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Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.

Non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases with a prevalence of 23%-25% globally, is an independent risk factor for cardiovascular diseases (CVDs). Growing evidence indicates that the development of NAFLD, ranging from non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), advanced fibrosis to cirrhosis, and even hepatocellular carcinoma, is at substantial risk for CVDs, which clinically contribute to increased cardiovascular morbidity and mortality. Non-invasive serum markers assessing liver fibrosis, such as fibrosis-4 (FIB-4) score, aspartate transaminase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), are expected to be useful tools for clinical management of patients with CVDs. This review aims to provide an overview of the evidence for the relationship between the progression of NAFLD and CVDs and the clinical application of non-invasive markers of liver fibrosis in managing patients with CVDs., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.

Liver biopsy is an important means of clinical diagnosis and treatment of liver diseases, but it is not easily accepted by patients because of its invasiveness. The most commonly employed liver biopsy approaches are percutaneous or transjugular. Endoscopic ultrasound-guided liver biopsy (EUS-LB), a newly emerging transjugular technique, has been widely studied and applied in recent years, but its application in China is less common. The EUS-LB has the advantages of high safety and comfort, simultaneous sampling of both liver lobes, and adequate sampling volume; however, it also has the disadvantages of high requirements for hardware, operators, and cost. This article reviews the clinical application of EUS-LB in accordance with pertinent research findings from recent years and discusses its advantages, disadvantages, and implementation feasibility.

Background: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear., Objectives: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure., Methods: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups., Results: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors., Conclusion: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Liver fibrosis is a key step in the developmental process of various chronic liver diseases, including cirrhosis. Therefore, the focus and difficulty of liver disease research have always been on how to reverse liver fibrosis. However, due to complex mechanisms, difficulties in endpoint evaluation, a lack of non-invasive diagnostic methods, and other factors, the research and development of new drugs are hindered and lengthy. Currently, some new drugs are being researched and developed, which signifies the prospect is optimistic.

Liver disease is a serious public health problem worldwide, affecting human health. However, there are still many unmet needs for the treatment of liver disease, especially with new therapeutic drugs. At present, there is no treatment method to eradicate the hepatitis B virus, nor are there therapeutic drugs for liver fibrosis, liver failure, and others. Chemotherapy and targeted immunotherapy are still unsatisfactory for liver cancer. This article provides an overview of the current status and challenges that arise in new drug research and development for liver diseases.

Chronic liver disease has emerged as a significant global concern, with primary hepatocellular carcinoma (HCC) representing a critical consequence of this disease. However, early detection of HCC remains challenging in clinical practice. Recently, there has been a growing interest in applying endoscopic ultrasound (EUS) as a diagnostic tool for gastrointestinal diseases. Nevertheless, using EUS to diagnose and treat HCC is uncommon. In this review we described the diagnostic and therapeutic applications of EUS in primary HCC and evaluated its clinical significance. The diagnostic procedures primarily involve EUS-guided fine-needle biopsy or aspiration, assessment of metastatic lymph nodes and portal vein thrombosis, portal pressure monitoring, and portal vein blood collection. Treatment mainly includes EUS-guided tumor ablation, brachytherapy, injectable chemotherapy, and managing variceal hemorrhage related to portal hypertension., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

A novel doubly interpenetrated indium-organic framework of 1 has been assembled by In 3+ ions and highly conjugated biquinoline carboxylate-based bitopic connectors (H 2 L). The isolated 1 exhibits an anionic framework possessing channel-type apertures repleted with exposed quinoline N atoms and carboxyl O atoms. Owing to the unique architecture, 1 displays a durable photoluminescence effect and fluorescence quenching sensing toward CrO 4 2- , Cr 2 O 7 2- , and Cu 2+ ions with reliable selectivity and anti-interference properties, fairly high detection sensitivity, and rather low detection limits. Ligand-to-ligand charge transition (LLCT) was identified as the essential cause of luminescence by modeling the ground state and excited states of 1 using DFT and TD-DFT. In addition, the negatively charged framework has the ability to rapidly capture single cationic MB, BR14, or BY24 and their mixture, including the talent to trap MB from the (MB + MO) system with high selectivity. Moreover, intrinsic light absorption capacity and band structure feature endow 1 with effective photocatalytic decomposition ability toward reactive dyes RR2 and RB13 under ultraviolet light. Notably, after further polishing the band structure state of 1 by constructing the S-scheme heterojunction of In 2 S 3 / 1 , highly efficient photocatalytic detoxification of Cr(VI) and degradation of reactive dyes have been fully achieved under visible light. This finding may open a new avenue for designing novel multifunctional MOF-based platforms to address some intractable environmental issues, i.e., detection of heavy metal ions, physical capture of pony-sized dyes, and photochemical decontamination of ultrastubborn reactive dyes and highly toxic Cr(VI) ions from water.

Objective: To estimate the performance of the FibroTouch-based ultrasound attenuation parameter (UAP) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD), with magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard., Methods: This prospective, cross-sectional study included 275 individuals in the training group and 110 individuals in the validation group, all of whom completed a standardized research visit, laboratory tests, MRI-PDFF, and UAP measurements over 1 month. Pearson correlation coefficient and Bland-Altman analysis were used to assess the agreement between UAP and MRI-PDFF for the detection of hepatic steatosis. The diagnostic value of UAP was evaluated by the area under the receiver operating characteristic (ROC) curve (AUROC). Confounding factors to UAP performance were identified by ROC curves and regression analyses., Results: The AUROC of UAP for detecting MRI-PDFF at ≥5%, ≥10%, and ≥20% were 0.95 (95% confidence interval [CI] 0.92-0.97), 0.86 (95% CI 0.81-0.90), and 0.90 (95% CI 0.86-0.93), respectively, and their optimal thresholds were 259, 274, and 295 dB/m, respectively. The UAP measurements had higher diagnostic accuracy in participants with lower waist circumference (≤90 cm for men and ≤80 cm for women) compared to those with higher waist circumference (AUROC values: 0.97 vs 0.84, P < 0.05). Bland-Altman analysis showed good agreement between UAP and MRI-PDFF (bias 0.00021). According to established regression analyses, hepatic steatosis could be accurately diagnosed using UAP estimation., Conclusions: FibroTouch-UAP has a high diagnostic potential for hepatic steatosis in NAFLD patients and helps clinical assessment and monitoring., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K&#95;m value was 209.90 μmol·L~(-1) and k&#95;(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.

