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Background: Primary healthcare institutions find identifying individuals with dementia particularly challenging. This study aimed to develop machine learning models for identifying predictive features of older adults with normal cognition to develop dementia., Methods: We developed four machine learning models: logistic regression, decision tree, random forest, and gradient-boosted trees, predicting dementia of 1,162 older adults with normal cognition at baseline from the Hubei Memory and Aging Cohort Study. All relevant variables collected were included in the models. The Shanghai Aging Study was selected as a replication cohort (n = 1,370) to validate the performance of models including the key features after a wrapper feature selection technique. Both cohorts adopted comparable diagnostic criteria for dementia to most previous cohort studies., Results: The random forest model exhibited slightly better predictive power using a series of auditory verbal learning test, education, and follow-up time, as measured by overall accuracy (93%) and an area under the curve (AUC) (mean [standard error]: 088 [0.07]). When assessed in the external validation cohort, its performance was deemed acceptable with an AUC of 0.81 (0.15). Conversely, the logistic regression model showed better results in the external validation set, attaining an AUC of 0.88 (0.20)., Conclusion: Our machine learning framework offers a viable strategy for predicting dementia using only memory tests in primary healthcare settings. This model can track cognitive changes and provide valuable insights for early intervention., Competing Interests: DISCLOSURES The authors declare no conflicts of interest related to this paper. This work was supported by grants from Science and Technology Innovation 2030 Major Projects (2022ZD0211600), National Natural Science Foundation of China (82371444, 82304172, 82473701, 82071200, 82071272, 82171491 and 72174159), and National College Students Innovation and Entrepreneurship Training Program (202310488042). The financial contributors had no role in the design, analysis, or writing of this article., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era., Methods: Data on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed., Results: The 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome., Conclusion: NPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local-regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina., Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study., Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk., Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants., Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Background: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately., Medtods: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application., Results: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025., Conclusions: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China., Competing Interests: The authors declare that they have no competing interests.

Introduction: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent., Methods: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses., Results: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD., Discussion: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia., Highlights: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Polarization imaging technique (PIT) based on a backward scattering 3 × 3 Mueller matrix polarization imaging experimental setup is able to study the optical information and microstructure of glioma and non-glioblastoma tissues from clinical treatment. However, the image contrast of Mueller Matrix Elements (MME) is far from sufficient to provide supplemental information in the clinic, especially in off-diagonal MME. The aim of this work is to propose an innovative method to improve the contrast and quality of PIT images of glioma and non-glioma tissues. The work first confirms the robustness of the method by evaluating the enhanced images and assessment coefficients on ex vivo unstained glioma and non-glioma sample bulks, then the optimal enhancement results are tested and presented based on the multi-sample tests. This PIT image enhancement method can greatly improve the contrast and detailed texture information of MMEs images, which can provide more useful clinical information, and further be used to identify glioma and residues in the intraoperative environment with PIT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Liang, Zhao, Ou and Wu.)

Background: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce., Methods: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated., Results: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively., Conclusions: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Despite the improved access to health services in China, inadequate diagnosis and management of dementia are common issues, especially in rural regions., Objective: The Hubei Memory & Aging Cohort Study was designed as a prospective study in Central China to determine the prevalence, incidence, and risk factors for dementia and mild cognitive impairment (MCI) among urban and rural older adults., Methods: From 2018-2020, participants aged ≥65 years were screened, and data regarding their life behaviors, families, socio-economic status, physical and mental health, social and psychological factors, and cognition were collected. Diagnoses of MCI and dementia were made via consensus diagnosis using the Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria., Results: Of 8,221 individuals who completed their baseline clinical evaluation, 4,449 (54.1%) were women and 3,164 (38.4%) were from remote rural areas (average age: 71.96 years; mean education period: 7.58 years). At baseline, 25.98%(95%confidence interval [CI]: 24.99-26.96) and 7.24%(95%CI: 6.68-7.80) of the participants were diagnosed with MCI and dementia, respectively. Prevalence showed a strong relationship with age. The substantial disparities between rural and urban regions in MCI and dementia prevalence and multiple dementia-related risk factors were revealed. Especially for dementia, the prevalence rate in rural areas was 2.65 times higher than that in urban regions., Conclusion: Our results suggested that public health interventions are urgently needed to achieve equitable diagnosis and management for people living with dementia in the communities across urban and rural areas.

