Anatomy of a selectively coassembled ß-sheet peptide nanofiber.

Peptide self-assembly, wherein molecule A associates with other A molecules to form fibrillar ß-sheet structures, is common in nature and widely used to fabricate synthetic biomaterials. Selective coassembly of peptide pairs A and B with complementary partial charges is gaining interest due to its potential for expanding the form and function of biomaterials that can be realized. It has been hypothesized that charge-complementary peptides organize into alternating ABAB-type arrangements within assembled ß-sheets, but no direct molecular-level evidence exists to support this interpretation. We report a computational and experimental approach to characterize molecular-level organization of the established peptide pair, CATCH. Discontinuous molecular dynamics simulations predict that CATCH(+) and CATCH(-) peptides coassemble but do not self-assemble. Two-layer ß-sheet amyloid structures predominate, but off-pathway ß-barrel oligomers are also predicted. At low concentration, transmission electron microscopy and dynamic light scattering identified nonfibrillar ∼20-nm oligomers, while at high concentrations elongated fibers predominated. Thioflavin T fluorimetry estimates rapid and near-stoichiometric coassembly of CATCH(+) and CATCH(-) at concentrations ≥100 µM. Natural abundance 13C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(-) coassemble into two-component nanofibers instead of self-sorting. However, 13C-13C dipolar recoupling solid-state NMR measurements also identify nonnegligible AA and BB interactions among a majority of AB pairs. Collectively, these results demonstrate that strictly alternating arrangements of ß-strands predominate in coassembled CATCH structures, but deviations from perfect alternation occur. Off-pathway ß-barrel oligomers are also suggested to occur in coassembled ß-strand peptide systems.

Dietary cholecalciferol and 25-hydroxycholecalciferol supplementation interact to modulate reproductive performance, egg quality, serum antioxidant capacity, intestinal morphology and tibia quality of breeder geese.

1. A study was conducted to evaluate the effects of dietary cholecalciferol (vitamin D3) and 25-hydroxycholecalciferol (25-OH-D3) supplementation on the reproductive performance, egg quality, eggshell ultrastructure, serum hormone level and antioxidant capacity, intestinal morphology and tibia quality of breeder geese during the laying period.2. The trial was designed as a 3 × 3 factorial arrangement with three levels (300, 400 and 500 IU/kg) of vitamin D3 supplementation and three levels (25, 50 and 75 µg/kg) of 25-OH-D3 supplementation in a 10-wk feeding trial.3. The results showed that the combined supplementation of 400 IU/kg vitamin D3 and 50 µg/kg 25-OH-D3 had a better feed conversion ratio and a higher egg laying rate than the other groups. Vitamin D3 supplementation significantly increased the rate of qualified eggs for hatching, eggshell strength and thickness, serum testosterone and progesterone levels, serum total superoxide dismutase and glutathione peroxidase activities, tibia ash content and bone mineral density (P < 0.05). Dietary 25-OH-D3 supplementation significantly increased serum glutathione peroxidase activity and duodenal villus height and villus height-to-crypt-depth ratio (P < 0.05). The geese receiving 500 IU/kg vitamin D3 and 75 µg/kg 25-OH-D3 had the highest tibia calcium and phosphorous content among all groups (P < 0.05).4. Feeding 400 IU/kg vitamin D3 plus 50 µg/kg 25-OH-D3 gave optimal effects on feed conversion ratio and egg laying rate. This combination could be a nutritional strategy for increasing the laying rate, eggshell quality, serum hormone levels and serum antioxidant function regardless of 25-OH-D3 supplementation. Supplementation of 50 µg/kg 25-OH-D3 could be a recommended dose for improving the serum antioxidant capacity and intestinal morphology regardless of vitamin D3 supplementation.

[Periodic dynamic observation and analysis of cellular and humoral immunity indexes of adults infected with Omicron BA.1].

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.

[Progress in the treatment of sarcopenia in patients with cirrhosis].

Sarcopenia, a common complication of cirrhosis, has an incidence rate as high as 40% ~ 70%. Furthermore, adverse events such as shortened survival, lower quality of life, prolonged hospital stay, increased complications, a higher mortality rate, and sometimes altering the liver transplantation prognostic outcome in patients with liver cirrhosis are closely related. In recent years, some progress has been made in the research on the treatment of sarcopenia, but there is no clear treatment plan at present; thus, research and development by researchers and clinicians still need to be strengthened. This article briefly describes the relevant treatment methods for sarcopenia in patients with cirrhosis.