Recent studies suggest that recompensation of liver function appears in decompensated cirrhosis after effective treatment. However, liver function recompensation degree, recompensation evaluation diagnostic criteria, how to predict recompensation from the perspective of liver function, and others still need to be further explored. Therefore, functional recompensation is explored here from the perspective of decompensated-stage cirrhosis.

Objective: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice., Methods: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed., Results: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella., Conclusions: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism., (© 2023. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is widespread worldwide and thereby a very serious public health problem. There are currently no effective drug treatment measures. Liver sinusoidal endothelial cells (LSECs) are the most abundant non-parenchymal cells in the liver; however, it is still not clear what role LSECs play in NAFLD. This article reviews the research progress of LSECs in NAFLD in recent years in order to provide some reference for subsequent research.

How to accurately detect and efficiently sweep Cr(VI) from contaminated water has come into focus. Zirconium-based metal-organic frameworks (MOFs) play vital roles in water environmental chemistry due to excellent hydrolysis-resistant stability. However, as photochemical probes and photocatalysts, poor performances in detection sensitivity, selectivity, and photosensitiveness limit sole Zr-MOFs' applications. So, it is urgent to quest valid strategies to break through the dilemmas. Embedding luminous dyes into MOFs has been considered one of the most feasible avenues. Herein, a dual-emissive RhB@Zr-MOF with orange-yellow fluorescence has been assembled by in situ-encapsulating rhodamine B (RhB) into a zirconium-biquinoline-based MOF. Actually, within RhB@Zr-MOF, the aggregation fluorescence quenching (ACQ) effect of RhB molecules was effectively avoided. Notably, RhB@Zr-MOF exhibits a rapid fluorescence quenching response toward Cr(VI) ions with high selectivity, sensitivity, and anti-interference abilities. More interestingly, unlike the most widely reported fluorescence resonance energy transfer (FRET) between MOFs and encapsulated guest modules, photoinduced electron transfer from RhB to Zr-MOF has been confirmed by modeling the ground state and excited states of RhB@Zr-MOF using density functional theory (DFT) and time-dependent DFT (TD-DFT). The effective electron transfer makes RhB@Zr-MOF more sensitive in probing Cr 2 O 7 2- and CrO 4 2- ions with ultralow detection limit (DL) values of 6.27 and 5.26 ppb, respectively. Prominently, the detection sensitivity based on DL values has been increased about 6 and 9 times, respectively, compared with pristine Zr-MOF. Moreover, rather negative CB and positive VB potentials make RhB@Zr-MOF have excellent photochemical scavenging ability toward Cr(VI) and MO.

Herein, a simple and straightforward method to reduce dramatically the lifetime of a pure organic thermally activated delayed fluorescence (TADF) material VIA metal coordination is demonstrated. We designed a mononuclear silver complex [Ag(PPh 2 CH 3 )(TCzBN-PyPz)]BF 4 (1) with a new emissive TCzBN-PyPz ligand. Even though the ligand and the metal complex have very similar emissive efficiencies and maximal peaks, over three orders of magnitude shorter lifetime of 0.59 μs for the complex than 2074 μs for ligand were obtained. Compared to other methods, the present protocol seems to be simple and highly effective.

Purpose: Macular degeneration is the leading cause of blindness worldwide. In this study, we aimed to define a new subtype of macular-retinal dystrophy and its genetic predisposition in 5 families., Methods: Exome sequencing was performed to determine the putative disease-causing genes in patients with inherited macular disorders confirmed through comprehensive ophthalmic examinations. To validate its functional consequence, adeno-associated virus-mediated mutant gene was delivered into the murine retina, and both structural and functional tests were performed to investigate its pathological effects in vivo., Results: In total, 5 multigenerational families diagnosed with autosomal dominant maculoretinopathy were found to carry a pathogenic variant in a new gene, CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Consistent with the disease phenotypes of patients, mice that received subretinal injections with the CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. Moreover, the optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in these mice., Conclusion: We have presented a new subtype of macular-retinal dystrophy in 5 families as well as a new pathogenic gene, CLEC3B, providing new insights into maculoretinopathy etiology., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The seeds of Tripterygium wilfordii are characterized by dormancy and a long germination cycle under natural sowing conditions. In this study, we developed a method for rapid germination of T. wilfordii seeds by analyzing the size, morphology, thousand-grain weight, viability, moisture content, physicochemical properties, and seed germination rates under different germination conditions. The seeds of T. wilfordii were fine columnar with a thick and hard outer seed coat. They had the length of 6.69 mm, the width of 2.14 mm, the thickness of 1.68 mm, the thousand-grain weight of 8.99 g, the moisture content of 8.86%, the soluble sugar content of 21.3 mg·g~(-1), the starch content of 28.9 mg·g~(-1), the soluble protein content of 44.2 mg·g~(-1), and the seed viability of only 54.0%. The seeds were respectively treated with distilled water, ultrasonication, low-temperature storage, 50 ℃ water, 100 mg·L~(-1) 6-BA, 0.6% KMnO&#95;4, 1% KNO&#95;3, 50 mg·L~(-1) NAA, and 100 mg·L~(-1) GA&#95;3 solution. The results showed that soaking the seeds in 100 mg·L~(-1) GA&#95;3 solution significantly promoted the germination. Further, the seeds were soaked in 50, 100, 250, 500, and 1 000 mg·L~(-1) GA&#95;3 solutions, which demonstrated that high concentration(500 mg·L~(-1), 1 000 mg·L~(-1)) of GA&#95;3 solutions increased the germination rate and speed and shortened the germination cycle from more than 3 months to less than 15 days. The findings of this study are of great significance to the breeding of T. wilfordii and lay a foundation for the large-scale propagation of T. wilfordii seeds and the excavation of T. wilfordii germplasm resources.

