The predictive, preventive, and personalized medicine of insomnia: gut microbiota and inflammation.

Background: The human gut microbiota (GM) has been recognized as a significant factor in the development of insomnia, primarily through inflammatory pathways, making it a promising target for therapeutic interventions. Considering the principles of primary prediction, targeted prevention, and personalized treatment medicine (PPPM), identifying specific gut microbiota associated with insomnia and exploring the underlying mechanisms comprehensively are crucial steps towards achieving primary prediction, targeted prevention, and personalized treatment of insomnia. Working hypothesis and methodology: We hypothesized that alterations in the composition of specific GM could induce insomnia through an inflammatory response, which postulates the existence of a GM-inflammation-insomnia pathway. Mendelian randomization (MR) analyses were employed to examine this pathway and explore the mediative effects of inflammation. We utilized genetic proxies representing GM, insomnia, and inflammatory indicators (including 41 circulating cytokines and C-reactive protein (CRP)), specifically identified from European ancestry. The primary method used to identify insomnia-related GM and examine the medicative effect of inflammation was the inverse variance weighted method, supplemented by the MR-Egger and weighted median methods. Our findings have the potential to identify individuals at risk of insomnia through screening for GM imbalances, leading to the development of targeted prevention and personalized treatment strategies for the condition. Results: Nine genera and three circulating cytokines were identified to be associated with insomnia; only the associations of Clostridium (innocuum group) and ß-NGF on insomnia remained significant after the FDR test, OR = 1.08 (95% CI = 1.04-1.12, P = 1.45 × 10-4, q = 0.02) and OR = 1.06 (95% CI = 1.02-1.10, P = 1.06 × 10-3, q = 0.04), respectively. CRP was associated with an increased risk of insomnia, OR = 1.05 (95% CI = 1.01-1.10, P = 6.42 × 10-3). CRP mediated the association of Coprococcus 1, Holdemania, and Rikenellaceae (RC9gut group) with insomnia. No heterogeneity or pleiotropy were detected. Conclusions: Our study highlights the role of specific GM alterations in the development of insomnia and provides insights into the mediating effects of inflammation. Targeting these specific GM alterations presents a promising avenue for advancing the transition from reactive medicine to PPPM in managing insomnia, potentially leading to significant clinical benefits. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00345-1.

Total and Regional Fat/Muscle Mass Ratio and Risks of Incident Cardiovascular Disease and Mortality.

Background To evaluate the sex-specific associations of total and regional fat/muscle mass ratio (FMR) with cardiovascular disease (CVD) incidence and mortality, and to explore the underlying mechanisms driven by cardiometabolites and inflammatory cells. We compared the predictive value of FMRs to body mass index. Methods and Results This population-based, prospective cohort study included 468 885 UK Biobank participants free of CVD at baseline. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device. FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, trunk, arm, and leg). Multivariable Cox proportional hazards models and mediation analyses were used. During 12.5 years of follow-up, we documented 49 936 CVD cases and 4158 CVD deaths. Higher total FMR was associated with an increased risk of incident CVD (hazard ratios [HRs] were 1.63 and 1.83 for men and women, respectively), ischemic heart disease (men: HR, 1.61; women: HR, 1.81), myocardial infarction (men: HR, 1.72; women: HR, 1.49), and congestive heart failure (men: HR, 2.25; women: HR, 2.57). The positive associations of FMRs with mortality from total CVD or its subtypes were significant mainly in trunk and arm for male patients (P for trend <0.05). We also identified 8 cardiometabolites and 5 inflammatory cells that partially mediated FMR-CVD associations. FMRs were modestly better at discriminating cardiovascular mortality risk. Conclusions Higher total and regional FMRs were associated with an increased risk of CVD and mortality, partly mediated through cardiometabolites and inflammatory cells. Early monitoring of FMR should be considered to alleviate CVD risk. FMRs were superior to body mass index in predicting CVD mortality.

High-resolution magnetic resonance imaging of acute intracranial artery thrombus.

