Mechanisms of eukaryotic transcription termination at a glance.

Transcription termination is the final step of a transcription cycle, which induces the release of the transcript at the termination site and allows the recycling of the polymerase for the next round of transcription. Timely transcription termination is critical for avoiding interferences between neighbouring transcription units as well as conflicts between transcribing RNA polymerases (RNAPs) and other DNA-associated processes, such as replication or DNA repair. Understanding the mechanisms by which the very stable transcription elongation complex is dismantled is essential for appreciating how physiological gene expression is maintained and also how concurrent processes that occur synchronously on the DNA are coordinated. Although the strategies employed by the different classes of eukaryotic RNAPs are traditionally considered to be different, novel findings point to interesting commonalities. In this Cell Science at a Glance and the accompanying poster, we review the current understanding about the mechanisms of transcription termination by the three eukaryotic RNAPs.

Association of preoperative frailty with the risk of postoperative delirium in older patients undergoing hip fracture surgery: a prospective cohort study.

OBJECTIVE: This study aimed to explore the correlation between preoperative frailty and the risk of postoperative delirium (POD) in older patients undergoing hip fracture surgery. METHODS: In total, 148 patients with hip fractures who were admitted to Tsinghua Changgung Hospital (Beijing, China) between January 2022 and January 2023 were involved in this study. Preoperative frailty scales were assessed, of which the CAM scale was postoperatively administered every morning and evening on days 1, 2, 3, 5, and 7. Binary logistic regression analysis was conducted to determine the correlation between preoperative frailty and the risk of POD. RESULTS: Among 148 older patients with hip fractures, 71 (48.0%) were identified as preoperative frail and 77 (52.0%) as non-frail. The overall incidence of POD on day 7 was 24.3% (36/148), and preoperative frailty was associated with a significantly higher risk of POD compared with non-frailty (42.3% vs. 7.8%, P < 0.001). The binary logistic regression analysis revealed that preoperative frailty was noted as an independent risk factor for the risk of POD in older patients undergoing hip fracture surgery (P = 0.002). CONCLUSION: Preoperative frailty increased the risk of POD in older patients undergoing hip fracture surgery. DISCUSSION: Preoperative assessment of frailty in geriatric hip surgery can timely identify potential risks and provide interventions targeting frailty factors to reduce the incidence of POD in older patients undergoing hip fracture surgery. The findings suggested that preoperative frailty could increase the risk of POD in older patients undergoing hip fracture surgery. Further research is necessary to determine whether perioperative interventions aimed at enhancing frailty can mitigate the risk of POD and improve prognosis in older patients undergoing hip fracture surgery.

Transcriptome characteristics of epithelial cells from advanced non-small cell lung cancer were revealed by single-cell RNA sequencing.

BACKGROUND: Lung adenocarcinoma (LUAD) is the prevalent malignancy worldwide. The aim is to explore differentially expressed genes (DEGs) associated with immune infiltration and survival time of LUAD patients, and predict transcriptional factors for shedding new light on molecular mechanisms and individual therapy of LUAD. METHOD: ScRNA-seq data of LUAD patients was downloaded from GSE148071 and analyzed by R packages. The clustering and protein-protein interaction network were constructed for screening DEGs. Gene Set Enrichment Analysis (GSEA) and GO enrichment analysis were performed in epithelial cell subgroups with high differentiation potential. Potential regulatory transcription factors were predicted. RESULTS: Sixteen epithelial cell types were required and top 20 genes were identified on cell subgroup Epi4 with the highest differentiation potential associated with poor prognosis of LUAD in PPI network. GSEA and GO annotation results showed that cell subgroup Epi4 was enriched in the biological processes of cell proliferation and energy metabolism, and positively regulated the function of cell proliferation. TPI1 was significantly highly expressed in LUAD samples (p < .0001). TPI1 demonstrated a negative correlation with the infiltration levels of CD8+ T cells, CD4+ T cells, B cells, and activated mast cells, whilst manifesting a positive correlation with the infiltration levels of resident mast cells, Th2 cells, and MDSC. Epi4 was regulated by transcription factors MXD3 and GATA4. CONCLUSION: Overexpression of TPI1 was identified as a novel biomarker for LUAD, and potential regulatory transcription factors MXD3 and GATA4 regulated the proliferation of LUAD with the poor prognosis, which may serve as potential targets to suppress the proliferation of LUAD.