Methods and Results: We conducted a retrospective study of 531 patients with ultrasonogram-confirmed NAFLD who underwent percutaneous coronary intervention (PCI). Then, all patients were separated into four categories by Gensini score (0, 0-9, 9-48, and ≥48) for use in ordinal logistic regression analysis to determine whether NAFLD fibrosis was associated with increased Gensini scores. Mediation analysis was used to investigate whether systemic inflammation is a mediating factor in the association between NAFLD fibrosis and CAD severity. FIB - 4 > 2.67 (OR = 5.67, 95% CI 2.59-12.38) and APRI > 1.5 (OR = 14.8, 95% CI 3.24-67.60) remained to be independent risk factors for the severity of CAD after adjusting for conventional risk factors, whereas among the inflammation markers, only neutrophils and neutrophil-to-lymphocyte ratio (NLR) were independently associated with CAD. Multivariable ordinal regression analysis suggested that increasing Gensini score (0, 0-9, 9-48, and ≥48) was associated with advanced NAFLD fibrosis. ROC curve showed that either fibrosis markers or inflammation markers, integrating with traditional risk factors, could increase the predictive capacity for determining CAD. Inflammation markers, especially neutrophils and NLR, were mediators of the relationship between NAFLD fibrosis and CAD severity., Conclusions: NAFLD patients with advanced fibrosis are at a high risk of severe coronary artery stenosis, and inflammation might mediate the association between NAFLD fibrosis and CAD severity., Competing Interests: The authors have no potential conflict of interest relevant to this article., (Copyright © 2021 Ling-zi Chen et al.)

Purpose: High myopia (HM) is one of the leading causes of irreversible vision loss in the world. Many myopia loci have been uncovered with linkage analysis, genome-wide association studies, and sequencing analysis. Numerous pathogenic genes within these loci have been detected in a portion of HM cases. In the present study, we aimed to investigate the genetic basis of 103 patients with nonsyndromic HM, focusing on the reported causal genes., Methods: A total of 103 affected individuals with nonsyndromic HM were recruited, including 101 patients with unrelated sporadic HM and a mother and son pair. All participants underwent comprehensive ophthalmic examinations, and genomic DNA samples were extracted from the peripheral blood. Whole exome sequencing was performed on the mother and son pair as well as on the unaffected father. Sanger sequencing was used to identify mutations in the remaining 101 patients. Bioinformatics analysis was subsequently applied to verify the mutations., Results: An extremely rare mutation in AGRN (c.2627A>T, p.K876M) was identified in the mother and son pair but not in the unaffected father. Another two mutations in AGRN (c.4787C>T, p.P1596L/c.5056G>A, p.G1686S) were identified in two unrelated patients. A total of eight heterozygous variants potentially affecting the protein function were detected in eight of the remaining 99 patients, including c.1350delC, p.V451Cfs*76 and c.1023&#95;1024insA, p.P342Tfs*41 in SLC39A5 ; c.244&#95;246delAAG, p.K82del in SCO2 ; c.545A>G, p.Y182C in P4HA2 ; c.415C>T, p.P139S in BSG ; c.3266A>G, p.Y1089C in ZNF644 ; and c.2252C>T, p.S751L and c.1708C>T, p.R570C in CPSF1 . Multiple bioinformatics analyses were conducted, and a comparison to a group with geographically matched controls was performed, which supported the potential pathogenicity of these variants., Conclusions: We provide further evidence for the potential role of AGRN in HM inheritance and enlarged the current genetic spectrum of nonsyndromic HM by comprehensively screening the reported causal genes., (Copyright © 2021 Molecular Vision.)

Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y reconstruction after total gastrectomy is difficult to be performed using routine tools. The aim of this study was to evaluate the feasibility and safety of cap-assisted routine adult colonoscope (CARAC) for ERCP in these patients., Methods: Sixteen consecutive patients with indications of ERCP who had previously undergone total gastrectomy with Roux-en-Y reconstruction at two tertiary care endoscopy centers were identified. All ERCP procedures were carried out by using CARAC. The success rate of reaching the papilla, biliary cannulation and procedure-related adverse events were analyzed., Results: The papilla was successful reached in 11 (68.8%) of the 16 cases, and biliary cannulation was subsequently reached in eight (72.7%) of the 11 cases. The procedures succeeded in three patients by using a percutaneous-endoscopic rendezvous procedure after failed cannulation. Overall clinical success was achieved in 11 (68.8%) of 16 patients. Procedure-related mild acute pancreatitis was observed in 25.0% (4/16) of the cases and mild cholangitis in 18.8% (3/16). No serious adverse events were reported., Conclusions: CARAC for therapeutic ERCP is safe and effective in treating patients with Roux-en-Y reconstruction after total gastrectomy., (© 2021 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the effect of one-stage treatment of bone morphogenetic protein 2 combined with Jifusheng in the experimental model of osteomyelitis in rabbits., Methods: The model of chronic osteomyelitis of tibia was established in 30 3-month-old male New Zealand white rabbits with a body weight of (2.0±0.5) kg, and the model was verified 4 weeks after operation. Thirty rabbits with osteomyelitis were randomly divided into 3 groups with 10 rabbits in each group ( n = 10). The model group did not do any treatment after focal debridement, treatment group A was implanted with musculosheng at the site of focal debridement and bone defect, and treatment group B was implanted with apolipoprotein 2-Jifusheng at the site of focal debridement and bone defect. The therapeuticeffect was evaluated by blood biochemical, microbiological, imaging, pathological and immunohistochemical examination 8 weeks after operation., Results: At 4 weeks after operation, 30 rabbits with osteomyelitis were successfully validated. The results of serological examination showed that the hypersensitive C-reactive protein (CRP) and white blood cell count(WBC)in the model group were significantly higher than those in the blank group at 2 and 4 weeks after operation. Eight weeks after treatment, the detection of blood indexes showed that the white blood cell count (WBC)and hypersensitive C reactive protein (CRP)in treatment group A and treatment group B were significantly lower than those in the model group ( P <0.05), but there was no significant difference between treatment group An and treatment group B ( P >0.05). Eight weeks after treatment, the bone defect area was measured. The bone volume/total volume (BV/TV) and bone mineral density (BMD)in treatment group A and B were significantly higher than those in the model group ( P <0.05), and the bone volume/total volume (BV/TV) and bone mineral density(BMD)in treatment group B were significantly higher than those in treatment group A ( P <0.05), the repair of bone defect was almost complete, and the bone volume and bone mineral density increased significantly. At 8 weeks after treatment, the number of osteoblasts/bone tissue area (N.Ob/T.Ar) and the number of osteoblasts/bone tissue perimeter (N.Ob/B.Pm) in treatment group A and B were significantly higher than those in model group, and the N.Ob/T.Ar and N.Ob/B.Pm in treatment group B were significantly higher than those in treatment group A. The immunohistochemical staining of TNF- α and IL-6 around bone tissue in treatment group A and treatment group B was significantly less than that in model group, but there was no significant difference between treatment group B and treatment group A., Conclusion: The combined application of apolipoprotein 2-Jifusheng can promote bone repair and reduce the inflammation of the focus. it can treat rabbits with osteomyelitis in one stage, provide objective basis for the formulation of clinical treatment strategy of osteomyelitis and further promote clinical research.

