OBJECTIVETo investigate aging-related ionic remodeling of L-type voltage dependent calcium channel (LVDCC) in left atria of canine.

METHODSSeven adult (2.0 - 2.5 years) and 10 aged (> 8 years) dogs were used. The current of LVDCC was recorded by patch clamp technique in the whole cell mode. The action potential duration (APD(90)), amplitude of action potential plateau (APA), I(Ca-L) peak current density of LVDCC were recorded. The mRNA and protein expressions of α1c subunit (Ca(V1.2)), sarcoplasmic reticulum Ca(2+)-ATPase (SECRA(2)), Calpain-I, ryanodine receptor (RYR(2)) were detected by quantitative RT-PCR and Western blot, respectively.

RESULTSI(Ca-L) peak current density [(-8.11 ± 0.54) pA/pF vs. (-14.04 ± 0.82) pA/pF, P < 0.05] was significantly reduced and action potential duration to 90% repolarization (APD(90)) significantly prolonged [(340.5 ± 10.1) ms vs. (320.0 ± 7.9) ms, P < 0.05] in aged group than in adult group. The mRNA gene expression level of Ca(V1.2) was significantly lower (0.90 ± 0.35 vs. 2.38 ± 0.40, P < 0.05) while mRNA expression of RYR(2) was significantly higher (4.39 ± 4.68 vs. 1.49 ± 1.69, P < 0.05) in the aged dogs than in the adult dogs. mRNA expression of SECRA(2) and Calpain-I was similar between the two groups. Similarly, the protein expression level of Ca(V1.2) was significantly lower (0.13 ± 0.10 vs. 0.29 ± 0.12, P < 0.05) while the protein expression level of RYR(2) was significantly higher (0.18 ± 0.21 vs. 0.08 ± 0.36, P < 0.05) in the aged dogs than in the adult dogs. Again, protein expression of SECRA(2), PLN(1) and Calpain-I was similar between the two groups.

CONCLUSIONThese data suggest that aging could induce mRNA and protein expression changes of Ca(V1.2) and RYR(2) of LVDCC which might serve as the molecular basis of I(Ca-L) remodeling in aged dogs and might be linked to the increased likelihood of developing atrial fibrillation (AF) in aged dogs.

Action Potentials ; Age Factors ; Animals ; Atrial Fibrillation ; metabolism ; physiopathology ; Calcium Channels, L-Type ; metabolism ; Dogs ; Heart Atria ; metabolism ; physiopathology ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Ryanodine Receptor Calcium Release Channel ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism

The present study aimed to investigate the mRNA expression levels of collagen, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) in the left and right atria in patients with chronic atrial fibrillation (CAF). Forty five patients with valvular heart disease were sampled in this study, including 18 patients with sinus rhythm (SR), 27 patients with CAF. Clinical data of these patients were collected, and the left and right atrial appendages were obtained from these patients during heart valvular replacement surgery. The mRNA levels of collagen type I, collagen type III, MMP1, MMP9, TMP1 of the atria were then measured by semi-quantitative RT-PCR. The results obtained were as follows. Compared to those in SR group, in atria of CAF group, the mRNA levels of collagen type I, MMP1 and MMP9 increased (P<0.05), while the mRNA level of TMP1 decreased (P<0.01). There were no significant differences in the mRNA levels of collagen type I, collagen type III, MMP1, MMP9 and TMP1 between the left and right atria of SR group (P>0.05). In CAF group, the mRNA level of MMP1 in the right atrium was higher than that in the left atrium (P<0.05), however, the mRNA level of MMP9 in the left atrium was higher than that in the right atrium (P<0.01). In both the left and right atria, the mRNA of collagen type I was positively correlated with the corresponding atrial diameter; the mRNA of MMP1 and MMP9 was positively correlated with the mRNA of collagen type I, and was negatively correlated with the mRNA of TMP1. These results suggest that the increased level of collagen type I associated with selective upregulation of MMP1, 9 and downregulation of TMP1, 9 in the atrium might be the molecular basis of atrial interstitial fibrosis in patients with CAF. Moreover, during CAF development, there is difference in the expression of MMPs between the left and right atria.
Aged ; Atrial Fibrillation ; physiopathology ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Heart Atria ; metabolism ; Humans ; Matrix Metalloproteinase 1 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; RNA, Messenger ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

OBJECTIVETo collect the data of measuring skin thickness of children of both genders of different ages and parts of body with non-invasive high-frequency ultrasound method.

