Empagliflozin and liraglutide ameliorate HFpEF in mice via augmenting the Erbb4 signaling pathway.

Heart failure with preserved ejection fraction (HFpEF) is closely associated with metabolic derangement. Sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) exert anti-HFpEF effects, but the underlying mechanisms remain unclear. In this study, we explored the anti-HFpEF effects of empagliflozin and liraglutide and the underlying molecular mechanisms in a mouse model of HFpEF. This model was established by high-fat diet (HFD) feeding plus Nω-nitro-L-arginine methyl ester (L-NAME) treatment. The mice were treated with empagliflozin (20 mg·kg-1·d-1, i.g.) or liraglutide (0.3 mg·kg-1·d-1, i.p.) or their combination for 4 weeks. At the end of the experimental protocol, cardiac function was measured using ultrasound, then mice were euthanized and heart, liver, and kidney tissues were collected. Nuclei were isolated from frozen mouse ventricular tissue for single-nucleus RNA-sequencing (snRNA-seq). We showed that administration of empagliflozin or liraglutide alone or in combination significantly improved diastolic function, ameliorated cardiomyocyte hypertrophy and cardiac fibrosis, as well as exercise tolerance but no synergism was observed in the combination group. Furthermore, empagliflozin and/or liraglutide lowered body weight, improved glucose metabolism, lowered blood pressure, and improved liver and kidney function. After the withdrawal of empagliflozin or liraglutide for 1 week, these beneficial effects tended to diminish. The snRNA-seq analysis revealed a subcluster of myocytes, in which Erbb4 expression was down-regulated under HFpEF conditions, and restored by empagliflozin or liraglutide. Pseudo-time trajectory analysis and cell-to-cell communication studies confirmed that the Erbb4 pathway was a prominent pathway essential for both drug actions. In the HFpEF mouse model, both empagliflozin and liraglutide reversed Erbb4 down-regulation. In rat h9c2 cells, we showed that palmitic acid- or high glucose-induced changes in PKCα and/or ERK1/2 phosphorylation at least in part through Erbb4. Collectively, the single-cell atlas reveals the anti-HFpEF mechanism of empagliflozin and liraglutide, suggesting that Erbb4 pathway represents a new therapeutic target for HFpEF. Effects and mechanisms of action of empagliflozin and liraglutide in HFpEF mice. HFpEF was induced with a high-fat diet and L-NAME for 15 weeks, and treatment with empagliflozin and liraglutide improved the HFpEF phenotype. Single nucleus RNA sequencing (snRNA-seq) was used to reveal the underlying mechanism of action of empagliflozin and liraglutide.

Treatment and diagnosis of hyperlipidemia acute pancreatitis in pregnancy associated with pre­pregnancy obesity and diabetes: A case report.

Hyperlipidemia acute pancreatitis (HLAP) is a specific type of pancreatitis mainly caused by elevated serum triglyceride (TG) levels. Therefore, knowledge of patients' medical history is crucial to the identification of those at high risk of HLAP. Diabetes and obesity are associated with high levels of triglycerides, a risk factor for the development of HLAP, which should be controlled before pregnancy. Moreover, HLAP is associated with additional diagnostic and management challenges related to hyperlipidemia (HL) and pregnancy. HLAP during pregnancy has a rapid onset and rapid progression, and complications are more likely to damage the function of multiple organs. HLAP is more common after 28 weeks of pregnancy, the cause is mostly high TG and the serum TG of the patient is often >1,000 mg/d1. Clinicians should be alert to the occurrence of server acute pancreatitis (AP). Therefore, clinicians need to identify and implement effective treatment in a timely manner to control the progression of HLAP during pregnancy and improve pregnancy outcomes. The present study reported the case of a 26-year-old pregnant patient who was hospitalized for epigastric pain at 35 weeks and 2 days of gestation. Medical and family history reported previous diagnoses of diabetes and obesity (weight before pregnancy, 103 kg; BMI, 36.40 kg/m2). Laboratory tests demonstrated high levels of lipase and amylase, a notable systemic inflammatory response, HL, coagulopathy, hypoproteinemia and hyperglycemia. Abdominal ultrasonography demonstrated a hypoechoic pancreatic head. A clinical diagnosis of AP was confirmed using CT scanning. Initial interventions for HLAP included aggressive intravenous hydration, bowel rest, pain control and a combination of heparin and insulin. Lipid-lowering agents were administered to reduce serum lipid levels. Hemoperfusion and continuous renal replacement therapy were also used to rapidly counteract the elevated lipid levels. Antibiotics were administered in the present case because inflammatory markers such as leukocytes, neutrophils and C-reactive protein were elevated. The patient and newborn were discharged 11 days after hospitalization, with an improvement in maternal clinical health and the infant was healthy. When evaluating pregnant patients with pre-obesity and diabetes presenting with abdominal pain, obstetricians should consider HLAP. Timely diagnosis and multi-team precision treatment are effective for good outcomes for mother and baby.

