Perihippocampal failure after hippocampal-avoidance brain radiotherapy in small cell lung cancer patients: Cases report and literature review.

RATIONALE: Brain metastasis is a major concern, and may occur in roughly 50% of patients during the clinical course of small cell lung cancer (SCLC). Because prophylactic cranial irradiation reduces the incidence of brain metastases and improves overall survival, prophylactic cranial irradiation is recommended for SCLC patients without distant metastases or an extensive stage and have responded well to systemic therapy. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) is preferred to preserve hippocampal function while minimizing negative cognitive effects. PATIENT CONCERNS: Reducing the dose delivered to the hippocampus below the therapeutic brain dose may increase the risk of hippocampal progression; thus, HA-WBRT may be associated with a risk of perihippocampal recurrence. DIAGNOSIS: Three patients with SCLC received HA-WBRT and developed intracranial failure during clinical follow-up; 3 relapsed with intracranial failure in the perihippocampal region after 12, 13, and 7 months, respectively. INTERVENTION AND OUTCOMES: Compared to the therapeutic brain dose of cases and the underdose region around the HA region, we matched MRI scans of intracranial failure and previous planning scans of simulation and found a deviation of the underdosed region within the perihippocampal failure of approximately 55% to 63%. LESSONS: Perihippocampal failure is a rare clinical outcome in SCLC patients following HA-WBRT. Perihippocampal failure could be caused by an underdose of radiation or by the aggressiveness of the cancer itself. More research into this topic is encouraged.

Clinical Validation of a Deep Learning-Based Software for Lumbar Bone Mineral Density and T-Score Prediction from Chest X-ray Images.

Screening for osteoporosis is crucial for early detection and prevention, yet it faces challenges due to the low accuracy of calcaneal quantitative ultrasound (QUS) and limited access to dual-energy X-ray absorptiometry (DXA) scans. Recent advances in AI offer a promising solution through opportunistic screening using existing medical images. This study aims to utilize deep learning techniques to develop a model that analyzes chest X-ray (CXR) images for osteoporosis screening. This study included the AI model development stage and the clinical validation stage. In the AI model development stage, the combined dataset of 5122 paired CXR images and DXA reports from the patients aged 20 to 98 years at a medical center was collected. The images were enhanced and filtered for hardware retention such as pedicle screws, bone cement, artificial intervertebral discs or severe deformity in target level of T12 and L1. The dataset was then separated into training, validating, and testing datasets for model training and performance validation. In the clinical validation stage, we collected 440 paired CXR images and DXA reports from both the TCVGH and Joy Clinic, including 304 pared data from TCVGH and 136 paired data from Joy Clinic. The pre-clinical test yielded an area under the curve (AUC) of 0.940, while the clinical validation showed an AUC of 0.946. Pearson's correlation coefficient was 0.88. The model demonstrated an overall accuracy, sensitivity, and specificity of 89.0%, 88.7%, and 89.4%, respectively. This study proposes an AI model for opportunistic osteoporosis screening through CXR, demonstrating good performance and suggesting its potential for broad adoption in preliminary screening among high-risk populations.

HyperArcTM volumetric modulated arc therapy for hypopharyngeal cancer with solitary recurrence in the cervical vertebra: A case report and literature review.

RATIONALE: It is difficult to reirradiate head and neck cancers because of the toxicity from previous radiation dose delivery. Conventional volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy often have poor target coverage. The new HyperArcTM VMAT (HA-VMAT) planning approach reportedly has better target coverage, higher conformity, and can spare normal organs compared to conventional VMAT; however, research on recurrent head and neck cancers is limited. Here, we report the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence in the first cervical vertebra (C1). PATIENT CONCERNS: A 52-year-old Asian male was diagnosed with a hypopharyngeal cancer. The patient received concurrent chemoradiotherapy with a radiation dose of 70 Gy in 33 fractions and achieved complete clinical response. Two years later, solitary recurrence was observed in the C1 vertebra. DIAGNOSES: Solitary recurrence in the C1 vertebra. INTERVENTIONS: Owing to concerns regarding the toxicity to adjacent organs, we decided to use HA-VMAT to achieve better tumor coverage and critical organ sparing. OUTCOMES: Tumor regression was observed on the imaging. At 9 months follow-up, the patient was disease-free and had no late toxicities. LESSONS: This is the first report regarding the clinical outcomes of HA-VMAT for previously irradiated hypopharyngeal cancer with solitary recurrence over the C1 vertebra. HA-VMAT achieves highly conformal dose distribution and excellent sparing of critical organs. There was a favorable initial clinical response with no toxicity. Long-term follow-up is essential in such cases.

