Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

OBJECTIVE: To construct a longitudinal trajectory model of arterial oxygen tension (PaO₂) within 24 hours after cardiac arrest (CA). METHODS: A retrospective cohort study was conducted. CA patients admitted to the ICU from 2014 to 2015 were selected from the eICU Collaborative Research Database (eICU-CRD). Data about patients' demographic characteristics, history of comorbidities, laboratory test indicators within 24 hours of intensive care unit (ICU) admission [including all PaO₂ data and arterial carbon dioxide tension (PaCO₂)], vasopressor use, and clinical outcomes were extracted from the database. The primary outcome variable was all-cause in-hospital mortality. Group-based trajectory model (GBTM) were built based on the changes in PaO₂ within 24 hours of ICU admission, and patients were grouped according to their initial static PaO₂ values upon ICU admission. Multivariable adjusted Poisson regression analysis was used to compare the in-hospital mortality risk among patients in different PaO₂ dynamic trajectory groups. Sensitivity analyses were performed using multivariable logistic regression and multivariable adjusted Poisson regression without imputation of missing values. RESULTS: A total of 3 866 CA patients were included. Three GBTM trajectory groups were identified based on PaO₂ changes within 24 hours of ICU admission: Group-1 (low level first increased then decreased, 148 cases), Group-2 (sustained low level, 3 040 cases), and Group-3 (first high level then decreased, 678 cases). Significant differences were found among the three groups in age, body weight, maximum serum potassium, maximum PaCO₂, minimum hemoglobin (Hb), vasopressor use, total hospitalization time, ICU stay, and hospital mortality. After incorporating variables with significant differences into the multivariable adjusted Poisson regression model, results showed that compared to Group-2 patients, patients in Group-1 and Group-3 had an increased risk of all-cause in-hospital mortality [Group-1 adjusted relative risk (aRR) = 1.20, 95% confidence interval (95%CI) was 1.02-1.41; Group-3 aRR = 1.11, 95%CI was 1.01-1.24]. Based on initial static PaO₂ values at ICU admission, patients were divided into four groups: PaO₂ < 100 mmHg (1 mmHg = 0.133 kPa; 1 217 cases), PaO₂ 100-200 mmHg (569 cases), PaO₂ 201-300 mmHg (547 cases), and PaO₂ > 300 mmHg (1 082 cases). Multivariable adjusted Poisson regression analysis indicated a significant upward trend in aRR for the latter three groups compared to the PaO₂ < 100 mmHg group. Sensitivity analyses revealed that compared to Group-2, patients in Group-1 and Group-3 had a significantly increased risk of all-cause in-hospital mortality (both P < 0.05). CONCLUSIONS Within 24 hours after return of spontaneous circulation in CA patients, PaO₂ exhibits different dynamic trajectories, and patients with hyperoxia have an increased risk of in-hospital mortality.
Humans ; Retrospective Studies ; Hospital Mortality ; Heart Arrest/blood* ; Prognosis ; Oxygen/blood* ; Intensive Care Units ; Cardiopulmonary Resuscitation ; Male ; Female ; Middle Aged

Objective:To investigate the current status of occupational stress among electronic manufacturing workers in Qingdao and analyze its effect on depressive symptoms and anxiety symptoms.Methods:From July to September 2022, a cluster random sampling method was employed to select frontline workers from 14 electronic manufacturing enterprises in Qingdao as the study subjects. A total of 1134 questionnaires were distributed, with 1000 valid questionnaires collected, yielding an effective response rate of 88.18%. The Core Occupational Stress Scale (COSS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were adopted to assess occupational stress, depressive symptoms, and anxiety symptoms, respectively. Binary logistic regression was employed to analyze influencing factors of occupational stress and its effects on depressive and anxiety symptoms.Results:The detection rates of occupational stress, depressive symptoms, and anxiety symptoms were 15.1% (15/1000), 7.9% (79/1000), and 13.8% (138/1000), respectively. The influencing factor analysis of occupational stress revealed that female gender ( OR=0.621, 95% CI: 0.434-0.890) and weekly working hours of 45-48 hours ( OR=0.537, 95% CI: 0.309-0.935) were protective factors ( P<0.05), while weekly working hours ≥55 hours ( OR=2.176, 95% CI: 1.290-3.670) and shift work ( OR=2.038, 95% CI: 1.412-2.940) were risk factors ( P<0.05). Spearman correlation analysis showed that the COSS score was positively related with the PHQ-9 score and the GAD-7 score ( rs=0.438, 0.289, P<0.01). Workers judged with occupational stress had 3.596 times (95% CI: 2.181-5.931, P<0.001) and 3.121 times (95% CI: 2.046-4.761, P<0.001) higher risks of detecting depressive and anxiety symptoms compared to those without occupational stress. Conclusion:Electronic manufacturing workers in Qingdao experience a certain level of occupational stress, which may increase the risk of developing depressive and anxiety symptoms. Enterprises should implement appropriate interventions to promote workers' mental health.

