Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Physical activity and sleep pattern in relation to incident Parkinson's disease: a cohort study.

BACKGROUND: How physical activity (PA) and different sleep traits and overall sleep pattern interact in the development of Parkinson's disease (PD) remain unknown. OBJECTIVE: To prospectively investigate the joint associations of PA and sleep pattern with risk of PD. METHODS: Included were 339,666 PD-free participants from the UK Biobank. Baseline PA levels were grouped into low (< 600 MET-mins/week), medium (600 to < 3000 MET-mins/week) and high (≥ 3000 MET-mins/week) according to the instructions of the UK Biobank. Healthy sleep traits (chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) were scored from 0 to 5 and were categorized into "ideal sleep pattern" (≥ 3 sleep scores) and "poor sleep pattern" (0-2 sleep scores). Hazard ratios (HRs) and 95% confidence intervals (CIs) of PD were estimated by Cox proportional hazards models. RESULTS: During a median of 11.8 years of follow-up, 1,966 PD events were identified. The PD risk was lower in participants with high PA (HR = 0.73; 95% CI: 0.64, 0.84), compared to those with low PA; and participants with ideal sleep pattern also had a lower risk of PD (HR = 0.78; 95% CI: 0.69, 0.87), compared to those with poor sleep pattern. When jointly investigating the combined effect, participants with both high PA and ideal sleep pattern had the lowest risk of incident PD (HR = 0.55; 95% CI: 0.44, 0.69), compared to those with low PA and poor sleep pattern; notably, participants with high PA but poor sleep pattern also gained benefit on PD risk reduction (HR = 0.74; 95% CI: 0.55, 0.99). CONCLUSIONS: Both high PA and ideal sleep pattern were independently associated with lower risk of developing PD, and those with both high PA level and ideal sleep pattern had the lowest risk. Our results suggest that improving PA levels and sleep quality may be promising intervention targets for the prevention of PD.

In-MIL-68 derived In2O3/Fe2O3 shuttle-like structures with n-n heterojunctions to improve ethanol sensing performance.

Metal-organic frameworks (MOFs) have a variety of structures and unique properties that make them suitable for use in gas sensors. Herein, In2O3/Fe2O3 was successfully synthesized using simple solvothermal and impregnation methods. The response to 100 ppm of ethanol gas reached 67.5 at an optimum working temperature of 200 °C, and the response/recovery time was 9 s/236 s. The composite also exhibited excellent selectivity, repeatability, and long-term stability. SEM, TEM, XRD, and XPS were used for the characterization of materials. The excellent sensing performance of the sensors is attributed to the construction of n-n heterojunctions, an increase in oxygen vacancies, and the unique structural characteristics of MOFs. The above experimental results indicate that In-MIL-68-derived In2O3/Fe2O3 is a promising ethanol sensing material.

Bilateral hearing loss as the initial presentation of reversible Wernicke's encephalopathy with splenial lesion.

BACKGROUND: Wernicke's encephalopathy (WE) is an acute neurological syndrome resulting from thiamine (vitamin B1) deficiency. It has been recognized increasingly in non-alcoholic patients, such as in the condition of malnutrition. Recent literature has shed light on uncommon symptoms and neuroimaging findings. CASE REPORT: We reported a case of a 44-year-old male who initially presented with bilateral hearing loss, and exhibited abnormality in the splenium of the corpus callosum on magnetic resonance imaging (MRI) diffusion-weighted imaging sequence. On the following day the patient developed new symptoms, including unstable walking, double vision and hallucination. The subsequent brain MRI demonstrated lesions involving periaqueductal grey matter and bilateral medial thalamus, indicating the diagnosis of WE. Empirical treatment with intravenous thiamine resulted in complete clinical and radiological resolution. CONCLUSION: To the best of our knowledge, the current case is the first report of WE in literature with uncommon but reversible manifestations. This case warns us to maintain a heightened level of suspicion for WE in malnourished patients with neurological deficits, despite the possibility of atypical presentations encompassing bilateral hearing disturbances and unusual neuroradiological results. Early diagnosis and timely administration of thiamine in WE are likely to lead to a favorable outcome and full recovery.