Application Value of Serum Neurofilament Light Protein for Disease Staging in Huntington's Disease.

BACKGROUND: Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL. METHODS: Serum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained. RESULTS: Baseline samples were available from 110 controls, 90 premanifest HD (pre-HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre-HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre-HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset. CONCLUSIONS: Although sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society.

The association between walking pace and hand grip strength with the risk of chronic obstructive pulmonary disease: a bidirectional Mendelian randomization study.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) currently ranks as the third leading cause of mortality worldwide, imposing substantial burdens on societal and individual health. Amongst health research tools, walking pace (WP) and hand grip strength (HGS) are cornerstones, extensively associated with diverse health conditions. However, the intricate interplay between these factors and COPD risk remains ambiguous. This study aims to elucidate the causal association of WP, HGS, with COPD risk through a bidirectional Mendelian randomization (MR) approach. METHODS: Bidirectional MR analysis was performed using Genome-wide association study (GWAS) data of European individuals for WP, HGS, and COPD. Inverse Variance Weighted (IVW) served as the primary MR analysis approach. To supplement the IVW findings, four additional MR methods [MR-Egger, weighted median, maximum likelihood, simple median] were used. To assess heterogeneity and pleiotropy, sensitivity analyses were performed. In addition, multivariate MR (MVMR) analysis was used to assess causality after adjustment for potential confounders. RESULTS: IVW method results show a significant negative association between WP and COPD risk in both initial (genome-wide threshold, odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.09-0.51, P = 5.06 × 10- 4) and secondary (locus-wide threshold, OR = 0.27, 95%CI: 0.18-0.41, P = 4.88 × 10- 10) MR analysis. The reverse MR analysis suggested that COPD also diminishes WP. Additionally, a causal risk reduction for COPD with right HGS (OR = 0.74, 95% CI: 0.58-0.94, P = 1.44 × 10- 2) was only found in secondary MR analysis. The outcomes of the four additional MR methods also suggested similar causal relationships, and sensitivity analyses endorsed their robustness. Lastly, the MVMR analysis demonstrated that the WP's effect on reducing COPD risk persisted independently of potential confounding variables. CONCLUSION: A bidirectional causal relationship exists between typical WP and COPD risk. Conversely, a decrease in right HGS is unidirectionally associated with an increased risk of COPD. The study suggests that WP may serve as a predictive factor for COPD or as a simple evaluative indicator for prognosis.

A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs have been identified in cancers, and their roles in HCC remain elusive. This study aimed to identify coding circRNAs and explore their function in HCC. METHODS: CircMAP3K4 was selected from the CIRCpedia database. We performed a series of experiments to determine the characteristics and coding capacity of circMAP3K4. We then used in vivo and in vitro assays to investigate the biological function and mechanism of circMAP3K4 and its protein product, circMAP3K4-455aa, in HCC. RESULTS: We found circMAP3K4 to be an upregulated circRNA with coding potential in HCC. IGF2BP1 recognized the circMAP3K4 N6-methyladenosine modification and promoted its translation into circMAP3K4-455aa. Functionally, circMAP3K4-455aa prevented cisplatin-induced apoptosis in HCC cells by interacting with AIF, thus protecting AIF from cleavage and decreasing its nuclear distribution. Moreover, circMAP3K4-455aa was degraded through the ubiquitin-proteasome E3 ligase MIB1 pathway. Clinically, a high level of circMAP3K4 is an independent prognostic factor for adverse overall survival and adverse disease-free survival of HCC patients. CONCLUSIONS: CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, circMAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. Targeting circMAP3K4-455aa may provide a new therapeutic strategy for HCC patients, especially for those with chemoresistance. CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution, preventing HCC cells from cell death under stress and promoting HCC progression.

Role for Biochemical Assays and Kayser-Fleischer Rings in Diagnosis of Wilson's Disease.

BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that impairs copper homeostasis and is caused by homozygous or compound heterozygous mutations in ATP7B, which encodes a copper-transporting P-type ATPase. Patients have variable clinical manifestations and laboratory test results, resulting in diagnostic dilemmas. We aimed to identify factors associated with symptoms and features of Wilson disease from a large cohort, over 15 years. METHODS: We collected data from 715 patients (529 with symptoms, 146 without symptoms, and 40 uncategorized) and a genetic confirmation of Wilson's disease (mean age of diagnosis, 18.84 years), recruited from 3 hospitals in China from 2004 through 2019. We analyzed clinical data along with serum levels of ceruloplasmin (available from 636 patients), 24-hr urinary copper excretion (collected from 131 patients), Kayser-Fleisher rings (copper accumulation in eyes, with neurologic data from 355 patients), and magnetic resonance imaging (MRI) abnormalities. Differences among the groups were analyzed using 1-way analysis of variance followed by Tukey multiple comparison test. RESULTS: Of the 529 patients with symptoms, 121 had hepatic features, 355 had neurologic features, 28 had osteomuscular features (premature osteoarthritis, skeletal deformities, and pathological bone fractures), and 25 had psychiatric symptoms. Age of onset was significantly younger in patients with hepatic (16.94 ± 1.03 years; P = .0105) or osteomuscular features (13 ± 1.33 years; P = .0001) than patients with neurological features (19.48 ± 0.46 years). Serum levels of ceruloplasmin differed among asymptomatic patients and patients with osteomuscular or neurologic symptoms of Wilson disease. Serum levels of ceruloplasmin ranged from 18.93 mg/L to approximately 120.00 mg/L (quantiles of 0.025 to approximately 0.975). Fifty-one of 131 patients (39%) had urinary copper excretion levels below 100 µg/24 hr; there was significant variation in levels of urinary copper excretion between patients older than 14 years vs 14 years or younger. Of the 355 patients with neurologic features, 244 patients (69%) had abnormal findings from MRI and Kayser-Fleisher rings; only 1 patient with abnormal findings from brain MRI was negative for Kayser-Fleisher rings. CONCLUSIONS: Serum level of ceruloplasmin, 24-hour urinary copper excretion, and Kayser-Fleisher rings can be used to identify patients who might have Wilson disease. Patients with serum levels of ceruloplasmin below 120 mg/L and children with urinary copper excretion above 40 µg should undergo genetic testing for Wilson's disease. Patients with movement disorders and brain MRI abnormalities without Kayser-Fleisher rings are not likely to have Wilson disease.

Puromycin-Modified Silica Microsphere-Based Nascent Proteomics Method for Rapid and Deep Nascent Proteome Profile.

Nascent proteome is crucial in directly revealing how the expression of a gene is regulated on a translation level. In the nascent protein identification, puromycin capture is one of the pivotal methods, but it is still facing the challenge in the deep profiling of nascent proteomes due to the low abundance of most nascent proteins. Here, we describe the synthesis of puromycin-modified silica microspheres (PMSs) as the sorbent of dispersive solid-phase microextraction and the establishment of the PMS-based nascent proteomics (PMSNP) method for efficient capture and analysis of nascent proteins. The modification efficiency of puromycin groups on silica microspheres reached 91.8% through the click reaction. After the optimization and simplification of PMSNP, more than 3500 and 3900 nascent proteins were rapidly identified in HeLa cells and mouse brains within 13.5 h, respectively. The PMSNP method was successfully applied to explore changes in the translation process in a biological stress model, namely, the lipopolysaccharide-stimulated HeLa cells. Biological functional analyses revealed the unique characters of the nascent proteomes and exhibited the superiority of the PMSNP in the identification of low abundance and secreted nascent proteins, thus demonstrating the sensitivity and immediacy of the PMSNP method.

Quantitative proteomics reveals stage-specific protein regulation of triple negative breast cancer.

