Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

Objective:To investigate the therapeutic outcomes of patients with horseshoe kidney and hydronephrosis under different surgical approaches and with or without isthmus division.Methods:This study is a retrospective case series research. A retrospective analysis was conducted on the clinical data of 23 patients with horseshoe kidney and hydronephrosis who underwent pyeloplasty at the Department of Urology, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, there were 11 males and 12 females, with an age of (33±15) years (range:7 to 64 years). Patients underwent preoperative examinations, including ultrasonography of the urinary system, intravenous urography, CT urography, or magnetic resonance urography. Retrograde urography or antegrade ureteropyelography was performed when necessary to clarify the degree of hydronephrosis, the location and length of ureteral stricture. For patients with severe hydronephrosis, a ureteral stricture segment >2 cm, a thick renal isthmus in horseshoe kidney, and markedly variant vasculature, open surgery or robotic surgery is preferred. For those with mild to moderate hydronephrosis, a ureteral stricture segment <2 cm, a thin renal isthmus in horseshoe kidney, and no significant vascular variations, laparoscopic surgery is the first choice. The decision to perform isthmectomy should be made based on a comprehensive intraoperative assessment, including the vascular supply to the isthmus, the degree of surrounding adhesions, and the thickness of the isthmus. Perioperative parameters and complications were recorded and analyzed, and regular follow-up was conducted for all patients.Results:All surgeries were successfully completed. Surgical approaches included open surgery in 4 cases, laparoscopic surgery in 14 cases, and robot-assisted laparoscopic surgery in 5 cases. The operative time for open surgery, laparoscopic surgery and robot-assisted laparoscopic surgery was (125±12) minutes (range: 112 to 141 minutes), (122±50) minutes (range: 60 to 233 minutes), and (130±36) minutes (range: 76 to 174 minutes), respectively. The blood loss ( M(IQR)) was 100 (25) ml (range: 50 to 100 mL) for open surgery, 35 (30) ml (range: 10 to 100 mL) for laparoscopic surgery, and 20 (10) ml (range: 20 to 50 ml) for robot-assisted laparoscopic surgery. Among 15 patients who underwent isthmus division with pyeloplasty (division group), the operation time was (138±42) minutes (range: 73 to 233 minutes), with blood loss of 50 (80) ml (range: 20 to 100 ml). For 8 patients in the non-division group who only underwent pyeloureteroplasty, the operation time was (98±27) minutes (range: 60 to 135 minutes), with blood loss of 20 (50) ml (range: 10 to 100 ml). The follow-up time of patients after surgery was 16.0 (49.0) months (range: 1.7 to 84.2 months), with a surgical success rate of 100%. Among the 8 patients in the non-division group, all demonstrated significant improvement in hydronephrosis severity compared to preoperative conditions. Notably, 6 patients who previously experienced frequent lower back pain showed no recurrence of symptoms after ureteral stent removal. In the division group of 15 patients, both subjective symptoms and hydronephrosis severity were markedly reduced. Conclusion:For patients with horseshoe kidney and hydronephrosis, the choice of surgical approach and isthmus management strategy should be determined based on a comprehensive consideration of the etiology of hydronephrosis, the degree of ureteral stricture, anatomical abnormalities, and vascular variations.