Biochemical and molecular analysis of pediatric patients with metachromatic leukodystrophy in South China: functional characterization of five novel ARSA variants.

Metachromatic leukodystrophy (MLD) is a rare hereditary neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). This study described the clinical and molecular characteristics of 24 Chinese children with MLD and investigated functional characterization of five novel ARSA variants. A retrospective analysis was performed in 24 patients diagnosed with MLD at Guangzhou Women and Children's Medical Center in South China. Five novel mutations were further characterized by transient expression studies. We recruited 17 late-infantile, 3 early-juvenile, 4 late-juvenile MLD patients. In late-infantile patients, motor developmental delay and gait disturbance were the most frequent symptoms at onset. In juvenile patients, cognitive regression and gait disturbance were the most frequent chief complaints. Overall, 25 different ARSA mutations were identified with 5 novel mutations.The most frequent alleles were p.W320* and p.G449Rfs. The mutation p.W320*, p.Q155=, p.P91L, p.G156D, p.H208Mfs*46 and p.G449Rfs may link to late-infantile type. The novel missense mutations were predicted damaging in silico. The bioinformatic structural analysis of the novel missense mutations showed that these amino acid replacements would cause severe impairment of protein structure and function. In vitro functional analysis of the six mutants, showing a low ARSA enzyme activity, clearly demonstrated their pathogenic nature. The mutation p.D413N linked to R alleles. In western blotting analysis of the ARSA protein, the examined mutations retained reduced amounts of ARSA protein compared to the wild type. This study expands the spectrum of genotype of MLD. It helps to the future studies of genotype-phenotype correlations to estimate prognosis and develop new therapeutic approach.

Effect of electrolytic zero-valent iron activated sodium hypochlorite on sludge dewatering performance.

Using electrolytic zero-valent iron-activated sodium hypochlorite (EZVI-NaClO) to pretreat sludge, the capillary suction time (CST) was utilized to evaluate sludge dewaterability. Ammonia nitrogen (NH4-N), dissolved phosphorus, and total phosphorus in the supernatant were used to analyze sludge disintegration. This approach aimed to evaluate the effectiveness of the pretreatment process and its impact on the sludge composition. The migration and transformation of extracellular polymeric substances (EPS), including dissolved EPS (S-EPS), loosely boundEPS, and tightly bound-EPS (TB-EPS), were analyzed by detecting protein and polysaccharide concentrations and three-dimensional fluorescence excitation-emission spectroscopy (3D-EEM). The sludge particle properties, including sludge viscosity and particle size, were also analyzed. The results suggested that the optimal pH value, NaClO dosage, current, and reaction time were 2, 100 mg/gDS (dry sludge), 0.2A, and 30 min, respectively, with a CST reduction of 43%. Protein and polysaccharide contents in TB-EPS were significantly reduced in the EZVI-NaClO group. Conversely, protein and polysaccharides contents in S-EPS increased, suggesting that EZVI-NaClO treatment could disrupt the EPS. Besides, the viscosity of the treated sludge decreased from 195.4 to 54.9 mPa·S, indicating that sludge fluidity became better. ZEVI-NaClO could enhance sludge dewaterability by destructing protein and polysaccharide structure and improving sludge hydrophobicity.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System.

AIMS: To investigate interstitial lung disease (ILD) in men with prostate cancer receiving hormone therapy. METHODS: We gathered cases diagnosed with prostate cancer based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2020. We divided the included cases into 3 groups based on the primary suspected drugs: a hormone therapy group, a positive control group (taxanes), and a negative control group. We employed reporting odds ratio, a disproportionality method, to detect the association between ILD events and target drugs. RESULTS: We finally included a total of 85 403 cases, 69 894 cases (628 ILD event cases) in the hormone therapy group, 2302 cases (158 ILD event cases) in the positive control group and 13 207 cases (72 ILD event cases) in the negative control group. There were 394 ILD event cases (62.74%) in the hormone therapy group in Japan; 78.68% of the ILD events occurred within the first year after hormone treatment. Disproportionality analysis indicated that ILD events were significantly associated with nilutamide, flutamide, bicalutamide, goserelin, degarelix and apalutamide; the reporting odds ratios (95% confidence interval) were 32.14 (11.03-93.63), 9.93 (3.62-27.21), 8.19 (6.01-11.16), 3.74 (2.61-5.37), 2.41 (1.55-3.75) and 1.94 (1.01-3.75), respectively. CONCLUSION: Based on this FAERS pharmacovigilance analysis, the association between ILD events and hormone therapy drugs, including bicalutamide, flutamide, nilutamide, goserelin, degarelix and apalutamide, should not be ignored, especially in the Japanese population. Lung function of prostate cancer patients should be monitored when receiving the hormone therapy drugs mentioned above, especially for the first year post medication.

