Systematical identification of key genes and regulatory genetic variants associated with prognosis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) stands as a highly lethal malignancy characterized by pronounced recurrence and metastasis, resulting in a bleak 5-year survival rate. Despite extensive investigations, encompassing genome-wide association studies, the identification of robust prognostic markers has remained elusive. In this study, leveraging four independent data sets comprising 404 ESCC patients, we conducted a systematic analysis to unveil pivotal genes influencing overall survival. our meta-analysis identified 278 genes significantly associated with ESCC prognosis. Further exploration of the prognostic landscape involved an examination of expression quantitative trait loci for these genes, leading to the identification of six tag single nucleotide polymorphisms predictive of overall survival in a cohort of 904 ESCC patients. Notably, functional annotation spotlighted rs11227223, residing in the enhancer region of nuclear paraspeckle assembly transcript 1 (NEAT1), as a crucial variant likely exerting a substantive biological role. Through a series of biochemistry experiments, we conclusively demonstrated that the rs11227223-T allele, indicative of a poorer prognosis, augmented NEAT1 expression. Our results underscore the substantive role of NEAT1 and its regulatory variant in prognostic predictions for ESCC. This comprehensive analysis not only advances our comprehension of ESCC prognosis but also unveils a potential avenue for targeted interventions, offering promise for enhanced clinical outcomes.

Adjusted Global Antiphospholipid Syndrome Score (aGAPSS) and PLT, APTT: Predictive Value of Thrombotic Risk Assessment in SLE Patients.

BACKGROUND: Risk assessment of vascular thrombosis in SLE patients with the presence of antiphospholipid antibodies (aPL) remains a challenge. The adjusted global antiphospholipid syndrome score (aGAPSS) has been validated and used to predict aPL-related thrombosis in SLE patients in some countries. Relevant data of aGAPSS in thrombotic evaluation in SLE population from China has not been reported. We aim to validate aGAPSS in thrombosis assessment in Chinese patients with SLE and to explore the correlations of aGAPSS with routine laboratory parameters and their clinical significance as well. METHODS: A total of 166 consecutive SLE patients were retrospectively analyzed. Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters in recurrent thrombosis risk in SLE. ROC was conducted to explore the discriminative ability of aGAPSS and platelet (PLT), activated partial thromboplastin time (APTT), alone or in combination. RESULTS: Significantly higher value of aGAPSS was seen in SLE patients with vascular thrombosis. ROC curve indicated that aGAPSS of 3.5 or more had the best diagnostic accuracy for the prediction of aPL-related thrombosis in SLE patients. PLT with cutoff of 187.5 x 109/L and APTT with 37.5 seconds were predictors of aPL-related thrombosis as well. The combination of aGAPSS with PLT and APTT improved AUC compared to aGAPSS alone. CONCLUSIONS: The aGAPSS could predict the risk of aPL-related vascular thrombosis in SLE patients from China. The combination of aGAPSS with PLT and APTT was first time proved to have better predictive performance in thrombosis risk assessment in SLE.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging.

BACKGROUND: The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS: In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS: We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

Determination of high-risk factors and related spatially influencing variables of heavy metals in groundwater.

Identifying high-risk factors (heavy metals (HMs) and pollution sources) by coupling receptor models and health risk assessment model (HRA) is a novel approach within the field of risk assessment. However, this coupled model ignores the contribution of spatial differentiation to high-risk factors, resulting in the assessment being subjective. Taking Dongting Plain (DTP) as an example, a coupling framework by jointly using the positive matrix factorization model (PMF), HRA, Monte Carlo simulation, and geo-detector was developed, aiming to identify high-risk factors in groundwater, and further explore key environmental variables influencing the spatial heterogeneity of high-risk factors. The results showed that at least 82.86 % of non-carcinogenic risks and 97.41 % of carcinogenic risks were unacceptable for people of all ages, especially infants and children. According to the relationships among HMs, pollution sources, and health risks, As and natural sources were defined as high-risk HMs and sources, respectively. The interactions among Holocene thickness, oxidation-reduction potential, and dissolved organic carbon emerged as the primary drivers of spatial variability in high-risk factors, with their combined explanatory power reaching up to 74%. This proposed framework provides a scientific reference for future studies and a practical reference for environmental authorities in developing effective pollution management measures.