Correlation analysis between foot deformity and diabetic foot with radiographic measurement.

Background: Foot deformity is a risk factor for diabetic foot ulcer. This study was aimed to investigate the relationship between hallux valgus (HV) and diabetic foot through the radiographic measurement. Methods: The patients with diabetic foot hospitalizing in the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University from September 2016 to June 2020 were selected. Then the foot plain X-ray radiographs were completed, and the size of HV angle (HVA) was measured. Their clinical data were collected, and the ulcer recurrence rate, amputation rate and mortality rate of the patients were followed up. Results: A total of 370 patients were included. According to HVA, patients were divided into non-HV group (HVA<15°), and mild (15°≤HVA ≤ 20°), moderate (20°40°) HV groups. The age, height, BMI, smoking history and glycosylated hemoglobin level among the non-HVA, mild, moderate, and severe HV group (P<0.05), while smoking history, HbA1c, eGFR and autonomic neuropathy were significantly lower in HV group than those in non-HV group (P<0.05). The ulcer area in patients with moderate HV was larger than that in non-HV patients, and the severity of infection in patients with severe HV was significantly higher than that the other three groups (P<0.05). Conclusion: The occurrence of HV is not only related to age and BMI, but also to the creatinine and eGFR level, autonomic neuropathy, lower limb arteriosclerosis occlusion, coronary heart disease and hypertension. Therefore, more attention should be paid to renal function screening, neuropathy screening and evaluation of lower extremity vascular lesions in patients with diabetes, especially those with moderate or higher HV.

Sarcopenia is an independent risk factor for all-cause mortality rate in patients with diabetic foot ulcers.

Objective: This study aimed to determine whether sarcopenia affects the all-cause mortality rate of patients with diabetic foot ulcers (DFUs). Research design and methods: The clinic-based observational study included 217 patients treated at the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University during a 4-year period. All subjects underwent dual-energy X-ray absorptiometry to determine their body composition during hospitalization. Diagnosis of sarcopenia was based on the Baumgartner diagnostic criteria. Patients were followed up regularly by phone calls until April 1, 2019, and their survival status was recorded.Univariate and multivariate Cox risk ratio regression models were used to analyze factors influencing the all-cause mortality rate of patients with DFUs. Results: Of the 217 patients, 158 people survived (82.7%), 33 died (17.3%), and 26 were lost to follow-up. The median follow-up time was 23 (Range 11-34) months. The majority of patients were male (68.6%), with a mean age of 67.29 ± 11.14 years. The 5-year survival rate was 68.3% and 45.9% for all study patients (n = 217) and sarcopenia patients (n = 81), respectively. Multivariate Cox risk regression model showed that age (HR 1.042[95%CI:1.006, 1.078], P = 0.021), sarcopenia (HR 5.051[95%CI:1.968, 12.961], P = 0.001), and serum creatinine (HR 1.007[95%CI: 1.003, 1.010], P < 0.001) were independent risk factors for all-cause mortality rate of patients with DFUs. Kaplan-Meier survival curve indicated that the survival rate of patients with sarcopenia was significantly lower than non-sarcopenia patients (P < 0.001). Conclusions: Sarcopenia is an independent risk factor for all-cause mortality of patients with DFUs and hence an important prognostic factor for patients with DFUs. Active prevention and improvement of sarcopenia can potentially improve the survival outcomes of this patient population.

Parallel Aligned Nickel Nanocone Arrays for Multiband Microwave Absorption.