[Clinical observation of bow-tie adjustable suture technique for overcorrection in intermittent exotropia].

Objective: To investigate the clinical effects of the bow-tie adjustable suture technique in managing overcorrection in patients with intermittent exotropia after surgery. Methods: This was a retrospective case series study. Clinical data were collected from children with intermittent exotropia who underwent strabismus correction surgery, including the bow-tie adjustable suture technique and conventional techniques, at the Department of Strabismus and Pediatric Ophthalmology, Shanxi Eye Hospital, from January 2020 to September 2021. Children with postoperative esodeviation≥15 prism diopters (PD) within the first 6 days were treated differently based on the surgical technique and their individual conditions, including suture adjustment and conservative treatment. The overcorrection rate and its changes among different surgical groups, the recovery of ocular alignment and binocular visual function after different treatment methods in children with overcorrection on the sixth postoperative day, and the postoperative complications in different surgical groups were observed. Statistical analysis was performed using independent samples t-test, Wilcoxon rank-sum test, repeated-measures analysis of variance, Bonferroni test, chi-square test, or Fisher's exact probability test, as appropriate. Results: A total of 643 children who underwent intermittent exotropia correction surgery were included in the study. Among them, 325 children underwent the bow-tie adjustable suture technique, with 185 males and 140 females, and the mean age was (9.50±2.69) years. The remaining 318 children underwent conventional techniques, with 176 males and 142 females, and the mean age was (9.90±2.67) years. There were no statistically significant differences in age and gender distribution between the two surgical groups (all P>0.05). On the first postoperative day, among children who underwent the bow-tie adjustable suture technique, 40 had an esodeviation of≥10 PD, resulting in an overcorrection rate of 12.3% (40/325), while among children who underwent conventional techniques, 32 had an esodeviation of≥10 PD, resulting in an overcorrection rate of 10.1% (32/318). On the sixth postoperative day, these rates decreased to 5.5% (18/325) and 3.1% (10/318) in the two groups, respectively. At 1, 6, and 12 months postoperatively, the overcorrection rate in children who underwent the bow-tie adjustable suture technique was 0, while in children who underwent conventional techniques, the overcorrection rate did not show a significant decrease compared to before surgery. The differences between the two surgical groups were statistically significant (all P<0.05). On the sixth postoperative day, among children with an esodeviation of≥15 PD, 13 underwent suture adjustment and 7 received conservative treatment. The results of repeated-measures analysis of variance showed statistically significant differences in near and distance esodeviation angles among children who received different treatment methods (F=145.20, 106.87, both P<0.001), as well as statistically significant differences in near and distance esodeviation angles at different time points within each group of children (F=81.67, 35.09, both P<0.001). There were also significant differences in the trends of change in near and distance esodeviation angles at different time points among children who received different treatment methods (F=79.90, 36.73, both P<0.001). Further pairwise comparisons showed significant differences in near and distance esodeviation angles between the sixth postoperative day and 1, 6, and 12 months postoperatively in children who underwent suture adjustment (all P<0.05), while no statistically significant differences were observed in children who received conservative treatment (all P>0.05). At 12 months postoperatively, among the 13 children who underwent suture adjustment, 12 achieved stereopsis, while among the 7 children who received conservative treatment, all became stereo-blind after removing the prismatic correction. No serious complications occurred in any of the children postoperatively. Conclusion: The proportion of children with intermittent exotropia who achieved orthotropic alignment one year after surgery was relatively low among those who had an overcorrection of≥15 PD on the sixth postoperative day. The bow-tie adjustable suture technique is a simple and effective approach for managing overcorrection in patients with intermittent exotropia. Adjusting the sutures on the sixth postoperative day can reduce the overcorrection rate and is considered a safe and effective method.

Side-Chain Chemistry Governs Hierarchical Order of Charge-Complementary ß-sheet Peptide Coassemblies.

