Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been acknowledged to commonly co-exist and lead to increased risks of stroke, whereas the association between various BMI-based metabolic phenotypes and development of intracranial atherosclerotic stenosis (ICAS) remained controversial. METHODS: A total of 5355 participants were included from the Asymptomatic Polyvascular Abnormalities Community (APAC) study. Participants were categorized into six groups according to their body mass index (BMI) and MetS status. ICAS was assessed using transcranial Doppler (TCD) Ultrasonography. Logistic regression was employed to evaluate the association between BMI-based metabolic phenotypes and ICAS. RESULTS: 704 participants were diagnosed with ICAS. Compared to the metabolic healthy normal weight (MH-NW) group, the metabolic unhealthy normal weight (MUH-NW) group demonstrated a higher risk of ICAS (full-adjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.42-2.57), while no significant association was observed in the metabolic unhealthy obesity (MUO) group (full-adjusted OR, 1.07; 95% CI, 0.70-1.65) and other metabolic healthy groups regardless of BMI. The results were consistent across gender, age, smoking, alcohol intake, and physical activity subgroups. CONCLUSION: The present study suggested that MUH-NW individuals had a significant association with increased risk of ICAS compared with MH-NW individuals.

Efficacy and safety of dual antiplatelet therapy in the elderly for stroke prevention: a subgroup analysis of the CHANCE-2 trial.

OBJECTIVES: Evidence of the optimal antiplatelet therapy for elderly patients who had a stroke is limited, especially those elder than 80 years. This study aimed to explore the efficacy and safety of dual antiplatelet therapy (DAPT) in old-old patients compared with younger patients in the ticagrelor or Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events-II (CHANCE-2) trial. METHODS: CHANCE-2 was a randomised, double-blind, placebo-controlled trial in China involving patients with high-risk transient ischaemic attack or minor stroke with CYP2C19 loss-of-function alleles. In our substudy, all enrolled patients were stratified by age: old-old (≥80 years), young-old (65-80 years) and younger (<65 years). The primary outcomes were stroke recurrence and moderate to severe bleeding within 90 days, respectively. RESULTS: Of all the 6412 patients, 406 (6.3%) were old-old, 2755 (43.0%) were young-old and 3251 (50.7%) were younger. Old-old patients were associated with higher composite vascular events (HR 1.41, 95% CI 1.00 to 1.98, p=0.048), disabling stroke (OR 2.43, 95% CI 1.52 to 3.88, p=0.0002), severe or moderate bleeding (HR 8.40, 95% CI 1.95 to 36.21, p=0.004) and mortality (HR 7.56, 95% CI 2.23 to 25.70, p=0.001) within 90 days. Ticagrelor-aspirin group was associated with lower risks of stroke recurrence within 90 days in younger patients (HR 0.68, 95% CI 0.51 to 0.91, p=0.008), which was no differences in old-old patients. CONCLUSION: Elderly patients aged over 80 in CHANCE-2 trial had higher risks of composite vascular events, disabling stroke, severe or moderate bleeding and mortality within 90 days. Genotype-guided DAPT might not be as effective in old-old patients as in younger ones. TRIAL REGISTRATION NUMBER: NCT04078737.

Circ_103128 is associated with the tumorigenesis of medulloblastoma.

