Prediction of Alzheimer's Disease Based on 3D Genome Selected circRNA.

Alzheimer's disease (AD) is a neurodegenerative disease and there is by far no effective treatment for it, especially in its late stage. Circular RNAs (circRNAs), known as a class of non-coding RNAs are widely observed in eukaryotic transcriptomes, and are reported to play an important role in neurodegenerative diseases including AD. circRNAs usually act as microRNA (miRNA) inhibitors or «sponges¼ to regulate the function of miRNAs, leading to subsequent changes in protein activities and functions. Accumulating evidence indicates that circRNAs can serve as potential biomarker in AD early prediction. The functional roles of circRNAs are very versatile including miRNAs binding - thus affecting downstream gene expression, generating abnormally translated protein peptides, and affecting epigenetic modifications which subsequently affect AD related gene expressions. Therefore, identifying AD-related circRNAs can contribute to AD early diagnosis and intervention. In this work, we collected and curated an AD-related circRNA dataset; by exploring the circRNAs' corresponding DNA loci distribution in chromatin 3D conformation (3D genome) and utilize the such 3D genome information, we were able to selected a concise yet predictively effective circRNA panel, based on which, significantly better AD prediction machine learning models were achieved.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results: Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20-60) and mature fibrosis of 30% (10%-50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%-15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial-least square regression machine learning, this study predicted the percentage of both immature (R 2 = 0.842) and mature (R 2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion: This study demonstrates that a point-of-care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

LED-pumped eye-safe pulse laser with an extracavity optical parametric oscillator.

An LED-side-pumped Nd:YAG/Cr4+:YAG passively Q-switched (PQS) laser containing an extracavity optical parametric oscillator (EOPO) is demonstrated. As far as we know, it is the first LED-pumped eye-safe laser. The Nd:YAG pump module is optimized to increase the PQS pulse energy to 24 mJ at 1064 nm. By using a single-pass EOPO design, the output energy of the signal pulse at 1573 nm is 7.44 mJ with a pulse width of 16 ns, the peak power is 434 kW, and the pump-to-signal conversion efficiency is 31%. For double-pass EOPO operation, the pump-to-signal conversion efficiency increases to 45.8%, the output energy of signal pulse is up to 10.98 mJ with a pulse width of 23.5 ns, and the peak power is 459 kW.

Lactobacillus coryniformis subsp. torquens inhibits bone loss in obese mice via modification of the gut microbiota.

High-fat diet (HFD)-induced obesity results in bone loss associated with an imbalanced gut microbiota and altered immune status. Probiotics are live microorganisms that are beneficial to the host and are important in maintaining bone health and gut homeostasis. In this study, the probiotic Lactobacillus coryniformis subsp. torquens (T3L) was isolated from traditional yak milk cheese produced in Lhasa and showed distinct acid and bile salt resistance as potential probiotics. Our data indicated that T3L not only reversed HFD-induced gut dysbiosis, as indicated by decreased Firmicutes-to-Bacteroidetes ratios but also reduced bone loss. The anti-obesity, microbiome-modulating, and bone-protective effects were transmissible via horizontal faeces transfer from T3L-treated mice to HFD-fed mice. The protective effects of T3L on bone mass were associated with regulatory T (Treg) cell-mediated inhibition of osteoclast differentiation. Our data indicate that T3L is a regulator of the gut microbiota and bone homeostasis in an animal model.

[Advances in studies on schistosome-host interactions mediated by extracellular vesicles].

Extracellular vesicles (EVs) are minute particles secreted by the cells of living organisms, which can encapsulate various bioactive molecules for long-distance transport to present biological functions. With the recent studies on parasite-host interactions, EVs, as a carrier for long-distance transport of worm-derived molecules, have been paid much attention during the across-species regulation of hosts. During schistosome infections, adult worms and eggs have been found to mediate hosts via secretion of EVs. This review presents the advances in the studies on schistosome-host interactions mediated by EVs.