Evaluation of the cushion effect in blunt abdominal trauma patients: A computerized analysis.

BACKGROUND: Obesity may serve as a protective factor in blunt abdominal trauma (BAT) patients due to a "cushion effect". In this study, we aim to use computed tomography (CT) scans to measure abdominal adiposity and its correlation with injury severity in BAT patients. METHODS: We conducted a retrospective analysis of male BAT patients who had undergone CT scans. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were manually measured and height-normalized for analysis at lumbar levels L2 and L3. Statistical methods were used to compare differences in adiposity between patients with and without severe abdominal injuries. For controls, we also compared adipose tissue in patients with and without severe trauma to the chest, where less fat typically accumulates. RESULTS: We included 361 male participants and conducted a comparative analysis of their demographic and injury characteristics. Patients without severe abdominal injuries had significantly higher SAT and VAT indices at both L2 and L3 (p < 0.05). However, these measures showed no significant differences between patients with and without severe chest trauma. Solid organ injuries, particularly liver injuries, were associated with decreased SAT and VAT. CONCLUSION: Increase abdominal adiposity was linked to lower abdominal injury severity and solid organ injuries, particularly liver injuries. In addition to conventional BMI for evaluating obesity, either subcutaneous or visceral adipose tissue over lumbar levels L2 and L3 can be used to assess the "cushion effect."

Orodental malformations associated with human MSX1 sequence variants.

BACKGROUND: MSX1 sequence variants have been known to cause human tooth agenesis (TA) with or without orofacial clefts. However, their roles during the whole processes of tooth development are not fully understood. This study aimed to characterize a 4-membered family with TA carrying a novel MSX1 pathogenic variant and investigate the disease mechanism. METHODS: The authors conducted whole exome analysis to define the disease-causing sequence variant. They performed microcomputed tomography, morphometric analyses, transcriptome profiling, and molecular characterization to study the affected teeth and the gene variant. RESULTS: The authors identified an MSX1 pathogenic variant, p.Glu232∗, in affected family members with TA and concomitant orodental anomalies, namely, prominent maxillary labial frenum, central incisor diastema, median maxillary anterior alveolar cleft, tooth fusion, mandibular molar dysmorphology, thin dentin layer, and slender dental roots. MSX1-defective teeth were not apparently microdontic but had thin dentin layers. The mandibular molars showed a homeotic transformation to maxillary counterparts. Genes involved in extracellular matrix organization and dentinogenesis, such as DMP1 and MMP20, were downregulated in dental pulp tissues of MSX1-defective teeth. The p.Glu232∗-truncated MSX1 properly localized to the nucleus but partially lost its transactivation ability. Analyzing reported cases indicated that truncation sequence variants within the homeobox domain of MSX1 caused a more severe TA phenotype than those outside of the homeobox domain, probably due to dominant negativity compared with haploinsufficiency. CONCLUSIONS: This study provides in vivo evidence that MSX1 contributes to developmental processes of various orodental tissues in humans. PRACTICAL IMPLICATIONS: Clinically, hypertrophic labial frenum, incisor diastema, and median maxillary anterior alveolar cleft might be considered diagnostic for MSX1-associated TA.

The role of adjuvant radiotherapy for intracranial malignant meningiomas: analysis of a nationwide database.

PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.

Measuring productive syntactic abilities in Mandarin-speaking children in Taiwan.

PURPOSE: This study aimed to develop a fine-grained measure for evaluating syntactic abilities in Mandarin-speaking children for educational and clinical purposes as a supplement to MLU. METHOD: In total, 99 typically developing children, aged 2;0 to 5;11, living in Taipei, Taiwan, participated in this study. Spontaneous language samples were elicited in free-play situations. The first 100 intelligible utterances were coded with a newly developed scheme: the Mandarin Assessment of Productive Syntax-Revised (MAPS-R). For the examination of concurrent validity, MLU was also computed. RESULTS: Significant age-related differences were observed in both MLU and MAPS-R scores. Strong correlations were found between MLU and MAPS-R scores, confirming the validity of MAPS-R as a measure of syntactic development. MAPS-R further revealed that Mandarin-speaking children expanded noun phrases with the general classifier 'GE' very early on, followed by a locative expression. Verb expansions began with resultative complements and aspect markers. Sentences with complex predication structures, such as serial verbs/pivotal sentences, were still not widely used when the MLU value is below 4.5. CONCLUSIONS: The study showed that MAPS-R is a reliable and valid measure that can provide a rich profile of the syntactic development of Mandarin-speaking children. It can be a useful reference for speech therapists to set a baseline for developing language intervention plans and to monitor their outcome.