Background: Dimensional measurements have been implemented on a variety of entities in morphological studies of the sub-axial cervical vertebral endplate. Despite great progress, little information between the mid-sagittal plane and bilateral uncinate processes has been acquired due to the lack of a reliable method to determine the para-sagittal planes. Also, few studies of this region are available. We proposed a new approach to defining the para-sagittal planes on a 3D cervical vertebral body model; in this approach, dimensions can be measured in a specific plane. The aim of this study was to assess the inter-observer and intra-observer reliability of the measurements in different sagittal planes on sub-axial cervical vertebral endplates of 3D models., Methods: We established mid-sagittal and bilateral quarter para-sagittal planes on the 3D model of a sub-axial cervical vertebral body based on landmarks labeled on the surface. By intersecting the vertebral body with the planes, three curves located at the three para-sagittal planes were generated. Linear dimensions were measured on every curve by two observers separately, and in total, 24 sub-axial cervical spines were included in the study. The first observer (O1) performed the procedure twice with an interval of 2 weeks. The paired t test, Wilcoxon matched-pairs signed-rank test and the interclass correlation coefficient (ICC) were employed to evaluate the inter- and intra-observer reliability of the proposed method., Results: There were no significant differences in most intra- and inter-observer comparisons, and higher non-significant proportions were found in the intra-observer comparisons than in comparisons between different observers. The interclass correlation coefficients (ICCs) in the measurements were excellent (> 0.75) in most circumstances, and the values in intra-observer comparisons were higher than those in inter-observer comparisons., Conclusions: In this study, we proposed an approach to determine the bilateral quarter para-sagittal planes in a 3D cervical vertebral body model; the results demonstrated that the method is reproducible with high intra- and inter-observer agreement., (© 2021. The Author(s).)

Background: To investigate the feasibility of using cortical bone trajectory (CBT) screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration and to provide a reference for clinical practice., Methods: Computed tomography scans of the lumbar spines of 36 patients in our hospital were used. Sixteen males and 20 females with an average age of 65.5 ± 10.5 years (range: 46 to 83 years) were included. Three-dimensional reconstruction was performed using computer software. Screws with appropriate sizes were selected for the L1 to L5 vertebral segments, and traditional pedicle screws were placed using the standard method. After completing screw placement, simulated placement of CBT screws was performed separately. No overlap occurred between the two screws in the process of CBT screw placement, and the placement point and direction were adjusted until screw placement completion. After all screw placement simulations were complete, according to the contact area of the cortical bone of the screw trajectory and the screw puncture position and distance through the trajectory, the screw placement results were categorized as excellent, good, general, and failure. Excellent and good ratings were considered successful, while a general rating was regarded as acceptable. Then, the success rate and acceptable rate of each segment of the lumbar spine were calculated., Results: Three hundred and sixty screw placement simulations were performed in lumbar pedicles, and 72 CBT screws were implanted in each vertebral body of the lumbar spine. The success rates in the L1 to L5 segments were 73.6%, 80.6%, 83.3%, 88.9%, and 77.8%, respectively, and the acceptable rates were 91.7%, 97.2%, 97.2%, 100%, and 91.7%, respectively. The overall success rate and acceptable rate of CBT screw placement in the lumbar spine were 80.8% and 95.6%, respectively., Conclusion: CBT screws are feasible for bridging fixation in lumbar adjacent segment degeneration revision surgery, and the accuracy of screw placement in different lumbar vertebrae varies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Patients with chronic liver disease generally have emotional disorders that typically manifest as depression, and seriously affects the quality of life. The mechanism of emotional disorders in patients with chronic liver disease is unclear, and may be related to variety of factors such as disease type, etiological treatment, economic, social support, and an individual psychology. Moreover, emotional disorders in patients with chronic liver disease can be assessed on a variety of scales and managed comprehensively through non-drug and drug therapy. This article reviews the potential pathogenesis, evaluation and treatment methods, in order to improve and provide more help for its effective treatment.

Introduction: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD)., Methods: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers., Results: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index., Discussion: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Endoscopic retrograde cholangiopancreatography (ERCP) is the most direct and effective method for the diagnosis and treatment of biliary and pancreatic diseases. Compared with surgery, ERCP has the advantages of minimal trauma, shorter surgery time, fewer complications, and shorter hospital stay. Liver cirrhosis, as the advanced stage of liver disease, has reduced tolerance to surgical stresses, and complications such as hepatic encephalopathy, esophagogastric varices, and coagulation dysfunction may occur during the decompensated stage, which poses a challenge to ERCP, and thus increase the intraoperative risk and postoperative complications. This article reviews and discusses the indications, risk and control management of ERCP in patients with liver cirrhosis.

