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The mass transfer from a stagnant CO2 gas pocket to the flowing water in a horizontal pipe was investigated experimentally, considering the application of pH adjustment by injecting gaseous CO2 for raw water in water treatment industries. In the experiments, the variation of the CO2 gas pocket volume and the corresponding pH values of the pipe flow with time under different conditions were recorded. The mass transfer coefficient of the CO2 gas pocket in the pipe flow was then calculated. The results showed that the injection of gaseous CO2 into the pipe flow could effectively adjust the pH. The volume of the CO2 gas pocket decreased exponentially. Different from most studies on bubble mass transfer, it was found that the ambient CO2 concentration could not be neglected in this study due to the large volume of the gas pocket and the restricted space in the pipe. The mass transfer coefficient increased with the increasing ratio of the CO2 injection rate to the water flow rate and exhibited a sharp reduction as the volume of the CO2 gas pocket decreased by about 80%. The outcomes of this paper can contribute to a better understanding of gas bubble mass transfer in pipe flows. HIGHLIGHTS The mass transfer of a large CO2 gas pocket in the horizontal pipe flow was investigated, which has been hardly reported before.; During mass transfer processes, the pH variation of the pipe flow could be divided into three regimes, and the volume of the gas pocket was reduced exponentially.; The CO2 concentration in the pipe flow is important to mass transfer due to the large volume of the gas pocket and the restricted space in the pipe.;

It is widely recognized that the water flow in pipes can be affected by trapped air pockets. However, the underlying air–water interactions of free flow with non-jacking downstream of the pipe are rarely investigated. There are no studies at this time that clearly elucidate the differences in pipe flow between the vacuum and the presence of air in the free flow case. To this end, the smoothed particle hydrodynamics (SPH) method is applied to study the air–water hydraulic dynamics in the pipe under free flow. We perform SPH simulations in several different scenarios and find that (i) the SPH method is competent to simulate both single- and two-phase flows in the pipe due to its outstanding advantages in capturing complex interfaces; (ii) only when the upstream water level is higher than the top of the pipe inlet, and the water level in the pipe rises to the top of the pipe due to air resistance, can a full pipe flow be formed; and (iii) the presence of air can cause the water to form a full pipe flow, causing a siphon-like effect that promotes pipe drainage. These results provide insights into the underlying complex air–water hydraulic properties in pipe flows. HIGHLIGHTS The smoothed particle hydrodynamics method is performed for air–water simulations of pipe drainage.; The air–water hydraulic dynamics in the pipe under free flow conditions are systematically explored by analyzing changes in the flow rate and flow state.; The results show that, contrary to the commonly recognized blocking effect of trapped air in submerged flow, air in free flow can actually facilitate pipe draining.;

The forecast of rainstorm in flood season has always been the key and difficult point in the meteorological forecasting operation. First, we used the daily precipitation data from 2 227 meteorological stations in Zhejiang Province from 2016 to 2021 during the flood season (April to October), and divided the precipitation region by applying the K-means clustering algorithm, which employed the Euclidean distance as the similarity measure. Then, the regional correction method is formed by combing the spatial-temporally improved bias correction method and divided regions. Finally, we applied this method to perform the regional correction and validation on the Zhejiang Multi-Model Objective Consensus Forecast (OCF), compared with the overall correction not combined with divided regions.The results are as follows. (1) The K-means clustering algorithm can divide Zhejiang Province into 7 precipitation-similar regions, which show distinct regional characteristics closely related to the topographic features of Zhejiang Province. (2) According to validation during the 2021 flood season, the regional correction performed better than the overall correction in the OCF forecasts.Its main advantages lie in effectively reducing the false alarm of precipitation in the clear-rain forecast and substantially increasing the hit rate (POD) for the heavy rain and above, especially for the rainstorm and above from 0.25 to 0.41. (3) The typical validation show that, for both systematic and convective precipitation, the regional correction can significantly improve the intensity and falling area of precipitation for the rainstorm and above. Especially for the systematic precipitation, the regional correction demonstrated more remarkable effects, which can predict heavy rainstorms.

