An observational study on the safety of COVID-19 vaccination in patients with myasthenia gravis.

OBJECTIVE: There is concern that the coronavirus disease (COVID-19) vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of COVID-19 vaccination on symptom severity in patients with myasthenia gravis (MG). METHODS: A total of 106 enrolled patients with MG who were vaccinated against COVID-19 were followed up, and a questionnaire was used to document in detail the exacerbation of muscle weakness after vaccination and all other uncomfortable reactions after vaccination. Demographic, clinical characteristics, medication, and vaccination data were collected by follow-up interview. The main observation outcome was whether the MG symptoms of patients were exacerbated. The definition of exacerbation is according to the subjective feeling of the patient or a 2-point increase in daily life myasthenia gravis activity score relative to before vaccination, within 30 days after vaccination. RESULTS: Of 106 enrolled patients [median age (SD) 41.0 years, 38 (35.8%) men, 53 (50.0%) with generalized MG, 74 (69.8%) positive for acetylcholine receptor antibody, and 21 (19.8%) with accompanying thymoma], muscle weakness symptoms were stable in 102 (96.2%) patients before vaccine inoculation. Muscle weakness worsened in 10 (9.4%) people after vaccination, of which 8 patients reported slight symptom worsening that resolved quickly (within a few days). Two (1.9%) of patients showed serious symptom aggravation that required hospitalization. CONCLUSION: Our results suggest that inactivated virus vaccines against COVID-19 may be safe for patients with MG whose condition is stable. Patients with generalized MG may be more likely to develop increased muscle weakness after vaccination.

[Application of pretrained model based on electronic medical record in recognition of acute respiratory infection].

Objective: To evaluate the recognition of acute respiratory infection (ARI) by a pretrained model based on electronic medical records (EMRs). Methods: 38 581 EMRs were obtained from Chongqing University Three Gorges Hospital in December 2021. Bidirectional encoder representation from transformers (BERT) pretrained model was used to identify ARI in EMRs. The results of medical professionals were considered as the gold standard to calculate the sensitivity, specificity, Kappa value, and area under the curve of the receiver operating characteristic (AUC). Results: There were 3 817 EMRs in the test set, with 1 200 ARIs. A total of 1 205 cases were determined as ARI by the model, with a sensitivity of 92.67% (1 112/1 200) and a specificity of 96.45% (2 524/2 617). The model identified ARI with similar accuracy in males and females (AUCs 0.95 and 0.94, respectively), and was more accurate in identifying ARI cases in those aged less than 18 than in adults 18-59 and adults 60 and older (AUCs 0.94, 0.89 and 0.94, respectively). The current model had a better identification of ARIs in outpatient patients than that in hospitalized patients, with AUCs of 0.74 and 0.95, respectively. Conclusion: The use of the BERT pretrained model based on EMRs has a good performance in the recognition of ARI cases, especially for the outpatients and juveniles. It shows a great potential to be applied to the monitoring of ARI cases in medical institutions.

[Characteristics of electromyography in 111 patients with generalized myasthenia gravis: a retrospective study].

Objective: To retrospectively analyze the characteristics of the electromyography (EMG) study in generalized myasthenia gravis (gMG) patients. Methods: A total of 111 gMG patients were enrolled. Patients were divided into two groups: 36 severe patients discontinuing pyridostigmine bromide (PB) for 8 hours were included in 8 h group, and 75 g MG patients discontinuing PB for at least 18 hours were included in>18 h group. The clinical information and EMG study data were collected and analyzed. Results: There were statistically significant differences in the initial location of the myasthenia muscle (P=0.027), the affected muscle detected by the EMG (P=0.015) and quantitative myasthenia gravis (QMG) score (P<0.01) between the two groups. Comparisons in each group revealed that the highest positive rate of low-frequency repetitive nerve stimulation (RNS) of facial in 8 h group and>18 h group was 94.4% and 60.0%, respectively. Comparisons between the two groups showed that the positive rate of low-frequency RNS in 8 h group was significantly higher than that in>18 h group (94.4% vs 70.7%, χ(2)=8.115, P=0.004). In particular, the positive rate of RNS in facial nerves and the extent of the amplitude decrease under different electrical stimulations (1 Hz, 3 Hz, and 5 Hz) were dramatically higher in the 8 h group (P<0.01). Conclusions: For gMG patients, the facial and accessory nerve detection can improve the positive rate of RNS. Different muscles had various sensitivity to PB, and orbicularis oculi muscle seemed the least sensitive muscle to PB. For suspect MG patients in severe condition, only discontinuing PB medication for 8 h before low-frequency RNS testing can avoid the deterioration and also obtain similar positive rate.