BACKGROUND & AIMS: Medulloblastoma (MB) is a primary malignant tumor of the brain. They are categorized as WHO grade IV neoplasms, and mostly occur in children. The traditional therapy for MB is surgery, followed by radiation and chemotherapy, but the clinical outcome is still poor and has a high possibility of recurrence. The mechanism underlying the development of MB should be further investigated to develop novel therapeutic strategies. METHODS: Research has demonstrated that circRNAs contribute to tumorigenesis, but the functional mechanism of circRNAs in MB has not been fully explored and remains vague. The differentially expressed circRNAs between MB and normal cerebellar tissues were analyzed based on the microarray expression profiles to characterize the potential mechanism of circRNAs in MB. RESULTS: The results revealed that circRNA_103128 was highly expressed in MB, and cellular and animal experiments were performed to verify its tumorigenic effect in MB. Furthermore, a bioinformatics analysis and literature review previous literature were performed, confirming miR-129-5p as a target gene downstream of circRNA_103128. In addition, SOX4 was predicted to be a downstream target protein of miR-129-5p. Subsequently, miR-129-5p expression was inhibited, which revealed the regulatory mechanism of circRNA_103128. The latter promotes MB cell growth, migration, and invasion by the sponge effect of miR-129-5p, thereby affecting the expression of SOX4. CONCLUSIONS: This study is the first to systematically demonstrate that circRNA_103128 may play an important regulatory role in MB through a sponge effect with miR-129 -5p, which affects SOX4 expression and regulates tumorigenesis and tumor cell development in MB.

Association of serum albumin to globulin ratio with outcomes in acute ischemic stroke.

BACKGROUND: Serum albumin to globulin ratio (A/G) has been widely used as a representative biomarker for assessing inflammation and nutrition status. However, in patients with acute ischemic stroke (AIS), the predictive value of serum A/G has rarely been reported. We aimed to evaluate whether serum A/G is associated with prognosis in stroke. METHODS: We analyzed data from the Third China National Stroke Registry. The patients were categorized into quartile groups according to the serum A/G at admission. Clinical outcomes included poor functional outcomes (modified Rankin Scale [mRS] score of 3-6 or 2-6) and all-cause mortality at 3 months and1 year. Multivariable logistic regressions and Cox proportional hazards regressions were used to evaluate the association of serum A/G with the risk of poor functional outcomes and all-cause mortality. RESULTS: A total of 11, 298 patients were included in this study. After adjustment for confounding factors, patients in the highest serum A/G quartile had a lower proportion of mRS score 2-6 (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.76-1.00) and mRS score 3-6 (OR, 0.87; 95% CI, 0.73-1.03) at 3 months follow-up. At 1 year follow-up, there was a significant association between higher serum A/G and mRS score 3-6 (OR, 0.68; 95% CI, 0.57-0.81). We also found that the highest serum A/G was related to decreased risk of all-cause mortality (hazard ratio [HR], 0.58; 95% CI, 0.36-0.94) at 3 months follow-up. Similar results were found at 1-year follow-up. CONCLUSIONS: Lower serum A/G levels were associated with poor functional outcomes and all-cause mortality at 3 months and 1-year follow-up in patients with acute ischemic stroke.

Association of Impaired Fasting Glucose With Cardiovascular Disease in the Absence of Risk Factor.

BACKGROUND: The association between impaired fasting glucose and cardiovascular disease (CVD) in participants without atherosclerotic CVD (ASCVD) risk factors based on current definitions is unclear. The study aimed to examine the association of fasting glucose levels with CVD and its subtypes in persons without ASCVD risk factors. METHODS: This study included 38 297 participants [men 62.1%; mean age 47.9 (12.9) years] who were free of a history of CVD and absent of ASCVD risk factors and had a fasting plasma glucose (FPG) level between 70 to 125 mg/dL at baseline from Kailuan Study during 2006 and 2007. Participants were followed until new-onset CVD event, death, or December 31, 2017. Cox proportional hazards models were performed to evaluate the associations. RESULTS: During a median follow-up of 11.0 years (interquartile range 10.7-11.2 years), we observed 1217 incident CVD events. Compared with participants with FPG 70 to 99 mg/dL, the multivariable adjusted hazard ratios for CVD among participants with FPG 100 to 109 mg/dL and 110 to 125 mg/dL were 1.18 (95% CI 1.02-1.38) and 1.27 (95% CI 1.03-1.55), respectively. Multivariable-adjusted spline regression model showed a J-shaped association between FPG and the risk of CVD. CONCLUSIONS: We found that among individuals without diabetes or other traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing abnormal FPG levels. These results highlight the importance of primordial prevention for FPG level increases along with other traditional ASCVD risk factors.