Bubble mass transfer is a common phenomenon in industrial applications. In this paper, bubble dynamics in both still and turbulent flow were introduced first, followed by the mass transfer properties of a single bubble and bubble swarms. Then, bubble mass transfer models for different scenarios were summarized, including three classical models, extended models, eddy diffusion and whirlpool theoretical models, and semi- or empirical correlations. Finally, existing methods for mass transfer intensification in industries were reviewed. Despite extensive researches, the mechanism for bubble mass transfer has not been fully understood. Models are commonly limited to some specific conditions and the accuracy is limited, especially for bubble swarms and bubble mass transfer in turbulent and non-Newtonian fluids. Also, the mass transfer intensification methods have their own limitations. Additional exploration of knowledge on bubble mass transfer models and further improvement in mass transfer intensification technologies are still required in the future.

Abstract Background Insulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD. Methods We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P

Abstract Using ERA5 reanalysis data from March 2021 to February 2022 and the China Meteorological Administration Global Forecasting System (CMA‐GFS) operational forecast dataset of 500 hPa geopotential height in the Northern Hemisphere in the same period, the multiscale features of forecast errors are analyzed. The results indicate that the anomaly correlation coefficient (ACC) of 500 hPa geopotential height and its multiscale components in the Northern Hemisphere keep decreasing with the extension of forecast lead time, and there are no seasonal differences in the evolution of the ACC. The effective forecast skills by season for the CMA‐GFS model are above 6 days at multiscale, with the highest skills in winter and the planetary‐scale components. In space, significant seasonal differences are observed in the locations of the extreme values of multiscale forecast errors for 500 hPa geopotential height, and the spatial distribution of forecast errors reflects the inadequate prediction of the intensity of large‐scale trough and ridge systems at middle and high latitudes and the phase‐shift prediction of small troughs and ridges at middle latitudes. Generally, the forecast errors of the original field and planetary‐scale component show wavelike or banded distribution, and the synoptic‐scale forecast errors are always distributed in latitudinal wavelike patterns alternating between positive and negative, without significant differences in the distribution of land, sea, and terrain. The first empirical orthogonal function modes of multiscale forecast errors almost retain their respective feature. In temporal, the spring, summer, and autumn time series all have quasi‐biweekly positive and negative phase transitions within the monthly scale, and the significant phase transition in winter only occurs around January 1st. These results deepen the understanding of the distribution and possible causes of forecast errors of the CMA‐GFS model and provide ideas for the improvement and revision of the model.

Polycystic kidney disease (Autosomal Dominant Polycystic Kidney Disease, ADPKD) is the most common genetic disease of the kidney, and the measurement of Total Kidney Volume (TKV) in clinical research of this disease is essential to study the progression of ADPKD. At present, the volume segmentation of polycystic kidneys mainly relies on doctors to manually outline the kidney boundary on the radiological image. This process is time-consuming, labor-intensive, inefficient, subjective, and difficult to guarantee consistency. In the research of this paper, A multi-module hybrid U-shape segmentation method is proposed (HUNet), which introduces wavelet pooling, cascade residual, and efficient multi-head self-attention into the U-shape structure. We use wavelet pooling instead of traditional down-sampling to reduce the loss of detailed features, the use of cascaded residual modules can improve the ability of model feature reuse, and the use of efficient multi-head self-attention modules can effectively capture global multi-scale information. In the decoding process of the U-shape, the corresponding loss value of each decoder will be calculated, and finally, the total loss value of the model will be obtained by weighted average. The method was trained and tested on the polycystic kidney dataset provided by Shanghai Changzheng Hospital. We automatically segmented the ADPKD in MRI images using the proposed method with a remarkably high Dice similarity coefficient relative to the manual segmentation (mean=0.915). The percentage difference between the total kidney volume values using manual and HUNet methods was only 0.4%. The proposed approach enables fast and accurate TKV measurement.

Resources reporting RNA editing sites from brain tissue have been published. Here, the authors provide an atlas of RNA editing events found in the aged and Alzheimer’s disease human brain tissue resulting in changes at protein level.

Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.