Self-assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side-chain chemistry affects the hierarchical co-assembly of a family of charge-complementary ß-sheet-forming peptide pairs known as CATCH(X+/Y-) at physiologic pH and ionic strength in water. In a concentration-dependent manner, the CATCH(6K+) (Ac-KQKFKFKFKQK-Am) and CATCH(6D-) (Ac-DQDFDFDFDQD-Am) pair formed either ß-sheet-rich microspheres or ß-sheet-rich gels with a micron-scale plate-like morphology, which were not observed with other CATCH(X+/Y-) pairs. This hierarchical order was disrupted by replacing D with E, which increased fibril twisting. Replacing K with R, or mutating the N- and C-terminal amino acids in CATCH(6K+) and CATCH(6D-) to Qs, increased observed co-assembly kinetics, which also disrupted hierarchical order. Due to the ambient assembly conditions, active CATCH(6K+)-green fluorescent protein fusions could be incorporated into the ß-sheet plates and microspheres formed by the CATCH(6K+/6D-) pair, demonstrating the potential to endow functionality.

Validation of a Novel Multitarget Blood Test Shows High Sensitivity to Detect Early Stage Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although biannual ultrasound surveillance with or without α-fetoprotein (AFP) testing is recommended for at-risk patients, sensitivity for early stage HCC, for which potentially curative treatments exist, is suboptimal. We conducted studies to establish the multitarget HCC blood test (mt-HBT) algorithm and cut-off values and to validate test performance in patients with chronic liver disease. METHODS: Algorithm development and clinical validation studies were conducted with participants in an international, multicenter, case-control study. Study subjects had underlying cirrhosis or chronic hepatitis B virus; HCC cases were diagnosed per the American Association for the Study of Liver Diseases criteria and controls were matched for age and liver disease etiology. Whole blood and serum were shipped to a central laboratory and processed while blinded to case/control status. An algorithm was developed for the mt-HBT, which incorporates methylation biomarkers (HOXA1, TSPYL5, and B3GALT6), AFP, and sex. RESULTS: In algorithm development, with 136 HCC cases (60% early stage) and 404 controls, the mt-HBT showed 72% sensitivity for early stage HCC at 88% specificity. Test performance was validated in an independent cohort of 156 HCC cases (50% early stage) and 245 controls, showing 88% overall sensitivity, 82% early stage sensitivity, and 87% specificity. Early stage sensitivity in clinical validation was significantly higher than AFP at 20 ng/mL or greater (40%; P < .0001) and GALAD (gender, age, Lens culinaris agglutinin-reactive AFP, AFP, and des-γ-carboxy-prothrombin score) of -0.63 or greater (71%; P = .03), although AFP and GALAD at these cut-off values had higher specificities (100% and 93%, respectively). CONCLUSIONS: The mt-HBT may significantly improve early stage HCC detection for patients undergoing HCC surveillance, a critical step to increasing curative treatment opportunities and reducing mortality. ClinicalTrials.gov number NCT03628651.

Optimisation of root traits to provide enhanced ecosystem services in agricultural systems: A focus on cover crops.

Roots are the interface between the plant and the soil and play a central role in multiple ecosystem processes. With intensification of agricultural practices, rhizosphere processes are being disrupted and are causing degradation of the physical, chemical and biotic properties of soil. However, cover crops, a group of plants that provide ecosystem services, can be utilised during fallow periods or used as an intercrop to restore soil health. The effectiveness of ecosystem services provided by cover crops varies widely as very little breeding has occurred in these species. Improvement of ecosystem service performance is rarely considered as a breeding trait due to the complexities and challenges of belowground evaluation. Advancements in root phenotyping and genetic tools are critical in accelerating ecosystem service improvement in cover crops. In this study, we provide an overview of the range of belowground ecosystem services provided by cover crop roots: (1) soil structural remediation, (2) capture of soil resources and (3) maintenance of the rhizosphere and building of organic matter content. Based on the ecosystem services described, we outline current and promising phenotyping technologies and breeding strategies in cover crops that can enhance agricultural sustainability through improvement of root traits.

[Short-term outcomes of prism treatment in a manner of reducing prism diopters step by step for small-angle acute acquired concomitant esotropia].

