TRIM65 deficiency alleviates renal fibrosis through NUDT21-mediated alternative polyadenylation.

Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the progression of CKD, but the mechanisms behind it are not fully understood, making treatment options limited. Here, we find that the E3 ligase TRIM65 is a positive regulator of renal fibrosis. Deletion of TRIM65 results in a reduction of pathological lesions and renal fibrosis in mouse models of kidney fibrosis induced by unilateral ureteral obstruction (UUO)- and folic acid. Through screening with a yeast-hybrid system, we identify a new interactor of TRIM65, the mammalian cleavage factor I subunit CFIm25 (NUDT21), which plays a crucial role in fibrosis through alternative polyadenylation (APA). TRIM65 interacts with NUDT21 to induce K48-linked polyubiquitination of lysine 56 and proteasomal degradation, leading to the inhibition of TGF-ß1-mediated SMAD and ERK1/2 signaling pathways. The degradation of NUDT21 subsequently altered the length and sequence content of the 3'UTR (3'UTR-APA) of several pro-fibrotic genes including Col1a1, Fn-1, Tgfbr1, Wnt5a, and Fzd2. Furthermore, reducing NUDT21 expression via hydrodynamic renal pelvis injection of adeno-associated virus 9 (AAV9) exacerbated UUO-induced renal fibrosis in the normal mouse kidneys and blocked the protective effect of TRIM65 deletion. These findings suggest that TRIM65 promotes renal fibrosis by regulating NUDT21-mediated APA and highlight TRIM65 as a potential target for reducing renal fibrosis in CKD patients.

Dexmedetomidine enhances Mitophagy via PINK1 to alleviate hippocampal neuronal Pyroptosis and improve postoperative cognitive dysfunction in elderly rat.

Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis.

CircRbms1 fosters MST1 mRNA and protein levels to motivate myocardial ischaemia-reperfusion injury via autophagic status.

AIMS: Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia-reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury. METHODS AND RESULTS: An in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative real-time PCR (qRT-PCR) and western blot. Cellular proliferation, apoptosis, pyroptosis, and autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual-luciferase reporter assay, RNA pull-down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up-regulated in A/R-induced HCMs and acted as a sponge for miR-142-3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P < 0.05). CircRbms1 knockout reduced cell pyroptosis, improved autophagy and proliferation level in A/R-induced HCMs (all P < 0.05). CircRbms1 knockout alleviated cardiac dysfunction and cell pyroptosis and enhanced autophagy and proliferation in mice through the miR-142-3p/MST1 axis. CONCLUSIONS: CircRbms1 inhibited the miR-142-3p/MST1 axis and played a protective role in myocardial I/R injury. It may provide a new therapeutic target for I/R heart injury.

Initial experience and short-term outcomes of single-port extraperitoneal transvesical robot-assisted radical prostatectomy: a two-center study.

Background: This study presents the procedure of single-port extraperitoneal transvesical approach to robot-assisted radical prostatectomy (SETvRARP) on the da Vinci Xi platform coupling with a 4-channel single port and evaluated the short-term outcomes in the first 72 prostate cancer (PCa) patients. Methods: Seventy-two patients with localized PCa were enrolled. Each operation was conducted by the same single robotic surgery group in two centers using the da Vinci Xi system. Results: The median operation time was 150 min, and the median estimated blood loss was 50 mL. All operations were successfully carried out without open conversion or transfusion. No ≥ Grade II complications were noted. Urethral catheters were routinely removed on postoperative day 7. Sixty-eight (94.4%) patients recovered to immediate urinary continence after surgery, with 72 (100%) patients achieving full continence on postoperative day 14. A positive surgical margin was observed in 15 (20.8%) patients. Postoperative urodynamic studies regarding peak urinary flow, bladder capacity, and residual urine were not statically different from the preoperative results. No biochemical recurrence was noted in all patients within the follow-up period. Postoperative erectile function was not statistically different from the preoperative results (P=0.1697). Conclusions: SETvRARP using the da Vinci Xi system coupling with a 4-channel single port is a valid radical prostatectomy technique in well-selected PCa patients, resulting in superior postoperative recovery of urinary continence. Meanwhile, the outcomes in functional protection and cancer control need to be further investigated with a long-term follow-up duration.