[Meta-analysis on the contents of trace elements in workers with occupational exposure to lead].

Objective: To quantitatively evaluate the content differences of trace elements in workers with occupational exposure to lead. Methods: In January 2021, relevant literatures on the contents of trace elements in workers with occupational exposure to lead published from 1990 to 2020 were searched through CNKI, Wanfang, VIP, PubMed, web of science and Embase. Screened and extracted the literatures, and evaluated the quality of the included literatures with Newcastle Ottawa Scale. Meta analysis was performed with Review Manager 5.3 software, and standardized mean difference (SMD) and its 95% confidence interval were used as effect indicators. Results: A total of 20 literatures were included, and the quality scores were 5-7. The results of Meta-analysis showed that compared with the control group, the contents of blood zinc (SMD=-1.01, 95%CI: -1.53, -0.49) , hair zinc (SMD=-0.17, 95%CI: -0.33, -0.01) , hair copper (SMD=-0.50, 95%CI: -1.01, 0) , hair iron (SMD=-3.91, 95%CI: -5.80, -2.03) and hair manganese (SMD=-1.09, 95%CI: -2.02, -0.15) in occupational lead exposure group were significantly lower (P<0.05) . Compared with the control group, the content of cobalt in hair of occupational lead exposure group (SMD=1.41, 95%CI: 0.72, 2.10) was higher, and the difference was statistically significant (P<0.05) . There was no significant difference in the contents of blood chromium, blood copper, blood iron, blood manganese, blood selenium and hair nickel between the two groups (P>0.05) . Conclusion: Workers with occupational exposure to lead have abnormal trace elements.

[Research advances on the clinical characteristics and diagnosis and treatment of autoimmune disease-related ulcers].

Studies have shown that autoimmune disease (AID)-related ulcers are disease complications that lead to serious poor prognosis such as infection and disability. It is difficult to make a clear diagnosis and there are contradictions between the applications of immunosuppressive therapy and anti-infectious therapy. Improper diagnosis and immunosuppressive therapy can easily delay the timing of anti-infectious therapy and surgery for patients, which bring adverse effects on the prognosis of patients. This paper reviews the concept, clinical characteristics and treatment suggestions of each subtype of AID-related ulcers, in order to provide more ideas for AID-related ulcers' clinical diagnosis and treatment.

Forecasting the monthly incidence of scarlet fever in Chongqing, China using the SARIMA model.

The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3-9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.

Prognostic value of regulator T cells in patients with pancreatic cancer: a systematic review and meta-analysis.

OBJECTIVE: This study focused on investigating the relationship between the level of regulatory T cells (Tregs) infiltration and the prognosis of pancreatic cancer patients by using meta-analysis to identify new clinical diagnostic markers. MATERIALS AND METHODS: We looked through PubMed, Embase, and the Cochrane Library for studies published between the database's inception and September 2021. We included studies that looked at the relationship between Tregs and pancreatic cancer prognosis. We exempted duplicate publications, studies without full text, insufficient information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. The data were analyzed using STATA 15.1. RESULTS: The pooled results show that high infiltrating Treg is highly correlated with lower OS of pancreatic cancer patients (HR=1.56, 95% CI: 1.23-1.990.000), but not with DFS of patients with pancreatic cancer (HR=1.29, 95% CI: 0.88-1.89, p=0.184). On the other hand, the results show that high infiltrating Treg is significantly associated with lower OS (HR=2.13, 95% CI: 1.70-2.67, p=0.000) and DFS (HR=1.79, 95% CI: 1.12-2.86, p=0.015) in patients from Asia, whereas it is not significantly associated with OS and DFS in patients from Europe and America. CONCLUSIONS: This meta-analysis suggests that the assessment of Tregs may help to predict the prognosis in pancreatic cancer patients. Advanced histological techniques for obtaining more detailed information about Treg activity may assist in the identification of novel treatment strategies.

