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 and analyze the surgical approach differences using CT parameters between mini-open transforaminal lumbar interbody fusion (MO-TLIF) and minimally invasive surgery of transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar diseases.Methods:A total of 68 consecutive patients with degenerative lumbar diseases undergoing surgery at the Second Affiliated Hospital of Soochow University from January 2022 to January 2023 were randomized into the MO-TLIF group (34 cases, percutaneous screw-assisted posterior midline MO-TLIF) and the MIS-TLIF group (34 cases, Wiltse approach MIS-TLIF using the Quadrant channel). Perioperative indicators (operative time, incision length, intraoperative blood loss, fluoroscopy frequency, postoperative bedrest duration, and hospital stay) and complications were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed preoperatively and at 3 days, 3 months, and 1 year postoperatively. Effective cross-sectional area (eCSA) of paraspinal muscles was evaluated on MRI preoperatively and 1 year postoperatively. CT parameters of surgical approaches, including spinous process-midline distance (SM), Wiltse-midline distance (WM), surgical approach angle, depth, and multifidus muscle displacement were compared. Pearson correlation and multivariate linear regression analyses were performed to explore associations between CT parameters, operative time, blood loss, and eCSA atrophy.Results:Baseline characteristics showed no significant differences between groups ( P>0.05). The MO-TLIF group exhibited shorter operative time (109.85±7.82 min vs. 133.82±20.22 min), reduced blood loss (77.21±21.83 ml vs. 141.18±31.44 ml), smaller incision length (6.09±0.22 cm vs. 7.00±0.43 cm), shorter bedrest duration (1.59±0.49 d vs. 2.38±0.50 d), and shorter hospital stay (8.93±1.44 d vs. 10.35±1.45 d), but higher fluoroscopy frequency (19.53±1.92 times vs. 16.29±1.78 times) compared to the MIS-TLIF group ( P<0.05). Complications included fat liquefaction (5 cases) and dural tears (2 cases). Both groups showed improved VAS and ODI postoperatively ( P<0.05). At 3 d postoperatively, the MO-TLIF group had lower VAS (2.74±0.47 points vs. 3.35±0.48 points) and ODI (27.46%±2.16% vs. 30.42%±2.52%) than the MIS-TLIF group ( P<0.05). Postoperative eCSA decreased significantly in the MIS-TLIF group ( P<0.05) but remained stable in the MO-TLIF group ( P>0.05). The MO-TLIF group demonstrated smaller SM (8.43±1.81 mm vs. 31.15±6.53 mm), approach angle, depth, and muscle displacement ( P<0.05). CT parameters in the MO-TLIF group showed no correlation with operative time, blood loss, or eCSA atrophy ( r<0.3, P>0.05), whereas parameters in the MIS-TLIF group correlated positively with these outcomes (0.3< r<0.6, P<0.05). Multivariate regression revealed a significant association between CT parameters and eCSA atrophy in the MIS-TLIF group ( R 2=0.474, P<0.05). Conclusion:Compared to MIS-TLIF, MO-TLIF reduces intraoperative blood loss, accelerates recovery, and minimizes paraspinal muscle trauma.

Objective:To investigate the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for biopsy-negative esophageal strictures suspected for malignancy.Methods:Patients who underwent EUS-FNA for esophageal strictures with negative endoscopic biopsies in Nanjing Drum Tower Hospital from January 2014 to March 2022 were analyzed retrospectively. The final diagnosis was based on the pathological outcomes of EUS-FNA or surgery, complemented by follow-up data. Diagnostic efficacy and complication rates of EUS-FNA were analyzed.Results:A total of 64 patients were included in this study,with 54 ultimately diagnosed with malignant lesions and 10 with benign lesions. Malignant lesions were diagnosed by EUS-FNA in 50 cases, suspected malignant lesions in 3 cases, and no clear basis for malignancy was observed in 11 cases. The diagnostic accuracy of EUS-FNA was 98.4% (63/64), with the malignant tumor detection rate of 98.1% (53/54). No post-procedure complications such as bleeding, perforation, or infection were observed in any patient.Conclusion:EUS-FNA is safe and effective for the diagnosis of biopsy-negative suspected malignant esophageal stricture with a high malignant lesion detection rate.

