Effect of low-dose rituximab treatment on autoimmune nodopathy with anti-contactin 1 antibody

BackgroundAutoimmune nodopathy with anti-contactin-1 (CNTN1) responds well to rituximab instead of traditional therapies. Although a low-dose rituximab regimen was administered to patients with other autoimmune diseases, such as myasthenia gravis and neuromyelitis optica spectrum disorders, and satisfactory outcomes were obtained, this low-dose rituximab regimen has not been trialed in anti-CNTN1-positive patients.MethodsAnti–CNTN1 nodopathy patients were enrolled in this prospective, open-label, self-controlled pilot study. A cell-based assay was used to detect anti-CNTN1 antibodies and their subclasses in both serum and cerebrospinal fluid. Clinical features were evaluated at baseline, 2 days, 14 days, and 6 months after single low-dose rituximab treatment (600 mg). The titers of the subclasses of anti-CNTN1 antibody and peripheral B cells were also evaluated at baseline, 2 days, and 6 months after the rituximab regimen.ResultsTwo patients with anti–CNTN1 antibodies were enrolled. Both patients had neurological symptoms including muscle weakness, tremor, sensory ataxia, numbness and mild nephrotic symptoms. In the field of neurological symptoms, sensory ataxia markedly improved, and the titer of anti-CNTN1 antibody as well as CD19+ B cells decreased only two days following low-dose rituximab treatment. Other neurological symptoms improved within two weeks of rituximab treatment. At the 6-month follow-up, all neurological symptoms steadily improved with steroid reduction, and both the anti-CNTN1 antibody titer and CD19+ B cells steadily decreased. No adverse events were observed after this single low-dose rituximab treatment.ConclusionsWe confirmed the clinical efficacy of low-dose rituximab by B cell depletion in autoimmune nodopathy with anti-CNTN1 antibody. This rapid and long-lasting response suggests that low-dose rituximab is a promising option for anti-CNTN1 nodopathy

Is carrot consumption associated with a decreased risk of lung cancer? A meta-analysis of observational studies

Findings of epidemiological studies regarding the association between carrot consumption and lung cancer risk remain inconsistent. The present study aimed to summarise the current epidemiological evidence concerning carrot intake and lung cancer risk with a meta-analysis. We conducted a meta-analysis of case–control and prospective cohort studies, and searched PubMed and Embase databases from their inception to April 2018 without restriction by language. We also reviewed reference lists from included articles. Prospective cohort or case–control studies reporting OR or relative risk with the corresponding 95 % CI of the risk lung cancer for the highest compared with the lowest category of carrot intake. A total of eighteen eligible studies (seventeen case–control studies and one prospective cohort study) were included, involving 202 969 individuals and 5517 patients with lung cancer. The pooled OR of eighteen studies for lung cancer was 0·58 (95%CI 0·45, 0·74) by comparing the highest category with the lowest category of carrot consumption. Based on subgroup analyses for the types of lung cancer, we pooled that squamous cell carcinoma (OR 0·52, 95 % CI 0·19, 1·45), small-cell carcinoma (OR 0·43, 95 % CI 0·12, 1·59), adenocarcinoma (OR 0·34, 95 % CI 0·15, 0·79), large-cell carcinoma (OR 0·40, 95 % CI 0·10, 1·57), squamous and small-cell carcinoma (OR 0·85, 95 % CI 0·45, 1·62), adenocarcinoma and large-cell carcinoma (OR 0·20, 95 % CI 0·02, 1·70) and mixed types (OR 0·61, 95 % CI 0·46, 0·81). Exclusion of any single study did not materially alter the pooled OR. Integrated epidemiological evidence from observational studies supported the hypothesis that carrot consumption may decrease the risk of lung cancer, especially for adenocarcinoma

Meta-analysis on the association between the frequency of tooth brushing and diabetes mellitus risk

BACKGROUND AND OBJECTIVE: Epidemiological studies suggested that the frequency of tooth brushing might be associated with the risk of diabetes mellitus (DM), but the results were inconsistent and no systematic review was conducted to focus on this topic. In this meta-analysis, we synthesized available observational epidemiological evidences to identify the association between tooth brushing and DM risk and investigate the potential dose-response relationship of them. METHODS: We searched PubMed and Embase from their inception through December 2017 to identify observational studies examining the association between tooth brushing and the risk of DM. Reference lists from retrieved articles were also reviewed. We quantitatively combined results of the included studies using a random-effects model. Dose-response meta-analysis was conducted to further examine the effect of tooth brushing frequency on DM risk. RESULTS: We identified 20 relevant studies (one cohort study, 14 case-control studies, and five cross-sectional studies) involving161,189 participants and 10,884 patients with DM. Compared with the highest tooth brushing frequency, the lowest level was significantly associated with an increased risk of DM (OR 1.32, 95% CI: 1.19 to 1.47), and there was no significant heterogeneity across the included studies (P = 0.119, I2 = 28.1%). Exclusion of any single study did not materially alter the combined risk estimate. The dose-response analysis indicated that the summary odds of DM for an increment of one time of tooth brushing per day was 1.20 (95% CI: 1.16-1.24). CONCLUSIONS: Integrated epidemiological evidence supports the hypothesis that low frequency of tooth brushing may be a risk factor of DM, and lower frequencies of tooth brushing were significantly associated with higher risk of DM

Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients

BackgroundLAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown.MethodsWe conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients.ResultsNormal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3–11), whereas frameshift variants are distributed in exons 12–65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain.ConclusionsMissense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23

Preliminary Evidence of Sex Differences in Cortical Thickness Following Acute Mild Traumatic Brain Injury

The main objective of this study was to evaluate sex differences in cortical thickness after acute mild traumatic brain injury (mTBI) and its associations with clinical outcomes. Thirty-two patients with mTBI at acute phase (2.4 ± 1.3 days post-injury) and 30 healthy controls were enrolled. All the participants underwent comprehensive neurocognitive assessments and MRI to assess cortical thickness. Significant sex differences were determined by using variance analysis of factorial design. Relations between the cortical thickness and clinical assessments were measured with the Spearman Correlation. Results revealed that patients with mTBI had significantly reduced cortical thickness in the left entorhinal cortex while increased cortical thickness in the left precuneus cortex and right lateral occipital cortex, compared with healthy controls. The interaction effect of the group × sex on cortical thickness was significant. Female patients had significant thicker cortical thickness in the left caudal anterior cingulate cortex (ACC) than male patients and had higher scores on Posttraumatic stress disorder Checklist—Civilian Version (PCL-C). Spearman correlational analysis showed a significantly positive correlations between the cortical thickness of the left caudal ACC and PCL-C ratings in female patients. Sex differences in cortical thickness support its potential as a neuroimaging phenotype for investigating the differences in clinical profiles of mild TBI between women and men

The rates and the determinants of hypertension according to the 2017 definition of hypertension by ACC/AHA and 2014 evidence-based guidelines among population aged ≥40 years old

Background : In November 2017, the American College of Cardiology/American Heart Association (ACC/AHA) updated their definition of hypertension from 140/90 mm Hg to 130/80 mm Hg. Objectives : We sought to assess the situation of hypertension and the impact of applying the new threshold to a geographically and ethnically diverse population. Methods : We analyzed selected data on 237,142 participants aged ≥40 who had blood pressure taken for the 2014 China National Stroke Screening and Prevention Project. Choropleth maps and logistic regression analyses were performed to estimate the prevalence, geographical distribution and risk factors of hypertension using both 2017 ACC/AHA guidelines and 2014 evidence-based guidelines. Results : The present cross-sectional study showed the age- and sex-standardized prevalence of hypertension was 37.08% and 58.52%, respectively, according to 2014 evidence-based guidelines and 2017 ACC/AHA guidelines. The distribution of hypertension and risk factors changed little between guidelines, with data showing a high prevalence of hypertension around Bohai Gulf and in south central coastal areas using either definition. The age- and sex-standardized prevalence of newly labeled as hypertensive was 21.44%. Interestingly, the high prevalence region of newly labeled as hypertensive was found in the north China. Conclusion : The prevalence of hypertension increased significantly on 2017 ACC/AHA guidelines compared to the prevalence when using 2014 evidence-based guidelines, with high prevalence areas of newly labeled as hypertensive now seen mainly in north China. There need to be correspondingly robust efforts to improve health education, health management, and behavioral and lifestyle interventions in the north

Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response

Occupational stress of physicians and nurses in emergency departments after contracting COVID-19 and its influencing factors: a cross-sectional study

BackgroundOccupational stress is one of the major occupational health hazards globally. This study investigated the current situation of and factors influencing the occupational stress of physicians and nurses in emergency departments (EDs) after contracting coronavirus disease (COVID-19).MethodsAn online questionnaire survey was conducted among physicians and nurses in EDs in China between January 5 and 8, 2023. A general descriptive analysis of variables was conducted, the differences in the occupational stress of physicians and nurses in EDs with different characteristics were analyzed using the chi-square test, and factors influencing occupational stress were investigated using generalized ordinal logistic regression.ResultsOf the 1924 physicians and nurses in EDs who contracted COVID-19, 64.71% considered their occupational stress high or very high, with overly intense work as the primary stressor. Those with ≥ 10 years of work tenure, working in tertiary hospitals and with higher professional titles were more stressed, while females, nurses, those with a master’s degree or higher, and those who continued to work after contracting COVID-19 were less stressed. There were differences in the predictors of occupational stress between physicians and nurses.ConclusionChina’s physicians and nurses in EDs had high occupational stress after contracting COVID-19. Attention should be given to the occupational mental health of physicians and nurses in EDs, and training on the prevention and treatment of COVID-19 infection should be strengthened