Association of pro-inflammatory diet with increased risk of all-cause dementia and Alzheimer's dementia: a prospective study of 166,377 UK Biobank participants.

BACKGROUND: Increasing evidence suggests an association between pro-inflammatory diets and cognitive function. However, only a few studies based on small sample sizes have explored the association between pro-inflammatory diets and dementia using the dietary inflammatory index (DII). Additionally, the relationship between DII and different subtypes of dementia, such as Alzheimer's dementia and vascular dementia, remains largely unexplored. Given the changes in brain structure already observed in patients with dementia, we also investigated the association between DII and magnetic resonance imaging (MRI) measures of brain structure to provide some hints to elucidate the potential mechanisms between pro-inflammatory diet and cognitive decline. METHODS: A total of 166,377 UK Biobank participants without dementia at baseline were analyzed. DII calculations were based on the information collected by the 24-h recall questionnaire. Brain structural anatomy and tissue-specific volumes were measured using brain MRI. Cox proportional hazards models, competing risk models, and restricted cubic spline were applied to assess the longitudinal associations. The generalized linear model was used to assess the association between DII and MRI measurements. RESULTS: During a median follow-up time of 9.46 years, a total of 1372 participants developed dementia. The incidence of all-cause dementia increased by 4.6% for each additional unit of DII [hazard ratio (HR): 1.046]. Besides, DII displayed a "J-shaped" non-linear association with Alzheimer's dementia (Pnonlinear = 0.003). When DII was above 1.30, an increase in DII was significantly associated with an increased risk of Alzheimer's dementia (HR: 1.391, 95%CI: 1.085-1.784, P = 0.009). For brain MRI, the total volume of white matter hyperintensities increased with an increase in DII, whereas the volume of gray matter in the hippocampus decreased. CONCLUSIONS: In this cohort study, higher DII was associated with a higher risk of all-cause dementia and Alzheimer's dementia. However, our findings suggested that the association with DII and vascular and frontotemporal dementia was not significant.

Paleo-Geomorphology Determines Spatial Variability of Geogenic Ammonium Concentration in Quaternary Aquifers.

Naturally occurring (i.e., geogenic) ammonium in groundwater has been widely detected globally, but the major controls on its regional distribution have been poorly characterized. Here, we identified the dominant role of paleo-geomorphology driven by paleo-climate in controlling the spatial variability of geogenic ammonium in groundwater using random forest algorithm and revealed the underlying mechanisms based on borehole sediment analysis of data obtained from the Dongting Lake Plain of the central Yangtze River basins in China. In the paleo-channel (PC) area, the aquifer depth-matched sediments were deposited during the last deglaciation when warm climate resulted in rapid filling into incised valleys, and terrestrial organic matter (OM) mainly as lignin experienced less degradation prior to sedimentation and had lower humification, higher N abundance, and nominal oxidation state of carbon (NOSC). In the paleo-interfluve (PI) area, the depth-matched sediments were deposited during the last glaciation, followed by intensive erosion in the surface during the last glacial maximum, and terrestrial OM mainly as lignin had been partly degraded into aliphatics prior to sedimentation and had higher humification, lower N abundance, and NOSC. As a result, under the present anaerobic conditions, less-humic and N-rich OM with more oxidized C tends to be more intensively mineralized into ammonium in the PC area than those in the PI area. These findings highlight the importance of paleo-geomorphology with paleo-climate in controlling the enrichment of geogenic ammonium in groundwater, which has a universal significance for understanding the genesis and distribution of high N loads in the aquatic environment worldwide.