Frailty Prevention Care Management Program (FPCMP) on Frailty and Health Function in Community-Dwelling Older Adults: A Quasi-Experimental Trial Protocol.

BACKGROUND: Frailty often results from deteriorating muscle strength and decreased physical function in older adults. Frailty includes not only physical components, but also psychological and social aspects. Previous research has shown that exercise programs, especially resistance exercises combined with nutritional care, can reduce frailty. OBJECTIVES: This study aimed to develop a Frailty Prevention Care Management Program that prevents frailty and improves physical activity and nutrition compared to usual care for community-dwelling older adults. METHODS: A quasi-experimental and single-blinded trial with a non-equivalent control group using a before-after design will be performed involving Frailty Prevention Care Management Program interventions, taking place both at the communities. Participants will be divided into two different intervention groups and two control groups. All groups will be assessed three times: at baseline, immediately after the intervention, and 3 months post intervention. A total of 72 community-dwelling older adults are recruited. This intervention includes an exercise program (design TRX program) and nutritional education. The control group will not receive any specific exercise training. The primary outcome shall comprise the effect of the Frailty Prevention Care Management Program on frailty using the Taiwanese version of the Tilburg frailty indicator. Secondary outcomes include the effect of physical activity using the Senior Fitness Test and nutrition measures using the Mini Nutritional Assessment-Short Form. A generalized estimating equation is constructed to analyze the effects of the intervention. CONCLUSIONS: This trial will provide vital information to guide interventions to improve outcomes (frailty, physical activity, and nutrition) and inform the integration of nutrition and TRX exercises in community-dwelling older adults.

Highly reliable GIGA-sized synthetic human therapeutic antibody library construction.

Background: Monoclonal antibodies (mAbs) and their derivatives are the fastest expanding category of pharmaceuticals. Efficient screening and generation of appropriate therapeutic human antibodies are important and urgent issues in the field of medicine. The successful in vitro biopanning method for antibody screening largely depends on the highly diverse, reliable and humanized CDR library. To rapidly obtain potent human antibodies, we designed and constructed a highly diverse synthetic human single-chain variable fragment (scFv) antibody library greater than a giga in size by phage display. Herein, the novel TIM-3-neutralizing antibodies with immunomodulatory functions derived from this library serve as an example to demonstrate the library's potential for biomedical applications. Methods: The library was designed with high stability scaffolds and six complementarity determining regions (CDRs) tailored to mimic human composition. The engineered antibody sequences were optimized for codon usage and subjected to synthesis. The six CDRs with variable length CDR-H3s were individually subjected to ß-lactamase selection and then recombined for library construction. Five therapeutic target antigens were used for human antibody generation via phage library biopanning. TIM-3 antibody activity was verified by immunoactivity assays. Results: We have designed and constructed a highly diverse synthetic human scFv library named DSyn-1 (DCB Synthetic-1) containing 2.5 × 1010 phage clones. Three selected TIM-3-recognizing antibodies DCBT3-4, DCBT3-19, and DCBT3-22 showed significant inhibition activity by TIM-3 reporter assays at nanomolar ranges and binding affinities in sub-nanomolar ranges. Furthermore, clone DCBT3-22 was exceptionally superior with good physicochemical property and a purity of more than 98% without aggregation. Conclusion: The promising results illustrate not only the potential of the DSyn-1 library for biomedical research applications, but also the therapeutic potential of the three novel fully human TIM-3-neutralizing antibodies.

Development, testing, and application of a mathematics learning scale of self-direction.

Many countries' curriculum reforms focus on developing the next generations' competencies of self-directed learning (SDL) to address rapid social changes and sustainable environmental development. Taiwan's curriculum reform corresponds with the global trend in education. The latest curriculum reform, which proposed a 12-year basic education, was implemented in 2018 and included SDL explicitly in its guidelines. The reformed curriculum guidelines have been followed for over 3 years. Thus, it is necessary to conduct a large-scale survey to examine its impact on Taiwanese students. However, existing research instruments help provide a generalized analysis of SDL and have yet to be designed specifically for SDL of mathematics. Therefore, we developed a mathematics SDL scale (MSDLS) and examined its reliability and validity in this study. Subsequently, MSDLS was utilized to investigate Taiwanese students' SDL of mathematics. The MSDLS consists of four sub-scales with 50 items. It has acceptable reliability, validity, and measurement invariance across gender and grade groups. The MSDLS was administered online to 5,575 junior high school students, and 5,456 valid responses were collected. The findings highlight the gender and grade differences in SDL of mathematics. Male students are higher than female students in many factors. It is noted that the SDL in mathematics does not increase with grade. In sum, the MSDLS is a helpful instrument for examining secondary school students' SDL of mathematics.

