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Objective: To explore whether miR-199a-5p regulated BBB integrity through PI3K/Akt pathway after ischemia stroke., Methods: Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion(MCAO) were used in experiment. The Ludmila Belayev 12-point scoring was used to measure the neurological function of MCAO rats. The Evans Blue Stain, immunofluorescence staining, western-blotting and RT-PCR were performed to evaluate the effects of miR-199a-5p mimic on BBB integrity in rats following MCAO., Results: The result suggested that miR-199a-5p mimic treatment possessed the potential to boost proprioception and motor activity of MCAO rats. MiR-199a-5p decreased the expression of PIK3R2 after MCAO, activated Akt signaling pathway, and increased the expression of Claudin-5 and VEGF in the ischemic penumbra. Furthermore, miR-199a-5p alleviated inflammation after cerebral ischemia. BBB leakage and neurocyte apoptosis were cut down in MCAO rats treated with miR-199a-5p mimic., Conclusions: MiR-199a-5p mimic decreased the expression of PIK3R2 and activated Akt signaling pathway after ischemia stroke, reduced the expression of inflammatory cytokines, and attenuated BBB disruption after ischemic stroke., Competing Interests: All authors declare that they have no conflicts of interest to report., (Copyright: © 2024 Ni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this paper, a method named Region Mosaicking on Laplacian Pyramids (RMLP) is proposed to fuse multi-focus images that is captured by microscope. First, the Sum-Modified-Laplacian is applied to measure the focus of multi-focus images. Then the density-based region growing algorithm is utilized to segment the focused region mask of each image. Finally, the mask is decomposed into a mask pyramid to supervise region mosaicking on a Laplacian pyramid. The region level pyramid keeps more original information than the pixel level. The experiment results show that RMLP has best performance in quantitative comparison with other methods. In addition, RMLP is insensitive to noise and can reduces the color distortion of the fused images on two datasets., Competing Interests: The authors have declared that no competing interests exist.

Objective: Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population., Methods: 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing., Results: Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively., Significance: This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.

Background: Progression to diabetes mellitus (DM) is variable and the screening time interval not well defined. The American Diabetes Association and US Preventive Services Task Force suggest screening every 3 years, but evidence is limited. The objective of the study was to develop a model to predict the probability of developing DM and suggest a risk-based screening interval., Methods: We included non-diabetic adult patients screened for DM in the Cleveland Clinic Health System if they had at least two measurements of glycated hemoglobin (HbA1c), an initial one less than 6.5% (48 mmol/mol) in 2008, and another between January, 2009 and December, 2013. Cox proportional hazards models were created. The primary outcome was DM defined as HbA1C greater than 6.4% (46 mmol/mol). The optimal rescreening interval was chosen based on the predicted probability of developing DM., Results: Of 5084 participants, 100 (4.4%) of the 2281 patients with normal HbA1c and 772 (27.5%) of the 2803 patients with prediabetes developed DM within 5 years. Factors associated with developing DM included HbA1c (HR per 0.1 units increase 1.20; 95%CI, 1.13-1.27), family history (HR 1.31; 95%CI, 1.13-1.51), smoking (HR 1.18; 95%CI, 1.03-1.35), triglycerides (HR 1.01; 95%CI, 1.00-1.03), alanine aminotransferase (HR 1.07; 95%CI, 1.03-1.11), body mass index (HR 1.06; 95%CI, 1.01-1.11), age (HR 0.95; 95%CI, 0.91-0.99) and high-density lipoproteins (HR 0.93; 95% CI, 0.90-0.95). Five percent of patients in the highest risk tertile developed DM within 8 months, while it took 35 months for 5% of the middle tertile to develop DM. Only 2.4% percent of the patients in the lowest tertile developed DM within 5 years., Conclusion: A risk prediction model employing commonly available data can be used to guide screening intervals. Based on equal intervals for equal risk, patients in the highest risk category could be rescreened after 8 months, while those in the intermediate and lowest risk categories could be rescreened after 3 and 5 years respectively.

This study aimed to explore the bidirectional relationships between retention and health-related quality of life (HRQoL) in patients from mainland China receiving methadone maintenance treatment (MMT). This prospective cohort study recruited 1,212 eligible MMT patients from the two largest MMT clinics (one privately and another publicly funded) in Xi'an. This study started in March 2012 with a 2-year follow-up until March 2014. Retention was assessed by repeated terminations, past treatment duration, premature terminations, and follow-up treatment duration. HRQoL was evaluated using the Chinese (simple) short-form 36 health survey version 2 (SF-36v2) and the quality of life scale for drug addicts (QOL-DAv2.0). Linear and Cox regression analyses were used to explore relationships between retention and HRQoL. A general linear model was used to further examine the global effect of past treatment duration on HRQoL. Multivariate analyses showed that repeated terminations had no significant impact on HRQoL scores in MMT patients; however, past treatment time (year) influenced the SF-36v2PCS (P = 0.004): treatment for ≥4 years showed a lower SF-36v2PCS score (regression coefficient: -2.39; 95% confidence interval [CI]: -3.80, -0.97; P = 0.001) than treatment for <1 year. In addition, patients with an SF-36v2PCS score > 49 (hazard ratio: 0.83; 95% CI: 0.69, 0.98; P = 0.03) were 17% less likely to terminate MMT than those with scores of ≤49. In conclusion, retention and HRQoL tended to have a bidirectional relationship, which should be considered in the development of retention and health-management programs for patients with MMT.

