAG2 males in the oldest-old group (OR, 3.38; 95% CI, 1.11-10.30; P = 0.032). In the longitudinal study, the Kaplan-Meier plot showed that higher sUA levels were associated with a higher risk of MetS in the young-old group of both genders (P < 0.001 sUAG3 vs. sUAG1 and sUAG2). Cox regression analysis further confirmed these results (young-old group: sUAG3 HR, 1.90; 95% CI, 1.42-2.54; P < 0.001; old-old group males: HR, 2.20; 95% CI, 1.04-4.65; P = 0.039; young-old females: HR, 1.83; 95% CI, 1.38 - 2.43; P < 0.001). CONCLUSIONS: Higher sUA levels in the young-old group of Chinese elderly were associated with a higher risk of developing MetS. sUA levels are thus regarded as a potential tool for early diagnosis of MetS. However, this association diminished in those over 75 years of age.

Proteome analysis of the liver in the Chinese fire-bellied newt Cynops orientalis.

The Chinese fire-bellied newt, Cynops orientalis, belonging to Amphibia, Caudata, Salamandridae is a species endemic to China. The liver, which is an important digestive gland and the largest amphibian organ, has various functions, including detoxification, glycogen storage, protein synthesis, and hormone production. However, the newt liver has rarely been studied at the molecular level. We performed histomorphology and high-throughput proteomic analysis of the Chinese fire-bellied newt liver, using hematoxylin and eosin (H&E) staining and two-dimensional electrophoresis coupled with mass spectrometry. The H&E staining showed that the newt liver nuclei are large and round, are located in the lateral cytoplasm, and contain a large quantity of lipid droplets. Melanins were abundantly present throughout the hepatic parenchyma. The proteome analysis showed a total of 545 proteins detected in the newt liver. Furthermore, a gene ontology analysis suggested that these proteins were associated with metabolism, immune response, cellular homeostasis, etc. Among these, proteins with metabolic functions were found to be the most abundant and highly expressed. This supports the role of the liver as the metabolic center. The proteomic results provide new insights into the aspects of the liver proteomes of the Chinese fire-bellied newt. The identification of a more global liver proteome in the newt may provide a basis for characterizing and comparing the liver proteomes from other amphibian species.

Correlation between polymorphisms in the glucocorticoid receptor gene NR3C1 and susceptibility to asthma in a Chinese population from the Henan Province.

The aim of this study was to investigate the association between four single nucleotide polymorphisms in NR3C1 (Tth111I, BclI, ER22/23EK, and N363S), which encode the glucocorticoid receptor, and asthma susceptibility in patients from the Henan Province of China. Three hundred and twenty-eight patients with asthma and 60 healthy volunteers were recruited to this study. The target SNPs were genotyped by polymerase chain reaction (PCR)-high resolution melting and PCR-restriction fragment length polymorphism. The frequencies of the AA (8.84%) and GG (30.79%) genotypes of Tth111I were higher, and that of the AG genotype was lower (60.37%), in the asthma patients compared to that seen in healthy controls (5.00, 26.67, and 68.33%, respectively). On the other hand, asthma patients showed higher frequencies of the AA genotype (78.05%) of N363S, and lower frequencies of the AG and GG genotypes (15.55 and 6.40%), compared to healthy volunteers (71.67, 18.33, and 10.00%, respectively). Neither of these differences were found to be statistically significant. Moreover, we observed no significant differences in the genotype or allele frequencies of the BclI and ER22/23EK SNPs between the patient and control groups. In conclusion, SNPs in NR3C1 were not significantly associated with asthma in patients from the Henan Province. Patients showed higher frequencies of the AA and GG genotypes of Tth111I and the AA genotype of the N363S SNP compared to healthy volunteers, although these differences were not significant.

The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873.

Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation. However, it is not yet clear whether lncRNAs can regulate necrosis in cardiomyocytes. Here, we report that a long noncoding RNA, named necrosis-related factor (NRF), regulates cardiomyocytes necrosis by targeting miR-873 and RIPK1 (receptor-interacting serine/threonine-protein kinase 1)/RIPK3 (receptor-interacting serine/threonine-protein kinase 3). Our results show that RIPK1 and RIPK3 participate in H2O2-induced cardiomyocytes necrosis. miR-873 suppresses the translation of RIPK1/RIPK3 and inhibits RIPK1/RIPK3-mediated necrotic cell death in cardiomyocytes. miR-873 reduces myocardial infarct size upon ischemia/reperfusion (I/R) injury in the animal model. In exploring the molecular mechanism by which miR-873 expression is regulated, we identify NRF as an endogenous sponge RNA and repress miR-873 expression. NRF directly binds to miR-873 and regulates RIPK1/RIPK3 expression and necrosis. Knockdown of NRF antagonizes necrosis in cardiomyocytes and reduces necrosis and myocardial infarction upon I/R injury. Further, we identify that p53 transcriptionally activates NRF expression. P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.Our results identify a novel mechanism involving NRF and miR-873 in regulating programmed necrosis in the heart and suggest a potential therapeutic avenue for cardiovascular diseases.

Intrafollicular expression and potential regulatory role of cocaine- and amphetamine-regulated transcript in the ovine ovary.

Follicular growth is regulated by a complex interaction of pituitary gonadotropins with local regulatory molecules. Previous studies demonstrated an important role for cocaine- and amphetamine-regulated transcript (CART) in regulation of granulosa cell estradiol production associated with dominant follicle selection in cattle. However, intraovarian expression and actions of CART in other species, including sheep, are not known. The objective of this study was to investigate the expression of CART in sheep follicles and determine the effects of CART on indices of ovine granulosa cell function linked to follicular development. Results demonstrated the expression of CART messenger RNA and prominent intraovarian localization of CART peptide in granulosa cells of sheep follicles. Granulosa cell CART messenger RNA was lower, but follicular fluid estradiol concentrations were higher in large (>5 mm) follicles vs smaller 3- to 5-mm follicles harvested from sheep ovaries of abattoir origin. CART treatment inhibited follicle stimulating hormone-induced estradiol production by cultured ovine granulosal cells and also blocked the follicle stimulating hormone-induced increase in granulosa cell numbers. Results demonstrate expression of CART in sheep follicular tissues and suggest potential biological actions of CART, which are inhibitory to ovine follicular growth and development.

NFAT4-dependent miR-324-5p regulates mitochondrial morphology and cardiomyocyte cell death by targeting Mtfr1.

Emerging evidence suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction and heart failure. However, the molecular components regulating mitochondrial network in heart remain largely unidentified. Here we report that NFAT4, miR-324-5p and mitochondrial fission regulator 1 (Mtfr1) function in one signaling axis that regulates mitochondrial morphology and cardiomyocyte cell death. Knocking down Mtfr1 suppresses mitochondrial fission, apoptosis and myocardial infarction. Mtfr1 is a direct target of miR-324-5p, and miR-324-5p attenuates mitochondrial fission, cardiomyocyte apoptosis and myocardial infarction by suppressing Mtfr1 translation. Finally, we show that transcription factor NFAT4 inhibits miR-324-5p expression. Knockdown of NFAT4 suppresses mitochondrial fission and protects cardiomyocyte from apoptosis and myocardial infarction. Our study defines the NFAT4/ miR-324-5p/Mtfr1 axis, which participates in the regulation of mitochondrial fission and cardiomyocyte apoptosis, and suggests potential new treatment avenues for cardiac diseases.

MicroRNA-532-3p regulates mitochondrial fission through targeting apoptosis repressor with caspase recruitment domain in doxorubicin cardiotoxicity.

