Prevalence and risk factors of depression and anxiety among patients with convulsive epilepsy in rural West China.

OBJECTIVES: To explore the prevalence and risk factors of depression and anxiety in patients with convulsive epilepsy (PWE) in rural West China. METHODS: PWE from rural West China were evaluated for depression and anxiety with the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E; Chinese version) and the Generalized Anxiety Disorder-7 (GAD-7; Chinese version). We also assessed their quality of life using the Quality of Life in Epilepsy Inventory (QOLIE-31) and their level of social support using the Social Support Rating Scale (SSRS). We used logistic regression analysis to identify independent risk factors of depression and anxiety and analysis of variance (ANOVA) to investigate the association between quality of life and depression and anxiety. RESULTS: Of the 458 PWE in our study, 33.4% have anxiety and 52.6% have depression. SSRS (P = 0.03) and seizure frequency (P = 0.007) are independent risk factors of anxiety, and annual income of the patients (P < 0.001) is an independent risk factor of depression. PWE with both depression and anxiety have significantly lower QOLIE-31 total and subtotal scores. CONCLUSIONS: PWE have a high prevalence of depression and anxiety in rural West China, which may be impacting their quality of life. PWE with depression and anxiety got a worse quality of life, and depression had a greater impact on quality of life for PWE than anxiety. The risk factors of depression and anxiety include seizure frequency and social support, while annual income is an additional risk factor of depression. Identifying risk factors early may be helpful in the timely management of these symptoms.

Terminal seizure frequency and its relation to SUDEP.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with epilepsy. Several risk factors have been implicated, including early age of onset, tonic-clonic seizures and antiepileptic drugs. However, whether patients who die from SUDEP have a greater frequency of seizures in the few months before death is unclear. We investigated the terminal seizure frequency and its relation to SUDEP among a large group of patients with tonic-clonic seizures in rural West China. METHODS: We used the database from the Convulsive Epilepsy Control and Management Program in West China, which routinely provides phenobarbital (PB) as a treatment for convulsive epilepsy. Patients with probable SUDEP were included according to pre-set criteria. A verbal autopsy was undertaken for each case. By matching each patient's age, sex, date of joining the program, time in follow-up, and baseline seizure frequency, we set up a 1:5 ratio control group. SPSS 21.0 statistics were applied to compare the differences in seizure frequency 3months prior to SUDEP between patients with probable SUDEP and controls. Furthermore, the dynamic changes of terminal seizure frequency 6-9months, 3-6months, and 3months prior to SUDEP was also analyzed. RESULTS: A total of 41 patients who died from probable SUDEP were identified out of 7844 patients during 10years of follow-up. The SUDEP group had a significantly higher tonic-clonic seizure frequency 3months before their deaths than the control group (p=0.023). At the same time, their seizure-free rate was lower than the control group (p=0.025). Patients with probable SUDEP who were followed up over 12months were further studied as a subgroup. They had more tonic-clonic seizures 3months prior to death compared to the control group (p=0.010). They also had an increase in seizure frequency in their terminal phase (3months prior) compared to an earlier stage (3-6months prior) (p=0.029). Furthermore, the terminal PB dose in the SUDEP group was higher than the control group (p=0.002). CONCLUSION: Patients who died from SUDEP had more frequent tonic-clonic seizures 3months before their deaths. Higher seizure frequency increases the exposure to peri-ictal pathophysiological events, which possibly relate to SUDEP. This phenomenon may be due to the drug resistance potential of these patients or the high dose of PB. Further research is required to ascertain the underlying mechanisms of SUDEP.

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.

Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14-19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c-Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/ß-catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.

Development and Initial Validation of the Positive and Negative Co-Rumination Scale.

This article presents two studies with data from 750 college students (58.67% females, Mage = 20.79 years) and 1035 school students (52.1% girls, Mage = 14.44 years) respectively, describing the development and initial validation of the Positive and Negative Co-Rumination Scale (PANCRS). The PANCRS consists of 32 items with 3 second-order factors: Positive Co-Rumination consisting of 3 first-order factors (i.e., Affirmation, Problem-Solving and Enhancing Friendship), Negative Co-Rumination consisting of 4 first-order factors (i.e., Worry About Evaluation, Inhibiting Happiness, Worry About Impact and Slack) and Frequency consisting of 2 first-order factors (i.e., Frequencies of Co-Rumination on Positive and Negative Events). Results from exploratory and confirmatory factor analyses confirmed the measure's 9 first-order and 3 second-order factors structure. Moreover, correlation analyses provided first evidence for the subscales' differential validity: (1) Positive Co-Rumination showed positive correlations with positive indicators of psychological adjustment (i.e., friendship quality and life satisfaction) and negative correlations with negative indicators of psychological adjustment (i.e., anxiety and depression); (2) Negative Co-Rumination showed non-significant or negative correlations with positive indicators of psychological adjustment and positive correlations with negative indicators of psychological adjustment; (3) Frequency showed positive correlations with both positive and negative indicators of psychological adjustment. In addition, all PANCRS scores showed satisfactory composite reliability (omegas) and temporal stability (test-retest). Overall the findings suggest that the PANCRS is a reliable and valid instrument to assess positive and negative aspects of Co-rumination.