MicroRNA-219-5p inhibits wound healing by targeting TMEM98 in keratinocytes under normoxia and hypoxia condition.

OBJECTIVE: Wound healing is closely related to the production of inflammatory cytokines, keratinocytes proliferation and migration. This study aims to investigate the role of transmembrane protein 98 (TMEM98) on wound healing and whether miRNA-219-5p could inhibit wound healing by targeting TMEM98 in keratinocytes. MATERIAL AND METHODS: Hypoxia model was established by CoCl2 (2000 µmol/L) treatment. TMEM98 protein expression, inflammatory cytokines (IL-6, IL-8, TNF-α) and cell proliferation and migration were detected in hypoxia group. RESULTS: Overexpression of TMEM98 could significantly reverse the effects caused by hypoxia. MiR-219-5p was markedly increased in hypoxia group and miR-219-5p could downregulate TMEM98 expression by direct binding its 3'-UTR. CONCLUSIONS: We demonstrated that miR-219-5p could inhibit wound healing by targeting TMEM98.

[Correlation factors of 127 times pre-crisis state in patients with myasthenia gravis].

Objective: To investigate the clinical features of the Pre-Crisis State and analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis. Methods: We included 93 patients with myasthenia gravis (MG) who experienced 127 times Pre-Crisis State between October 2007 and July 2016. Those patients were hospitalized in the MG specialize center, Department of Neurological Science, first Affiliated Hospital of Sun Yat-sen University. The information of the general situation, the clinical manifestations and the blood gas analysis in those patients were collected using our innovated clinical research form. Statistic methods were applied including descriptive analysis, univariate logistic analysis, multivariate correlation logistic analysis, etc. Results: (1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100% not requiring intubation or non-invasive ventilation), bulbar-muscle weakness (121 times, 95.28%), the increased blood partial pressure of carbon dioxide (PCO(2)) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The occurrence of dyspnea in combination with bulbar-muscle weakness (P=0.002) or the increased blood PCO(2) (P=0.042) often indicated the tendency of crisis. (2) The MG symptoms which were proportion to the occurrence of crisis includes: bulbar-muscle weakness (P=0.028), fever (P=0.028), malnutrition (P=0.066), complications (P=0.071), excess oropharyngeal secretions (P=0.005) and the increased blood PCO(2) (P=0.007). The perioperative period of thymectomy would not increase the risk of crisis. Conclusions: Dyspnea indicates the occurrence of the Pre-Crisis State of MG. In order to significantly reduce the morbidity of myasthenia crisis, the bulbar-muscle weakness, the increased blood PCO(2), expectoration weakness, sleep disorders, infection & fever and excess oropharyngeal secretions should be treated timely.

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice.

Successful embryo implantation requires functional luminal epithelia to establish uterine receptivity and blastocyst-uterine adhesion. During the configuration of uterine receptivity from prereceptive phase, the luminal epithelium undergoes dynamic membrane reorganization and depolarization. This timely regulated epithelial membrane maturation and precisely maintained epithelial integrity are critical for embryo implantation in both humans and mice. However, it remained largely unexplored with respect to potential signaling cascades governing this functional epithelial transformation prior to implantation. Using multiple genetic and cellular approaches combined with uterine conditional Rac1 deletion mouse model, we demonstrated herein that Rac1, a small GTPase, is spatiotemporally expressed in the periimplantation uterus, and uterine depletion of Rac1 induces premature decrease of epithelial apical-basal polarity and defective junction remodeling, leading to disrupted uterine receptivity and implantation failure. Further investigations identified Pak1-ERM as a downstream signaling cascade upon Rac1 activation in the luminal epithelium necessary for uterine receptivity. In addition, we also demonstrated that Rac1 via P38 MAPK signaling ensures timely epithelial apoptotic death at postimplantation. Besides uncovering a potentially important molecule machinery governing uterine luminal integrity for embryo implantation, our finding has high clinical relevance, because Rac1 is essential for normal endometrial functions in women.