To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE ( p = 0.002, p c = 0.04). HLA-B*38:02 was associated with CBZ-MPE ( p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE ( p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE., Competing Interests: Authors YM and HL were employed by the company BGI-Shenzhen. The remaining authors declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Wang, Min, Bian, Mao, Mao, Qin, Li, Ou, Hou, Zou, Guan, He, Chen, Li, Wang, Deng, Liu, Shen, Liu, Yi, Zhou, Zhou, Kwan and Liao.)

Sepsis induces critical myocardial dysfunction, resulting in an increased mortality. Gracillin (GRA) is a natural steroidal saponin, showing strong capacities of anti-inflammation, but its pharmacological effects on lipopolysaccharide (LPS)-induced acute cardiac injury still remain unclear. In this study, we attempted to explore if GRA was effective to attenuate cardiac injury in LPS-challenged mice and the underlying mechanisms. First, we found that GRA treatments markedly up-regulated the expression of miR-29a in cardiomyocytes. LPS-induced cytotoxicity in cardiomyocytes was significantly alleviated by GRA treatment, as evidenced by the improved cell viability and reduced lactate dehydrogenase (LDH) release. In addition, LPS-triggered apoptotic cell death was clearly ameliorated in cardiomyocytes co-treated with GRA. Notably, LPS-exposed cells showed significantly reduced expression of miR-29a, while being rescued by GRA treatment. In vivo, LPS apparently impaired cardiac function in mice, which was, however, alleviated by GRA administration. In addition, GRA markedly attenuated apoptosis in hearts of LPS-challenged mice by decreasing the expression of cleaved Caspase-3. LPS-triggered inflammatory response in cardiac tissues was also suppressed by GRA through blocking nuclear factor κB (NF-κB) signaling pathway. We also found that miR-29a expression was highly reduced in hearts of LPS-treated mice but was rescued by GRA pretreatment. Besides, miR-29a mimic alleviated LPS-induced apoptosis and inflammation in cardiomyocytes; however, LPS-caused effects were further accelerated by miR-29a. Of note, the protective effects of GRA on LPS-injured cardiac tissues were significantly abrogated by miR-29a suppression. In conclusion, our findings demonstrated that GRA exerted an effective role against LPS-induced acute cardiac injury through impeding apoptosis and inflammation regulated by miR-29a., (Copyright © 2019. Published by Elsevier Inc.)

