The CnB1 p.D102A variant is linked to dilated cardiomyopathy via impaired Calcineurin activity.

BACKGROUND: The role of calcineurin (protein phosphatase 2B (PP2B)) in the pathogenesis of human dilated cardiomyopathy (DCM) has not been fully elucidated. We determined the potential involvement of calcineurin in the pathogenesis of DCM caused by mutations in CnB1, a subunit of calcineurin. METHODS: By whole-exome sequencing, we identified a new CnB1 variant in a Han Chinese proband with cardiomyopathy from a 3-generation family with 2 normal individuals and 3 individuals with familial dilated cardiomyopathy. The potential pathogenic variant was validated by Sanger sequencing. We performed functional and mechanistic experiments in a CnB1-knockin (KI) mouse model and at the cellular level. RESULTS: We detected a rare heterozygous CnB1 variant (p.D102A) in a proband with dilated cardiomyopathy. This variant was localized to the EF hand 3 region of CnB1, where no variants have been previously reported. KI mice harboring the p.D102A variant exhibited decreased cardiac function and cardiac dilatation. Immunoblotting, RT-PCR and immunofluorescence results showed decreased cardiomyocyte size and heart failure-related protein expression. A calcineurin activity assay demonstrated decreased calcineurin activity in the KI mice, accompanied by the decreased ability of CnB1 to bind CnA. CONCLUSIONS: CnB1 p.D102A is a disease-associated variant that confers susceptibility to cardiac dilatation. This variant is associated with impaired calcineurin activity and a subsequent decrease in the ability of CnB1 to bind CnA.

[Summary of clinical research progression of apatinib combined with docetaxel in second-line treatment of advanced gastric cancer].

Objective: To investigate the progression-free survival (PFS) and safety of apatinib combined with docetaxel treated patients with advanced gastric cancer after failure of first-line chemotherapy. Methods: From March 2017 to May 2018, 23 patients with advanced gastric cancer who had received a failure of first-line chemotherapy (either fedocetaxel or paclitaxel) were treated with apatinib combined with docetaxel. The short-term efficacy and safety of the patients were observed. Results: The therapeutic effects of 20 patients were evaluated. Among them, 4 cases were partial response (PR), 13 patients were stable disease (SD), 3 patients were progressive disease (PD). The objective remission rate (ORR) was 20.0%, the disease control rate (DCR) was 85.0%, the median PFS (mPFS) was 4.5 months. The main adverse reactions were hypertension, vomiting and weakness. Conclusion: Apatinib combined with docetaxel applied in the second-line treatment of gastric cancer is safe and effective.

[Development and application syndromic surveillance and early warning system in border area in Yunnan Province].

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

Improving rowing performance by adjusting oar blade size and angle.

The principal aim of the work presented here is to investigate and demonstrate that a forward tilted rowing blade would result in a more efficient and effective motion of the blade through the water that would result in a higher boat speed when an equal input power is provided. A 1:5 scaled rowing boat is used to determine the performance of rowing blades with different sizes and blade angles. This is used to validate the results of a previous study where the optimal blade angle of 15 ∘ with respect to the oar shaft was determined ( 1). The input power and speed of the rowing boat can be compared between original and modified oar blades. Measurements in a towing tank demonstrate that a modified rowing blade result in faster rowing by 0.4% at the same input power. Maintaining the same stroke rate, the improvement of the blade efficiency is compensated by using a 4-6% increased blade area to yield the same input power.

Improvement of conversion efficiency for multi-junction solar cells by incorporation of Au nanoclusters.

We studied the photoluminescence (PL) and photovoltaic current-voltage characteristics of the three-junction InGaP/InGaAs/Ge solar cells by depositing Au nanoclusters on the cell surface. The increases of the PL intensity and short-circuit current after incorporation of Au nanoclusters are evident. An increase of 15.3% in energy conversion efficiency (from 19.6 to 22.6%) is obtained for the three-junction solar cells in which Au nanoclusters have been incorporated. We suggest that the increased light trapping due to radiative scattering from Au nanoclusters is responsible for improving the performance of the three-junction solar cells.

Artificial vascular graft for inferior vena cava reconstruction in living donor liver transplantation: a case report.