BACKGROUNDS: Triple negative breast cancer (TNBC) is a heterogeneous disease with more aggressive clinical courses than other subtypes of breast cancer. In this study, we performed high-resolution mass spectrometry-based quantitative proteomics with TNBC clinical tissue specimens to explore the early and sensitive diagnostic signatures and potential therapeutic targets for TNBC patients. METHODS: We performed an iTRAQ labeling coupled LC-MS/MS approach to explore the global proteome in tumor tissues and corresponding para-tumor tissues from 24 patients with grade I-II and grade III primary TNBC. Relative peptide quantification and protein identification were performed by Proteome Discoverer™ software with Mascot search engine. Differentially expressed proteins were analyzed by bioinformatic analyses, including GO function classification annotation and KEGG enrichment analysis. Pathway analyses for protein-protein interactions and upstream regulations of differentially expressed candidates were performed by Ingenuity Pathway Analysis (IPA) software. RESULTS: Totally, 5401 unique proteins were identified and quantified in different stage of TNBCs. 845 proteins were changed in patients with grade I or II TNBC, among which 304 were up-regulated and 541 were down-regulated. Meanwhile, for patients with grade III TNBC, 358 proteins were increased and 651 proteins were decreased. Comparing to para-cancerous tissues, various signaling pathways and metabolic processes, including PPAR pathways, PI3K-Akt pathway, one-carbon metabolism, amino acid synthesis, and lipid metabolism were activated in TNBC cancer tissues. Death receptor signaling was significantly activated in grade I-II TNBCs, however, remarkably inhibited in grade III TNBCs. Western blot experiments were conducted to validate expression levels of CYCS, HMGA1 and XIAP with samples from individual patients. CONCLUSIONS: Overall, our proteomic data presented precise quantification of potential signatures, signaling pathways, regulatory networks, and characteristic differences in each clinicopathological subgroup. The proteome provides complementary information for TNBC accurate subtype classification and therapeutic targets research.

Multilayered N-Glycoproteome Profiling Reveals Highly Heterogeneous and Dysregulated Protein N-Glycosylation Related to Alzheimer's Disease.

Protein N-glycosylation is ubiquitous in the brain and is closely related to cognition and memory. Alzheimer's disease (AD) is a multifactorial disorder that lacks a clear pathogenesis and treatment. Aberrant N-glycosylation has been suggested to be involved in AD pathology. However, the systematic variations in protein N-glycosylation and their roles in AD have not been thoroughly investigated due to technical challenges. Here, we applied multilayered N-glycoproteomics to quantify the global protein expression levels, N-glycosylation sites, N-glycans, and site-specific N-glycopeptides in AD (APP/PS1 transgenic) and wild-type mouse brains. The N-glycoproteomic landscape exhibited highly complex site-specific heterogeneity in AD mouse brains. The generally dysregulated N-glycosylation in AD, which involved proteins such as glutamate receptors as well as fucosylated and oligomannose glycans, were explored by quantitative analyses. Furthermore, functional studies revealed the crucial effects of N-glycosylation on proteins and neurons. Our work provides a systematic multilayered N-glycoproteomic strategy for AD and can be applied to diverse biological systems.

Fast and precise quantification of serum biomarkers and simultaneous recognition of multiple diseases enabled by a stable isotope-labelled peptides assisted high-throughput MRM strategy.

Serum/plasma holds promise as an important source of disease-related proteins and even biomarkers in clinical practice. However, the discovery of biomarker candidates in serum/plasma remains challenging. In this study, we constructed an MS strategy that enables the fast and precise quantification of serum biomarkers through coupling a high-throughput scheduled MRM strategy with a stable isotope-labelled (SIL) peptide panel from more than 500 plasma proteins as internal standards. With this strategy, we discovered relevant serum proteins of atherosclerosis (AS), lung cancer (LC) and breast cancer (BC), which can simultaneously recognize these diseases. The results indicate that the powerful strategy we constructed has the potential for serum biomarker screening and disease detection.

"Sandwich" mesh reconstruction of female giant urethral diverticulum: a case report.