Objective:To investigate the therapeutic outcomes of patients with horseshoe kidney and hydronephrosis under different surgical approaches and with or without isthmus division.Methods:This study is a retrospective case series research. A retrospective analysis was conducted on the clinical data of 23 patients with horseshoe kidney and hydronephrosis who underwent pyeloplasty at the Department of Urology, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, there were 11 males and 12 females, with an age of (33±15) years (range:7 to 64 years). Patients underwent preoperative examinations, including ultrasonography of the urinary system, intravenous urography, CT urography, or magnetic resonance urography. Retrograde urography or antegrade ureteropyelography was performed when necessary to clarify the degree of hydronephrosis, the location and length of ureteral stricture. For patients with severe hydronephrosis, a ureteral stricture segment >2 cm, a thick renal isthmus in horseshoe kidney, and markedly variant vasculature, open surgery or robotic surgery is preferred. For those with mild to moderate hydronephrosis, a ureteral stricture segment <2 cm, a thin renal isthmus in horseshoe kidney, and no significant vascular variations, laparoscopic surgery is the first choice. The decision to perform isthmectomy should be made based on a comprehensive intraoperative assessment, including the vascular supply to the isthmus, the degree of surrounding adhesions, and the thickness of the isthmus. Perioperative parameters and complications were recorded and analyzed, and regular follow-up was conducted for all patients.Results:All surgeries were successfully completed. Surgical approaches included open surgery in 4 cases, laparoscopic surgery in 14 cases, and robot-assisted laparoscopic surgery in 5 cases. The operative time for open surgery, laparoscopic surgery and robot-assisted laparoscopic surgery was (125±12) minutes (range: 112 to 141 minutes), (122±50) minutes (range: 60 to 233 minutes), and (130±36) minutes (range: 76 to 174 minutes), respectively. The blood loss ( M(IQR)) was 100 (25) ml (range: 50 to 100 mL) for open surgery, 35 (30) ml (range: 10 to 100 mL) for laparoscopic surgery, and 20 (10) ml (range: 20 to 50 ml) for robot-assisted laparoscopic surgery. Among 15 patients who underwent isthmus division with pyeloplasty (division group), the operation time was (138±42) minutes (range: 73 to 233 minutes), with blood loss of 50 (80) ml (range: 20 to 100 ml). For 8 patients in the non-division group who only underwent pyeloureteroplasty, the operation time was (98±27) minutes (range: 60 to 135 minutes), with blood loss of 20 (50) ml (range: 10 to 100 ml). The follow-up time of patients after surgery was 16.0 (49.0) months (range: 1.7 to 84.2 months), with a surgical success rate of 100%. Among the 8 patients in the non-division group, all demonstrated significant improvement in hydronephrosis severity compared to preoperative conditions. Notably, 6 patients who previously experienced frequent lower back pain showed no recurrence of symptoms after ureteral stent removal. In the division group of 15 patients, both subjective symptoms and hydronephrosis severity were markedly reduced. Conclusion:For patients with horseshoe kidney and hydronephrosis, the choice of surgical approach and isthmus management strategy should be determined based on a comprehensive consideration of the etiology of hydronephrosis, the degree of ureteral stricture, anatomical abnormalities, and vascular variations.

[Objective] To analyze the influencing factors of postoperative patency of longitudinal single suture intussusception microsurgical vasoepididymostomy, to provide reference for improving the repetition rate. [Methods] The clinical data of 82 patients with epididymal obstructive azoospermia who underwent longitudinal single suture intussusception microsurgical vasoepididymostomy in our hospital during Sep.2020 and Jan.2023 were retrospectively analyzed.The postoperative patency and spouse pregnancy were followed up by face to face and / or telephone interview.The effects of age, course of disease, body mass index (BMI), previous medical history (epididymitis, operation history, none), preoperative seminal plasma elastase (SPE) level, anastomosis site, unilateral and bilateral lesion, sperm quality, operation time and hospital stay on the postoperative patency rate were analyzed. [Results] All operations were successful, the follow-up rate was 95.12% (78/82), 78 were married, and the postoperative patency was 78.21% (61/78). Of the 61 patients who achieved patency, 56 were married, and the natural pregnancy rate of spouse was 45.21% (33/73). Univariate analysis showed that patients with age <30 years, course of disease <2 years, preoperative SPE level <290 ng/mL, bilateral anastomosis, body or tail anastomosis and motile sperm had higher postoperative patency rate (P>0.05). BMI, previous history, the number of motile sperms examined by epididymal fluid, the length of operation and hospital stay had no significant effects on postoperative patency (P>0.05). The results of multivariate logistic regression analysis showed that preoperative SPE level (OR=0.998, 95%CI: 0.997-1.000, P=0.008) and (OR=10.724, 95%CI: 2.243-51.283, P=0.003) were significantly correlated with postoperative patency. [Conclusion] The preoperative SPE level and anastomosis site are significant influencing factors of postoperative patency, which is higher in patients with age <30 years, course of disease <2 years, preoperative SPE level <290 ng/mL, bilateral anastomosis, body or tail anastomosis and motile sperm.