The ADRENAL score: A comprehensive scoring system for standardized evaluation of adrenal tumor.

Objectives: To propose an original and standardized scoring system to quantify the functional and anatomical characteristics of adrenal tumor. Materials and methods: Four groups of consecutive adrenalectomies (n = 458) with heterogeneity in tumor characteristics and surgical approaches, including 212 laparoscopic cases (Group 1) and 105 robotic cases (Group 2) from The First Affiliated Hospital of Nanchang University, 28 robotic cases from Temple University Hospital (Group 3) and 113 laparoscopic cases from The First Affiliated Hospital of Guangxi Medical University (Group 4). All patients were followed up for 4.5 to 5.5 years. Six parameters including functional status or suspicion of malignancy, tumor size, relationship to adjacent organs, intratumoral enhancement on CT, nearness of the tumor to major vessels and body mass index were assessed and scored on a 0, 1 and 2 points scale. Correlation between the sum of the 6 scores and tumor laterality (ADRENAL score) verse operative time (OT), estimated blood loss (EBL), perioperative complications, transfusion, conversion and length of hospital stay was analyzed. Results: ADRENAL score was a strong predictor of both OT and EBL in all four groups (p < 0.05 for all tests). In Group 2 and 4, higher ADRENAL score seemed to correlate with longer hospital stay. No statistically significant correlation between ADRENAL score and complication, transfusion or conversion was noted yet. Conclusions: ADRENAL score appears to be a valid predictor of surgical outcomes. It may provide a common reference for adrenal surgery training program, preoperative risk assessment and stratified comparative analysis of adrenal surgeries via different techniques and approaches.

Clinical Study on Anesthesia with Remifentanil and Propofol in Patients with High Hemodynamics.

Objective: To study the effect of remifentanil and propofol as an anesthesia regimen in patients with high hemodynamics. Methods: From January 2019 to October 2020, 200 patients with high hemodynamics undergoing surgery at the First Affiliated Hospital of Nanchang University in China were selected as study participants, including 100 patients anesthetized with remifentanil and propofol (research group), and 100 patients anesthetized with fentanyl and propofol (control group). Vital signs, hemodynamic changes and recovery time after anesthesia were compared in the 2 groups and any adverse events while under anesthesia were recorded. Results: Both groups had significant fluctuations in vital signs and hemodynamics during anesthesia (P > .05), but the research group showed smaller changes with more stable vital signs and hemodynamics (P < .05). In addition, postoperative recovery time from anesthesia was shorter and the incidence of adverse events was lower in the research group than in the control group (P < .05). Conclusion: Remifentanil-propofol anesthesia is simple, convenient, safe and reliable in patients with high hemodynamics, and can integrate narcotic drugs with blood pressure control.

Is robot-assisted retroperitoneal adrenalectomy safe? An investigation of perioperative hypertensive crisis among hypertensive and normotensive patients.

BACKGROUND: Objective: We examined the incidence of perioperative hypertensive crisis in robot-assisted retroperitoneal laparoscopic adrenalectomy. METHODS: A consecutive series of 120 patients with adrenal tumours undergoing robot-assisted retroperitoneal laparoscopic adrenalectomy were included. Patients were divided into two groups: group A (hypertension group, 58 cases, mean age 43.59 years) and group B (normotension group, 62 cases, mean age 48.01 years). General anaesthesia was applied using endotracheal intubation and haemodynamic changes were closely monitored. RESULTS: A total of nine (7.5%) hypertensive crisis cases were observed. After intravenous infusion of sodium nitroprusside, seven cases of them were quickly controlled and two cases experienced transient severe hypertension. The incidence of hypertensive crisis was 13.7% and 1.6% in groups A and B, respectively (p < 0.05). CONCLUSION: These findings highlight the importance of strengthening the monitoring of anaesthesia and taking various measures to effectively control the blood pressure in robot-assisted retroperitoneal laparoscopic adrenalectomy, especially among hypertensive patients.