Magnetic nanostructures with conical shape are highly desired for pursuing extraordinary magnetic properties and microwave absorption. However, the fabrication of such nanostructures with controlled shape and size uniformities and alignment is not yet realized. Accordingly, the magnetic properties and their application as microwave absorber are not well understood. Here, we report on the first demonstration of controlled fabrication of soft magnetic nickel nanocone arrays with sharp geometry, large aspect ratio, uniform size, and parallel alignment. The imaginary part of the relative complex permeability shows multiband absorption in the 2-17 GHz range. Such an exceptional microwave absorption results from the uniform conical shape and size and the parallel alignment. The absorption mechanisms are discussed under the framework of natural resonance and exchange resonance. The natural resonance is dependent on the shape anisotropy and facilitated by the conical geometry. The exchange resonance is well explained by the observation of the bulk spin waves with exchange coupling at the tip of nanocones using the inelastic light scattering and is consistent with exchange theory predictions for the quantization of bulk spin waves. We expect that our work will shed light on the physical insights into the magnetic properties of nanocones and find great potential in applications of microwave absorption.

Early diagnosis and precision treatment of right ovarian vein and inferior vena cava thrombosis following caesarean section: A case report.

Ovarian vein thrombosis (OVT) is a rare medical complication that is most often diagnosed in the post-partum period. OVT can lead to conditions, including sepsis, inferior vena cava (IVC), pulmonary emboli and mortality. The current study outlines a case of a patient who experienced pain in the lower abdomen and waist without fever postpartum following caesarean section (CS). Plasma FDP, D-Dimer and fibrinogen levels were markedly increased following CS and this was an indicator of the rapid progression of blood coagulation and fibrinolysis. Increased maternal lipid may be one of the risk factors for thrombosis. Based on the clinical presentation, a CT scan demonstrated thrombosis of the right ovarian vein and inferior vena cava, and a diagnosis of OVT and IVC thrombosis was subsequently made. In the current case, an anticoagulant therapy was started with a subcutaneous injection low molecular weight heparin calcium, an intravenous urokinase drip as a thrombolytic agent and implantation of inferior vena cava filters as a novel method of treatment for thrombosis. The patient was discharged from hospital 20 days following treatment in a good condition. The current study reports a case of OVT associated with IVC that was successfully managed without complication.

Correlation Between Diabetic Peripheral Neuropathy and Sarcopenia in Patients with Type 2 Diabetes Mellitus and Diabetic Foot Disease: A Cross-Sectional Study.

PURPOSE: The present study was designed to determine the relationships between sarcopenia and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM) and diabetic foot disease (DFD) respectively. PATIENTS AND METHODS: A total of 1104 patients with T2DM and 257 patients with DFD were included in the study, which was designed as a cross-sectional study. Body composition was assessed using dual-energy X-ray-absorptiometry (DXA). The diagnosis of sarcopenia was based on the Baumgartner criteria. DPN was assessed by Neuropathy symptom score (NSS) and Neuropathy disability score (NDS), and the severity of neuropathy was divided into non-neuropathy symptom (NS), Mild NS, Moderate NS and Severe NS according to NSS. Logistic regression analyses were carried out to determine the relations of sarcopenia and DPN in patients with T2DM and NSS in patients with DFD, respectively. RESULTS: The prevalence of DPN was 80.0% in T2DM patients with sarcopenia and 70.3% in non-sarcopenia patients (P=0.007). Logistic regression analyses showed DPN was one of the independent risk factors for sarcopenia in T2DM patients (OR 1.564 [95% CI: 1.004, 2.435], P=0.048). The prevalence of DPN had no statistical significance in DFD patients with or without sarcopenia. However, the NSS of DFD patients with sarcopenia was higher than that of non-sarcopenia patients. In the multivariate logistic regression analysis, NSS was determined to be associated with sarcopenia in DFD patients (OR 1.387[95% CI: 1.074, 1.789], P=0.012). The appendicular lean mass (ALM) of DFD patients without NS was higher than patients with mild, moderate and severe NS (20.71±2.73 vs 16.57±3.62 vs 17.99±3.54 vs 17.23±3.29 Kg, P=0.028). CONCLUSION: DPN is an independent risk factor for sarcopenia in patients with T2DM and NSS is also independently correlated with sarcopenia in patients with DFD, with the latter being more obvious with the aggravation of neurological symptoms in DFD patients.

[Photo-physiological and photo-biochemical characteristics of several herbaceous and woody species based on FvCB model]. / 基于FvCBæ¨¡åž‹çš„å‡ ç§è‰æœ¬å’Œæœ¨æœ¬æ¤ç‰©å ‰åˆç”Ÿç†ç”ŸåŒ–ç‰¹æ€§.