BACKGROUND:With the popularization of implant technology,the incidence of peri-implantitis is increasing year by year,but the etiological mechanism is still unclear.Highly plastic macrophages can be polarized into M1 and M2 types under microenvironment stimulation,which play pro-inflammatory and anti-inflammatory effects,respectively,and play an important role in host defense,immune response,and maintenance of internal environment homeostasis in peri-implant tissues.The polarization trend of M1/M2 macrophages is closely related to the balance of foreign body response around implants.OBJECTIVE:Lipopolysaccharide and titanium particles are important pathogenic factors causing peri-implantitis,in order to further explore their inducible effect on macrophage polarization in peri-implant tissues.METHODS:The Chinese keywords were"peri-implantitis,macrophage polarization,lipopolysaccharide,titanium particles."The English keywords were"macrophage polarization,peri-implant inflammation,peri-implantitis,LPS,TLRs,NF-κB."The CNKI and PubMed databases were searched,and the relevant literature was screened and sorted to analyze the induction effect and related mechanism of lipopolysaccharide and titanium particles on M1/M2 polarization of macrophages in peri-implant tissues.RESULTS AND CONCLUSION:(1)Lipopolysaccharide and titanium particles may induce macrophage polarization in peri-implant tissues through Toll-like receptor/nuclear factor κB and other related signaling pathways,causing M1/M2 polarization imbalance and thus affecting the occurrence and progression of peri-implantitis.Some drugs can also regulate macrophage M1/M2 polarization through Toll-like receptor/nuclear factor κB signaling pathway to treat related inflammatory diseases.(2)By analyzing the induction effect of lipopolysaccharide and titanium particles on macrophage M1/M2 polarization in peri-implant tissues,the mechanism of their regulation of Toll-like receptor/nuclear factor κB signaling pathway to induce macrophage polarization is further explained,in order to provide some new ideas and strategies for the study of immune prevention and treatment of peri-implantitis.

Objective:To investigate the current status of occupational stress among electronic manufacturing workers in Qingdao and analyze its effect on depressive symptoms and anxiety symptoms.Methods:From July to September 2022, a cluster random sampling method was employed to select frontline workers from 14 electronic manufacturing enterprises in Qingdao as the study subjects. A total of 1134 questionnaires were distributed, with 1000 valid questionnaires collected, yielding an effective response rate of 88.18%. The Core Occupational Stress Scale (COSS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were adopted to assess occupational stress, depressive symptoms, and anxiety symptoms, respectively. Binary logistic regression was employed to analyze influencing factors of occupational stress and its effects on depressive and anxiety symptoms.Results:The detection rates of occupational stress, depressive symptoms, and anxiety symptoms were 15.1% (15/1000), 7.9% (79/1000), and 13.8% (138/1000), respectively. The influencing factor analysis of occupational stress revealed that female gender ( OR=0.621, 95% CI: 0.434-0.890) and weekly working hours of 45-48 hours ( OR=0.537, 95% CI: 0.309-0.935) were protective factors ( P<0.05), while weekly working hours ≥55 hours ( OR=2.176, 95% CI: 1.290-3.670) and shift work ( OR=2.038, 95% CI: 1.412-2.940) were risk factors ( P<0.05). Spearman correlation analysis showed that the COSS score was positively related with the PHQ-9 score and the GAD-7 score ( rs=0.438, 0.289, P<0.01). Workers judged with occupational stress had 3.596 times (95% CI: 2.181-5.931, P<0.001) and 3.121 times (95% CI: 2.046-4.761, P<0.001) higher risks of detecting depressive and anxiety symptoms compared to those without occupational stress. Conclusion:Electronic manufacturing workers in Qingdao experience a certain level of occupational stress, which may increase the risk of developing depressive and anxiety symptoms. Enterprises should implement appropriate interventions to promote workers' mental health.