The purpose of this study was to compare the complications of patients treated for a benign parotid tumour (BPT) by extracapsular dissection (ECD) vs. partial superficial parotidectomy (PSP). A comprehensive literature investigation was conducted by searching electronic databases. A systematic review and meta-analysis of comparative studies were performed to assess ECD and PSP for the treatment of BPTs with fixed-effects models. The outcomes analysed were transient or permanent facial nerve injury, Frey syndrome, recurrence rate, infection, and salivary fistula/sialocele. A total of 1641 patients from seven studies (1120 ECD-treated and 521 PSP-treated patients) were included in this meta-analysis. Transient facial nerve injury (odds ratio (OR)=0.28, 95% confidence interval (CI): 0.11-0.71; p=0.008) and Frey syndrome (OR=0.12, 95% CI: 0.03-0.48; p=0.003) were less prevalent in the ECD group. The rates of permanent facial nerve injury (OR=0.77, 95% CI: 0.35-1.70; p=0.520), recurrence rate (OR=0.17, 95% CI: 0.02-1.75; p=0.14), infection (OR=0.70, 95% CI: 0.07-6.67; p=0.76), and salivary fistula/sialocele (OR=0.40, 95% CI: 0.06-2.66; p=0.350) were similar in both groups. Although there was a trend that ECD showed a reduced risk for complications, the present results are not sufficient to conclude that ECD is more beneficial than PSP., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Antiepileptic drugs frequently cause cutaneous adverse reactions (cADRs). Numerous studies have reported associations between human leukocyte antigen (HLA) alleles and cADRs caused by single antiepileptic drug in Southern Han Chinese people. However, the relationship between the HLA allele and cADRs sequentially induced by two or more antiepileptic drugs (AEDs-induced cross-reactivity) is unclear. To explore the associations between HLA alleles and AEDs-induced cross-reactivity, we prospectively recruited patients with AEDs-induced cross-reactivity from 2009 to 2017 and performed high-resolution genotyping to detect the HLA-A, B, C, and DRB1 alleles in patients for comparison with normal controls. To verify the important genotype, we compared its presence in patients with cross-reactivity to enlarged normal controls, and its presence in patients with carbamazepine (CBZ)-induced maculopapular exanthema (MPE) to CBZ-tolerant controls. Further, the important allele was replicated by meta-analysis. Twenty-three patients with AED-induced cross-reactivity and 500 healthy individuals were enrolled from Southern China. All patients had a mild rash without mucosal or systemic involvement. The HLA-B * 13:01 allele was present in 34.78% (8/23) of patients, 14.60% (73/500) of healthy individuals, and 14.5% (763/5,270) healthy individuals, revealing a significant association (8/23 vs. 73/500; P = 0.02; OR: 3.12; 95% CI: 1.28-7.62; 8/23 vs. 763/5,270; P = 0.014; OR: 3.15; 95% CI: 1.33-7.46). HLA-B * 13:01 was presented numerically higher in CBZ-induced MPE than that in CBZ-tolerant individuals without statistical significance (33/145, 22.76%, vs. 28/179, 15.64%; P = 0.103). Meta-analysis revealed an association between HLA-B * 13:01 and cADRs induced by single AEDs or/and non-AEDs in Chinese and Thai populations ( P = 0.000). This study suggests that HLA-B * 13:01 is potentially associated with AED-cADRs in general, possibly with stronger effect in cross-reactivity. Screening for HLA-B * 13:01 prior to starting AEDs therapy may help to avoid cADRs. However, this association requires further analysis in a multi-center study with a larger sample size.

Sample preparation is a critical process in mass spectrometry (MS) analysis of carbohydrates. Although matrix-assisted laser desorption/ionization (MALDI) MS is the method of choice in carbohydrate analysis, poor ion signal and data reproducibility of carbohydrate samples continue to be severe problems. For quantitative analysis of carbohydrates, an effective analytical protocol providing superior data quality is necessary. This video demonstrates sample preparation protocols to improve signal intensity and minimize data variation of carbohydrates in MALDI-MS. After drying and crystallization of sample droplets, the crystal morphology is reformed by methanol before mass spectrometric analysis. The enhancement in carbohydrate signal is examined with MALDI imaging mass spectrometry (IMS). Experimental results show that crystal reformation adjusts crystalline structures and redistributes carbohydrate analytes. In comparison with the dried droplet preparation method in conventional MALDI-MS, reforming carbohydrate crystal morphologies with methanol shows significantly better signal intensity, ion image distribution, and data stability. Since the protocols demonstrated herein do not involve changes in sample composition, they are generally applicable to various carbohydrates and matrixes.