Valproic acid (VPA) is widely used as a major drug in the treatment of epilepsy. Despite the undisputed pharmacological importance and effectiveness of VPA, its potential hepatotoxicity is still a major concern. Being a simple fatty acid, the hepatotoxicity induced by VPA has long been considered to be due primarily to its interference with fatty acid β-oxidation (β-FAO). The aim of this study was to investigate the biomarkers for VPA-induced abnormal liver function in epileptic children and to determine potential mechanisms of its liver injury. Targeted metabolomics analysis of acylcarnitines (ACs) was performed in children’s serum. Metabolomic analysis revealed that VPA -induced abnormal liver function resulted in the accumulation of serum long-chain acylcarnitines (LCACs), and the reduced expression of β-FAO relevant genes (Carnitine palmitoyltrans-ferase (CPT)1, CPT2 and Long-chain acyl-CoA dehydrogenase (LCAD)), indicating the disruption of β-FAO. As direct peroxisome proliferator-activated receptor a (PPARα)- regulated genes, CPT1A, CPT2 and LCAD were up-regulated after treatment with PPARα agonist, fenofibrate (Feno), indicating the improvement of β-FAO. Feno significantly ameliorated the accumulation of various lipids in the plasma of VPA-induced hepatotoxic mice by activating PPARα, significantly reduced the plasma ACs concentration, and attenuated VPA-induced hepatic steatosis. Enhanced oxidative stress and induced by VPA exposure were significantly recovered using Feno treatment. In conclusion, this study indicates VPA-induced β-FAO disruption might lead to liver injury, and a significant Feno protective effect against VPA -induced hepatotoxicity through reversing fatty acid metabolism.

BackgroundNowadays, intelligent medicine is gaining widespread attention, and great progress has been made in Western medicine with the help of artificial intelligence to assist in decision making. Compared with Western medicine, traditional Chinese medicine (TCM) involves selecting the specific treatment method, prescription, and medication based on the dialectical results of each patient’s symptoms. For this reason, the development of a TCM-assisted decision-making system has lagged. Treatment based on syndrome differentiation is the core of TCM treatment; TCM doctors can dialectically classify diseases according to patients’ symptoms and optimize treatment in time. Therefore, the essence of a TCM-assisted decision-making system is a TCM intelligent, dialectical algorithm. Symptoms stored in electronic medical records are mostly associated with patients’ diseases; however, symptoms of TCM are mostly subjectively identified. In general electronic medical records, there are many missing values. TCM medical records, in which symptoms tend to cause high-dimensional sparse data, reduce algorithm accuracy. ObjectiveThis study aims to construct an algorithm model compatible for the multidimensional, highly sparse, and multiclassification task of TCM syndrome differentiation, so that it can be effectively applied to the intelligent dialectic of different diseases. MethodsThe relevant terms in electronic medical records were standardized with respect to symptoms and evidence-based criteria of TCM. We structuralized case data based on the classification of different symptoms and physical signs according to the 4 diagnostic examinations in TCM diagnosis. A novel cross-feature generation by convolution neural network model performed evidence-based recommendations based on the input embedded, structured medical record data. ResultsThe data set included 5273 real dysmenorrhea cases from the Sichuan TCM big data management platform and the Chinese literature database, which were embedded into 60 fields after being structured and standardized. The training set and test set were randomly constructed in a ratio of 3:1. For the classification of different syndrome types, compared with 6 traditional, intelligent dialectical models and 3 click-through-rate models, the new model showed a good generalization ability and good classification effect. The comprehensive accuracy rate reached 96.21%. ConclusionsThe main contribution of this study is the construction of a new intelligent dialectical model combining the characteristics of TCM by treating intelligent dialectics as a high-dimensional sparse vector classification task. Owing to the standardization of the input symptoms, all the common symptoms of TCM are covered, and the model can differentiate the symptoms with a variety of missing values. Therefore, with the continuous improvement of disease data sets, this model has the potential to be applied to the dialectical classification of different diseases in TCM.

Abstract Accumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimer’s disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, β-amyloid (Aβ) and phosphorylated tangles (TAU). However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brain’s transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibus P = 0.005) but not the other four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P

Imbalance of microglial phenotypes in the aging brain might underlie their involvement in late onset neurodegenerative diseases. Here we report the population structure of microglia in the aged human brain and the reduction of a particular microglia subset in individuals with Alzheimer’s disease .

Abstract Background Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Methods Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Results Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with AD-related traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant. Conclusions Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD.

