Spatiotemporal variations in cardiovascular disease mortality in China from 1991 to 2009.

BACKGROUND: In China, the spatiotemporal variations in cardiovascular disease (CVD) mortality are seldom characterized to understand their epidemiological features. It would be helpful to evaluate the performance of CVD-related interventions for subsequent adjustments. METHODS: The 2010 Census data as well as the coronary heart disease (CHD) and stroke mortality data from the Disease Surveillance Points (DSPs) were used to calculate the age standardized death rates (ASDRs) of CVD in the DSP counties during 1991-1995, 1996-2000, 2004-2005, and 2006-2009. The ordinary kriging (OK) method was used to estimate the county-level death rates of CHD and stroke and achieved satisfactory results. RESULTS: The goodness-of-fit between measured and estimated values of CVD mortality was significant at the 0.01 level (0.34 < R2 < 0.98). The counties with high CHD death rates (> 75 per 105) were located in the Northwest, North, and Northeast in 1991-2000 and then extended toward the North, Central, and South, yielding an inverted-triangle-shaped area in 2004-2009. The counties with a CHD death rate increase greater than 100% were concentrated in the Northeast and South. The Northeast-Southwest regions with a high stroke death rate gradient (> 150 per 105) narrowed in1991-2000, was followed by a slight expansion during 2004-2005, finally reducing in 2006-2009. The counties with a stroke mortality increase greater than 100% were scattered across the Northeast, Northwest, Central, and South. CONCLUSION: The epidemiological characteristics of both CHD and stroke mortality in China was spatiotemporally featured on the county level during 1991-2009.

Development of a protein-ligand-binding site prediction method based on interaction energy and sequence conservation.

We present a new method for predicting protein-ligand-binding sites based on protein three-dimensional structure and amino acid conservation. This method involves calculation of the van der Waals interaction energy between a protein and many probes placed on the protein surface and subsequent clustering of the probes with low interaction energies to identify the most energetically favorable locus. In addition, it uses amino acid conservation among homologous proteins. Ligand-binding sites were predicted by combining the interaction energy and the amino acid conservation score. The performance of our prediction method was evaluated using a non-redundant dataset of 348 ligand-bound and ligand-unbound protein structure pairs, constructed by filtering entries in a ligand-binding site structure database, LigASite. Ligand-bound structure prediction (bound prediction) indicated that 74.0 % of predicted ligand-binding sites overlapped with real ligand-binding sites by over 25 % of their volume. Ligand-unbound structure prediction (unbound prediction) indicated that 73.9 % of predicted ligand-binding residues overlapped with real ligand-binding residues. The amino acid conservation score improved the average prediction accuracy by 17.0 and 17.6 points for the bound and unbound predictions, respectively. These results demonstrate the effectiveness of the combined use of the interaction energy and amino acid conservation in the ligand-binding site prediction.

Atrial fibrillation increases sympathetic and parasympathetic neurons in the intrinsic cardiac nervous system.