METHODSTwo hundred and twenty-one children from 1 to 18 years of age,without systemic disease or injury in skin, were enrolled in the study and divided into 4 groups: i.e., infant group (112 years of age), pre-school age group (3-6 years of age), school age group (7-12 years for boys and 7-11 years for girls), adolescent age group (13-18 years for boys and 12-18 years for girls), and each group was subdivided into 2 groups according to the gender. The skin thicknesses of children in cheek, chest, abdomen, forearms, fundament and thigh was respectively measured by 13 MHz high-frequency ultrasound.

RESULTSThe region with thinnest skin in children was the cheek, and the thickest was the back and buttock. (1) There were no significant differences in thickness of skin in the same region between genders and also among different age groups (P > 0.05). (2) There were also no obvious differences of thickness of the dermis and the whole skin in the same region between male and female, or among infants, pre-school age and school age groups (P > 0.05). In adolescent group, the average thickness of dermis in male was (1.16 +/- 0.04 ) - (1.98 +/- 0.47) mm, the average whole thickness of skin in male was (1.27 +/- 0.12) - (2.20 +/- 0.45) mm, while those of female were (1.00 +/- 0.18) - (1.60 +/- 0.30) mm and (1.10 +/- 0.17) - (1.83 +/- 0.29) mm (P < 0.05).

CONCLUSIONIt is reliable to measure the skin thickness by 13MHz ultrasound as a non-invasive method. The main factor which determined the thickness of the skin is dermal thickness, especially in males. The significant differences of skin thickness among cheek, back and buttock provide the basis for us to choose the appropriate thickness of skin grafts harvested from different body parts.

Adolescent ; Child ; Child, Preschool ; Dermis ; diagnostic imaging ; Epidermis ; diagnostic imaging ; Female ; Humans ; Infant ; Male ; Sex Factors ; Skin ; diagnostic imaging ; Skinfold Thickness ; Ultrasonography

BACKGROUNDSmall noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins. However, their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood. The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF.

METHODSThree groups of dogs were studied: adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing. The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction. Pathohistological and ultrastructural changes were tested by light and electron microscopy. Apoptosis index of myocytes was detected by TUNEL.

RESULTSSamples of atrial tissue showed the abnormal pathohistological and ultrastructural changes, the accelerated fibrosis, and apoptosis with aging and/or in AF dogs. Compared to the adult group, the expressions of microRNAs-21 and -29 were significantly increased, whereas the expressions of microRNAs-1 and -133 showed obvious downregulation tendency in the aged group. Compared to the aged group, the expressions of microRNAs-1, -21, and -29 was significantly increased in the old group in AF; contrastingly, the expressions of microRNA-133 showed obvious downregulation tendency.

CONCLUSIONThese multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.

Age Factors ; Animals ; Apoptosis ; Atrial Fibrillation ; etiology ; Atrial Remodeling ; Connective Tissue Growth Factor ; physiology ; Dogs ; Electrocardiography ; Fibrosis ; In Situ Nick-End Labeling ; MicroRNAs ; analysis ; physiology ; Myocardium ; pathology ; ultrastructure

Objective: To conduct a knowledge survey on heart failure (HF) guidelines for HF diagnosis and treatment in physicians in China. Methods: A questionnaire including15 multiple-choice and 10 blank-filling questions was developed based on Chinese HF diagnosis and treatment guidelines 2014. The survey was conducted in physicians who registered at Chinese HF study from 88 hospitals in China and the knowledge level was presented by the correction rate of questionnaire survey. Results: A total of 2146 physicians finished the survey including 56.2％ female and 43.8％ male with the mean age of (35.6±7.6) years. The ratios of resident, attending physician, associate chief physician and chief physician were 28.2％, 43.6％, 20.3％ and 7.9％ respectively; the ratios of cardiovascular specialists, physician and general practitioners were 62.1％, 28.8％and 9.1％ respectively. Physicians from community hospital, 2nd grade hospital and 3rd grade hospital were 5.4％, 26.5％, and 68.2％ respectively. The correct answer for 15 multiple-choice questions was only 32.6％ and for 10 blank-filling questions regarding the target doses of anti-HF drugs was 42.5％. Physicians with the higher professional title had greater awareness of HF guidelines than those with the lower title, P<0.001. The compliance and command to HF guidelines were different among hospital levels, P<0.001; the command to HF prevention and treatment were different among physicians in different practice scopes, P<0.001. Conclusion: The knowledge for HF diagnosis and treatment had deficiency in physicians in China, further systemically study should be enforced.