Background: Endoscopic stenting to manage malignant hilar biliary obstruction has no consensus regarding the optimal stenting strategy. In this multicenter study, we compared transpapillary parallel-style bilateral metal stenting with bilateral plastic stenting, and evaluated short- and long-term outcomes., Methods: We recruited 262 consecutive patients (Bismuth classification types II-IV) who underwent either bilateral metal or plastic stenting as primary therapy at four tertiary centers. To overcome selection bias, we performed 1:1 propensity score matching. Our primary outcome was overall survival., Results: After propensity score matching, each group comprised 96 patients, with no significant differences in any baseline characteristics. The median survival was significantly longer in the metal stenting group than in the plastic stenting group (7.2 months [95% CI 6.0-8.5] vs. 4.1 months [95% CI 2.9-5.3]; P = 0.015). The clinical success rates were significantly higher in the metal stenting group than in the plastic stenting group (99.0% vs. 71.9%, respectively; P < 0.001), and lower post-procedure cholangitis incidence (7.3% vs. 26.0%; P < 0.001), longer median symptom-free stent patency (9.2 months [95% CI 7.6-10.6] vs. 4.8 months [95% CI 4.2-5.3]; P < 0.001), and fewer total interventions (1.3 ± 0.6 vs. 2.0 ± 1.4; P < 0.001). In multivariate Cox analysis of the overall survival, metal stenting (HR 0.589, P = 0.002), hilar cholangiocarcinoma (HR 0.419, P = 0.009), and adjuvant treatment (HR 0.596, P = 0.006) were independent predictors of death., Conclusions: Endoscopic therapy using bilateral metal stenting is superior to bilateral plastic stenting, with prolonged overall survival, higher clinical success, and longer stent patency in patients with advanced hilar biliary malignancies., (© 2020 Japan Gastroenterological Endoscopy Society.)

Objective: To evaluate whether patients with malignant biliary obstruction (MBO) benefit from balloon dilation before the placement of a self-expanding metal stent (SEMS) for palliative biliary drainage., Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with SEMS placement for palliative management of MBO were retrospectively included. Comparative analyses of serum bilirubin levels, post-procedural adverse events, stent patency time, stent dysfunction, and patient survival were performed between the dilation and non-dilation groups., Results: A total of 221 patients underwent palliative endoscopic SEMS implantation for MBO from January 2014 to June 2018. Dilation significantly improved the percentage of serum bilirubin improvement (37.0% vs 14.3%, P = 0.001), with a decreasing trend in the incidence of post-procedural cholangitis (2.5% vs 7.8%, P = 0.075), while the rates of other complications such as pancreatitis and bleeding were not increased. The patency time of SEMS and patient survival did not significantly differ between patients with and without dilation. Patients had endoscopic nasobiliary drainage (ENBD) but not dilation showed similar short-term outcomes as patients underwent dilation but without ENBD., Conclusions: Dilation with a small-caliber balloon catheter before the placement of SEMS is a safe and effective approach for MBO. Balloon dilation may improve the short-term efficacy of SEMS placement, while long-term outcomes are not obviously affected. The short-term effect of stricture dilation may be achieved by ENBD. Further studies are needed to confirm our results., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Aims: The endoscopic management of malignant hilar biliary obstruction (MHBO) remains extremely challenging without universal consensus. For the first time, we compared 4 major modalities aiming to determine the optimal strategy., Methods: We reviewed 1239 patients with advanced MHBO who underwent endoscopic stent placement as the primary treatment in 4 tertiary centers. Among them, 633 eligible patients were identified and classified into 4 groups: bilateral metal stent placement (BMS), unilateral metal stent placement (UMS), bilateral plastic stent placement (BPS), and unilateral plastic stent placement (UPS). The outcomes were compared before and after propensity score matching (PSM)., Results: After PSM, 87, 97, 91, and 81 patients in the BMS, UMS, BPS, and UPS groups, respectively, were matched. The clinical success rates were 98.9%, 83.5%, 71.4%, and 65.4% in the BMS, UMS, BPS, and UPS groups (P < .001), respectively. The postprocedural cholangitis rates were 8.0%, 17.5%, 26.4%, and 29.6% (P = .002), respectively. The median symptom-free stent patency was 9.6, 6.8, 4.6, and 4.2 months (P < .001), respectively. The mean number of interventions required was 1.2 ± 0.5, 1.7 ± 0.8, 2.0 ± 1.4, and 1.9 ± 1.3 (P < .001), respectively. The median (95% confidence interval) overall survival (OS) was 7.1 (6.0-8.2), 4.4 (3.8-4.9), 4.1 (2.9-5.2), and 2.7 (1.8-3.7) months (P = .001), respectively. Compared with plastic stent placement, metal stent placement achieved higher success in all outcome parameters (P ≤ .001). Bilateral stent placement was superior to unilateral stent placement in terms of clinical success (P = .024), stent patency (P = .018), and OS (P = .040)., Conclusions: If technically possible, dual metal stent placement is a preferred palliation for inoperable MHBO, and unilateral metal stent placement is the second option., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Myopia is one of the leading ocular disorders causing visual impairment worldwide, with the prevalence increasing rapidly. It's a significant global public health concern in 21st century. Myopia, particularly high myopia, often exhibits apparent familial aggregation, and multiple evidences have shown that genetic factors significantly contribute to its pathogenesis. Recent molecular technologies such as linkage analysis, candidate gene authentication, genome-wide association study (GWAS), and next-generation sequencing (NGS) have identified many myopia-associated loci and genetic mutations or variants. There exist ethnic variations in myopia occurrence as observed in populations of different genetic backgrounds, and different genetic components are found to be associated with the development of myopia-related phenotypes. A better understanding of the genetic basis triggering and controlling myopic changes may further help in myopia prevention. This review is to provide an updated overview of genetic findings in non-syndromic myopia., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: High myopia (HM) is defined as a refractive error worse than -6.00 diopter (D). This study aims to update the phenotypic and genotypic landscape of nonsyndromic HM and to establish a biological link between the phenotypic traits and genetic deficiencies., Methods: A cross-sectional study involving 731 participants varying in refractive error, axial length (AL), age, myopic retinopathy, and visual impairment. The phenotypic traits were analyzed by four ophthalmologists while mutational screening was performed in eight autosomal causative genes. Finally, we assessed the clinical relevance of identified mutations under the guidance of the American College of Medical Genetics and Genomics., Results: The relationship between refractive error and AL varied in four different age groups ranging from 3- to 85-years old. In adult groups older than 21 years, 1-mm increase in AL conferred 10.84% higher risk of pathologic retinopathy (Category ≥2) as well as 7.35% higher risk of low vision (best-corrected visual acuities <0.3) with P values < 0.001. The prevalence rates of pathologic retinopathy and low vision both showed a nonlinear positive correlation with age. Forty-five patients were confirmed to harbor pathogenic mutations, including 20 novel mutations. These mutations enriched the mutational pool of nonsyndromic HM to 1.5 times its previous size and enabled a statistically significant analysis of the genotype-phenotype correlation. Finally, SLC39A5, CCDC111, BSG, and P4HA2 were more relevant to eye elongation, while ZNF644, SCO2, and LEPREL1 appeared more relevant to refracting media., Conclusions: Our findings shed light on how multiple HM-related phenotypes are associated with each other and their link with gene variants.