Mindfulness-based intervention for clinical and subthreshold perinatal depression and anxiety: A systematic review and meta-analysis of randomized controlled trial.

OBJECTIVES: About one in four mothers will experience depression and anxiety during pregnancy and within their first year following childbirth. The meta-analysis aggregated the findings of randomized controlled trials (RCTs) evaluating the immediate post-intervention and maintenance effects of MBI on perinatal depression and anxiety. METHODS: A systematic search was conducted in PubMed, PsycINFO, Medline, Scopus, and Web of Science for English-language journal articles from the first available date until Oct 27th, 2022. RESULTS: Twenty-five published RCTs were identified and reviewed, with a total of 2495 perinatal women. MBI was superior to controls for clinical and subthreshold perinatal depression and anxiety. The benefit for depression reduction was stable over time and sustained to the postpartum period, but the maintenance effect on perinatal anxiety was less conclusive. Moreover, MBI's post-intervention effects on depression and anxiety were moderated by perinatal women's symptom severity. The post intervention effects were significantly greater among women in Low- and Middle-Income countries, where perinatal mental health care is less available and accessible. Greater improvement in mindfulness was also associated with a significantly larger post-intervention effect on perinatal depression. CONCLUSIONS: This meta-analysis suggests that MBIs may complement and extend the available range of effective interventions for clinical and subthreshold perinatal depression and anxiety.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Application of PCR-RFLP for quick identification of MSTN mutants in MSTN mutant pig breeding.

Knockout of the MSTN gene is linked to the enlarged tongue, and it causes suckling difficulty in animals. The suckling difficulty has a severe effect on animal mortality. Thus, special care was required to ensure their survivability. Here, it is critical to promptly ascertain the genotype of all pigs after birth. The main objective of the present study was to develop the restriction enzyme-mediated PCR-RFLP assay for MSTN mutant pig genotyping. To accomplish this, conserved oligonucleotide primer and restriction site were deduced according to the mutated sequence of the MSTN mutant pigs. PCR amplification yielded a 176 bp band for all homozygous MSTN mutant (MSTN-/-), heterozygous MSTN mutant (MSTN+/-) and wild-type (WT) pigs. However, MSTN+/- samples produced two fragments with 176 and 87 bp, and WT samples produced one fragment with 87 bp after being digested by BstNI. MSTN-/- samples were not digested by BstNI and yielded a 176 bp band. Thus, we were able to determine the genotype of all pigs using BstNI restriction enzyme-mediated PCR-RFLP method. Overall, the present study reported a simple and fast PCR-RFLP genotyping method for MSTN mutant pig breeding. The present study may contribute to the establishment of commercial breeding systems and the production of double muscle pigs.

Pathological features in 'humanized' neonatal pig.

Cytidine monophosphate-Nacetylneuraminic acid (Neu5Ac) hydroxylase (CMAH) and glycoprotein, alpha1, 3-galactosyltransferase (GGTA1) double knockout (DKO) pig models were produced to reduce immune reaction for xenotransplantation. However, the role of Neu5Gc and α-Gal in pigs has not been fully elucidated and it is necessary to consider the after-effect of inactivation of GGTA1 and CMAH in pigs. Hematological profiles of DKO pigs were analyzed through complete blood count (CBC). Histology of liver and spleen of DKO were investigated, and lectin blotting and mass spectrometry (MS) were performed to explore glycosylation changes in red blood cell (RBC) membranes of DKO pigs. DKO pigs showed common clinical signs such as weakness (100%), dyspnea (90%) and constipation (65%). DKO pigs revealed a significant decrease in RBC, hemoglobin (HGB) and hematocrit (HGB), and an increase in white blood cell (WBC), lymphocyte (LYM), monocyte (MON), and erythrocyte mean corpuscular volume (MCV). DKO piglets showed swollen liver and spleen, and exhibited raised deposition of hemosiderin and severe bleeding. Lectin assay and MS proved variations in glycosylation on RBC membranes. GGTA1/CMAH DKO pigs developed pathological features which are similar to anemic symptoms, and the variations in glycosylation on RBC membranes of DKO pigs may be attributed to the pathologies observed.