A single fas gene mutation changes lupus onset, severity, location, and molecular abnormalities in mice.

Although genetic predisposition plays a major role in the progression of systemic lupus erythematosus (SLE) and its variation in symptoms, the precise relationships between genetic changes and disease status are not well understood. Here, to demonstrate the effect of a single gene mutation on disease etiology, we examined two mouse models of SLE with the same genetic background but different Fas genes. Mice with the Fas(lpr) gene developed severe SLE with renal dysfunction and inflammatory responses in the lung and kidney. By contrast, mice with the Fas(+) gene showed disease-related abnormalities in the liver and joints. Patterns of inflammatory disease markers differed across organs between the two lines of mice. Fas(lpr) mice showed greater MMP signals in the kidney and IL-11 signals in the lung than Fas(+) mice. Fas(+) mice had higher IL-11 signal intensity in the knee region and higher CXCR4 signal intensity in the liver than Fas(lpr) mice. Our results exemplify the complexity of disease and suggest the need for individualized target-specific treatment regimens. Strengths and Limitations of this Study: Fas gene is a well characterized gene in this disease. The molecular components in human disease need more clinical data.

Farnesoid X receptor regulates vascular reactivity through nitric oxide mechanism.

Farnesoid X receptor (FXR), a ligand-activated transcription factor and a member of nuclear receptor family, is not only highly expressed in the adrenal cortex, intestine, kidney and liver, but also has recently been found in the vasculature. However, the evidence on the roles of FXR in the vasculature is limited and whether FXR regulates vascular reactivity is poorly understood. In present study, we investigated the expression of FXR protein in rat vasculature by immunohistochemical method and tested the effects of FXR activation by chenodeoxycholic acid (CDCA) on thoracic aortic contraction and dilation. We also detected the level of nitrite/nitrate (NOx) and superoxide in the thoracic aortic segments. We found that FXR was expressed in rat carotid arteries, thoracic aorta, abdominal aorta and femoral arteries. FXR activation by CDCA significantly (P<0.01) inhibited the contractile responses of rat thoracic aorta rings to KCl and phenylephrine. The cumulative concentrations of CDCA caused a concentration-dependent relaxation, which could be partly impaired by L-NAME, an inhibitor of nitric oxide (NO) synthase. The NOx content in thoracic aorta significantly (P<0.01) increased when treated with CDCA. Meanwhile, the vascular redox status was not altered by high concentration of CDCA. The present study suggested that FXR regulated vascular reactivity through NO mechanism, which merits further attention.

Accumulation and distribution of α-synuclein and ubiquitin in the CNS of Gaucher disease mouse models.

Gaucher disease, a prevalent lysosomal storage disease, is caused by insufficient activity of acid ß-glucosidase (GCase) and resultant glucosylceramide accumulation. Recently in Parkinson disease (PD) patients, heterozygous mutations in GCase have been associated with earlier onset and more progressive PD. To understand the pathogenic relationships between GCase variants and Parkinsonism, α-synuclein and ubiquitin distributions and levels in the brains of several mouse models containing GCase variants were evaluated by immunohistochemistry. Progressive α-synuclein and ubiquitin aggregate accumulations were observed in the cortex, hippocampus, basal ganglia, brainstem, and some cerebellar regions between 4 and 24 weeks in mice that were homozygous for GCase [D409H (9H) or V394L (4L)] variants and also had a prosaposin hypomorphic (PS-NA) transgene. In 4L/PS-NA and 9H/PS-NA mice, this was coincident with progressive neurological manifestations and brain glucosylceramide accumulation. Ultrastructural studies showed electron dense inclusion bodies in neurons and axons of 9H/PS-NA brains. α-synuclein aggregates were also observed in ventricular, brainstem, and cerebellar regions of older mice (>42-weeks) with the GCase variant (D409H/D409H) without overt neurological disease. In a chemically induced GCase deficiency, α-synuclein aggregates and glucosylceramide accumulation also occurred. These studies demonstrate a relationship between glucosylceramide accumulation and α-synuclein aggregates, and implicate glucosylceramide accumulation as risk factor for the α-synucleinopathies.