BACKGROUND:With the popularization of implant technology,the incidence of peri-implantitis is increasing year by year,but the etiological mechanism is still unclear.Highly plastic macrophages can be polarized into M1 and M2 types under microenvironment stimulation,which play pro-inflammatory and anti-inflammatory effects,respectively,and play an important role in host defense,immune response,and maintenance of internal environment homeostasis in peri-implant tissues.The polarization trend of M1/M2 macrophages is closely related to the balance of foreign body response around implants.OBJECTIVE:Lipopolysaccharide and titanium particles are important pathogenic factors causing peri-implantitis,in order to further explore their inducible effect on macrophage polarization in peri-implant tissues.METHODS:The Chinese keywords were"peri-implantitis,macrophage polarization,lipopolysaccharide,titanium particles."The English keywords were"macrophage polarization,peri-implant inflammation,peri-implantitis,LPS,TLRs,NF-κB."The CNKI and PubMed databases were searched,and the relevant literature was screened and sorted to analyze the induction effect and related mechanism of lipopolysaccharide and titanium particles on M1/M2 polarization of macrophages in peri-implant tissues.RESULTS AND CONCLUSION:(1)Lipopolysaccharide and titanium particles may induce macrophage polarization in peri-implant tissues through Toll-like receptor/nuclear factor κB and other related signaling pathways,causing M1/M2 polarization imbalance and thus affecting the occurrence and progression of peri-implantitis.Some drugs can also regulate macrophage M1/M2 polarization through Toll-like receptor/nuclear factor κB signaling pathway to treat related inflammatory diseases.(2)By analyzing the induction effect of lipopolysaccharide and titanium particles on macrophage M1/M2 polarization in peri-implant tissues,the mechanism of their regulation of Toll-like receptor/nuclear factor κB signaling pathway to induce macrophage polarization is further explained,in order to provide some new ideas and strategies for the study of immune prevention and treatment of peri-implantitis.

Oral inflammatory diseases caused by odontogenic infections cover a wide range and have a high incidence rate,which can affect the morphology and function of the maxillofacial area and seriously en-danger oral health.Macrophages are important immunoactive cells in oral tissues,which can be polarized into M1/M2 type in different microenvironments,and then exert pro-inflammatory or anti-inflammatory effects,and are widely involved in the progression of odontogenic infectious diseases.In infections caused by oral mi-crobial factors such as bacteria,the distribution characteristics and polarization direction of macrophages in tis-sues are specific.At present,the research on macrophage polarization-related inflammatory diseases has attrac-ted more and more attention,and the regulation of macrophage M1/M2 polarization is gradually being used in the treatment of related diseases,and many research progress has been made in the diagnosis and treatment of odontogenic infectious diseases.In this paper,we elaborate on the distribution characteristics,polarization trends and related applications of macrophage polarization in common oral inflammatory diseases such as pul-pitis,apical periodontitis,periodontitis and peri-implantitis which are mainly caused by dental infections.The aim is to provide new ideas and targets for the diagnosis and treatment of oral inflammatory diseases.

