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 investigate the clinical characteristics and prognosis of patients with left ventricular assist device (LVAD) implantation during the perioperative period.Methods:This retrospective study included 14 patients with end-stage heart failure who underwent LVAD implantation in the department of intensive care medicine of Nanjing Hospital Affiliated to Nanjing Medical University from February 2022 to March 2023, including 12 males and 2 females patients, the mean age was (57.6±9.8)years old. All patients were implanted with Corheart 6 implantable left ventricular assist system, did not use other mechanical assisted circulatory devices. The clinical data of enrolled patients were collected, and the clinical characteristics and prognosis during ICU treatment were analyzed.Results:Dilated cardiomyopathy (DCM) was the most common primary cause of heart failure. The results of transthoracic echocardiography showed that the left ventricular ejection fraction (0.297±0.074 vs. 0.238±0.064, P=0.031) of patients was significantly increased, while the left ventricular end diastolic diameter[69.0(65.8, 74.3)mm vs. 76.5(72.8, 83.0)mm, P=0.003]and systolic end systolic diameter[61.5(53.7, 65.3)mm vs. 68.3(63.8, 71.9)mm, P=0.005]were significantly decreased post LVAD implantation as compared to before LVAD implantation. Within one week after implantation, there was no significant difference in LVAD rotational speed, flow rate, and pulsation index ( P>0.05). During ICU treatment, dobutamine (13 cases) was the most commonly used vasoactive agent. 9 patients used phosphodiesterase Ⅲ inhibitors for perioperative pulmonary hypertension. Targeted management of volume and pressure indicators was conducted for enrolled patients to prevent postoperative right heart failure and to reduce right heart burden. Within 72 hours after LVAD implantation, the average pulmonary artery pressure of patients was 24 (22, 26) mmHg to 26 (21, 28)mmHg (1 mmHg=0.133 kPa), while the fluid balance was(-581±778)ml to(-1 209±1 134)ml. All enrolled patients survived to 28 days after LVAD implantation. The length of stay in the ICU was (8.0±1.8) days and the total length of hospital stay was 33 (29, 41)days, while the time of mechanical ventilation was 8 (5, 28)h. Conclusion:LVAD implantation can help improve left ventricular systolic function, prolong survival time so as to serve as an important means of terminal treatment or bridging therapy for heart transplantation of patients with end-stage heart failure. To strengthen the perioperative hemodynamic regulation and maintain the cardiac function of patients with LVAD implantation is the important purposes of ICU postoperative management.

Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.

Background Bisphenol compounds are non-persistent environmental endocrine disruptors and frequently detected in drinking water systems, indicating potential human health risks through drinking water. Objective To establish and optimize a simultaneous determination method for 16 BPs in drinking water by online solid-phase extraction-ultra high-performance liquid chromatography-triple quadrupole mass spectrometry, in order to efficiently monitoring BPs in drinking water. Methods Candidate online solid-phase extraction conditions, chromatographic columns, mobile phase systems, mass spectrometry parameters, and other conditions were compared by chromatographic peaks of BPs, and processing conditions such as water sample preservation and pretreatment were optimized. The pH level of drinking water samples was adjusted and solid particles were removed. After extraction and purification by an online solid-phase extraction system, samples were detected by ultra-high performance liquid chromatography tandem mass spectrometry and quantified by isotope internal standard method. The proposed method was verified by pure water and terminal tap water, and evaluated by spiked recovery rate and relative standard deviation. Eighty-eight tap water samples from different regions of local pipeline network were collected for method application. Results For the 16 BPs, the calibration curves showed good linearity between 1.0 and 75 ng·L⁻¹ and the correlation coefficients were greater than 0.995. The detection limit of the method was less than 0.30 ng·L⁻¹, and the quantification limit of the method was less than 1.0 ng·L⁻¹. When the spiked concentrations for the 16 BPs were 5.0, 15, and 40 ng·L⁻¹, the average spiked recovery rates of the test substances were between (100 ± 10)%, and the relative standard deviations were all below 10%. In the method application to the local terminal water samples, the positive rates of bisphenol S (BPS), bisphenol A (BPA), and bisphenol AF (BPAF) were as high as 93.2%, 77.3%, and 29.5%, respectively. The concentrations of BPS were from not detected (N.D.) to 37.8 ng·L⁻¹, and the concentrations of BPA were from N.D. to 52.0 ng·L⁻¹. Conclusion The method using an online solid-phase extraction system is established, featuring simple pre-treatment, small sample volume, high degree of automation, low detection limit, and good accuracy and precision. This method can be applied to the quantitative monitoring of 16 BPs at ng·L⁻¹ level in drinking water.

