Distinct patterns of electrophysiologic-neuroimaging correlations between Parkinson's disease and multiple system atrophy.

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.

Spinal cord stimulation for postural abnormalities in Parkinson's disease: 1-year prospective pilot study.

BACKGROUND: Postural abnormalities (PA) are common in the advanced stages of Parkinson's disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. METHODS: T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. RESULTS: Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. CONCLUSIONS: Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

Screening and molecular dynamics simulation of ACE inhibitory tripeptides derived from milk fermented with Lactobacillus delbrueckii QS306.

Peptides in milk fermented with Lactobacillus delbrueckii QS306 before and after ultrahigh pressure treatment were identified using proteomics. Subsequently, 16 stable tripeptides were screened out based on activity score prediction, PeptideCutter analysis, and hydrophobicity calculations. Among them, WRP, WSR, and YRP showed the best angiotensin-converting enzyme (ACE) inhibitory activity, and their semi-inhibitory concentrations were 46.707, 300.121, and 89.555 µM, respectively. WRP and WSR were competitive inhibitors, whereas YRP was non-competitive. Gastrointestinal simulation revealed that WRP and YRP had better gastrointestinal stability. The values of RMSD, ΔGbind, ΔGpol, and RSMF obtained from molecular dynamics simulation indicated that the interaction of WRP and ACE was stable. Thus, Lactobacillus delbrueckii QS306-fermented milk can serve as an important source of ACE inhibitory peptides both before and after ultrahigh pressure treatment. The strategy of in silico screening, activity evaluation, and molecular dynamics simulation adopted in this study can be applied to the large-scale screening of novel peptides with high ACE inhibitory activity.

High glucose-increased miR-200c contributes to cellular senescence and DNA damage in neural stem cells.

BACKGROUND: Maternal diabetes increases the risk for neural tube defects (NTDs). It is unclear if miRNAs, senescence, and DNA damage are involved in this process. In this study, we used neural stem cells as an in vitro proxy of embryonic neuroepithelium to investigate whether high glucose triggers neural stem cell senescence and DNA damage by upregulating miR-200c, which may be responsible for NTDs. METHODS: C17.2 neural stem cells were cultured with normal glucose (5 mM) or high glucose (≥16.7 mM) at different doses and time points for detecting miR-200c levels, markers of senescence and DNA damage. Neural stem cells were exposed to antioxidant SOD1 mimetic Tempol and high glucose for 48 h to test roles of oxidative stress on the miR-200c, senescence, and DNA damage levels. An miR-200c mimic and an inhibitor were transfected into neural stem cells to increase or decrease miR-200c activities. RESULTS: High glucose upregulated miR-200c in neural stem cells. A time course study of the effect of high glucose revealed that miR-200c initially increased at 12 h and reached its zenith at 18 h. Tempol reduced miR-200c levels caused by high glucose. High glucose induced markers of senescence and DNA damage in neural stem cells. Tempol abolished high glucose-induced markers of senescence and DNA damage. The miR-200c inhibitor suppressed high glucose-induced markers of senescence and DNA damage. Treatment with miR-200c mimic imitates high glucose-induced markers of senescence and DNA damage. CONCLUSIONS: We show that high glucose increases miR-200c, which contributes to cellular senescence and DNA damage in neural stem cells and provides a potential pathway for maternal diabetes-induced neural tube defects.

