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Self-germinated seedlings of Citrus sinensis and C. grandis were supplied with nutrient solution with 0 mM AlCl(3)·6H(2)O (control, −Al) or 1 mM AlCl(3)·6H(2)O (+Al) for 18 weeks. The DW (Dry weights) of leaf, stem, shoot and the whole plant of C. grandis were decreased and the ratio of root DW to shoot DW in C. grandis were increased by Al, whereas these parameters of C. sinensis were not changed by Al. Al treatment dramatically decreased the sulfur (S) content in C. grandis roots and the phosphorus (P) content in both C. sinensis and C. grandis roots. More Al was transported to shoots and leaves in C. grandis than in C. sinensis under Al treatment. Al treatment has more adverse effects on C. grandis than on C. sinensis, as revealed by the higher production of superoxide anion (O(2)(·−)), H(2)O(2) and thiobarbituric acid reactive substace (TBARS) content in C. grandis roots. Via the Illumina sequencing technique, we successfully identified and quantified 12 and 16 differentially expressed miRNAs responding to Al stress in C. sinensis and C. grandis roots, respectively. The possible mechanism underlying different Al tolerance of C. sinensis and C. grandis were summarized as having following aspects: (a) enhancement of adventitious and lateral root development (miR160); (b) up-regulation of stress and signaling transduction related genes, such as SGT1, PLC and AAO (miR477, miR397 and miR398); (c) enhancement of citrate secretion (miR3627); (d) more flexible control of alternative glycolysis pathway and TCA cycle (miR3627 and miR482); (e) up-regulation of S-metabolism (miR172); (f) more flexible control of miRNA metabolism. For the first time, we showed that root development (miR160) and cell wall components (cas-miR5139, csi-miR12105) may play crucial roles in Al tolerance in citrus plants. In conclusion, our study provided a comprehensive profile of differentially expressed miRNAs in response to Al stress between two citrus plants differing in Al tolerance which further enriched our understanding of the molecular mechanism underlying Al tolerance in plants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12298-020-00895-y) contains supplementary material, which is available to authorized users.

Mitochondrial abnormalities play critical roles in diabetic tubular injury progression. Dipeptidyl peptidase-4 (DPP4) inhibitors are widely used antihyperglycemic agents that exert renal protective and positive effects against mitochondrial dysfunction in diabetic kidney disease (DKD). However, their underlying mechanism remains unclear. In this study, DPP4 upregulation, mitochondrial fragmentation, and altered mitochondrial dynamics-associated protein expression were observed in the tubules of DBA2/J (D2) diabetic mice with unilateral nephrectomy and in albumin-stimulated tubular cells. The inhibition of DPP4 by sitagliptin (Sita) ameliorated these mitochondrial perturbations both in vivo and in vitro, whereas DPP4 overexpression aggravated mitochondrial fusion-fission disorder and tubular cell injury in albumin-treated HK-2 cells. Downstream of DPP4, the SDF-1α/CXCR4 pathway was significantly suppressed in diabetic tubules. After Sita treatment, this signaling pathway was restored, and the mitochondrial dynamics was improved. Furthermore, a direct interaction between STAT3 and OPA1 was found in the mitochondria of tubular cells, and this effect was weakened by overloading albumin and by CXCR4 siRNA treatment, suggesting a possible link between DPP4-mediated SDF-1α/CXCR4/STAT3 signaling and mitochondrial dysfunction in diabetic tubular cells. The results suggest that a novel mechanism links the DPP4 enzyme to impaired mitochondrial dynamics homeostasis during tubular injury in DKD and highlight that the SDF-1α/CXCR4/STAT3 signaling pathway could become a potential target for managing DKD.

A retrospective study on complete blood count (CBC) with differential results of patients who presented to the fever clinic of Tongji Hospital with symptoms of COVID-19-like illness between February 1, 2020 and February 20, 2020 was performed through case reviewing Inclusion criteria were fever with a body temperature above 37 3 degreesC, accompanied or not accompanied by cough, chest tightness, muscle ache, shortness of breath and diarrhea Patients with hematopathy, cancer and sepsis were excluded The SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing of throat swab was performed in the laboratory of Tongji Hospital These patients with COVID-19-like symptoms were divided into two groups Patients diagnosed with COVID-19 according to the WHO interim guidance and confirmed by RT-PCR testing were included in the SARS-CoV-2-positive patient group (SPPG) Patients with two or more consecutive negative RT-PCR test results were included in the SARS-CoV-2-negative patient group (SNPG) Patients with co-infection of SARS-CoV-2 and other respiratory viruses including influenza A/B, respiratory syncytial virus and adenovirus were also excluded in SPPG Sysmex XN-9000 hematology analyzer was used to obtain the CBC with differential results for patients in each group CBC with differential results at the request of clinicians at the initial evaluations was recorded along with age and gender for each patient Decreased WBC*LYM was observed in SARS-CoV-2-infected patients compared with SARS-CoV-2-negative patients with suspected symptoms in this study WBC*LYM can be used as a supplementary parameter to help clinicians in their first contact with suspected patients awaiting SARS-CoV-2 RT-PCR results

Since December 2019, the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has spread to many countries around the world, developing into a global pandemic with increasing numbers of deaths reported worldwide. To data, although some vaccines have been developed, there are no ideal drugs to treat novel coronavirus pneumonia (coronavirus disease 2019 (COVID-19)). By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide, this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2. We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage (DAD) of the lungs and microthrombus formation, resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure. Although direct evidence of viral infection can also be found in other organs and tissues, the viral load is relatively small. The conclusion that the injuries of the extra-pulmonary organs are directly caused by the virus needs further investigation.

Background To predict the risk and severity of acute respiratory distress syndrome (ARDS) following severe acute pancreatitis (SAP) by artificial neural networks (ANNs) model. Methods ANNs model was constructed by clinical data of 217 SAP patients. The model was first trained on 152 randomly chosen patients, validated and tested on the 33 patients and 32 patients respectively. Statistical analysis was used to assess the value of it. Results The training, validation, and test set were not significantly different for 13 variables. After training, ANNs retained excellent pattern recognition ability. When ANNs model was applied to the test set, it revealed a sensitivity of 87.5%, and an accuracy of 84.43%. Significant differences were found between ANNs model and logistic regression model. When ANNs model is used to identify ARDS, the area under ROC was 0.859 + 0.048. Meanwhile, pancreatic necrosis rate, lactic dehydrogenase and oxyhemoglobin saturation were the most important independent variables. Compared with the Berlin definition, the ANN model shows a good accuracy of 73.1% for total severity of ARDS. Conclusion ANNs model is a valuable tool in dealing with risk prediction of ARDS following SAP. In addition, it can extract informative risk factors of ARDS via the ANNs model.

Low cell tolerance is a basic issue in high-glucose fermentation under high temperature to economically obtain high product titer. Candida glycerinogenes, an industrial yeast, has excellent tolerance to the combined heat and high-glucose stress than Saccharomyces cerevisiae. The potential mechanism responsible for the high tolerance was illustrated here. The transcription of the potential stress-responsive genes in two strains were varied under single stress (heat or high-glucose), especially the ribosome-related genes. Unlike S. cerevisiae, C. glycerinogenes up-regulated 17 genes, including most of the single stress responsive genes, and genes Avt1 and Pfk1 under the combined stress, indicating a more systematic stress-responsive system in C. glycerinogenes. Further down-regulating the 17 potential key responsive genes indicated that genes Dip5, Gpd1, Pfk1, Hxt4, Hxt6, and Ino4 are important for cell tolerance to the combined stress. Furthermore, most of the ribosomal function related genes, such as Mrt4, Nug1, Nop53, Rpa190, Rex4, and Nsr1, play important role in cell tolerance. Therefore, the wider responsive gene spectrum and the activated expression of ribosomal function related genes might be key and prerequisite factors for the excellent tolerance to the combined stress of C. glycerinogenes.

With the increasing incidence of colorectal cancer (CRC) and continued difficulty in treating it using immunotherapy, there is an urgent need to identify an effective immune-related biomarker associated with the survival and prognosis of patients with this disease. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of autoimmunity, aging, and cancer. In this study, we aimed to identify a novel immune-related methylated signature to aid in predicting the prognosis of patients with CRC. We investigated DNA methylation patterns in patients with stage II/III CRC using datasets from The cancer genome atlas (TCGA). Overall, 182 patients were randomly divided into training (n = 127) and test groups (n = 55). In the training group, five immune-related methylated CG sites (cg11621464, cg13565656, cg18976437, cg20505223, and cg20528583) were identified, and CG site-based risk scores were calculated using univariate Cox proportional hazards regression in patients with stage II/III CRC. Multivariate Cox regression analysis indicated that methylated signature was independent of other clinical parameters. The Kaplan–Meier analysis results showed that CG site-based risk scores could significantly help distinguish between high- and low-risk patients in both the training (P = 0.000296) and test groups (P = 0.022). The area under the receiver operating characteristic curve in the training and test groups were estimated to be 0.771 and 0.724, respectively, for prognosis prediction. Finally, stratified analysis results suggested the remarkable prognostic value of CG site-based risk scores in CRC subtypes. We identified five methylated CG sites that could be used as an efficient overall survival (OS)-related biomarker for stage II/III CRC patients.