BACKGROUND AND PURPOSE: The development of high-resolution magnetic resonance imaging (HR-MRI) has enabled submillimeter-level evaluation of intracranial artery plaque and luminal thrombus. We sought to investigate the value of HR-MRI in assessing the pathogenesis of acute intracranial artery thrombus. METHODS: We examined the presence of intracranial thrombus on three-dimensional T1-weighted HR-MRI in acute ischemic stroke patients with intracranial artery occlusion on magnetic resonance angiography. We defined two thrombus-related HR-MRI features (peri-thrombus plaque and distal residual flow beyond the thrombus) and analyzed their association with potential embolic sources. RESULTS: Luminal thrombus and a shrunken artery without luminal thrombus were detected in 162 (96.4%) and six (3.6%) of 168 patients with intracranial artery occlusion, respectively. Among 111 patients with culprit major artery thrombus, peri-thrombus plaques were observed in 46.8% and distal residual flow beyond the thrombus in 64.0%. Patients with peri-thrombus plaque had a higher prevalence of diabetes (44.2% vs. 25.4%; p = 0.037), a lower prevalence of potential sources of cardioembolism (0% vs. 16.9%; p = 0.002), and a nonsignificantly lower prevalence of potential embolic sources from extracranial arteries (9.6% vs. 20.3%; p = 0.186) than those without. Patients with distal residual flow beyond the thrombus had a lower prevalence of potential sources of cardioembolism (1.4% vs. 22.5%; p < 0.001) and smaller infarct volumes (5.0 [1.4-12.7] mL vs. 16.6 [2.4-94.6] mL; p = 0.012) than those without. CONCLUSIONS: Our study showed that HR-MRI helps clarify the pathogenesis of acute intracranial artery thrombus. The presence of peri-thrombus plaque and distal residual flow beyond the thrombus favor the stroke mechanism of atherosclerosis rather than cardioembolism.

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population-based study.

BACKGROUND: Arterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all-cause mortality. METHODS: We examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid-femoral (cfPWV) and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic-femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log-transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis. RESULTS: Among 1079 diabetic patients, biomarkers including high-density lipoprotein cholesterol, glycated hemoglobin, high-sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG (R = 0.078, -0.193, -0.155, -0.153, -0.116, and -0.137, respectively) and cfPWV (R = -0.068, 0.175, 0.128, 0.066, 0.202, and 0.062, respectively). Compared with the lowest tertile of afSG, the risk of all-cause mortality was lower in the highest tertile (hazard ratio 0.543; 95% confidence interval 0.328-0.900). CONCLUSION: Certain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV, suggesting that these putative risk factors are likely to be important atherosclerosis mechanisms in diabetic patients. AfSG may be an independent predictor of mortality among diabetic populations.

"Life's Essential 8" Cardiovascular Health and Dementia Risk, Cognition, and Neuroimaging Markers of Brain Health.

OBJECTIVE: To evaluate associations of Life's Essential 8 (LE8) score, the recently updated metric for promoting cardiovascular health (CVH), with the risk of incident dementia and its subtypes, cognition, and neuroimaging outcomes and to determine whether these associations differ among apolipoprotein E (APOE)-ε4 genotypes. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: A total of 316,669 participants [mean (SD) age, 56.3 (8.1) years] without prior cardiovascular disease or dementia from the UK Biobank study at baseline survey (2006-2010) were enrolled. METHODS: A modified version of the LE8 score was created (range: 0-100) and categorized into poor (0-49), intermediate (50-79), and optimal (80-100) CVH. Cox proportional hazard and multivariable linear regression models were used. RESULTS: During a median 12.6 years of follow-up, 4238 all-cause dementia cases including 1797 Alzheimer's disease and 939 vascular dementia (VaD) occurred. Individuals with optimal CVH had 44% (95% CI, 0.48-0.64) lower incident all-cause dementia risk and 71% (95% CI, 0.22-0.38) lower VaD risk compared with those who had poor CVH. A 10-point increment in LE8 was associated with higher fluid intelligence scores (ß, 0.088; 95% CI, 0.073-0.102) and numeric memory scores (ß, 0.054; 95% CI, 0.043-0.065), and was also associated with lower white matter hyperintensity volume (ß, -0.673; 95% CI, -0.751 to -0.596), larger total brain volume (ß, 77.93; 95% CI, 62.03-93.84), and hippocampal volume (ß, 0.197; 95% CI, 0.106-0.288). In addition, the association between LE8 profiles and dementia diagnosis differed by APOE genotype (all P for interaction ≤ .001), and was more evident among APOE-ε4 noncarriers. CONCLUSIONS AND IMPLICATIONS: Individuals with a higher LE8 score experienced fewer dementia events (driven especially by incident VaD) and were associated with better neurocognitive brain health profiles. CVH optimization may be beneficial to the maintenance of brain health.