BACKGROUND: Chronic atrial fibrillation (AF) leads to heterogeneous autonomic nerve innervation termed neural remodeling. The quantitative changes in neural density as a function of autonomic remodeling and its association with sustained AF has not been previously determined. METHOD AND RESULTS: Seven dogs (paced group) were chronically paced with electrodes sutured to the epicardium of left atrial appendages. Seven dogs (control animals) were not paced. All paced dogs developed sustained AF by 5 weeks of pacing. The fat pads on the atrial epicardium containing ganglionated plexuses (GP) were separated along with underlying myocardial tissue. Immunocytochemical techniques were used to identify the neurons immunoreactive to anti-tyrosine hydroxylase (TH) and anti-acetylcholine antibodies. After chronic AF, sympathetic and parasympathetic neurons in the atrial intrinsic cardiac ganglia increased significantly. In paced dogs, the density of sympathetic neurons was 3,022 ± 507 µm(2) /mm(2) in the right atrial GP (vs control P < 0.01), 8,571 ± 476 µm(2) /mm(2) in the ventral left atrial GP (vs control P < 0.0001)， 6,422 ± 464 µm(2) /mm(2) in the dorsal atrial GP (vs control P < 0.0001) and 5,392 ± 595 µm(2) /mm(2) in the inferior vena cava-inferior atrial GP (vs control P <0.0001), respectively. The density of parasympathetic neurons was 4,396 ± 877 µm(2) /mm(2) in the right atrial GP, 7,769 ± 465 µm(2) /mm(2) in the ventral left atrial GP， 7,016.47 ± 687 µm(2) /mm(2) in the dorsal atrial GP and 5,485 ± 554 µm(2) /mm(2) in the inferior vena cava-inferior atrial GP, respectively, which was higher than control cohorts in corresponding GP (P < 0.05). CONCLUSIONS: This study provides evidence for the remodeling in atrial intrinsic cardiac ganglia in the dogs with pacing induced AF. A significant increase of sympathetic and parasympathetic neurons was present in atrial intrinsic cardiac ganglia.

The effect of health education video on ocular massage after trabeculectomy.

The aim of this study was to investigate the effect of different ocular massage health education methods on ocular massage in glaucoma patients after trabeculectomy. Eighty-six patients with glaucoma after trabeculectomy (86 eyes) were randomly divided into two health education groups. One group was a watch video group (43 patients, 43 eyes), while the other was an orally taught health education group (43 patients, 43 eyes). Patients were followed up for 1 week, 1 month, and 3, 6, and 12 months after discharge. Records of the patient responses after health education, compliance of patients with follow-up, and intraocular pressure were determined. Measurements included intraocular pressure and differences between the watch video and orally taught health education groups. The differences between the watch video group and orally taught health education group were not statistically significant at 1 week and 1 month, while the differences were statistically significant at 3, 6, and 12 months. The results indicated that health education videos can enable glaucoma patients to have a better mastery of ocular massage after trabeculectomy. According to the needs of patients, health education video use produced good results and should be promoted.

Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Estimation of natural methane emissions from the largest oil sand deposits on earth.

Worldwide methane emission by various industrial sources is one of the important human concerns due to its serious climate and air-quality implications. This study investigates less-considered diffusive natural methane emissions from the world's largest oil sand deposits. An analytical model, considering the first-order methane degradation, in combination with Monte Carlo simulations, is used to quantitatively characterize diffusive methane emissions from Alberta's oil sands formations. The results show that the average diffusive methane emissions from Alberta's oil sands formations is 1.56 × 10-4 kg/m2/year at the 90th percentile of cumulative probability. The results also indicate an annual diffusive methane emissions rate of 0.857 ± 0.013 Million tons of CO2e/year (MtCO2e/year) from Alberta's oil sands formations. This finding suggests that natural diffusive leakages from the oil sands contribute an additional 1.659 ± 0.025 and 5.194 ± 0.079% to recent Canada's 2019 and Alberta's 2020 methane emission estimates from the upstream oil and gas sector, respectively. The developed model combined with Monte Carlo simulations can be used as a tool for assessing methane emissions and current inventories.

Feedback-AVPGAN: Feedback-guided generative adversarial network for generating antiviral peptides.

In this study, we propose Feedback-AVPGAN, a system that aims to computationally generate novel antiviral peptides (AVPs). This system relies on the key premise of the Generative Adversarial Network (GAN) model and the Feedback method. GAN, a generative modeling approach that uses deep learning methods, comprises a generator and a discriminator. The generator is used to generate peptides; the generated proteins are fed to the discriminator to distinguish between the AVPs and non-AVPs. The original GAN design uses actual data to train the discriminator. However, not many AVPs have been experimentally obtained. To solve this problem, we used the Feedback method to allow the discriminator to learn from the existing as well as generated synthetic data. We implemented this method using a classifier module that classifies each peptide sequence generated by the GAN generator as AVP or non-AVP. The classifier uses the transformer network and achieves high classification accuracy. This mechanism enables the efficient generation of peptides with a high probability of exhibiting antiviral activity. Using the Feedback method, we evaluated various algorithms and their performance. Moreover, we modeled the structure of the generated peptides using AlphaFold2 and determined the peptides having similar physicochemical properties and structures to those of known AVPs, although with different sequences.