Endoscopic resection for colorectal laterally spreading tumors in East Asian countries: a systematic review.

Background: To assess the efficacy and safety of different endoscopic resection methods for colorectal laterally spreading tumors (LSTs) in East Asian countries. Methods: A literature search was performed in PubMed, Embase, Cochrane Library and Web of Science databases. Colorectal LSTs of the included studies were resected with endoscopic mucosal resection (EMR) and/or endoscopic submucosal dissection (ESD). The main outcomes involved rates of en bloc resection, R0 resection, adverse events and recurrence. Results: A total of 20 studies were finally included in the present study. The total number of lesions were 3,903 (EMR: 1,230, ESD: 2,673). EMR-en bloc resection was obtained in 395/591 (66.8%), with ESD-en bloc resection reported in 2,020/2,265 (89.2%) [odds ratio (OR) 0.244, P<0.0001, 95% confidence interval (CI): 0.197-0.304]. EMR-R0 resection was achieved in 409/547 (74.8%), which was lower than that of ESD (1,895/2,241, 84.6%) (OR 0.541, P<0.0001, 95% CI: 0.432-0.677). Bleedings occurred more frequently in EMR than in ESD group (10.4% vs. 3.1%, OR 3.559, P<0.0001, 95% CI: 2.618-4.836). Rates of perforations in EMR and ESD were 0.4% and 4.1% (OR 0.099, P<0.0001, 95% CI: 0.036-0.27). Recurrence of EMR was higher than ESD group (6.3% vs. 1.0%, OR 6.732, P<0.0001, 95% CI: 3.751-12.082). Discussion: Endoscopic resections of colorectal LSTs are safe and effective. ESD leads to higher rates of en bloc and R0 resection, as well as lower rates of bleeding and recurrence, but it has a high risk of perforation, compared with EMR.

Network Pharmacology-Based Strategy to Identify the Pharmacological Mechanisms of Pulsatilla Decoction against Crohn's Disease.

Purpose: To explore pharmacological mechanisms of Pulsatilla decoction (PD) against Crohn's disease (CD) via network pharmacology analysis followed by experimental validation. Methods: Public databases were searched to identify bioactive compounds and related targets of PD as well as related genes in patients with CD. Analyses using the drug-compound-target-disease network, the protein-protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the core targets and pathways of PD against CD. Colon tissue resected from patients with CD and tissue samples from a mouse model of CD fibrosis treated with PD were assessed to verify the major targets of PD in CD predicted by network pharmacologic analysis. Results: A search of the targets of bioactive compounds in PD and targets in CD identified 134 intersection targets. The target HSP90AA1, which was common to the drug-compound-target-disease and PPI networks, was used to simulate molecular docking with the corresponding bioactive compound. GO and KEGG enrichment analyses showed that multiple targets in the antifibrotic pathway were enriched and could be experimentally validated in CD patients and in a mouse model of CD fibrosis. Assays of colon tissues from CD patients showed that intestinal fibrosis was greater in stenoses than in nonstenoses, with upregulation of p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, p-PKC, and PKC targets. Treatment of CD fibrosis mice with PD reduced the degree of fibrosis, with downregulation of the p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, and PKC targets. Conclusion: Network pharmacology analysis was able to predict bioactive compounds in PD and their potential targets in CD. Several of these targets were validated experimentally, providing insight into the pharmacological mechanisms underlying the biological activities of PD in patients with CD.

Prognostic and therapeutic implication of m6A methylation in Crohn disease.

BACKGROUND: N6-methyladenosine (m6A) methylation has been reported to participate in inflammatory bowel disease (including Crohn disease [CD]). However, the prognostic and therapeutic implication of m6A methylation modification in CD is still unclear. METHODS: Genomic information of CD patients was integrated to assess disease-related m6A regulators, and difference and correlation analyses of m6A regulators were explored by using the R packages. Next, CD patients were classified by the expression of differential and intersecting genes in m6A regulators, and difference and correlation analyses were conducted among immune infiltration and therapeutic responses. Finally, colon tissue resected from patients with CD were assessed to verify expression of Wilms tumor 1-associated protein (WTAP) and METTL14 from these m6A regulators. RESULTS: We identified 23 m6A regulators in CD patients. Difference analysis of these regulators showed that expression of METTL14, WTAP, RBM15 and YTHDF2/3 was upregulated in the treatment group compared with the control group, with expression of METTL3, YTHDF1, leucine-rich pentatricopeptide repeat motif-containing protein, HNRNPA2B1, IGF2BP1 and fat mass and obesity-associated protein downregulated. Moreover, RBM15, WTAP, leucine-rich pentatricopeptide repeat motif-containing protein, YTHDF1 and YTHDF3 were considered the characteristic genes of CD in m6A regulators. In addition, we identified 4 intersection genes of 3 m6A cluster patterns. Based on the expression of these intersection genes, difference analysis among m6A regulators indicated that the expression of 8 m6A regulators had statistical differences among the 3 geneCluster patterns. Assays of colon tissues from CD patients showed that expression of WTAP and METTL14 were higher in areas of stenosis than non-stenosis. CONCLUSION: m6A methylation modification might affect disease risk, immune infiltration and therapeutic responses in CD. Evaluating the expression of m6A regulators might provide insight into the prediction of disease prognosis and therapeutic responses.