Artificial grafts are not recommended because of the high incidence of thrombogenic effects. However, in some situations, such as emergency or when no vascular bank is available, an artificial graft must be used. We present a case in which a polytetrafluoroethyline graft was used as a conduit to reconstruct the retrohepatic vena cava severed during living donor liver transplantation (LDLT). A 48-year-old woman had end-stage primary biliary cirrhosis for 5 years received a right lobe liver graft from her son. The retrohepatic vena cava was divided and ligated in several sequences. The upper end of the severed retrohepatic vena cava retracted into the liver parenchyma. The lower end of the severed vena cava was distended, with multiple stitches. A 16-mm artificial graft was used as a conduit to replace the inferin vena cava for outflow reconstruction. The patient tolerated the complicated procedure well. No anticoagulant was used throughout the entire course. The patient has been well with excellent liver function after follow-up for more than 5 years. Magnetic resonance imaging and Doppler ultrasonographic studies showed good patency of the cava with no evidence of thrombosis. We suggest use of an artificial graft in living donor liver transplantation, in particular in urgent situations when autologous or allogeneic vessels are not available.

Automation model of sewerage rehabilitation planning.

The major steps of sewerage rehabilitation include inspection of sewerage, assessment of structural conditions, computation of structural condition grades, and determination of rehabilitation methods and materials. Conventionally, sewerage rehabilitation planning relies on experts with professional background that is tedious and time-consuming. This paper proposes an automation model of planning optimal sewerage rehabilitation strategies for the sewer system by integrating image process, clustering technology, optimization, and visualization display. Firstly, image processing techniques, such as wavelet transformation and co-occurrence features extraction, were employed to extract various characteristics of structural failures from CCTV inspection images. Secondly, a classification neural network was established to automatically interpret the structural conditions by comparing the extracted features with the typical failures in a databank. Then, to achieve optimal rehabilitation efficiency, a genetic algorithm was used to determine appropriate rehabilitation methods and substitution materials for the pipe sections with a risk of mal-function and even collapse. Finally, the result from the automation model can be visualized in a geographic information system in which essential information of the sewer system and sewerage rehabilitation plans are graphically displayed. For demonstration, the automation model of optimal sewerage rehabilitation planning was applied to a sewer system in east Taichung, Chinese Taiwan.

The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest.

Bu-Zhong-Yi-Qi-Tang (BZYQT), a Chinese herbal medicine, inhibited the proliferation of human hepatoma cell lines (Hep3B, HepG2 and HA22T) dose-dependently. The IC50s of BZYQT on the proliferation of Hep3B, HepG2 and HA22T were 432.5+/-31.8 microg/ml, 455.4+/-24.2 microg/ml, and 2284.3+/-77.2 microg/ml respectively on day 3. However, BZYQT did not significantly inhibit the proliferation of normal human hepatocytes (Chang liver, CCL-13) at the concentration under 5,000 microg/ml. Major compounds of BZYQT, including astragaloside IV, ginsenoside Rb1 and Rg1, saikosaponin a and c, and glycyrrhizin, have been identified. To investigate the key inhibitors of BZYQT. Hep3B cells were treated with BZYQT, individual major compounds of BZYQT, and mixture of major compounds in the same ratio as present in BZYQT. Significant inhibition of proliferation was detected in BZYQT and its major compounds mixture in a comparable level. Not any individual major compound examined could suppress the proliferation of Hep3B cells. This data indicated that there could be synergistic or additive effects of the ingredients in BZYQT. BrdU incorporation, cell cycle analysis and DNA fragmentation assay revealed that BZYQT suppressed the proliferation of hepatoma cells via G0/G1 cell cycle arrest and inhibition of DNA synthesis followed by apoptosis.

The use of dual phase 201Tl thyroid scan for equivocal fine-needle aspiration results in cold thyroid nodules.

We assessed the usefulness of dual phase 201Tl thyroid scan for equivocal fine-needle aspiration (FNA) biopsy results to differentiate malignant from benign lesions. The findings of the dual phase 201TI thyroid scan were compared with those of surgical histopathology for 27 patients with cold thyroid nodules. The FNA results were assessed and classified by experienced pathologists equivocal ENS results. Dual phase thyroid scan, including an early image and a delayed image, were acquired 10 minutes and 3 hours, respectively after mCi (74 MBq) of 201TI was injected intravenously. Dual phase 201Tl thyroid scan findings were visually interpreted as positive or negative results. Based on the final diagnoses of the surgical histopathology results, the dual phase Tl thyroid scan showed a sensitivity, specificity, and accuracy of 100%, 90%, and 96%, respectively. We concluded that dual phase Tl thyroid scan was very helpful in differentiating between benign and malignant thyroid nodules when FNA results were equivocal.

Usefulness of technetium-99m methoxyisobutylisonitrile liver single photon emission computed tomography to detect hepatocellular carcinoma.

Technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) has been shown to be useful in identifying several types of tumors, such as breast, lung and thyroid cancers. The usefulness of Tc-99m MIBI liver imaging in detecting hepatocellular carcinoma (HCC) is still controversial. In this study, 22 patients with HCC performed Tc-99m MIBI liver single photon emission computed tomography (SPECT). Twenty of 22 patients (90.9%) showed negative liver SPECT findings without significant Tc-99m MIBI uptake in HCC, and only 2 patients (9.1%) showed positive liver SPECT findings with significant Tc-99m MIBI uptake in HCC. In addition, no significant correlation between liver SPECT findings with sex, age, alpha feto-protein serum level, HCC differentiation, and virus hepatitis status was found. We concluded that Tc-99m MIBI liver SPECT is not a sensitive tool to detect HCC.

Changes in health conditions in the Huainan coal mine in the past three decades.

Health conditions in the Huainan Coal Mine have improved greatly since 1950. In particular, the work and living environments, the underground dust concentration, the water supply and waste disposal systems, and the nutritional value of miners' food have become much better. Thus the rates of occupational, infectious, and parasitic diseases and nutritional deficiency diseases have decreased considerably among miners. The decreases in the prevalence of anthracosilicosis and hookworm have been especially striking.

Gastrectomy for advanced gastric carcinoma with invasion to the serosa.

A review of gastrectomy for 332 patients who had advanced gastric cancer with serosal exposed (S2) or adjacent organs invaded (S3) was made. Simple gastrectomy (SG) was carried out in 144 patients while radical gastrectomy (RG), which consisted of systemic lymphadenectomy in addition to SG, was used for the other 188 patients. The type of gastrectomy was chosen arbitrarily by the surgeons except that SG was usually selected when some non-curable factors were present. The operative mortality of SG was 2.7% and that of RG was 3.2%. More lymphnodes could be obtained by RG. Of the 152 patients with S2 who received RG, 46.7% of metastatic lymphnodes could not be identified by SG, while of the 36 patients with S3, 75% of metastatic nodes would be misjudged if SG was carried out. The 5-year-survival rate of RG for stage 3 patients was 42.4% and that for stage 4 patients was 28.2%. Better postoperative long-term-survival was achieved by RG than SG in both stage 3 and 4 patients. When considering the curability of the gastrectomy, the best outcome in stage 3 patients was found in those who underwent an absolute curative resection. Of the stage 4 patients those who received an absolute non-curative resection had the worst result. We recommend that RG be the procedure of choice in treatment of serosal gastric cancer in the absence of non-curable factors. Other adjuvant therapies may be considered after an absolute non-curative gastrectomy in stage 4 serosal cancer patients when multiple non-curable factors were present.

Knockdown of neuropilin-1 suppresses invasion, angiogenesis, and increases the chemosensitivity to doxorubicin in osteosarcoma cells - an in vitro study.

OBJECTIVES: Neuropilin-1 (NRP-1) is a novel co-receptor for vascular endothelial growth factor (VEGF). NRP-1 expression in osteosarcoma tissues was significantly higher, and high NRP-1 expression was more frequently occurred in osteosarcoma tissues with advanced clinical stage, positive distant metastasis and poor response to chemotherapy. We tested a hypothesis that the NRP-1 gene plays a role in the invasiveness, angiogenesis and chemoresistance of human OS. MATERIALS AND METHODS: To determine the role of NRP-1 in OS, NRP-1 was stably transfected into the human OS cell line MG-63 to increase the NPR-1 level, and NRP-1 siRNA was stably transfected into the human OS cell line SaOS-2 to knockdown of NRP-1. The effect of NRP-1 on invasion and angiogenesis was assessed by Matrigel invasion assay and in vitro angiogenesis assay. Chemosensitivity to doxorubicin was assessed by MTT assay in the MG-63 and SaOS-2 cells following NRP-1 overexpression or siRNA-induced downregulation of NRP-1. RESULTS: The NRP-1 transfected MG-63 cells showed a markedly higher level of invasion in Matrigel invasion assay. The capillary-like structure formation of endothelial cells was also increased by coculture with the NRP-1 transfected MG-63 cells. On the contrary, the NRP-1 siRNA transfected SaOS-2 cells showed a markedly lower level of invasion in Matrigel invasion assay. The capillary-like structure formation of endothelial cells was also repressed by coculture with the NRP-1 siRNA transfected SaOS-2 cells. NRP-1 overexpression in MG-63 cells increased survival of cells after exposure to doxorubicin. In contrast, downregulation of NRP-1 expression in SaOS-2 cells markedly increased chemosensitivity after exposure to doxorubicin. CONCLUSIONS: We suggest that NRP-1 could be used as a biomarker for OS progression and a novel therapeutic or chemopreventive target for human OS treatment.