Catheter-based intravascular optical coherence tomography (IVOCT) is a powerful imaging modality for visualization of atherosclerosis with high resolution. Quantitative characterization of various tissue types by attenuation coefficient (AC) extraction has been proven to be a potentially significant application of OCT attenuation imaging. However, existing methods for AC extraction from OCT suffer from the challenge of variability in complex tissue types in IVOCT pullback data such as healthy vessel wall, mixed atherosclerotic plaques, plaques with a single component and stent struts, etc. This challenge leads to the ineffectiveness in the tissue differentiation by AC representation based on single scattering model of OCT signal. In this paper, we propose a novel method based on multiple scattering model for parametric imaging of optical attenuation by AC retrieval from IVOCT images conventionally acquired during cardiac catheterization. The OCT signal characterized by the AC is physically modeled by Monte Carlo simulation. Then, the pixel-wise AC retrieval is achieved by iteratively minimizing an error function regarding the modeled and measured backscattered signal. This method provides a general scheme for AC extraction from IVOCT without the premise of complete attenuation of the incident light through the imaging depths. Results of computer-simulated and clinical images demonstrate that the method can avoid overestimation at the end of the depth profile in comparison with the approaches based on the depth-resolved (DR) model. The energy error depth and structural similarity are improved by about 30% and 10% respectively compared with DR. It provides a useful way to differentiate and characterize arterial tissue types in IVOCT images.

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures of arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cysteines within the DNA-binding domain, distal to the zinc-binding site. Arsenic binding stabilizes the DNA-binding loop-sheet-helix motif alongside the overall β-sandwich fold, endowing p53 mutants with thermostability and transcriptional activity. In cellular and mouse xenograft models, ATO reactivates mutant p53 for tumor suppression. Investigation of the 25 most frequent p53 mutations informs patient stratification for clinical exploration. Our results provide a mechanistic basis for repurposing ATO to target p53 mutations for widely applicable yet personalized cancer therapies.

Surgery is the mainstream treatment for melanoma, but its clinical implementation suffers from some major drawbacks including residual infiltrating melanoma cells at resection margins and severe tissue injury. In this study, a nanocomposite scaffold is developed for in-situ therapy after melanoma surgery as well as wound healing, which is fabricated by embedding photothermal-capable black phosphorus nanosheets (BPNSs) into bioresorbable Gelatin-PCL (GP) nanofibrous scaffold. GP scaffold is a clinically-tested biomaterial with temperature sensitivity and tissue-healing effect, while the BPNSs are loaded with the anticancer antibiotic of doxorubicin (DOX) and conjugated with NH2-PEG-FA for tumor-targeted delivery. The GP scaffold could undergo a sol-gel transition upon NIR irritation and release the BPNSs in situ. During this process, most of the BP-based nanoformulations were selectively internalized by the melanoma cells for the cooperative photothermal therapy and heat-triggerable DOX therapy, while some of the loaded DOX was released into the wound tissue to create a tumor-suppressive microenvironment. Moreover, BPNSs could be gradually degraded to phosphates/phosphonates and thus enhance tissue repair by activating the ERK1/2 and PI3K/Akt pathway. Meanwhile, the detached DOX molecules would also enter the wound tissues for continuous melanoma inhibition. Considering the anti-melanoma and wound healing effect of this composite scaffold, it may offer a facile strategy for the wound treatment after melanoma surgery.

Adult mammalian cardiomyocytes may reenter the cell cycle and cause cardiac hypertrophy. Triptolide (TP) can regulate the expressions of various cell cycle regulators in tumor cells. However, its effects on cell cycle regulators in myocardial hypertrophy and mechanism are poorly understood. This study was designed to explore the profile of cell cycle of cardiomyocytes and the temporal expression of their regulators during cardiac hypertrophy, as well as the effects of TP. The hypertrophy models employed were neonatal rat ventricular myocytes (NRVMs) stimulated with angiotensin II (Ang II) for scheduled times (from 5 min to 48 h) in vitro and mice treated with isoprenaline (Iso) for from 1 to 21 days, respectively. TP was used in vitro at 1 μg/L and in vivo at 10 μg/kg. NRVMs were analyzed with flow cytometry to detect the cell cycle, and the expression levels of mRNA and protein of various cell cycle regulators were determined using real-time PCR and Western blot. It was found NRVM numbers in phases S and G2 increased, while that in the G1 phase decreased significantly after Ang II stimulation. The mRNA expression levels of p21 and p27 increased soon after stimulation, and thereafter, mRNA expression levels of all cell cycle factors showed a decreasing trend and reached their lowest levels in 1-3 h, except for cyclin-dependent kinase 1 (CDK1) and CDK4 mRNA. The expression levels of CDK1, p21, and p27 mRNA increased significantly after stimulation with Ang II for 24-48 h. In myocardium tissue, CDK and cyclin expression levels peaked in 3-7 days, followed by a decreasing trend, while those of p21 and p27 mRNA remained at a high level on day 21. All protein expression levels were consistent with the results of mRNA in NRVMs or mice. The influence of Ang II or Iso on protein expression was more obvious than that on mRNA. TP treatment effectively prevented the imbalance in the expression of cell cycle regulators in the hypertrophy model group. In Conclusion, an imbalance in the expression of cell cycle regulators occurs during cardiac hypertrophy, and triptolide corrects these abnormal expression levels and attenuates cardiac hypertrophy.

Background In the context of the COVID‐19 outbreak of worldwide, we aim to analyze the laboratory risk factors of in‐hospital death in patients with severe COVID‐19. Methods All ≥18‐year‐old patients with confirmed severe COVID‐19 admitted to Tongji Hospital (Wuhan, China) from February 3 to February 20, 2020, were retrospectively enrolled and followed up until March 20, 2020. Epidemiological, clinical, laboratory, and treatment data were collected and explored the risk factors associated with in‐hospital death. Results A total of 73 severe patients were enrolled in the study, of whom 20 (27%) patients died in hospital during the average 28 days of follow‐up period. The median age of non‐survivors was significantly older than survivors (69 [64‐76.5] years vs 64 [56‐71.3] years, P = .033) and 15 (75%) patients were males. The laboratory abnormalities of non‐survivors mainly presented in serious inflammation response and multiple organ failure, with high levels of cytokines and deranged coagulation parameters. Multivariable regression showed that neutrophil count greater than 4.47 × 109/L (OR, 58.35; 95%CI: 2.16‐1571.69; P = .016), hypersensitivity C‐reactive protein greater than 86.7 mg/L (OR, 14.90; 95%CI: 1.29‐171.10; P = .030), creatine kinase greater than 101 U/L (OR, 161.62; 95%CI: 6.45‐4045.20; P = .002), and blood urea nitrogen greater than 6.7 mmol/L (OR, 11.18; 95%CI: 1.36‐91.62; P = .024) were risk factors for in‐hospital death. Conclusion The risk factors of neutrophil count, hypersensitivity C‐reactive protein, creatine kinase, and blood urea nitrogen could help clinicians to early identify COVID‐19 severe patients with poor outcomes on admission. Virus direct attack and cytokine storm play a major role in the death of COVID‐19., Neutrophil count, hypersensitivity C‐reactive protein, creatine kinase, and blood urea nitrogen were risk factors for in‐hospital death in patients with severe COVID‐19. Virus direct attack and cytokine storm play a major role in fatal outcomes.

This study explores nitrogen removal performance, bioelectricity generation, and the response of microbial community in two novel tidal flow constructed wetland-microbial fuel cells (TFCW-MFCs) when treating synthetic wastewater under two different chemical oxygen demand/total nitrogen (COD/TN, or simplified as C/N) ratios (10:1 and 5:1). The results showed that they achieved high and stable COD, NH4 +-N, and TN removal efficiencies. Besides, TN removal rate of TFCW-MFC was increased by 5-10% compared with that of traditional CW-MFC. Molecular biological analysis revealed that during the stabilization period, a low C/N ratio remarkably promoted diversities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in the cathode layer, whereas a high one enhanced the richness of nitrite-oxidizing bacteria (NOB) in each medium; the dominant genera in AOA, AOB, and NOB were Candidatus Nitrosotenuis, Nitrosomonas, and Nitrobacter. Moreover, a high C/N ratio facilitated the growth of Nitrosomonas, while it inhibited the growth of Candidatus Nitrosotenuis. The distribution of microbial community structures in NOB was separated by space rather than time or C/N ratio, except for Nitrobacter. This is caused by the differences of pH, dissolved oxygen (DO), and nitrogen concentration. The response of microbial community characteristics to nitrogen transformations and bioelectricity generation demonstrated that TN concentration is significantly negatively correlated with AOA-shannon, AOA-chao, 16S rRNA V4-V5-shannon, and 16S rRNA V4-V5-chao, particularly due to the crucial functions of Nitrosopumilus, Planctomyces, and Aquicella. Additionally, voltage output was primarily influenced by microorganisms in the genera of Nitrosopumilus, Nitrosospira, Altererythrobacter, Gemmata, and Aquicella. This study not only presents an applicable tool to treat high nitrogen-containing wastewater, but also provides a theoretical basis for the use of TFCW-MFC and the regulation of microbial community in nitrogen removal and electricity production.

Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being5 μm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.

Background: Despite the high mortality of cardiovascular disease (CVD) in diabetic patients with renal injury, few studies have compared cardiovascular characteristics and outcomes between patients with diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). Methods: A total of 326 type 2 diabetes mellitus patients with renal biopsy were assigned to DN and NDRD groups. Echocardiography and Doppler ultrasound were performed to evaluate left ventricular hypertrophy (LVH) and peripheral atherosclerosis disease (PAD). Renal and cardiovascular survival rates were compared between the DN and NDRD groups by Kaplan-Meier analysis. Risk factors for renal and cardiovascular events in DN patients were identified by a Cox proportional hazards model. Results: In total, 179 patients entered the DN group (54.9%) and 147 made up the NDRD group (45.1%). The presence of diabetic retinopathy, family history of diabetes, and dependence on insulin therapy were associated with the presence of DN. DN patients had more CVD with more severe LVH and PAD. Poorer renal (log-rank χ2 = 26.534, p < 0.001) and cardiovascular (log-rank χ2 = 16.257, p < 0.001) prognoses were seen in the DN group. DR (HR 1.539, 95% CI 1.332–1.842), eGFR (HR 0.943, 95% CI 0.919–0.961), and 24-h proteinuria (HR 1.211, 95% CI 1.132–1.387) were identified as risk factors for renal endpoints. Age (HR 1.672, 95% CI 1.487–1.821), HbA1C (HR 1.398, 95% CI 1.197–1.876), and 24-h proteinuria (HR 1.453, 95% CI 1.289–1.672) were associated with cardiovascular endpoints. Conclusion: Patients with DN had more severe CVD along with poorer renal and cardiovascular prognoses than those with NDRD.

Ferroptosis is a recently discovered form of programed cell death caused by the metabolically regulated lipid peroxidation and holds promise for cancer treatment, but its regulatory mechanisms remain elusive. In this study, we observe that lactate-rich liver cancer cells exhibit enhanced resistance to the ferroptotic damage induced by common ferroptosis inducers such as Ras-selective lethal small molecule 3 (RSL3) and Erastin and that the monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids. Additionally, blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. In vitro and in vivo evidence confirms that lactate regulates the ferroptosis of HCC cells and highlights its translational potential as a therapeutic target for ferroptosis-based tumor treatment. Published version

BackgroundTo develop targeted antifibrotic therapy for glaucoma filtration surgery; this study determines the effectiveness of small interfering RNA (siRNA) to reduce in vivo secreted protein acidic and rich in cysteine (SPARC) expression using the mouse model of conjunctival scarring.MethodsExperimental surgery was performed as described for the mouse model of conjunctival scarring. Scrambled (siScram) or Sparc (siSparc) siRNAs, loaded on layer-by-layer (LbL) nanoparticles, were injected into the conjunctiva immediately after surgery. Expression ofSparc,Col1a1,Fn1andMmp14was measured by real-time PCR and immunoblotting on days 7 and 14 postsurgery. Live imaging of the operated eyes was performed using slit lamp, anterior segment-optical coherence tomography and confocal microscopy. Tissue pathology was evaluated by histochemical and immunofluorescent analyses of operated conjunctival cryosections. Tissue apoptosis was quantitated by annexin V assay.Results siSparc, delivered via expanded LbL nanoparticles, significantly inhibitedSparctranscription in both day 7 (2.04-fold) and day 14 (1.39-fold) treated tissues.Sparcsuppression on day 7 was associated with a significant reduction ofCol1a1(2.52-fold),Fn1(2.89-fold) andMmp14(2.23-fold) mRNAs. At the protein level, both SPARC and collagen 1A1 (COL1A1) were significantly reduced at both time points with siSparc treatment. Nanoparticles were visualised within cell-like structures by confocal microscopy, while overt tissue response or apoptosis was not observed.Conclusions SPARC targeted therapy effectively reduced both SPARC and collagen production in the operated mouse conjunctiva. This proof-of-concept study suggests that targeted treatment of fibrosis in glaucoma surgery is safe and feasible, with the potential to extend to a range of potential genes associated with fibrosis.

Citrus grandis seedlings were irrigated with nutrient solutions with four Al-P combinations [two Al levels (0 mM and 1.2 mM AlCl3·6H2O) × two P levels (0 μM and 200 μM KH2PO4)] for 18 weeks. Al dramatically inhibited the growth of C. grandis seedlings, as revealed by a decreased dry weight of roots and shoots. Elevating P level could ameliorate the Al-induced growth inhibition and organic acid (malate and citrate) secretion in C. grandis. Using a comparative proteomic approach revealed by the isobaric tags for relative and absolute quantification (iTRAQ) technique, 318 differentially abundant proteins (DAPs) were successfully identified and quantified in this study. The possible mechanisms underlying P-induced alleviation of Al toxicity in C. grandis were proposed. Furthermore, some DAPs, such as GLN phosphoribosyl pyrophosphate amidotransferase 2, ATP-dependent caseinolytic (Clp) protease/crotonase family protein, methionine-S-oxide reductase B2, ABC transporter I family member 17 and pyridoxal phosphate phosphatase, were reported for the first time to respond to Al stress in Citrus plants. Our study provides some proteomic details about the alleviative effects of P on Al toxicity in C. grandis, however, the exact function of the DAPs identified herein in response to Al tolerance in plants must be further investigated.

Background Ongoing neuropathic pain is difficult to treat. The authors examined whether dermorphin [D-Arg2, Lys4] (1–4) amide, a peripherally acting µ-opioid receptor agonist, attenuates ongoing pain-associated manifestations after nerve injury in rats and mice. Methods Using conditioned place preference assay, the authors tested whether animals show a preference to the environment associated with drug treatment. Wide-dynamic range and dorsal root ganglion neuronal activities were measured by electrophysiology recording and calcium imaging. Results Nerve-injured animals stayed longer in dermorphin [D-Arg2, Lys4] (1–4) amide–paired chamber after conditioning than during preconditioning (rats: 402.4 ± 61.3 vs. 322.1 ± 45.0 s, 10 mg/kg, n = 9, P = 0.009; mice: 437.8 ± 59.4 vs. 351.3 ± 95.9 s, 2 mg/kg, n = 8, P = 0.047). Topical ganglionic application of dermorphin [D-Arg2, Lys4] (1–4) amide (5 μM, 1 μl, n = 5) reduced the numbers of small-diameter dorsal root ganglion neurons that showed spontaneous activity (1.1 ± 0.4 vs. 1.5 ± 0.3, P = 0.044) and that were activated by test stimulation (15.5 ± 5.5 vs. 28.2 ± 8.2, P = 0.009) after injury. In neuropathic rats, dermorphin [D-Arg2, Lys4] (1–4) amide (10 mg/kg, n = 8) decreased spontaneous firing rates in wide-dynamic range neurons to 53.2 ± 46.6% of predrug level, and methylnaltrexone (5 mg/kg, n = 9) blocked dermorphin [D-Arg2, Lys4] (1–4) amide–induced place preference and inhibition of wide-dynamic range neurons. Dermorphin [D-Arg2, Lys4] (1–4) amide increased paw withdrawal threshold (17.5 ± 2.2 g) from baseline (3.5 ± 0.7 g, 10 mg/kg, n = 8, P = 0.002) in nerve-injured rats, but the effect diminished after repeated administrations. Conclusions Peripherally acting μ-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance.

Objective To investigate the effect of hypothermia on the pharmacokinetics and pharmacodynamics of nimodipine in rabbits using in vivo and in vitro methods. Methods Five healthy New Zealand rabbits received a single dose of nimodipine (0.5 mg/kg) intravenously under normothermic and hypothermic conditions. Doppler ultrasound was used to monitor cerebral blood flow, vascular resistance, and heart rate. In vitro evaluations of protein binding, hepatocyte uptake and intrinsic clearance of liver microsomes at different temperatures were also conducted. Results Plasma concentrations of nimodipine were significantly higher in hypothermia than in normothermia. Nimodipine improved cerebral blood flow under both conditions, but had a longer effective duration during the hypothermic period. Low temperature decreased the intrinsic clearance of liver microsomes, with no change in protein binding or hepatocyte uptake of nimodipine. Conclusion Nimodipine is eliminated at a slower rate during hypothermia than during normothermia, mainly due to the decreased activity of cytochrome P450 enzymes. This results in elevated system exposure with little enhancement in pharmacological effect.