Effects of myostatin gene knockout on porcine extraocular muscles.

Myostatin (MSTN), a negative regulator of skeletal muscle mass, is not well known in extraocular muscles (EOMs). EOMs are specialized skeletal muscles. Hence, in this study, the effect of MSTN on the superior rectus (SR) and superior oblique (SO) of 2-month-old MSTN knockout (MSTN-/-) and wild-type (WT) pigs of the same genotype was investigated. SR (P < 0.01) and SO (P < 0.001) fiber cross-sectional areas of MSTN-/- pigs were significantly larger than those of WT pigs. Compared with WT pigs, MSTN-/- SO displayed a decrease in type I fibers (WT: 27.24%, MSTN-/-: 10.32%, P < 0.001). Type IIb fibers were higher in MSTN-/- pigs than in WT pigs (WT: 30.38%, MSTN-/-: 62.24%, P < 0.001). The trend in SR was the same as that in SO, although the trend in SO was greater than that in SR. The expression of myogenic differentiation factor (MyoD) and myogenic (MyoG) showed a significant increase in MSTN-/- SO (about 2.5-fold and 2-fold, respectively at the gene expression level, about 1.5-fold at the protein level) compared with WT pigs. MSTN plays an important role in the development of EOMs and regulates the muscle fiber type by modulating the gene expression of MyoD and MyoG in pigs.

DABCO-Catalyzed Mono-/Diallylation of N-Unsubstituted Isatin N,N'-Cyclic Azomethine Imine 1,3-Dipoles with Morita-Baylis-Hillman Carbonates.

Allylation of N-unsubstituted isatin N,N'-cyclic azomethine imines with Morita-Baylis-Hillman carbonates in the presence of 1-10 mol% DABCO in DCM at room temperature, rapidly gave N-allylated and N, ß-diallylated isatin N,N'-cyclic azomethine imine 1,3-dipoles in moderate to high yields. The reaction features mild reaction conditions, easily practical operation, and short reaction times in most cases. Furthermore, the alkylated products were transformed into novel bicyclic spiropyrrolidine oxoindole derivatives through the [3+2] or [3+3]-cycloaddition with maleimides or Knoevenagel adducts.

Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome: A state-of-the-art review.

The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.

Myostatin deficiency decreases cardiac extracellular matrix in pigs.

Myostatin (MSTN), a member of the TGF-ß superfamily, negatively regulates muscle growth. MSTN inhibition has been known to cause a double-muscled phenotype in skeletal muscle and fibrosis reduction in the heart. However, the role of MSTN in the cardiac extracellular matrix (ECM) needs more studies in various species of animal models to draw more objective conclusions. The main objective of the present study was to investigate whether loss of MSTN affects the cardiac extracellular matrix in pigs. Three MSTN knockouts (MSTN-/-) and three wild type (WT) male pigs were generated by crossing MSTN ± heterozygous gilts and boars. Cardiac ECM and underlying mechanisms were determined post-mortem. The role of MSTN on collagen expression was investigated by treating cardiac fibroblasts with active MSTN protein in vitro. MSTN protein was detected in WT hearts, while no expression was detected in MSTN-/- hearts. The heart-to-body weight ratio was significantly decreased in MSTN-/- pigs. The morphometric analyses, including picrosirius red staining, immunofluorescent staining, and ultra-structural thickness examination of the endomysium, revealed a significant reduction of connective tissue content in MSTN-/- hearts compared to WT. Hydroxyproline, type I collagen (Col1A), and p-Smad3/Smad3 levels were significantly lower in MSTN-/- hearts in vivo. On the contrary, cardiac fibroblasts treated with exogenous MSTN protein overexpressed Col1A and activated Smad and AKT signaling pathways in vitro. The present study suggests that inhibition of MSTN decreases cardiac extracellular matrix.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

Awareness and prevalence of e-cigarette use among Chinese adults: policy implications.