【Objective】 To analyze the application value of penile vibrating perception threshold measurement in the diagnosis of erectile dysfunction (ED) and provide reference for the seversity of ED patients. 【Methods】 The clinical data, Erectile Hardness Scale (EHS) score, International Index of Erectile Function Questionnaire-5 (IIEF-5) score, and the vibrating perception threshold (VPT) of the penis of 257 patients with decreased erectile function as the main complaint or accompanying symptoms treated during Jan. and Dec.2021 were retrospectively collected and analyzed.Patients with EHS=4 and IIEF-5≥22 were classified into the normal group, and the rest into the ED group.The differences in VPT in patients with different EHS scores were compared, and the correlation between IIEF-5 and VPT was analyzed.The diagnostic value of VPT for ED was evaluated with receiver operating characteristic (ROC) curve. 【Results】 The difference in penile VPT among patients with different EHS scores was statistically significant (P<0.05).With the decrease of EHS score, VPT showed an increasing trend.Glans VPT was negatively correlated with IIEF-5 score (ρ=-0.22, P<0.001), and penile shaft VPT was also negatively correlated with IIEF-5 score (ρ=-0.26, P<0.001).The VPT of glans penis [(4.17±1.37) V vs.(3.47±1.24) V, P=0.009] and the VPT of penis body [(3.73±1.41) V vs.(2.99±1.14)V, P=0.003] in the ED group were both higher than those in the normal group.The area under the ROC curve (AUC) of the glans VPT was 0.642.When the cut-off value was 3.537 V, the sensitivity was 63.4%, and the specificity was 63.6%.The AUC of the penile shaft VPT was 0.659.When the cut-off value was 2.775 V, the sensitivity was 72.3%, with a specificity of 54.5%. 【Conclusion】 The penile VPT of ED patients is higher than that of normal ones, and there is a correlation between VPT and the severity of ED.Severe ED is associated with higher VPT.The measurement of penile VPT is helpful for the clinical diagnosis of ED patients.

【Objective】 To introduce a modified microdot two-layer microsurgical vasovasostomy (MVV) and to analyze its effectiveness in patients with vas deferens obstruction caused by inguinal herniorrhaphy. 【Methods】 Clinical data of patients treated during Mar.2015 and Oct.2020 were retrospectively analyzed. According to different surgical methods, the patients were divided into the modified group and traditional group. The general data, intraoperative conditions, efficacies and complications of the two groups were compared. 【Results】 There were 59 cases in the modified group, 54(91.5%) of whom were successfully followed up, and 41 cases in the traditional group, 38(92.7%) of whom were successfully followed up. There were no significant differences in age, inguinal herniorrhaphy history, and unilateral/bilateral ratio between the two groups (P>0.05). The average operation time for unilateral lesions in the modified group was shorter than that in the traditional group [(89.44±24.86) vs. (112.04±43.40) min, P=0.032]. The postoperative patency rate (83.3% vs.73.7%, P>0.05) and natural pregnancy rate (33.3% vs.28.9%, P>0.05) of the modified group and traditional group were comparable. Incision fat liquefaction occurred in 2 cases (3.70%) in the modified group and in 1 case (2.63%) in the traditional group (P>0.05). 【Conclusion】 The modified microdot two-layer MVV is a safe surgical method with comparable effectiveness as the traditional approach. By adjusting the position of the marking points and the order of suturing, it helps the management of sutures, reduces the difficulty of vasovasostomy, shortens operation time, and can be applied to repair vas deferens obstruction caused by inguinal herniorrhaphy.