The independent and joint association of accelerometer-measured physical activity and sedentary time with dementia: a cohort study in the UK Biobank.

BACKGROUND: Research on the association of physical activity and sedentary time with dementia is accumulating, though elusive, and the interaction effects of the two remain unclear. We analysed the joint associations of accelerometer-measured physical activity and sedentary time with risk of incident dementia (all-cause dementia, Alzheimer's disease and vascular dementia). METHODS: A total of 90,320 individuals from the UK Biobank were included. Accelerometer-measured total volume of physical activity (TPA) and sedentary time were measured at baseline and dichotomised by median (low TPA [< 27 milli-gravity (milli-g)], high TPA [≥ 27 milli-g]; low sedentary time [< 10.7 h/day], high sedentary time [≥ 10.7 h/day]). Cox proportional hazards models were used to evaluate the joint associations with incident dementia on both additive and multiplicative scales. RESULTS: During a median follow-up of 6.9 years, 501 cases of all-cause dementia were identified. Higher TPA was associated with a lower risk of all-cause dementia, Alzheimer's disease and vascular dementia; the multivariate adjusted hazard ratios (HRs) (95% CI) per 10 milli-g increase were 0.63 (0.55-0.71), 0.74 (0.60-0.90) and 0.69 (0.51-0.93), respectively. Sedentary time was only found to be linked to all-cause dementia, and the HR for high sedentary time was 1.03 (1.01-1.06) compared with that for low sedentary time. No additive and multiplicative relationship of TPA and sedentary time to incident dementia was found (all P values > 0.05). CONCLUSION: Higher TPA level was related to a lower risk of incident dementia irrespective of sedentary time, which highlighted the implication of promoting physical activity participation to counteract the potential detrimental effect of sedentary time on dementia.

The association between daytime napping and risk of type 2 diabetes is modulated by inflammation and adiposity: Evidence from 435 342 UK-Biobank participants.

BACKGROUND: Existing evidence concerning the relationship between daytime napping and type 2 diabetes (T2D) is inconsistent, and whether the effects of napping differ by body fat percentage (BFP) and C-reactive protein (CRP) is unclear. We aimed to investigate the association between daytime napping frequency and T2D risk and whether such an association was modified by BFP and CRP. METHODS: We included 435 342 participants free of diabetes from the UK Biobank. Participants were categorized as nonnappers, occasional nappers, and frequent nappers based on napping frequency, and BFP/CRP was divided into quartiles. Cox proportional hazards models were used. RESULTS: During a median follow-up of 9.2 years, 17 592 T2D cases occurred. Higher frequency of daytime napping was significantly associated with an increased risk of T2D. Compared with nonnappers, the adjusted hazard ratios (HRs) for occasional nappers and habitual nappers were 1.28 (95% confidence interval [CI]: 1.24-1.32) and 1.49 (95% CI: 1.41-1.57), respectively. There was a significant additive and multiplicative interaction (relative excess risk due to interaction [RERI] = 0.490, 95% CI 0.307-0.673; p for multiplicative interaction <.001) between napping and BFP, whereby a higher hazard of T2D associated with more frequent napping was greatest among participants in the highest BFP quartile (HR = 4.45, 95% CI: 3.92-5.06). The results for CRP were similar (RERI = 0.266, 95% CI: 0.094-0.439; p for multiplicative interaction <.001). CONCLUSIONS: Higher daytime napping frequency is associated with an increased T2D risk, and such relationships are modified by BFP and CRP. These findings underscore the importance of adiposity and inflammation control to mitigate diabetes risk.

