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 feasibility,safety and effectiveness of robot-assisted laparo-scopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture.Methods:The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted lapa-roscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology,Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed.Intraoperative conditions,postoperative complications and follow-up data were also recorded and analyzed.Results:The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery.The study in-cluded 14 males and 6 females with a mean age of(41±11)years(range:19 to 60 years)and a mean body mass index of(24.3±3.6)kg/m2(range:18.2 to 31.8 kg/m2).There were 9 cases on the left side and 11 cases on the right side.The strictures of all the patients were located in the proximal segment of the ureter(including the ureteropelvic junction).The mean preoperative serum creatinine was(92.2±23.3)μmol/L(range:49.2 to 138.9 μmol/L),and the mean length of ureteral stricture was(2.8±0.9)cm(range:1.0 to 4.0 cm).Ten patients had previously undergone unsuccessful reconstructive surgery.During the operation,12 patients received posteriorly augmented anastomosis with ventral onlay.The mean length of the buccal mucosa graft harvested during the operation was(3.1±0.6)cm(range:2.0 to 4.3 cm),and the median width was 1.5 cm(range:1.0 to 2.0 cm).The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases.The median operative time was 154 min(range:113 to 300 min),and the median estimated blood loss was 45 mL(range:0 to 100 mL).The median postoperative hospital stay was 4 d(range:4 to 14 d).The mean postoperative follow-up time was(15.0±1.7)months(range:12.5 to 17.9 months),and the surgical success rate was 100.0％in this study.After surgery,11 patients reported mild discomfort at the oral donor site,2 patients deve-loped urinary tract infection,and no postoperative complications were reported in the other 7 patients.The mean serum creatinine was(90.9±23.9)μmol/L(range:60.0 to 153.0 μmol/L)six months after surgery.Conclusion:Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications,which has shown good feasibility,safety and effectiveness.However,large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Objective:To explore the clinical value of modified upper urinary tract video urodynamics in evaluating the surgical effect and guiding the follow-up treatment after ureteral reconstruction.Methods:From December 2018 to November 2020, sixty-nine patients underwent upper urinary tract reconstruction and received modified video urodynamics at the time of nephrostomy removal 3 months after the surgery in the RECUTTER database (29 cases in Peking University First Hospital, 22 cases in Emergency General Hospital, and 18 cases in Beijing Jiangong Hospital). There were 39 males and 30 females, with an average age of (40.4±12.7)years. The stricture was located in left in 34 patients, right side in 27 patients, and bilateral sides in 8 patients. The upper, middle, and lower thirds of the ureter were affected in 26, 10, and 33 cases, respectively. The preoperative creatinine was (92.3±26.9)μmol/L, and the estimated glomerular filtration rate (eGFR) was (85.1±23.2)ml/(min·1.73m 2). The upper urinary tract reconstruction included ileal replacement of ureter in 25 cases (36.2%), pyeloplasty in 8 cases (11.6%), ureteroneocystostomy in 9 cases (13.0%), boari flap in 6 cases (8.7%), lingual mucosal graft ureteroplasty in 9 cases (13.0%), appendiceal onlay ureteroplasty in 3 cases (4.3%), ureteroureterostomy in 3 cases (4.3%), and balloon dilation in 6 cases (8.7%). Based on the pressure and imaging, the results could be divided into three types, type Ⅰ, the pressure difference remained stable near baseline, and the renal pelvis pressure was below 22 cmH 2O(1 cmH 2O=0.098 kPa), and the reconstructed ureter is well visualized during the whole perfusion process; type Ⅱ, the pressure difference increases with the perfusion, but it can decrease to a normal level with the ureteral peristalsis; type Ⅲ, the pressure difference exceeds 15 cmH 2O, and the ureteral peristalsis is weak or disappears at the same time. The management strategies and treatment effects of different subtypes were analyzed. Successful treatment was defined as no further treatment required, the absence of hydronephrosis-related symptoms, and the improved or stabilized degree of hydronephrosis. Results:All 69 patients successfully completed upper urinary tract video urodynamics. The pressure difference was higher than 15 cmH 2O in 8 patients, and the median pressure difference was 37(19-54)cmH 2O. The renal pelvis pressure exceeded 22 cmH 2O in 10 patients, and the median pressure was 63.5 (24-155) cmH 2O. Video urodynamic results of upper urinary tract were classified as type Ⅰ in 60 cases, type Ⅱ in 5 cases, and type Ⅲ in 4 cases. Patients in type Ⅰ do not require other treatment after nephrostomy tube removal. Patients in type Ⅱ should avoid holding urine after the removal of nephrostomy and D-J tubes. All patients in type Ⅲ received further treatment, of which 2 patients replaced D-J tube regularly, 1 patient underwent long-term metal ureteral stent replacement, and 1 patient underwent ureteroscopic balloon dilation. The median follow-up time was 24 (18-42) months. All patients in type Ⅰ met the criteria for surgical success, The pre-and postoperative creatinine in type Ⅰ patients were (88.71±23.09)μmol/L and (88.75±23.64)μmol/L ( P=0.984), and eGFR were (88.06±22.66)ml/(min· 1.73m 2)and (87.97±23.01)ml/(min·1.73m 2), respectively( P=0.969). For type Ⅱ patients, ultrasound showed that the degree of hydronephrosis improved in 3 cases and remained stable in 2 cases. The pre-and postoperative creatinine were (105.97±7.75)μmol/L and (97.63±7.56)μmol/L ( P=0.216), and eGFR were (69.08±14.74)ml/(min·1.73m 2)and (75.95±14.02)ml/(min·1.73m 2)( P=0.243), respectively. For type Ⅲ patients, ultrasound showed that the degree of hydronephrosis remained stable. The pre-and postoperative creatinine were (105.14±44.34)μmol/L and (101.49±57.02)μmol/L ( P=0.684), and eGFR were (65.32±19.85)ml/(min·1.73m 2) and (73.42±27.88) ml/(min·1.73m 2), respectively( P=0.316). Conclusions:The pressure and imaging results of modified upper urinary tract video urodynamics can assist in evaluating the surgical effect of ureteral reconstruction, and the classification has certain guiding significance for further treatment.

