Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS. METHODS: We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching. RESULTS: Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported. CONCLUSIONS: Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed. TRAIL REGISTRATION: ChiCTR2200063759, September 16, 2022.

Triglyceride-Glucose Index is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients with HBV-Related Liver Cirrhosis.

Aim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC. Results: The median follow-up time was 37 months (range: 6-123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P<0.01), DC (P<0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P<0.01), and HBV DNA positivity (P<0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, <0.01, 0.05, and <0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P<0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively. Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.

Estimated glomerular filtration rate partially recovered in patients without Hypertriglyceridemia during Tenofovir disoproxil fumarate treatment.

BACKGROUND: Decrease in estimated glomerular filtration rate (eGFR) during Tenofovir disoproxil fumarate (TDF) treatment remains a concern, and few patients experience partial recovery of eGFR. This study aimed to investigate the risk factors for eGFR recovery in patients with and without hypertriglyceridemia. METHODS: A total of 203 patients with chronic HBV infection were prospectively recruited and followed up for three years. Data were collected at baseline, first, second, and third years during TDF treatment. RESULTS: Most patients achieved normal ALT (80.0% vs. 82.5%) and undetectable HBV DNA (95.0% vs. 95.6%) in both groups (p > 0.05). For patients with hypertriglyceridemia, eGFR and cholesterol did not change significantly during the 3-year follow-up, while triglyceride (TG) decreased significantly in the first year and persisted at a lower level in the subsequent two years. For patients without hypertriglyceridemia, eGFR declined significantly in the first year of treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG at the four time points. Fifteen (15/183, 8.2%) patients without hypertriglyceridemia experienced eGFR partial recovery in the third year. Univariate and multivariate analyses showed that baseline eGFR <90 mL/(min·1.73 m2) (p < 0.01; 95% CI: 0.019-0.284) and age (p < 0.01; 95% CI: 0.817-0.960) were independent risk factors for eGFR recovery. CONCLUSION: eGFR partially recovered in patients without hypertriglyceridemia during TDF treatment, and TG regulation might be a useful strategy to hinder renal function decline, although larger, confirmatory studies are necessary to validate our findings.Key messagesFor patients with normal triglyceride, eGFR declined significantly at the first year of TDF treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG. Baseline eGFR <90 mL/(min·1.73 m2) and age were independent risk factors for eGFR recovery.

Dynamic changes of estimated glomerular filtration rate are conversely related to triglyceride in non-overweight patients.

BACKGROUND: Correlation between Triglyceride (TG) and estimated glomerular filtration rate (eGFR) remains largely unknown in overweight and non-overweight patients. AIM: To investigated the dynamic changes of eGFR and lipid profiles during 3-year tenofovir disoproxil fumarate (TDF) treatment in patients with chronic hepatitis B (CHB) and overweight. METHODS: A total of 202 CHB patients who received TDF treatment at the Third People's Hospital of Changzhou (Changzhou, China) and Nanjing Drum Tower Hospital (Nanjing, China) between January 2016 and May 2018 were retrospectively enrolled. According to the body mass index (BMI) at the initiation of TDF treatment, CHB patients were divided into overweight (BMI ≥ 25 kg/m2) and non-overweight (BMI < 25 kg/m2) groups. Logistic regression was applied for the analysis of risk factors for eGFR < 90 mL/(min·1.73 m2). RESULTS: There is no significant difference in hepatitis B virus DNA (HBV DNA) negativity and hepatitis Be antigen (HBeAg) loss between patients with overweight and non-overweight (both P > 0.05). More patients in non-overweight group achieved alanine aminotransferase normalization compared with those in overweight group (χ 2 = 11.036, P < 0.01). In non-overweight patients, the eGFR significantly declined in the 1st year (P < 0.01), then remained at a relatively lower level. TG significantly declined in the 2nd year (P = 0.02) and increased in the 3rd year. Moreover, TG was negatively correlated with GFR at the four-time points (P = 0.002, 0.030, 0.007, 0.008, respectively). In overweight patients, eGFR and TG remained relatively stable during the 3-year treatment, and eGFR showed no significant relationship with TG. Moreover, multivariate analysis showed that age [P < 0.01, 95%CI (0.97-1.005)] and baseline eGFR [P < 0.01, 95%CI (5.056-33.668)] were independent risk factors for eGFR < 90 mL/(min·1.73 m2) at the 3rd year. CONCLUSION: Dynamic changes in renal function were conversely related to TG during TDF treatment in patients with CHB and normal BMI, but not with overweight.

Sentinel lymph node metastasis diagnosis using ultrasound plus magnetic resonance lymphangiography in breast cancer.

