Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective: To explore the relationship between dietary behavior, dietary frequency and central precocious puberty (CPP) among children in Wuhan, so as to provide a scientific basis for elucidating the possible and related dietary factors leading to precocious puberty. Methods: From February to December 2023, 100 children with CPP and 100 healthy children were collected in Wuhan Children s Hospital for a case control study. Questionnaires and interviews were used to collect demographic information, child lifestyle, as well as dietary behavior and dietary frequency in the past six months. Conditional Logistic regression model was used to analyze the relationship of children s dietary behavior and dietary frequency with CPP. Results: No associations were found between three dietary behavior, including emotional eating, restrictive eating, and external eating, with CPP at baseline ( P >0.05). In the association analysis of dietary frequency and CPP, the risk of CPP was higher in those who consumed red meat >5 times/week ( OR =1.93, 95% CI =1.01-3.68), carbonated beverages ≥4 times/month ( OR =2.70, 95% CI =1.03-7.08), fruit juices ≥4 times/month ( OR =2.31, 95% CI =1.02-5.25), and nutritional supplementation ( OR =2.77, 95% CI =1.47- 5.22 ), whereas the risk of CPP was lower in those who consumed nuts ≥4 times/month ( OR =0.21, 95% CI =0.08-0.57) ( P < 0.05 ). Conclusion Consumption of higher amounts of red meat, high frequency of carbonated and juice based sugary drinks, and nutrient supplementation may be contributing factors to the development of CPP, whereas regular consumption of nuts is less likely to be associated with the development of CPP.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

Background and objective Both of lung cancer incidence and mortality rank first among all cancers in China.Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers.Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia.This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer.Methods Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography(LDCT)for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography(2018 version).The detection rate of positive nodules was calculated.Before the LDCT examination,residents were required to complete a"lung cancer risk factors questionnaire".The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator(LASSO)penalized Logistic regression analysis.Results A total of 6256 residents were included in this study.1228 positive nodules(19.63％)and 117 lung cancers were confirmed,including 6 cases of Tis,103 cases of stage Ⅰ(accounting for 88.03％of lung cancer).The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr(OR=1.07,95％CI:1.06-1.07),history of cancer(OR=3.29,95％CI:3.22-3.37),textile industry(OR=1.10,95％CI:1.08-1.13),use coal for cooking in childhood(OR=1.14,95％CI:1.13-1.16)and food al-lergy(OR=1.10,95％CI:1.07-1.13)were risk factors of lung cancer for female in this district.Conclusion This study highlighted that numerous early stages of lung cancer cases were detected by LDCT,which could be applied to screen-ing of lung cancer in women.Besides,age ≥50 yr,personal history of cancer,textile industry and use coal for cooking in childhood are risk factors for women in this district,which suggested that it's high time to raise the awareness of early lung cancer screening in this group.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

Objective:To use three-dimensional (3D) scanning to measure the preoperative and postoperative nasal parameters of the patients received rhinoplasty with ear cartilage and silicone prosthesis, and to evaluate the clinical effect of the surgery.Methods:Sixteen female patients with an average age of 28.3 years, ranged from 21 to 35 years, received rhinoplasty with ear cartilage and silicone prosthesis in Wuhan Tongji Hospital from June 2018 to February 2019. Preoperative and postoperative 3D scanning was performed to measure nasal parameters, including linear length, angle, and proportional index.Results:All patients were satisfied with the postoperative outcomes. The postoperative nasal length, nasal height, and nasal depth increased significantly, and the postoperative nasal width and nasal tip width decreased. The postoperative nasolabial angle and nasofrontal angle were statistically improved, while the preoperative and postoperative data of columellar facial angle, nasal tip angle, and nasal column-lobular angle were not significantly different. The ratios of nasal depth and nasal width, nasal index and nasal tip protrusion were improved after surgery, while the postoperative ratios of nasal columella and nasal lobules length were not statistically improved.Conclusions:The 3D scanning allows for comprehensive and accurate measurement of the nasal parameters. The rhinoplasty with ear cartilage and silicone prosthesis is more effective in improving the overall contour of the nose, but less effective in improving the aesthetics of the nasal tip.