Sex-related differences in the hypertriglyceridemic-waist phenotype in association with hyperuricemia: a longitudinal cohort study.

BACKGROUND: There is limited longitudinal evidence supporting the association between the hypertriglyceridemic-waist (HTGW) phenotype and hyperuricemia. This study aimed to examine the longitudinal relationship between hyperuricemia and the HTGW phenotype among males and females. METHODS: A total of 5562 hyperuricemia-free participants aged 45 or over from the China Health and Retirement Longitudinal Study (mean age: 59.0) were followed for 4 years. The HTGW phenotype was defined as having elevated triglyceride levels and enlarged waist circumference (cutoffs for males: 2.0 mmol/L and 90 cm; females: 1.5 mmol/L and 85 cm). Hyperuricemia was determined by uric acid cutoffs (males: 7 mg/dl; females: 6 mg/dl. Multivariate logistic regression models were used to assess the association between the HTGW phenotype and hyperuricemia. The joint effect of the HTGW phenotype and sex on hyperuricemia was quantified, and the multiplicative interaction was assessed. RESULTS: During the four-year follow-up, 549 (9.9%) incident hyperuricemia cases were ascertained. Compared with those with normal levels of triglycerides and waist circumference, participants with the HTGW phenotype had the highest risk of hyperuricemia (OR: 2.67; 95% CI: 1.95 to 3.66), followed by an OR of 1.96 (95% CI: 1.40 to 2.74) for only higher triglyceride levels and 1.39 (95% CI: 1.03 to 1.86) for only greater waist circumference. The association between HTGW and hyperuricemia was more prominent among females (OR = 2.36; 95% CI: 1.77 to 3.15) than males (OR = 1.29; 95% CI: 0.82 to 2.04), with evidence of a multiplicative interaction (P = 0.006). CONCLUSIONS: Middle-aged and older females with the HTGW phenotype may at the highest risk of hyperuricemia. Future hyperuricemia prevention interventions should be primarily targeted for females with the HTGW phenotype.

Binocular summation of visual acuity and contrast sensitivity in children with intermittent exotropia.

PURPOSE: To investigate the binocular summation (BiS) of visual acuity (VA) and contrast sensitivity (CS) in children with intermittent exotropia (IXT) before and after surgery and to probe the relationship between the two BiS phenomena and corresponding influencing factors. METHODS: This prospective study included 21 IXT children (11 males and 10 females; aged 6-13 years) who underwent strabismus surgery in Tianjin Eye Hospital from January to April 2022. The visual function was assessed preoperatively and 2.95 ± 0.14 months postoperatively, including monocular/ binocular visual acuity (MVA/BVA) at 100% contrast and 2.5% contrast as well as monocular/binocular contrast sensitivity (MCS/BCS), deviation, near and distant stereopsis, and fusion. RESULTS: All patients had postoperative deviation ranging from 0 to -4 PD. Either preoperative or postoperative BVA at 2.5% contrast was superior to the MVA. The postoperative BiS at 2.5% contrast was significantly superior to the preoperative BiS for 2.5% contrast and postoperative BiS for 100% contrast (P < 0.05). Except for 3 c/d, the MCS and BCS at 6 c/d, 12 c/d and 18 c/d spatial frequencies were all notably improved postoperatively. The postoperative binocular summation ratio of CS (BSR) was highest while interocular difference ratio of CS (IOR) was the lowest at 6 c/d among 4 spatial frequencies. The deviation, distant and near stereopsis, and fusion performance were all remarkably improved after surgery (p = 0.001; p = 0.041; p = 0.000), all of which were not related to BVA at 2.5% contrast, BiS, BSC and BSR. The BCS at middle and high frequencies (6 c/ds, 12 c/ds, and 18 c/ds) was significantly negatively correlated with the BVA at 2.5% contrast, and BSR was irrelevant to the corresponding IOR across different spatial frequencies. CONCLUSION: BVA at low contrast and BCS examinations were not equivalent to stereopsis and fusion status, which contributed to the evaluation of binocular function in the real environment and in the different aspects. BVA in 2.5% contrast is related with BCS in moderate and high spacial frequencies (especially 18c/d) but BCS in 6c/d presents more binocular summation of contrast sensitivity. MCS, BCS and the BSR persist inhibition at 3c/d after surgery. The improvement of BCS is better than that of BSR to evaluate the binouclar function in IXT. Those two methods showed different sensitivities to impairment and rehabilitation of binocular summation and inhibition.