To explore the photosynthetic capacity and the leaf photosynthetic apparatus for plants with different life forms, CO2 response curves of 7 woody species and 4 herbaceous species were fitted by the modified rectangular hyperbolic model and the FvCB model, and the photosynthetic parameters, including maximum net photosynthetic rate (Pn max), maximal Rubisco carboxylation rate (Vc max), maximal electron transport rate (Jmax), day respiration (Rd), and mesophyll resistance to CO2 transport (rm), were compared among different woody species, among different herbaceous species, and between woody and herbaceous life-forms, respectively. The results showed Pn max of seven woody species descended in the order of Sapium sebiferum and Boehmeria nivea ＞ Machilus pingii and Pittosporum tobira ＞ Cyclobalanopsis glauca, Castanopsis sclerophylla, and Quercus nuttallii. Vc max of S. sebiferum, B. nivea, M. pingii, and P. tobira was significantly higher than that of C. glauca and C. sclerophylla. Jmax of woody species was in descending order as S. sebiferum ＞ B. nivea and P. tobira ＞ Q. nuttallii, C. sclerophylla, and C. glauca. rm of M. pingii and C. sclerophylla was higher than that of S. sebiferum, P. tobira and B. nivea. Pn max of Phytolacca acinosa was significantly higher than that of Ageratum conyzoides and Achyranthes aspera. There was no significant difference in Vc max among 4 herbaceous species. Jmax of P. acinosa was higher than that of A. conyzoides. rm of S. nigrum and A. aspera was higher than that of A. conyzoides. Rd of P. acinosa was higher than that of A. conyzoides and A. aspera. The photosynthetic parameters (Pn max, Vc max, Jmax and rm) of woody species were significantly higher than those of herbaceous species, but no significant difference was found in Rd between woody and herbaceous species. In conclusion, the difference in photosynthetic capacity among different species and between the two plant life-forms resulted from the difference in Rubisco carboxylation capacity, electron transport capacity, and mesophyll resistance among these species.

The effects of dried root aqueous extract of Salvia miltiorrhiza and its major ingredient in acceleration of orthodontic tooth movement in rat.

OBJECTIVES: Salvia miltiorrhiza (SM) is a popular and classic herb in traditional Chineses medicines. The objective is to confirm the effects of aqueous extract of S. miltiorrhiza (ESM) and its main ingredient on the promotion of orthodontic tooth movement and healing of periodontal ligament in rat. MATERIALS AND METHODS: Male Sprague-Dawley rats (n= 150) were divided into five groups: model control group (0.5 ml/kg phosphate-buffered saline (PBS) injection), ESM group (0.75 g/kg/day of crude drugs) and Danshensu subgroups (250, 500, 750 mg/kg/day of body weight). All rats were administered intramuscularly into the buccal vestibular mucosa of first molar of left maxillary. The indicators such as the moving distance of orthodontic tooth, nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) expression and osteoclasts were tested. RESULTS: The expressions of RANKL and OPG in the treatment groups were obviously enhanced compared with control group (P<0.05). The increase rate of OPG expression was slower than that of RANKL. But, RANKL decreased conspicuously after no orthodontic pressure was applied, especially in the treatment groups (Danshengsu high dose group at day 30: 2.17 versus 3.47 of control, P<0.01). ESM groups promoted osteoclasts proliferation in the first 20 days. CONCLUSION: There is a relationship between RANKL/OPG ratio and the number of osteoclasts. ESM might accelerate periodontal alteration of rat orthodontic tooth via producing more osteoclasts.

Effects of dipolar interaction on magnetic properties of Fe(x)(SiO2)1-x nanocomposites.

The effects of dipolar interaction on the magnetic properties of the Fe(x)(SiO2)1-x nanocomposites (22 wt% < or = x < or = 51 wt%) synthesized by mechanochemical reduction reaction have been studied by Mössbauer spectroscopy and magnetic measurements. As the average particle size of the Fe particles in the Fe(x)(SiO2)1-x nanocomposites changes very little with increasing Fe content x, the dipolar interaction strength can be tuned by adjusting the distance between the Fe particles through controlling the Fe content x. Thus the effects of dipolar interaction on the magnetic properties of the Fe(x)(SiO2)1-x nanocomposites can be clearly studied. Due to the dipolar interaction, the Fe particles transit from superparamagnetic state to the blocked state. With x increasing from 22 wt% to 48 wt%, due to dipolar interaction, the Fe particle moment arrangements change from random orientation to ordered arrangements, which induced an additional anisotropy, leading to the increase in the coercivity H(c) and remanence ratio M(r)/M(s). For x increasing beyond 48 wt%, the dipolar interaction strength further increases, and the Fe particle moment arrangements tend to form the flux-closure configurations in order to reduce the dipolar interaction energy among the particles, which result in the decreases of H(c) and M(r)/M(s) with increasing x.