BACKGROUND: There is no consensus between urologists on the diagnosis and treatment of female urethral diverticula. Once the diagnosis has been established, the most common treatment approach is surgical excision and reconstruction. Whether a staged procedure or simultaneous management is more appropriate for treating concomitant urethral diverticula and stress urinary incontinence remains controversial. CASE PRESENTATION: A 63-year-old woman was hospitalized for repeated frequent urination, urgent urination, odynuria, and dysuria accompanied by intermittent overflow urinary incontinence for over 10 years. She had a 5 year history of urinary stress incontinence prior to onset of these symptoms and had had four urethral caruncles resected on four separate occasions. There was visible leakage of urine when abdominal pressure was increased during physical examination and urodynamic studies. Additionally, turbid urine was discharged when the anterior vaginal wall was squeezed. Cystourethrography showed circumferential filling with contrast and multiple bladder diverticulae in the mid plane of the pubic symphysis. Urethrocystoscopy showed an orifice to a diverticulum at 7 o'clock in the proximal urethra, into which an F19.8 urethroscope could be inserted, enabling examination of most of the diverticulae. The urethral diverticulae were resected, followed by mesh reconstruction of the urethra. During a 20-month follow-up, the treatment outcomes were satisfactory. CONCLUSION: We here report a case of a giant circumferential urethral diverticulum combined with stress urinary incontinence that was successfully managed by an uncommon surgical reconstructive technique: a minimally invasive "Sandwich" mesh repair procedure utilizing synthetic mesh wrap in the midurethral region.

In Situ Synthesis of Magnetic Mesoporous Phenolic Resin for the Selective Enrichment of Glycopeptides.

Protein glycosylation is a significant participant in a mass of biological processes, which is a pivotal protein post-translational modification. Due to the low contents of glycopeptides compared with nonglycopeptides and the microheterogeneity of glycosylation sites, highly selective enrichment methods for the purification of glycopeptides are required for the comprehensive characterization of glycoproteomics. In this work, a type of magnetic mesoporous phenolic resin (MMP) was prepared using branched polyethylenimine (PEI) as a cross-linker from a homogeneous magnetic Fe3O4@SiO2 solution in a resorcinol/formaldehyde monomer aqueous system via an in situ emulsion polymerization procedure. The results showed that MMP exhibited good biocompatibility, a mesoporous structure, nitrogen-containing functionality, excellent hydrophilicity, and solvent resistance by using multiple characterization methods. By taking advantage of the interaction between hydrophilic groups on the MMP and glycan components on the glycopeptides, the acquired MMP was utilized to the selective capture of N-glycopeptides (human IgG or HRP tryptic digests/BSA proteins = 1:50), good recovery yield (70.18-97.23%), superior binding capacity (400 mg g-1), and excellent reproducibility. Based on the outstanding performance in standard glycoproteins tryptic digests enrichment, MMP was further used to capture N-glycopeptides from tryptic digests of human serum. A total of 15 unique N-glycopeptides were identified from an ultralow sample volume (0.025 µL) of human serum. Overall, we identified 356 unique N-glycopeptides corresponding to 119 glycoproteins from human serum (0.35 µL) in the overlap of three replicate analyses. All the results have demonstrated that MMP has great potential in large-scale N-glycoproteomics research.

Study on behaviors and performances of universal N-glycopeptide enrichment methods.

Glycosylation is a crucial process in protein biosynthesis. However, the analysis of glycopeptides through MS remains challenging due to the microheterogeneity and macroheterogeneity of the glycoprotein. Selective enrichment of glycopeptides from complex samples prior to MS analysis is essential for successful glycoproteome research. In this work, we systematically investigated the behaviors and performances of boronic acid chemistry, ZIC-HILIC, and PGC of glycopeptide enrichment to promote understanding of these methods. We also optimized boronic acid chemistry and ZIC-HILIC enrichment methods and applied them to enrich glycopeptides from mouse liver. The intact N-glycopeptides were interpreted using the in-house analysis software pGlyco 2.0. We found that boronic acid chemistry in this study preferred to capture glycopeptides with high mannose glycans, ZIC-HILIC enriched most N-glycopeptides and did not show significant preference during enrichment and PGC was not suitable for separating glycopeptides with a long amino acid sequence. We performed a detailed study on the behaviors and performances of boronic acid chemistry, ZIC-HILIC, and PGC enrichment methods and provide a better understanding of enrichment methods for further glycoproteomics research.

TLR4 polymorphisms affect stroke risk and inflammatory response in Chinese ischemic stroke patients.