Continuous theta burst stimulation over the bilateral supplementary motor area in obsessive-compulsive disorder treatment: A clinical randomized single-blind sham-controlled trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) can cause substantial damage to quality of life. Continuous theta burst stimulation (cTBS) is a promising treatment for OCD patients with the advantages of safety and noninvasiveness. OBJECTIVE: The present study aimed to evaluate the treatment efficacy of cTBS over the bilateral supplementary motor area (SMA) for OCD patients with a single-blind, sham-controlled design. METHODS: Fifty-four OCD patients were randomized to receive active or sham cTBS treatment over the bilateral SMA for 4 weeks (five sessions per week, 20 sessions in total). Patients were assessed at baseline (week 0), the end of treatment (week 4), and follow-up (week 8). Clinical scales included the YBOCS, HAMD24, HAMA14, and OBQ44. Three behavioral tests were also conducted to explore the effect of cTBS on response inhibition and decision-making in OCD patients. RESULTS: The treatment response rates were not significantly different between the two groups at week 4 (active: 23.1% vs. sham: 16.7%, p = 0.571) and week 8 (active: 26.9% vs. sham: 16.7%, p = 0.382). Depression and anxiety improvements were significantly different between the two groups at week 4 (HAMD24: F = 4.644, p = 0.037; HAMA14: F = 5.219, p = 0.028). There was no significant difference between the two groups in the performance of three behavioral tests. The treatment satisfaction and dropout rates were not significantly different between the two groups. CONCLUSIONS: The treatment of cTBS over the bilateral SMA was safe and tolerable, and it could significantly improve the depression and anxiety of OCD patients but was not enough to improve OCD symptoms in this study.

Neuroprotective Effects of Intermittent Theta Burst Stimulation in Parkinson's Disease (NET-PD): A Study Protocol for a Delayed-Start Randomized Double-Blind Sham-Controlled Trial.

BACKGROUND: As a typical high-disability neurodegenerative disease, Parkinson's disease (PD) progresses variably, and patients who are clinically insensitive to dopaminergic therapy and whose symptoms fail to improve are commonly observed. As a result, achieving early neuron protection is critical. METHODS/DESIGN: The NET-PD study is a 2-year prospective single-center, double-blind, multi-arm, delayed-start, sham-controlled clinical trial assessing the long-term neuroprotective effect of intermittent theta burst stimulation (iTBS) in PD patients. Patients diagnosed with PD, aged 50-80, Hoehn-Yahr stage ≤4, and who maintain medication stability during the study will be enrolled. Clinical assessment and multi-modal markers are used to clarify the clinical improvement and dynamic neuronal changes in PD patients. With a standard deviation of 2, a test level of 0.05, a dropout rate of 10%, and a degree of certainty of 0.9, 60 PD patients are required for this study. RESULTS: The NET-PD project was funded in March 2022, data collection began in July 2022, and is currently in the recruitment phase with two PD patients already enrolled. Data collection is expected to be completed in June 2024. The results are expected for publication in December 2024. DISCUSSION: Previous research has demonstrated a rudimentary method for assessing and delaying PD progression in clinical medication trials. The NET-PD study adopts a rigorous methodology and specific disease-modifying designs to demonstrate the neuroprotective effect of iTBS on PD and investigate the potential mechanism of iTBS in regulating brain and motor functions. We hope to provide supposition for the subsequent exploration of diverse neuroprotection methods.

The functional connectivity predictor of therapeutic effect of continuous theta burst stimulation on obsessive-compulsive disorder: A preliminary study.

OBJECTIVE: To evaluate the efficacy of continuous theta burst stimulation (cTBS) on the bilateral supplementary motor area (SMA) among patients with obsessive-compulsive disorder (OCD) and to explore the potential predictors of cTBS outcome based on neuroimaging. METHODS: 29 OCD patients and 29 healthy controls (HCs) were enrolled in this pilot study. Twenty consecutive cTBS intervention targeting at bilateral SMA was applied. MRI scan was carried out before cTBS and 15 regions in the executive control and sensorimotor network were chosen and analyzed using MATLAB, DPABI, and SPM12. RESULTS: 11 out of 29 patients responded to cTBS (37.93%), and the clinical symptom of OCD patients was significantly relieved after receiving regular cTBS. Also, the FC between Cerebelum_Crus2_L and Frontal_Inf_Tri_L of OCD patients showed positive prognosis for the efficacy of cTBS, with the area under the curve (AUC) of 0.85 (95% confidence interval: 0.718-0.989, p = 0.002). None of the patients had any serious adverse event. CONCLUSION: cTBS intervention on bilateral SMA can significantly improve the symptoms of medicated OCD patients with moderate severity. And the pretherapy FC could be a valuable potential predictor of the cTBS treatment outcome among OCD patients.