Explaining the intention and behaviours of interinstitutional collaboration in chronic disease management among health care personnel: a cross-sectional study from Fujian Province, China.

BACKGROUND: The increasing number of chronic diseases consumes a large amount of health resources and puts a huge burden on health service system. The integrated management of chronic diseases in Sanming City aims to improve the efficiency and quality of chronic disease management through the collaboration between different levels of medical institutions. AIM: The aim of the present study was to use the theory of planned behaviour (TPB) to examine the intention and behaviours of interinstitutional collaboration in chronic disease management (ICCDM) among healthcare personnel. METHODS: A cross-sectional study of 274 health care personnel was conducted in medical institutions in Fujian Province, China, from March 2022 to April 2022. A self-administered questionnaire based on TPB theory was applied to measure the participants' ICCDM behaviours. RESULTS: The proposed TPB model revealed that attitude was significantly and positively associated with behaviour intention, and behaviour intention and perceived behavioural control were significant predictors of ICCDM behaviour. CONCLUSION: TPB provides insights into ICCDM behaviour. Due to the fact that attitude, perceived behavioural control, and behavioural intention towards ICCDM behaviour were demonstrated to be significant predictors of ICCDM behaviour, these factors may be a promising focus of ICCDM interventions in the integrated management of chronic diseases in China.

Follow-Up of 108 Patients with Chronic Hepatitis B Virus Infection Treated with Polyethylene Glycol-Conjugated Derivatives of Interferon-Alpha and Monitoring of Off-Treatment Virological Relapse.

BACKGROUND This single center study, which enrolled 108 patients with chronic hepatitis B virus infection treated with pegylated interferon-alpha (PEG-IFN-alpha), aimed to follow up and monitor off-treatment responses, including virological relapse, and analyze predictors of long-term efficacy of the PEG-IFN-alpha regimen. MATERIAL AND METHODS In total, 108 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B who had completed the PEG-IFN-alpha regimen and achieved virological suppression were enrolled. The patients were followed up for 5 years to monitor off-treatment responses. Twenty-eight relevant factors, including the history of antiviral therapy and HBeAg seroconversion, were analyzed using the Cox proportional hazards regression model. RESULTS The cumulative rates of virological suppression were 75.70%, 68.68%, 65.25%, 63.91%, and 63.91% at 1, 2, 3, 4, and 5 years of the follow-up period, respectively. Compared with the rates of virological suppression, the cumulative rates of clinical suppression were 88.41%, 79.83%, 78.59%, 75.65%, and 75.65%, respectively, for the 5 years. Alanine aminotransferase (ALT) normalization at 24 weeks after off-therapy (relative risk [RR]=3.430, P=0.013) was a potential predictor for sustained virological suppression, and the history of anti-viral therapy (RR=0.164, P=0.004), quantitative value of hepatitis B virus surface antigen (HBsAg) at 48 weeks of anti-viral therapy (RR=2.697, P=0.039), and ALT normalization at 24 weeks after off-therapy (RR=5.467, P=0.004) were potential predictors for sustained clinical suppression. CONCLUSIONS Our results suggested that increased HBsAg levels at 48 weeks and normalization of ALT at 24 weeks after off-therapy might be predictive factors for long-term treatment efficacy.[color=red] [/color].

