Objective:To explore the effects of canagliflozin on cardiac function and its regulation of ferroptosis in rats with heart failure with preserved ejection fraction (HFpEF).Methods:Thirty-two 7-week-old Dahl salt-sensitive rats were selected and randomly divided into four groups: the control group (fed with low-salt diet), the HFpEF group (fed with high-salt diet), the canagliflozin 20 group (fed with high-salt diet and 20 mg·kg -1·d -1 canagliflozin), and the canagliflozin 30 group (fed with high-salt diet and 30 mg·kg -1·day -1 canagliflozin). Body weight and blood pressure of the rats in each group were monitored. Metabolic cage tests were conducted at the10 th week of the experiment, and echocardiography was performed at the 12 th week, after which the rats were killed. Blood and left ventricular samples were collected. HE staining, Masson staining, Prussian blue iron staining, and reactive oxygen species staining were performed to observe the cardiomyocyte size and shape, degree of interstitial fibrosis, iron staining, reactive oxygen species production under optical microscope. The ultrastructure of cardiomyocytes was observed under electron microscope. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression levels of proteins and mRNA related to ferroptosis in left ventricular myocardial tissue of rats in each group. Results:After 1 week of adaptive feeding, all rats survived. Metabolic cage results showed that compared with control group, rats in the HFpEF group, canagliflozin 20 group and canagliflozin 30 group had more food intake, water intake and urine output, and lower body weight (all P<0.05). These changes were more pronounced in canagliflozin 20 group and canagliflozin 30 group than in HFPEF group, and only the body weight at the 12 th week showed a statistically significant difference between canagliflozin 20 group and canagliflozin 30 group ( P<0.05). The blood pressure of 6 th week and 12 th week, heart weight and left ventricular corrected mass of 12 th week of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while the ratio of early mitral valve peak velocity to late mitral valve peak velocity of 12 th week was lower (all P<0.05). HE and Masson staining showed that compared to control group, the myocardial fibers in the left ventricular myocardial tissue of rats in HFpEF group were disordered, with larger cell diameter ((0.032±0.004) mm vs. (0.023±0.003) mm, P<0.05), irregular shape, obvious proliferation of interstitial collagen fibers, and higher collagen volume fraction (0.168±0.028 vs. 0.118±0.013, P<0.05). Compared with HFpEF group, rats in the canagliflozin 20 group and canagliflozin 30 had more orderly arranged myocardial fibers, more regular cardiomyocyte shape, smaller cell diameter, and lower collagen volume fraction ( P<0.05). It was observed under electron microscopy that, compared to control group, most of the striated muscles in myocardial tissue of HFpEF group were broken, and the Z line and M line could not be clearly distinguished, some changes such as mitochondrial swelling, membrane thickening, cristae reduction or even disappearance occurred. In the canagliflozin 20 group and canagliflozin 30 group, the arrangement of striated muscles in the myocardial tissue of rats tended to be more regular, and the morphological changes of mitochondria were milder. Prussian blue iron staining results showed that the iron content in myocardial tissue of rats in HFpEF group was higher than that in control group, canagliflozin 20 group and canagliflozin 30 group. Reactive oxygen species staining results showed that the reactive oxygen species content in the myocardial tissue of rats in HFpEF group was higher than that of control group, canagliflozin 20 group and canagliflozin 30 group. Biochemical analysis of myocardial tissue showed that Fe 2+ and malondialdehyde content in myocardial tissue of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while glutathione content was lower (all P<0.05). Western blot and RT-qPCR detection results showed that compared to control group, rats in HFpEF group had higher expression levels of transferrin receptor 1 (protein relative expression level: 1.37±0.16 vs. 0.31±0.12), acyl-CoA synthetase long-chain family member 4 (protein relative expression level: 1.31±0.15 vs. 0.63±0.09) protein and mRNA, and lower expression levels of ferritin heavy chain 1 (protein relative expression level: 0.45±0.08 vs. 1.41±0.15) protein and mRNA (all P<0.05). There was no statistically significant difference in these indicators between canagliflozin 20 group and the canagliflozin 30 group (all P>0.05). There was no significant difference in levels of glutathione peroxidase 4 protein and mRNA expression in myocardial tissue of rats in four groups( P>0.05). Conclusion:Canagliflozin improves cardiac function in HFpEF rats by regulating the ferroptosis mechanism.