OBJECTIVE: To assess the awareness and prevalence of electronic cigarettes (e-cigarettes) and associated factors among Chinese adults (15 years and older). METHOD: This study examined data from Global Adults Tobacco Survey China Project, which was nationally representative and used stratified multiphase cluster randomised sampling design. Data were collected in 2018 through a household survey with in-person interviews using tablet computers. Complex sampling weighted analysis method was used. RESULTS: 48.5% of Chinese adults had heard of e-cigarettes. The proportions of Chinese adults who had ever used, had used in the last 12 months, and currently used e-cigarettes were 5.0%, 2.2% and 0.9%, respectively; people in the 15-24 years group showed the highest rates of ever use, last 12-month use and current use at 7.6%, 4.4%, and 1.5%, respectively. Among males, higher e-cigarette use was associated with 15-24 years age group, college/university or above education, and daily use of combustible cigarettes. Among all e-cigarette users, 90.6% also used combustible cigarettes. The most common reason for e-cigarette use was smoking cessation (46.2%) while among ever smokers, 9.5% of ever e-cigarette users had quit smoking and 21.8% of never e-cigarette users had quit smoking (adjusted OR 0.454, 95% CI 0.290 to 0.712). CONCLUSION: Prevalence of e-cigarettes among Chinese adults had increased since 2015, especially among young people aged 15-24. The high level of dual use and lower quit rate among e-cigarette users indicated e-cigarettes had not shown cessation utility at the population level in China. Regulation of e-cigarettes is needed to protect youth and minimise health risks.