[Determination of methyl isobutyl ketone in urine by headspace coupled with gas chromatography-mass spectrometry].

Objective: To establish a method for the determination of methyl isobutyl ketone (MIBK) in urine samples by headspace-gas chromatography-mass spectrometry. Methods: Automatic headspace sampling technique was adopted to optimize the headspace conditions (headspace bottle heating temperature and equilibration time) and gas chromatographic conditions. A total of 5 ml samples were taken and added with 3.0 g ammonium sulfate into a 20 ml headspace bottle. After heated at 60 ℃ for 30 mins, gas from the upper part of headspace bottle was injected into gas chromatography with an injection volume of 100 µl. The target was separated by HP-5MS UI (30 m×0.25 mm×0.25 µm) capillary column and then detected by mass spectrometry detector. The retention time and external standard method were used for qualitative and quantitative analysis of MIBK in samples, respectively. Results: The standard curve of MIBK showed significant linearity between 20.0-1 000.0 µg/L. The standard curve was y=62.9x-652.5, and the correlation coefficient r=0.9998. The detection limit of MIBK was 5.0 µg/L and the quantification limit of MIBK was 16.0 µg/L. The average recovery rate was 95.3%~100.2% at three spiked concentrations of low (50.0 µg/L) , medium (200.0 µg/L) and high (500.0 µg/L) . The intra-day and inter-day precisions were 1.7%~3.8% (n=6) and 1.2%~4.0% (n=6) respectively. This method was stable for the determination of MIBK, and the urine could be kept 14 d at -20 ℃ without significantly loss. Conclusion: This method is proved to be simple, practical and highly sensitive. It can satisfy the request for the determination of urine samples of workers exposed to MIBK.

[The clinical effect of ultrasonic bone curette-assisted "zoning" style laminectomy for the treatment of severe ossification of thoracic ligamentum flavum].

Objective: To investigate the safety and clinical efficacy of "zoning" style laminectomy by ultrasonic bone curette in patients with severe thoracic ossification of the ligamentum flavum(TOLF). Methods: The clinical data of 36 patients with severe TOLF treated by "zoning" style laminectomy at Department of Spinal Surgery,Zhengzhou Orthopaedic Hospital from October 2015 to October 2018 were respectively analyzed.There were 17 males and 19 females,aged(57.3±10.2)years(range:43 to 80 years).According to the anatomical characteristics of the thoracic ligamentum flavum and the pathological process of ossionization,each decompression segment was divided into the upper 1/3 area of the lamina,the bilateral area of the ossionum flavum,the transitional area,and the area of close contact between the ossionum flavum and the spinal cord.Different surgical strategies were used for decompression in turn.The modified Japanese Orthopedic Association (mJOA) was used to evaluate the neurological function status before and after surgery,to evaluate the surgical effect of patients,and to observe the surgical complications.Paired sample T test was used for data analysis. Results: All 36 patients successfully completed the operation,the operation time was (88.6±24.6) minutes(range:60 to 150 minutes).The intraoperative blood loss was (426.7±167.4) ml(range:250 to 800 ml).Follow-up time was (27.2±7.7) months(range:12 to 48 months).The mJOA score at the last follow-up was 9.0±1.5,which was statistically significant compared with the preoperative score 5.4±1.8 (t=13.59,P<0.01).The improvement rate of mJOA score was (65.7±22.1) %,of which 17 cases were excellent (47.2%),13 cases were good (36.1%),4 cases were normal (11.1%),2 cases were ineffective (5.6%).Ten patients had cerebrospinal fluid leakage during the separation or removal of dural ossification and were cured after a series of comprehensive conservative treatment.Two patients showed transient neurological deterioration,and the neurological function gradually recovered to the preoperative state after comprehensive treatment such as increasing the mean arterial pressure and using neurotrophic drugs.During the follow-up,no aggravation of neurological dysfunction and segmental kyphosis were found. Conclusions: The ultrasonic bone curette-assisted "zoning" style laminectomy for the treatment of severe TOLF can directly observed the position relationship between ossification of the ligamentum flavum and the spinal canal structure during the operation,and accurately guide the surgical decompression.It has the advantages of safe operation and complete decompression,which provides an important reference for the selection of clinical surgery.