PAX9 mutations and genetic synergism in familial tooth agenesis.

Familial tooth agenesis (FTA) is one of the most common craniofacial anomalies in humans. Loss-of-function mutations in PAX9 and WNT10A have been known to cause FTA with various expressivity. In this study, we identified five FTA kindreds with novel PAX9 disease-causing mutations: p.(Glu7Lys), p.(Val83Leu), p.(Pro118Ser), p.(Ser197Argfs*23), and c.771+4A>G. Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. All overexpressed PAX9s showed proper nuclear localization, excepting the p.(Pro118Ser) mutant. Various missense mutations caused differential loss of PAX9 transcriptional ability. PAX9 overexpression in dental pulp cells upregulated LEF1 and AXIN2 expression, indicating a positive regulatory role for PAX9 in canonical Wnt signaling. Analyzing 176 cases with 63 different mutations, we observed a distinct pattern of tooth agenesis for PAX9-associated FTA: Maxillary teeth are in general more frequently affected than mandibular ones. Along with all second molars, maxillary bicuspids and first molars are mostly involved, while maxillary lateral incisors and mandibular bicuspids are relatively less affected. Genotypically, missense mutations are associated with fewer missing teeth than frameshift and nonsense variants. This study significantly expands the phenotypic and genotypic spectrums of PAX9-associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.

Applying the theory of planned behavior to investigate type 2 diabetes patients' intention to receive injection therapy.

Objectives: This study applied the theory of planned behavior (TPB) in shared decision making (SDM) to understand behavioral intention in patients with type 2 diabetes with regard to injection therapy for blood sugar control. Methods: A cross sectional study was conducted. Two hundred and fifty-four patients with type 2 diabetes participated this study and were interviewed by pharmacists in different clinics. A patient decision aid (PDA) entitled "Should I receive injection therapy regarding my type 2 diabetes condition?" was developed for this study and served as interview agenda which comprised 18 items to inquire their willingness to use injection therapy and related considerations during the SDM process. Results: The questionnaires were revised using item analysis, exploratory factor analysis, and a criteria of Cronbach's α > 0.7. This resulted in three constructs for all questionnaires that fit the TPB model. Attitude (ß = 0.432; P < 0.001) and PBC (ß = 0.258; P < 0.001) were directly correlated with intention. TPB explained 35.2% of the variance in intention toward the use of injection therapy. Conclusions: Attitude and PBC toward injection therapy positively and significantly influence the patients' intention to use injection therapy. Practical implications: These findings identify a key association for understanding behavioral intention in patients with type 2 diabetes with regard to blood sugar control during SDM.

NLRP3 Gene Polymorphisms in Rheumatoid Arthritis and Primary Sjogren's Syndrome Patients.

Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.

Methylation of TET2 Promoter Is Associated with Global Hypomethylation and Hypohydroxymethylation in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients.

(1) Background: It is widely accepted that aberrant methylation patterns contribute to the development of systemic lupus erythematosus (SLE). Ten-eleven translocation (TET) methylcytosine dioxygenase is an essential enzyme of which there are three members, TET1, 2, and 3, involved in hydroxymethylation, a newly uncovered mechanism of active DNA methylation. The epigenomes of gene transcription are regulated by 5-hydroxymethylcytocine (5-hmC) and TETs, leading to dysregulation of the immune system in SLE. The purpose of this study was to investigate the global hydroxymethylation status in SLE peripheral blood mononuclear cells (PBMCs) and to explore the role of TETs in changing the patterns of methylation. (2) Methods: We collected PBMCs from 101 SLE patients and 100 healthy donors. TaqMan real-time polymerase chain-reaction assay was performed for the detection of 5-methylcytosine (5-mC), 5-hmC, and TET2 mRNA expression and single-nucleotide polymorphism genotyping. The methylation rates in different CpG sites of TET2 promoters were examined using next-generation sequencing-based deep bisulfite sequencing. Putative transcription factors were investigated using the UCSC Genome Browser on the Human Dec. 2013 (GRCh38/hg38) Assembly. (3) Results: 5-mC and 5-hmC were both decreased in SLE. The mRNA expression level of TET2 was notably high and found to be correlated with the levels of immunologic biomarkers that are indicative of SLE disease activity. The analysis of methylation rates in the TET2 promoter revealed that SLE patients had significantly higher and lower rates of methylation in TET2 105146072-154 and TET2 105146218-331, respectively. (4) Conclusions: TET2 may play an important role in 5-mC/5-hmC dynamics in the PBMCs of SLE patients. The epigenetic modification of TET2 promoters could contribute to the pathogenesis of SLE and the intensity of the immunologic reaction.