Objective: To investigate the short-term efficacy of the prism treatment in a manner of reducing prism diopters step by step for small-angle acute acquired concomitant esotropia (AACE). Methods: Retrospective case series study. The clinical data of 17 AACE patients with strabismus ≤25 prism degrees (PD) including 6 males and 11 females, aged 14 to 60 years, who underwent the prism treatment in the Strabismus and Pediatric Ophthalmology Clinic of Shanxi Eye Hospital from October 2018 to June 2020 were collected. The prism treatment was conducted by a step-by-step reduction of prism diopters. An under-corrected prism was applied to the patient for the first time, and the degree of the prism was reduced gradually with the decrease in the degree of strabismus. Statistical analysis was performed after 6 months of treatment. The treatment success was defined as obtaining orthotropia and deleting diplopia when prism glasses were weaned off. The strabismus degree, Worth 4 dot test results, near stereopsis (Titmus stereopsis) and synoptophore fusion function before and after treatment were compared, and the factors affecting the curative effect were analyzed. Statistical methods mainly included paired t-test, Wilcoxon rank sum test, the Fisher exact test and univariate logistic regression analysis. Results: Among these 17 patients, 15 had myopia and 2 had emmetropia. Pretherapeutic esodeviation was (13.94±5.83) PD at near (33 cm), and was (15.76±5.24) PD at distance (6 m). After 6 months of treatment, 7 patients were successfully cured. The deviation angle at distance [(10.60±7.16) PD] and near [(9.80±6.00) PD] of the remaining 10 patients at 6 months after prismatic treatment was significantly smaller than that before treatment [(17.50±5.40) PD and (16.10±5.47) PD; t=3.69, 4.10; both P<0.01]. The Titmus stereogram showed that 2 cases had no stereopsis, 6 cases had peripheral stereopsis, 3 cases had macular stereopsis, and 6 cases had foveal stereopsis before treatment. Stereopsis was significantly improved at 6 months after prismatic treatment, with 3 cases havimg macular stereopsis and 14 cases having foveal stereopsis (Z=-2.99; P<0.01). The Worth-4-dot test disclosed that, the number of patients who saw four lamps at distance and near was 0 and 2 before treatment, and 7 and 9 after treatment, respectively, and the difference was statistically significant (both P<0.05). The divergent fusional amplitude and convergent fusional amplitude in the synoptophore at 6 month after treatment was not significantly different from that before treatment (both P>0.05). The efficacy of treatment was not significantly related to the duration from onset to treatment, the pretherapeutic esodeviation, the Titmus stereoacuity, cycloplegic refractive error, and age (all P>0.05). None of the 7 patients, who were successfully cured had a recurrence of esotropia or diplopia during the observation period of 6 to 24 months (median, 11 months). Conclusions: Prism treatment in a manner of step-by-step reduction of prism diopters can significantly diminish the degree of esotropia and improve the binocular function in small-angle AACE. Furthermore, some patients could be cured, achieving orthophoria without diplopia.

Single-cell RNA-seq analysis identifies unique chondrocyte subsets and reveals involvement of ferroptosis in human intervertebral disc degeneration.

OBJECTIVE: Nucleus pulposus (NP) plays a central role in disc degeneration pathogenesis, however, as a heterogeneous tissue, cell subsets in NP and their corresponding biological process in intervertebral disc degeneration (IVDD) are unreported. METHOD: Nucleus pulposus were isolated from normal control and IVDD, and then subjected to single-cell RNA sequencing (scRNA-seq). Unsupervised clustering of the cells based on the gene expression profiles using the Seurat package and passed to tSNE for clustering visualization. Rat model of disc degeneration was built to validate the pathways identified by scRNA-Seq. RESULTS: Seven chondrocyte subsets were revealed in NP based on differential gene expression, among which 4 subsets (C1-C4) were reported for the first time. Furthermore, GO and KEGG analyses discovered that ferroptosis pathways were enriched. Rat model of disc degeneration was built (n = 6/group, control vs. model) to validate the pathways identified by scRNA-Seq. Iron levels of NP were significantly higher in model group than control group (means 0.712 vs. 0.248, respectively, mg/gpro, p = 0.0026), and the levels of Heme Oxygenase 1 (HO-1) were also elevated in model group (means 14.33 vs. 5.16 IOD, respectively, p = 0.0002). However, the levels of ferritin light chain (FTL) were significantly decreased in model group compared to control group (means 26.17 vs. 9.00 FTL+ cell number, respectively, p = 0.0011). CONCLUSIONS: Novel chondrocyte subsets in nucleus pulposus were discovered through scRNA-Seq, which provided novel insight to understand the pathological change during the development of IVDD. Ferroptosis participated in disc degeneration pathogenesis and it might serve as a new target for intervening IVDD.

Transcatheter aortic valve replacement in atypical valve anatomy using the Lotus valve : A Chinese single-center experience.