ObjectiveTo observe that effect of Ersi decoction on rats with rheumatoid arthritis （RA） induced by using the complete Freund's adjuvant emulsion containing bovine type Ⅱ collagenand and elucidate underlying menchanisms involving to inhibit inflammation and joint synovial angiogenesis. MethodThe rat model of RA was established by immune induction with complete Freund's adjuvant emulsion containing bovine type Ⅱ collagen. All male SD rats were randomly divided into blank group， RA model group， methotrexate group（1.0 mg·kg^-1）， and low-， medium- and high-dose group（30，15，7.0 g·kg^-1·d^-1）of Ersi decoction， with 8 rats in each group. Except the blank group， rats in the methotrexate group and Ersi decoction groups were given corresponding doses of methotrexate and Ersi decoction after establishment of RA induced by strengthen immunity，respectively，and those in the model group and blank group received normal saline of equivalent volume，once a day for 28 days. After the administration， the degree of joint swelling of rats in each group was analyzed by joint swelling volume and index. The small animal ultrasound imaging system was used to detect the score and area of synovial hyperplasia of knee joint in right lower limb of rats and hematoxylin-eosin（HE）staining to observe the histomorphological changes in joint synovium of rats. The levels of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） were measured by enzyme-linked immunosorbent assay（ELISA）. Immunohistochemistry was employed to analyze the expression of CD31 and vascular endothelial growth factor receptor 2（VEGFR2） in in joint synovium. ResultCompared with the blank group， the model group demonstrated significant increase in joint swelling volume and index， inflammatory cytokines including TNF-α and IL-1β in serum， the score and area of synovial hyperplasia of knee joint in right lower limb， obvious pathological changes in the synovium and the expression of CD31 and VEGFR2 in joint synovium. Medium and high-dose Ersi decoction significantly alleviated the pathological changes of synovium tissue， attenuated joint swelling volume and index and decreased the expression of CD31 and VEGFR2 in joint synovium as compared with the model group. Moreover， high-dose Ersi decoction showed significantly lower levels of TNF-α and IL-1β in serum， and the score and area of synovial hyperplasia of knee joint in right lower limb. But medium-dose Ersi decoction only showed lower levels of TNF-α and area of synovial hyperplasia of knee joint. ConclusionErsi decoction could reduce synovial inflammation and hyperplasia through inhibiting synovial angiogenesis in rats with RA induced by bovine type Ⅱ collagen for achieving the effect of reducing RA joint damage， which provides an important reference for anti-RA of Ersi decoction in clinical application.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Stroke/drug therapy*

OBJECTIVETo investigate the association between the KCNE1 gene G38S and the KCNE4 gene E145D and atrial fibrillation in Uygur and Han populations living in Xinjiang.

METHODSKCNE1 gene G38S and the KCNE4 gene E145D genotype and frequency were determined using PCR restriction fragment length polymorphism (PCR-RFLP) in 488 atrial fibrillation patients (237 Uygur and 251 Han residents) and 488 age-and-gender matched controls (237 Uygur and 251 Han residents).

RESULTSGenotype and allele frequency of KCNE1 gene G38S were similar between atrial fibrillation group and control group in the Han population (P = 0.556, P = 0.946). In the Uygur population, there was a statistical difference between atrial fibrillation group and control group (P = 0.018, P = 0.003). Logistic regression analysis revealed the KCNE1 38 G was one of the independent risk factors for atrial fibrillation in the Uygur population (OR = 1.634, 95%CI: 1.192-2.240, P = 0.002). The KCNE4 gene E145D, genotype and allele frequency were significantly different between atrial fibrillation group and control group in the Uygur population and Han population (P = 0.041, P = 0.015;P = 0.032, P = 0.013) . Logistic regression analysis revealed the KCNE4 145D was one of the independent risk factors for atrial fibrillation in the Uygur population and Han population (OR = 1.636, 95%CI:1.173-2.281, P = 0.004; OR = 1.491, 95%CI:1.076-2.065, P = 0.016) .

CONCLUSIONSKCNE1 G38S is not associated with atrial fibrillation in the Han population while the KCNE1 G38S is associated with atrial fibrillation in the Uygur population. KCNE4 gene E145D is associated with atrial fibrillation in both Uygur population and Han population.

Aged ; Asian Continental Ancestry Group ; genetics ; Atrial Fibrillation ; ethnology ; genetics ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Potassium Channels, Voltage-Gated ; genetics ; Risk Factors