Clinical application of the mixed reality technique to assist the location and anatomy of perforator vessels of the anterolateral femoral flap / 口腔疾病防治

Objective@#To explore the clinical application value of mixed reality technology in locating perforator vessels and assisting perforator vessel dissection to harvest anterolateral thigh flaps.@*Methods@#Six patients who needed anterolateral thigh flap repair after resection of oral and maxillofacial tumors were recruited from the Department of Oral and Maxillofacial Surgery of Nanchong Central Hospital from January 2020 to January 2021. Before surgery, the CT angiography data of the lower limbs of the patients carrying the calibration points were imported into the data workstation to perform 3D reconstruction of the perforator vessels and surrounding tissues of the thigh, and the reconstruction results were imported into Microsoft HoloLens 2 glasses. During the operation, calibration was performed at the calibration point of the operative area so that the preoperative reconstruction results were superimposed on the operative area through Microsoft HoloLens 2 glasses. The clinical application value of mixed reality technology assisted perforator vessel location and anatomy of anterolateral femoral perforator flap was discussed from six aspects: whether the perforator vessel was reconstructed preoperatively, intraoperative calibration time, whether the actual position of the perforating vessels passing through the fascia lata fulcrum deviated from the preoperative reconstruction result within 1 cm, time required to harvest the flap, and whether the actual route of the perforator vessel was consistent with the reconstruction result, and whether the postoperative flap survived.@*Results @# The position and course of perforating vessels were successfully reconstructed in 6 cases before the operation. The actual course of perforating vessels during the operation was consistent with the reconstruction results. The deviation between the actual position of the perforating points and the preoperative reconstruction results was within 1 cm, which met the requirements of the actual asisting of the anterolateral thigh flap. The average time of flap harvest was (70.50 ± 7.20) min. The average calibration time was (13.33 ± 5.50) min. All flaps survived.@* Conclusions @# Mixed reality technology projects the reconstruction results of anterolateral femoral perforator vessels directly into the operative area, which provides a new method for asisting localization and anatomy of anterolateral femoral flap perforator vessels and reduces the possibility of injury to perforator vessels.

Serum Phosphate and 1-Year Outcome in Patients With Acute Ischemic Stroke and Transient Ischemic Attack.

Objective: To determine the association between serum phosphate level and 1-year clinical outcomes in patients with acute ischemic stroke and transient ischemic attack. Methods: We included 7,353 patients with acute ischemic stroke and transient ischemic attack from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to serum phosphate quartiles. Composite end point included recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Poor functional outcome is defined as modified Rankin Scale score of 3 to 6. Multivariable Cox regression or logistic regression was used to evaluate the independent association of serum phosphate with 1-year all-cause mortality, recurrent stroke, composite end point and poor functional outcome. Results: The mean age of the included 7,353 patients was 62.5 years, and 68.6% of them were men. Plotting hazard ratios over phosphate levels suggested a U-shaped association especially for recurrent stroke and composite end point, and therefore the third quartile group was set as reference group. Compared with the third quartile of phosphate (1.06-1.20 mmol/L), the adjusted hazard ratios/odds ratios (95% CI) of the lowest quartile (<0.94 mmol/L) were 0.98 (0.67-1.42) for all-cause mortality, 1.31 (1.05-1.64) for stroke recurrence, 1.26 (1.02-1.57) for composite end point, and 1.27 (1.01-1.61) for poor functional outcome, and the adjusted odds ratio of the highest quartile (≥1.2 mmol/L) was 1.40 (1.11-1.77) for poor functional outcome. Conclusions: Serum phosphate may be an independent predictor of stroke recurrence, composite end point and poor functional outcome after ischemic stroke.

Contribution of WNT2B Genetic Variants to Ischemic Stroke Occurrence in a Chinese Han Population.