Ecthyma Gangrenosum Secondary to Methicillin-Sensitive Staphylococcus aureus in an Atopic Child with Transient Neutropenia: A Case Report and Review of the Literature.

In addition to Pseudomonas aeruginosa, other organisms including Staphylococcus aureus have been reported to have associations with ecthyma gangrenosum (EG). There are very limited reports of Staphylococcus aureus EG causing systemic symptoms in an immunocompetent child. We present the case of an atopic child with transient neutropenia developing characteristic skin lesions of EG. Culture of the skin wounds yielded methicillin-susceptible Staphylococcus aureus (MSSA), and incisional biopsy of the skin lesions revealed aggregates of Gram-positive cocci at the subepidermal area and necrotic vasculitis but without perivascular bacterial invasion. In the literature review, seven cases of Staphylococcus aureus EG were reported, and only two were pediatric cases. From this case, we emphasize the importance of early culturing for microorganisms in cases presenting with EG. When toxin-mediated systemic symptoms accompany EG-like skin lesions, MSSA should be considered in an atopic child with transient neutropenia.

Associations of Parity With Change in Global Cognition and Incident Cognitive Impairment in Older Women.

Background: The evidence of the association between parity and risk of mild cognitive impairment (MCI) or dementia is mixed, and the relationship between parity and longitudinal cognitive changes is less clear. We investigated these issues in a large population of older women who were carefully monitored for development of MCI and probable dementia. Methods: Using the Women's Health Initiative Memory Study, 7,100 postmenopausal women (mean age 70.1 ± 3.8 years) with information on baseline parity (defined as the number of term pregnancies), measures of global cognition (Modified Mini-Mental State Examination score) from 1996-2007, and cognitive impairment (centrally adjudicated diagnoses of MCI and dementia) from 1996-2016 were included. Multivariable linear mixed-effects models were used to analyze the rate of changes in global cognition. Cox regression models were used to evaluate the risk of MCI/dementia across parity groups. Results: Over an average of 10.5 years, 465 new cases of MCI/dementia were identified. Compared with nulliparous women, those with a parity of 1-3 and ≥4 had a lower MCI/dementia risk. The HRs were 0.75 (0.56-0.99) and 0.71 (0.53-0.96), respectively (P < 0.01). Similarly, a parity of 1-3 and ≥4 was related to slower cognitive decline (ß = 0.164, 0.292, respectively, P < 0.05). Conclusion: Higher parity attenuated the future risk for MCI/dementia and slowed the rates of cognitive decline in elderly women. Future studies are needed to determine how parity affects late-life cognitive function in women.

Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study).

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

In Vitro and In Vivo Antifibrotic Effects of Fraxetin on Renal Interstitial Fibrosis via the ERK Signaling Pathway.

Fraxetin, a natural derivative of coumarin, is known to have anti-inflammatory, anti-oxidant, and hepatoprotective effects in multiple diseases and in liver fibrosis. Whether fraxetin exerts similar effects against renal fibrosis is unknown. In a Unilateral Ureteral Obstruction (UUO) mouse model of renal fibrosis, fraxetin decreased UUO-induced renal dysfunction with a marked reduction in renal interstitial collagen fibers as detected by Masson's Trichrome staining. Fraxetin treatment also inhibited the expression of α-SMA, Collagen I, Collagen IV, fibronectin, N-cadherin, vimentin, phosphorylated-ERK, and increased the expression of E-cadherin in UUO mice, as shown by immunohistochemical staining and western blot analysis. In vitro studies showed that fraxetin and indoxyl sulfate had no cytotoxic effects on MES13 kidney cells, but that fraxetin significantly decreased IS-induced cell motility and decreased protein expression of α-SMA, N-cadherin, vimentin, and Collagen IV via the ERK-mediated signaling pathway. These findings provide insight into the mechanism underlying fraxetin-induced inhibition of fibrogenesis in renal tissue and suggest that fraxetin treatment may be beneficial for slowing CKD progression.

