Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

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.

OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1

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.

Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Objective To investigate the efficacy and safety of tenofovir alafenamide fumarate(TAF)in the treatment of patients with decompensated hepatitis B cirrhosis.Methods We retrospective analyzed 41 patients with decompensated hepatitis B cirrhosis receiving TAF antiviral therapy for 24 weeks at Wuwei Tumor Hospital in Gansu province from June 2022 to June 2023.Primary endpoint was proportion of patients achieving virologic response(HBV DNA<20 IU/mL).Other endpoints included changes in ALT,AST,TBIL,Child-Pugh score(CTP),and MELD score from baseline to week 24.In terms of safety,changes in Scr,eGFR and adverse events from baseline to week 24 were observed.Results Of 41 patients,73.2%were male(n = 30),with mean age of 53.49 years.24 weeks after treatment with TAF,HBV DNA was undetectable in 90.2%of the patients.The median levels of ALT,AST and total bilirubin(TBIL)were 50.70 U/L,48.70 U/L and 26.40 μmol/L respectively at base-line,and reduced significantly to 31.50 U/L,37.8 U/L and 23.8 μmol/L(P<0.05)respectively after 24-week therapy with TAF.CTP score was improved in 58.6%of the patients(n = 24),and so was MELD score in 63.4%of the patients(n = 26)at week 24.The median serum creatinine and eGFR were 58.5 μmol/L and 106.15 mL/(min·1.73 m2)respectively at baseline,and creatinine and eGFR were stable during treatment.No drug-related adverse events or severe adverse events occurred during treatment,neither did creatinine and eGFR liver transplan-tation,HCC or death.Conclusions Our clinical studies demonstrated better effectiveness and safety of TAF for decompensated CHB patients.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

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