A Rare Case of Endometriosis of the Small Bowel.

Endometriosis of the small bowel is a rare clinical event. The clinical condition presents with vague abdominal symptoms and is usually not diagnosed acutely, unless clinicians have a high index of suspicion. Most patients are diagnosed after multiple clinical encounters. We present a case of endometriosis causing small bowel obstruction diagnosed postsurgically.

Comparison of influenza hospitalization outcomes among adults, older adults, and octogenarians: a US national population-based study.

OBJECTIVES: This study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention. METHODS: In this retrospective cohort analysis of data from the Nationwide Readmission Database, patients with influenza as a primary or secondary discharge diagnosis were separated into three age groups: 55 638 adults aged 20-64 years, 36 862 adults aged 65-79 years and 41 806 octogenarians aged ≥80 years. Propensity score (PS) weighting was performed to isolate age from other baseline differences. Crude and PS-weighted hazard ratios (HR) were calculated from the in-hospital all-cause 30-day mortality rate. Admission threshold bias was minimized by comparison of influenza with bacterial pneumonia mortality. RESULTS: Adults aged 20-64 years experienced higher in-hospital 30-day mortality compared with older adults aged 65-79 years (HR 0.66; 95% CI 0.55-0.79). Octogenarians had the highest mortality rate, but this was statistically insignificant compared with the adult cohort (HR 1.09; 95% CI 0.94-1.27). This trend was not explained by admission threshold bias: the 30-day mortality rate due to in-hospital bacterial pneumonia increased consistently with age (older adult HR 1.45; 95% CI 1.32-1.59; octogenarian HR 1.99; 95% CI 1.82-2.18). CONCLUSIONS: Adults aged 20-64 years and octogenarians were more likely to experience all-cause 30-day mortality during influenza hospitalization compared with older adults aged 65-79 years. These data emphasize the importance of prevention and suggest the need for more tailored treatment interventions based on risk stratification that includes age.

G protein regulated inducer of neurite outgrowth 1 is a potential marker for lung cancer prognosis.

Lung cancer mortality remains high, and only approximately 15% of patients with non-small cell lung cancer survive for more than five years. The purpose of this research was to investigate the prognostic value and biological functions of G protein regulated inducer of neuritis outgrowth 1(GPRIN1) in lung cancer. We used the Kaplan-Meier method to analyze the correlation between GPRIN1 and overall survival, and performed Cox regression to determine whether GPRIN1 might be an independent predictive factor for lung adenocarcinoma prognosis. qRT-PCR and Western blot assays were conducted to detect GPRIN1 expression in lung cancer cells and normal control cells. To detect the functional effects of knockdown/overexpression of GPRIN1 on lung cancer cells, we performed CCK-8, colony formation and Transwell assays. Through the Kaplan-Meier method, we found that GPRIN1 expression correlated with overall survival and adverse prognosis, and Cox regression indicated that GPRIN1 is as an independent predictive factor for lung adenocarcinoma. Furthermore, the mRNA and protein expression levels of GPRIN1 in lung cancer cells were markedly higher than those in normal cells. Downregulation of GPRIN1significantly decreased cell viability, colony formation, the number of invasive and migrating cells, and levels of epithelial-mesenchymal transition-related proteins in A549 cells. Overexpression of GPRIN1showed the opposite effect in Calu-1 cells. Together, these results indicated that GPRIN1 facilitates lung cancer proliferation and migration, possibly by affecting the epithelial-mesenchymal transition of lung cancer cells, suggesting that GPRIN1may be used as an effective target for the treatment of lung cancer.