Frailty and Quality of Life among Older Adults in Communities: The Mediation Effects of Daily Physical Activity and Healthy Life Self-Efficacy.

As the global population ages, frailty, which has been shown to affect and predict the quality of life (QoL) of older adults, has become a central issue. The aim of this study was to explore the mediating effects of daily physical activity (DPA) and healthy life self-efficacy (HLSE) on the relationship between frailty and QoL in older adults using a serial multiple mediation model. The cross-sectional study was conducted among 210 community-dwelling older adults in Taiwan. Data were collected using the Taiwanese version of the Tilburg Frailty Indicator, the EuroQoL visual analog scale, the Kihon Checklist, and the Chronic Disease Self-Efficacy Scales. The PROCESS macro for SPSS based on the bootstrap method was used to determine the mediating effects of DPA and HLSE on the relationship between frailty and QoL. The results showed that frailty was found to have both direct and indirect effects on QoL. As predicted, DPA and HLSE partially mediated the relationship between frailty and quality of life (DPA: B = −0.71, p < 0.001; HLSE: B = −0.32, p < 0.001). In addition, serial mediation analyses indicated that the association between frailty and QoL was partially mediated by DPA and HLSE in a sequential manner (B = −0.16, p < 0.001). The serial mediation has a causal chain linking DPA and HLSE, with a specified direction of causal flow. According to the results of the serial multiple mediation model, the elderly should be encouraged to continue their activities in daily life, which not only improves self-efficacy and confidence in maintaining health but also reduces the negative impact of frailty on QoL.

The Effects of Laser Acupuncture Therapy on Nocturnal Enuresis: A Systematic Review and Meta-Analysis.

Introduction: Nocturnal enuresis (NE), often known as bedwetting, is a common condition in children and, as a result, they may have subsequent social impairments. The aim of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in children with NE. Methods: International databases with laser- and NE-related keywords were searched, and only randomized controlled trials (RCTs) that used any type of LLLT to treat NE and compared it with any type of control intervention were included. Eleven studies using laser acupuncture therapy (LAT), involving 927 participants, were included for a systematic review. A meta-analysis was conducted using full and partial response-rate variables. The analysis was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and the Cochrane risk-of-bias tool and Grading of Recommendations Assessment Development and Evaluation recommendations for quality of evidence were used to rate all included publications. Results: The LAT groups showed significant improvement, compared with control groups when full response rates were analyzed. There was no significant difference between the groups treated with LAT and the groups who underwent medication therapy alone when full response rates were analyzed. Red and infrared wavelengths and continuous waves were the most commonly used LAT modalities, and lower abdomen and back acupoints were the most-common sites. Conclusions: LAT seems to be an effective and safe treatment for NE; however, the quality of evidence available in the literature was relatively low. More-rigorous and higher-quality trials are needed to investigate this treatment modality further.

Synthesis of Holmium-Oxide Nanoparticles for Near-Infrared Imaging and Dye-Photodegradation.

The development of multifunctional nanomaterials has received growing research interest, thanks to its ability to combine multiple properties for severing highly demanding purposes. In this work, holmium oxide nanoparticles are synthesized and characterized by various tools including XRD, XPS, and TEM. These nanoparticles are found to emit near-infrared fluorescence (800-1100 nm) under a 785 nm excitation source. Imaging of the animal tissues was demonstrated, and the maximum imaging depth was found to be 2.2 cm. The synthesized nanoparticles also show the capability of facilitating dye (fluorescein sodium salt and rhodamine 6G) degradation under white light irradiation. The synthesized holmium oxide nanoparticles are envisioned to be useful for near-infrared tissue imaging and dye-degradation.

Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis.