Abstract Background With the development and progression of genetic technology, preimplantation genetic testing (PGT) has made it possible to block the inheritance of autosomal dominant polycystic kidney disease (ADPKD) as early as possible. However, we need to know the patients’ fertility intentions and their acceptance of PGT. Methods A questionnaire survey was conducted to collect data on the basic demographic data, quality of life, social support, fertility willingness, and level of understanding of genetic testing for blocking the inheritance of ADPKD among patients aged 18–45 years in seven hospitals from January 2018 to December 2018. After verification, statistics were calculated. Results A total of 260 patients with ADPKD were interviewed, including 137males (52.7%) and 123 females (47.3%). The overall fertility willingness rate was low (n = 117, 45.0%). The proportion of married patients aged 25–34 years that were at the optimal reproductive age but did not yet have children was relatively high (n = 77, 67.0%). The fertility intentions of ADPKD patients were significantly influenced by age (OR: 0.101, 95% CI 0.045–0.225, P

This paper experimentally studied the features of air-water flow during the emptying of a water-filled prismatic tank with a bottom orifice under different conditions. The experiments were conducted with both circular and elliptical orifices, with and without ventilation. The evolution of bubbles, water pressure variation, and water level change with time were recorded in the experiments and analyzed. Based on the results, the evolution of bubbles could be mainly divided into three stages of formation, deformation, and decomposition. Ventilation was found important to the emptying process, with which the drainage efficiency was much higher than that under the unventilated condition. Additionally, under the unventilated condition, the drainage efficiency with the circular orifice was slightly higher than that with the elliptical orifice.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common potentially life-threatening inherited kidney diseases. It is the fourth most common cause of end-stage renal disease requiring renal replacement therapy. There are few management options for controlling disease progression. Hence, identification of alternative treatments for patients is important. The Chinese herbal yinang formulation (YNF), which is derived from a Chinese patent medicine, appears to have a satisfactory effect in treating ADPKD. Because a considerable proportion of ADPKD patients presenting with chronic kidney disease (CKD) stages III–IV are diagnosed with the spleen, kidney deficiency, and blood stasis syndrome according to the diagnostic criteria of traditional Chinese medicine (TCM), we hypothesize that YNF may be a complementary drug for ADPKD patients with the corresponding syndrome. Therefore, we have designed a strict clinical trial to evaluate the safety and efficacy of YNF for ADPKD patients with CKD stages III–IV exhibiting the TCM syndrome of spleen, kidney deficiency, and blood stasis. Methods/design This is a multi-center prospective double-blind randomized controlled trial. The total target sample size is planned to be 72 participants, with a balanced treatment allocation (1:1). The experimental intervention will be YNF plus conventional therapy and the control intervention will be a placebo plus conventional therapy for 24 weeks. An additional 24 weeks of follow-up will be conducted after treatment completion. The primary outcome will be the estimated glomerular filtration rate (eGFR). Changes in total kidney volume (TKV), serum creatinine (Scr), blood urea nitrogen (BUN), TCM symptoms, and pain will be the secondary outcomes. Adverse events (AEs) will be monitored throughout the trial. Discussion This study will be the first placebo-controlled randomized controlled trial to assess whether YNF plus conventional therapy has a beneficial effect on eGFR, TKV, Scr, and BUN, and whether it can alleviate TCM clinical symptoms, reduce ADPKD-related pain, and reduce the frequency of AEs for ADPKD patients with CKD stages III–IV with the spleen, kidney deficiency, and blood stasis syndrome. The results of this trial may provide an evidence-based recommendation for clinicians. Trial registration Chinese Clinical Trials Register, ChiCTR-INR-16009914. Registered on 18 November 2016.

Abstract Background Persistent left superior vena cava (PLSVC) is a common vena cava malformation, and drains blood into the right atrium via the dilated coronary sinus in most cases. It is usually asymptomatic and detected incidentally during invasive procedures or imaging. Whether the hemodialysis catheters can be placed in PLSVC is still controversial now (Stylianou et al. Hemodial Int 11:42-45, 2007). Case presentation Here we report a rare case of catheterization through PLSVC in an end-stage renal disease (ESRD) male patient whose PLSVC connected with pulmonary vein with insufficient blood flow eventually. Among the other 28 cases included in the literature review, 16 cases were non-tunneled catheter and 12 cases were cuffed, tunneled catheter and most of them could provide adequate blood flow. Conclusion PLSVC is a rare malformation and mostly asymptotic, we believe that PLSVC drains blood into the right atrium with enough inner diameter and blood flow can serve as an alternative site for conventional dialysis access. However, the feasibility of hemodialysis catheterization through it and measures to avoid serious complications are still needed to be discussed.