OBJECTIVES: Diarrheal disease continues to be a significant cause of morbidity and mortality. We investigated how anomalies in monthly average temperature, precipitation, and surface water storage (SWS) impacted bacterial, and viral diarrhea morbidity in Taiwan between 2004 and 2015. METHODS: A multivariate analysis using negative binomial generalized estimating equations was employed to quantify age-specific and cause-specific cases of diarrhea associated with anomalies in temperature, precipitation, and SWS. RESULTS: Temperature anomalies were associated with an elevated rate of all-cause infectious diarrhea at a lag of 2 months, with the highest risk observed in the under-5 age group (incidence rate ratio [IRR], 1.03, 95% confidence interval [CI], 1.01 to 1.07). Anomalies in SWS were associated with increased viral diarrhea rates, with the highest risk observed in the under-5 age group at a 2-month lag (IRR, 1.27; 95% CI, 1.14 to 1.42) and a lesser effect at a 1-month lag (IRR, 1.18; 95% CI, 1.06 to 1.31). Furthermore, cause-specific diarrheal diseases were significantly affected by extreme weather events in Taiwan. Both extremely cold and hot conditions were associated with an increased risk of all-cause infectious diarrhea regardless of age, with IRRs ranging from 1.03 (95% CI, 1.02 to 1.12) to 1.18 (95% CI, 1.16 to 1.40). CONCLUSIONS The risk of all-cause infectious diarrhea was significantly associated with average temperature anomalies in the population aged under 5 years. Viral diarrhea was significantly associated with anomalies in SWS. Therefore, we recommend strategic planning and early warning systems as major solutions to improve resilience against climate change.

Objective:To investigate the Graf classification results and risk factors of infants for developmental dysplasia of the hip (DDH) by B-ultrasound screening in Tianjin.Methods:A retrospective analysis was conducted from January 2013 to December 2020 using the three-tier maternal and child health care management and the Tianjin maternal and child health information system for the early B-ultrasound screening data of 6-8 weeks old infants. The "2+1" screening model of "primary screening-re-screening-diagnostic treatment" was applied. The positive screening rate and age of infants at the time of referral for treatment in different years and different Graf classifications were analyzed, and the differences in positive infants with different sex, parity, fetal position, mode of production, gestational age, birth weight, and family history were compared. Binary logistic regression was used to analyze risk factors for DDH.Results:A total of 807 889 babies were screened, and 2 039 children (2 841 hips) were detected with B-ultrasound Graf classification count IIa and above, with the positive rate was 2.52‰ (2 039/807 889). Among the abnormal hips, 685 were type IIa(+) hips, 959 were type IIa(-) hips, 367 were type IIb hips, 262 were type IIc hips, 227 were type D hips, 265 were type III hips, and 76 were type IV hips. Type IIa(-) was the most common, accounting for 33.76% (959/2 841), type IIa(+) accounted for 24.11% (685/2 841), type D and above was 19.99%(568/2 841). The abnormality rate of the left hip was 2.02‰ (1 632/807 889), which was greater than 1.50‰ (1 209/807 889) of the right side, and the difference is statistically significant (χ 2=63.09, P<0.001). The rate of hip abnormalities in female infants was 3.27‰ (2 541/777 272), greater than 0.36‰ (300/838 506) in male infants, which the difference between the sexes had statistically significant (χ 2=1 947.871, P<0.001). The positive rate of DDH in male infants was 0.50‰ (209/419 253), and that in female infants was 4.71‰ (1 830/388 636). The detection ratio of male to female infants was 1∶8.76, and the difference in the positive rate of DDH between the sexes was statistically significant (χ 2=1 420.102, P<0.001). Different fetal position (cephalic position/breech presentation), delivery method (normal delivery/cesarean section), birth weight (normal/low weight), family history (with DDH/without DDH) showed statistically significant differences in the positive rate of DDH ( P<0.05), whereas there was no significant difference in the positive rate of DDH at different parity (first/second and above) and gestational age (term/premature) ( P>0.05). Logistic regression analysis showed that gender ( OR=10.50, P<0.001) and fetal position ( OR=3.40, P<0.001) were independent risk factors for DDH, and gestational age ( OR=0.91, P<0.001) was a protective factor for DDH. Differences in referral age of infants with different B-ultrasound Graf classification from year to year were statistically significant ( P<0.05). Conclusion:Through the "2+1" screening model of "primary screening-re-screening-diagnostic treatment", the DDH positive rate in 6-8 weeks old infants in Tianjin was 2.52‰, and the positive rate of DDH in female infants and left hip was higher. The more severe the Graf classification of B-ultrasound was, the younger the age of referral was. Women and infants with breech presentation had a higher risk of developing DDH, and the risk of DDH in preterm infants was lower.