Doxorubicin (DOX) is a wide-spectrum antitumor drug, but its clinical application is limited by its cardiotoxicity. However, the mechanisms underlying DOX-induced cardiomyopathy remain mostly unclear. Here we observed that apoptosis repressor with caspase recruitment domain (ARC) was downregulated in mouse heart and cardiomyocytes upon DOX treatment. Furthermore, enforced expression of ARC attenuated DOX-induced cardiomyocyte mitochondrial fission and apoptosis. ARC transgenic mice demonstrated reduced cardiotoxicity upon DOX administration. DOX-induced mitochondrial fission required the activity of dynamin-related protein 1 (Drp1). In elucidating the molecular mechanism by which ARC was downregulated upon DOX treatment, miR-532-3p was found to directly target ARC and participated in DOX-induced mitochondrial fission and apoptosis. MiR-532-3p was not involved in DOX-induced apoptosis in cancer cells. Taken together, these findings provide novel evidence that miR-532-3p and ARC constitute an antiapoptotic pathway that regulates DOX cardiotoxicity. Therefore, the development of new therapeutic strategies based on ARC and miR-532-3p is promising for overcoming the cardiotoxicity of chemotherapy for cancer therapy.

Downregulation of basic fibroblast growth factor is associated with femoral head necrosis in broilers.

Femoral head necrosis (FHN) is a metabolic cartilage disease of rapidly growing broilers. The aim of the present study was to investigate the role of basic fibroblast growth factor (bFGF) in the apoptotic processes associated with FHN. Broilers were selected and categorized based on clinical examination in 3 groups: healthy, femoral head separation, or femoral head separation with growth plate lacerations. Hematoxylin and eosin staining showed fewer chondrocytes in the resting zone of the growth plates when FHN occurred. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed a significant increase in chondrocyte apoptosis. Furthermore, immunohistochemical assays and real-time quantitative PCR analysis demonstrated a decline in bFGF expression. In addition, reduced Bcl-2 mRNA expression was observed along with a corresponding increase in Bax and caspase-3 mRNA expression in FHN samples. There was a correlation between bFGF protein expression and the proportion of TUNEL-positive cells and a correlation between bFGF mRNA expression and expression of Bax, and caspase-3. The results of the study suggested that the expression of bFGF was reduced in the process of chondrocyte apoptosis, which could play an important role in the pathogenesis of FHN in chickens.

Influence of Regional Difference in Bone Mineral Density on Hip Fracture Site in Elderly Females by Finite Element Analysis.

Hip fracture is a kind of osteoporotic fractures in elderly patients. Its important monitoring indicator is to measure bone mineral density (BMD) using DXA. The stress characteristics and material distribution in different parts of the bones can be well simulated by three-dimensional finite element analysis. Our previous studies have demonstrated a linear positive correlation between clinical BMD and the density of three-dimensional finite element model of the femur. However, the correlation between the density variation between intertrochanteric region and collum femoris region of the model and the fracture site has not been studied yet. The present study intends to investigate whether the regional difference in the density of three-dimensional finite element model of the femur can be used to predict hip fracture site in elderly females. The CT data of both hip joints were collected from 16 cases of elderly female patients with hip fractures. Mimics 15.01 software was used to reconstruct the model of proximal femur on the healthy side. Ten kinds of material properties were assigned. In Abaqus 6.12 software, the collum femoris region and intertrochanteric region were, respectively, drawn for calculating the corresponding regional density of the model, followed by prediction of hip fracture site and final comparison with factual fracture site. The intertrochanteric region/collum femoris region density was [(1.20 ± 0.02) × 10(6)] on the fracture site and [(1.22 ± 0.03) × 10(6)] on the non-fracture site, and the difference was statistically significant (P = 0.03). Among 16 established models of proximal femur on the healthy side, 14 models were consistent with the actual fracture sites, one model was inconsistent, and one model was unpredictable, with the coincidence rate of 87.5 %. The intertrochanteric region or collum femoris region with lower BMD is more prone to hip fracture of the type on the corresponding site.