Objective:To observe the activation of cerebral regions during swallowing by magnetoencephalography (MEG), and discuss the temporal and spatial characteristics of neural circuit.Methods:Ten healthy subjects were selected, and the magnetic signals of their brains were recorded using 148 channel full head type MEG system in the magnetic shielding room.Data were analyzed using CURRY8 analysis software and the localization algorithm was based on minimum modulus low resolution electromagnetic imaging method (LORETA). Every 300 ms data were set as an independent analysis stage and made the highest position of the cerebral cortex F-distribution values (F-distributed) as the activation area.The activation areas were analyzed during swallowing through time and space location.Results:Paracentral lobule, anterior central gyrus, medulla oblata, posterior central gyrus, inferior frontal gyrus, parietal lobules, angular gyrus, corpus callosum, middle frontal gyrus, cingulate gyrus, orbital gyrus, thalamus, bottom of third ventricle, corona radiata, precuneus, frontal insula, cerebellopontine angle, superior frontal gyrus and basal ganglia area were activated during swallowing, in which the top eight brain regions were paracentral lobule, anterior central gyrus, corpus callosum, posterior central gyrus, superior parietal lobule, middle frontal gyrus, cingulate gyrus, and basal ganglia.When the 10 subjects performed the deglutition, MEG signals of 8 subjects were mainly activated by the left cerebral hemisphere at 0-300 ms, the bilateral cerebral hemisphere or intermediate region at 301-600 ms, and the right cerebral hemisphere at 601-900 ms.MEG signal of 1 subject was activated by the right cerebral hemisphere at 0-300 ms, and the left cerebral hemisphere at 301-600 ms and 601-900 ms.MEG signal of 1 subject was mainly activated by the right cerebral hemisphere at 0-300 ms and 601-900 ms, and in the intermediate region at 301-600 ms.Conclusion:During swallowing the MEG signals appeared left laterality in the early stage and right laterality in the later stage, and showed a close correlation with time.There may be a swallowing neural circuit composed by the central region, corpus callosum, superior parietal lobule, middle frontal gyrus, cingulate gyrus and basal ganglia, in which the central region is the core.

