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 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: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: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: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.

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.