Study on the mechanisms of action of berberine combined with fluconazole against fluconazole-resistant strains of Talaromyces marneffei.

Talaromyces (Penicillium) marneffei (T. marneffei) is a thermally dimorphic fungus that can cause opportunistic systemic mycoses. Our previous study demonstrated that concomitant use of berberine (BBR) and fluconazole (FLC) showed a synergistic action against FLC-resistant T. marneffei (B4) in vitro. In this paper, we tried to figure out the antifungal mechanisms of BBR and FLC in T. marneffei FLC-resistant. In the microdilution test, the minimum inhibitory concentration (MIC) of FLC was 256 µg/ml before FLC and BBR combination, and was 8 µg/ml after combination, the partial inhibitory concentration index (FICI) of B4 was 0.28. After the treatments of BBR and FLC, the studies revealed that (i) increase reactive oxygen species (ROS), (ii) reduce ergosterol content, (iii) destroy the integrity of cell wall and membrane, (iv) decrease the expression of genes AtrF, MDR1, PMFCZ, and Cyp51B however ABC1 and MFS change are not obvious. These results confirmed that BBR has antifungal effect on T. marneffei, and the combination with FLC can restore the susceptibility of FLC-resistant strains to FLC, and the reduction of ergosterol content and the down-regulation of gene expression of AtrF, Mdr1, PMFCZ, and Cyp51B are the mechanisms of the antifungal effect after the combination, which provides a theoretical basis for the application of BBR in the treatment of Talaromycosis and opens up new ideas for treatment of Talaromycosis.

Identification of prognostic genes and construction of a novel gene signature in the skin melanoma based on the tumor microenvironment.

ABSTRACT: Skin melanoma remains a highly prevalent and yet deadly form of cancer, with the exact degree of melanoma-associated mortality being strongly dependent upon the local tumor microenvironment. The exact composition of stromal and immune cells within this microenvironmental region has the potential to profoundly impact melanoma progression and prognosis. As such, the present study was designed with the goal of clarifying the predictive relevance of stromal and immune cell-related genes in melanoma patients through comprehensive bioinformatics analyses. We therefore analyzed melanoma sample gene expression within The Cancer Genome Atlas database and employed the ESTIMATE algorithm as a means of calculating both stromal and immune scores that were in turn used for identifying differentially expressed genes (DEGs). Subsequently, univariate analyses were used to detect DEGs associated with melanoma patient survival, and through additional functional enrichment analyses, we determined that these survival-related DEGs are largely related to inflammatory and immune responses. A prognostic signature comprised of 10 genes (IL15, CCL8, CLIC2, SAMD9L, TLR2, HLA.DQB1, IGHV1-18, RARRES3, GBP4, APOBEC3G) was generated. This 10-gene signature effectively separated melanoma patients into low- and high-risk groups based upon their survival. These low- and high-risk groups also exhibited distinct immune statuses and differing degrees of immune cell infiltration. In conclusion, our results offer novel insights into a number of microenvironment-associated genes that impact survival outcomes in melanoma patients, potentially highlighting these genes as viable therapeutic targets.

[Mechanism of α-lipoic acid promoting iron efflux in substantia nigra cells of Parkinson's disease rats].