ABSTRACT: Wnt signaling pathway-related WNT2B gene was upregulated in ischemic brain damage. We aimed to assess the contribution of WNT2B genetic variant to ischemic stroke (IS) susceptibility in the Chinese Han population. Five polymorphisms including rs3790606, rs351364, rs3790608, rs12037987, and rs10776752 in WNT2B were genotyped using Agena MassARRAY platform in 476 healthy controls and 501 patients with IS. Odds ratio (OR) and 95% confidence interval (CI) adjusted for age and gender were estimated by logistic regression analysis. Analysis of variance was used to evaluate the association between genotypes of WNT2B variants and blood lipid parameters. Rs12037987 (OR = 1.82, 95% CI: 1.18-2.82, P = 0.007) and rs10776752 (OR = 1.74, 95% CI: 1.13-2.68, P = 0.012) were related to the increased IS susceptibility. Interestingly, rs12037987 (OR = 2.01, P = 0.028) and rs10776752 (OR = 2.02, P = 0.028) had the higher IS risk in the subjects younger than or equal to 65 years. Rs12037987 (OR = 2.70, P = 0.013), rs10776752 (OR = 2.71, P = 0.012), and rs3790606 (OR = 1.89, P = 0.036) manifested an increasing-risk association with IS occurrence in women. Moreover, rs3790606 genotype was related to serum levels of triglyceride (P = 0.008) and total cholesterol (P = 0.001). Our study reported that rs12037987 and rs10776752 were associated with the increased risk for IS in the Chinese Han population. Our findings may be useful for insight into the contribution of WNT2B variants to the complex pathogenesis of IS.

Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers.

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0-2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1-2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9-1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.

Inhibition of long non-coding RNA HOXA11-AS against neuroinflammation in Parkinson's disease model via targeting miR-124-3p mediated FSTL1/NF-κB axis.

BACKGROUND: Studies have revealed that lncRNA HOXA11-AS contributes to regulating inflammation, while the role of HOXA11-AS in Parkinson's disease (PD) remains unclear. METHODS: Both in vivo and in vitro PD models were induced. Gain- or loss-assays of HOXA11-AS and miR-124-3p were conducted. The neurological functions, dopaminergic neurons damage, microglia activation of PD mice were measured. Afterwards, the expressions of inflammatory factors were examined with RT-PCR. Western blot was employed to detect the level of FSTL1, NF-κB and NLRP3 inflammasome. Meanwhile, bioinformatics analysis and dual-luciferase reporter assay were utilized to confirm the targeting relationships among miR-124-3p, HOXA11-AS and FSTL1. RESULTS: HOXA11-AS promoted MPTP-mediated SH-SY5Y neuronal injury and LPS-induced microglia activation, while miR-124-3p had the opposite effects. Additionally, miR-124-3p was the target of HOXA11-AS and FSTL1. HOXA11-AS overexpression enhanced the expression of inflammatory factors and FSTL1, NF-κB and NLRP3 inflammasome, while inhibiting NF-κB weakened HOXA11-AS-mediated neuronal damage and microglia activation. Moreover, HOXA11-AS1 downregulation ameliorated MPTP-induced neurological damages and neuroinflammation in mice. CONCLUSION: Inhibition of HOXA11-AS protects mice against PD through repressing neuroinflammation and neuronal apoptosis through miR-124-3p-FSTL1-NF-κB axis.

Serum calcium and long-term outcome after ischemic stroke: Results from the China National stroke registry III.