Legg-Calvé-Perthes disease (LCPD) is an idiopathic necrosis of the femoral head in childhood, the deformities of the femoral head occurring in the progress of disease could result in osteoarthritis. Treatment can be surgical or nonsurgical, but the timing and indications remain unclear. Understanding of the prognostic factors of LCPD is helpful to predict the outcome and guide the clinical management. This study reviewed the literatures about the prognosis of LCPD since 2000, the prognostic factors were summarized from three categoriesas general factors, disease factors and intervention factors. The general factors were the characteristic information of patient that can be obtained at the first time clinically. The age of onset is the most definite prognostic factor, the younger the age, the better the prognosis, and 6-8 years is an important watershed. Disease factors refer to the disease characteristic information obtained through evaluation. The modified Waldenstr?m stage of the disease needs to be confirmed first, early treatment can ensure better prognosis. Then the severity was evaluated, including the involvement of necrosis, morphological changes and extrusion of the femoral head. The more severe the disease, the worse the prognosis. Most predicters, such as Catterall grading and Herring lateral column typing, have to be used in late-stage of LCPD. The degree of femoral head perfusion evaluated in enhanced MRI or DWI-MRI is an early predictor of LCPD, but it is still in the preliminary exploratory. Intervention factors are the effects of different methods of treatment on prognosis, including the comparison of surgery or non-surgery, different non-surgical and different surgical methods. The determination of surgical or non-surgical treatment mainly depends on the age of onset and severity of disease, and the younger and milder cases tend to be non-surgical treatment, but the specific indications are still controversial.

Objective To explore the clinical efficacy of acupuncture combined with SSRIs in the treatment of patients with depression. Methods A total of 83 patients with depression admitted to our hospital between January 2019 and January 2020 were selected as the research objects. Patients in the control group were treated with SSRIs, and the combined treatment (observation) group was treated with acupuncture on the basis of the control group. The clinical efficacy, anxiety (HAMD) and depression scale (HAMD) of patients in the two groups were compared. Results After treatment, the clinical efficacy of depression patients in the observation group was significantly higher than that in the control group (P<0.05). HAMA and HAMD scores showed statistical difference between the two groups. HAMA and HAMD scores of patients in the observation group were lower than those in the control group (P<0.05). Conclusion Acupuncture combined with SSRIs in the treatment of depression can significantly improve the patient's condition, reduce the patient's anxiety and depression, and has a positive significance for the treatment of the patients.