Objective To observe the clinical efficacy of extracorporeal shock wave (ESW) plus electroacupuncture in treating periarthritis of shoulder.Method Ninety patients with periarthritis of shoulder were randomized into an electroacupuncture (EA) group, an ESW group, and an ESW plus EA group, 30 cases in each group. The EA group was intervened by EA, the ESW group was treated with ESW, and the ESW plus EA group by ESW and EA. The three groups were treated once every 2 d, with successive 10 sessions as a treatment course. The Visual Analogue Scale (VAS) score and shoulder range of motion (ROM) score were evaluated before and after the treatment in the three groups. Result The VAS scores dropped significantly in the three groups after the intervention (P<0.05); there was no significant difference in comparing the VAS score between the EA group and ESW group after the intervention (P>0.05); the VAS score in the ESW plus EA group was significantly different from that in the EA group and ESW group after the treatment (P<0.05). The ROM scores were significantly improved in the three groups after the intervention (P<0.05); there was no significant difference in comparing the ROM score between the EA group and the ESW group after the intervention (P>0.05); the ROM score in the ESW plus EA group was significant different from that in the other two groups (P<0.05).Conclusion ESW plus EA can more significantly ease the pain and improve the shoulder ROM in treating periarthritis of shoulder compared with the two methods used separately.

Objective To observe the clinical efficacy of Zhuang’s Moxibustion plus acupuncture in treating spastic paralysis due to craniocerebral injury.Method Ninety-two patients with spastic paralysis due to craniocerebral injury were randomized into a treatment group of 60 cases and a control group of 32 cases. The control group was intervened by conventional internal medicine and rehabilitation, while the treatment group was intervened by Zhuang’s moxibustion plus acupuncture in addition to the intervention given to the control group. The modified Ashworth Scale (MAS) was adopted to evaluate the clinical efficacy.Result The total effective rate was 75.0% in the treatment group versus 65.6% in the control group, and the between-group difference was statistically significant (P<0.01).Conclusion Zhuang’s moxibustion plus acupuncture is an effective approach in treating spastic paralysis due to craniocerebral injury.

Objective To observe the effect of Tung’s acupuncture on walk and balance function in patients with Parkinson’s disease (PD). Method Ninety-two eligible PD patients were randomized into a control group and a treatment group, 46 cases in each group. The control group was intervened by Levodopa, while the treatment group was additionally intervened by Tung’s acupuncture. The two groups were both treated for 20 d. Before and after the treatment, the walk and balance function were evaluated by the indices of NeuroCom Balance Master, including Walk Across (WLK), Step/Quick Turn (SNT), and Timed Up & Go Test (TUGT), and the results were compared between the two groups. Result The walk speed, step length, swing in turning, time-consumption in turning, and TUGT were improved after the intervention in both groups (P<0.05), and the improvements in the treatment group were more significant than that in the control group (P<0.05). Conclusion Tung’s acupuncture plus oral administration of Levodopa can markedly improve the walk and balance function in patients with PD.

Objective:To establish a UPLC method for the determination of ginsenoside Rg1 , ginsenoside Re and ginsenoside Rb1 in Yi’ nianjin. Methods: The column was ZORBAX Eclipse Plus C18 (2. 1 mm × 50 mm,1. 8 μm), the flow rate was 0. 21 ml· min-1 , the column temperature was 30℃, the mobile phase consisted of acetonitrile-water with gradient elution, the detection wave-length was 203nm, and the sample size was 1μl. Results:The linear range of ginsenoside Rg1 was 0. 020 3-0. 303 9 mg·ml-1 ( r=0. 999 6), and the average recovery was 99. 05% (RSD=1. 3%, n=6). The linear range of ginsenoside Re was 0. 020 2-0. 302 7 mg·ml-1(r=0. 999 8), and the average recovery was 101. 31% (RSD=1. 1%, n=6). The linear range of ginsenoside Rb1 was 0. 020 3-0. 305 1 mg·ml-1(r=0. 999 8), and the average recovery of 100. 71% (RSD=0. 9%, n=6). Conclusion: The method is simple and accurate, and can determine the three components simultaneously. The method can be used in the quality control of Yi’ nianjin.