Dropshafts are vertical structures widely used in urban drainage systems and buildings for water transportation. In this paper, a physical model study was conducted to investigate the air entrainment in the dropshaft under various flow regimes with and without air ventilation. Observed from the experiments, the air entrainment mechanisms varied with the water flow regimes in the dropshaft. When there was no water plug formed in the dropshaft, air could be supplied directly from downstream. Once the water plug was formed, while without venting, the air was replenished only from downstream intermittently and then in the form of large air bubble traveling upwards to the airspace at the top; while with venting, air was mainly replenished from the dropshaft top and no large air bubble was observed. The experimental results also showed that the amount of entrained air in the dropshaft with venting was greater than that without venting. Keywords: Air entrainment, Air supply, Bubble, Flow regime, Dropshaft

Geological records indicated the termination of the Holocene Thermal Maximum (dramatic drying) occurred progressively later at lower latitudes in both North Africa and East Asia, along with the coherent weakening of local summer monsoon. Here we show that this time-transgressive evolution was dominated by the southward migration of monsoon fringe (shrinking monsoon domain) under monsoon weakening, as illustrated in a transient climate-terrestrial ecosystem model simulation. The monsoon fringe retreating southward during the Holocene, as well as expanding northward during the last deglaciation, occurred synchronously in a belt extending from North Africa to East Asia, which induced a locally humid-arid transition and the subsequent dramatic environment impact. The migration of Afro-Asia monsoon fringe since the Last Glacial Maximum was modulated by the orbital forcing through its impact on land-ocean thermal contrast, aiding by the variation of CO2 concentration.

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with mutations in PKD1 or PKD2. This study aimed to identify novel PKD1 and PKD2 mutations in Chinese patients with ADPKD. Methods: Mutational analyses of both PKD genes were performed in 120 Chinese families with inherited ADPKD using long-range PCR and targeted next-generation sequencing approaches. Sanger sequencing was performed to check the positive mutations, while multiplex ligation-dependent probe amplification was adopted to examine those without mutations for the presence of large deletions. Results: A total of 93 mutations in PKD1 and PKD2 were identified in 98 Chinese families with ADPKD inheritance and the detection rate was 81.7% (98/120). The mutation rates of PKD1 and PKD2 were 91.4% (85/93) and 8.6% (85/93), respectively. Among the 93 mutations, 59.1% (55/93) were reported for the first time. A total of 65 mutations (26 nonsense, 33 frameshift, 2 large deletion, and 4 typical splicing mutations) were identified as definite pathogenic mutations. The remaining 28 mutations (21 missense, 3 in-frame deletion, and 4 atypical splicing mutations) were determined as probable pathogenic mutations. In addition, 9 de novo mutations were found by pedigree analysis. Correlation analysis between genotype and phenotype revealed that patients with PKD1 mutations or truncating mutations exhibited the most severe clinical outcome. Conclusion: The newly identified sites for known mutations will facilitate the early diagnosis and prediction of prognosis in patients with ADPKD, and provide fundamental genetic information for clinical intervention to prevent the inheritance of this disease in affected families.

Abstract Background Simultaneous consideration of two neuropathological traits related to Alzheimer’s disease (AD) has not been attempted in a genome-wide association study. Methods We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs. control brains using gene expression data. Results Genome-wide significant pleiotropic associations were observed for the joint model of NP and NFT (NP + NFT) with the single-nucleotide polymorphism (SNP) rs34487851 upstream of C2orf40 (alias ECRG4, P = 2.4 × 10−8) and for the joint model of NFT and CAA (NFT + CAA) with the HDAC9 SNP rs79524815 (P = 1.1 × 10−8). Gene-based testing revealed study-wide significant associations (P ≤ 2.0 × 10−6) for the NFT + CAA outcome with adjacent genes TRAPPC12, TRAPPC12-AS1, and ADI1. Risk alleles of proxy SNPs for rs79524815 were associated with significantly lower expression of HDAC9 in the brain (P = 3.0 × 10−3), and HDAC9 was significantly downregulated in subjects with AD compared with control subjects in the prefrontal (P = 7.9 × 10−3) and visual (P = 5.6 × 10−4) cortices. Conclusions Our findings suggest that pleiotropy analysis is a useful approach to identifying novel genetic associations with complex diseases and their endophenotypes. Functional studies are needed to determine whether ECRG4 or HDAC9 is plausible as a therapeutic target.