Biodegradation of polyurethane (PUR) pollutants by microorganisms has received widespread attention currently. Identification of microorganisms capable of efficiently degrading PUR plastics is a key point. In this study, a strain P10 capable of degrading PUR was isolated from the plastic wastes, and identified as a bacterium belonging to the genus of Brevibacillus based on colony morphology and 16S rDNA phylogenetic analysis. Brevibacillus sp. P10 was capable of degrading 71.4% of waterborne polyurethane (Impranil DLN) after 6 days growth in MSM medium with DLN as a sole carbon source. In addition, strain P10 can use commercial PUR foam as the sole carbon source for growth. Brevibacillus sp. P10 can degrade 50 mg PUR foam after 6 days growth in MSM medium supplemented with 5% (V/V) LB after optimization of degradation conditions. This indicates that Brevibacillus sp. P10 has potential to be used in biodegradation of PUR waste.
Bacteria ; Biodegradation, Environmental ; Phylogeny ; Polyurethanes

Objective To observe the effects of Yuanzhi San (YZS) on the ethology and cerebral acetylcholinesterase(AchE) activity of mouse model of memory disorder induced by scopolamine. Methods Sixty mice were randomly divided into six groups, namely blank control group, model group, positive medicine group, and low-dose, middle-dose and high-dose YZS groups. Except for the blank control group and model group were given the normal saline, the mice in other groups were administered with the corresponding drugs for 10 days. And then, mice in the medication groups were given subcutaneous injection of scopolamine in the dose of 3mg/kg to induce memory disorder model. Morris water maze test and step-down test were adopted for the observation of the learning-memory ability of the mice, and at the end of the tests, the activity of AchE in mouse cerebral cortex was measured by a biochemical method. Results Compared with the model group, escape latency was decreased, and retention time and swimming distance in the effective area in Morris water maze test were prolonged in YZS groups (P<0.05); latency in step-down test was also prolonged (P<0.05). YZS had an effect on decreasing AchE activity in the cerebral cortex of model mice (P < 0.05 compared with the model group). However, the differences were insignificant among the medication groups(P>0.05). Conclusion YZS exerts certain effect on improving learning-memory ability of memory disorder mice induced by scopolamine , and the mechanism might be related with the inhibition of AchE activity in the cerebral cortex of model mice.

Objective To assess the feasibility of double phase subtraction angiography with second generation (128-slice )dual-source CT in low dose Flash spiral scan mode for the evaluation of cerebral vessel,compared with dual-energy subtraction angiogra-phy.Methods 60 patients underwent double phrase CT angiography were divided into group A (n = 30,with Flash spiral scan mode),group B(n=30,with dual-energy scan mode).The signal-to-noise ratio(SNR),the contrast-to-noise ratio(CNR)and the av-erage radiation of double phrase subtraction images were measured in two groups,respectively.The double phase subtraction images quality were graded by 2 independent readers on a 5-point scale(5=excellent)in double-blind,according to various degrees of the re-sidual bones,the vessel displayed and luminal integrity,respectively.Differences between two groups were analyzed by Mann-whit-ney test and t test.Results The double phrase image SNR showed no difference to both two groups(P >0.05).The image CNR of arterial and venous phase in group A were higher than that of group B(40.89±8.89 and 40.27 ±9.90 in group A vs 35.28 ±8.43 and 34.89±8.66 in group B;P <0.05)respectively.There were no singnificant difference in the bone removal image scores of doub-le phase and in the vessel image scores of venous phase to both two groups respectively(P >0.05).The vessel image scores of arterial phase were higher in group A than that of group B(4.93±0.25 vs 3.87±0.97;P <0.05).Some internal carotid in the base of skull has not good luminal integrity in group B.The mean dose length product (DLP)in group A was lower than that of group B,with a 39 percent reduction[(226±5.69 )mGy/cm vs (368 ± 21.35 )mGy/cm,P < 0.05 ].Conclusion With the roughly similar image quality to dual-energy double phase subtraction angiography,the cerebral vessels can be assessed using dual-source CT subtraction angiography in Flash spiral scan mode and a lower radiation dose.