A one-step platform for screening high-efficient and minimal off-target CRISPR/Cas13 crRNAs to eradicate SARS-CoV-2 virus for treatment of COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is a new respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and now spreads globally. Currently, therapeutics and effective treatment options remain scarce and there is no proven drug to treat COVID-19. Targeting the positive-sense RNA genome and viral mRNAs of SARS-CoV-2 to simultaneously degrade viral genome templates for replication and viral mRNAs for essential gene expression would be a strategy to completely realize virus elimination. Type VI CRISPR enzymes Cas13 have recently been identified as programmable RNA-guided, RNA-targeting Cas proteins with nuclease activity that allows for RNA cleavage and degradation. The precise viral RNA detection and antiviral application of the CRISPR/Cas13 system depend on high-efficient and minimal off-target crRNAs. Although a computer-based algorithm has been applied for the design of crRNAs targeting SRAS-CoV-2, the experimental screening system to identify optimal crRNA is not available. We develop a one-step experimental screening system to identify high-efficient crRNAs with minimal off-target effects for CRISPR/Cas13-based SARS-CoV-2 elimination. This platform provides the foundation for CRISPR/Cas13-based diagnostics and therapeutics for COVID-19. This platform is versatile and could also be applied for crRNAs screening for other RNA viruses.

Transcranial direct current stimulation improve symptoms and modulates cortical inhibition in obsessive-compulsive disorder: A TMS-EEG study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling condition for which approximately 40% of patients do not respond to first-line treatment. Transcranial direct current stimulation (tDCS) is a safe and accessible technique that modulates cortical excitability and inhibition, but evidence of its efficacy for OCD is insufficient. OBJECTIVE: To investigate the efficacy of tDCS for OCD and alterations of cortical excitability and inhibition after treatment measured by concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). METHODS: Twenty-four OCD patients underwent 10 20-min sessions of 1.5 mA high-definition tDCS with a cathode placed over the right orbitofrontal cortex (OFC) and anode electrodes set around the cathodal electrode. TMS-EEG was performed before and after tDCS treatment. OCD symptom severitys was assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Beck Depression Inventory-Ⅱ (BDI-Ⅱ), and Beck Anxiety Inventory (BAI) were used to assess the severity of depression and anxiety symptoms. Twenty-seven healthy controls were recruited with TMS-EEG recorded. RESULTS: Following tDCS, the Y-BOCS, BDI-Ⅱ, and BAI scores decreased significantly (all p = 0.000). TMS-evoked N100 amplitude, thought to be related to GABAB receptor function, was significantly reduced after tDCS (Z = -2.143, p = 0.032) which was higher in OCD patients than in healthy controls at baseline (Z = -2.151, p = 0.031). LIMITATIONS: Pharmacotherapy during tDCS treatment may influence the effect of tDCS and EEG. CONCLUSIONS: Cathodal high-definition tDCS applied over the OFC could improve OCD, depression, and anxiety symptoms along with alleviation of GABAB receptor function.

Dynamic postural balance indices can help discriminate between patients with multiple system atrophy and Parkinson's disease.

Background: Patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) show similar symptoms but have different clinical treatments. It will be helpful to discriminate between these two kinds of patients at an early or middle stage. The purpose of this study is to highlight the differences in posturographic characterization between patients with PD and those with MSA during quiet standing and perturbed standing. Methods: A total of clinically diagnosed 42 patients with PD and 32 patients with MSA participated in the experiment. Patients were asked to first stand on a static balance force platform and then on a dynamic balance (medial-lateral rocker) force platform to measure the center of pressure (COP) trajectory during an eyes-open (EO) state. The posturographic parameters were obtained under the two standing conditions for statistical analysis. Results: Four posturographic variables were calculated and analyzed, namely, the standard deviation of COP position (SD), sway path of COP position (SP), an elliptical area covering the 95% COP position trajectory (EA), sway path of COP position (SP), and integral area of the power spectral density at 0-0.5 Hz frequency band (PSD). Except for variable EA, the other three variables are all in the medial-lateral (ML) direction. In the static balance experiment, there were no significant differences between the four variables between patients with PD and those with MSA. However, in the dynamic balance experiment, the obtained four variables all presented significant differences between patients with PD and those with MSA. Conclusion: The dynamic posturographic variables with significant differences between patients with PD and those with MSA imply that patients with MSA have worse postural control ability in the medial-lateral (ML) direction compared to patients with PD. The obtained dynamic indices may help supplemental clinical evaluation to discriminate between patients with MSA and those with PD.