Background: Ultrasound diagnosis is a highly specific tool and widely applied, but is associated with low sensitivity in detection of sentinel lymph nodes (SLNs). The diagnostic value of routine ultrasound combining magnetic resonance lymphangiography (MRL) for the detection of SLNs in breast cancer metastasis is still unclear. This study used ultrasound combined with MRL to explore the diagnostic value of detecting SLN metastasis in breast cancer. Methods: This study included female breast cancer patients who received modified radical mastectomy at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2019. The gold standard of SLNs is pathological results. The patients were divided into three groups: (I) Group A: an ultrasound plus MRL (contrast agent injected outside the areola) group; (II) Group B: an ultrasound plus MRL (contrast agent injection around the areola) group; and (III) Group C: an ultrasound plus MRL group (this group comprised patients from the two aforementioned groups). Results: A total of 432 patients were included. The overall detection rate and overall diagnostic accuracy of SLNs in breast cancer differed significantly among the three groups (all P<0.05). Ultrasound plus MRL showed a best overall detection rate 56.02%, and a best diagnostic accuracy 95.83%. The detection rate and diagnostic accuracy of axillary SLNs varied markedly among the three groups (P<0.05). The detection rate and diagnostic accuracy when the internal mammary node was the SLN differed notably between the ultrasound plus MRL (contrast agent injected outside the areola) and ultrasound plus MRL (contrast agent injection around the areola) groups and between the ultrasound plus MRL (contrast agent injection around the areola) and ultrasound plus MRL groups (all P<0.05). Conclusions: Ultrasound plus MRL may be advantageous for the detection of SLN metastasis in breast cancer and predicting breast cancer prognosis.

Exploring highly reliable substructures in auto-reconstructions of a neuron.

The digital reconstruction of a neuron is the most direct and effective way to investigate its morphology. Many automatic neuron tracing methods have been proposed, but without manual check it is difficult to know whether a reconstruction or which substructure in a reconstruction is accurate. For a neuron's reconstructions generated by multiple automatic tracing methods with different principles or models, their common substructures are highly reliable and named individual motifs. In this work, we propose a Vaa3D-based method called Lamotif to explore individual motifs in automatic reconstructions of a neuron. Lamotif utilizes the local alignment algorithm in BlastNeuron to extract local alignment pairs between a specified objective reconstruction and multiple reference reconstructions, and combines these pairs to generate individual motifs on the objective reconstruction. The proposed Lamotif is evaluated on reconstructions of 163 multiple species neurons, which are generated by four state-of-the-art tracing methods. Experimental results show that individual motifs are almost on corresponding gold standard reconstructions and have much higher precision rate than objective reconstructions themselves. Furthermore, an objective reconstruction is mostly quite accurate if its individual motifs have high recall rate. Individual motifs contain common geometry substructures in multiple reconstructions, and can be used to select some accurate substructures from a reconstruction or some accurate reconstructions from automatic reconstruction dataset of different neurons.

Suppression of lncRNA HOXA11-AS/miR-124 Axis Inhibits Glioma Progression.

Our aim was to clarify the regulations of lncRNA HOXA11-AS (HOXA11-AS) played on the progression of glioma as well as to investigate the mechanisms by which HOXA11-AS modulated development of glioma. This study confirmed the regulations of miR-124 and HOXA11-AS on the progression of glioma. Here, HOXA11-AS was overexpressed and miR-124 was underexpressed in glioma. Expression of miR-124 was negatively related to that of HOXA11-AS. Silencing of HOXA11-AS suppressed cell proliferation, invasion, and promoted apoptosis in glioma cells in vitro. Moreover, inhibition of HOXA11-AS expression repressed glioma xenograft tumor growth. Expression of miR-124 was repressed by HOXA11-AS functioning as sponge. In addition, miR-124 knockdown partially abolished the inhibitory roles of HOXA11-AS downregulation in glioma cells. Conclusively, this study suggested that silencing of HOXA11-AS restrained proliferation, invasion, induced apoptosis of glioma cells, and repressed xenograft growth via modulating miR-124 expression and thus inhibited glioma progression.

Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues.

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

Retrieving similar substructures on 3D neuron reconstructions.

Since manual tracing is time consuming and the performance of automatic tracing is unstable, it is still a challenging task to generate accurate neuron reconstruction efficiently and effectively. One strategy is generating a reconstruction automatically and then amending its inaccurate parts manually. Aiming at finding inaccurate substructures efficiently, we propose a pipeline to retrieve similar substructures on one or more neuron reconstructions, which are very similar to a marked problematic substructure. The pipeline consists of four steps: getting a marked substructure, constructing a query substructure, generating candidate substructures and retrieving most similar substructures. The retrieval procedure was tested on 163 gold standard reconstructions provided by the BigNeuron project and a reconstruction of a mouse's large neuron. Experimental results showed that the implementation of the proposed methods is very efficient and all retrieved substructures are very similar to the marked one in numbers of nodes and branches, and degree of curvature.

Impact of a real-time automatic quality control system on colorectal polyp and adenoma detection: a prospective randomized controlled study (with videos).