BACKGROUND AND AIMS: Serum calcium abnormality is associated with adverse cardiovascular outcomes, but the effects of serum calcium level on stroke outcomes remain unknown. We aimed to assess the relationship between serum calcium level and 1-year outcomes in patients with acute ischemic stroke and transient ischemic attack. METHODS: We included 9375 stroke patients from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to albumin corrected-calcium quartiles. Composite end point comprised recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Multivariable Cox or logistic regression was used to evaluate the independent association of albumin corrected-calcium with all-cause mortality, recurrent stroke, composite end point, and poor functional outcome (modified Rankin Scale score ≥3). RESULTS: Compared with the lowest calcium quartile (<2.16 mmol/L), the adjusted hazard ratio (95% CI) of the top quartile (≥2.31 mmol/L) was 1.56 (1.11-2.18) for all-cause mortality, 1.06 (0.87-1.28) for recurrent stroke and 1.08 (0.90-1.01) for composite end point, and the adjusted odds ratio for poor functional outcome was 1.18 (0.96-1.44). The addition of serum calcium to conventional risk factors improved risk prediction of all-cause mortality, leading to a small but significant increase in C-statistics and reclassification with non-significant integrated discrimination improvement (C-statistics, p = 0.02; net reclassification index 11.8%, p = 0.038; integrated discrimination improvement 0.08%, p = 0.42). CONCLUSIONS: High serum calcium levels at baseline were associated with all-cause mortality at 1-year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke.

[Application of high frequency color Doppler ultrasonography combined with microvascular stapler in maxillofacial defect repair].

Objective:To evaluate the clinical application value of high frequency color Doppler ultrasound（HFCUS） combined with microvascular stapler in the repair of oral and maxillofacial defects with the anterolateral thigh perforator flap. Method:Forty maxillofacial malignant tumor patients were divided into HFCUS+stapler group（23 cases） and control group（17 cases）. All of cases used anterolateral thigh flap without fascia lata to repair the soft tissue defect in the operative area. One artery and two veins were anastomosed during the operation. The flaps were harvested from 6.0 cm×7.0 cm to 10.0 cm×12.0 cm, and the donor sites were closed and sutured at the same time. In group HFCUS+stapler, HFCUS was used to locate the perforating vessels and mark the location on the body surface the operation, and the vein was anastomosed intraoperatively with a stapler. In the control group, only iliac patella line was fixed before operation, and the vein was manually sutured during operation. The clinical data of 2 groups was evaluated by comparing the time consumption of flap harvest, the vascular anastomosis, the incidence of postoperative venous crisis, and the long-term survival rate of flap. Result:In the HFCUS+stapler group, a total of 27 perforators were found before the operation, 24 perforators within 1.0 cm from the preoperative marker were actually detected during the operation, and the remaining 3 perforators were about 1.7 cm, 2.0 cm and 2.5 cm from the marker respectively, with an accuracy rate of 88.9%. HFCUS+stapler group used （63.17±7.80） min to harvest the flap, while the control group used （85.47±7.41） min HFCUS+stapler group took significantly less time than the control group（P<0.001）. The arterial anastomat time in the HFCUS+stapler group was （9.48±1.20） min and it was （9.18±1.13） min in the control group. The difference between the two groups was not statistically significant（P=0.426）. The total anastomosis time of the two veins was （14.87±2.62） min in the HFCUS+stapler group and （33.06±3.86） min in the control group. The HFCUS+stapler group had significantly less anastomosing time than the control group（P<0.001）. In HFCUS+stapler group, no arteriovenous crisis occurred after operation, and all flaps survived well 15 days after operation. In the control group, 2 cases had venous crisis after operation（P=0.091）. Conclusion:HFCUS combined with iliac patellar line can improve the accuracy of anatomical perforated vessels, reduce the time of flap harvesting, and reduce the possibility of accidental injury of perforated vessels. The use of microvascular stapler for vein anastomosis can reduce the operation time and improve the survival rate of flap. The combination of the two can significantly reduce the operation time of microsurgical repairing maxillofacial soft tissue defect, improve the operation quality, and has higher clinical application value.

Blood Pressure Variability and Severity of Early Prognosis in Patients with Acute Pontine Infarction.