BACKGROUND: In the West, the safety and efficacy of the Lotus valve have been demonstrated; however, data in the Chinese population are still lacking. Few studies have compared the clinical outcomes of transcatheter aortic valve replacement (TAVR) with the Lotus valve in patients with bicuspid or tricuspid aortic valve stenosis. Our aim was to assess TAVR outcomes with the Lotus aortic valve in a Chinese patient cohort. METHODS: In total, 23 symptomatic, high-surgical risk patients with severe aortic valve stenosis were enrolled. Among them, nine patients (39%) had bicuspid aortic valves, and three patients had a large annulus dimension. The Lotus valve was successfully implanted in all patients. To facilitate accurate positioning, partial re-sheathing was attempted in ten patients (43.5%), while one patient had a full retrieval. One-year clinical follow-up was completed in all patients. RESULTS: There were no deaths, strokes, or major adverse cardiac and cerebrovascular events in 22 of the 23 patients at 30 days; the all-cause mortality rate at 1 year was 4.4% (1 of 23 patients). The mean aortic valve gradient decreased from 51.5 ± 8.8 mm Hg at baseline to 13.4 ± 4.9 mm Hg (p < 0.001) and the valve area increased from 0.6 ± 0.2 cm2 to 1.5 ± 0.4 cm2 (p < 0.001) at 30 days. Paravalvular leakage was absent or mild (22%), and no patient had severe paravalvular leakage. Six patients (26.1%) required a postprocedural pacemaker. There was no difference regarding the procedural and the 1­year outcomes between patients with bicuspid and tricuspid aortic valve stenosis. CONCLUSION: Our single-center experience demonstrated that the Lotus valve is feasible and effective for Chinese patients with aortic valve stenosis, including atypical cases with bicuspid aortic valves or large aortic annulus size.

Multiple-Scale Analysis of Water Quality Variations and Their Correlation with Land use in Highly Urbanized Taihu Basin, China.

Understanding the relationship between land use and water quality at different scales is essential in the restoration and protection of water quality. On March 2014, we collected 97 samples in highly urbanized Taihu Basin and analyzed their water quality characteristics. Spatial differences in water quality were evident in sub-basins. The Hu Xi zone with the largest forest area had the best water quality among all the sub-basins. The correlation analysis indicated that the proportions of forest and construction land were significantly associated with multiple water quality variables from buffer to sub-basin scale. Farmland was significantly related to NO3-N at the sub-basin scale. The impact of landscape metrics at the sub-basin was insignificant. Forest and construction land in the 1-2 km buffer zone appeared to have a greater influence on the water quality than the buffers with smaller distance. These results are beneficial toward the understanding of water quality status in highly urbanized watersheds and provide a reference for water quality conservation and land use management in the future.

Diabetes at the front door. A guideline for dealing with glucose related emergencies at the time of acute hospital admission from the Joint British Diabetes Society (JBDS) for Inpatient Care Group.

People with diabetes account for nearly one-fifth of all inpatients in English and Welsh hospitals; of these, up to 90% are admitted as an emergency. Most are admitted for a reason other than diabetes with only 8% requiring admission for a diabetes-specific cause. Healthcare professionals working in emergency departments experience numerous clinical challenges, notwithstanding the need to know whether each individual with diabetes requires urgent admission. This document has been developed and written by experts in the field, and reviewed by the parent organizations of the Joint British Diabetes Societies for Inpatient Care-Diabetes UK, the Diabetes Inpatient Specialist Nurse Group and the Association of British Clinical Diabetologists. The document aims to support staff working in emergency departments and elsewhere by offering practical advice and tools for effective, appropriate and safe triage. Each section relates to the commonest diabetic specific emergencies and algorithms can be printed off to enable ease of access and use.

A higher level of total bile acid in early mid-pregnancy is associated with an increased risk of gestational diabetes mellitus: a prospective cohort study in Wuhan, China.