Objective:To analyze the feasibility and safety of breast-conserving surgery for young women with breast cancer whose tumor is close to nipple areola complex after neoadjuvant therapy.Methods:Young female breast cancer patients treated at Maoming People’s Hospital from Jan. 2016 to Jan. 2022 were selected. The inclusion criteria were primary solitary tumors located within ≤2 cm from the areola margin (excluding carcinoma in situ, nipple discharge, and Paget’s disease), tumor diameter ranging from 1 to 3 cm, and no abnormal adhesion between the tumor and the areola, breast skin, or chest wall. A total of 87 patients were enrolled, including 44 who underwent NAC-sparing breast-conserving surgery (NAC-preservation group) and 43 who underwent breast-conserving surgery without NAC preservation (non-NAC-preservation group). All patients received postoperative radiotherapy and continued systemic therapy. Local recurrence and distant metastasis were compared between the two groups.Results:No statistically significant differences were observed between the two groups in pre-neoadjuvant therapy tumor stage, tumor location, tumor diameter, lymph node metastasis, or molecular subtype ( χ2=0.22, 0.67, 0.80, 1.25, 1.76, respectively; P>0.05). At the 2-year postoperative follow-up, no local recurrence was detected in either group. Distant metastasis occurred in one case in the NAC-preservation group and three cases in the non-NAC-preservation group, with no statistically significant difference (2.27% vs. 6.98%, χ2=1.097, P=0.295) . Conclusions:This study, to some extent, validates the feasibility of both patient groups undergoing breast-conserving surgery with or without NAC preservation after neoadjuvant therapy, in young breast cancer patients with tumors located near the nipple areola complex. Routine NAC excision does not improve therapeutic outcomes.

Objective:To analyze the feasibility and safety of breast-conserving surgery for young women with breast cancer whose tumor is close to nipple areola complex after neoadjuvant therapy.Methods:Young female breast cancer patients treated at Maoming People’s Hospital from Jan. 2016 to Jan. 2022 were selected. The inclusion criteria were primary solitary tumors located within ≤2 cm from the areola margin (excluding carcinoma in situ, nipple discharge, and Paget’s disease), tumor diameter ranging from 1 to 3 cm, and no abnormal adhesion between the tumor and the areola, breast skin, or chest wall. A total of 87 patients were enrolled, including 44 who underwent NAC-sparing breast-conserving surgery (NAC-preservation group) and 43 who underwent breast-conserving surgery without NAC preservation (non-NAC-preservation group). All patients received postoperative radiotherapy and continued systemic therapy. Local recurrence and distant metastasis were compared between the two groups.Results:No statistically significant differences were observed between the two groups in pre-neoadjuvant therapy tumor stage, tumor location, tumor diameter, lymph node metastasis, or molecular subtype ( χ2=0.22, 0.67, 0.80, 1.25, 1.76, respectively; P>0.05). At the 2-year postoperative follow-up, no local recurrence was detected in either group. Distant metastasis occurred in one case in the NAC-preservation group and three cases in the non-NAC-preservation group, with no statistically significant difference (2.27% vs. 6.98%, χ2=1.097, P=0.295) . Conclusions:This study, to some extent, validates the feasibility of both patient groups undergoing breast-conserving surgery with or without NAC preservation after neoadjuvant therapy, in young breast cancer patients with tumors located near the nipple areola complex. Routine NAC excision does not improve therapeutic outcomes.