This study aimed to evaluate the association of the toll-like receptor 4 (TLR4) polymorphisms rs1927914, rs10759932, and rs11536889 with susceptibility to ischemic stroke (IS) and the serum levels of inflammatory cytokines. A total of 816 IS patients and 816 control subjects were genotyped using Sequenom MassARRAY technology. The serum levels of interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNFα) were measured by enzyme-linked immunosorbent assay. rs1927914 was significantly associated with male IS patients in the additive model [odds ratio (OR) = 0.81; 95% confidence interval (CI) = 0.67-0.99; P = 0.039] and in the allele model (OR = 0.81; 95% CI = 0.66-0.99; P = 0.037). In the dominant model, rs10759932 was significantly associated with the serum TNFα level of the male IS patients [regression coefficient (ß) = 0.15; 95% CI = 0.01-0.29; P adj = 0.042]. This polymorphism was also correlated with the serum IL-8 level of female IS patients in the additive model (ß = 0.24; 95% CI = 0.25-0.43; P adj = 0.021) and in the recessive model (ß = 0.65; 95% CI = 0.11-1.11; P adj = 0.026). The TLR4 gene rs1927914 polymorphism was associated with susceptibility to IS in males. Moreover, the rs10759932 polymorphism may affect inflammatory response in IS patients.

Thermococcus Eurythermalis Endonuclease IV Can Cleave Various Apurinic/Apyrimidinic Site Analogues in ssDNA and dsDNA.

Endonuclease IV (EndoIV) is a DNA damage-specific endonuclease that mainly hydrolyzes the phosphodiester bond located at 5' of an apurinic/apyrimidinic (AP) site in DNA. EndoIV also possesses 3'-exonuclease activity for removing 3'-blocking groups and normal nucleotides. Here, we report that Thermococcus eurythermalis EndoIV (TeuendoIV) shows AP endonuclease and 3'-exonuclease activities. The effect of AP site structures, positions and clustered patterns on the activity was characterized. The AP endonuclease activity of TeuendoIV can incise DNA 5' to various AP site analogues, including the alkane chain Spacer and polyethylene glycol Spacer. However, the short Spacer C2 strongly inhibits the AP endonuclease activity. The kinetic parameters also support its preference to various AP site analogues. In addition, the efficient cleavage at AP sites requires ≥2 normal nucleotides existing at the 5'-terminus. The 3'-exonuclease activity of TeuendoIV can remove one or more consecutive AP sites at the 3'-terminus. Mutations on the residues for substrate recognition show that binding AP site-containing or complementary strand plays a key role for the hydrolysis of phosphodiester bonds. Our results provide a comprehensive biochemical characterization of the cleavage/removal of AP site analogues and some insight for repairing AP sites in hyperthermophile cells.

Clinical features and outcome in patients with osseomuscular type of Wilson's disease.

BACKGROUND: Wilson's disease with osseomuscular type is a rare condition, which often lacks typical hepatic and neurological symptoms and causes misdiagnoses easily. During the past 10 years, eight Chinese patients of osseomuscular type of Wilson's disease were identified in our clinic. METHODS: Clinical information was gathered from medical records and follow-ups. The genetic testing was performed in each patient. Serum ceruloplasmin, Kayser-Fleischer rings, liver function, brain magnetic resonance imaging and abdominal ultrasonography were also evaluated. RESULTS: The median age of onset is 12 years of age. The patients had their initial musculoskeletal conditions with arthralgia or joint deformity, while the hepatic or neurologic signs were minimal. Most patients (6/8) eventually developed clinical neurological symptoms afterwards with a median interval of 36 months. All of them had normal liver function and low serum ceruloplasmin (<0.1 g/L). Most patients (6/8) present with Kayser-Fleischer rings and abnormal hepatic ultrasonography. The arthralgia was resolved with copper chelation therapy. CONCLUSIONS: Wilson's disease with osseomuscular type occurs without typical hepatic or neurological symptoms, which makes the clinical diagnosis challenging. Serum ceruloplasmin, abdominal ultrasonography, ophthalmic examination and genetic testing help to establish the diagnosis. Early diagnosis can initiate an effective treatment and prevent the further damage.