Background: The treatment of difficult common bile duct stones (CBDS) remains a big challenge around the world. Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography. Fully covered self-expanding metal stent (FCSEMS) has gained increasing attention in the management of difficult CBDS., Aim: To manufacture a drug-eluting FCSEMS, which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS., Methods: Customized covered nitinol stents were adopted. Sodium cholate (SC) and disodium ethylene diamine tetraacetic acid (EDTA disodium, EDTA for short) were used as stone-dissolving agents. Three different types of drug-eluting stents were manufactured by dip coating (Stent I), coaxial electrospinning (Stent II), and dip coating combined with electrospinning (Stent III), respectively. The drug-release behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method. And the selected stone-dissolving stents were further put into porcine CBD to evaluate their biosecurity., Results: Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d. In still buffer, the final stone mass-loss rate of each group was 5.19% ± 0.69% for naked FCSEMS, 20.37% ± 2.13% for Stent I, 24.57% ± 1.45% for Stent II, and 33.72% ± 0.67% for Stent III. In flowing bile, the final stone mass-loss rate of each group was 5.87% ± 0.25% for naked FCSEMS, 6.36% ± 0.48% for Stent I, 6.38% ± 0.37% for Stent II, and 8.15% ± 0.27% for Stent III. Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile, which was significantly higher than those of other groups ( P < 0.05). In vivo , Stent III made no difference from naked FCSEMS in serological analysis ( P > 0.05) and histopathological examination ( P > 0.05)., Conclusion: The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro . When conventional endoscopic techniques fail to remove difficult CBDS, SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.

Adenosine diphosphate (ADP)-ribosylation factor-like 2 (ARL2) protein participates in a broad range of cellular processes and acts as a mediator for mutant ARL2BP in cilium-associated retinitis pigmentosa and for mutant HRG4 in mitochondria-related photoreceptor degeneration. However, mutant ARL2 has not been linked to any human disease so far. Here, we identified a de novo variant in ARL2 (c.44G > T, p.R15L) in a Chinese pedigree with MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome through whole-exome sequencing and co-segregation analysis. Co-immunoprecipitation assay and immunoblotting confirmed that the mutant ARL2 protein showed a 62% lower binding affinity for HRG4 while a merely 18% lower binding affinity for ARL2BP. Immunofluorescence images of ARL2 and HRG4 co-localizing with cytochrome c in HeLa cells described their relationship with mitochondria. Further analyses of the mitochondrial respiratory chain and adenosine triphosphate production showed significant abnormalities under an ARL2-mutant condition. Finally, we generated transgenic mice to test the pathogenicity of this variant and observed retinal degeneration complicated with microcornea and cataract that were similar to those in our patients. In conclusion, we uncover ARL2 as a novel candidate gene for MRCS syndrome and suggest a mitochondria-related mechanism of the first ARL2 variant through site-directed mutagenesis studies., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intrahepatic cholestasis is a pathological condition in which the synthesis, secretion, and excretion of bile are blocked, and thus the bile does not flow normally into the duodenum and bloodstream. According to cytological damage site, it can be divided into hepatocellular cholestasis, biliary duct cell cholestasis and mixed cell cholestasis. The two kinds of pathophysiological models [ascending or upstream (damage begins with cholangiocytes and then extends to the hepatocytes) and descending or downstream (the damage starts from the liver cells and then extends to the bile duct cells)] has distinct features in the process of disease occurrence and development. This article mainly elaborates the "descending" pathophysiological model of cholestatic liver disease (hepatocytic damage progresses to biliary duct cell), and further explores its etiology, pathogenesis and treatment methods.

Whole-genome or whole-exome sequencing (WGS/WES) of the affected proband together with normal parents (trio) is commonly adopted to identify de novo germline mutations (DNMs) underlying sporadic cases of various genetic disorders. However, our current knowledge of the occurrence and functional effects of DNMs remains limited and accurately identifying the disease-causing DNM from a group of irrelevant DNMs is complicated. Herein, we provide a general-purpose discussion of important issues related to pathogenic gene identification based on trio-based WGS/WES data. Specifically, the relevance of DNMs to human sporadic diseases, current knowledge of DNM biogenesis mechanisms, and common strategies or software tools used for DNM detection are reviewed, followed by a discussion of pathogenic gene prioritization. In addition, several key factors that may affect DNM identification accuracy and causal gene prioritization are reviewed. Based on recent major advances, this review both sheds light on how trio-based WGS/WES technologies can play a significant role in the identification of DNMs and causal genes for sporadic diseases, and also discusses existing challenges., (© 2017 Cambridge Philosophical Society.)

Systemic lupus erythematosus (SLE) is a typical autoimmune disease. Lymphotoxin β receptor (LTβR) signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%±6.98% in CD3 + cells of SLE patients, while there were almost no LTβR positive cells in CD3 + cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3, CD4 and CD8 positive T cells of active SLE patients than non/low active patients (all P <0.05), and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23R and IL-17A, and apoptosis of T cells. In conclusion, we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.

Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is heavily involved in immune response elicitation. As an important member of interferon regulatory factor (IRF) family, IRF1 can activate the expression of multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In this study, a sequence in the promoter region of the optineurin gene was compared to the 5' flanking region of the porcine isg15 gene. Porcine IRF1 also possesses antiviral activity against several swine viruses (Li et al., 2015), but the mechanism is not well understood. Herein, we report that porcine IRF1 and ISG15 were up-regulated in porcine kidney (PK-15) cells following stimulation with double-stranded RNA (dsRNA) or classical swine fever virus (CSFV) infection. We also found that siRNA-mediated knockdown of IRF1 expression resulted in lower ISG15 expression in response to polyinosinic:polycytidylic acid [poly(I:C)] or CSFV infection. The overexpression of IRF1 resulted in ISG15 up-regulation. IRF1 was shown to translocate to the nucleus in response to dsRNA stimulation. To further identify the functional domain of the isg15 gene that promotes IRF1 transcriptional activity, firefly luciferase and ISG15 reporter systems were constructed. The results of the firefly luciferase and ISG15 reporter assay suggested that IRF1 mediates the up-regulation of ISG15. Nucleotides -487 to -325, located in the 5' flanking region of the isg15 gene, constituted the promoter region of IRF1. ChIP assay indicated that IRF1 protein was able to interact with the DNA in the 5'fr of isg15 gene in cells. As an innate immune response protein with broad-spectrum antiviral activity, the up-regulation of ISG15 mediated by IRF1 in porcine cells is reported for the first time. These results warrant further investigation into the antiviral activity of porcine IRF1 against reported swine viruses., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In candidate gene era, dozens of single-nucleotide polymorphisms (SNPs) within renin-angiotensin-aldosterone system (RAAS) have been reported to be significantly associated with hypertension. However, the unbiased genome-wide association studies (GWAS) rarely identified the SNPs within RAAS were associated with hypertension or blood pressure (BP) traits. In order to figure out whether genetic polymorphisms of RAAS are really associated with hypertension, we systemically searched the GWAS Catalogue and identified all the known RAAS genes and relevant diseases/traits. After data processing, we found that polymorphisms within REN, AGT, ACE2, CYP11B2, ATP6AP2 and HSD11B2 were not associated with any disease or trait. SNPs within ACE, AGTR1, AGTR2, MAS1, RENBP and NR3C2 were associated with other diseases or traits, but showed no direct connection with hypertension. The only SNP associated with a BP trait, systolic BP was rs17367504. However, it is located in the intronic region of MTHFR near many plausible candidate genes, including CLCN6, NPPA, NPPB and AGTRAP. Therefore, the effect of RAAS polymorphisms may have been overestimated during the 'candidate gene era'. In the time of 'precision medicine', the power of RAAS variants needs to be reconsidered when evaluating one's susceptibility of hypertension.

Digested piggery wastewater(DPW) contains high concentrations of nitrogen and phosphorus which could be used as a cost-effective culture medium for Spirulina platensis . However, Spirulina platensis would be limited by many factors in the complex composition of DPW, especially the high concentration of ammonium. In this paper, a traditional sequencing batch reactor(SBR) was used to remove these inhibitors in DPW. The retention of nitrate and nitrite in the effluent, which was used as nitrogen source for cultivating Spirulina platensis , was studied at different ratios of chemical oxygen demand(COD) to total nitrogen(TN) in the influent. By comparing the growth of Spirulina platensis in the related effluents, the operation condition of SBR was optimized. The lab-scale cultivation results showed that Spirulina platensis possessed a high biomass yield of 0.084 g·(L·d) -1 in the effluent when the COD/TN ratio of SBR influent was 3.0. In particular, the concentrations of ammonium, nitrate and nitrite in the effluent were 51.2 mg·L -1 , 91.6 mg·L -1 and 213.1 mg·L -1 , respectively. Furthermore, the aforementioned effluent was also used to culture Spirulina platensis in a 120 L outdoor raceway pond, and the growth rate of Spirulina platensis reached(0.075±0.003)g·(L·d) -1 after 10-day culture. The protein content of Spirulina platensis was approximately 60% and the removal efficiency of ammonium was 99%. This study provides an alternative method for the utilization of DPW.

MicroRNAs (miRNAs) are known to be essential for retinal maturation and functionality; however, the role of the most abundant miRNAs, the miR-183/96/182 cluster (miR-183 cluster), in photoreceptor cells remains unclear. Here we demonstrate that ablation of two components of the miR-183 cluster, miR-183 and miR-96, significantly affects photoreceptor maturation and maintenance in mice. Morphologically, early-onset dislocated cone nuclei, shortened outer segments and thinned outer nuclear layers are observed in the miR-183/96 double-knockout (DKO) mice. Abnormal photoreceptor responses, including abolished photopic electroretinography (ERG) responses and compromised scotopic ERG responses, reflect the functional changes in the degenerated retina. We further identify Slc6a6 as the cotarget of miR-183 and miR-96. The expression level of Slc6a6 is significantly higher in the DKO mice than in the wild-type mice. In contrast, Slc6a6 is down-regulated by adeno-associated virus-mediated overexpression of either miR-183 or miR-96 in wild-type mice. Remarkably, both silencing and overexpression of Slc6a6 in the retina are detrimental to the electrophysiological activity of the photoreceptors in response to dim light stimuli. We demonstrate that miR-183/96-mediated fine-tuning of Slc6a6 expression is indispensable for photoreceptor maturation and maintenance, thereby providing insight into the epigenetic regulation of photoreceptors in mice., Competing Interests: The authors declare no conflict of interest.

Purpose: Familial exudative vitreoretinopathy (FEVR) is a severe hereditary retinal disorder characterized by defects in retinal vascular development. To date, six genes have been reported to be responsible for this disease, including LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to investigate the genetic defects in Chinese patients with FEVR through mutational analyses of 31 pedigrees., Methods: Clinical data and peripheral blood were collected from 31 pedigrees with FEVR. All coding sequences and intron/exon junctions were amplified and sequenced comprehensively, followed by cosegregation testing to verify suspected variants in the family members. Finally, we assessed clinical relevance of the identified mutations, according to the standards and guidelines from the American College of Medical Genetics and Genomics., Results: Twelve index cases (12/31, 38.7%) were confirmed to harbor mutations in the known genes, including one previously reported mutation and 11 novel mutations. Among the detected mutations, LRP5 accounted for the largest proportion with a mean mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31, 6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were predicted to be pathogenic by a series of bioinformatics analyses., Conclusions: We comprehensively screened six known disease-causing genes in 31 pedigrees with FEVR and achieved a clear picture of the mutation spectrum in Chinese patients with FEVR, which highlights the importance and utility of clinical genetic diagnosis.