Dandy-Walker malformation (DWM) is the most prevalent congenital malformation in cerebellum, however, pathological mechanism of DWM has not been fully clarified. This study aims to investigate effects of NDUFA4 on growth of neurons. LV5-NDUFA4 and LV3-NDUFA4-RNAi lentivirus were constructed and transfected to neurons. Ciclosporin A, together with the two lentivirus were applied to neurons to observe neuron growth, apoptosis, and related protein expression. MTT assay was used to observe neuron growth. Apoptosis was detected by using flow cytometry assay. Real-time PCR was utilized to examine NDUFA4 mRNA expression. Western blot and immunohistochemistry assay were used to detect nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), brain fibroblast growth factor (bFGF) and cytochrome C (Cyt C) expression. Results indicated that NDUFA4 significantly enhanced neuron activity and inhibited neuron apoptosis ( P <0.05). NDUFA4 significantly increased Bcl-2 and decreased cleave caspase-3 expression compared to normal control group ( P <0.05). NDUFA4 up-regulated growth factors, including NGF, BDNF, bFGF and Cyt C and inhibited Cyt C expression. NDUFA4 interfere inhibits antagonistic effect of ciclosporin A on apoptosis and decrease up-regulative effect of ciclosporin A on neuron growth. NDUFA4 over-expression enhances antagonistic effect of ciclosporin A on apoptosis and increases up-regulative effect of ciclosporin A on neuron growth. In conclusion, NDUFA4 enhances neuron growth by triggering NGF, BDNF and bFGF expression, inhibits neuron apoptosis by increasing Bcl-2 expression and decreasing cyto C expression. Meanwhile, NDUFA4 regulates the antagonistic effect of ciclosporin A on apoptosis and the up-regulative effect of ciclosporin A on neuron growth., Competing Interests: None.

Carbohydrate analysis is challenging due to lack of sensitive detection and efficient separation methods. Although matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is a sensitive tool, the low ionization efficiency of carbohydrates makes mass analyses inefficient. This work systematically examines the correlation between MALDI-MS sensitivity and carbohydrate sample morphology. Depending on the properties of the matrix used, the morphology changes through sample recrystallization after drying or imposition of hydrodynamic flows during droplet drying. Observation shows that amorphous solids and finer crystals offer higher carbohydrate sensitivity and spatial homogeneity than larger crystals. Clear evidences of an inverse correlation between sensitivity and crystal size are obtained when various kinds of carbohydrates are mixed with different matrixes. Similar experiments on proteins and peptides showed a negative or negligible effect. The result serves as a general guideline for improving efficiency in routine carbohydrate analysis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The highly pharmacokinetic variability of tacrolimus makes it difficult to adjust the dose. In the current study, we investigated the influence of gene polymorphisms and other clinical factors on long-term tacrolimus dosing in Chinese renal transplant recipients., Methods: A total of 276 renal transplant recipients were enrolled. The tacrolimus trough concentration and other clinical variables were recorded for 5 years following transplantation. Eight single nucleotide polymorphisms in four genes (CYP3A5, CYP3A4, ABCB1, and NR1I2) were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and sequencing. The dose-adjusted tacrolimus trough concentrations were calculated and compared among patients according to allelic status., Results: The alleles CYP3A5*3 and CYP3A4*18B were significantly associated with dose-adjusted tacrolimus blood trough concentrations and had a strong time-genotype interaction with tacrolimus pharmacokinetics. NR1I2 g.7635A>G had a significant interaction with time, but the dose-adjusted tacrolimus concentration did not significantly differ over 5 years posttransplantation, except for the GG genotype of NR1I2 g.7635A>G. Sex differences had an important influence on tacrolimus concentration during the later post-transplantation period., Conclusions: The interindividual variability of tacrolimus concentration appears to be due in part to the effects of these identified genetic variants and clinical characteristics. Thus, genotyping of the CYP3A4 and CYP3A5 genes should be considered with respect to determining tacrolimus dose regimens during the post-transplantation period.