PURPOSE: To assess the longitudinal associations between maternal total bile acid (TBA) levels during early mid-pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). METHODS: In a prospective cohort study, pregnant women who were enrolled prior to gestational week 16 were followed until delivery. TBA levels were tested during weeks 14-18 of gestation. Using logistic regression, we analyzed the associations between quartiles of TBA and GDM based on a 75-g oral glucose tolerance test (OGTT) at 24-28 gestational weeks. RESULTS: The GDM rate was 7.9% (114/1441). The mean TBA level was higher in women with GDM than in those without GDM (2.1 ± 2.0 vs 1.5 ± 1.0 µmol/L, P = 0.000). The highest TBA level quartile (2.1-10.7 µmol/L) had a 1.78-fold (95% CI 1.01, 3.14) increased risk of GDM compared with that of the lowest quartile (0.0-0.8 µmol/L) after adjusting for pre-pregnancy body mass index (BMI), gestational, age at TBA test and other confounders. High TBA levels were involved in the fasting glucose level rather than that at 1 h and 2 h after OGTT in all participants. CONCLUSIONS: Pregnant women with higher serum TBA levels during early mid-pregnancy have a higher risk of developing GDM. TBA may be a new risk factor for GDM.

[A new perspective on acute-on-chronic liver failure based on clinical outcome of dynamic classification criteria].

Objective: To analyze the clinical characteristics among types of acute-on-chronic liver failure (ACLF) and explore the new classification criteria for judging the prognosis of acute-on-chronic liver failure, so as to provide a basis for the formulation of more precise therapeutic schedule. Methods: 388 cases with ACLF diagnosed in two tertiary level hospitals were included. Patients demographic characteristics, clinical examination information, diagnostic and treatment process information were collected. Laboratory examination data of day 1, 3, 7, 14, 21, 28 and of week 12 or prior to discharge after improvement and at 24 h prior to liver transplantation or death from the diagnosis of ACLF were collected. According to the change trend of the patient's prothrombin activity (PTA), the changes within 4 weeks and 12 weeks were divided into: increased to > 40 %, increase but still ≤ 40%, progressively decreasing or not continuously rising. Moreover, the change trend of total bilirubin (TBil) was divided into: decreasing degree≥50%, decreasing degree < 50%, progressively increasing or not decreasing. Patients meeting the requirements of dynamic classification were screened. PTA and TBil variation tendency of each patient at week 4 and 12 was synthesized, and prognostic condition for dynamic classification was formulated. The clinical characteristics of ACLF patients were analyzed by χ (2) test. Results: A total of 262 screened cases were enrolled. At the 4th week of the course of disease, 45% of the patients' PTA had increased to > 40%, and 40.8% of the patients' TBIL had decreased by 50%. When the course of disease was progressed to 12 weeks, 65.3% of the patients' PTA had increased to > 40%, and 63.4% of the patients' TBIL had decreased by 50%. Combined with the prognosis of the patients at the 4th and 12th week, the patients' disease evolution process was divided into five types: Type A: 60 cases (22.9%) of rapid progression; Type B: 82 cases (31.3%) of rapid recovery; Type C: 48 cases (18.3%) of slow progression; Type D: 43 cases (16.4%) of slow recovering; Type E: 29 cases (11.1%) of slow persistence. The proportions of patients with rapid progression combined with upper gastrointestinal hemorrhage, hepatic encephalopathy, and acute renal injury were 16.7%, 33.3%, and 33.3%, respectively; while the above-mentioned complications accounted for 3.7%, 7.3%, and 12.2% only in the rapid recovery type, χ (2) = 14.411, 20.060, 12.140, P < 0.05, and the differences were statistically significant. Fungal infection rates were 21.7%, and 10.4% in patients who died of disease or liver transplantation (i.e., patients with rapid progression and slow-progressing types), respectively, and 1.2%, 14%, and 6.9% in patients with rapid progression type, slow-recovering type, and slow persistence type, respectively, and the difference between the rapid progression type and the rapid recovery type was significant, χ (2) = 18.925, and the difference was statistically significant (P < 0.05). Conclusion: The course of disease progression in ACLF patients can be divided into rapid progression type, rapid recovery type, slow progression type, slow recovering type, and slow persistence type. The basis of liver disease, accompanied with fungal infection, gastrointestinal hemorrhage, hepatic encephalopathy and acute renal injury can affect the development of ACLF.

[Comparison of clinical features between patients with acute-on-chronic liver failure and decompensated liver cirrhosis combined with acute kidney injury].

