Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

Objective:To construct a prior based on the inherent properties of PET to accurately segment the lesion areas.Methods:A network framework for PET tumor segmentation driven by geodesic priors was proposed (geodesic network for short). Specifically, partial differential equations were constructed to characterize the geodesic distances between different regions in PET images. Tumor marker points identified by CT labeling were used as the initial conditions for the equations. To enhance the contrast between areas of lung or breast tumors and normal tissues, a smooth Heaviside function was utilized to map the geodesic distances. The network framework adopted a dual-branch architecture, using geodesic priors to assist in PET image segmentation.Results:The proposed method achieved a Dice coefficient of 94.92% in lung cancer segmentation and 90.12% in breast cancer segmentation. With the addition of geodesic priors in the Unet, the Dice coefficient for breast cancer increased by 32.37% (from 42.50% to 74.87%).Conclusion:Geodesic priors can significantly improve segmentation outcomes and enhance the generalization capability of the network.

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

Objective:To construct a prior based on the inherent properties of PET to accurately segment the lesion areas.Methods:A network framework for PET tumor segmentation driven by geodesic priors was proposed (geodesic network for short). Specifically, partial differential equations were constructed to characterize the geodesic distances between different regions in PET images. Tumor marker points identified by CT labeling were used as the initial conditions for the equations. To enhance the contrast between areas of lung or breast tumors and normal tissues, a smooth Heaviside function was utilized to map the geodesic distances. The network framework adopted a dual-branch architecture, using geodesic priors to assist in PET image segmentation.Results:The proposed method achieved a Dice coefficient of 94.92% in lung cancer segmentation and 90.12% in breast cancer segmentation. With the addition of geodesic priors in the Unet, the Dice coefficient for breast cancer increased by 32.37% (from 42.50% to 74.87%).Conclusion:Geodesic priors can significantly improve segmentation outcomes and enhance the generalization capability of the network.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To observe the clinical effect and safety of edaravone and dexborneol concentrated solution for injection combined with rosuvastatin calcium capsules in the treatment of patients with acute posterior circulation cerebral infarction.Methods Patients with acute posterior circulation cerebral infarction were divided into control group and treatment group according to cohort method.The control group was treated with rosuvastatin calcium 5 mg,while the treatment group was treated with intravenous drip of edaravone and dexborneol concentrated solution for injection 15 mL on the basis of control group.The clinical effect,neurological function,biochemical indicators,oxidative stress response indicators,the levels of Toll like receptor 4/nuclear factor κB(TLR4/NF-κB)signaling pathway molecules,prognosis,and adverse drug reactions were compared between the two groups.Results There were 49 cases in control group and 51 cases in treatment group.After treatment,the total effective rates in treatment group and control group were 92.16％(47 cases/51 cases)and 77.55％(38 cases/49 cases),with statistically significant difference(P＜0.05).After treatment,the levels of neuron specific enolase in treatment group and control group were(11.67±1.35)and(16.77±1.94)μg·L-1;the levels of central nervous system-specific protein were(1.01±0.12)and(1.54±0.16)μg·L-1;the levels of low density lipoprotein cholesterol were(2.03±0.24)and(3.74±0.38)mmol·L-1;the levels of triglyceride were(1.28±0.14)and(2.12±0.23)mmol·L-1;the levels of total cholesterol were(3.11±0.32)and(4.15±0.42)mmol·L-1;the levels of creatine kinase isozyme were(8.76±1.02)and(10.12±1.06)U·L-1;the levels of high-sensitivity C-reactive protein were(11.01±1.25)and(15.32±1.64)mg·L-1;the levels of serum reactive oxygen species were(387.68±39.24)and(473.11±48.23)μmol·L-1;the levels of malondialdehyde were(3.02±0.39)and(4.14±0.45)nmol·mL-1;the levels of superoxide dismutase were(59.24±6.05)and(41.67±4.97)U·mL-1;the relative expression levels of TLR4 mRNA were 0.26±0.03 and 0.43±0.04;the relative expression levels of NF-KB mRNA were 0.17±0.02 and 0.25±0.03;the modified Rankin scale scores were 2.02±0.29 and 2.94±0.30;the activity of daily living scores were 56.34±5.74 and 45.64±4.69.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 31.37％and 26.53％,with no statistically significant difference between the two groups(P＞0.05).Conclusion Edaravone and dexborneol concentrated solution for injection combined with rosuvastatin calcium capsules is effective in the treatment of patients with acute posterior circulation cerebral infarction,and can effectively regulate the patients'neurological function,oxidative stress response,blood lipid levels and TLR4/NF-κB signaling pathway molecules,and significantly improve the prognosis.