Gene expression in developing fibres of Upland cotton (Gossypium hirsutum L.) was massively altered by domestication.

BACKGROUND: Understanding the evolutionary genetics of modern crop phenotypes has a dual relevance to evolutionary biology and crop improvement. Modern upland cotton (Gossypium hirsutum L.) was developed following thousands of years of artificial selection from a wild form, G. hirsutum var. yucatanense, which bears a shorter, sparser, layer of single-celled, ovular trichomes ('fibre'). In order to gain an insight into the nature of the developmental genetic transformations that accompanied domestication and crop improvement, we studied the transcriptomes of cotton fibres from wild and domesticated accessions over a developmental time course. RESULTS: Fibre cells were harvested between 2 and 25 days post-anthesis and encompassed the primary and secondary wall synthesis stages. Using amplified messenger RNA and a custom microarray platform designed to interrogate expression for 40,430 genes, we determined global patterns of expression during fibre development. The fibre transcriptome of domesticated cotton is far more dynamic than that of wild cotton, with over twice as many genes being differentially expressed during development (12,626 versus 5273). Remarkably, a total of 9465 genes were diagnosed as differentially expressed between wild and domesticated fibres when summed across five key developmental time points. Human selection during the initial domestication and subsequent crop improvement has resulted in a biased upregulation of components of the transcriptional network that are important for agronomically advanced fibre, especially in the early stages of development. About 15% of the differentially expressed genes in wild versus domesticated cotton fibre have no homology to the genes in databases. CONCLUSIONS: We show that artificial selection during crop domestication can radically alter the transcriptional developmental network of even a single-celled structure, affecting nearly a quarter of the genes in the genome. Gene expression during fibre development within accessions and expression alteration arising from evolutionary change appears to be 'modular' - complex genic networks have been simultaneously and similarly transformed, in a coordinated fashion, as a consequence of human-mediated selection. These results highlight the complex alteration of the global gene expression machinery that resulted from human selection for a longer, stronger and finer fibre, as well as other aspects of fibre physiology that were not consciously selected. We illustrate how the data can be mined for genes that were unwittingly targeted by aboriginal and/or modern domesticators during crop improvement and/or which potentially control the improved qualities of domesticated cotton fibre.See Commentary: http://www.biomedcentral.com/1741-7007/8/137.

Differential effects of esomeprazole on the antiplatelet activity of clopidogrel in healthy individuals and patients after coronary stent implantation.

Clopidogrel plus aspirin is a standard antiplatelet aggregation regimen in cardiovascular diseases, especially after implantation of a coronary stent. Interaction between clopidogrel and proton pump inhibitors theoretically reduces clopidogrel's antiaggregation effect, but the evidence is controversial. A total of 30 healthy subjects and 74 patients with a coronary stent were given a 300 mg loading dose of aspirin and 300 mg clopidogrel and then 100 mg aspirin/75 mg clopidogrel daily for 14 days. Subgroups were concomitantly treated or not treated with esomeprazole (20 mg/day). Clopidogrel significantly reduced adenosine diphosphate-induced platelet aggregation in healthy and stent-implanted subjects on days 7 and 14. Healthy subjects receiving esomeprazole showed a significantly higher platelet aggregation rate than those not receiving esomeprazole, but esomeprazole had no effect in patients with a stent. Aspirin plus clopidogrel did not result in significant gastrointestinal complications. These differential effects of esomeprazole on the antiplatelet activity of clopidogrel in healthy individuals and patients after coronary stent implantation merit further investigation.