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study.

BACKGROUND: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. METHODS: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). RESULTS: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. CONCLUSIONS: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.

Peak Systolic Velocity Measurements with Transcranial Doppler Ultrasound Is a Predictor of Incident Stroke among the General Population in China.

BACKGROUND AND OBJECTIVE: It is necessary to develop an effective and low-cost screening tool for identifying Chinese people at high risk of stroke. Transcranial Doppler ultrasound (TCD) is a powerful predictor of stroke in the pediatric sickle cell disease population, as demonstrated in the STOP trial. Our study was conducted to determine the prediction value of peak systolic velocities as measured by TCD on subsequent stroke risk in a prospective cohort of the general population from Beijing, China. METHODS: In 2002, a prospective cohort study was conducted among 1392 residents from 11 villages of the Shijingshan district of Beijing, China. The cohort was scheduled for follow up with regard to incident stroke in 2005, 2007, and 2012 by a study team comprised of epidemiologists, nurses, and physicians. Univariate and multivariate Cox proportional hazard regression models were used to determine the factors associated with incident stroke. RESULTS: Participants identified by TCD criteria as having intracranial stenosis had a 3.6-fold greater risk of incident stroke (hazard ratio (HR) 3.57, 95% confidence interval (CI) 1.86-6.83, P<0.01) than those without TCD evidence of intracranial stenosis. The association remained significant in multivariate analysis (HR 2.53, 95% CI 1.31-4.87) after adjusting for other risk factors or confounders. Older age, cigarette smoking, hypertension, and diabetes mellitus remained statistically significant as risk factors after controlling for other factors. CONCLUSIONS: The study confirmed the screening value of TCD among the general population in urban China. Increasing the availability of TCD screening may help identify subjects as higher risk for stroke.

Anti-N-methyl-d-aspartate receptor encephalitis in a patient with neuromyelitis optica spectrum disorders.

We described a female patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis occurring sequentially with neuromyelitis optica spectrum disorders (NMOSD). The 19-year-old patient initially presented a diencephalic syndrome with aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) and brain lesions which involving bilateral medial temporal lobes and periependymal surfaces of the third ventricle on magnetic resonance imaging (MRI). Ten months later, the patient developed cognitive impairment, psychiatric symptoms and dyskinesia with left basal ganglia lesions on brain MRI. Meanwhile, the anti-NMDAR antibodies were positive in the patient's serum and cerebrospinal fluid, while the screening tests for an ovarian teratoma and other tumors were all negative. Hence, the patient was diagnosed NMOSD and anti-NMDAR encephalitis followed by low-dose rituximab treatment with a good response. This case was another evidence for demyelinating syndromes overlapping anti-NMDAR encephalitis in Chinese patients.

Prehospital Identification of Stroke Subtypes in Chinese Rural Areas.

BACKGROUND: Differentiating intracerebral hemorrhage (ICH) from cerebral infarction as early as possible is vital for the timely initiation of different treatments. This study developed an applicable model for the ambulance system to differentiate stroke subtypes. METHODS: From 26,163 patients initially screened over 4 years, this study comprised 1989 consecutive patients with potential first-ever acute stroke with sudden onset of the focal neurological deficit, conscious or not, and given ambulance transport for admission to two county hospitals in Yutian County of Hebei Province. All the patients underwent cranial computed tomography (CT) or magnetic resonance imaging to confirm the final diagnosis based on stroke criteria. Correlation with stroke subtype clinical features was calculated and Bayes' discriminant model was applied to discriminate stroke subtypes. RESULTS: Among the 1989 patients, 797, 689, 109, and 394 received diagnoses of cerebral infarction, ICH, subarachnoid hemorrhage, and other forms of nonstroke, respectively. A history of atrial fibrillation, vomiting, and diabetes mellitus were associated with cerebral infarction, while vomiting, systolic blood pressure ≥180 mmHg, and age <65 years were more typical of ICH. For noncomatose stroke patients, Bayes' discriminant model for stroke subtype yielded a combination of multiple items that provided 72.3% agreement in the test model and 79.3% in the validation model; for comatose patients, corresponding agreement rates were 75.4% and 73.5%. CONCLUSIONS: The model herein presented, with multiple parameters, can predict stroke subtypes with acceptable sensitivity and specificity before CT scanning, either in alert or comatose patients. This may facilitate prehospital management for patients with stroke.