Objective To observe the effect of α-lipoic acid (α-LA) on the expressions of iron regulatory protein 2 (IRP2) and ferroportin1 (FP1) in substantia nigra of rats with Parkinson's disease (PD) and explore the mechanism by which α-LA regulates iron efflux in substantia nigra cells of PD rat models. Methods Sixty healthy male SD rats were randomly divided into a sham group (n=15) and a model group (n=45). To establish the PD model, the rats of the model group were injected with 6-hydroxydopamine (6-OHDA) into their right striatum by the stereotactic technique, and the sham operation group was injected with the same dose of normal saline. Four weeks later, 30 model rats were randomly picked and divided into a PD model group (n=15) and a PD treatment group (n=15). The PD treatment group was intraperitoneally injected with α-LA (50 mg/kg) daily for 2 weeks, and the PD model group was given the same dose of saline. After 14 days of treatment, the left forelimb use rate was tested by cylinder test. The right middle cerebral substantia nigra was taken from each group, and the expression and distribution of tyrosine hydroxylase (TH) was detected by immunohistochemical staining; the number of iron positive cells was determined by Prussian blue staining; and the levels of IRP2 and FP1 were examined by Western blotting. Results Compared with the sham operation group, the left forelimb use rate of the PD model group was significantly reduced. The number of TH positive cells significantly decreased, and the number of iron positive cells in the substantia nigra significantly increased. The level of IRP2 significantly increased, and the level of FP1 decreased remarkably. Compared with PD model group, the left forelimb use rate of the PD treatment group was significantly raised. The number of TH positive cells was significantly elevated, and the number of iron positive cells in the substantia nigra was significantly reduced. The IRP2 level decreased and the FP1 level increased. Conclusion By decreasing the IRP2 level and via the IRP2/IRE pathway, α-LA can increase FP1 level, promote the outflow of iron ions from cells, and reduce iron deposition in the substantia nigra of PD model rats, thereby alleviating brain injury in PD rats induced by 6-OHDA.

Value of bedside high-flow continuous blood purificationcombined with Xuebijing in the treatment of severe sepsis / 中国医师进修杂志

Objective:To investigate the effect of bedside high-flow continuous blood purification (CBP) combined with Xuebijing in the treatment of severe sepsis (SS) and the influence on the patient′s coagulation-fibrinolysis index, immunity index and expression of peripheral blood Toll-like receptor 4 (TLR4).Methods:Ninety-three patients with SS who were admitted and treated in the Lianyungang First People′s Hospitalfrom January 2017 to October 2019 were selected. They were divided into the combined group (51 cases, treatment with bedside high-flow CBP and Xuebijing injection based on bundle therapy) and the control group (42 cases, treatment with Xuebijing injection based on bundle therapy). The changes in coagulation and fibrinolysis index, immunity index, biochemical index such as TLR4 before treatment and after 1 week of treatment were compared between the two groups. The incidences of complications in both groups were statistically analyzed, and the discharge time from ICU, mechanical ventilation time and 28-day mortality were recorded.Results:After 1 week of treatment, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the two groups were shortened, D-dimer (D-D) and fibrinogen (FIB) were decreased ( P<0.05); and the levels of PT and APTT in the combined group were shorter than those in the control group, the levels of DD and FIB were lower than those in the control group, there were statistical differences ( P<0.05). After 1 week of treatment, the levels of CD 4+ and CD 4+/CD 8+ ratio in both groups were increased ( P<0.05), and the levels of CD 4+ and CD 4+/CD 8+ ratio in the combined group were higher than those in the control group ( P<0.05). After 1 week of treatment, the levels of TLR4, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), blood lactate (Lac), blood urea nitrogen (BUN) and serum creatinine (Scr) in both groups were decreased ( P<0.05), meanwhile, the above indexes in the combined group were lower than those in the control group ( P<0.05). The incidence of multiple organ failure and the 28-day mortality rate in the combined group were lower than those in the control group: 3.92%(2/51) vs. 19.05%(8/42), 13.73%(7/51) vs. 30.95%(13/42), there were statistical differences ( P<0.05). The discharge time from ICU and mechanical ventilation time in the combined group were shorter than those in the control group: (12.35 ± 2.14) d vs. (14.17 ± 3.36) d, (7.12 ± 2.23) d vs. (8.51 ± 2.39) d, there were statistical differences ( P<0.05). Conclusions:Bedside high-flow CBP combined with Xuebijing injection in the treatment of SS can improve the patient′s condition, regulate the balance of coagulation and fibrinolysis, avoide the activation of coagulation, inhibite inflammatory response, reduce the expression of TLR4 in peripheral blood, improve immune function, protecte kidney function and promotethe patient′s recovery.