Several animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD. In a retrospective study of 51 patients with AKI, increased expression of RTN1A and other ER stress markers were associated with the severity of kidney injury and with progression to CKD. In an inducible tubular cell–specific RTN1A-knockdown mouse model subjected to folic acid nephropathy (FAN) or aristolochic acid nephropathy, reduction of RTN1A expression during the initial stage of AKI attenuated ER stress and kidney cell injury in early stages and renal fibrosis development in later stages. Treatment of wild-type mice with tauroursodeoxycholic acid, an inhibitor of ER stress, after the induction of kidney injury with FA facilitated renoprotection similar to that observed in RTN1A-knockdown mice. Conversely, in transgenic mice with inducible tubular cell–specific overexpression of RTN1A subjected to FAN, induction of RTN1A overexpression aggravated ER stress and renal injury at the early stage and renal fibrosis at the late stage of FAN. Together, our human and mouse data suggest that the RTN1A-mediated ER stress response may be an important determinant in the severity of AKI and maladaptive repair that may promote progression to CKD.

Calophaca sinica Rehd. is a tree species with high economic value, whose resource has been declining due to unreasonable exploitation. In this study, we sequenced, assembled, and annotated the complete chloroplast genome of C. sinica. The whole chloroplast genome size is 129,345 bp, it lacks an inverted repeat (IR) region. The GC content of the whole chloroplast genome is 34.51%. The chloroplast genome comprises 112 unique genes, including 77 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and 5 ribosomal RNA (rRNA) genes. Phylogenetic analyses of chloroplast genomes derived from 15 species indicated that C. sinica is close to Caragana and Tibetia species in Papilionoideae.

Aluminum (Al) treatment significantly decreased the dry weight (DW) of stem, shoot and whole plant of both Citrus sinensis and C. grandis, but did not change that of root. Al significantly decreased leaf DW of C. grandis, increased the ratio of root to shoot and the lignin content in roots of both species. The higher content of Al in leaves and stems and lignin in roots of C. grandis than that of C. sinensis might be due to the over-expression of Al sensitive 3 (ALS3) and cinnamyl alcohol deaminase (CAD) in roots of C. grandis, respectively. By using yeast-two-hybridazation (Y2H) and bimolecular fluorescence complementation (BiFC) techniques, we obtained the results that glutathione S-transferase (GST), vacuolar-type proton ATPase (V-ATPase), aquaporin PIP2 (PIP2), ubiquitin carboxyl-terminal hydrolase 13 (UCT13), putative dicyanin blue copper protein (DCBC) and uncharacterized protein 2 (UP2) were interacted with ALS3 and GST, V-ATPase, Al sensitive 3 (ALS3), cytochrome P450 (CP450), PIP2, uncharacterized protein 1 (UP1) and UP2 were interacted with CAD. Annotation analysis revealed that these proteins were involved in detoxification, cellular transport, post-transcriptional modification and oxidation-reduction homeostasis or lignin biosynthesis in plants. Real-time quantitative PCR (RT-qPCR) analysis further revealed that the higher gene expression levels of most of these interacting proteins in C. grandis roots than that in C. sinensis ones were consistent with the higher contents of lignin in C. grandis roots and Al absorbed by C. grandis. In conclusion, our study identified some key interacting components of Al responsive proteins ALS3 and CAD, which could further help us to understand the molecular mechanism of Al tolerance in citrus plants and provide new information to the selection and breeding of tolerant cultivars, which are cultivated in acidic areas.

Background To explore the characteristics and regularity of complete blood count (CBC) changes among influenza A–positive child patients and to discover parameters that can help with the diagnosis and differential diagnosis. Methods One hundred and ninety‐one influenza A–positive children, two hundred and nineteen influenza A–negative children with influenza‐like symptoms, and two hundred and forty‐seven healthy children were included in this study. They were divided into three groups: influenza A–positive patient group, influenza A–negative patient group, and control group. Reverse transcriptase polymerase chain reaction testing and Sysmex XS‐800i hematology analyzer were used to obtain influenza A and CBC results, respectively. CBC along with parameters including lymphocyte‐to‐monocyte ratio (LMR), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), mean platelet volume/platelet ratio (MPV/PLT), and lymphocyte*platelet (LYM*PLT) was calculated and recorded for each child. The differences in these parameters among different groups were tested with SPSS 15.0. The diagnostic values were also evaluated. Results The LYM and PLT of child patients with influenza A were significantly lower than those of both influenza A–negative patients with influenza‐like symptoms and healthy controls. Among all the parameters, LYM*PLT has the largest area under the curve and the highest diagnostic value, followed by MPV/PLT. Compared with using LMR or MPV/PLT, the diagnostic value of using LYM alone was, on the contrary, higher. Conclusions Low LYM*PLT and high MPV/PLT may indicate influenza A infection in children with influenza‐like symptoms, which can be a useful indicator for diagnosis and differentiation of influenza A infection.

BACKGROUND: Acute graft versus host disease (aGvHD) is a major factor that limits the successful outcomes of allogeneic hematopoietic cell transplantation (alloHSCT). Currently, there are few validated biomarkers that can help predict the risk of aGvHD in clinical settings. METHODS: We performed an integrated metabolomics and transcriptomics study and identified biomarkers that distinguish alloHSCT recipients with aGvHD from alloHSCT recipients without aGvHD in 2 separate cohorts. RESULTS: Pathway analysis of 38 significantly altered metabolites and 1,148 differentially expressed genes uncovered a distinctly altered glycerophospholipid (GPL) metabolism network. Subsequently, we developed an aGvHD risk score (GRS) based on 5 metabolite markers from GPL metabolism to predict the risk of aGvHD. GRS showed a positive predictive value of 92.2% and 89.6% in the training and validation cohorts, respectively. In addition, high GRS was correlated with poor overall survival. Gene expressions of GPL-related lipases were significantly altered in aGvHD samples, leading to dysregulated GPLs. CONCLUSION: Using integrative “Omic” analysis, we unraveled a comprehensive view of the molecular perturbations underlying the pathogenesis of aGvHD. Our work represents an initial investigation of a unique metabolic and transcriptomic network that may help identify aGvHD at an early stage and facilitate preemptive therapy. FUNDING: National Natural Science Foundation of China (NSFC; 81530047, 81870143, 81470321, 81770160, 81270567, 81270638, 81573396, 81703674) provided funding for material, processing, metabolomics, and transcriptomics studies. This work was also supported by Shanghai Sailing Program from Science and Technology Commission Shanghai Municipality (17YF1424700), the Scholarship from Shanghai Municipal Health and Family Planning Commission (2017BR012), and the Special Clinical Research in Health Industry in Shanghai (20184Y0054). The projects supporting young scholars are 17YF1424700 (to YL), 2017BR012 (to XH), and 20184Y0054 (to QC).

Magnesium (Mg) deficiency is one of the major constraining factors that limit the yield and quality of agricultural products. Uniform seedlings of the Citrus sinensis were irrigated with Mg deficient (0 mM MgSO4) and Mg sufficient (1 mM MgSO4) nutrient solutions for 16 weeks. CO2 assimilation, starch, soluble carbohydrates, TBARS content and H2O2 production were measured. Transcriptomic analysis of C. sinensis leaves was performed by Illumina sequencing. Our results showed that Mg deficiency decreased CO2 assimilation, but increased starch, sucrose, TBARS content and H2O2 production in C. sinensis leaves. A total of 4864 genes showed differential expression in response to Mg deficiency revealed by RNA-Seq and the transcriptomic data were further validated by real-time quantitative PCR (RT-qPCR). Gene ontology (GO) enrichment analysis indicated that the mechanisms underlying Mg deficiency tolerance in C. sinensis may be attributed to the following aspects: a) enhanced microtubule-based movement and cell cycle regulation, b) elevated signal transduction in response to biotic and abiotic stimuli, c) alteration of biological processes by tightly controlling phosphorylation especially protein phosphorylation, d) down-regulation of light harvesting and photosynthesis due to the accumulation of carbohydrates, e) up-regulation of cell wall remodeling and antioxidant system. Our results provide a comprehensive insight into the transcriptomic profile of key components involved in the Mg deficiency tolerance in C. sinensis and enrich our understanding of the molecular mechanisms by which plants adapted to a Mg deficient condition.

