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 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 develop and validate a risk model of postoperative 3-year all-cause mortality for the elderly patients with hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 325 elderly patients with hip fracture who had been treated at The Fourth Medical Center, The General Hospital of PLA from January 2020 to December 2021. There were 90 men and 235 women with an age of (80.9±8.9) years, and 191 intertrochanteric fractures and 134 femoral neck fractures. The patients with hip fractures admitted from January 2020 to June 2021 were assigned to a modeling group (244 cases), and those admitted from July to December 2021 to a validation group (81 cases). Recorded were age, gender, fracture type, pre-injury disease, hematological indicators, time from injury to surgery, previous use of anticoagulant drugs, bone density, American Society of Anesthesiologists (ASA) grading, body mass index, and blood transfusion volume in the 2 groups of patients. The data in the modeling group were used to screen the independent risk factors for the postoperative 3-year all-cause mortality in the elderly patients with hip fracture through logistic regression analysis and receiver operating characteristic (ROC) curve analysis and consequently to construct a prediction model. The data in the validation group were used to analyze the predictive performance of the model through the ROC curve, and the fitting degree of the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test.Results:Respectively, 75 cases in the modeling group and 29 cases in the validation group died 3 years after surgery. There was no statistically significant difference in the baseline data between the 2 groups, indicating comparability ( P>0.05). Logistic univariate analysis showed that gender, age, coronary atherosclerotic heart disease before injury, stroke before injury, pulmonary infection before injury, hemoglobin, albumin, high-density lipoprotein, body mass index, time from injury to surgery and ASA grade were related to the mortality of patients 3 years after surgery ( P<0.05). The ROC curve analysis showed that the variables with predictive ability included age, hemoglobin, albumin, body mass index, and time from injury to surgery. Logistic multivariate analysis showed male, age ≥ 83 years, pre-injury stroke, time from injury to surgery ≥ 4.5 days, ASA grade Ⅲ, and ASA grade Ⅳ were significantly related to the postoperative 3-year all-cause mortality in the elderly patients with hip fracture ( P<0.05). In the prediction model based on the above indicators, the area under the ROC curve was 0.792 (95% CI: 0.730 to 0.855, P<0.001), the cutoff value 0.459, sensitivity 56%, and specificity 90.5%, showing a good fit of the model ( χ2=5.818, P=0.668). Conclusions:Male, age ≥ 83 years, pre-injury stroke, time from injury to surgery ≥ 4.5 days, and ASA grades Ⅲ and Ⅳ are risk factors for postoperative 3-year all-cause mortality in the elderly patients with hip fracture. The risk prediction model based on these indicators demonstrates good predictive efficacy.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To investigate the effect of Lumbricus protein on the phenotypic transformation of corporal cavernosum smooth muscle cells(CCSMC)and erectile function in diabetic erectile dysfunction(DMED)rats.Methods Sixty male SD rats with normal erectile function were randomly divided into a blank group,a model group,a Sildelafil group(5 mg·kg-1),and a Lumbricus protein low-,medium-,and high-dose group(45,90,and 180 mg·kg-1),with 10 rats in each group.The diabetic rat model was established by intraperitoneal injection of Streptozotocin(STZ,50 mg·kg-1)combined with high-fat feed feeding;after 8 weeks,the DMED rat model was prepared by neck injection of Apomorphine(APO,100 μg·kg-1).After successful modeling,the rats were administered with a dose of Apomorphine by gavage once a day for 4 weeks.The blood glucose levels and body mass of rats in each group were measured before modeling,on the third day of modeling,and after 4 weeks of drug administration.The intracavernous pressure(ICP)and carotid artery pressure(MAP)were measured by multi-channel physiological recorder,and the ICP/MAP ratio was calculated.The expressions of contractile markers α-smooth muscle actin(α-SMA),smooth muscle myosin heavy chain(SMMHC)and synthetic markers Collagen I and osteopontin(OPN)in corpus cavernosum were detected by immunohistochemistry.The mRNA expression levels of α-SMA,SMMHC and Collagen I in corpus cavernosum were detected by RT-PCR.The protein expression levels of α-SMA,Desmin,Collagen I and OPN in corpus cavernosum were detected by Western Blot.Results Compared with the blank group,the blood glucose levels of the rats in the model group were significantly increased on the third day of modeling and after 4 weeks of administration(P＜0.01),and the body mass was significantly decreased after 4 weeks of administration(P＜0.01).ICP and ICP/MAP ratio were significantly decreased(P＜0.01).The protein expression levels of α-SMA,SMMHC and Desmin in penile corpus cavernosum were significantly decreased(P＜0.01),and the protein expression levels of Collagen I and OPN were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly decreased(P＜0.01),and the mRNA expression level of Collagen I was significantly increased(P＜0.01).Compared with the model group,there was no significant change in blood glucose and body mass of rats in the administration group(P＞0.05).ICP and ICP/MAP ratio were significantly increased(P＜0.01).The expression levels of α-SMA,SMMHC and Desmin in corpus cavernosum were significantly increased(P＜0.01),while the expression levels of Collagen I and OPN were significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly increased(P＜0.01),and the mRNA expression level of Collagen I was significantly decreased(P＜0.01).Conclusion Lumbricus protein can improve the erectile function of DMED rats,and its mechanism may be related to the inhibition of CCSMC from'contractile'to'synthetic(proliferative)'transformation.

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.

Objective:To investigate the correlation between strong ion gap (SIG) and prognosis of adult hospitalized patients who experienced cardiac arrest (CA).Methods:A retrospective cohort study was conducted on adult CA patients (≥18 years old) who were admitted to the intensive care unit (ICU) for the first time from the Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database from 2001 to 2012. The patients were divided into 3 groups based on the tertiles of serum SIG value. The clinical baseline characteristics and related data of CA patients were compared. Kaplan-Meier method was used to draw the 28- and 90-day cumulative survival curves of CA patients. Meanwhile, the log-rank test was used to compare the differences in the survival curves among different groups, and Cox proportional hazard regression model was established to analyze whether SIG was an independent predictor of all-cause mortality in CA patients.Results:Six hundred and six adult CA patients were eligible for final analysis. The patients were divided into 3 groups based on the tertiles of serum SIG value [<3.91 mmol/L ( n=202), 3.91~7.32 mmol/L ( n=202) and >7.32 mmol/L ( n=202)]. The mean age was (66.91±15.95) years and 382 patients (63.04%) were male. The all-cause mortality rates of ICU, 28 days and 90 days were 36.47%, 49.17% and 56.93%, respectively. There were significant differences in SOFA score, SIG, anion gap, pH, lactic acid, white blood cells, prothrombin time, creatinine, blood potassium, blood phosphorus, hypertension, coronary heart disease, cardiogenic shock, and ICU, 28-day and 90-day all-cause mortality among the 3 groups (all P<0.05). The Kaplan-Meier survival curves showed that the 28- and 90-day cumulative survival rates of CA patients decreased gradually with the increase of SIG level, and the differences were statistically significant among the 3 groups (all P<0.001). Multivariate Cox proportional hazard models showed that the increase of SIG level (>7.32 mmol/L) was an independent risk factor for 28-day ( HR=1.610, 95% CI: 1.177-2.203, P=0.003) and 90-day all-cause mortality ( HR=1.506, 95% CI: 1.123-2.019, P=0.006) among CA patients, after adjusting for the related confounders. Conclusions:The elevated SIG level (>7.32 mmol/L) is an independent predictor of 28- and 90-day all-cause mortality in CA patients. The calculation of SIG level in these patients is helpful for early identification of patients with poor prognosis.