Objective: To compare the clinical features between patients with acute-on-chronic liver failure (ACLF) and decompensated liver cirrhosis (DC) combined with acute kidney injury (AKI). Methods: Demographic data, clinical examination results, diagnosis and treatment information of ACLF and DC patients were collected retrospectively. Clinical characteristics of ACLF combined with AKI and DC combined with AKI and their impact on the 90-day mortality risk were compared. Results: The clinical characteristics of patients with ACLF-AKI and DC-AKI were compared. The results showed that the leukocyte count, absolute neutrophil count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) of ACLF-AKI patients were higher than those of DC-AKI patients, while prothrombin activity (PTA), and albumin were lower than those of DC-AKI patients, and the difference was statistically significant (P < 0.05). The co-infection rate in patients with ACLF-AKI was significantly higher than that of DC-AKI group (96.9% vs. 39.5%) (P < 0.05), and during the diagnosis of AKI, the median value of serum creatinine in ACLF patients was 147 µmol / L (IQR: 122-189), while that in DC group was 123.5 µmol / L (IQR: 103.8-155.5), and the difference between the two groups was statistically significant (P < 0.05). According to the HRS-AKI diagnostic criteria for liver cirrhosis, 44 (68.8%) cases of ACLF-AKI met the diagnosis of HRS -AKI, which was significantly higher than the proportion of 18 (47.4%) cases of DC-AKI (P < 0.05). Four (10.5%) cases of DC-AKI had died or underwent liver transplantation within 30 days and eight (21.1%) cases had died or underwent liver transplantation within 90 days, while 22 (34.4%) cases of ACLF-AKI patients had died or underwent liver transplantation within 30 days and 35 (54.7%) cases had died or underwent liver transplantation within 90 days, and χ (2) values was 7.140 and 11.062, respectively (P < 0.05). The results of multivariate regression analysis suggested that the independent risk factors that affect the 90-days mortality rate of DC patients were hepatic encephalopathy, gastrointestinal bleeding, and TBil, while the independent risk factors affecting the 90-days death risk of ACLF patients included AKI, PTA and TBil. Conclusion: Compared with DC-AKI patients, ACLF-AKI patients have a higher proportion of infection rate, higher serum creatinine level when diagnosed AKI, and faster disease progression, leading to a greater risk of death.

[Long-term clinical effects of the bilateral superior oblique tendon suture spacer in the treatment of A-pattern strabismus].

Objective: To investigate the long-term clinical efficacy and safety of the bilateral superior oblique tendon suture spacer in treatment of A-pattern strabismus with superior oblique overaction (SOOA). Methods: Retrospective case series study. Twenty-one A-pattern strabismus patients who received the quantitative bilateral superior oblique tendon suture spacer with a complete follow-up from January 2009 to August 2017 were enrolled. Among these patients, 19 were exotropic and 2 were esotropic, including 11 males and 10 females, aged (14±9) years. Patients with unilateral superior oblique overaction, Broun syndrome or Helveston syndrome were excluded. The A-pattern strabismus, objective torsion, function of the superior oblique muscle and binocular vision were examined pre-and post-operatively. Paired t-test was used for normal distribution data, Wilcoxon rank-sum test was used for non-normal distribution data, Spearman rank correlation test and simple linear regression were used to analyze the correlation between the two variables. Results: The follow-up was 12 to 109 months (mean, 26±17 months). Twenty patients showed good alignment in the primary position with a deviation angle less than 10 prism diopter (PD), and 1 patient with esotropia had an angle greater than 15 PD. All the patients had no A pattern after surgery. The average pre-and post-operative A-patterns were (23.81±9.47) PD and (0.90±3.59) PD (t=11.29, P<0.01), respectively, and the average corrected A pattern was (23.52±9.68) PD.The average pre-and post-operative torsion was 3.18°±3.26° and -4.81°±4.13° (t=8.87, P<0.01), espectively, and the average corrected torsion was 7.95°±3.88°. No patient complained of torsional diplopia after surgery. The average amount of pre-and post-operative SOOA was 3.0 (2.0) and 0.0 (1.0) in 42 eyes (Z=-5.78, P<0.01), respectively. Suture extension of the superior oblique tendon was related with the pre-operative SOOA (r=0.47, P<0.01), but was not related with the pre-operative torsion (r=0.02, P=0.88). The linear regression results was suture extension=2.71× the grade of pre-operative SOOA (t=27.93, P<0.01). Conclusions: The bilateral superior oblique tendon suture spacer can improve the A-pattern, objective torsion and SOOA, with no torsional diplopia or V pattern after the long-term follow-up. It is a safe and effective superior oblique muscle weakening procedure. (Chin J Ophthalmol, 2020, 56: 853-858).

The combination of apolipoprotein E4, age and Alzheimer's Disease Assessment Scale - Cognitive Subscale improves the prediction of amyloid positron emission tomography status in clinically diagnosed mild cognitive impairment.