Introduction: China is considered a country of low HIV prevalence (780,000 people living with HIV), however, HIV infections among high-risk populations continue to grow at alarming rates. Voluntary Counseling and Testing services were first implemented in 2003, and oral rapid HIV testing (ORHT) began in 2012. Dentists, as oral health experts, would be well placed to conduct ORHT. We assessed willingness of dentists to undertake ORHT in their clinical practice., Methods: A cross-sectional, paper-based survey of dentists from the Xi'an region of China was conducted from April to June 2013. Dentists were recruited from Shaanxi Stomatological Association using a stratified sampling methodology. A 40-item survey was used to measure knowledge of HIV, attitudes toward people living with HIV and willingness to conduct ORHT., Results: 477 dentists completed the survey with a mean HIV knowledge test score of 13.2/18 (SD 1.9). If made available in the dental setting, 276 (57.9%) preferred to use blood to diagnose HIV, only 190 (39.8%) preferred saliva or both. Four hundred and thirty-five (91.2%) thought that ORHT was needed in dental clinics. Female dentists felt more accepting of ORHT than males (93.8% vs. 87.8%; χ2=5.145; p<0.05). 42.6% of the participants who responded thought that lack of education on ORHT for dentists was the most urgent problem to solve for ORHT, 144 (31.3%) thought that lack of support for ORHT from patients was the most urgent problem. There was statistically significant difference among dental hospital, dentistry and department of dentistry (χ2=24.176; p<0.05)., Conclusions: The majority of Chinese dentists thought that ORHT was needed in the dental setting. Providing opportunities for dentists and dental students to learn about HIV testing guidelines and practices is needed as well as feasibility and implementation science research.

Metallothioneins (MTs) are small, cysteine-rich, heavy metal-binding proteins involved in metal homeostasis and detoxification in living organisms. In the present study, we cloned two MT genes (OcMT1 and OcMT2) from Oxya chinensis, analyzed the expression patterns of the OcMT transcripts in different tissues and at varying developmental stages using real-time quantitative PCR (RT-qPCR), evaluated the functions of these two MTs using RNAi and recombinant proteins in an E. coli expression system. The full-length cDNAs of OcMT1 and OcMT2 encoded 40 and 64 amino acid residues, respectively. We found Cys-Cys, Cys-X-Cys and Cys-X-Y-Z-Cys motifs in OcMT1 and OcMT2. These motifs might serve as primary chelating sites, as in other organisms. These characteristics suggest that OcMT1 and OcMT2 may be involved in heavy metal detoxification by capturing the metals. Two OcMT were expressed at all developmental stages, and the highest levels were found in the eggs. Both transcripts were expressed in all eleven tissues examined, with the highest levels observed in the brain and optic lobes, followed by the fat body. The expression of OcMT2 was also relatively high in the ovaries. The functions of OcMT1 and OcMT2 were explored using RNA interference (RNAi) and different concentrations and treatment times for the three heavy metals. Our results indicated that mortality increased significantly from 8.5% to 16.7%, and this increase was both time- and dose-dependent. To evaluate the abilities of these two MT proteins to confer heavy metal tolerance to E. coli, the bacterial cells were transformed with pET-28a plasmids containing the OcMT genes. The optical densities of both the MT-expressing and control cells decreased with increasing concentrations of CdCl2. Nevertheless, the survival rates of the MT-overexpressing cells were higher than those of the controls. Our results suggest that these two genes play important roles in heavy metal detoxification in O. chinensis.

Objective: To test psychometrics of the Short Form 36 Health Survey version 2 (SF-36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese mainland patients with methadone maintenance treatment (MMT)., Methods: A total of 1,212 patients were recruited from two MMT clinics in Xi'an, China. Reliability was estimated with Cronbach's α and intra-class correlation (ICC). Convergent and discriminant validity was assessed using multitrait-multimethod correlation matrix. Sensitivity was measured with ANOVA and relative efficiency. Responsiveness was evaluated by pre-post paired-samples t-test and standardized response mean based on the patients' health status changes following 6-month period., Results: Cronbach's α of the SF-36v2 physical and mental summary components were 0.80 and 0.86 (eight scales range 0.73-0.92) and the QOL-DAv2.0 was 0.96 (four scales range: 0.80-0.93). ICC of the SF-36v2 two components were 0.86 and 0.85 (eight scales range: 0.72-0.87) and the QOL-DAv2.0 was 0.94 (four scales range: 0.88-0.92). Convergent validity was lower between the two instruments (γ <0.70) while discriminant validity was acceptable within each instrument. Sensitivity was satisfied in self-evaluated health status (both instruments) and average daily methadone dose (SF-36v2 physical functioning and vitality scales; QOL-DAv2.0 except psychology scale). Responsiveness was acceptable in the improved health status change (SF-36v2 except vitality scale; QOL-DAv2.0 except psychology and symptoms scales) and deteriorated health status change (SF-36v2 except vitality, social functioning and mental health scales; QOL-DAv2.0 except society scale)., Conclusions: The SF-36v2 and the QOL-DAv2.0 are valid tools and can be used independently or complementary according to different emphases of health-related quality of life evaluation in patients with MMT.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recently in Chinese patients, including five newly described missense mutations (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two known missense mutations (S69L, T118M). We found MLC1(wt) was localized to the cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X and A275T transcript decreased and all mutants except R22Q had lower protein expression in transfected U373MG cells. Therefore, we propose that all these eight MLC1 mutations had functional effect either on their protein/mRNA expression, or on their intracellular protein localization, or both.