Objective: To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug-induced cutaneous adverse reactions., Methods: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes., Results: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome ( p = 5.63 × 10 -15 ). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group ( p = 1.02 × 10 -5 ) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls ( p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association., Conclusions: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: We describe the changes over a 4-year period in the number of diagnostic testing after the introduction of non-invasive prenatal testing (NIPT)., Methods: The rate of NIPT as an indication in women who received amniocentesis, and the number of amniocentesis required for detection of one case with major aneuploidy were compared between a 1-year baseline period before the introduction of NIPT, and the 3 years following NIPT introduction., Results: A total of 7536 amniocentesis procedures were performed over the 4-year study period. During the baseline period of the year 2011, the number of invasive testing required for detection of one common trisomy was 57. During the first 2 years that NIPT was offered, NIPT averaged 1.7 percent of the total indications for amniocentesis, and the required number of invasive testing decreased to 30. With the increase of the percentage of NIPT during the 3rd year, the required number of invasive testing further decreased to 26., Conclusion: After the clinical introduction of NIPT, invasive prenatal diagnostic testing had not decreased at a Chinese prenatal diagnostic unit, but a remarkably improved detection rate of major aneuploidies in diagnostic procedures was observed.

This protocol demonstrates a simple sample preparation to reduce spatial heterogeneity in ion signals during matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The heterogeneity of ion signals is a severe problem in MALDI, which results in poor data reproducibility and makes MALDI unsuitable for quantitative analysis. By regulating sample plate temperature during sample preparation, thermal-induced hydrodynamic flows inside droplets of sample solution are able to reduce the heterogeneity problem. A room-temperature sample preparation chamber equipped with a temperature-regulated copper base block that holds MALDI sample plates facilitates precise control of the sample drying condition. After drying of sample droplets, the temperature of sample plates is returned to room temperature and removed from the chamber for subsequent mass spectrometric analysis. The areas of samples are examined with MALDI-imaging mass spectrometry to obtain the spatial distribution of all components in the sample. In comparison with the conventional dried-droplet method that prepares samples under ambient conditions without temperature control, the samples prepared with the method demonstrated herein show significantly better spatial distribution and signal intensity. According to observations using carbohydrate and peptide samples, decreasing substrate temperature while maintaining the surroundings at ambient temperature during the drying process can effectively reduce the heterogeneity of ion signals. This method is generally applicable to various combinations of samples and matrices.

Quantitative analysis with mass spectrometry (MS) is important but challenging. Matrix-assisted laser desorption/ionization (MALDI) coupled with time-of-flight (TOF) MS offers superior sensitivity, resolution and speed, but such techniques have numerous disadvantages that hinder quantitative analyses. This review summarizes essential obstacles to analyte quantification with MALDI-TOF MS, including the complex ionization mechanism of MALDI, sensitive characteristics of the applied electric fields and the mass-dependent detection efficiency of ion detectors. General quantitative ionization and desorption interpretations of ion production are described. Important instrument parameters and available methods of MALDI-TOF MS used for quantitative analysis are also reviewed.This article is part of the themed issue 'Quantitative mass spectrometry'., (© 2016 The Author(s).)

This work demonstrates a method to prepare homogeneous distributions of analytes to improve data reproducibility in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Natural-air drying processes normally result in unwanted heterogeneous spatial distributions of analytes in MALDI crystals and make quantitative analysis difficult. This study demonstrates that inducing Marangoni flows within drying droplets can significantly reduce the heterogeneity problem. The Marangoni flows are accelerated by changing substrate temperatures to create temperature gradients across droplets. Such hydrodynamic flows are analyzed semi-empirically. Using imaging mass spectrometry, changes of heterogeneity of molecules with the change of substrate temperature during drying processes are demonstrated. The observed heterogeneities of the biomolecules reduce as predicted Marangoni velocities increase. In comparison to conventional methods, drying droplets on a 5 °C substrate while keeping the surroundings at ambient conditions typically reduces the heterogeneity of biomolecular ions by 65%-80%. The observation suggests that decreasing substrate temperature during droplet drying processes is a simple and effective means to reduce analyte heterogeneity for quantitative applications. Graphical Abstract ᅟ.