BACKGROUND AND PURPOSE: Randomized clinical trials involving anti-amyloid interventions focus on the early stages of Alzheimer's disease (AD) with proven amyloid pathology, using amyloid positron emission tomography (amyloid-PET) imaging or cerebrospinal fluid analysis. However, these investigations are either expensive or invasive and are not readily available in resource-limited centres. Hence, the identification of cost-effective clinical alternatives to amyloid-PET is highly desirable. This study aimed to investigate the accuracy of combined clinical markers in predicting amyloid-PET status in mild cognitive impairment (MCI) individuals. METHODS: In all, 406 MCI participants from the Alzheimer's Disease Neuroimaging Initiative database were dichotomized into amyloid-PET(+) and amyloid-PET(-) using a cut-off of >1.11. The accuracies of single clinical markers [apolipoprotein E4 (ApoE4) genotype, demographics, cognitive measures and cerebrospinal fluid analysis] in predicting amyloid-PET status were evaluated using receiver operating characteristic curve analysis. A logistic regression model was then used to determine the optimal model with combined clinical markers to predict amyloid-PET status. RESULTS: Cerebrospinal fluid amyloid-ß (Aß) showed the best predictive accuracy of amyloid-PET status [area under the curve (AUC) = 0.927]. Whilst ApoE4 genotype (AUC = 0.737) and Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 13 (AUC = 0.724) independently discriminated amyloid-PET(+) and amyloid-PET(-) MCI individuals, the combination of clinical markers (ApoE4 carrier, age >60 years and ADAS-Cog 13 > 13.5) improved the predictive accuracy of amyloid-PET status (AUC = 0.827, P < 0.001). CONCLUSIONS: Cerebrospinal fluid Aß, which is an invasive procedure, is most accurate in predicting amyloid-PET status in MCI individuals. The combination of ApoE4, age and ADAS-Cog 13 also accurately predicts amyloid-PET status. As this combination of clinical markers is cheap, non-invasive and readily available, it offers an attractive surrogate assessment for amyloid status amongst MCI individuals in resource-limited settings.

Management of adults with diabetes on the haemodialysis unit: summary of guidance from the Joint British Diabetes Societies and the Renal Association.

Diabetic nephropathy remains the principal cause of end-stage renal failure in the UK and its prevalence is set to increase. People with diabetes and end-stage renal failure on maintenance haemodialysis are highly vulnerable, with complex comorbidities, and are at high risk of adverse cardiovascular outcomes, the leading cause of mortality in this population. The management of people with diabetes receiving maintenance haemodialysis is shared between diabetes and renal specialist teams and the primary care team, with input from additional healthcare professionals providing foot care, dietary support and other aspects of multidisciplinary care. In this setting, one specialty may assume that key aspects of care are being provided elsewhere, which can lead to important components of care being overlooked. People with diabetes and end-stage renal failure require improved delivery of care to overcome organizational difficulties and barriers to communication between healthcare teams. No comprehensive guidance on the management of this population has previously been produced. These national guidelines, the first in this area, bring together in one document the disparate needs of people with diabetes on maintenance haemodialysis. The guidelines are based on the best available evidence, or on expert opinion where there is no clear evidence to inform practice. We aim to provide clear advice to clinicians caring for this vulnerable population and to encourage and improve education for clinicians and people with diabetes to promote empowerment and self-management.

Post-assembly α-helix to ß-sheet structural transformation within SAF-p1/p2a peptide nanofibers.

We report an unanticipated helix-to-sheet structural transformation within an assembly of SAF-p1 and SAF-p2a designer peptides. Solid-state NMR spectroscopic data support the assembled structure that was targeted by rational peptide design: an α-helical coiled-coil co-assembly of both peptides. Subsequent to assembly, however, the system converts to a ß-sheet structure that continues to exhibit nearest-neighbor interactions between the two peptide components. The structural transition occurs at pH 7.4 and exhibits strongly temperature-dependent kinetics between room temperature (weeks) and 40 °C (minutes). We further observed evidence of reversibility on the timescale of months at 4 °C. The structural conversion from the anticipated structure to an unexpected structure highlights an important aspect to the challenge of designing peptide assemblies. Furthermore, the conformational switching mechanism mediated by a prerequisite α-helical nanostructure represents a previously unknown route for ß-sheet designer peptide assembly.