In a previous paper, we reported that triptolide (TP), a commonly used immunomodulator, could attenuate cardiac hypertrophy. This present study aimed to further explore the inhibition of cardiac fibrosis by TP and the possible mechanism from the perspective of the NOD-like receptor protein 3 (NLRP3) inflammasome. Hematoxylin-eosin and Masson&rsquo, s staining, immunohistochemistry, and immunofluorescence were performed to observe cardiac fibrotic changes in mice and mouse cardiac fibroblasts (CFs). The Western blot, colocalization, and immunoprecipitation were applied to detect protein expression and interactions. Results suggested that TP dose-dependently inhibited cardiac fibrosis induced by isoproterenol and collagen production of CFs induced by angiotensin II. TP exhibited an antifibrotic effect via inhibiting activation of the NLRP3 inflammasome, which sequentially decreased IL-1&beta, maturation, myeloid differentiation factor 88 (MyD88)-related phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase 1/2 (ERK1/2), and TGF-&beta, 1/Smad signaling, and ultimately resulted in less collagen production. Moreover, TP showed no antifibrotic effect in Nlrp3-knockout CFs. Notably, TP inhibited the expression of NLRP3 and apoptosis-associated speck-like proteins containing a caspase recruitment domain (ASC) as well as inflammasome assembly, by interrupting the NLRP3-ASC interaction to inhibit inflammasome activation. Finally, TP indeed inhibited the NLRP3-TGF&beta, 1-Smad pathway in vivo. Conclusively, TP was found to play a dual role in interrupting the activation of the NLRP3 inflammasome to attenuate cardiac fibrosis.

Inadequate endometrial receptivity may be responsible for the low implantation rate of transferred embryos in in vitro fertilization (IVF) treatments. Patients with repeated implantation failure (RIF) impact the clinical pregnancy rate for IVF. We collected endometrial tissue during the implantation window of hysteroscopy biopsies from September 2016 to December 2019 and clinical data were collected simultaneously. Patients were divided into RIF and pregnant controls group according to pregnancy outcomes. A total of 82 differentially expressed endometrial proteins were identified, including 55 up-regulated proteins (>1.50-fold, P P

Background Decreased ovarian reserve (DOR) is a common reproductive barrier in female. Bushen Huoxue (BSHX) method of TCM is widely applied to treat DOR clinically. The purpose of this study is to provide a systemic and comprehensive evaluation of BSHX in the treatment of DOR. Methods We have registered this protocol with OSF registry and the DOI is 10.17605/OSF.IO/QNUE2. We will search 4 English databases (PubMed, EMBASE, MEDLINE, Cochrane Library) and four Chinese databases (China national knowledge infrastructure database, Wanfang database, VIP and Superstar database) from their inception to August 10, 2020. Two authors will search and extract independently all related studies. RevMan 5.3 software will be applied to synthesize data. Results The results of this study will be published in a scientific journal after peer-review. Conclusion This systematic review will provide reliable evidences for clinicians, and help them make decisions in DOR management.

Objectives: Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we report the successful development of a new nanocarrier system for the management of fibrosis. Methods: The new carrier has a hydroxyapatite core, with alternating layers of siRNA and a cationic peptide. The siRNA used here targets secreted protein acidic and rich in cysteine (SPARC), a key matricellular protein involved in the regulation of collagen fibrillogenesis and assembly. We have also used FRET studies to elucidate the fate of the particles inside cells, including the mechanistic details of layer-by-layer detachment. Results: In vitro studies using murine conjunctiva fibroblasts show sustained release over 2 weeks, and that such released siRNA sustained SPARC knockdown without affecting cell growth, and maintained siRNA presence in the cells for at least two weeks with a single-dose treatment. Release studies of siRNA from particles in vitro gave insight on how the particles delivered prolonged gene-silencing effects. Conclusion: A single treatment of the layer-by-layer nanoparticle designed can achieve sustained gene silencing over 2 weeks. Localized delivery of stabilized siRNA with sustained-release capabilities opens the door for many other applications of siRNA-based gene regulation. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore)

Background/Aims: Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages. Methods: 159 non-dialysis type 2-DN patients from 2008 to 2015 were enrolled to measure the plasma concentration of soluble CD146 (sCD146). 94 type 2 diabetes mellitus patients without DN and 100 healthy subjects were used as controls. The patients with CKD stage 1-3 were referred as early stage patients. Another independent cohort of 48 patients with biopsy-proved DN was used for the immunohistochemistry study of CD146. Renal outcomes were defined as doubling of serum creatinine, initiation of renal replacement therapy or death. Results: We found that plasma level of sCD146 was upregulated and associated with renal function in DN patients. sCD146 was proved to be a more optimal marker than urine albumin creatinine ratio to evaluate disease severity in these DN patients. The kidney expression of CD146 was co-localized with endothelial marker CD31 and increased in DN. CD146 staining in kidney was correlated with the severity of pathological changes in DN patients. Survival analysis suggested that both plasma and biopsy expression of CD146 were correlated with renal outcomes. Conclusions: CD146 is associated with kidney injury and could be a good marker to predict renal outcomes in patients with early stages of DN.

Background This study aims to investigate the imprecision of internal quality control of routine chemistry analytes so that we can have an overall knowledge of imprecision level of measurement in laboratories in China. Methods The internal quality control information including two kinds of coefficient of variations (CVs) of 22 analytes were collected via an on-line questionnaire. Then, the percentages of laboratories meeting the quality requirement for each analyte were calculated according to five imprecision criteria. Results Among these 22 analytes, creatine kinase got the most satisfied result, the percentages of laboratories whose current CV met 1/3 total allowable error (1/3TEa), 1/4TEa, and the specifications based on biological variation were 99.3%, 95.9%, 99.6%, 99.9%, and 90.6%, respectively, while Na got the lowest satisfaction rate according to these specifications, which were 4.15%, 22.4%, 4.2%, 9.0%, and 1.3%, respectively. From an overall perspective, most of the 22 analytes got a satisfied result when applying the criteria defined by CLIA'88, while only a small amount of laboratories can meet the requirement when applying the specifications derived from biological variation. Conclusions There is huge space for us to enhance and substantial effort is needed in improving and implementing quality management in China.

The fast urbanization of China potentially affects development of diabetes. Fuyang is one of the typical cities being involved but its epidemiological characteristics of diabetes is not clear. In this study, 4131 adults in randomly selected families from all the townships and streets of Fuyang were investigated. This study showed that the standardized prevalence of diabetes was 8.10 % in Fuyang. The prevalence of prediabetes was 11.3 %. The prevalence of isolated impaired glucose tolerance (IGT) was 10.51 %. The prevalence of diabetes in urban areas was slightly higher than that of rural areas (14.3 % vs. 13.0 %). The prevalence of prediabetes in urban areas was also higher than that of rural areas (19.1 % vs. 15.6 %). Among all the patients diagnosed with diabetes, 46.02 % of them received treatment. Age, family history of diabetes, obesity, high level of triglyceride, and low-density lipoprotein were risk factors of diabetes.

SUMMARY OBJECTIVES To evaluate the epidemiological characteristics of acute pancreatitis (AP) and explore potential relationships between these factors and severity. METHODOLOGY Data-sets of 5,659 patients with AP from health statistics and the Information Center of Jiangsu province, between 2014 and 2016, were analyzed. A self-organizing map (SOM) neural network was used for data clustering. RESULTS Biliary acute pancreatitis (BAP) (86.7%) was the most frequent etiological factor. A total of 804 (14.2%) patients had severe acute pancreatitis (SAP). The mean age of patients was 53.7 + 17.3 (range 12~94y). Most of the AP patients were married (75.4%); 6% of mild /moderately severe AP (MAP/MASP) patients were unmarried, which was less than SAP patients (P=0.016). AP patients with blood type AB in the general population (8.8%) was significantly lower than that of AP cases (13.9%) (P=0.019) and SAP cases(18.7%) (P=0.007). The number of AP patients in southern Jiangsu was much higher than that in northern Jiangsu province, especially in Nanjing (1229, 21.7%). The proportion of acute alcoholic pancreatitis (AAP) in the north of Jiangsu (Xuzhou 18.4%) was much higher than that in southern Jiangsu (Suzhou 2.6%). The whole sample was divided into five classes by SOM neural network. If BAP patients were male, old, divorced, and blood type AB or B, they were more likely to develop SAP. Middle-age, unmarried or divorced male patients with blood type B/AB who suffered from HAP or AAP were also more likely to develop SAP. CONCLUSIONS The number of unmarried patients with MAP/MASP was smaller than that of SAP. Blood types AB and B were more frequent in AP, especially in SAP. The differences between southern Jiangsu and northern Jiangsu, in number of AP patients and the proportion of AAP, were significant. In class I and class IV, the ratio of SAP was much higher than in other classes and the whole sample.