Interventions for reducing inflammation in familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF), a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine may potentially prevent FMF attacks. For people who are colchicine-resistant or intolerant, drugs such as anakinra, rilonacept, canakinumab, etanercept, infliximab or adalimumab might be beneficial. This is an update of the review last published in 2018. OBJECTIVES: To evaluate the efficacy and safety of interventions for reducing inflammation in people with FMF. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and four Chinese databases on in August 2021. We searched clinical trials registries and references listed in relevant reports. The last search was 17 August 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of people with FMF, comparing active interventions (including colchicine, anakinra, rilonacept, canakinumab, etanercept, infliximab, adalimumab, thalidomide, tocilizumab, interferon-α and ImmunoGuard (herbal dietary supplement)) with placebo or no treatment, or comparing active drugs to each other. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We assessed certainty of the evidence using GRADE. MAIN RESULTS: We included 10 RCTs with 312 participants (aged three to 53 years), including five parallel and five cross-over designed studies. Six studies used oral colchicine, one used oral ImmunoGuard, and the remaining three used rilonacept, anakinra or canakinumab as a subcutaneous injection. The duration of each study arm ranged from one to eight months. There were inadequacies in the design of the four older colchicine studies and the two studies comparing a single to a divided dose of colchicine. However, the four studies of ImmunoGuard, rilonacept, anakinra and canakinumab were generally well-designed.  We aimed to report on the number of participants experiencing an attack, the timing of attacks, the prevention of amyloid A amyloidosis, adverse drug reactions and the response of a number of biochemical markers from the acute phase of an attack; but no study reported on the prevention of amyloid A amyloidosis. Colchicine (oral) versus placebo After three months, colchicine 0.6 mg three times daily may reduce the number of people experiencing attacks (risk ratio (RR) 0.21, 95% confidence interval (CI) 0.05 to 0.95; 1 study, 10 participants; low-certainty evidence). One study (20 participants) of colchicine 0.5 mg twice daily showed there may be no difference in the number of participants experiencing attacks at two months (RR 0.78, 95% CI 0.49 to 1.23; low-certainty evidence). There may be no differences in the duration of attacks (narrative summary; very low-certainty evidence), or in the number of days between attacks: (narrative summary; very low-certainty evidence). Regarding adverse drug reactions, one study reported loose stools and frequent bowel movements and a second reported diarrhea (narrative summary; both very low-certainty evidence). There were no data on acute-phase response. Rilonacept versus placebo There is probably no difference in the number of people experiencing attacks at three months (RR 0.87, 95% CI 0.59 to 1.26; moderate-certainty evidence).  There may be no differences in the duration of attacks (narrative summary; low-certainty evidence) or in the number of days between attacks (narrative summary; low-certainty evidence). Regarding adverse drug reactions, the rilonacept study reported there may be no differences in gastrointestinal symptoms, hypertension, headache, respiratory tract infections, injection site reactions and herpes, compared to placebo (narrative summary; low-certainty evidence). The study narratively reported there may be no differences in acute-phase response indicators after three months (low-certainty evidence). ImmunoGuard versus placebo The ImmunoGuard study observed there are probably no differences in adverse effects (moderate-certainty evidence) or in acute-phase response indicators after one month of treatment (moderate-certainty evidence). No data were reported for the number of people experiencing an attack, duration of attacks or days between attacks. Anakinra versus placebo A study of anakinra given to 25 colchicine-resistant participants found there is probably no difference in the number of participants experiencing an attack at four months (RR 0.76, 95% CI 0.54 to 1.07; moderate-certainty evidence).  There were no data for duration of attacks or days between attacks. There are probably no differences between anakinra and placebo with regards to injection site reaction, headache, presyncope, dyspnea and itching (narrative summary; moderate-certainty evidence). For acute-phase response, anakinra probably reduced C-reactive protein (CRP) after four months (narrative summary; moderate-certainty evidence). Canakinumab versus placebo Canakinumab probably reduces the number of participants experiencing an attack at 16 weeks (RR 0.41, 95% CI 0.26 to 0.65; 1 study, 63 colchicine-resistant participants; moderate-certainty evidence). There were no data for the duration of attacks or days between attacks. The included study reported the number of serious adverse events per 100 patient-years was probably 42.7 with canakinumab versus 97.4 with placebo among people with colchicine-resistant FMF (moderate-certainty evidence). For acute-phase response, canakinumab probably caused a higher proportion of participants to have a CRP level of 10 mg/L or less compared to placebo (68% with canakinumab versus 6% with placebo; 1 study, 63 participants; moderate-certainty evidence). Colchicine single dose versus divided dose There is probably no difference in the duration of attacks at three months (MD -0.04 hours, 95% CI -10.91 to 10.83) or six months (MD 2.80 hours, 95% CI -5.39 to 10.99; moderate-certainty evidence). There were no data for the number of participants experiencing an attack or days between attacks. There is probably no difference in adverse events (including anorexia, nausea, diarrhea, abdominal pain, vomiting and elevated liver enzymes) between groups (narrative summary; moderate-certainty evidence). For acute-phase response, there may be no evidence of a difference between groups (narrative summary; low- to moderate-certainty evidence). AUTHORS' CONCLUSIONS: There were limited RCTs assessing interventions for people with FMF. Based on the evidence, three times daily colchicine may reduce the number of people experiencing attacks, colchicine single dose and divided dose may not be different for children with FMF, canakinumab probably reduces the number of people experiencing attacks, and anakinra or canakinumab probably reduce CRP in colchicine-resistant participants; however, only a few RCTs contributed data for analysis. Further RCTs examining active interventions, not only colchicine, are necessary before a comprehensive conclusion regarding the efficacy and safety of interventions for reducing inflammation in FMF can be drawn.

Lymphomatosis cerebri: a rare diffuse leukoencephalopathy you should never miss.

INTRODUCTION: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma that diffusely involves throughout the brain. In recent years, increasingly reported cases have notably broadened the spectrum of clinical and radiological features; however, it remains a great diagnostic challenge. CASE REPORT: We reported an atypical case of LC presented with subacute onset of focal neurological deficits and diffuse T2 hyperintensities without contrast enhancement on magnetic resonance imaging. He was initially considered as inflammatory leukoencephalopathy and received empirical corticosteroids, showing a dramatically clinical response. Three months later, the patient relapsed with deteriorating symptoms and enlarged brain lesions with mass-like enhancement. A diagnosis of LC was finally established according to the radiological and pathological findings. DISCUSSION: Though rare, LC should always be kept as a differential diagnosis of diffuse leukoencephalopathy. Neurologists should be aware of every detailed information about LC to avoid a delay of diagnostic biopsy in clinical practice.