Objective To investigate the methods and therapeutic effects of anterolateral thigh perforator free flaps for reconstruction of soft tissue defects around the ankle.Methods A retrospective case series study was made on 30 patients treated with anterolateral thigh perforator free flaps for traumatic soft tissue defects around the tibia between January 2010 and June 2016.There were 22 males and eight females,with the age range of 16-58 years [(41.5 ± 1.2) years].Dimension of the soft tissue defect ranged from 9 cm ×4 cm to 23 cm × 12 cm.Flap stabilization time,flap survival rate,postoperative complications,second plastic surgery rate,and ankle joint function by Baird-Jackson score were recorded.Results All patients were followed up for (13.0 ± 5.4) months (range,6-24 months).Time for flap stabilization was (6.5 ± 1.1) days.All flaps survived except in one patients with flap loss due to postoperative arterial thrombosis.Postoperatively,one patient had arterial crisis,one had venous thrombosis,and one presented sinus formation due to infection.No second plastic surgery was carried out.According to the Baird-Jackson score,the results were excellent in 25 patients and good in five.Conclusion Anterolateral thigh perforator free flaps for reconstruction of traumatic soft tissue defects around the tibia has advantages of easy harvesting and survival,less postoperative complications,less second surgery,and good function recovery.

Objective To compare the outcomes of endovascular treatment between intracranial large artery atherosclerosis stroke (LAA) and cardioembolic stroke (CE) in Chinese patients with acute anterior circulation ischemic stroke.Methods Patients with acute anterior circulation ischemic stroke treated with the Solitaire stent retriever were enrolled.The patients were divided into either a LAA group or a CE group according to etiological subtype.The outcomes were compared between 2 groups.Multivariable logistic regression analysis was used to determine the independent risk factors for poor outcome (defined as the modified Rankin Scale score ＞2 at 90 d after onset).Results A total of 126 patients were enrolled in the study,including 62 (49.2％) in the LAA group and 64 (50.8％) in the CE group.The proportions of poor outcome at 90 d (59.0％ vs.41.0％;x2 =5.482,P =0.019) and symptomatic intracerebral hemorrhage at 72 h (12.5％ vs.1.6％;Fisher exact test P =0.033) in the CE group were significantly higher than those in the LAA group.Multivariate logistic regression analysis showed that high baseline National Institutes of Health Stroke Scale scores was independently associated with poor outcome (odds ratio [OR] 1.119,95％ confidence interval [CI] 1.026-1.221;P =0.011),good collateral circulation was was independently associated with good outcome (OR 0.227,95％ CI 0.097-0.788;P =0.016),and etiological subtype was not independently associated with outcome (OR 1.280,95％ CI O.454-3.633;P =0.630).Conclusion Etiological subtype is not associated with outcome in patients with acute anterior circulation ischemic stroke treated with the Sofitaire stent retriever.

BACKGROUND AND PURPOSE: External counterpulsation (ECP) is a noninvasive method used to enhance cerebral perfusion by elevating the blood pressure in ischemic stroke. However, the response of the beat-to-beat blood pressure variability (BPV) in ischemic stroke patients during ECP remains unknown. METHODS: We enrolled recent ischemic stroke patients and healthy controls. Changes in the blood flow velocities in bilateral middle cerebral arteries and the continuous beat-to-beat blood pressure before, during, and after ECP were monitored. Power spectral analysis revealed that the BPV included oscillations at very low frequency (VLF; <0.04 Hz), low frequency (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.40 Hz), and the total power spectral density (TP; <0.40 Hz) and LF/HF ratio were calculated. RESULTS: We found that ECP significantly increased the systolic and diastolic blood pressures in both stroke patients and controls. ECP decreased markedly the systolic and diastolic BPVs at VLF and LF and the TP, and the diastolic BPV at HF when compared with baseline. The decreases in diastolic and systolic BPV reached 37.56% and 23.20%, respectively, at VLF, 21.15% and 12.19% at LF, 8.76% and 16.59% at HF, and 31.92% and 23.62% for the total TP in stroke patients, which did not differ from those in healthy controls. The change in flow velocity on the contralateral side was positively correlated with the total TP systolic BPV change induced by ECP (r=0.312, p=0.035). CONCLUSIONS: ECP reduces the beat-to-beat BPV when increasing the blood pressure and cerebral blood flow velocity in ischemic stroke patients. ECP might be able to improve the clinical outcome by decreasing the beat-to-beat BPV in stroke patients, and this should be explored further in future studies.
Blood Flow Velocity ; Blood Pressure* ; Cerebrovascular Circulation* ; Counterpulsation* ; Humans ; Methods ; Middle Cerebral Artery ; Perfusion ; Stroke*