Traditional Chinese medicine (TCM) is based on a unique disease diagnosis and treatment system that has been developed over the last 2,300 years. In the TCM, “syndrome differentiation and treatment”(SDAT) is a core method for doctors to deal with diseases. This diagnostic and therapeutic technique that infer the occurrence and the development of diseases by observing symptoms as a whole, not only has its own uniqueness but also has been recognized by the public in oriented medical fields for its clinical efficacy. With recent developments in computer science, the Internet, big data, and artificial intelligence, a study based on the SDAT algorithm has aroused much attention. This paper encompasses three stages spanning 30 years to accomplish the following: 1) the TCM data and the modern SDAT system were collated and summarized based on 35,706 reference data on the TCM, starting from the syndrome differentiation of four aspects, such as the cause, location, characteristics, and conditions of the disease (CLCC), we constructed a quantitative model of the TCM SDAT regarding the CLCC of the disease, collected the symptom information on the diagnosed subject, and transferred them to the SDAT assistant algorithm for calculation and analysis, to determine the CLCC, Based on the therapy recommended by the differentiation results in the knowledge base and the prescription and traditional Chinese medicines recommended by the therapy, any stage of all diseases could determine a syndrome type by differentiating the CLCC, we constructed the basic SDAT algorithm integrating theory, method, prescription, and medicine and realized the calculability in the TCM diagnosis and treatment process; 2) based on the SDAT algorithm, we developed the TCM doctor's workstation software and introduced it to more than 80 TCM institutions in Sichuan province, China, we collated a large-scale trove of samples of the TCM data platform that was established with more than 2.9 million TCM electronic medical records (EMRs) and reference data, and had the compliance tested and algorithm verified on the 9,300 EMRs of the common diseases in the TCM; and 3) based on the dimension reduction and degree elevation optimization of the technology with a directed graph to the basic algorithm, the algorithm complexity was reduced and the accuracy of the algorithm was improved. It was demonstrated that the coincidence rate of the basic model was 80.47% and the basic coincidence rate was 96.19%. After optimizing the basic algorithm (for example, for gastric abscess), the coincidence rate increased by 7.04%. The test results demonstrated the efficacy of the model study. This model realized a computable SDAT to specify and assist in the differentiation diagnosis and in the treatment processes of the TCM and improve the service quality of the TCM diagnosis and treatment.

Background/Aims: In this retrospective study we aimed to compare the effect of tranexamic acid (TXA) vs etamsylate, two hemostatic agents, on hematuria duration in autosomal dominant polycystic kidney disease (ADPKD) patients with persistent gross hematuria. Methods: This is a retrospective study of 40 patients with ADPKD and macroscopic hematuria. 20 patients receiving TXA and snake venom blood clotting enzyme injection were compared with 20 matched patients receiving etamsylate and snake venom blood clotting enzyme injection. The primary outcome was hematuria duration and the secondary outcomes were blood transfusion requirements and adverse events. Results: The hematuria duration was shorter in the TXA group compared with the etamsylate group (4[3-5] d vs 7[6-10] d, P

Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs, as VPA-induced hepatotoxicity is one of the most severe adverse reaction that can lead to death. The objective of this study was to gain an understanding of dysregulated lipid metabolism in mechanism of hepatotoxicity. Nontargeted lipidomics analysis with liquid chromatography–quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) was performed to explore differential lipids from the patient serum and L02 cells. Lipidomics data interpretation was augmented by gene expression analyses for the key enzymes in lipid metabolism pathways. From patient serum lipidomics, pronouncedly changed lipid species between abnormal liver function (ALF) patients and normal liver function (NLF) patients were identified. Among these lipid species, LPCs, Cers, and SMs were markedly reduced in the ALF group and showed negative relationships with liver injury severity [alanine aminotransferase (ALT) levels], while significantly increased triacylglycerols (TAG) with higher summed carbon numbers demonstrated a positive relationship with ALT levels. Regarding lipidomics in hepatic L02 cells, TAG was markedly elevated after VPA exposure, especially in TAGs with more than 53 summed carbons. Besides, gene expression analysis revealed dysregulated lipid metabolism in VPA-treated L02 cells. Peroxime proliferators-activated receptor (PPARγ) pathway played an important role in VPA-induced lipid disruption through inducing long-chain fatty acid uptake and TAG synthesis, which was also regulated by Akt pathway. Our findings present that VPA-induced lipid metabolism disruption might lead to lipotoxicity in the liver. This approach is expected to be applicable for other drug-induced toxicity assessments.