Research progress of bio-metal organic frameworks in drug delivery system / 中国药科大学学报

@#In recent years, bio-metal organic frameworks (Bio-MOFs) synthesized with biocompatible ligands have been widely investigated as a potential drug delivery carrier due to their large specific surface area and porosity, rich host-guest intermolecular interactions, and good biocompatibility.In this review, we summarized the design methods of Bio-MOFs including structural and toxic factors, as well as a variety of drug loading methods including click chemistry, with particular focus on recent research advances in Bio-MOFs for pulmonary drug delivery systems, improving pharmaceutical properties of drugs, sustained and controlled drug release, stimulation response and targeted drug delivery systems.Finally, we summarized the bottlenecks that constrain the development of Bio-MOFs in clinical studies of actual pharmaceutical formulations and their future directions for approved formulations, aiming to provide some theoretical reference for promoting the application of Bio-MOFs in drug delivery systems.

Long noncoding RNA MRAK088388 is involved in the progression of childhood allergic asthma via miR-30a/ATG5 axis / 西安交通大学学报(医学版)

【Objective】 To investigate the association between the long-stranded non-coding ribonucleic acid (lncRNA) MRAK088388 and allergic asthma in children. 【Methods】 A total of 15 healthy children and 15 children with asthma were monitored for disease progression over a 2-year period. Blood samples were collected from patients during the chronic phase of the disease for lncRNA/mRNA expression microarray analysis. Competing endogenous RNA networks (MRAK088388/miR-30a/ATG5) were identified by bioinformatics analysis. In vitro cultured bronchial epithelial (16HBE) cells were used to quantify gene and associated protein expression levels by real-time fluorescent quantitative polymerase chain reaction (qPCR) and protein blotting, respectively. Cell Counting Kit-8 and transwell assays were used to assess the proliferation and migration of 16HBE cells and verify the effects of MRAK088388, miR-30a and ATG5 on asthma. 【Results】 Six lncRNA-miRNA-mRNAs were identified by correlation analysis. By qRT-PCR analysis, MRAK088388/miR-30a/ATG5 was selected to construct the ceRNA network in this study. mRAK088388 and ATG5 expressions were high in the peripheral blood of children with asthma, while the expression of miR-30a was low (P<0.05). The expression level of E-cadherin was significantly higher in 16HBE cells after si-MRAK088388+TGF-β1 group, while the expression levels of Vimentin and α-SMA were significantly lower (P<0.05), indicating that knockdown of MRAK088388 inhibited the epithelial mesenchymal transition in 16HBE cells. Compared with si-NC+ TGF-β1 group, the cell morphology of si-MRAK088388+TGF-β1 group was similar to that of the control group, indicating that MRAK088388 knockdown attenuated TGF-β1-induced cell morphological changes; in addition, MRAK088388 knockdown inhibited TGF-β1-induced proliferation and migration of 16HBE cells. MRAK088388 was confirmed by qPCR and protein blotting to promote the progression of childhood asthma by targeting the miR-30a/ATG5 axis. 【Conclusion】 Childhood asthma is associated with the MRAK088388/miR-30a/ATG5 axis, and MRAK088388 is involved in the process of childhood allergic asthma by negatively regulating miR-30a expression and regulating elevated ATG5 expression levels to affect bronchial epithelial cell mesenchymal transition, proliferation, and migration.