Budesonide suspension nebulization treatment in Chinese pediatric patients with cough variant asthma: a multi-center observational study.

OBJECTIVE: To describe the impact of nebulized budesonide inhalation suspension (BIS) on guardian-reported symptoms in Chinese pediatric patients with cough variant asthma (CVA). METHODS: This was a secondary analysis of a prospective, non-interventional study conducted at 39 Chinese sites. Patients with CVA aged ≤5 years were classified according to the severity of baseline symptoms: mild (symptom score ≤3) or severe (symptom score >3). Daytime and night-time symptom scores, disease control, use of bronchodilators, and improvements in symptoms control were compared after 1, 3, 5 and 7 weeks of treatment between groups. RESULTS: Among 914 patients, 821 (89.8%) completed the 7-week treatment. Among all patients, 368 (40.3%) were classified as mild CVA and 529 (57.9%), as severe CVA. Symptom scores in the severe group were higher than those in the mild group at weeks 1, 3, and 5 (p < 0.05), but not at week 7 (p > 0.05). Further, more patients in the mild group achieved disease control at any time point (98.6% at 3 weeks and 99.7% at 7 weeks), compared with the patients in the severe group (p < 0.001). The proportion of patients requiring bronchodilators differed between the groups until week 5 (p < 0.001). No severe or drug-related adverse events were reported. CONCLUSIONS: Individualized BIS treatment should be formulated according to the severity of baseline symptoms in CVA patients. Patients with mild CVA showed improvement after a shorter treatment time, while patients with severe CVA might require a longer time to respond to the treatment.

The prevalence and incidence of Parkinson's disease in China: a systematic review and meta-analysis.

Parkinson's disease (PD) is a chronic neurodegenerative disorder affecting older individuals. There is inconsistent evidence about the prevalence and incidence of PD in China at present. The aim of the meta-analysis was to estimate the prevalence and incidence of PD and its relation to age, gender, and stage in China. The literature search was conducted using PubMed, EMBASE, Chinese Biological Medical Literature database (CBM), Chinese National Knowledge Infrastructure database (CNKI), Chinese Wanfang and Chongqing VIP database for studies investigating the prevalence and incidence of PD in China from the commencement of the database until August 2012; both English and Chinese publications were included. We estimated the prevalence and incidence of PD using meta-analysis. Thirteen eligible articles were collected. The results showed that the pooled prevalence and incidence of PD were 2 per 100,000 population and 797 per 100,000 person-years. A higher prevalence of PD was found in males than in females (OR 1.29, 95 % CI 1.05-1.57). The prevalence of PD increased with age: the highest was 1,663 per 100,000 in those aged 80 and older. The overall prevalence of PD is lower in China than in developed countries, but the incidence is higher than in some developed countries. Overall, the prevalence of PD appears to increase with age and there are sex differences evident in Chinese individuals.

Association of the T102C polymorphism in the HTR2A gene with major depressive disorder, bipolar disorder, and schizophrenia.

A number of studies have assessed a relationship between the T102C polymorphism in the HTR2A gene with an increased risk of major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). However, the results have been inconsistent. Hence, we performed this study to further evaluate potential associations between the T102C polymorphism and MDD, BPD, and SCZ. The strength of separate associations between the T102C polymorphism and the risk of MDD, BPD, or SCZ was measured by ORs and 95% confidence intervals (CIs) in six genetic models. Cochran's chi-square-based Q-statistic and I(2) were used to evaluate the heterogeneity between studies. The funnel plot and the Egger's test were used to assess the publication bias. Cumulative meta-analysis was also performed to evaluate the trend in OR over time. No significant association was found in the overall analysis of MDD, BPD and SCZ with a sample size of 17,178 cases and 20,855 control subjects. In a further analysis by ethnicity, the OR and 95% CIs indicated the T102C polymorphism was not associated with MDD, BPD, or SCZ in Caucasian, Asian or Chinese populations. No publication bias was observed in the meta-analysis, and the cumulative analyses indicated the robust stability of the results. Thus, the results of our study indicate that the T102C polymorphism is not associates with increased susceptibility to MDD, BPD, and SCZ.