Slanted recession on bilateral lateral rectus for the treatment of intermittent Exotropia with convergence insufficiency.

PURPOSE: To evaluate the efficacy and safety of slanted bilateral lateral rectus recession (S-BLRc) for the treatment of convergence insufficiency-type intermittent exotropia (CI-IXT) in children and to probe the relationship of the slanted amount and surgical outcomes. METHODS: Retrospective study. Fifty-eight patients with CI-IXT, aged 4 to 10 years old, underwent S-BLRc procedures. According to the different slanted amount between the upper and lower poles of lateral rectus, all the patients were grouped: Group A (slanting 1 mm, n = 22), Group B (slanting 1.5 mm, n = 18) and Group C (slanting 2 mm, n = 18). The successful surgical outcome was defined as deviation in the primary position ranging from exotropia< 8△ to esotropia< 5△ both at near and at distant as well as the near-distance difference (NDD) < 5△. We analyzed and compared the preoperative and postoperative data including deviations both at near and at distance, NDD, objective torsion, horizontal deviation at up and down gaze, lateral incomitance, binocular vision and surgical success rate among three groups. RESULTS: The average deviations were significantly decreased from - 37.1△ ± 4.2△ (-,exotropia) to - 1.4△ ± 4.6△ at near (P < 0.05) and from - 25.8△ ± 3.7△ to - 0.1 ± 4.1△ at distance (P < 0.05). The postoperative NDD on average was significantly reduced from 10.0△ to 1.8△ in Group A (P < 0.05), from 11.2△ to 0.8△ in Group B (P < 0.05) and from 13.3△ to 0.9△ in Group C (P < 0.05). There was a significant difference in the mean corrections of NDD among the three groups (8.2△ in group A, 10.3△ in group B and 12.4△ in group C respectively, P < 0,05). All the patients attained various improvement of stereopsis after surgery. None had torsional diplopia, A-V pattern and lateral incomitance after strabismic surgery. Totally, the surgical success rate was 89.7% in our series at the 6- to 8-month follow-up. CONCLUSIONS: Slanted bilateral lateral rectus recession is an effective and safe procedure for the treatment of CI-IXT in children. S-BLRc can successfully collapse exotropia both at distance and at near, decrease NDD and benefit to gain binocular vision. The correction of NDD was associated with the slanted amount.

Circ_0000463 contributes to the progression and glutamine metabolism of non-small-cell lung cancer by targeting miR-924/SLC1A5 signaling.

BACKGROUND: Circular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non-small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated. METHODS: Cell proliferation ability was analyzed by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA-924 (miR-924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α-ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth. RESULTS: Circ_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR-924, and circ_0000463 interference-mediated anti-tumor effects were largely reversed by the silence of miR-924 in NSCLC cells. miR-924 interacted with the 3' untranslated region (3'UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR-924 overexpression-mediated anti-tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR-924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo. CONCLUSION: Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR-924/SLC1A5 axis.

The association between healthy aging index and trajectories of disability: a population-based cohort study.

BACKGROUND: Healthy aging index (HAI) could predict adverse health consequences including mortality and disability independent of age and comorbidity. We investigated the role of HAI on trajectories of disability throughout later life based on a nationally representative sample. METHODS: We examined 1733 participants aged over 60 years from the China Health and Retirement Longitudinal Study (CHARLS) followed for 7 years/4 waves repeatedly. Systolic blood pressure [SBP], cognitive function, cystatin C, peak expiratory flow [PEF], and fasting glucose were categorized using tertile or clinical reference range, and scored as 0 (healthiest), 1 (less healthy) and 2 (least healthy) respectively to further generate HAI summary scores (range 0-10). Disability was defined as the sum of impaired activities of daily living (ADL) and instrumental activities of daily living (IADL). We used linear mixed-effects model to study the association between HAI and trajectories of disability. RESULTS: A total of 10.5% of participants represented in the healthiest group and 22.5% ended up as the least healthy. After adjusting for all potential confounders, disability progression was significantly faster (ß = 0.27, 95% CI 0.11-0.42) in the least healthy group when comparing with the healthiest. CONCLUSION: Our findings suggest that HAI is associated with disability progression among adults aged over 60 years old. It might be beneficial for future interventions to specifically target older adults with high HAI scores as a means of reducing disability.