Inhibition of M2 macrophage polarization and reduction of airway inflammation in asthmatic mice with lncRNA MRAK088388 knockout / 细胞与分子免疫学杂志

Objective To investigate the long non-coding RNA(lncRNA) MRAK08838 regulates macrophage function to influence the development of asthmatic airway inflammation. Methods MRAK088388 gene knockout (MRAK088388-/-) mouse model was prepared and allergic asthma was induced by dust mite protein Dermatophagoides farinae 1 (Der f1). The mice were sacrificed after 28 days of modeling, and serum was collected to measure IgE and IgG. The FinePointe RC system was used to measure airway hyperresponsiveness and evaluate lung function in mice. Lung tissue was taken for HE staining, and periodic acid-Schiff (PAS) staining was used to evaluate inflammatory infiltration and mucus secretion in mouse lungs. Fluorescence quantitative PCR was used to detect the expression level of lncRNA MRAK08838 in bronchoalveolar lavage fluid (BALF) cells and lung tissue of asthmatic mice. ELISA was used to detect the levels of inflammatory cytokines IFN-γ, IL-4, IL-5, IL-13, IL-10 and IL-17A. Flow cytometry was used to evaluate the phenotype of macrophages in BALF and lung tissue, as well as the proportion of neutrophils, eosinophils, and alveolar macrophages. The changes of the above indicators were detected in mice by adoptive transfer of bone marrow-derived macrophages (BMDM). Results Under the challengle of Der f1, MRAK088388-/- mice showed reduced allergic airway inflammation, including reduced eosinophils in BALF and reduced production of IgE and IgG1. In addition, Der f1-treated MRAK088388-/- mice had fewer M2 macrophages than wild-type asthmatic mice. Wild-type mouse BMDM (M0) and Der f1-treated MRAK088388-/- mice also showed mild inflammatory response. Conclusion Knockout of MRAK088388 alleviates airway inflammation in asthmatic mice by inhibiting M2 polarization of airway macrophages.

Thoughts on the timing of targeted therapy initiation for thyroid cancer / 中华核医学与分子影像杂志

The treatment of persistent/recurrent and metastatic thyroid cancer and medullary thyroid cancer has made significant progress through the use of molecule-targeted therapy. While this approach has shown promise in improving patient outcomes and clinical symptoms, it also carries potential risks. The primary focus and challenge of targeted therapy is to optimize benefits while managing risks within predetermined thresholds. This review examines current targeted treatment practices in thyroid cancer and investigates the correlation between the timing of targeted therapy initiation and the patient benefits, aiming to lay the groundwork for subsequent research.

Clinical application of non-invasive myocardial work imaging in ST-segment elevation myocardial infarction patients with left ventricular remodeling after percutaneous coronary intervention / 中华超声影像学杂志