Objective To investigate the prognostic value of red cell distribution width(RDW)on neurological prognosis in patients with cardiac arrest(CA).Methods Retrospective analysis the case data,RDW and biochemical indicators of 107 CA patients treated in our department(January 2020 to November 2023).According to cerebral performance category(CPC),patients were divided into good neurological prognosis group and bad neurological prognosis group.The differences in clinical data and RDW between the two groups were compared.Multivariate Logistic regression analysis was used to investigate the risk factors on neurological prognosis.Predictive effect of RDW on poor neurological prognosis in CA patients was assessed by receiver operating characteristic(ROC)curve.According to the optimal cut-off value of RDW,it was divided into high RDW group(≥ 13.45％)and low RDW group(＜13.45％)to compare the incidence of poor neurological prognosis.Results Totally 107 CA patients were included,34 patients in the good neurological prognosis group and 73 patients in the bad neurological prognosis group,the incidence of poor prognosis of neurological function was 68.22％.Compared with good neurological prognosis group,the acute physiology and chronic health evaluation Ⅱ score,RDW,cardiopulmonary resuscitation(CPR)time,age,serum sodium and glutamic-pyruvic transaminase in bad neurological prognosis group were significantly increased(P＜0.05).Multivariate Logistic regression analysis showed that RDW,age and CPR time were independent risk factors for poor prognosis of neurological function(P＜0.05).ROC curve analysis showed that the area under the curve of RDW to predict poor neural function prognosis in CA patients was 0.766.When the optimal threshold of RDW was 13.45％,the sensitivity was 73％and the specificity was 71％.The incidence of poor prognosis of neurological function in high RDW group was 84.13％,which was significantly higher than 45.45％in low RDW group(P＜0.05).Conclusion Elevated RDW is an independent risk factor for increased risk of poor neurological outcomes in patients with CA.It has certain predictive value for neurological outcomes in patients with CA.

Chemical pollution-induced damage to ecosystem function has been a global challenge.The latest"Kunming-Montreal Global Biodiversity Framework"proposed reducing pollution risks to levels harmless to biodiversity and function,placing higher demands on chemical risk management at the ecosystem level.Conventional ecotoxicity tests have focused on single species,only to neglect genetic diversity protection and simplify species interactions.Here,we proposed using environmental RNA(eRNA)and metatranscriptomic analysis to establish a multi-species,multi-biological level chemical pollution ecological risk assessment approach in exposed communities.We reviewed the current status and trends of eRNA in chemical pollution risk assessment and proposed a strategy for bioeffect testing from molecules to communities based on eRNA,constructing ecological risk assessment models for different protection goals.Finally,we summarized the theoretical and technical challenges facing eRNA-based toxicity testing and outlined the future applications of eRNA in capturing real ecological effects of chemical pollution in the field.

Objective To evaluate the value of red cell volume distribution width(RDW)in the prognosis of patients with cardiac arrest(CA).Methods Clinical data of 146 CA patients admitted to intensive care unit(ICU)of Huzhou Central Hospital from January 2018 to October 2022 were retrospectively analyzed,and the patients were divided into survival group and death group according to the prognosis during ICU stay.The clinical data of two groups were compared,and the risk factors affecting the prognosis of CA patients were analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of RDW in CA patients.The survival curve was plotted by Kaplan-Meier method.Results A total of 146 CA patients were included in the analysis,among which 49 patients survived and 97 patients died,the mortality rate of CA patients in ICU was 66.44%.The scores of acute physiology and chronic health evaluation Ⅱ,RDW,blood sodium and alanine aminotransferase in death group were significantly higher than those in survival group,the time of cardiopulmonary resuscitation was significantly longer than that in survival group,and the length of ICU stay was significantly shorter than that in survival group(P<0.05).Multivariate Logistic regression analysis showed that RDW and time of cardiopulmonary resuscitation were independent risk factors for predicting death during ICU stay in CA patients(P<0.05).ROC curve results showed that RDW predicted death in CA patients with the area under curve of 0.742,the best cut-off value was 13.95%,the sensitivity was 59.8%,and the specificity was 85.7%.Patients with low RDW had significantly higher one-year cumulative survival rate than those with high RDW(χ2=18.757,P<0.001).Conclusion RDW was an independent risk factor for predicting death during ICU stay in CA patients.