The aim of this study was to describe our experience with prenatal diagnosis of thalassemia in twin pregnancies at a tertiary referral centre in mainland China. All cases of twin pregnancies at risk of α- or β-thalassemias were followed over an eight-year period. There were 32 twin pregnancies at a mean gestation of 14 weeks (range, 11-21 weeks) at risk of thalassemias, including 19 at risk of α-thalassemia and 13 at risk of β-thalassemia. Chorionicity was determined by ultrasound before prenatal diagnosis. In 19 twin pregnancies at risk of α-thalassemia, there were four where both foetuses were affected, 13 where both foetuses were not affected, and two where one foetus was affected and the other one was not affected. In 13 twin pregnancies at risk of β-thalassemia, there were five where both foetuses were affected, six where both foetuses were not affected, and two where one foetus was affected and the other one was not affected. The pregnancies with two affected foetuses were aborted (including four affected by α-thalassemia and five affected by β-thalassemia), and in pregnancies with one normal twin and one affected twin, the affected foetuses were selectively aborted (including two twins affected by α-thalassemia, and two twins affected by β-thalassemia). Efforts should be taken to reduce the risks of the mother and foetuses in prenatal diagnosis without compromising the precise diagnosis.

Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aims: Radixin has recently been shown to correlate with the metastasis of gastric cancer, but the pathogenesis is elusive. Adhesion proteins contribute to the regulation of metastasis, and thus this study sought to investigate the role of radixin in the migration, invasion and adhesion of gastric cancer cells, as well as its interaction with adhesion proteins in vitro., Methods: Radixin stable knockdown human gastric carcinoma SGC-7901 cells were constructed. Alterations in the migration, invasion and adhesion ability were examined by matrigel-coated plate and transwell assays. The expression pattern of adhesion proteins, including E-cadherin, β-catenin and claudin-1, was determined by quantitative real-time PCR and western blot. Possible involvement of NF-κB/snail pathway was also evaluated., Results: Stable knockdown of radixin significantly suppressed migration and invasion, but enhanced adhesion in SGC-7901 cells. The expression of E-cadherin was manifestly increased in radixin knockdown cells, whereas the expression of β-catenin and claudin-1 was unchanged. The nuclear exclusion of NF-κB followed by conspicuous reduction of snail expression was involved in the regulation of E-cadherin expression., Conclusions: Radixin knockdown suppresses the metastasis of SGC-7901 cells in vitro by up-regulation of E-cadherin. The NF-κB/snail pathway contributes to the regulation of E-cadherin in response to depletion of radixin., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

The trimethylsilyl (TMS) derivative is one of the most widely utilized derivatives for analyzing polar compounds by gas chromatography. An ion two mass units higher than the protonated molecular ion was observed in analyzing TMS-monocarboxylic acids by using gas chromatography electrospray ionization mass spectrometry (GC-ESI/MS). The structure of the M + 2 compound was investigated using tandem mass spectrometry and high-resolution mass spectrometry. The results suggest that one methyl group bound to the silicon atom was replaced by a hydroxyl group during the ESI process. One possible mechanism for the formation of the M + 2 compound is proposed. This observation suggests the possibility of synthesizing an organic compound by using ESI.