[Cervical spondylosis misdiagnosed as cerebral infarction: a case report].

Here we report a case of cervical spondylosis misdiagnosed as cerebral infarction. The patient was a 55-year-old man with a one-day history of weakness in his right extremities. Brain magnetic resonance imaging (MRI) showed no acute abnormality, cerevical MRI showed that cervical spondylisis, C4/5, C5/6 disc herniation, spinal canal stenosis and compression of the spinal cord. Then the patient was transferred to the Department of Orthopaedics and underwent surgical treatment of cervical spondylosis. Followed-up for six months, the weakness of his right extremities returned to normal.

YKL-40 regulated epithelial-mesenchymal transition and migration/invasion enhancement in non-small cell lung cancer.

BACKGROUND: YKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. However, the function of this protein is still unclear. METHODS: The clinical prognosis of non-small cell lung cancers (NSCLC) patients and their clinical YKL-40 expressions were obtained from the Prognoscan database. The expressions of YKL-40 in patient samples were determined by Western Blotting assay. YKL-40 gene knockdown and overexpression were performed on NSCLC cancer cells (CL1-1 and CL1-5). The cells were investigated for their epithelial-mesenchymal transition (EMT) markers gene modulation through Western Blotting and RT-PCR. Further cell metastatic abilities were assessed by transwell migration and invasion assay. RESULT: In this study, YKL-40 was observed to be highly expressed in NSCLC specimens. Furthermore, determined by the PrognoScan database analysis, patients with high expression levels of YKL-40 were found with poor prognosis. In the in vitro study, different characteristics of NSCLC cell lines (CL1-1, H23, H838, CL1-5, and H2009) were used as study models, where YKL-40 expression levels were determined to correlate with the phenotypic characteristics of cancer metastasis. In this study,YKL-40 was demonstrated to regulate EMT marker expressions such as Twist, Snail, Slug, N-cadherin, Vimentin, and E-cadherin. The protein's affects in cancer cell migration and invasion were also observed in YKL-40 overexpression or knock down NSCLC cell lines. CONCLUSION: All of results from this study suggest that YKL-40 is a major factor in NSCLC metastasis. Thus, YKL-40 may serve as therapeutic targets for NSCLC patients in the future.

Clinical features of acute corpus callosum infarction patients.

The clinical manifestation of acute corpus callosum (CC) infarction is lack of specificity and complex, so it is easily missed diagnosis and misdiagnosis in the early stage. The present study aims to describe the clinical features of the acute CC infarction. In this study, 25 patients with corpus callosum infarction confirmed by the brain MRI/DWI and the risk factors were summarized. Patients were classified into genu infarction (3 cases), body infarction (4 cases), body and genu infarction (4 cases), body and splenium infarction (1 case), splenium infarction (13 cases) according to lesion location. Clinical manifestation and prognosis were analyzed among groups. The results indicated that CC infarction in patients with high-risk group accounted for 72%, moderate-risk group accounted for 20%, low-risk group (8%). The main risk factors are carotid intimal thickening or plaque formation, hypertension, hyperlipidemia, cerebral artery stenosis, and so on. The CC infarction often merged with other parts infarction, and splenium infarction had the highest incidence, the clinical symptoms in the body infarction which can appear typical signs and symptoms, but in other parts infarction which always merged many nerve defect symptoms. The body infarction prognosis is poor; the rest parts of infarction are more favorable prognosis. In conclusion, CC infarction has the highest incidence in the stroke of high-risk group; neck color Doppler and TCD examination can be found as early as possible to explore the pathogenic factors. Prognosis is usually much better by treatment according to the location and risk factors.