Rational engineering strategies for achieving high-yield, high-quality and high-stability of natural product production in actinomycetes.

Actinomycetes are recognized as excellent producers of microbial natural products, which have a wide range of applications, especially in medicine, agriculture and stockbreeding. The three main indexes of industrialization (titer, purity and stability) must be taken into overall consideration in the manufacturing process of natural products. Over the past decades, synthetic biology techniques have expedited the development of industrially competitive strains with excellent performances. Here, we summarize various rational engineering strategies for upgrading the performance of industrial actinomycetes, which include enhancing the yield of natural products, eliminating the by-products and improving the genetic stability of engineered strains. Furthermore, the current challenges and future perspectives for optimizing the industrial strains more systematically through combinatorial engineering strategies are also discussed.

Association between detectable SARS-COV-2 RNA in anal swabs and disease severity in patients with coronavirus disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in the intestines and feces, but its clinical significance is not completely clear. We aim to characterize the longitudinal test results of SARS-CoV-2 RNA in anal swabs and to explore the association with disease severity. METHODS: We included laboratory-confirmed coronavirus disease 2019 (COVID-19) patients, who were hospitalized in Guangzhou Eighth People's Hospital and excluded those who had not received anal swabs for SARS-COV-2 RNA testing. Epidemiological, clinical, and laboratory data were obtained. Throat swabs and anal swabs were collected periodically for SARS-COV-2 RNA detection. RESULTS: Two hundred and seventeen eligible patients (median aged 50 years, 50.2% were females) were analyzed. 21.2% (46/217) of the patients were detected with SARS-CoV-2 RNA in anal swabs. The duration of viral RNA was longer, but the viral load was lower in anal swabs than throat swabs in the early stage of the disease. During a median follow-up of 20 days, 30 (13.8%) patients were admitted to the intensive care unit (ICU) for high-flow nasal cannula or higher-level oxygen support measures to correct hypoxemia. Detectable viral RNA in anal swabs (adjusted hazard ratio [aHR], 2.50; 95% confidence interval [CI], 1.20-5.24), increased C-reactive protein (aHR, 3.14; 95% CI, 1.35-7.32) and lymphocytopenia (aHR, 3.12; 95% CI, 1.46-6.67) were independently associated with ICU admission. The cumulative incidence of ICU admission was higher among patients with detectable viral RNA in anal swabs (26.3% vs 10.7%, P = .006). CONCLUSION: Detectable SARS-CoV-2 RNA in the digestive tract was a potential warning indicator of severe disease.

The impact of topical lidocaine and timing of LMA removal on the incidence of airway events during the recovery period in children: a randomized controlled trial.