Objective: To determine the influence of free invasive prenatal testing on the uptake of non-invasive prenatal testing (NIPT)., Study Design: Over a 2-year period at a Chinese tertiary prenatal diagnostic unit, women at risk of fetal trisomy were given the option of NIPT or invasive prenatal testing. Invasive prenatal testing was offered free of charge to women with a local Hukou (household registration); however, women without a local Hukou were charged for invasive prenatal testing. Both women with and without a local Hukou were charged for NIPT., Results: During the first year, 2647 women with a positive trisomy 21 screening test were referred (474 women with a local Hukou and 2173 women without a local Hukou). Only 1.6% of the women with a local Hukou underwent NIPT, while this proportion was 20.6% in the women without a local Hukou. During the second year, the price of NIPT was reduced. The total number of women referred was 3047 (502 women with a local Hukou and 2545 women without a local Hukou). The uptake of NIPT in women without a local Hukou doubled, but the uptake of NIPT remained stable in women with a local Hukou., Conclusion: The financial impact on the uptake of NIPT should not be underestimated., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the efficacy of the sonographic cardiothoracic ratio (CTR) in early pregnancy for the prediction of fetal haemoglobin (Hb) Bart's disease., Study Design: Over a 1.5-year period at a Chinese tertiary obstetric centre, women at risk of Hb Bart's disease were given the option of a non-invasive approach to exclude an affected pregnancy between 11 weeks and 13 weeks and 6 days of gestation, with a routine rescan after a 2-week interval. The fetal CTR, a sonographic marker, was assessed, and invasive testing followed in cases of fetal cardiomegaly. The diagnosis of fetal Hb Bart's disease was based on DNA analysis from chorionic villus sampling., Results: Of 154 at-risk cases studied, five cases (four at 11 weeks of gestation) were subjected to direct invasive testing because of an unsatisfactory scan. Of the remaining 149 cases, non-invasive ultrasound examinations were performed successfully. Thirty-four (22.8%) affected pregnancies were revealed, including one picked up on rescan. The sensitivity and specificity of the non-invasive approach were 97.1% and 100%, respectively. The need for an invasive test was reduced by 74.7%, and all affected pregnancies except one were diagnosed before 14 weeks of gestation., Conclusion: CTR can differentiate reliably between pregnancies with and without Hb Bart's disease. This non-invasive approach for the exclusion of Hb Bart's disease can be used in early pregnancy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Studies have shown that tiotropium once daily reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. Mechanisms underlying the effects of the muscarinic receptor antagonist tiotropium on COPD have not been fully understood., Objective: In this study, we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD., Methods: Twenty subjects with severe COPD were randomized into two groups: no treatment (Control, n = 10, 63.6 ± 4.6 years, FEV1 29.6 ± 13.3%pred) or inhaled tiotropium 18 μg once daily for 1 month (n = 10, 66.5 ± 5.4 years, FEV1 33.0 ± 11.1%pred). All subjects were allowed to continue their daily medications other than anti-cholinergics during the study. Constant cycle exercise with 75% of maximal workload and spirometry were performed before and 1 month after treatment. Diaphragmatic EMG (EMGdi) and respiratory pressures were recorded with multifunctional esophageal catheter. Efficiency of neural respiratory drive, defined as the ratio of minute ventilation (VE) and diaphragmatic EMG (VE/EMGdi%max), was calculated. Modified British Medical Research Council Dyspnea Scale (mMRC) was used for the evaluation of dyspnea before and after treatment., Results: There was no significant difference in spirometry before and after treatment in both groups. Diaphragmatic EMG decreased significantly at rest (28.1 ± 10.9% vs. 22.6 ± 10.7%, P < 0.05) and mean efficiency of neural respiratory drive at the later stage of exercise increased (39.8 ± 2.9 vs. 45.2 ± 3.9, P < 0.01) after 1-month treatment with tiotropium. There were no remarkable changes in resting EMGdi and mean efficiency of neural respiratory drive post-treatment in control group. The score of mMRC decreased significantly (2.5 ± 0.5 vs. 1.9 ± 0.7, P < 0.05) after 1-month treatment with tiotropium, but without significantly difference in control group., Conclusion: Tiotropium significantly reduces neural respiratory drive at rest and improves the efficiency of neural respiratory drive during exercise, which might account for the improvement in exercise tolerance in COPD., (Copyright © 2014. Published by Elsevier Ltd.)