Meta-analysis: the effect and adverse events of Lactobacilli versus placebo in maintenance therapy for Crohn disease.

BACKGROUND: Lactobacilli are used in an attempt to maintain remission for Crohn disease. The aim of this study was to evaluate the efficacy and adverse events of Lactobacilli compared with placebo in maintenance therapy for Crohn disease. METHODS: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID and BIOSIS. All randomized trials comparing Lactobacilli with placebo in maintenance therapy for Crohn disease were included. RESULTS: Six randomized controlled trials with a total of 359 participants met the inclusion criteria. From the meta-analyses, the relative risk (RR) of clinical relapse rate was 1.15 (95% confidence interval (CI) 0.90-1.48) comparing Lactobacilli with placebo and RR of endoscopic relapse rate was 1.31 (95%CI 0.57-3.00). Subgroup analyses showed RR for clinical relapse rates of Lactobacilli versus placebo was 0.99 (95%CI 0.76-1.29) in adults, 1.85 (95%CI 1.00-3.41) in children, 1.68 (95%CI 1.07-2.64) in Lactobacillus rhamnosus strain GG and 0.91 (95%CI 0.68-1.23) in Lactobacillus johnsonii respectively. The pooled RR of adverse events was 0.83 (95%CI 0.61-1.12). CONCLUSION: Our meta-analysis suggests that compared with placebo, administration of L. rhamnosus strain GG as maintenance therapy may increase the relapse rates of Crohn disease. L. johnsonii is inefficacious in reducing the incidence of relapse.

Treatment of xenografted ovarian carcinoma using paclitaxel-loaded ultrasound microbubbles.

RATIONALE AND OBJECTIVES: The aim of this study was to explore the antitumor effects on mice xenografted ovarian carcinoma using the technique of ultrasound-mediated drug release from paclitaxel-loaded lipid microbubbles (PLMs). MATERIALS AND METHODS: Twenty-five ovarian cancer-bearing nude mice were randomly divided into five groups of five mice each. Each group received a unique kind of treatment once a day. These treatments were PLMs combined with ultrasound, intravenous paclitaxel administration, non-drug-loaded microbubbles combined with ultrasound, intravenous PLM administration, and normal saline administration (the control group). After 7 days of consecutive treatment, all mice were sacrificed, and their tumors were harvested to measure volumes and weights. The tumor inhibition rate was calculated by weight. Expressions of vascular endothelial growth factor (VEGF) and p53 in tumor tissues were detected by immunohistochemical staining. RESULTS: Mean tumor volume and weight were the lowest in the first group (PLMs combined with ultrasound), so this group's tumor inhibition rate was the highest (P < .05). On immunohistology, VEGF and p53 expression levels were lowest (P < .05) in the first group. CONCLUSION: Ultrasound irradiation mediates PLM destruction so that the drug is released from the vehicles at the same time. It helps achieve targeted chemotherapy in tumor tissues. This technique has potential to be adopted as a novel tool for ovarian cancer chemotherapy.

Effect of viral load on the outcome of herpes zoster.

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks.

Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types.

Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple alpha and beta papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited.

Fatal sporotrichosis.

Disseminated sporotrichosis is a serious fungal infection caused by the soil inhabitant Sporothrix schenckii. It is seen in immunocompromised patients, with a substantial number of recent cases involving patients with acquired immunodeficiency syndrome (AIDS). However, individuals with other conditions that affect the immune system also are at increased risk. We report a case of fatal disseminated sporotrichosis in a patient with liver disease and a diagnosis of a granulomatous condition presumed to be sarcoidosis; the patient was receiving systemic corticosteroid therapy. The various presentations of S schenckii infection, the risk of disseminated disease in immunocompromised hosts, and the importance of making accurate histologic diagnoses are reviewed.