BACKGROUND: Increased blood pressure (BP) variability may worsen the prognosis of stroke. This study aimed at investigating the association between BP variability and early functional prognosis in patients with pontine infarction. METHODS: According to types of pontine infarction, all the 137 patients were divided into two groups: 70 patients with paramedian pontine infarction (PPI) and 67 patients with deep pontine infarction (DPI). Common risk factors, 24-hour continuous blood pressure monitoring data, and the coefficient of variation were collected after admission in the hospital. Functional outcomes were evaluated with modified Rankin scale (mRS) at 3 months after discharge (favorable outcome: mRS scores ≤ 2; poor outcome: mRS scores > 2). RESULTS: The level of Glu, HbA1c, LDL, and NIHSS scores in the PPI group was significantly higher than that in the DPI group, and the concentration of blood uric acid was lower in the PPI group. Diastolic pressure in the PPI group is significantly higher than that in the DPI group, and coefficient of variation (CV) of systolic pressure in PPI is higher when compared with DPI ((88.77 ± 1.71) mmHg vs. (80.74 ± 1.31) mmHg; (11.54 ± 0.35) vs. (10.24 ± 0.25)). In multivariate analyses, the CV of systolic pressure, diastolic pressure, NIHSS scores, and the paramedian pontine infarction was independently associated with 3-month clinical outcome (OR = 1.94, 95% CI = 1.252-2.994, P=0.003; OR = 1.08, 95% CI = 1.002-1.166, P=0.04; OR = 1.58, 95% CI = 1.164-2.159, P=0.003; OR = 9.87, 95% CI = 1.045-32.193, P=0.04). CONCLUSION: In conclusion, increased 24-hour (BP) variability, NIHSS scores, and paramedian pontine were associated with early poor prognosis in patients with acute pontine infarction.

The Impact of PPARD and PPARG Polymorphisms on Glioma Risk and Prognosis.

Recent studies showed that peroxisome proliferator-activated receptors (PPARs) had effects on the progression of multiple tumors, but the role of PPARD and PPARG in glioma remains poorly understand. We conducted a case-control study to investigate the association of polymorphisms in PPARD and PPARG with glioma risk and prognosis in the Chinese Han population. Seven polymorphisms (PPARD: rs2016520, rs67056409, rs1053049 and rs2206030; PPARG: rs2920503, rs4073770 and rs1151988) were genotyped using the Agena MassARRAY system in 568 glioma patients and 509 healthy controls. The odd ratios (OR) and 95% confidence interval (CI) were calculated to assess the association of PPARD and PPARG polymorphisms with glioma risk. The Multifactor dimensionality reduction (MDR) method was used to analysis interactions of genetic polymorphisms on glioma risk. Then, we conducted log-rank test, Kaplan-Meier analysis and Cox regression model to evaluate the relationship of PPARD and PPARG polymorphisms with glioma prognosis. We found PPARD polymorphisms (rs2016520, rs67056409, rs1053049) were significantly associated with glioma risk in multiple models (P < 0.05). Stratified analysis showed rs2016520, rs67056409, rs1053049 of PPARD significantly decreased risk of glioma in the subgroup of age > 40 and astrocytoma (P < 0.05). For male, PPARD rs1053049 had a strong relationship with glioma risk in allele (P = 0.041), dominant (P = 0.040) and additive (P = 0.040) models. The effect of PPARG rs2920503 on glioma risk was related to glioma grade (P < 0.05). MDR showed that a seven-locus model was the best polymorphisms interaction pattern. Moreover, surgery and chemotherapy had strongly impact on overall survival and progression free survival of glioma patients. Our findings suggested that PPARD and PPARG polymorphisms were associated with glioma risk and prognosis in the Chinese Han population, and further studies are need to confirm our results.

Adult-onset neuronal intranuclear inclusion disease presenting with typical MRI changes.