Object To discover whether cirrhotic portal hypertension patients with symptomatic cholelithiasis would benefit from cholecystolithotomy combined with Armillarisin A in the authors hospital. Methods: Sixty-one patients with cirrhotic portal hypertension and symptomatic gallstone disease who underwent either cholecystolithotomy combined with Armillarisin A (group A) or cholecystectomy (group B) for cholelithiasis from Feb 2007 to March 2011 were retrospectively reviewed. These patients were undergoing simultaneous procedure for esophageal varices. The operation-relevant information, change of laboratory examination data, postoperative complications and symptoms were analyzed. Results: There were no significant differences between group A and group B in mean operative time, intraoperative blood loss, time to resume diet postoperatively and length of hospital stay (P 0.05). The hepatic function biochemical profile and Child-Pugh'™s score at 2 weeks and 1 month after operations were both altered significantly less in group A than in group B (ALT, 0.008, 0.011; AST, 0.006, 0.003; Child-Pugh'™s score, 0.010, 0.016, respectively). However, at 6 months postoperatively, the changes were not significant (P 0.05). Except for gallstone recurrence and wound infection, occurrences or development of postoperative complications including biliary fistula, liver failure and subphrenic infection showed significant differences between the two groups (P = 0.037, P = 0.041, P = 0.019, respectively). After a mean follow-up of 4.2 years, all patients remain alive. Twenty-seven patients in group A (93%) are free of biliary symptoms. Conclusion Cholecystolithotomy combined with using Armillarisin A is a useful treatment for symptomatic gallstones in patients with cirrhotic portal hypertension who are at high risk for cholecystectomy. It preserves gallbladder function and reduces the possibility of liver failure; moreover the rate of recurrent gallstones are relatively low.

Background/Aims: Adult cardiomyocytes can re-enter cell cycle as stimulated by prohypertrophic factors although they withdraw from cell cycle soon after birth. p21 WAF1/CIP1 , a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution to this process remains largely unclear. Methods: The gene expression profile in left ventricle (LV) of spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats was determined using quantitative PCR array and verified by real-time PCR and Western blotting. Hypertrophic response of H9c2 cells and neonatal rat ventricular myocytes (NRVM) were induced by angiotensin II (1 µmol/L). Cardiac hypertrophy of mice was elicited by isoproterenol (ISO) infusion (40 mg/kg per day for 14 days). p21-adenovirus and p21-siRNA were employed to transfect NRVM, and sterigmatocystin (STE, 3 mg/kg, ip, qd) was used to inhibit p21 activity. mRNA and protein expression levels of α- and β-myosin heavy chain (MHC), p21 WAF1/CIP1 , calcineurin (CaN) and atrial natriuretic peptide (ANP) were assayed by realtime PCR and WB, respectively. Results: Sixteen genes showed two-fold or greater changes between SHR and WKY rats, in which the expression of p21 WAF1/CIP1 was upregulated by 4.15-fold ( P =0.002) and reversed by losartan. Surface area, protein content, mRNA and protein expressions of β-MHC, ANP and p21 WAF1/CIP1 in H9c2 cells treated with AngII elevated significantly compared with control group. p21-Ad transfection markedly increased the surface area and β-MHC mRNA expression of normal NRVMs, and p21-siRNA transfection decreased them in AngII-treated NRVMs. STE treatment decreased HW/BW and cross-sectional area, expression levels of β-MHC, ANP and p21 significantly in ISO-treated mice. Conclusion: Our findings suggest that p21 facilitates the development of cardiac hypertrophy, and regulating the expression of p21 may be an approach to attenuate hypertrophic growth of cardiomyocytes.

Introduction The aim of the study was to investigate the state-of-the-art of the performance of critical value reporting and provide recommendations for laboratories setting critical value reporting time frames. Materials and methods The National Centre for Clinical Laboratories in China initiated a critical value reporting investigation in 2015. A questionnaire related to critical value reporting policy was sent to 1589 clinical laboratories in China online. The questionnaire consisted of a set of questions related to critical value reporting policy and a set of questions related to timeliness of critical value reporting. The survey data were collected between March and April 2015. Results A total survey response rate was 61.2%. The critical value unreported rate, unreported timely rate, and clinical unacknowledged rate of more than half of participants were all 0.0%. More than 75.0% of participants could report half of critical values to clinicians within 20 minutes and could report 90.0% of critical values to clinicians within 25 minutes (from result validation to result communication to the clinician). The median of target critical value reporting time was 15 minutes. "Reporting omission caused by laboratory staff", "communications equipment failure to connect", and "uncompleted application form without contact information of clinician" were the three major reasons for unreported critical value. Conclusions The majority of laboratories can report critical values to responsible clinical staff within 25 minutes. Thus, this value could be recommended as suitable critical value reporting time frame for biochemistry laboratories in China. However, careful monitoring of the complete reporting process and improvement of information systems should ensure further improvement of critical value reporting timeliness.

The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson's trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, triptolide can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes.

The Chinese central government launched the Health System Reform Plan in 2009 to strengthen disease control and health promotion and provide a package of basic public health services. Village doctors receive a modest subsidy for providing public health services associated with the package. Their beliefs about this subsidy and providing public health services could influence the quality and effectiveness of preventive health services and disease surveillance.To understand village doctors' perspectives on the subsidy and their experiences of delivering public health services, we performed 10 focus group discussions with village doctors, 12 in-depth interviews with directors of township health centres and 4 in-depth interviews with directors of county-level Centers for Disease Control and Prevention.The study was conducted in four counties in central China, two in Hubei province and two in Jiangxi province.Village doctors prioritize medical services but they do their best to manage their time to include public health services. The willingness of township health centre directors and village doctors to provide public health services has improved since the introduction of the package and a minimum subsidy, but village doctors do not find the subsidy to be sufficient remuneration for their efforts.Improving the delivery of public health services by village doctors is likely to require an increase in the subsidy, improvement in the supervisory relationship between village clinics and township health centres and the creation of a government pension for village doctors.Résumé PROBLÈME: Le gouvernement central chinois a lancé le plan de réforme du système de santé en 2009 pour renforcer la lutte contre les maladies et l'amélioration de la santé, et pour fournir un paquet de services de base en termes de santé publique. Les médecins de village reçoivent une subvention modeste pour offrir des services de santé publique liés à ce paquet. Leurs opinions sur cette subvention et la fourniture de services de santé publique pourraient avoir une influence sur la qualité et l'efficacité des services de santé préventive et sur la surveillance des maladies. APPROCHE: Pour comprendre les perspectives des médecins de village sur la subvention et leur expérience dans le domaine de la fourniture de services de santé publique, nous avons organisé 10 discussions de groupe cible avec des médecins de village, 12 entrevues approfondies avec des directeurs de centres de santé cantonaux et 4 entrevues approfondies avec des directeurs départementaux de centres pour la lutte et la prévention des maladies. ENVIRONNEMENT LOCAL: L'étude a été effectuée dans quatre comtés du centre de la Chine, deux dans la province de Hubei et deux dans la province du Jiangxi. CHANGEMENTS SIGNIFICATIFS: Les médecins de village donnent la priorité aux services médicaux, mais ils font de leur mieux pour gérer leur temps de manière à inclure les services de santé publique. La volonté des directeurs de centres de santé cantonaux et des médecins de village d’offrir des services de santé publique s'est accrue depuis l'introduction du paquet et d'une subvention minimale, mais les médecins de village ne considèrent pas que cette subvention constitue une rémunération suffisante pour leurs efforts. LEÇONS TIRÉES: Il est possible que l’amélioration de la fourniture de services de santé publique par les médecins de village nécessite une augmentation de la subvention, l'amélioration de la relation de supervision entre cliniques de village et centres de santé cantonaux et la création d'une pension gouvernementale pour les médecins de village.Resumen SITUACIÓN: En el año 2009, el gobierno central chino puso en marcha el plan de reforma del sistema sanitario con el objetivo de reforzar el control de las enfermedades y fomentar la salud, así como proporcionar un paquete de servicios básicos de salud pública. Los médicos rurales perciben una modesta subvención por la prestación de los servicios de salud pública relacionados con dicho paquete. Sus opiniones acerca de dicha subvención y la prestación de los servicios de salud pública podrían influir en la calidad y la eficacia de los servicios sanitarios preventivos y de la vigilancia de las enfermedades. ENFOQUE: Con objeto de comprender los puntos de vista de los médicos rurales acerca de la subvención y sus experiencias en la prestación de servicios sanitarios, hemos llevado a cabo 10 debates con grupos focales de médicos rurales, 12 entrevistas en detalle con directores de centros de salud municipales y 4 entrevistas en detalle con directores de Centros para el Control y Prevención de las Enfermedades provinciales. MARCO REGIONAL: El estudio se llevó a cabo en cuatro condados del centro de China, dos de ellos en la provincia de Hubei y otros dos en la de Jiangxi. CAMBIOS IMPORTANTES: Los médicos rurales dan prioridad a los servicios médicos, pero hacen todo lo posible por gestionar su tiempo a fin de incluir los servicios de salud pública. La disposición de los directores de los centros sanitarios municipales y de los médicos rurales para prestar los servicios de salud pública ha aumentado desde la introducción del paquete y de la subvención mínima, si bien los médicos rurales no consideran que sea una retribución suficiente por sus esfuerzos. LECCIONES APRENDIDAS: Es probable que, para mejorar la prestación de servicios de salud pública por parte de los médicos rurales, sea necesario un aumento de la subvención, una mejora en la relación de supervisión entre las clínicas rurales y los centros de salud municipales, así como la creación de una pensión gubernamental para los médicos rurales.ملخص المشكلة : أطلقت الحكومة المركزية الصينية خطة إصلاح النظام الصحي في عام 2009 لتعزيز مكافحة الأمراض وتعزيز الصحة وتقديم حزمة من خدمات الصحة العمومية الأساسية. ويتلقى الأطباء القرويون إعانة متواضعة نظير تقديم خدمات الصحة العمومية المرتبطة بالحزمة. ويمكن أن تؤثر معتقداتهم بشأن هذه الإعانة وتقديم خدمات الصحة العمومية على جودة الخدمات الصحية الوقائية وفعاليتها وترصد الأمراض. الأسلوب : لفهم وجهات نظر الأطباء القرويين بشأن الإعانة وخبراتهم في إيتاء خدمات الصحة العمومية، أجرينا عشر مناقشات جماعية مع أطباء قرويين واثنتي عشرة مقابلة متعمقة مع مديري المراكز الصحية بالبلدة وأربع مقابلات متعمقة مع مديري مراكز مكافحة الأمراض والوقاية منها على مستوى المقاطعة. المواقع المحلية : تم إجراء الدراسة في أربع مقاطعات في وسط الصين، اثنتين في مقاطعة هوبي واثنتين في مقاطعة جيانغشي. التغيّرات ذات الصلة : يقوم الأطباء القرويون بتحديد أولويات الخدمات الطبية، غير أنهم يبذلون ما بوسعهم لإدارة وقتهم ليتضمن خدمات الصحة العمومية. وزاد استعداد مديري المراكز الصحية بالبلدة والأطباء القرويين لتقديم خدمات الصحة العمومية منذ تقديم الحزمة وإعانة دنيا، غير أن الأطباء القرويين لا يجدون الإعانة أجراً كافياً نظير جهودهم. الدروس المستفادة : من المرجح أن يتطلب تحسين إيتاء خدمات الصحة العمومية من جانب الأطباء القرويين زيادة في الإعانة، وتحسين في العلاقة الإشرافية بين العيادات القروية والمراكز الصحية بالبلدة وتقديم معاش حكومي للأطباء القرويين.摘要 问题: 中国中央政府在2009 年推出了卫生系统改革计划，旨在加强疾病控制，推进健康并提供基本的公共卫生服务包。乡村医生因提供与此服务包相关的公共卫生服务而获得适度补贴。他们对此补贴的信任以及公共卫生服务提供活动可能影响预防保健服务和疾病监测的质量和效率。 方法: 为了解乡村医生对补贴的看法及其提供公共卫生服务的经验，我们与乡村医生进行了10 个重点小组讨论，与乡镇卫生院的负责人进行了12 次深度访谈，与县级疾病控制和预防中心的负责人进行4 次深度访谈。 当地状况: 这项研究在华中地区的四个县执行，其中两个县在湖北省，两个县在江西省。 相关变化: 乡村医生以医疗服务为优先事务，但他们尽最大努力安排自己的时间将公共卫生服务纳入其中。在引入服务包和最低补贴之后，乡镇卫生院中心负责人和乡村医生提供公共卫生服务的意愿得以改善，但乡村医生发现补贴不足以偿付其付出的努力。 经验教训: 改善乡村医生提供公共卫生服务的状况，很可能需要增加补贴、改善乡村卫生室和乡镇卫生院的监督关系以及创立为乡村医生提供的津贴。Резюме Проблема: Центральное правительство Китая в 2009 г. приняло План реформирования системы здравоохранения, целью которого является улучшение контроля над заболеваниями, укрепление здоровья и предоставление населению пакета основных услуг общественного здравоохранения. Сельские врачи получают скромные субсидии за предоставление услуг общественного здравоохранения в составе базового пакета. Их отношение к этой субсидии и предоставлению услуг общественного здравоохранения может повлиять на качество и эффективность профилактических медицинских услуг и наблюдения за заболеваниями. Подход: Чтобы понять отношение сельских врачей к субсидии и предоставлению услуг общественного здравоохранения, было проведено 10 дискуссий с участием фокус-групп их сельских врачей, 12 подробных интервью с руководителями городских медицинских центров и 4 подробных интервью с руководителями окружных центров по контролю и профилактике заболеваний. Местные условия: Исследование было проведено в четырех округах в центральном Китае – два в провинции Хубэй и два в провинции Цзянси. Осуществленные перемены: Сельские врачи отдают приоритет медицинским услугам, но они делают все возможное, чтобы выделять часть своего рабочего времени на услуги общественного здравоохранения. Желание руководителей поселковых медицинских центров и сельских врачей предоставлять услуги общественного здравоохранения возросло с введением пакетов и минимальных субсидий, но сельские врачи не считают эти субсидии достаточным вознаграждением за их усилия. Выводы: Чтобы улучшить качество оказания услуг общественного здравоохранения сельскими врачами, вероятно, потребуется увеличение субсидий, улучшение надзора за сельскими клиниками со стороны городских медицинских центров и предоставление государственной пенсии сельским врачам.