[Effect of ultrasound-guided right stellate ganglion block on perioperative atrial fibrillation in patients undergoing lung lobectomy: a randomized controlled trial]. / Efeito do bloqueio do gânglio estrelado direito guiado por ultrassom na fibrilação atrial perioperatória em pacientes submetidos a lobectomia pulmonar: estudo controlado randomizado.

OBJECTIVE: To observe the effects of preoperative right stellate ganglion block on perioperative atrial fibrillation in patients undergoing lung lobectomy. METHODS: Two hundred patients who underwent a scheduled lobectomy were randomly divided into the S and C groups. The S group was injected with 4mL of 0.2% ropivacaine under ultrasound guidance, and the C group did not receive stellate ganglion block. The patients underwent continuous ECG monitoring, and the incidences of atrial fibrillation and other types of arrhythmias were recorded from the start of surgery to 24hours after surgery. RESULTS: The respective incidences of atrial fibrillation in the S group and the C group were 3% and 10% (p=0.045); other atrial arrhythmias were 20% and 38% (p=0.005); and ventricular arrhythmia were 28% and 39% (p=0.09). CONCLUSIONS: The results of the study indicated that preoperative right stellate ganglion block can effectively reduce the incidence of intraoperative and postoperative atrial fibrillation.

Effect of ultrasound-guided right stellate ganglion block on perioperative atrial fibrillation in patients undergoing lung lobectomy: a randomized controlled trial / Efeito do bloqueio do gânglio estrelado direito guiado por ultrassom na fibrilação atrial perioperatória em pacientes submetidos a lobectomia pulmonar: estudo controlado randomizado

Abstract Objective: To observe the effects of preoperative right stellate ganglion block on perioperative atrial fibrillation in patients undergoing lung lobectomy. Methods: Two hundred patients who underwent a scheduled lobectomy were randomly divided into the S and C groups. The S group was injected with 4 mL of 0.2% ropivacaine under ultrasound guidance, and the C group did not receive stellate ganglion block. The patients underwent continuous ECG monitoring, and the incidences of atrial fibrillation and other types of arrhythmias were recorded from the start of surgery to 24 hours after surgery. Results: The respective incidences of atrial fibrillation in the S group and the C group were 3% and 10% (p = 0.045); other atrial arrhythmias were 20% and 38% (p = 0.005); and ventricular arrhythmia were 28% and 39% (p = 0.09). Conclusions: The results of the study indicated that preoperative right stellate ganglion block can effectively reduce the incidence of intraoperative and postoperative atrial fibrillation.

Resumo Objetivo: Observar os efeitos do bloqueio do gânglio estrelado na fibrilação atrial no período perioperatório em pacientes submetidos a lobectomia pulmonar. Método: Duzentos pacientes programados para lobectomia foram divididos aleatoriamente nos grupos S e C. O grupo S recebeu infusão de 4 mL de ropivacaína a 0,2% orientada por ultrassom e o grupo C não foi submetido a bloqueio do gânglio estrelado. Os pacientes foram submetidos à monitoração contínua de ECG, e as incidências de fibrilação atrial e outros tipos de arritmias foram registradas do início da cirurgia até 24 horas depois da cirurgia. Resultados: As incidências de fibrilação atrial no grupo S e no grupo C foram 3% e 10%, respectivamente (p = 0,045); as de outras arritmias atriais foram 20% e 38% (p = 0,005); e de arritmias ventriculares, 28% e 39% (p = 0,09). Conclusões: Os resultados do estudo indicaram que o bloqueio do gânglio estrelado no pré-operatório pode ser efetivo na redução da incidência de fibrilação atrial nos períodos intra- e pós-operatório.