The etiology of the highly myopic condition has been unclear for decades. We investigated the genetic contributions to early-onset high myopia (EOHM), which is defined as having a refraction of less than or equal to -6 diopters before the age of 6, when children are less likely to be exposed to high educational pressures. Trios (two nonmyopic parents and one child) were examined to uncover pathogenic mutations using whole-exome sequencing. We identified parent-transmitted biallelic mutations or de novo mutations in as-yet-unknown or reported genes in 16 probands. Interestingly, an increased rate of de novo mutations was identified in the EOHM patients. Among the newly identified candidate genes, a BSG mutation was identified in one EOHM proband. Expanded screening of 1,040 patients found an additional four mutations in the same gene. Then, we generated Bsg mutant mice to further elucidate the functional impact of this gene and observed typical myopic phenotypes, including an elongated axial length. Using a trio-based exonic screening study in EOHM, we deciphered a prominent role for de novo mutations in EOHM patients without myopic parents. The discovery of a disease gene, BSG , provides insights into myopic development and its etiology, which expands our current understanding of high myopia and might be useful for future treatment and prevention., Competing Interests: The authors declare no conflict of interest.

Background: Endoscopic ultrasonography-guided drainage has been established as a good treatment modality in the management of walled-off pancreatic necrosis, but the unmanageable infection of postoperation is still a thorny problem due to the poor drainage ability for solid necrotic debris only through transmural stent and nasocystic catheter., Aims: Introduce a novel therapeutic method, namely endoscopic ultrasonography-guided drainage combined with cyclic irrigation technique in managing patients with walled-off pancreatic necrosis., Methods: 18 patients with severe acute pancreatitis complicated with walled-off pancreatic necrosis received treatment with endoscopic ultrasonography-guided drainage combined with cyclic irrigation were involved in this retrospective study., Results: 17 of 18 patients with walled-off pancreatic necrosis were treated by this new therapeutic method. Subsequent surgery was performed in 1 case due to uncontrolled infection, complications such as perforation, bleeding or multiple organ failure were not observed. Treatment success rate was high (16 in 17, 94.12%)., Conclusion: Endoscopic ultrasonography-guided drainage combined with cyclic irrigation is an effective treatment option for symptomatic walled-off pancreatic necrosis to facilitate drainage and obviate the need for subsequent surgery or endoscopic necrosectomy., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The natural extract artemisinin and its derivatives have good anticancer activity. The present study aimed to investigate the in vitro inhibitory effects of combined dihydroartemisinin (DHA) and doxorubicin (DOX) treatment on a variety of tumor cell lines (HeLa, OVCAR-3, MCF-7, PC-3 and A549), as well as the underlying mechanisms. In addition, the in vivo effects of DHA and DOX were evaluated using a mouse HeLa tumor model. The HeLa, OVCAR-3, MCF-7, PC-3 and A549 cells were treated with a combination of DHA and DOX, and the effect on cell viability was detected by Cell Counting kit-8. The cells were observed under a fluorescence microscope after staining with Hoechst 33258 dye to observe morphological changes in the nuclei in order to determine whether the cells in the treatment group exhibited apoptosis. Apoptosis of the cells was further detected by flow cytometry, and statistical analysis was performed. The specific inhibitors of caspase-3, -8 and -9 were used to determine the intrinsic and extrinsic pathways of cell apoptosis. The cervical cancer HeLa cells treated with the combination of DHA and DOX showed up to a 91.5% decrease in viability, which was higher than that of the same cells treated with DHA or DOX alone at the same concentration, respectively (P<0.01). The optimal concentrations of the drugs used in combination were DHA at 10 µg/ml and DOX at 10 µg/ml. DHA + DOX also had a significant inhibitory effect on the ovarian cancer (OVCAR-3), breast cancer (MCF-7), lung cancer (A549) and prostate cancer (PC-3) cells. The images observed under fluorescence microscope after Hoechst 33258 staining showed marked pyknosis in the cells treated with DHA + DOX, similar to that when treated with DHA or DOX alone, which is typical in apoptosis. As determined by flow cytometry, the apoptotic rate of the cells treated with DHA + DOX at optimal concentrations was up to 90%, which was significantly higher than that of the cells treated with DHA or DOX alone at the same concentration. Caspase-9 and -3 inhibitors significantly increased the viability of the cells treated with DHA + DOX. At 6 days post-intratumoral injection of DHA + DOX, the tumor volume was markedly reduced. In vivo toxicity results revealed that the combination of the drugs had basically no effect on the body weight of the mice and had no significant toxicity on the liver, spleen, kidneys and heart of the animals. Overall, the combination of DHA and DOX markedly inhibited the viability of the HeLa, OVCAR-3, MCF-7, PC-3 and A549 cells, and acted on the HeLa cells through the intrinsic apoptotic pathway mediated by caspase-9 and caspase-3. DHA + DOX also had a significant treatment effect in vivo . This study provides a novel idea for the development of a clinical medication against several types of cancer.

Stargardt disease (STGD1) is a juvenile macular degeneration predominantly inherited in an autosomal recessive pattern, characterized by decreased central vision in the first 2 decades of life. The condition has a genetic basis due to mutation in the ABCA4 gene, and arises from the deposition of lipofuscin-like substance in the retinal pigmented epithelium (RPE) with secondary photoreceptor cell death. In this study, we describe the clinical and genetic features of Stargardt patients from four unrelated Chinese cohorts. The targeted exome sequencing (TES) was carried out in four clinically confirmed patients and their family members using a gene panel comprising 164 known causative inherited retinal dystrophy (IRD) genes. Genetic analysis revealed eight ABCA4 mutations in all of the four pedigrees, including six mutations in coding exons and two mutations in adjacent intronic areas. All the affected individuals showed typical manifestations consistent with the disease phenotype. We disclose two novel ABCA4 mutations in Chinese patients with STGD disease, which will expand the existing spectrum of disease-causing variants and will further aid in the future mutation screening and genetic counseling, as well as in the understanding of phenotypic and genotypic correlations.