Objective:To investigate the risk factors for the relapse of autoimmune pancreatitis (AIP) after steroid therapy.Methods:Clinical data of 72 AIP patients treated with steroids in Nanjing Drum Tower Hospital from January 2012 to December 2023 were collected retrospectively. AIP patients were divided into relapse group ( n=25) and non-relapse group ( n=47) based on the presence or absence of their relapse after steroid therapy. Patients' age of onset, gender, history of diabetes mellitus, first clinical manifestations, serum IgG4 and CA19-9 level, imaging features and other organ involvements were recorded. Oral prednisone was used at an initial dose of 0.6 mg·kg -1·d -1, gradually reduced to 5-10 mg/d and then maintained at a low dose. The follow-up period started from steroid initiation to the last follow-up or relapse. The presence of maintenance steroid treatment, time interval between onset and steroid initiation, the presence of significant IgG4 decrease and the presence of persistently enlarged pancreas after therapy were recorded. The cumulative relapse rate curve after steroid therapy was drawn by Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazard regression model. The receiver operator characteristic curves (ROC) were plotted and the area under the curve (AUC) was calculated. The Log-Rank test was used to analyze the differences on the relapse between different groups. The subgroup forest plot was drawn to assess the effect of risk factors on the relapse of AIP in different subgroups. Results:The 72 patients with AIP had a median follow-up of 42 (12-127) months. 34.7% (25/72) of patients relapsed after steroid therapy during the follow-up period. The percentages of patients whose first clinical manifestation was abdominal distension or acute pancreatitis, whose interval between onset and steroid initiation was more than 1 year and whose pancreases were persistently enlarged after steroid therapy in the relapse group were higher than those in the non-relapse group, and the differences were all statistically significant (all P value <0.05). The 1-, 3- and 5-year cumulative relapse rate after steroid therapy was 20.8%, 34.1% and 37.8%, respectively. Univariate analysis found that the first clinical manifestations of abdominal distension or acute pancreatitis, interval between onset and steroid initiation more than 1 year, and persistently enlarged pancreas after steroid therapy were all significantly associated with relapse (all P value <0.05). Multivariate analysis found that interval between onset and steroid initiation more than 1 year and persistently enlarged pancreas after steroid therapy were independent risk factors for relapse of AIP [hazard ratio ( HR)=3.606 and 6.515, 95% confidence interval (95% CI) 1.362-9.854 and 2.088-20.326]. Kaplan-Meier survival curves showed that the relapse rate after steroid therapy was higher in AIP patients whose interval between onset and steroid initiation was more than 1 year than in those whose interval was less than 1 year (55.6% versus 27.8%), and the relapse rate in AIP patients with persistently enlarged pancreas after steroid therapy was higher than that in those without it (77.8% versus 28.6%), and the differences were both statistically significant (both P<0.05). Subgroup forest plot showed that persistently enlarged pancreas after steroid therapy was an independent risk factor for relapse of AIP regardless of the presence of a diabetes mellitus history, the first manifestation of abdominal pain, the diffuse or focal type in pancreatic imaging, and the presence of dilated pancreatic duct or not (all P value <0.05). Conclusions:Time interval between onset and steroid initiation more than 1 year and persistently enlarged pancreas after steroid therapy were independent risk factors for the relapse of AIP after steroid therapy.