Objective:To explore the application value of non-invasive myocardial work imaging in evaluating the cardiac function of ST-segment elevation myocardial infarction (STEMI) patients with left ventricular remodeling (LVR) after percutaneous coronary intervention (PCI).Methods:One hundred and twenty-six patients with STEMI undergoing PCI in General Hospital of Ningxia Medical University from December 2021 to September 2022 were prospectively collected and divided into left ventricular remodeling group (LVR group, 34 cases) and non left ventricular remodeling group (NLVR group, 92 cases) according to whether there was left ventricular remodeling 3 months after surgery. General data were collected. Routine echocardiography and noninvasive myocardial work imaging were performed before, 1 week, 1 month, and 3 months after surgery, the differences in the above parameters between the two groups were compared. Pearson correlation analysis was used to analyze the correlation between the indicators.Logistic regression analysis was used to determine the independent risk factors of left ventricular remodeling after STEMI, and a predictive model was obtained. The diagnostic value of the model was judged by ROC curve.Results:①General information comparison: There were statistically significant differences between the two groups in BMI, systolic blood pressure, diastolic blood pressure, average number of stents implanted, and history of hyperlipidemia (all P<0.05), but there was no significant difference in other data (all P>0.05). There was no statistically significant difference in two-dimensional transthoracic echocardiography (2D-TTE) parameters and non-invasive myocardial work (MW) parameters between the two groups before and 1 week after operation (both P>0.05). ②2D-TTE parameter comparison: LVESV and LVEDV at 3 months after PCI in the LVR group were significantly higher than those in the NLVR group, and LVEF and E/A were significantly lower than those in the NLVR group (all P<0.05); There were no significant differences in other indexes between the two groups by conventional echocardiography at 3 months after PCI(all P>0.05). ③Comparisons of noninvasive myocardial work parameters: GLS, GWE, GWI, GCW at 1 month and 3 months after PCI in the LVR group were significantly lower than those in the NLVR group, and GWW were significantly higher than those in the NLVR group ( P<0.001). ④Correlation analysis: GLS, GWE, GCW, GWI and LVEDV were negatively correlated at 1 month after operation ( r=-0.42, -0.38, -0.50, -0.53, all P<0.001), GWW was positively correlated with LVEDV ( r=0.45, P<0.001). ⑤Logistic regression analysis: GLS<17%, GCW<1 900 mmHg%, GWW>105 mmHg%, and GWE<90 mmHg% at 1 month after PCI were independent predictors for LVR in STEMI patients after PCI (all P<0.05). The predictive model was Logit (P)=0.692GLS+ 0.804GCW+ 0.972GWW+ 0.880GWE. The AUC of this model was 0.886, 95% CI=0.845-0.926, which was significantly higher than single index, the sensitivity was 0.86, and the specificity was 0.79. Conclusions:GLS, GWE, GWI, GCW are positively correlated with LVR, while GWW is negatively correlated with left ventricular remodeling. Noninvasive myocardial work parameters are independent risk factors for left ventricular remodeling in patients with STEMI after PCI surgery. This technique can be used to evaluate LVR and has great clinical application value.

Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling / 中国结合医学杂志

OBJECTIVE@#To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).@*METHODS@#According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.@*RESULTS@#EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.@*CONCLUSION@#EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity and pulse pressure on all-cause mortality / 中华心血管病杂志

Objective: To evaluate the impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP) on all-cause mortality. Methods: This study is a prospective cohort study. Individuals participated in the Kailuan Study and completed baPWV measurements between 2010 and 2016 were included in this study. After stratifying by sex, 75th percentile baPWV and PP values for different age group were calculated at five years interval. BaPWV and PP values below the 75th percentile were defined as normal, and those above or equal to the 75th percentile were defined as increased. The participants were allocated to four groups according to their PP and baPWV status: normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group. The primary outcome was all-cause mortality during the follow-up period. Cox proportional hazards models were used to explore the impact of individual and combined assessment of baPWV and PP on all-cause mortality events. Results: A total of 39 339 participants were enrolled in this study, aged (49.3±12.8) years, of which 28 731 (73.03%) were males. There were 23 268, 6 025, 6 210 and 3 836 cases in the normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group, respectively. The average follow-up duration was (4.98±2.53) years. During the follow-up period, all-cause mortality occurred in 998 individuals. Multivariate Cox regression analysis showed increased risk of all-cause mortality in the high baPWV/normal PP group (HR=1.27, 95%CI 1.07-1.50), and in the high baPWV/PP group (HR=1.33, 95%CI 1.08-1.65) compared to the normal baPWV/PP group. Increased pulse pressure alone had no impcat on all-cause death (HR=1.06, 95%CI 0.87-1.29). Conclusions: The risk of all-cause mortality significantly increases with increased age-and sex-specific baPWV and PP values. BaPWV may be a better predictor of all-cause mortality than PP in this cohort.

Correlation Analysis of Molecularly-Defined Cortical Interneuron Populations with Morpho-Electric Properties in Layer V of Mouse Neocortex / 神经科学通报·英文版

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis / 中国中药杂志

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.