CRISPR/Cas9-mediated gene editing on Sox2ot promoter leads to its truncated expression and does not influence neural tube closure and embryonic development in mice.

Sox2 overlapping transcript (Sox2ot) is a long non-coding RNA (lncRNA), which harbors one of the major regulators of pluripotency, the Sox2 gene, in its intronic region. Sox2ot is primarily expressed in the developing neuroepithelium. However, its role in neural tube closure and embryonic development remains unclear. To investigate if Sox2ot is required for neural tube closure and embryonic development, Sox2ot promoter was deleted by CRISPR-Cas9 genome editing technology to prevent Sox2ot gene expression in mice. We designed 9 guide RNAs to specifically target the Sox2ot promoter and 3 gRNAs induced gene editing on the promoter of the Sox2ot gene in cells transfected with Cas9 mRNA and gRNAs. Then, these gRNAs and Cas9 mRNA were injected into mouse zygotes and implanted into pseudopregnant mice. A Sox2ot promoter-deleted mouse line was identified with complete deletion of promoter as well as deletion of exon 1 and exon 2. Sox2ot transcript was truncated with a lack of exon 1 and exon 2 in Sox2ot promoter-deleted mice. Furthermore, neural tube closure and embryonic development were checked at E9.5, E10.5, E14.5, E17.5 and after-birth (P2) and we did not find any failure of neural tube closure and aberrant embryonic development in Sox2ot promoter-deleted mice. Thus, our study demonstrated that CRISPR-Cas9 gene editing in Sox2ot promoter leads to its truncated expression and does not influence neural tube closure and embryonic development.

Intermediation of perceived stress between early trauma and plasma M/P ratio levels in obsessive-compulsive disorder patients.

OBJECTIVES: This study is to find the correlation among BDNF metabolism, early trauma, and current stress status of OCD patients. As well as to study the BDNF metabolism-stress related pathological mechanism in OCD development. METHODS: A total of 140 participants were recruited in this study, including 64 drug-naïve OCD patients (OCDs) and 76 healthy controls (HCs). The clinical data of the subjects were measured using YBOCS, CTQ, and PSS. The plasma mBDNF and proBDNF values were measured by ELISA while the M/P ratio was calculated. RESULTS: The mBDNF, proBDNF plasma levels, and M/P ratio of unmedicated OCD individuals decreased evidently comparing with HCs. Also, positive associations were found between PSS and CTQ and between CTQ and M/P ratio. The negative correlation included proBDNF and PSS as well as proBDNF and CTQ. Intermediary analysis generated by SPSS has showed that the perceived stress played a complete mediating role between early trauma and plasma M/P ratio levels, and the mediating effect was 0.043 in non-medication OCD patients. CONCLUSIONS: Findings from this study suggested that early trauma experience and stress state work together in regulating BDNF metabolism level in OCD patients. The nucleus accumbens and reward loop are also pivotal in the pathogenesis of OCD.

Long Noncoding RNA SOX2-OT: Regulations, Functions, and Roles on Mental Illnesses, Cancers, and Diabetic Complications.