BACKGROUND AND AIMS: Quality control can decrease variations in the performance of colonoscopists and improve the effectiveness of colonoscopy to prevent colorectal cancers. Unfortunately, routine quality control is difficult to carry out because a practical method is lacking. The aim of this study was to develop an automatic quality control system (AQCS) and assess whether it could improve polyp and adenoma detection in clinical practice. METHODS: First, we developed AQCS based on deep convolutional neural network models for timing of the withdrawal phase, supervising withdrawal stability, evaluating bowel preparation, and detecting colorectal polyps. Next, consecutive patients were prospectively randomized to undergo routine colonoscopies with or without the assistance of AQCS. The primary outcome of the study was the adenoma detection rate (ADR) in the AQCS and control groups. RESULTS: A total of 659 patients were enrolled and randomized. A total of 308 and 315 patients were analyzed in the AQCS and control groups, respectively. AQCS significantly increased the ADR (0.289 vs 0.165, P < .001) and the mean number of adenomas per procedure (0.367 vs 0.178, P < .001) compared with the control group. A significant increase was also observed in the polyp detection rate (0.383 vs 0.254, P = .001) and the mean number of polyps detected per procedure (0.575 vs 0.305, P < .001). In addition, the withdrawal time (7.03 minutes vs 5.68 minutes, P < .001) and adequate bowel preparation rate (87.34% vs 80.63%, P = .023) were superior for the AQCS group. CONCLUSIONS: AQCS could effectively improve the performance of colonoscopists during the withdrawal phase and significantly increase polyp and adenoma detection. (Clinical trial registration number: NCT03622281.).

Photochemical route for synthesizing Co-P alloy decorated ZnIn2S4 with enhanced photocatalytic H2 production activity under visible light irradiation.

A series of amorphous Co-P alloy modified ZnIn2S4 composite samples were synthesized through a one-step photochemical method. The as-prepared samples were systematically characterized and the photocatalytic activity for H2 production under visible-light irradiation was investigated. It was found that the Co-P/ZnIn2S4 composite samples exhibited higher photocatalytic activity, which is 44 times higher than that of pure ZnIn2S4 and higher than that of the 1 wt% Pt/ZnIn2S4 sample. After modifying with amorphous Co-P alloy, the composite samples showed enhanced photocurrent, reduced photoelectric impedance, weakened fluorescence intensity and extended fluorescence lifetime, which accelerate the separation and transfer of photoinduced charge effectively, thus improving the catalytic activity of the composite sample. This work could provide a new strategy for the design and synthesis of low-cost, high-efficiency composite materials for photocatalytic hydrogen evolution and is promising for energy conversion and utilization.

M-AMST: an automatic 3D neuron tracing method based on mean shift and adapted minimum spanning tree.

BACKGROUND: Understanding the working mechanism of the brain is one of the grandest challenges for modern science. Toward this end, the BigNeuron project was launched to gather a worldwide community to establish a big data resource and a set of the state-of-the-art of single neuron reconstruction algorithms. Many groups contributed their own algorithms for the project, including our mean shift and minimum spanning tree (M-MST). Although M-MST is intuitive and easy to implement, the MST just considers spatial information of single neuron and ignores the shape information, which might lead to less precise connections between some neuron segments. In this paper, we propose an improved algorithm, namely M-AMST, in which a rotating sphere model based on coordinate transformation is used to improve the weight calculation method in M-MST. RESULTS: Two experiments are designed to illustrate the effect of adapted minimum spanning tree algorithm and the adoptability of M-AMST in reconstructing variety of neuron image datasets respectively. In the experiment 1, taking the reconstruction of APP2 as reference, we produce the four difference scores (entire structure average (ESA), different structure average (DSA), percentage of different structure (PDS) and max distance of neurons' nodes (MDNN)) by comparing the neuron reconstruction of the APP2 and the other 5 competing algorithm. The result shows that M-AMST gets lower difference scores than M-MST in ESA, PDS and MDNN. Meanwhile, M-AMST is better than N-MST in ESA and MDNN. It indicates that utilizing the adapted minimum spanning tree algorithm which took the shape information of neuron into account can achieve better neuron reconstructions. In the experiment 2, 7 neuron image datasets are reconstructed and the four difference scores are calculated by comparing the gold standard reconstruction and the reconstructions produced by 6 competing algorithms. Comparing the four difference scores of M-AMST and the other 5 algorithm, we can conclude that M-AMST is able to achieve the best difference score in 3 datasets and get the second-best difference score in the other 2 datasets. CONCLUSIONS: We develop a pathway extraction method using a rotating sphere model based on coordinate transformation to improve the weight calculation approach in MST. The experimental results show that M-AMST utilizes the adapted minimum spanning tree algorithm which takes the shape information of neuron into account can achieve better neuron reconstructions. Moreover, M-AMST is able to get good neuron reconstruction in variety of image datasets.