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 compare the clinical efficacy of percutaneous transhepatic choledochoscope lithotomy (PTCSL) with laparoscopic choledocholithotomy (LD) in treatment of choledocholithiasis.Methods:Data of 132 patients with choledocholithiasis treated at the First Affiliated Hospital of Guangzhou Medical University from July 2012 to December 2018 were retrospectively analyzed. There were 75 males and 57 females, with an average age of 62.7 years. For 76 patients underwent PTCSL (the PTCSL group) and 56 underwent LD (the LD group). The data of the patients the success rate of lithotomy, stone residual rate, operation time, postoperative complications and stone recurrence, chronic cholangitis, and acute cholangitis 1 month after operation were compared between the two groups.Results:The ratio of upper abdominal operation history and biliary tract infection in the PTCSL group was higher than that in the LD group, and the difference was statistically significant (both P<0.05). In the PTCSL group, the calculi were successfully removed in 64 patients in one treatment session, while residual calculi were removed through subsequent sinus choledochoscopy in 9 patients. In the remaining 3 patients, the residual calculi were removed with LD or laparotomy operations. Postoperative complications occurred in 14 patients (19.2%, 14/73). In the LD group, the calculi were successfully removed in one session in 46 patients while in 8 patients the residual calculi were removed by choledochoscopy (1 patient still had residual calculi after choledochoscopy). The remaining 2 patients underwent open surgery due to anatomical difficulties. Postoperative complications occurred in 11 patients (20.4%, 11/54). There were no significant differences between the two groups in the one-off stone removal rate, postoperative stone residual rate, final stone removal rate and postoperative complication rate (all P>0.05). The operation time of the PTCSL group was (156±60) min, which was significantly shorter than the LD group (203±59) min ( P<0.05). There was no significant difference between the two groups in the incidence of postoperative chronic cholangitis and recurrence rate of calculi (both P>0.05). The incidence of acute cholangitis in the PTSCL group was significantly higher than that in the LD group ( P<0.05). Conclusion:PTCSL was as safe and effective as LD, with fewer complications and faster recovery. It is especially suitable for patients with previous upper abdominal surgery, recurrence of calculi and repeated biliary tract infection.

OBJECTIVE：  To improve the method for the content determination of astragaloside Ⅳ in Xiangju granules， and to evaluate the consistency of relevant preparations with the components of original formulation， so as to provide evidence for the modern preparation of TCM compound. METHODS： HPLC-ELSD method was established for the content determination of astragaloside Ⅳ in Xiangju granules， and compared with original standard TLC scanning. Using critrinin， ferulic acid， calycosin glucoside， liquiritin， glycyrrhizic acid， rosmarinic acid， buddleoside and magnoline as control， HPLC method was used to determine the release components of self-made Xiangju granules， Xiangju capsules， Xiangju tablets in water. Fingerprint characteristics chromatogram of different Xiangju preparations and original formulation extract were compared by using Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 version）. At the same time， HPLC-ELSD method was used to determine and compare the release rate of astragaloside Ⅳ from different Xiangju preparations and original formulation extract in water. RESULTS： Established HPLC-ELSD method was specific. The linear range of astragaloside Ⅳ was 0.13-2.10 mg/mL. RSDs of precision， repeatability and stability tests were all lower than 3％ （n＝6）， and average recovery was 97.66％ （RSD＝1.01％，n＝6）. Average content of astragaloside Ⅳ by this method was 0.398 mg/g （RSD＝1.01％， n＝3）， which had better reproducibility than TLC scanning. The comparative results of characteristic fingerprints showed that the similarity among Xiangju granules， Xiangju capsules， Xiangju tablets and the original formulation dry extract powder was more than 0.850. Average release rates of astragaloside Ⅳ in Xiangju granules， Xiangju capsules， Xiangju tablets and the original formulation extract were 0.392， 0.358， 0.349， 0.389 mg， respectively. Compared with original formulation extract， there was no statistical significance in release rate of astragaloside Ⅳ in Xiangju granules （P＞0.05）， while there was statistical significance in Xiangju capsules and Xiangju tablets （P＜0.01）. CONCLU- SIONS： Established HPLC-ELSD method is accurate and feasible， and is suitable for the content determination of astragaloside Ⅳ in Xiangju granules. The main components of Xiangju granules are consistent with original formulation.

Object　To determine the amount of acacetin-7-O-β-D-glucoside and apigenin-7-O-β-D-glucoside in Chrysanthemum morifolium Ramat. from different localities. Methods　By the use of HPLC. Results　The contents of acacetin-7-O-β-D-glucoside in Boju1, Chuju2, Gongju3 and Hangju4 were 0.082 6%～0.124 9%, 0.015 7% and 0.033 5% respectively; the contents of apigenin-7-O-β-D-glucoside in Chuju, Boju, Gongju and Hangju were 0.012 6%, 0.027 4%, 0.117 7% and 0.587 7% respectively. Conclusion　The contents of the two flavone glycoside in C. morifolium from different localities were markedly different.

Objective: To determine luteolin 7 O ? D glucoside in Chrysanthemum morirolium Ramat. Methods: The content of luteolin 7 O ? D glucoside was determined by HPLC on Symmetry Shield TM RP S column with MeoH H 2O(49∶51) as a mobile phase and detection wavelength at 348nm. Results: The liuear relationship of this method was well and the average recovery of the added sample is 99.74%. Conclusion: The analytical time is short, separating degree is good and results are accurate when luteolin 7 O ? D glucoside is determined by this method.