Objective To observe the clinical effect and safety of camrelizumab combined with albumin-bound paclitaxel and cisplatin in preoperative neoadjuvant chemotherapy for patients with stage Ⅲa non-small cell lung cancer(NSCLC).Methods Patients with stage Ⅲ a NSCLC were divided into the treatment group and the control group.The control group was treated with intravenous infusion of 130 mg·m-2 of paclitaxel injection on day 1 and day 8,and intravenous infusion of 75 mg·m-2 of cisplatin injection on day 1.In addition to the treatment of control group,the treatment group was treated with intravenous infusion of 200 mg of camrelizumab injection on day 1.Both groups were given 2 cycles of treatment.Clinical efficacy,tumor markers,tumor metastasis markers,T lymphocyte subsets,and safety were compared between the two groups.Results After treatment,the objective remission rate(ORR)of the treatment group and the control group was 69.64％(39 cases/56 cases)and 38.98％(23 cases/59 cases),respectively;the disease control rate(DCR)was 89.29％(50 cases/56 cases)and 72.88％(43 cases/59 cases),respectively;cytokeratin-19-fragment(Cyfra21-1)levels were(3.47±0.86)and(4.01±1.24)ng·mL-1;carcinoembryonic antigen(CEA)levels were(4.55±0.93)and(5.26±1.04)ng·mL-1;neuron-specific enolase(NSE)levels were(16.38±2.51)and(19.02±2.95)ng·mL-1;basic fibroblast growth factor(bFGF)levels were(15.82±2.34)and(18.64±2.59)μg·L-1;carbohydrate antigen 15-3(CA15-3)levels were(22.54±3.10)and(29.41±3.82)ng·mL-1;CD4+/CD8+were 1.42±0.51 and 1.30±0.32.The above indexes were significantly different between the control group and the treatment group(all P＜0.05).The adverse drug reactions in the treatment group and the control group were mainly neutropenia,thrombocytopenia,alopecia,gastrointestinal reaction and radiation pneumonia.There were no significant difference in the incidence of adverse drug reactions between the two groups(all P＞0.05).Conclusion Camrelizumab combined with albumin-bound paclitaxel and cisplatin is effective in the treatment of patients with stage Ⅲa NSCLC.

Inertial microfluidics,as a microfluidic technology with the ability to precisely manipulate particles and cells with high throughput,has attracted widespread attention.However,challenges remain in achieving particle focusing with insensitivity to flow rates in large-scale channels,mainly due to the instability of secondary flows within the inertial microfluidic chip.This study developed a microstructure-assisted ultra-low aspect ratio spiral microchannel,which utilized the stability and acceleration of secondary flows to achieve inertial particle focusing.The research results demonstrated successful particle focusing within a 1 mm-wide spiral channel chip,for different diameter sizes(7.3 μm and 15.5 μm),within a wide range of flow rates(0.5-3 mL/min).The focusing efficiencies for these particles were measured to be above 94%and 99%,respectively.Additionally,it was observed that the particle focusing position was approximately 100 μm away from the channel walls,significantly larger than other inertial focusing chips.Consequently,by incorporating ordered microstructures within the spiral channel chip,the stability and enhancement of secondary flows were achieved,resulting in flow rate and particle size-insensitive inertial focusing.Compared to traditional methods of inertial focusing,this design had advantages of not requiring additional sheath flow operations,and boasted high throughput and ease of manufacturing.This innovative structure opened up vast prospects for the development of portable inertial microfluidic chips,and could be used in the fields such as cell analysis and detection,flow cytometry,and online sample processing.