Transvesical robot-assisted radical prostatectomy: initial experience and surgical outcomes.

OBJECTIVES: To describe in detail the techniques for transvesical robot-assisted radical prostatectomy (RARP) using the da Vinci Si/Xi system (Intuitive Surgical, Sunnyvale, CA, USA) and to evaluate functional and oncological outcomes in 35 patients with prostate cancer. PATIENTS AND METHODS: Thirty-five patients with localized prostate cancer were enrolled for transvesical RARP. The patients' preoperative data (mean ± sd age 63.4 ± 8.1 years, body mass index 28.6 ± 5.3 kg/m2 , total prostate-specific antigen 10.8 ± 4.9 ng/mL and prostate volume 30.6 ± 14.4 mL, and median [interquartile range {IQR}] biopsy Gleason score 6 [6-7], and International Index of Erectile Function [IIEF]-5 score 18 [16-20]) were collected. Preoperative assessment revealed 28 cases of cT2a and seven cases of cT2b disease. All patients were continent preoperatively (defined as no pad required or one dry pad per day as a precaution). Surgical results and peri-operative complications were assessed. All patients were followed up for at least 12 months postoperatively. RESULTS: The mean operating time was 150 ± 35 min. Estimated blood loss was 100 ± 45 mL. Urinary infection was noted in one patient and managed with levofloxacin. Another patient complained of nocturia on postoperative day 14, which was relieved with solifenacin succinate. Urethral catheters were removed on postoperative day 7. Thirty-two patients achieved immediate urinary continence, with three patients returning to full continence on postoperative day 14. Postoperative pathology confirmed 24 pT2a cases, nine pT2b cases and two pT2c cases (median [IQR] Gleason score 6 [6-7]). Positive surgical margins were found in four patients (11.4%). No urethral stricture or urinary leakage was noted on urethrocystography taken 3 months after surgery. Urodynamic studies were performed preoperatively and 6 months after surgery: median (IQR) maximum urinary flow 12.2 (10.2-14.9) vs 13.7 (10.1-15.0) mL/s; bladder capacity 385.3 (351.3-410.2) vs 370.2 (330.1-395.4) mL; and voiding phase detrusor contractility 38.5 (27.8-42.3) vs 35.6 (28.3-41.3) mmH2 O, respectively. During a minimum of 12 months of follow-up, no biochemical recurrence was noted in any patient. The median (IQR) IIEF-5 score was 17 (16-19). CONCLUSIONS: The transvesical approach is a valid alternative to RARP in selected patients, providing promising postoperative urinary continence. Long-term functional and oncological results require further investigation.

Remifentanil inhibits the traumatic stress response in emergent trauma surgery.

OBJECTIVE: The aim of this study was to explore whether remifentanil could inhibit the stress response in emergent trauma surgery more effectively than sufentanil. PATIENTS AND METHODS: Sixty trauma patients for emergent surgery were randomly divided into remifentanil group (R group, n = 30) or sufentanil group (S group, n = 30). The patients in the R group were continuously intravenously infused with remifentanil, while those in the S group were administrated with sufentanil. The plasma contents of cortisol (COR), epinephrine (E), norepinephrine (NE), and blood glucose were measured before anesthesia induction (T1), 5 minutes after intratracheal intubation (T2) and 5 minutes (T3), 30 minutes (T4), and 1 hour (T5) after surgery, respectively. The blood pressure (BP) and the heart rate (HR) at these time points were recorded as well. RESULTS: The results showed that the patients in the R group had more stable hemodynamics during the surgery and had a significantly lower HR at T2-T5 than those in the S group. The plasma levels of norepinephrine at time points T3-T5 and levels of cortisol at T4-T5 in the R group were significantly lower than those in the S group (P < 0.05). CONCLUSIONS: The results in the present study indicated that remifentanil could inhibit the stress response in emergent trauma surgery patients more effectively than sufentanil.