Objective To assess the early prognosis of 117 patients after carduopulmonary resuscitation (CPR) in ICU by using the markers of inflammation,Glasgow Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores.Methods A total of 117 CPR patients admitted between 2010 January to 2012 December were enrolled for study.Within 24 h after admission,inflammatory markers,blood routine items,hepatorenal function,electrolytes of blood were measured.The GCS and APACHE Ⅱ scores were recorded.Arterial blood gas analyses were performed at 0,12,and 24 h after hospitalization,and the 12-h and 24-h lactate clearance rates were calculated.Seven days after treatment,according to the outcomes,the patients were divided into survival group and death group,and the clinical data of two groups were analyzed.Results (1) Of them,73 patients died and 44 survived.Factor analysis showed that age,time elapsed from resuscitation to ICU admission,D-dimer,arterial oxygenation index (FiO2),arterial blood pH,arterial blood lactate concentration upon ICU admission,GCS score and APACHE Ⅱ score were significantly different between the two groups (P ＜ 0.05or P ＜ 0.01); (2) Two classification logistic regression analysis showed that D-Dimer,GCS score and APACHE Ⅱ score significantly correlated with the mortality risk of the patients in the wake of CPR with relative odds ratios of 1.000,2.091,and 0.531,respectively (P ＜ 0.05 or P ＜ 0.01) ; (3) Receiver operating characteristic curve analysis indicated that the area under the curve of GCS (0.821) and APACHE Ⅱ (0.869) had higher predictive value than D-dimer (0.655).The highest accuracy (84.6％) in predicting patient survival was achieved when the GCS score was 6.5.Meanwhile,the highest accuracy (82.1％) in predicting patient death was achieved when the APACHE Ⅱ score was 17.5.Conclusions Both GCS score and APACHE Ⅱ score has obvious correlation with the prognosis of the critically ill patients after CPR and could be used to predict prognosis at early stage.

BACKGROUNDThe initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we developed a novel amorphous calcium phosphate (ACP)/poly(L-lactic acid) (PLLA) material that demonstrated morphologic variations in its microstructure. The aim of this study was to investigate the initial interaction between this material and osteoblastic cells. Cellular attachment and the corresponding signal transduction pathways were investigated.

METHODSA porous ACP/PLLA composite and PLLA scaffold (as a control) were incubated in fetal bovine serum (FBS) containing phosphate-buffered saline (PBS), and the protein adsorption was determined. Osteoblastic MG63 cells were seeded on the materials and cultured for 1, 4, 8, or 24 hours. Cell attachment was evaluated using the MTS method. Cell morphology was examined using scanning electron microscopy (SEM). The expression levels of the genes encoding integrin subunits α1, α5, αv, β1, focal adhesion kinase (FAK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using real-time reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe ACP/PLLA material significantly increased the protein adsorption by 6.4-fold at 1 hour and 2.4-fold at 24 hours, compared with the pure PLLA scaffold. The attachment of osteoblastic cells to the ACP/PLLA was significantly higher than that on the PLLA scaffold. The SEM observation revealed a polygonal spread shape of cells on the ACP/ PLLA, with the filopodia adhered to the scaffold surface. In contrast, the cells on the PLLA scaffold exhibited a spherical or polygonal morphology. Additionally, real-time RT-PCR showed that the genes encoding the integrin subunits α1, αv, β1, and FAK were expressed at higher levels on the ACP/PLLA composite.

CONCLUSIONSThe ACP/PLLA composite promoted protein adsorption and osteoblastic adhesion. The enhanced cell adhesion may be mediated by the binding of integrin subunits α1, αv, and β1, and subsequently may be regulated through the FAK signal transduction pathways.

Biocompatible Materials ; chemistry ; Calcium Phosphates ; chemistry ; Cell Adhesion ; physiology ; Cells, Cultured ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Humans ; Integrin alpha1 ; metabolism ; Integrin alpha5 ; metabolism ; Integrin alphaV ; metabolism ; Integrin beta1 ; metabolism ; Integrins ; genetics ; metabolism ; Lactic Acid ; chemistry ; Osteoblasts ; cytology ; Porosity ; Tissue Engineering ; methods