Diabetic cardiovascular diseases are characterized by progressive hyperglycemia, which results in excessive production of oxidative stress and pro-inflammatory cytokines. Cystic fibrosis (CF) is characterized by chronic inflammation due to mutations in CF transmembrane conductance regulator (CFTR). However, little information is available about the role of CFTR in hyperglycemia‑induced endothelial cell oxidative stress and inflammation. In the present study, a high glucose‑treatment was applied in human umbilical vein endothelial cells with CFTR overexpression or inhibition, and the oxidative and inflammatory characteristics were measured. It was shown that CFTR protein and mRNA expression were reduced by glucose in a concentration‑dependent manner. Overexpression of CFRT via adenoviral infection significantly inhibited the production of reactive oxygen species and inflammatory biomediators induced by high glucose. Conversely, pharmacological inhibition of CFTR led to the opposite effects. Mechanistically, nuclear factor‑κB (NF‑κB) and mitogen‑activated protein kinase (MAPK) signaling were activated following high glucose treatment, which were inhibited by CFTR overexpression and enhanced by CFTR inhibition. The pro‑inflammatory effect of CFTR inhibition was abolished by pharmacological inhibition of the NF‑κB or MAPK pathways. Moreover, inhibition of MAPK abrogated CFTR inhibition‑induced NF‑κB nuclear translocation, whereas NF‑κB inhibitor produced no effects on MAPK activation. Additionally, antioxidant treatment inhibited the high glucose‑induced decrease in CFTR expression and the increase in inflammatory responses. Collectively, these findings revealed that CFTR attenuates high glucose‑induced endothelial cell oxidative stress and inflammation through inactivation of NF‑κB and MAPK signaling, indicating that elevation of CFRT expression may be a novel strategy in preventing endothelial dysfunction in diabetes.

This study aimed to investigate the possible association between diabetes susceptibility gene transcription factor 7-like 2 (TCF7L2) and gestational diabetes mellitus (GDM) in a Chinese Han population. A total of 556 GDM patients and 500 Non-GDM were included. Eighteen single nucleotide polymorphisms (SNPs) were evaluated. Fifteen tag SNPs were selected from HapMap CHB database with a minor allele frequency of >0.2 and r2 of >0.8. Three additional SNPs were also chosen because these SNPs are associated with type 2 diabetes in East Asians. TCF7L2 rs290487, rs6585194, and rs7094463 polymorphisms were found to be significantly associated with GDM. In multivariate analysis, rs290487 genetic variation (OR = 2.686 per each C allele, P = 0.002), pre-BMI > 24 kg/m2 (OR = 1.592, P = 0.018), age > 25 years (OR = 1.780, P = 0.012) and LDL-C > 3.6 mmol/L (OR = 2.034, P = 0.009) were identified as independent risk factors of GDM, rs7094463 genetic variation (OR = 0.429 per each G allele, P = 0.005) was identified as independent protect factor of GDM. This finding suggests that TCF7L2 rs290487, and rs7094463 were a potential clinical value for the prediction of GDM.

Essentials Predicting the occurrence of portosplenomesenteric vein thrombosis (PSMVT) is difficult. We studied 72 patients with acute pancreatitis. Artificial neural networks modeling was more accurate than logistic regression in predicting PSMVT. Additional predictive factors may be incorporated into artificial neural networks. Summary Objective To construct and validate artificial neural networks (ANNs) for predicting the occurrence of portosplenomesenteric venous thrombosis (PSMVT) and compare the predictive ability of the ANNs with that of logistic regression. Methods The ANNs and logistic regression modeling were constructed using simple clinical and laboratory data of 72 acute pancreatitis (AP) patients. The ANNs and logistic modeling were first trained on 48 randomly chosen patients and validated on the remaining 24 patients. The accuracy and the performance characteristics were compared between these two approaches by SPSS17.0 software. Results The training set and validation set did not differ on any of the 11 variables. After training, the back propagation network training error converged to 1 × 10-20 , and it retained excellent pattern recognition ability. When the ANNs model was applied to the validation set, it revealed a sensitivity of 80%, specificity of 85.7%, a positive predictive value of 77.6% and negative predictive value of 90.7%. The accuracy was 83.3%. Differences could be found between ANNs modeling and logistic regression modeling in these parameters (10.0% [95% CI, -14.3 to 34.3%], 14.3% [95% CI, -8.6 to 37.2%], 15.7% [95% CI, -9.9 to 41.3%], 11.8% [95% CI, -8.2 to 31.8%], 22.6% [95% CI, -1.9 to 47.1%], respectively). When ANNs modeling was used to identify PSMVT, the area under receiver operating characteristic curve was 0.849 (95% CI, 0.807-0.901), which demonstrated better overall properties than logistic regression modeling (AUC = 0.716) (95% CI, 0.679-0.761). Conclusions ANNs modeling was a more accurate tool than logistic regression in predicting the occurrence of PSMVT following AP. More clinical factors or biomarkers may be incorporated into ANNs modeling to improve its predictive ability.