BACKGROUND: This study aims to analyze the clinical, imaging, electrophysiological, and dermatopathological features of a patient with adult-onset neuronal intranuclear inclusion disease (NIID) and to explore the diagnostic methods of adult-onset NIID. CASE PRESENTATION: We here report a 63-year-old male with recurrent acute encephalopathy syndrome and autonomic nervous system damage syndrome characterized by sexual dysfunction and urinary and fecal dysfunction. Cranial diffusion-weighted magnetic resonance imaging (DWI) demonstrated symmetrically distributed strip-shaped high-intensity signal in bilateral fronto-occipital-parietal cortical-medullary junction. Electrophysiological test revealed that the main site of injury was myelin sheath in both motor and sensory nerves. Skin biopsy revealed eosinophilic spherical inclusion bodies in the nucleus of sweat gland epithelial cells. CONCLUSION: This case suggests that adult NIID is a chronic neurodegenerative disease with high clinical heterogeneity. Subcortical strip-shaped high-intensity signal on DWI has high diagnostic significance. Eosinophilic intranuclear inclusion bodies detected by skin biopsy contribute to diagnosis.

The Third China National Stroke Registry (CNSR-III) for patients with acute ischaemic stroke or transient ischaemic attack: design, rationale and baseline patient characteristics.

Background and purpose: Stroke is the leading cause of mortality and disability in China. Precise aetiological classification, imaging and biological markers may predict the prognosis of stroke. The Third China National Stroke Registry (CNSR-III), a nationwide registry of ischaemic stroke or transient ischaemic attack (TIA) in China based on aetiology, imaging and biology markers, will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke. Methods: Between August 2015 and March 2018, the CNSR-III recruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China. Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews. Patients were followed for clinical outcomes at 3 months, 6 months and 1-5 year annually. Brain imaging, including brain MRI and CT, were completed at baseline. Blood samples were collected and biomarkers were tested at baseline. Results: A total of 15 166 stroke patients were enrolled, among which 31.7% patients were women with the average age of 62.2±11.3 years. Ischaemic stroke was predominant (93.3%, n=14 146) and 1020 (6.7%) TIAs were enrolled. Conclusions: CNSR-III is a large scale nationwide registry in China. Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.

Variants in MME are associated with autosomal-recessive distal hereditary motor neuropathy.

OBJECTIVE: To identify a new genetic cause in patients segregating distal hereditary motor neuropathy (dHMN) with an autosomal recessive pattern. METHODS: Whole-exome sequencing was conducted in two siblings and was combined with segregation analysis. Additionally, 83 unrelated dHMN patients with unknown genetic cause were screened. RNA analysis was performed using blood lymphocytes and HEK293 cells transfected with mutant plasmids. Immunohistochemistry and Western blot analysis was applied to the nerve tissue. The enzymatic activities of mutant proteins were measured in the cultured cells to verify the pathogenicity of variants. RESULTS: The clinical features of the patients showed late-onset phenotype of distal motor neuropathy without sensory involvement. We identified that compound heterozygous variants of c.1342C>T and c.2071_2072delGCinsTT in the membrane metalloendopeptidase (MME) gene co-segregated with the phenotype in a dHMN family. In an additional group of 83 patients with dHMN, compound heterozygous variants of c.1416+2T>C and c.2027C>T in MME were identified in one patient. The splice site variant c.1416+2T>C results in skipping of exon 13. The stop variant c.1342C>T induces mRNA degradation via nonsense-mediated mRNA decay. Transcript levels of MME in the lymphocytes showed no significant differences between the patients and controls. We also identified that MME variants were associated with mild decrease in protein expression in the sural nerve and significant impairments of enzymatic activity. INTERPRETATION: Variants in the MME gene were associated with not only a Charcot-Marie-Tooth neuropathy phenotype but also with an autosomal-recessive dHMN phenotype. Loss of function may play a role in the pathogenesis of dHMN.

Acute phase serum cathepsin S level and cathepsin S/cystatin C ratio are the associated factors with cerebral infarction and their diagnostic value for cerebral infarction.