BACKGROUND: The timing of laryngeal mask airway (LMA) removal remains undefined. This study aimed to assess the optimal timing for LMA removal and whether topical anesthesia with lidocaine could reduce airway adverse events. METHODS: This randomized controlled trial assessed one-to-six-year-old children with ASA I-II scheduled for squint correction surgery under general anesthesia. The children were randomized into the LA (lidocaine cream smeared to the cuff of the LMA before insertion, with mask removal in the awake state), LD (lidocaine application and LMA removal under deep anesthesia), NLA (hydrosoluble lubricant application and LMA removal in the awake state) and NLD (hydrosoluble lubricant application and LMA removal in deep anesthesia) groups. The primary endpoint was a composite of irritating cough, laryngeal spasm, SpO2 < 96%, and glossocoma in the recovery period in the PACU. The secondary endpoints included the incidence of pharyngalgia and hoarseness within 24 h after the operation, duration of PACU stay, and incidence of agitation in the recovery period. The assessor was unblinded. RESULTS: Each group included 98 children. The overall incidence of adverse airway events was significantly lower in the LA group (9.4%) compared with the LD (23.7%), NLA (32.6%), and NLD (28.7%) groups (P=0.001). Cough and laryngeal spasm rates were significantly higher in the NLA group (20.0 and 9.5%, respectively) than the LA (5.2 and 0%, respectively), LD (4.1 and 1.0%, respectively), and NLD (9.6 and 2.1%, respectively) groups (P=0.001). Glossocoma incidence was significantly lower in the LA and NLA groups (0%) than in the LD (19.6%) and NLD (20.2%) groups (P< 0.001). At 24 h post-operation, pharyngalgia incidence was significantly higher in the NLA group (15.8%) than the LA (3.1%), LD (1.0%), and NLD (3.2%) groups (P< 0.001). CONCLUSIONS: LMA removal in the awake state after topical lidocaine anesthesia reduces the incidence of postoperative airway events. TRIAL REGISTRATION: ChiCTR, ChiCTR-IPR-17012347 . Registered August 12, 2017.

The trend of direct medical costs and associated factors in patients with chronic hepatitis B in Guangzhou, China: an eight-year retrospective cohort study.

BACKGROUND: Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the medical costs associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the problem, we investigated the trend of direct medical costs and associated factors in patients with chronic HBV infection. METHODS: A retrospective cohort study of 65,175 outpatients and 12,649 inpatients was conducted using a hospital information system database for the period from 2008 to 2015. Generalized estimating equations (GEE) were applied to explore associations between annual direct medical costs and corresponding factors, meanwhile quantile regression models were used to evaluate the effect of treatment modes on different quantiles of annual direct medical costs stratified by medical insurances. RESULTS: The direct medical costs increased with time, but the proportion of antiviral costs decreased with CHB progression. Antiviral costs accounted 54.61% of total direct medical costs for outpatients, but only 6.17% for inpatients. Non-antiviral medicine costs (46.06%) and lab tests costs (23.63%) accounted for the majority of the cost for inpatients. The direct medical costs were positively associated with CHB progression and hospitalization days in inpatients. The direct medical costs were the highest in outpatients with medical insurance and in inpatients with free medical service, and treatment modes had different effects on the direct medical costs in patients with and without medical insurance. CONCLUSIONS: CHB patients had a heavy economic burden in Guangzhou, China, which increased over time, which were influenced by payment mode and treatment mode.

Developing a reliable and valid competency model for assistant dentists in China.

BACKGROUND: The shortage of dentists is one of the various medical-resource problems found around the world. More and more countries are improving the provision of oral services by training dental therapists and hygienists. In China, they are called assistant dentists, and they supplement dental services, but thus far, no research has been conducted on the competence of this group. OBJECTIVE: The purpose of this study was to establish a competency model for Chinese assistant dentists. This model can provide a more scientific basis for the education, training, and evaluation of these professionals, as well as provide a reference for the capacity of dental therapists in various countries. METHODS: We established a system of competency characteristics using theoretical analysis and focus group discussions, after which we established an initial competency model by consulting a Delphi panel of 29 experts. Finally, we collected data from 1389 assistant dentists from 14 provinces in China, and the reliability and validity of the model were confirmed by factor analysis of this data. RESULTS: After three rounds of Delphi panels, the competency model came to include seven ability levels and 50 indicators. In exploratory-factor analysis, three indicators were eliminated, and the questionnaire could explain 68.41 % of total variance. In confirmatory-factor analysis, the established model and data fit well (goodness-of-fit index [GFI] = 0.914, root mean square error of approximation [RMSEA] = 0.047). The results showed that the entire model has good reliability and validity. CONCLUSIONS: Our competency model for dental assistants in China includes seven elements. This is consistent with the current health situation in China, and it has distinct Chinese characteristics. Some of our findings, like those reported in other countries with dental therapists, offer ideas for other developing countries.