Objective:To compare the clinical efficacy and analyze the surgical approach differences using CT parameters between mini-open transforaminal lumbar interbody fusion (MO-TLIF) and minimally invasive surgery of transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar diseases.Methods:A total of 68 consecutive patients with degenerative lumbar diseases undergoing surgery at the Second Affiliated Hospital of Soochow University from January 2022 to January 2023 were randomized into the MO-TLIF group (34 cases, percutaneous screw-assisted posterior midline MO-TLIF) and the MIS-TLIF group (34 cases, Wiltse approach MIS-TLIF using the Quadrant channel). Perioperative indicators (operative time, incision length, intraoperative blood loss, fluoroscopy frequency, postoperative bedrest duration, and hospital stay) and complications were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed preoperatively and at 3 days, 3 months, and 1 year postoperatively. Effective cross-sectional area (eCSA) of paraspinal muscles was evaluated on MRI preoperatively and 1 year postoperatively. CT parameters of surgical approaches, including spinous process-midline distance (SM), Wiltse-midline distance (WM), surgical approach angle, depth, and multifidus muscle displacement were compared. Pearson correlation and multivariate linear regression analyses were performed to explore associations between CT parameters, operative time, blood loss, and eCSA atrophy.Results:Baseline characteristics showed no significant differences between groups ( P>0.05). The MO-TLIF group exhibited shorter operative time (109.85±7.82 min vs. 133.82±20.22 min), reduced blood loss (77.21±21.83 ml vs. 141.18±31.44 ml), smaller incision length (6.09±0.22 cm vs. 7.00±0.43 cm), shorter bedrest duration (1.59±0.49 d vs. 2.38±0.50 d), and shorter hospital stay (8.93±1.44 d vs. 10.35±1.45 d), but higher fluoroscopy frequency (19.53±1.92 times vs. 16.29±1.78 times) compared to the MIS-TLIF group ( P<0.05). Complications included fat liquefaction (5 cases) and dural tears (2 cases). Both groups showed improved VAS and ODI postoperatively ( P<0.05). At 3 d postoperatively, the MO-TLIF group had lower VAS (2.74±0.47 points vs. 3.35±0.48 points) and ODI (27.46%±2.16% vs. 30.42%±2.52%) than the MIS-TLIF group ( P<0.05). Postoperative eCSA decreased significantly in the MIS-TLIF group ( P<0.05) but remained stable in the MO-TLIF group ( P>0.05). The MO-TLIF group demonstrated smaller SM (8.43±1.81 mm vs. 31.15±6.53 mm), approach angle, depth, and muscle displacement ( P<0.05). CT parameters in the MO-TLIF group showed no correlation with operative time, blood loss, or eCSA atrophy ( r<0.3, P>0.05), whereas parameters in the MIS-TLIF group correlated positively with these outcomes (0.3< r<0.6, P<0.05). Multivariate regression revealed a significant association between CT parameters and eCSA atrophy in the MIS-TLIF group ( R 2=0.474, P<0.05). Conclusion:Compared to MIS-TLIF, MO-TLIF reduces intraoperative blood loss, accelerates recovery, and minimizes paraspinal muscle trauma.

Objective:Primary bladder chondroma is extremely rare in clinical practice.We report a case of primary bladder chondroma. The patient presented with urinary frequency and urgency for over one month, and a hypoechoic nodule on the anterior bladder wall was detected via urinary tract ultrasound. Preoperative evaluation suggested a benign bladder lesion, and transurethral resection of the bladder tumor was performed. Postoperative histopathology confirmed the diagnosis of bladder chondroma. Regular follow-up for over one year revealed no signs of recurrence or metastasis.

Objective:Primary bladder chondroma is extremely rare in clinical practice.We report a case of primary bladder chondroma. The patient presented with urinary frequency and urgency for over one month, and a hypoechoic nodule on the anterior bladder wall was detected via urinary tract ultrasound. Preoperative evaluation suggested a benign bladder lesion, and transurethral resection of the bladder tumor was performed. Postoperative histopathology confirmed the diagnosis of bladder chondroma. Regular follow-up for over one year revealed no signs of recurrence or metastasis.

Objective:To investigate the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for biopsy-negative esophageal strictures suspected for malignancy.Methods:Patients who underwent EUS-FNA for esophageal strictures with negative endoscopic biopsies in Nanjing Drum Tower Hospital from January 2014 to March 2022 were analyzed retrospectively. The final diagnosis was based on the pathological outcomes of EUS-FNA or surgery, complemented by follow-up data. Diagnostic efficacy and complication rates of EUS-FNA were analyzed.Results:A total of 64 patients were included in this study,with 54 ultimately diagnosed with malignant lesions and 10 with benign lesions. Malignant lesions were diagnosed by EUS-FNA in 50 cases, suspected malignant lesions in 3 cases, and no clear basis for malignancy was observed in 11 cases. The diagnostic accuracy of EUS-FNA was 98.4% (63/64), with the malignant tumor detection rate of 98.1% (53/54). No post-procedure complications such as bleeding, perforation, or infection were observed in any patient.Conclusion:EUS-FNA is safe and effective for the diagnosis of biopsy-negative suspected malignant esophageal stricture with a high malignant lesion detection rate.

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.