Cathepsin S plays an important role in the pathogenesis of several cardiovascular diseases; however, the relationship between serum cathepsin S and cerebral infarction (CI) is still unknown. This study aimed to investigate the relationship between acute phase serum cathepsin S level and cerebral infarction. A total of 202 stroke patients were enrolled into this study, and were divided into cerebral infarction (n = 140) group and non-cerebral infarction group (non-CI, n = 62). Fifty healthy individuals were recruited as the control group. Serum levels of cathepsin S and cystatin C were measured at days 1, 7, and 14 posthospitalization. Compared to the non-CI group, the CI group had significantly higher rates of hypertension, dyslipidemia, and smoking (all P < 0.05). The CI group had significantly higher cathepsin S levels and cathepsin S to cystatin C ratio (CatS/CysC) at both days 1 and 7 posthospitalization (both P < 0.05). Multivariate logistic regression analysis demonstrated that cathepsin S level (day 7) and CatS/CysC (days 1 and 7) were the associated factors with CI (all P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the Area Under Curve (AUC) value of CatS-day7, CatS/CysC-day1, and CatS/CysC-day7 were 0.726 (95% CI: 0.652-0.800, P < 0.001), 0.641 (95% CI: 0.559-0.723, P = 0.001), and 0.721 (95% CI: 0.645-0.797, P = 0.039), respectively. Cathepsin S and CatS/CysC were associated with acute CI, and may have the potential to be the diagnostic biomarkers for CI. Our findings help to better understand the role of serum cathepsin S level in CI.

Systematic analysis of genes involved in oral cancer metastasis to lymph nodes.

Oral cancer remains a deadly disease worldwide. Lymph node metastasis and invasion is one of the causes of death from oral cancer. Elucidating the mechanism of oral cancer lymph node metastasis and identifying critical regulatory genes are important for the treatment of this disease. This study aimed to identify differentially expressed genes (gene signature) and pathways that contribute to oral cancer metastasis to lymph nodes. The GSE70604-associated study compared gene profiles in lymph nodes with metastasis of oral cancer to those of normal lymph nodes. The GSE2280-associated study compared gene profiles in primary tumor of oral cancer with lymph node metastasis to those in tumors without lymph node metastasis. There are 28 common differentially expressed genes (DEGs) showing consistent changes in both datasets in overlapping analysis. GO biological process and KEGG pathway analysis of these 28 DEGs identified the gene signature CCND1, JUN and SPP1, which are categorized as key regulatory genes involved in the focal adhesion pathway. Silencing expression of CCND1, JUN and SPP1 in the human oral cancer cell line OECM-1 confirmed that those genes play essential roles in oral cancer cell invasion. Analysis of clinical samples of oral cancer found a strong correlation of these genes with short survival, especially JUN expression associated with metastasis. Our study identified a unique gene signature - CCND1, JUN and SPP1 - which may be involved in oral cancer lymph node metastasis.

Differences in molecular regulation between osteochondroma and bizarre parosteal osteochondromatous proliferation.

The differences in molecular mechanisms between osteochondroma and bizarre parosteal osteochondromatous proliferation (BPOP) remain to be fully elucidated. In the present study, the differentially expressed genes between BPOP and osteochondroma were obtained from the Gene Expression Omnibus online database, and the associations among these genes were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online bioinformatics software. The results revealed several differentially expressed genes between human BPOP and osteochondroma. These differentially expressed genes were also enriched in different subgroups based on the analysis using DAVID online software, including 'transforming growth factor ß receptor signaling pathway', 'BMP signaling pathway', 'Wnt receptor signaling pathway', 'response to chemical stimulus', 'regulation of inflammatory response', 'response to stress', 'glycosaminoglycan binding', 'polysaccharide binding', 'extracellular matrix structural constituent' and 'growth factors binding'. Taken together, these findings led to the conclusion that different gene regulatory mechanisms exist between BPOP and osteochondroma. Environmental stimulation and inflammation may contribute to BPOP or osteochondroma, and differences in extracellular matrix may contribute to differences in biological characteristics between BPOP and osteochondroma.