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 evaluate the early efficacy of local application of tranexamic acid on the osteotomy surface during hallux valgus surgery in reducing postoperative occult blood loss and thus postoperative swelling. METHODS: The data of 40 cases with hallux valgus osteotomy admitted to the Department of Foot and Ankle Surgery of Jishuitan Hospital from July 11, 2022 to October 8, 2022, including 5 males and 35 females were retrospectively analyzed. According to the inclusion and exclusion criteria, 32 cases were finally divided into 16 cases in the observation group (application of tranexamic acid) and 16 cases in the control group (no application of tranexamic acid). The observation group was paired with the control group one by one in accordance with the operation style, and the change in the anterior and posterior diameter of the first metatarsal head, the change in the circumferential diameter of the foot, the length of the first metatarsal midline and the length of the plumbline of the foot measured by postoperative CT were compared between the two groups before and after surgery, in order to evaluate the degree of swelling around the incision after the surgery. The first metatarsal midline and plumb line were measured by reference to the two auxiliary lines that intersect the soft tissue border in the sesamoid bone position to measure the rotation angle of the first metatarsal. A total of three clinicians completed the measurements of these two line segments and interobserver comparisons were performed. RESULTS: By interobserver comparison, the consistency of the length of the midline of the first metatarsal and the plumbline measured by CT was high and could be considered a reliable measurement. After the paired t-test, there was no statistical difference in the amount of changes in the anteroposterior diameter of the first metatarsal before and after surgery between the observation and control groups (P>0.05), and the amount of changes in the circumferential diameter of the foot before and after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05); the length of the midline of the first metatarsal and the plumbline of the foot measured by CT after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05). CONCLUSION Local application of tranexamic acid on the osteotomy surface during hallux valgus osteotomy can relieve postoperative swelling to some extent, which may be related to the fact that tranexamic acid reduces occult blood loss in the postoperative period.
Humans ; Hallux Valgus/surgery* ; Tranexamic Acid/administration & dosage* ; Female ; Male ; Osteotomy/adverse effects* ; Retrospective Studies ; Edema/etiology* ; Adult ; Middle Aged ; Postoperative Complications/prevention & control* ; Antifibrinolytic Agents/administration & dosage*

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

The production of healthy agricultural products has increased the demand for innovative and sustainable plant protection technologies, and the rapid advancement of nanotechnology has brought revolutionary breakthroughs to traditional agriculture. Nanocarrier-based drug delivery systems can not only significantly improve the utilization efficiency of pesticides, achieving enhanced efficacy and reduced application, but also decrease the pesticide residues and environmental pollution. Additionally, they have made breakthrough progress in the stability and persistence of RNA pesticides. This review summarized the research progress on nanopesticides and RNA pesticides, focusing on the mechanisms of nanocarriers in improving pesticide bioactivity and RNA interference (RNAi) efficiency. It also systematically summarized the types of nanomaterials and their applications in pest and disease management and provided an in-depth outlook for the future development of nanopesticides and RNA pesticides, which provided technical support for the high-quality development of agriculture in the future.
Pesticides/chemistry* ; Nanotechnology ; Nanostructures ; RNA ; Agriculture/methods* ; RNA Interference ; Drug Delivery Systems