SRY-box transcription factor 2 (SOX2) overlapping transcript (SOX2-OT) is an evolutionarily conserved long noncoding RNA. Its intronic region contains the SOX2 gene, the major regulator of the pluripotency of embryonic stem cells. The human SOX2-OT gene comprises multiple exons and has multiple transcription start sites and generates hundreds of transcripts. Transcription factors (IRF4, AR, and SOX3), transcriptional inhibitors (NSPc1, MTA3, and YY1), and miRNAs (miR-211 and miR-375) have been demonstrated to control certain SOX2-OT transcript level at the transcriptional or posttranscriptional levels. Accumulated evidence indicates its crucial roles in the regulation of the SOX2 gene, miRNAs, and transcriptional process. Restricted expression of SOX2-OT transcripts in the brain results in the association between SOX2-OT single nucleotide polymorphisms and mental illnesses such as schizophrenia and anorexia nervosa. SOX2-OT is notably elevated in tumor tissues, and a high level of SOX2-OT is well correlated with poor clinical outcomes in cancer patients, leading to the establishment of its role as an oncogene and a prognostic or diagnostic biomarker for cancers. The emerging evidence supports that SOX2-OT mediates diabetic complications. In summary, SOX2-OT has diversified functions and could be a therapeutic target for various diseases.

Dissipation and residues of picoxystrobin in peanut and field soil by QuEChERS and HPLC-MS/MS.

The dissipation and final residues of picoxystrobin in peanut and soil were determined by a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The dissipation and final residue of picoxystrobin at three different provinces (Hebei, Hubei, and Shandong) in China were studied. The fortification experiments at three different spiking levels of 0.01, 0.05, and 0.5 mg kg(-1) in all matrices (soil, peanut seedling, shell, stalk, and kernels) were conducted, and the recoveries were 79-114% with relative standard deviations of 3-12 (n = 5). The dissipation half-lives of picoxystrobin were 1.5-8.6 days in soil, and 2.1-2.8 days in seedlings. The final residues of picoxystrobin in supervised field trials were 0.05-6.82 mg kg(-1) in stalk, ≤0.381 mg kg(-1) in soil, ≤0.069 mg kg(-1) in shells, and ≤0.005 mg kg(-1) in peanut kernels. Considering the final residue levels and the maximum residue limits (MRLs), the pre-harvest interval of 14 days was recommended for the safe use of picoxystrobin in peanut crop.

p53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells.

The p53 tumor repressor gene is commonly mutated in human cancers. The tumor inhibitory effect of metformin on p53-mutated breast cancer cells remains unclear. Data from the present study demonstrated that p53 knockdown or mutation has a negative effect on metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. We also found that p53 reactivating agent nutlin-3α and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively. Treatment of MCF-7 cells with metformin or phenformin induced increase in p53 protein levels and the transcription of its downstream target genes, Bax and p21, in a dose-dependent manner. Moreover, we demonstrated that AMPK-mTOR signaling played a role in metformin-induced p53 up-regulation. The present study showed that p53 is required for metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. The combination of metformin with p53 reactivating agents, like nutlin-3α and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations.

Determination and dissipation of fipronil and its metabolites in peanut and soil.

In this study, a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was established for the extraction and cleanup of fipronil and its three metabolites (fipronil solfone, sulfide, and desulfinyl) in peanut kernel, shell, straw, seedling, and soil samples, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for analysis. The average recoveries were 66-116% at the level of 0.001-0.1 mg/kg with the RSD <19%, and the limit of detection was 0.3 ng/g for all matrices. The dissipation experiment results demonstrated that fipronil dissipated more rapidly in peanut seedling than in soil, with half-lives of <1 day in peanut seedling and 32-57 days in soil depending on the soil pH. The final residues at harvest of peanut kernels were all below 0.02 mg/kg, whereas in peanut shell and straw, the total highest residues were 0.99 and 0.30 mg/kg, respectively. Fipronil-desulfinyl and fipronil-sulfone were the highest residue metabolites in peanut plant (seedling and straw) and soil samples, respectively.

Dissipation and residues of trifloxystrobin and its metabolite in rice under field conditions.