【Objective】 To investigate the application of different ureteral length measurement methods in the indwelling of double-J stent. 【Methods】 Clinical data of 260 patients with double-J stent indwelling after ureteroscopic surgery during Jul.2018 and Dec.2020 were prospectively analyzed. The patients were randomly divided into height calculation group, CT measurement group, KUB group and ureteroscopic measurement group. The length of ureter was calculated accordingly and the appropriate length of double-J stent was selected. KUB was performed on the first day after operation and before extubation to determine the position of double-J stent. The patients completed the ureteral stent-related symptom questionnaire (USSQ), urinary symptom score, lower urinary tract symptom (LUTS) score, pain score, hematuria score, and quality of life score before and after double-J catheter placement. 【Results】 There were no significant differences in age, gender, height, side of stent and urinary symptom score among the four groups (P>0.05). The average lengths of the ureters measured by the four methods were (21.5±1.0) cm, (21.5±1.8) cm, (23.8±1.3) cm and (21.7±1.8) cm, respectively. There were no significant differences among the height calculation group, CT measurement group and ureteroscope group, but there was significant difference between the three groups and the KUB group. The ideal ureteral stent length indwelling ratio in the ureteroscopic group was 76.9%, which was better than that in the other three groups. Postoperative indwelling time was 7-42 d (mean 29.8 d). The USSQ score of the ureteroscopic group before extubation was (14.1±1.5), which was lower than that of the other three groups (P<0.05). The ureteroscopic group was better than the other three groups in the comparison of frequency and urgency of urination, nocturia, hematuria, quality of life score, and pain score (P<0.05). 【Conclusion】 Intraoperative ureteroscopic measurement of the ureteral length is a simple and feasible method in guiding the indwelling of double-J stent to reduce ureteral stent related symptoms.

Objective:To compare the clinical characteristics and prognosis of bacterial liver abscess in patients with or without diabetes mellitus (DM), to provide a reference for clinical diagnosis and treatment.Methods:Patients with bacterial liver abscesses hospitalized in Tongren Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to August 2021 were enrolled, and their clinical data were collected. The patients were divided into diabetic and non-diabetic groups for comparison according to whether they had comorbid DM. Statistical analysis was performed by chi-square test or Fisher′s exact test, and multivariate logistic regression analysis.Results:A total of 131 patients with bacterial liver abscesses were included, including 47 cases in the diabetic group and 84 cases in the non-diabetic group. The percentages of platelet count <100×10 9/L, C-reactive protein>10 mg/L, and total bilirubin>17.5 μmol/L were lower in the diabetic group than that in the non-diabetic group, and the differences were all statistically significant ( χ2=3.90, 6.44 and 5.56, respectively, all P<0.05). The percentage of multiple abscesses in the diabetic group was 10.6%(5/47), which was lower than 29.8%(25/84) in the non-diabetic group, and the difference was statistically significant ( χ2=6.24, P=0.012). The positive rate of pus culture for Klebsiella pneumoniae was 64.9%(24/37) in the diabetic group, which was higher than 41.5%(27/65) in the non-diabetic group, with a statistically significant difference ( χ2=5.13, P=0.023). The incidences of pleural effusion and abscesses at other sites in the diabetic group were 29.8%(14/47) and 10.6%(5/47), respectively, which were both higher than 14.3%(12/84) and 1.2%(1/84) in the non-diabetic group, respectively, and the differences were statistically significant ( χ2=4.55, Fisher′s exact test, both P<0.05). The proportion of hospital stays>21 d was 34.0%(16/47) in the diabetic group, which was higher than 16.7%(14/84) in the non-diabetic group, with a statistically significant difference ( χ2=5.15, P=0.023). DM (odds ratio ( OR)=2.654, 95% confidence interval ( CI) 1.020 to 6.907, P=0.046) and abscess maximum diameter>10 cm ( OR=11.045, 95% CI 4.493 to 27.154, P<0.001) were significant risk factors for hospital stay>21 d. Conclusions:Bacterial liver abscesses combined with DM are more common with single abscess, a higher rate of Klebsiella pneumoniae infection, and more likely to develop pleural effusions and abscesses at other sites. Liver abscesses>10 cm in maximum diameter and comorbid DM would prolong hospital stay.