The aim of this study was to describe the experience of transabdominal chorionic villus sampling (CVS) at a mainland Chinese hospital. During a 7-year period, 1,172 pregnant women chose to have CVS for prenatal diagnosis. Details and outcome of all of these cases were reviewed. The median maternal age was 29 years (range 19-45). The median gestational age was 12 weeks (range 10-14). Fetal karyotyping and thalassaemia couples were the main indications (97.2%). Overall, 112 (9.7%) chromosomal abnormalities were identified. There were 91 (7.8%) major chromosomal abnormalities, including autosomal trisomy in 70 patients, sex chromosomal abnormalities in 17, triploidy in two and unbalanced chromosomal rearrangement abnormality in two. Additionally, 137 fetuses with severe thalassaemia syndrome were found, including 86 homozygous β-thalassaemia, and 51 homozygous α-thalassaemia or non-deletional haemoglobin H disease. The procedure failed to obtain an adequate sample in four (0.3%) patients. There were 229 pregnancies terminated for medical indications after CVS. There were three (0.3%) potentially procedure-related fetal losses. CVS is a safe and reliable prenatal diagnostic technique. It should be one of the options available to pregnant women who require prenatal diagnosis.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

Purpose: Oxcarbazepine (OXC) is a promising alternative for patients who cannot tolerate carbamazepine. Recently, however, it has been reported that OXC-induced cutaneous adverse drug reactions (cADRs) are prevalent and may lead to drug discontinuation. Additionally, these reactions are thought to be associated with HLA-B*1502. This study aims to investigate the incidence, features and risk factors of OXC-cADRs, and to explore their relation to HLA-B alleles in Southern Han Chinese., Methods: A prospective study was performed to investigate the incidence, features and risk factors of OXC-cADRs, in which 252 new users were recruited. To examine the association between OXC-cADRs and HLA-B alleles, 14 maculopapular eruption (MPE) cases, including 9 additional cases beyond this prospective observation, were genotyped by PCR-SSP and sequencing. Thirty-five OXC-tolerant patients served as controls., Results: Five patients (2.0%) developed an OXC-cADR, and all were mild MPE. History of other AED allergy (p=0.005, OR=121.23) and non-AED allergy (p=0.006, OR=59.92) were significant risk factors for OXC-cADRs in multivariate logistic regression analysis. Only one patient with OXC-MPE was positive for HLA-B*1502; and the frequency of HLA-B*1502 in OXC-MPE did not differ significantly from that in OXC-tolerant controls. Four HLA-B*1302 alleles were detected in OXC-MPE cases, which was significantly different from that in general population of southern Han Chinese (p=0.001, OR=7.83)., Conclusions: The incidence of OXC-induced cADRs was low, and no severe reactions occurred. Patients with a history of allergy are more susceptible to OXC-cADRs. No significant association between HLA-B*1502 and OXC-MPE was found. The associations between OXC-MPE and HLA alleles warrant further studies., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The title compound, [CoK(C(2)H(6)NO(3)S)(3)](n), is isotypic with its Ni(II) analogue. The Co(II) atom is chelated by the three taurinate ligands in a distorted octa-hedral geometry and in a facial manner. Each taurinate ligand bridges two K(+) ions via its sulfonate group, forming a three-dimensional framework. Weak N-H⋯O hydrogen bonding is observed in the crystal structure.

Glial choristoma of the tongue is an extremely rare developmental malformation. The authors report a case of a 5-month-old male baby with a congenital glial choristoma located on the posterior part of midline of the left dorsal tongue. Histological examination of the resected specimen revealed a poorly demarcated submucosal mass containing neuroglial tissue, scattered neuron, choroids plexus and ependyma. In addition to neuroglial tissue, a sheet of leptomeningeal tissue was observed more rarely in the case. The clinical and pathological characteristics of previous cases and their probable embryogenesis were also reviewed.

Purpose: The purpose of the study was to evaluate the effects of anchorage by Twin-wires on canine retraction., Methods: A sample of 15 patients with severe anterior crowding was selected (6 males, 9 females, age average: 13.7 years). All patients underwent removal of the four first premolars during orthodontic treatment. Retraction of canine was achieved by using 0.018 stainless steel wire and NiTi wire. Anchorage reinforcement as a result of this movement was evaluated. The length and width of the dental arch models were measured. Self-control t test was used for data analysis., Results: The length and width of the dental arches, the canine and molar relationships remained unchanged after orthodontic treatment., Conclusion: Application of Twin-wires leads to canine retraction and sufficient anchorage consolidation.