Foreign body removal is a challenging procedure. Firstly we have to identify properly the foreign body and the position of the obstruction. Secondly we have to choose the proper removal equipment and finally the appropriate method of patient ventilation during the procedure. In our case report we present a challenging procedure with the removal of a metallic needle with minimum resources and equipment in a young girl in Djibouti, Africa. Keywords: Foreign body, Bronchoscopy, Biopsy forceps

Cuticular waxes of plant and organ surfaces play an important role in protecting plants from biotic and abiotic stress and extending the freshness, storage time and shelf life in the post-harvest agricultural products. WRI1, a transcription factor of AP2/SHEN families, had been found to trigger the related genes taking part in the biosynthesis of seed oil in many plants. But whether WRI1 is involved in the biosynthesis of the cuticular waxes on the Malus fruits surface has been unclear. We investigated the changes of wax composition and structure, the related genes and WRI1 expression on Malus asiatica Nakai and sieversii fruits with the low temperature treatments, found that low temperature induced the up-regulated expression of McWRI1, which promoted gene expression of McKCS, McLACs and McWAX in very-long-chain fatty acid biosynthesis pathway, resulting in the accumulation of alkanes component and alteration of wax structure on the fruit surface. Corresponding results were verified in McWRI1 silenced by VIGS, and WRI1 silenced down-regulated the related genes on two kinds of fruits, it caused the diversity alteration in content of some alkanes, fatty acid and ester component in two kinds of fruits. We further conducted Y1H assay to find that McWRI1 transcription factor activated the promoter of McKCS, McLAC and McWAX to regulate their expression. These results demonstrated that McWRI1 is involved in regulating the genes related synthesis of very long chain fatty acid on surface of apple fruits in storage process, providing a highlight for improvement of the modified atmosphere storage of apple fruits.

Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration.To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥ 30 ml/min/1.73 m(2). Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes.The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3 ± 10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222) and higher TKV (r = 0.134).This large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

BACKGROUND:Neighboring genes PIK3CA and KCNMB3 are both important for insulin signaling and β-cell function, but their associations with glucose-related traits are unclear. OBJECTIVE:The objective was to examine associations of PIK3CA-KCNMB3 variants with glucose-related traits and potential interaction with dietary fat. DESIGN:We first investigated genetic associations and their modulation by dietary fat in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 820). Nine single-nucleotide polymorphisms (SNPs) were selected for analysis, covering more than 80% of the SNPs in the region. We then sought to replicate the findings in the Boston Puerto Rican Health Study (BPRHS) (n = 844). RESULTS:For KCNMB3 missense mutation rs7645550, meta-analysis indicated that homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower in minor allele T homozygotes compared with major allele C carriers (pooled P-value = 0.004); for another SNP rs1183319, which is in moderate LD with rs7645550, minor allele G carriers had higher HOMA-IR compared with non-carriers in both populations (pooled P-value = 0.028). In GOLDN, rs7645550 T allele homozygotes had lower HOMA-IR only when dietary n-3: n-6 PUFA ratio was low (≤0.11, P = 0.001), but not when it was high (>0.11, P-interaction = 0.033). Similar interaction was observed between rs1183319 and n-3: n-6 PUFA ratio on HOMA-IR (P-interaction = 0.001) in GOLDN. Variance contribution analyses in GOLDN confirmed the genetic association and gene-diet interaction. In BPRHS, dietary n-3: n-6 PUFA ratio significantly modulated the association between rs1183319 and HbA1c (P-interaction = 0.034). CONCLUSION:PIK3CA-KCNMB3 variants are associated with insulin resistance in populations of different ancestries, and are modified by dietary PUFA.

BackgroundIdiopathic membranous nephropathy (IMN) is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.ObjectivesTo assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.MethodsPubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager.Main results17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect, mycophenolate mofetil (MMF) showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15).ConclusionsThis analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.