Structure and microwave characteristics of Co/TiO2 nanocomposites prepared by ball milling.

Co/TiO2 nanocomposites were fabricated via direct ball milling. The structure and microwave characteristics of the Co/TiO2 nanocomposites were investigated. The results show that the hcp and fcc Co phases coexist in the nanocomposites for a long milling duration. The accumulation of the stacking faults in Co and the increase of the Co/TiO2 interfaces were detected by nuclear magnetic resonance. The measured relative complex permittivity of the ComTiO2 nanocomposite-paraffin wax mixture indicates that a high electrical resistivity and a dielectric loss exist in the Co/TiO2 nanocomposites. The dielectric loss mainly results from the polarisation of the metal/insulator interfaces. The imaginary part of the relative complex permeability of the mixture exhibits a broad resonance peak at 5.1 GHz which originates from the natural resonance in Co. The broadening of the resonance peak can be attributed to the fluctuating magnetocrystalline anisotropy at the stacking faults and interfaces regions. The calculated reflection loss curves show that the minimal reflection loss value of the Co/TiO2 nanocomposite-paraffin wax mixture can reach -32 dB at 4.0 GHz with a 3 mm sample thickness. The improved microwave absorption properties may result from the high electrical resistivity, dielectric loss and natural resonance.

[Follow-up study of mental developments in high-risk children].

OBJECTIVE: To study the mental developments in high risk children and the impact of the high risk factors on neurologic abnormalities, mental defect and long-term outcome. METHODS: The mental development of 122 children who had been exposed to high-risk factors and treated between March 1994 to May 1995 during their newborn periods was evaluated. Gesell development scales were performed when they were at 6 and 12 months old. And Wechsler intelligence scales for children (Chinese version) were performed at 6 approximately 7 years old. RESULTS: The children exposed to hypoglycemia during their newborn period and preterm labor had significantly lower IQ, VIQ and PIQ scores (P <0.05). The other risk factors in order were low birth weight, severe anoxia, asphyxia at birth, erythrocythemia, hyperbilirubinemia. There was significant difference between the children exposed to one risk factor and those exposed to two or more risk factors (P <0.05). And there was significant correlation between developmental assessment at 6 and 12 months and mental development at 6 approximately 7 years old (P<0.01). CONCLUSION: The impact of the high risk factors at birth on children's mental development is not negligible. And the risk of development abnormalities will increase if the children were exposed to multiple risk factors. The evaluation of development at 6 approximately 12 months is of predictive value for long-term outcome.

Follow-up study of mental developments in high-risk children / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the mental developments in high risk children and the impact of the high risk factors on neurologic abnormalities, mental defect and long-term outcome.</p><p><b>METHODS</b>The mental development of 122 children who had been exposed to high-risk factors and treated between March 1994 to May 1995 during their newborn periods was evaluated. Gesell development scales were performed when they were at 6 and 12 months old. And Wechsler intelligence scales for children (Chinese version) were performed at 6 approximately 7 years old.</p><p><b>RESULTS</b>The children exposed to hypoglycemia during their newborn period and preterm labor had significantly lower IQ, VIQ and PIQ scores (P <0.05). The other risk factors in order were low birth weight, severe anoxia, asphyxia at birth, erythrocythemia, hyperbilirubinemia. There was significant difference between the children exposed to one risk factor and those exposed to two or more risk factors (P <0.05). And there was significant correlation between developmental assessment at 6 and 12 months and mental development at 6 approximately 7 years old (P<0.01).</p><p><b>CONCLUSION</b>The impact of the high risk factors at birth on children's mental development is not negligible. And the risk of development abnormalities will increase if the children were exposed to multiple risk factors. The evaluation of development at 6 approximately 12 months is of predictive value for long-term outcome.</p>