Objective:To evaluate the role of secreted protein acidic and rich in cysteine like protein 1 (SPARCL1) in spinal dorsal horns in the development of remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Forty-eight healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 6 groups ( n=8 each) using a random number table method: control group (group C), incisional pain group (group I), remifentanil group (group R), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus negative control group (group I+ R+ N), and incisional pain plus remifentanil plus SPARCL1-siRNA group (group I+ R+ S). In I+ R+ N and I+ R+ S groups, 1×10 8 IFU/ml negative control siRNA and SPARCL1-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C, I, R and I+ R groups.After transfection was stable, normal saline 0.1 ml was intravenously injected through the tail vein for 4 consecutive times at 15 min interval in C and I groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was intravenously injected via the tail vein for 4 consecutive times at 15 min interval in R, I+ R, I+ R+ N and I+ R+ S groups.The incisional pain model was established after the first administration via the tail vein in R, I+ R, I+ R+ N and I+ R+ S groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusing normal saline or remifentanil (T 0) and 3, 6, 24 and 48 h after stopping infusion (T 1-4). Animals were sacrificed after measuring pain threshold at T 4, and L 4-6 segments of the spinal cord were removed for determination of the expression of SPARCL1 protein and mRNA by Western blot and quantitative real-time polymerase chain reaction, respectively. Results:Compared with group C, MWT was significantly decreased and TWL was shortened at T 1-4 in I+ R and I+ R+ N groups and at T 2-4 in I, R and I+ R+ S groups, and the expression of SPARCL1 protein and mRNA was significantly up-regulated in R, I+ R and I+ R+ C groups ( P<0.05 or 0.01). Compared with group I and group R, MWT was significantly decreased, TWL was shortened, and the expression of SPARCL1 protein and mRNA was up-regulated in group I+ R ( P<0.01). Compared with group I+ R, MWT was significantly increased and TWL was prolonged at T 1-4, and the expression of SPARCL1 protein and mRNA was down-regulated in group I+ R+ S ( P<0.05 or 0.01). Conclusion:Enhanced activity of SPARCL1 in the spinal dorsal horns is involved in the development of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective: To evaluate the role of neuroligin 1 (NL-1) in trafficking of GluR1-containing AMPA receptor to cell membrane in spinal cord dorsal horns during remifentanil-induced hyperalgesia in mice with incisional pain. Methods: Forty SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 5 groups (n=8 each) using a random number table method: control group (group C), NL1-shRNA plasmid group (group NL), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus blank vector group (group I+ R+ B), and incisional pain plus remifentanil plus NL-1-shRNA plasmid group (group I+ R+ NL). Negative lentivirus was intrathecally injected in group I+ R+ B.In NL and I+ R+ NL groups, 10 μl NL-1-shRNA lentivirus at 1×10⁸ IFU/ml was intrathecally injected once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected at the same time point in C and I+ R groups.After transfection was stable, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at 15 min intervals in C and NL groups.In I+ R, I+ R+ B and I+ R+ NL groups, 0.1 ml remifentanil 10 μg/kg was injected via the caudal vein for 4 consecutive times at 15 min intervals, and the model of incisional pain was established after the first administration.The mechanical paw withdrawal threshold (MWT) and tail-flick latency (TFL) were measured at 24 h before normal saline or remifentanil administration (T₀) and at 3, 6, 24 and 48 h after the end of administration (T_1-4). The animals were sacrificed after measurement of pain threshold at T₄, and L_4-6 segments of the spinal dorsal horn were then collected for determination of the expression of NL-1 protein and mRNA and AMPA receptors, and the ratio of AMPA receptor expression in the membrane protein to that in the total protein (m/t ratio) was calculated. Results: Compared with group C, the MWT was significantly decreased, and TFL was shortened at T_1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was up-regulated, and m/t ratio was increased in I+ R and I+ R+ B groups (P<0.05). Compared with I+ R and I+ R+ B groups, the MWT was significantly increased and TFL was prolonged at T_1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was down-regulated, and m/t ratio was decreased in group I+ R+ NL (P<0.05). Conclusion NL-1 in spinal cord dorsal horns can promote