Research Advances in Genetic Mechanisms of Major Cucumber Diseases Resistance.

Cucumber (Cucumis sativus L.) is an important economic vegetable crop worldwide that is susceptible to various common pathogens, including powdery mildew (PM), downy mildew (DM), and Fusarium wilt (FM). In cucumber breeding programs, identifying disease resistance and related molecular markers is generally a top priority. PM, DM, and FW are the major diseases of cucumber in China that cause severe yield losses and the genetic-based cucumber resistance against these diseases has been developed over the last decade. Still, the molecular mechanisms of cucumber disease resistance remain unclear. In this review, we summarize recent findings on the inheritance, molecular markers, and quantitative trait locus mapping of cucumber PM, DM, and FM resistance. In addition, several candidate genes, such as PM, DM, and FM resistance genes, with or without functional verification are reviewed. The data help to reveal the molecular mechanisms of cucumber disease resistance and provide exciting new opportunities for further resistance breeding.

Trend of Sudden Unexpected Death in Epilepsy Incidence Rate in Rural West China.

Objectives: To explore the trend of sudden unexpected death in epilepsy (SUDEP) incidence rate over time in rural west China. Methods: We scanned probable SUDEP patients from the epilepsy program between 2010 and 2019 in rural West China and performed a verbal autopsy for each eligible patient. We calculated the crude and sex-adjusted incidence rate of SUDEP per person-year over a calendar year and the year of follow-up. We calculated the incidence rate ratio with the Poisson model in STATA 12.0 and calculated the annual percentage change (APC) and average annual percentage change in Joinpoint Trend Analysis Software 4.8.0.1 to analyze the trend of SUDEP incidence rate. Results: In 2010-2019, 44 probable SUDEPs were identified from 10,128 patients with a total person-year of 31,347. The crude and sex-adjusted incidence rates of SUDEP were 1.40 and 1.45%0. Twenty-five (56.8%) of the 44 probable SUDEPs had no generalized tonic-clonic seizure 3 months before their death. The incidence of probable SUDEP decreased significantly in the calendar year [APC = -11.7, 95% confidence interval (CI): -21.7 to -0.3] and in time of follow-up (average annual percentage change = -21.2, 95% CI: -34.3 to -5.4). Comparing the first 5 years in follow-up with the subsequent 3 years, the incidence rate of SUDEP decreased significantly (estimated incidence rate ratio = 0.4, 95% CI: 0.2 to 0.8). Significance: SUDEP happened to 1.4 cases per thousand patient-years in convulsive epilepsy in rural west China between 2010 and 2019. The incidence rate of SUDEP presented a downward trend over the time of follow-up.

Long-term seizure, comorbidity and socioeconomic outcomes of patients with convulsive epilepsy in rural West China.

PURPOSE: This study aimed to investigate the long-term outcomes of patients with convulsive epilepsy in rural West China and to explore potential related factors. METHODS: Patients who were provided Phenobarbital as a treatment and followed-up monthly were enrolled from the Convulsive Epilepsy Control and Management Program in West China. Their clinical and demographic information were obtained from the program database and a questionnaire. Seizure outcomes, comorbidities, annual income, marital status, employment and quality of life (QOL) were evaluated as long-term outcomes. Logistic regression was used to analyze the related factors. RESULTS: Of 473 eligible patients with a median follow-up time of nearly 7 years, 312 (66 %) had one-year terminal remission. A total of 320 (67.7 %) patients had a low annual income (<5000 Yuan), and 198 (41.9 %) patients reported a comorbidity. Among 460 patients of marriageable age, 137 (29.8 %) were unmarried. 60.4 % (333) patients reported improved QOL. Time of follow-up, seizure frequency during early treatment, compliance, annual cost for epilepsy treatment and annual income were related to the seizure outcome. Baseline seizure frequency was associated with comorbidities. Sex, annual cost for epilepsy treatment and seizure outcomes were associated with annual income. Age, sex and age at onset were correlated with current marital status. Compliance and taking traditional Chinese medicine were associated with QOL. CONCLUSION: The prognosis of epilepsy goes beyond being seizure-free. Comorbidities, income and marriage outcomes in resource-poor areas are less promising. Systematic management considering prognosis-related factors for epilepsy by a collaboration of health providers and society is needed.