The atherogenic index of plasma plays an important role in predicting the prognosis of type 2 diabetic subjects undergoing percutaneous coronary intervention: results from an observational cohort study in China.

BACKGROUND: Many studies have reported the predictive value of the atherogenic index of plasma (AIP) in the progression of atherosclerosis and the prognosis of percutaneous coronary intervention (PCI). However, the utility of the AIP for prediction is unknown after PCI among type 2 diabetes mellitus (T2DM). METHODS: 2356 patients with T2DM who underwent PCI were enrolled and followed up for 4 years. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCEs), considered to be a combination of cardiogenic death, myocardial infarction, repeated revascularization, and stroke. Secondary endpoints included all-cause mortality, target vessel revascularization (TVR), and non-target vessel revascularization (non-TVR). Multivariate Cox proportional hazards regression modelling found that the AIP was correlated with prognosis and verified by multiple models. According to the optimal cut-off point of the ROC curve, the population was divided into high/low-AIP groups. A total of 821 pairs were successfully matched using propensity score matching. Then, survival analysis was performed on both groups. RESULTS: The overall incidence of MACCEs was 20.50% during a median of 47.50 months of follow-up. The multivariate Cox proportional hazards regression analysis before matching suggested that the AIP was an independent risk factor for the prognosis of T2DM after PCI (hazard ratio [HR] 1.528, 95% CI 1.100-2.123, P = 0.011). According to the survival analysis of the matched population, the prognosis of the high AIP group was significantly worse than that of the low AIP group (HR (95% CI) 1.614 (1.303-2.001), P < 0.001), and the difference was mainly caused by repeat revascularization. The low-density lipoprotein-cholesterol (LDL-C) level did not affect the prognosis of patients with T2DM (P = 0.169), and the effect of the AIP on prognosis was also not affected by LDL-C level (P < 0.001). CONCLUSIONS: The AIP, a comprehensive index of lipid management in patients with T2DM, affects prognosis after PCI. The prognosis of diabetic patients with high levels of the AIP included more MACCEs and was not affected by LDL-C levels. It is recommended to monitor the AIP for lipid management in diabetic patients after PCI and ensure that the AIP is not higher than 0.318. Trial registration This is an observational cohort study that does not involve interventions. So we didn't register. We guarantee that the research is authentic and reliable, and hope that your journal can give us a chance.

Comprehensive dissection of dispensable genomic regions in Streptomyces based on comparative analysis approach.

BACKGROUND: Large-scale genome reduction has been performed to significantly improve the performance of microbial chassis. Identification of the essential or dispensable genes is pivotal for genome reduction to avoid synthetic lethality. Here, taking Streptomyces as an example, we developed a combinatorial strategy for systematic identification of large and dispensable genomic regions in Streptomyces based on multi-omics approaches. RESULTS: Phylogenetic tree analysis revealed that the model strains including S. coelicolor A3(2), S. albus J1074 and S. avermitilis MA-4680 were preferred reference for comparative analysis of candidate genomes. Multiple genome alignment suggested that the Streptomyces genomes embodied highly conserved core region and variable sub-telomeric regions, and may present symmetric or asymmetric structure. Pan-genome and functional genome analyses showed that most conserved genes responsible for the fundamental functions of cell viability were concentrated in the core region and the vast majority of abundant genes were dispersed in the sub-telomeric regions. These results suggested that large-scale deletion can be performed in sub-telomeric regions to greatly streamline the Streptomyces genomes for developing versatile chassis. CONCLUSIONS: The integrative approach of comparative genomics, functional genomics and pan-genomics can not only be applied to perform a multi-tiered dissection for Streptomyces genomes, but also work as a universal method for systematic analysis of removable regions in other microbial hosts in order to generate more miscellaneous and versatile chassis with minimized genome for drug discovery.