the trafficking of GluR1-containing AMPA receptors to cell membrane, which is involved in the development and maintenance of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective: To evaluate the role of spinal COX-1 and COX-2 in remifentanil-induced hyperalgesia in mice with incisional pain. Methods: Thirty-two male C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), incisional pain plus remifentanil group (group IR), incisional pain plus remifentanil plus selective COX-1 inhibitor group (group IR+ SC560), and incisional pain plus remifentanil plus selective COX-2 inhibitor group (group IR+ SC236). In IR, IR+ SC560 and IR+ SC236 groups, normal saline 10 μl, SC560 25 μg and SC236 25 μg were intrathecally injected, respectively, 15 min later remifentanil 10 μg/kg was injected via the tail vein for 4 times at 15 min intervals.An incisional pain model was established after the first injection of remifentanil.The mechanical paw withdrawal threshold (MWT) was measured at 24 h before normal saline or remifentanil injection and 3, 6, 24 and 48 h after the last injection (T₀-T₄). The mice were sacrificed after the last measurement of pain threshold, and the L_4-6 segments of the spinal cord were removed for determination of the expression of COX-1 and COX-2 (by Western blot) and expression of COX-1 and COX-2 mRNA (by quantitative real-time polymerase chain reaction). Results: Compared with group C, the MWT was significantly decreased, and the expression of COX-2 protein and mRNA was up-regulated in IR, IR+ SC560 and IR+ SC236 groups (P<0.05). Compared with group IR, the MWT was significantly increased in IR+ SC560 and IR+ SC236 groups (P<0.05). There was no significant difference in the MWT at each time point between IR+ SC560 and IR+ SC236 (P>0.05) .There was no significant difference in the expression of COX-2 protein and mRNA among group IR, group IR+ SC560 and group IR+ SC236 (P>0.05). There was no significant difference in the expression of COX-1 protein and mRNA among the four groups (P>0.05). Conclusion Compared with COX-1, spinal COX-2 plays a major role in the pathophysiological mechanism of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective To evaluate the effect of oxycodone on intestinal ischemia-reperfusion injury in rats and the role of autophagy.Methods Twenty-four healthy adult male Sprague-Dawley rats,aged 6-9 weeks,weighing 180-220 g,were divided into 4 groups (n =6 each) using a random number table method:sham group (group S),intestinal I/R group (group I/R),oxycodone group (group O) and oxycodone plus autophagy inhibitor 3-methyladenine (3-MA) group (group O+3-MA).Intestinal I/R was induced via clamping the superior mesenteric artery for 1 h,followed by 2-h reperfusion in all the groups except for group S.Oxycodone 0.5 mg/kg was injected via caudal vein at 15 min before ischemia in group O and group O+3-MA.3-MA 30 mg/kg was intraperitoneally injected at 10 min before ischemia in group O+3-MA.Rats were gavaged with fluorescein-isothiocyanate-conjugated dextran (FITC-dextran) immediately before ischemia.Blood samples were collected from the cardiac apex at 2 h of reperfusion to detect the level of serum FITC-dextran.Blood samples were collected from the cardiac apex at 2 h of reperfusion to measure the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in serum by enzyme-linked immunosorbent assay.Small intestinal tissues were obtained at 2 h of reperfusion for examination of the pathological changes and for determination of the expression of occludin,Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3) (by Western blot).Intestinal damage was assessed and scored according to Chiu.The ratio of LC3 Ⅱ expression to LC3 Ⅰ expression (LC3 Ⅱ / Ⅰ) was calculated.Results Compared with group S,the Chiu's score,levels of serum FITC-dextran,TNF-α and IL-1β and LC3 Ⅱ/Ⅰ ratio were significantly increased,the expression of Beclin-1 was up-regulated,and the expression of occludin was down-regulated in group I/R (P＜0.05).Compared with group I/R,the Chiu's score and levels of serum FITC-dextran,TNF-α and IL-1β were significantly decreased,LC3 Ⅱ / Ⅰ ratio was increased,and the expression of occludin and Beclin-1 was up-regulated in group O (P＜0.05),and no significant change was found in the parameters mentioned above in group O+ 3-MA (P＞0.05).Compared with group O,the Chiu's score and levels of serum FITC-dextran,TNF-α and IL-1β were significantly increased,LC3 Ⅱ / Ⅰ ratio was decreased,and the expression of occludin and Beclin-1 was down-regulated in group O + 3-MA (P＜ 0.05).Conclusion Oxycodone can ameliorate intestinal I/R injury,and the mechanism may be related to enhancing autophagy in intestinal tissues of rats.