Objective:To investigate the relationship between n7-methylguanosine (m7G) related long non-coding RNA (lncRNA) expression and glioma prognosis, and to construct a prognosis model with m7G-related lncRNA in patients with glioma.Methods:Data related to the test set and validation set were downloaded from the Cancer and Tumor Genome Atlas (TCGA) database and the China Glioma Genome Atlas (CGGA) database. LASSO regression and random forest algorithm were used to establish the glioma prognosis model with m7G related lncRNA. Individualized risk scores were calculated using the weighted expression levels of the 12 extracted lncRNA coefficients, and test set and validation set glioma patients were categorized into high and low risk groups based on median risk score. Kaplan-Meier survival curve was drawn, the comparison method used log rank test. The efficacy of risk score in predicting the 1-, 2- and 5-year survival rate in patients with glioma was evaluated using the receiver operating characteristics (ROC) curve.Results:A total of 12 lncRNA associated with m7G were obtained, with a risk score = 1.026 × AC002454.1 + 1.086 × AC131097.4 + 1.039 × AC147651.3 + 1.01 × AGAP2-AS1 + 1.036 × CRNDE + 0.733 × GDNF-AS1 + 1.321 × HOXD-AS2 + 0.934 × LINC00641 + 1.183 × PAXIP1-AS2 + 1.258 × PVT1 + 0.909 × SOX21-AS1 + 0.754 × TTC28-AS1, with a median risk score of - 0.45 scores. Kaplan-Meier survival curve analysis result showed that the median survival time in high risk group was significantly shorter than that in low risk group (1.98 years vs. 9.51 years, log-rank χ2 = 131.78, P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of risk score in predicting the 1-, 2- and 5-year survival rate in patients with glioma was 0.891, 0.923 and 0.912. In the validation set of glioma patients, Kaplan-Meier survival curve analysis result showed that the median survival time in high risk group was significantly shorter than that in low risk group (1.29 years vs. 6.88 years, log-rank χ2 = 103.27, P<0.01); ROC curve analysis result showed that the AUC of risk score in predicting the 1-, 2- and 5-year survival rate in patients with glioma was 0.724, 0.795 and 0.762. In the test set and validation set, multivariate Cox regression analysis result showed that the risk score was the independent risk factors of prognosis in patients with glioma ( HR = 1.992 and 1.247, P<0.01 or <0.05). Conclusions:A risk score model with m7G related lncRNA based on transcriptome is a novel approach to predict the prognosis of glioma patients.

Retinopathy of prematurity (ROP) is a disease which the retinal vascular system is not mature at birth, leading to cessation of development and abnormal proliferation of blood vessels, in a relatively high oxygen environment.Adiponectin (APN) is an endogenous bioactive protein secreted by adipocytes.It has functions of regulating Glucose and lipid metabolism, inhibiting atherosclerosis and protecting the cardiovascular system.APN can inhibit angiogenesis which may be involved in the occurrence and development of ROP in recent research.APN may be regulating the serum level of tumor necrosis factor α (TNF-α), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) A to prevent the development of ROP.The expression of APN is also affected by fibroblast growth factor 21 (FGF-21) and long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) at the same time.Understanding the role of APN in ROP can provide new ideas for further study of the pathogenesis and prevention and treatment of ROP.

Objective : To construct a visual literacy evaluation system for pupils by Delphi expert consultation method（Delphi method）. Methods : The visual literacy evaluation indices for pupils were preliminarily constructed through literature review. Twenty experts in relevant fields were invited and the visual literacy evaluation system for pupils was established by two rounds of expert consultation based on Delphi method. Results : The average age of 20 experts was（48.35±5.79）years old,of which 19 experts had senior titles,and 17 experts had master's degree or above. The enthusiasm of the experts in two rounds of consulting was both 100.00%. The average authoritative coefficient（W）of the experts was 0.88. For the first consulting round,the W of importance scores from experts was 0.91（P<0.01）;the W of operability scores from experts was 0.89（P<0.01）,which indicated satisfactory consistency. For the second consulting round,the W of importance scores from experts was 0.79（P<0.01）;the W of operability scores from experts was 0.77（P<0.01）,which also indicated satisfactory consistency. The finalized visual literacy evaluation system for pupils after two rounds of expert consultation included three primary indices（eye care knowledge literacy,eye care attitude literacy and eye care behavior literacy）,six secondary indices（basic knowledge,eye care behavior,eye care attitude,eye care willingness,bad eye care behavior and eye protection）and 40 tertiary indices（≥5.0 of eyesight among normal people,always wearing glasses due to poor eyesight and so on）. Conclusion The experts who participated in the construction of visual literacy evaluation system for pupils had strong professional representativeness,high enthusiasm,high authority and good coordination,and the evaluation system can be used for evaluating pupils visual literacy.