Objective : Based on glycolysis of hypoxia inducible factor-1α(HIF-1α)/Bcl2/adenovirus E1B interacting protein 3(BNIP3) pathway, to study the mechanism of oxygen-induced retinal angiogenesis in neonatal mice. Methods : Human umbilical vein endothelial cells(HUVECs) were divided into normoxic group, hypoxia+si-NC group, hypoxia +si-HIF-1α group and hypoxia+si-HIF-1α+BNIP group. In normoxic group, HUVECs were exposed to normoxic(21% O2) and cultured. Hypoxia +si-NC group, hypoxia +si-HIF-1α group and hypoxia +si-HIF-1α+BNIP3 group were treated with si-NC, si-HIF-1α or si-HIF-1α combined with BNIP3 plasmid for 36 h, and then exposed to hypoxia(1% O2) for culture. The autophagy, glycolysis, proliferation, migration and tube formation of mitochondria were investigated by immunofluorescence, metabolic measurement, cell viability, scratch experiment and tube formation experiment. On the 7th day after birth, C57BL/6J mice were randomly assigned to different treatment groups: control group, oxygen-induced retinopathy(OIR) group, OIR+si-HIF-1α group and OIR+si-BNIP group. The neovascularization and vascular occlusion were measured. Results: Compared with normoxic group, the rate of LC3+MitoTracker+ spots, glucose uptake and lactic acid release in HUVECs in hypoxia +si-NC group increased significantly(P<0.001). Compared with hypoxia +si-NC group, the rate of LC3+MitoTracker+ spots, glucose uptake and lactic acid release in HUVECs in hypoxia +si-HIF-1α group decreased significantly(P<0.01). Compared with normoxic group, the proliferation activity of HUVECs in hypoxia +si-NC group decreased significantly(P<0.05), and the wound healing area and the number of tubes formed increased significantly(P<0.01). Compared with hypoxia+si-NC group, the proliferation activity of HUVECs in hypoxia +si-HIF-1α group decreased significantly at the 24th, 48th and 72th hours of culture(P<0.05), and the wound healing area and the number of tubes formed decreased significantly(P<0.001). Overexpression of BNIP3 reversed the effects of HIF-1α knock-down on mitochondrial autophagy, glycolysis and biological function. Compared with OIR group, the neovascularization and vascular occlusion areas in retina of mice in OIR+si-HIF-1α group and OIR+si-BNIP3 group reduced significantly(P<0.05). Conclusion HIF-1α/BNIP3 signaling pathway promotes mitochondrial autophagy activation in HUVECs under hypoxia, which plays an important role in controlling endothelial function and angiogenesis.

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Objectives:To explore the relationship between insomnia symptoms and neuroticism in patients with COVID-19,and to explore the role of anxiety and psychological capital in the relationship.Methods:Totally 687 patients with COVID-19 were recruited from Shanghai Fangcang Hospital.The Athens Insomnia Scale(AIS),Eysenck Personality Questionnaire-Revised Short Scale for Chinese Neuroticism Subscale(EPQ-RSC-N),Self-Rat-ing Anxiety Scale(SAS)and Psychological Capital Questionnaire(PCQ)were used to measure insomnia symp-toms,neuroticism personality trait,anxiety symptoms and psychological capital levels.The deviation-corrected per-centile Bootstrap method was used to test the mediating effect,and the PROCESS program was used to test the moderated effect.Results:The detection rate of insomnia symptoms was 49.93％.The AIS scores were lower in male patients than in female patients(P＜0.01).The SAS scores partly mediated the relationship between neuroti-cism scores and AIS scores,with an effect size of 0.03,accounting for 18.29％of the total effect.With the im-provement of PCQ scores,the predictive effect of SAS scores on AIS scores gradually decreased(β=-0.01,t=-4.41,P＜0.001).Conclusions:Anxiety symptoms in patients with COVID-19 play a partial mediating role in the positive relationship between insomnia symptoms and neuroticism.The psychological capital moderates the relation-ship between insomnia and anxiety symptoms.

Objective:To analyze the clinical data of patients with end-stage ankle and hindfoot ar-thropathy who underwent tibiotalocalcaneal(TTC)arthrodesis by the same surgeon,explore the short-and mid-term clinical results,complications and functional improvement,and discuss the clinical progno-sis and precautions of TTC arthrodesis.Methods:Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020.In this study,23 males and 17 females were included,with an average age of(49.1±16.0)years.All the patients underwent unilateral surgery.The clinical characteristics,imaging manifestations,main diagno-sis and specific surgical techniques of the patients were recorded.The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score and visual analogue scale(VAS)between pre-operation and at the last follow-up.The fusion healing time,symptom improvement(significant improvement,certain improvement,no improvement or deterioration)and postoperative complications were also recorded.Results:The median follow-up time was 38.0(26.3,58.8)months.The preoperative VAS score was 6.0(4.0,7.0),and the AOFAS score was 33.0(25.3,47.3).At the last follow-up,the median VAS score was 0(0,3.0),and the AOFAS score was 80.0(59.0,84.0).All the significantly improved compared with their preoperative corre-sponding values(P＜0.05).There was no wound necrosis or infection in the patients.One patient suf-fered from subtalar joint nonunion,which was syphilitic Charcot arthropathy.The median bony healing time of other patients was 15.0(12.0,20.0)weeks.Among the included patients,there were 25 cases with significant improvement in symptom compared with that preoperative,8 cases with certain improve-ment,4 cases with no improvement,and 3 cases with worse symptoms than that before operation.Con-clusion:TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot ar-thropathy.The function of most patients was improved postoperatively,with little impact on daily life.The causes of poor prognosis included toe stiffness,stress concentration in adjacent knee joints,nonunion and pain of unknown causes.