To evaluate the role of TCF7L2, a key regulator of glucose homeostasis, in estradiol (E2) and progesterone (P4)-modulated glucose metabolism, mouse insulinoma cells (MIN6) and human liver cancer cells (hepG2 and HUH7) were treated with physiological concentrations of E2 or P4 in the up- and down-regulation of TCF7L2. Insulin/proinsulin secretion was measured in MIN6 cells, while glucose uptake and production were evaluated in liver cancer cells. E2 increased insulin/proinsulin secretion under both basal and stimulated conditions, whereas P4 increased insulin/proinsulin secretion only under glucose-stimulated conditions. An antagonistic effect, possibly concentration-dependent, of E2 and P4 on the regulation of islet glucose metabolism was observed. After E2 or P4 treatment, secretion of insulin/proinsulin was positively correlated with TCF7L2 protein expression. When TCF7L2 was silenced, E2- or P4-promoted insulin/proinsulin secretion was significantly weakened. Under glucotoxicity conditions, overexpression of TCF7L2 increased insulin secretion and processing. In liver cancer cells, E2 or P4 exposure elevated TCF7L2 expression, enhanced the activity of insulin signaling (pAKT/pGSK), reduced PEPCK expression, subsequently increased insulin-stimulated glucose uptake and decreased glucose production. Silencing TCF7L2 eliminated effects of E2 or P4. In conclusion, TCF7L2 regulates E2- or P4-modulated islet and hepatic glucose metabolism. The results have implications for glucose homeostasis in pregnancy.

Background: Studies into the costs of syndromic surveillance systems are rare, especially for estimating the direct costs involved in implementing and maintaining these systems. An Integrated Surveillance System in rural China (ISSC project), with the aim of providing an early warning system for outbreaks, was implemented; village clinics were the main surveillance units. Village doctors expressed their willingness to join in the surveillance if a proper subsidy was provided. This study aims to measure the costs of data collection by village clinics to provide a reference regarding the subsidy level required for village clinics to participate in data collection. Methods: We conducted a cross-sectional survey with a village clinic questionnaire and a staff questionnaire using a purposive sampling strategy. We tracked reported events using the ISSC internal database. Cost data included staff time, and the annual depreciation and opportunity costs of computers. We measured the village doctors’ time costs for data collection by multiplying the number of full time employment equivalents devoted to the surveillance by the village doctors’ annual salaries and benefits, which equaled their net incomes. We estimated the depreciation and opportunity costs of computers by calculating the equivalent annual computer cost and then allocating this to the surveillance based on the percentage usage. Results: The estimated total annual cost of collecting data was 1,423 Chinese Renminbi (RMB) in 2012 (P25 = 857, P75 = 3284), including 1,250 RMB (P25 = 656, P75 = 3000) staff time costs and 134 RMB (P25 = 101, P75 = 335) depreciation and opportunity costs of computers. Conclusions: The total costs of collecting data from the village clinics for the syndromic surveillance system was calculated to be low compared with the individual net income in County A.

Background This survey was initiated to estimate the current status of turnaround time (TAT) monitoring of clinical biochemistry in China, provide baseline data for establishment of quality specifications and analyze the impact factors of TAT. Methods 738 laboratories were included. Questionnaires involved general information and data of related indicators of TAT during 1 week were provided to participating laboratories. Nine quality indicators were covered, which were medians, 90th and outlier rates of pre-examination, examination, and post-examination TAT. The 25th percentile, median, and 75th percentile of TATs were calculated as optimum, desirable, and minimum quality specifications. Percentages and sigma values were used to describe the outlier rates. Mann–Whitney and Kruskal–Wallis tests were used to identify the potential impacts of TAT. Results Response rate of this survey was 46.44%. More than 50% of the laboratories indicated they had set up target TATs in three time intervals and monitored TATs generally. The post-examination TAT of most laboratories was 0min, while the pre-examination and examination TAT varied. Sigma values of outlier rates for 45%~60% of laboratories were above 4, while 15%~20% of labs whose sigma values were below 3. Group comparisons suggested nurse or mechanical pipeline transportation, link laboratory information system with hospital information system, and using computer reporting instead of printing report were related to shorter TATs. Conclusions Despite of the remarkable progresses of TATs in China, there was also room to improve. Laboratories should strengthen the construction of information systems, identify reasons for TAT delay to improve the service quality continuously.

Purpose: To investigate the anti-hyperuricemic effect of Dioscorea tokoro Makino extract (DTME) in potassium oxonate-induced hyperuricemic mice. Method: The effect of DTME was investigated in the hyperuricemic mice induced by potassium oxonate. DTME. The extract was administered to the mice daily at doses of 220, 440 and 880 mg/kg for 10 days; allopurinol (5 mg/kg) was given as positive control. Serum and urine levels of uric acid and creatinine were determined by colorimetric method. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the rat kidney were analyzed by Western blotting. Results: Compared with control, a high dose of DTME inhibited xanthine oxidase (XOD) activity in both serum (18.12 ± 1.33 U/L) and in liver (70.15 ± 5.20 U/g protein) ( p < 0.05); decreased levels of serum uric acid (2.04 ± 0.64 mg/L) ( p < 0.05), serum creatinine (0.35 ± 0.18 μmol/L) and blood urea nitrogen (BUN) (8.83 ± 0.71 mmol/L) ( p < 0.05). Furthermore, the extract increased levels of urine uric acid (38.34 ± 8.23 mg/L), urine creatinine (34.38 ± 1.98 mmol/L), down regulated of URAT1 and up regulated of OAT1 protein expressions ( p < 0.05) in the renal tissue of hyperuricemic mice. Conclusion: DTME improves renal dysfunction in rats by regulating renal urate transporters in hyperuricemic rats. This may find therapeutic application in antihypertensive therapy. Keywords: Dioscorea tokoro Makino, Hyperuricemic, Renal urate transporters, Uric acid, Creatinine

Aim: To systematically evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) for the detection of gallbladder carcinoma. Material and method: Relevant studies were identified searching PubMed, Embase, Elsevier, the CNKI (China National Knowledge Infrastructure) database and the Cochrane Trial Register searches until August 2015. Patient clinical characteristics, sensitivity and specificity were extracted. The summary receiver operating characteristic (ROC) curve was used to examine the accuracy of CEUS. A meta-analysis was performed to evaluate the clinical utility in the diagnosis of gallbladder carcinoma. Sensitivity analysis was performed after omitting outliers identified in a bivariate boxplot and publication bias was assessed with Egger testing. Results: From 89 citations, 16 were included in the meta-analysis with a total of 1673 lesions. We detected heterogeneity between studies and evidence of publication bias. The methodological quality was moderate. The pooled weighted sensitivity with a corresponding 95% confidence interval (CI) was 0.92 (95%CI: 0.90, 0.94), the specificity was 0.91 (95%CI: 0.89, 0.93), the positive likelihood ratio was 10.01 (95%CI: 7.02, 14.29), the negative likelihood ratio was 0.10 (95%CI: 0.07, 0.14), and the diagnostic odds ratio was 123.02 (95%CI: 78.40, 193.03). The area under the ROC curve was 0.9689 (95%CI: 0.9376, 0.9879). Conclusions: CEUS is a reliable, non-invasive, and no-radiation-exposure imaging modality with a high sensitivity and specificity for detection of gallbladder carcinoma. Nonetheless, it should be applied cautiously, and large scale, well-designed trials are necessary to assess its clinical value.

SUMMARY The APnet information platform aims at assisting patients suffering from acute pancreatitis, health professionals and patients' relatives in the acute pancreatitis care pathway by providing an integrated information system. The system consists of a mobile platform and a Clinical Information System. The system is currently on the formal operation phase focusing on addressing the needs of citizens of China. RESUMO A plataforma de informações APnet tem como objetivo auxiliar pacientes que sofrem de pancreatite aguda, profissionais da saúde e familiares de pacientes no percurso de cuidados para a pancreatite aguda, oferecendo um sistema integrado de informações. O sistema consiste de uma plataforma móvel e um Sistema de Informações Clínicas. Ele atualmente se encontra na fase de operação formal, focado em atender às necessidades dos cidadãos da China.