Residue analysis of trifloxystrobin and its metabolite (CGA 321113) in rice matrices, paddy water, and soil was developed using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and high-performance liquid chromatography-tandem mass spectrometry. The method was used to evaluate the dissipation rate of trifloxystrobin and CGA 321113 in rice seedling, soil, and paddy water as well as the residual level in harvest rice (grain, hull, straw) and soil. The results demonstrated that the dissipation half-lives of trifloxystrobin in rice seedling, soil, and water were 1.9 d to 4.7 d, 0.35 d to 0.54 d, and 0.28 d to 0.51 d, respectively. The final total residue of trifloxystrobin and CGA 321113 was highest in rice hull and lowest in paddy soil. The highest total residues in husked rice, rice hull, straw, and paddy soil at 28 d after spraying were 0.39 mg kg(-1), 3.82 mg kg(-1), 0.29 mg kg(-1), and 0.15 mg kg(-1), respectively. According to the final residue data and the maximum residue limits of trifloxystrobin in rice grain and straw (Codex Alimentarius) and in rice hull (US Environmental Protection Agency), 28 d could be recommended as the preharvest interval for trifloxystrobin application in the rice field. The data show that CGA 321113 constitutes a small amount of the final total residues in rice matrices, whereas it is much higher than its parent compound in soil samples.

Residues and dissipation of trifloxystrobin and its metabolite in tomatoes and soil.

A simple residue analytical method using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure for the determination of trifloxystrobin and its metabolite trifloxystrobin acid (CGA321113) in tomato and soil was developed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The limits of detection were 0.0005 mg/kg for trifloxystrobin and 0.001 mg/kg for trifloxystrobin acid, respectively. The average recoveries in tomato and soil ranged from 73-99 % for trifloxystrobin and 75-109 % for trifloxystrobin acid, with relative standard deviations below 15 %. The method was then used to study the dissipation and residues in tomato and soil. The dissipation half-lives of trifloxystrobin in tomato were 2.9 days (Beijing) and 5.4 days (Shandong), while in soil were 1.9 days (Beijing) and 3.0 days (Shandong), respectively. The final results showed that the major residue compound was trifloxystrobin in tomato whereas it was its metabolite, trifloxystrobin acid, in soil. The final residues of total trifloxystrobin (including trifloxystrobin acid) were below the EU maximum residue limit of 0.5 mg kg(-1) in tomato 3 days after the treatment.

Prevalence and age, gender and geographical area distribution of esophageal squamous cell carcinomas in North China from 1985 to 2006.

OBJECTIVE: To establish the prevalence and distribution profile of esophageal squamous cell carcinomas (ESCCs) over a 22-yr period in North China. METHODS: Using endoscopy for primary diagnosis and histological analysis for the further confirmation, a total of 74,854 ESCC patients aged 20-89 between January 1985 and December 2006 were investigated to analyze the epidemiological profile including prevalence rates, distribution of age-of-onset, gender and geographical area of ESCC in Luoyang, the highest incidence area of North China. RESULTS: A total of 4092 cases of ESCC were finally diagnosed among 74,854 patients who had their first endoscopies. The prevalence among males was higher than that among females (p<0.01), resulting in an overall male:female OR of 1.2 (95%CI, 1.2-1.3). The prevalence in rural areas was higher than in urban areas (p<0.01), resulting in an overall rural:urban OR of 2.6 (95%CI, 2.4-2.9). The rural:urban ORs and the 95% CI increased continuously from 2.6, 2.3-3.0 to 2.7, 2.2-3.3, respectively, for 4 consecutive periods during the 22-yr study period. Moreover, the median age of onset among females was higher than that among males (p<0.01). For both sexes and in both areas, the prevalence rates declined and the median age of onset rose for 4 consecutive periods in the 22-yrs time frame (p<0.01). CONCLUSIONS: [corrected] These data reveal the epidemiological profile of ESCC in the area of North China, and suggest that urban areas and rural people account for a growing proportion of the ESCC patients although the prevalence of ESCC significantly declined and the median age-of-onset postponed over the 22-yrs period. Moreover, the prevalence status of ESCC in rural areas also underlines the need for public health initiatives aimed at reducing risk factors of this fatal disease.