BACKGROUND: Genetic and epigenetic factors are strongly associated with the autoimmune disease rheumatoid arthritis (RA). Cyclic AMP response element modulator (CREM), a gene related to immune system regulation, has been implicated in various immune-mediated inflammatory processes, although it remains unknown whether CREM is involved in RA. METHODS: This study enrolled 278 RA patients and 262 controls. Three variants [rs12765063, rs17499247, rs1213386] were identified through linkage disequilibrium and expression quantitative trait locus analysis, and CREM transcript abundance was determined by quantitative real-time polymerase chain reaction. The identified variants were genotyped using the TaqMan Allelic Discrimination assay, and CREM promoter methylation was assessed by bisulphite sequencing. Differences between groups and correlations between variables were assessed with Student's t-tests and Pearson's correlation coefficients. Associations between phenotypes and genotypes were evaluated with logistic regression. RESULTS: Rheumatoid arthritis patients exhibited increased CREM expression (p < .0001), which was decreased by methotrexate (p = .0223) and biologics (p = .0001), but could not be attributed to CREM variants. Interestingly, rs17499247 displayed a significant association with serositis (p = .0377), and rs1213386 increased the risk of lymphadenopathy (p = .0398). Furthermore, seven CpG sites showed decreased methylation in RA (p = .0477~ p < .0001). CONCLUSIONS: Collectively, our results indicate that CREM hypomethylation and CREM upregulation occur in RA and that CREM variants are involved in the development of serositis and lymphadenopathy in RA. This study highlights the novel roles of CREM in RA pathophysiology.

Lower HDAC6 mRNA expression and promoter hypomethylation are associated with RA susceptibility.

BACKGROUND/PURPOSE: Recent studies showed that Histone deacetylases 6 (HDAC6) inhibitors could improve arthritis in rheumatoid arthritis (RA) rodent models, whereas lower HDAC6 expression was observed in RA patients' synovial fibroblasts, raising the concerns to use HDAC6 inhibitors to treat RA patients. In the present study, we investigated the involvement of HDAC6 mRNA expression and promoter methylation in RA. METHODS: The DNA and RNAs were extracted from the peripheral blood mononuclear cells (PBMCs) from 138 RA patients and 102 healthy controls. The pyrosequencing technique was used for promoter methylation analysis. The quantitative real-time polymerase chain reaction was used to determine the HDAC6 mRNA expression. The patients' clinical characteristics and disease biomarkers were recorded when blood sampling. RESULTS: The HDAC6 mRNA expression was lower in the RA patients than controls (p = 0.001). The RA patients had significant hypomethylation of the HDAC6 promoter (p < 0.001). The HDAC6 promoter was hypo-methylated in the -229, -225, -144, and -142 CpG sites in RA patients (p < 0.05). Unexpectedly, promoter methylation and mRNA expression of the HDAC6 gene were positively associated (p < 0.001). The HDAC6 mRNA expression and promoter methylation status were associated with the risk of RA (p = 0.006 and 0.002, respectively). The inflammatory cytokines, TNF-α and IL-6, were significantly increased after HDAC6 knockdown in PMA-stimulated THP1 cells and SW982 cells (p < 0.05). CONCLUSION: The HDAC6 mRNA expression and promoter methylation were lower in RA patients. Both HDAC6 mRNA expression level and promoter hypomethylation were associated the susceptibility of RA. HDAC6 inhibitors seem not proper for RA patients' treatment.

Mucin 1 and interleukin-11 protein expression and inflammatory reactions in the intestinal mucosa of necrotizing enterocolitis children after surgery.

BACKGROUND: Necrotizing enterocolitis (NEC) of the newborn is a frequently occurring clinical disease in infants. The mortality rate of NEC in premature infants is as high as 50%, and the morbidity rate is on the rise. NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families. AIM: To investigate the expression and significance of mucin 1 (MUC1) and interleukin-11 (IL-11) in the intestinal mucosa of infants with neonatal NEC after surgery. METHODS: Forty-eight postoperative intestinal mucosal specimens from children with NEC (NEC group) and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia (control group) were collected in our hospital. Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups. The serum levels of tumor necrosis factor-α (TNF-α) and IL-1ß in the two groups were measured by enzyme-linked immunosorbent assay, and the relationship between MUC-1 and IL-11 protein expression and serum TNF-α and IL-1ß levels was analyzed by the linear correlation method. RESULTS: The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group, and the difference was statistically significant (P < 0.05). The levels of serum TNF-α and IL-1ß in the NEC group were significantly higher than those in the control group (P < 0.05). The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-α and IL-1ß levels (P < 0.05). There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-α and IL-1ß in the NEC group. CONCLUSION: The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery. This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.