Metanephric adenoma is a rare renal epithelial tumor with a low incidence and lack of specific clinical manifestations，resulting in a lack of uniformity in clinical understanding and treatment. Its etiology and pathogenesis are still unclear，and it may be related to the abnormal number and structure of chromosomes 2，7，and 17，as well as mutations in genes such as BRAF V600E，NF1，and NOTCH1，etc. There may be a transformed relationship between this tumor and Wilms’ tumor and papillary renal cell carcinoma. For diagnosis，it has diverse but non-specific clinical manifestations，and it is difficult to accurately differentiate it from other tumors in the imaging examination，and the confirmation of diagnosis relies on pathological and immunohistochemical staining. Treatment is mainly based on surgery to preserve the renal unit，such as partial nephrectomy，etc.，but the difficulty of preoperative diagnosis often leads to over-treatment，and there is a lack of standardized treatment protocols for metastatic posterior renal adenoma. The aim of this article is to provide a reference for the in-depth understanding of posterior renal adenomas and to optimize the clinical diagnosis and treatment strategies.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

Objective:To compare postoperative complications between acellular dermal matrix（ADM）and direct suture for tongue mucosa defect repair during lingual mucosa urethroplasty.Methods:A retrospective analysis was conducted on 106 patients with anterior urethral stricture who underwent lingual mucosal urethroplasty at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to July 2024. According to the needs of urethral reconstruction，lingual mucosa was harvested（graft length 0.5 cm longer than the stricture length）. Using an instrumental variable method based on the surgeon’s preference，the tongue wound was repaired either with ADM or direct suture. The ADM group included 56 patients，aged（46.2±18.7）years；diabetes in 8 cases（14.3%），hypertension in 15 cases（26.8%），cardiopulmonary dysfunction in 3 cases（5.3%）；stricture location：penile segment in 44 cases（78.6%），penoscrotal junction in 12 cases（21.4%）；etiology：lichen sclerosus in 8 cases（14.3%），urethritis in 8 cases（14.3%），trauma in 24 cases（42.9%），and re-stricture after hypospadias surgery in 16 cases（28.6%）；maximum urinary flow rate（5.8±2.9）ml/s；graft length（4.02±1.72）cm. The direct suture group included 50 patients，aged（45.8±19.2）years；diabetes in 6 cases（12.0%），hypertension in 12 cases（24.0%），cardiopulmonary dysfunction in 2 cases（4.0%）；etiology：lichen sclerosus in 6 cases（12.0%），urethritis in 8 cases（16.0%），trauma in 25 cases（50.0%），and re-stricture after hypospadias surgery in 11 cases（22%）；stricture location：penile segment in 36 cases（72.0%），penoscrotal junction in 14 cases（28.0%）；maximum urinary flow rate（6.2±3.1）ml/s；graft length（4.18±1.68）cm. There were no statistically significant differences in the above baseline characteristics between the two groups（ P>0.05）.ADM group after electrocautery hemostasis，an ADM patch tailored to the wound size was used to cover the donor site. The edges of the ADM were overlapped with the wound margin and sutured to the submucosal layer using interrupted 4-0 polyglactin sutures. Direct suture group after electrocautery hemostasis，the wound was stretched into a diamond shape and closed in layers by suturing the mucosal layer down to the muscle layer using interrupted 4-0 polyglactin sutures. The primary outcome measures were postoperative tongue complications including hemorrhage，hematoma，and infection（Clavien-Dindo classification）. Secondary outcomes included VAS pain scores，functional recovery（difficulty drinking，difficulty eating，speech impairment，limited mouth opening），and sensory recovery（sensory disturbance，taste disturbance）. Results:The follow-up period ranged from 6 to 24 months，with a mean of 9.2 months. The 6-month follow-up rate was 100%. No Clavien-Dindo grade Ⅲ or higher complications（hemorrhage，hematoma，infection）occurred by the end of follow-up. Regarding secondary outcomes，the VAS pain score on postoperative day 1 was significantly better in the ADM group than in the suture group［0（0，3）vs. 2（0，3），P=0.013］.Functional impact：The incidence of difficulty drinking［24 cases（42.9%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 21 cases（42.0%）］，difficulty eating［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］，and speech impairment［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］on postoperative day 1，day 7，and within the first month，respectively，was significantly lower in the ADM group（all P<0.05）. On postoperative day 1 and day 7，the incidence of limited mouth opening was higher in the ADM group［0 cases vs. 6 cases（12.0%），0 cases vs. 6 cases（12.0%）］（ P<0.05）.Sensory recovery：The incidence of taste disturbance was higher in the ADM group at 7 days［8 cases（14.3%）vs. 0 cases］，1 month［8 cases（14.3%）vs. 0 cases］，and 3 months［8 cases（14.3%）vs. 0 cases］postoperatively（ P<0.05）. The incidence of sensory disturbance was higher in the ADM group at 1 day［20 cases（35.7%）vs. 6 cases（12.0%）］，7 days［16 cases（28.6%）vs. 6 cases（12.0%）］，and 1 month［16 cases（28.6%）vs. 6 cases（12.0%）］postoperatively（ P<0.05）. Pain scores and complication rates were zero in both groups after 6 months. Conclusions:ADM repair improves early recovery but may increase transient sensory complications. Both methods are safe for clinical application.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

Objective:To compare postoperative complications between acellular dermal matrix（ADM）and direct suture for tongue mucosa defect repair during lingual mucosa urethroplasty.Methods:A retrospective analysis was conducted on 106 patients with anterior urethral stricture who underwent lingual mucosal urethroplasty at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to July 2024. According to the needs of urethral reconstruction，lingual mucosa was harvested（graft length 0.5 cm longer than the stricture length）. Using an instrumental variable method based on the surgeon’s preference，the tongue wound was repaired either with ADM or direct suture. The ADM group included 56 patients，aged（46.2±18.7）years；diabetes in 8 cases（14.3%），hypertension in 15 cases（26.8%），cardiopulmonary dysfunction in 3 cases（5.3%）；stricture location：penile segment in 44 cases（78.6%），penoscrotal junction in 12 cases（21.4%）；etiology：lichen sclerosus in 8 cases（14.3%），urethritis in 8 cases（14.3%），trauma in 24 cases（42.9%），and re-stricture after hypospadias surgery in 16 cases（28.6%）；maximum urinary flow rate（5.8±2.9）ml/s；graft length（4.02±1.72）cm. The direct suture group included 50 patients，aged（45.8±19.2）years；diabetes in 6 cases（12.0%），hypertension in 12 cases（24.0%），cardiopulmonary dysfunction in 2 cases（4.0%）；etiology：lichen sclerosus in 6 cases（12.0%），urethritis in 8 cases（16.0%），trauma in 25 cases（50.0%），and re-stricture after hypospadias surgery in 11 cases（22%）；stricture location：penile segment in 36 cases（72.0%），penoscrotal junction in 14 cases（28.0%）；maximum urinary flow rate（6.2±3.1）ml/s；graft length（4.18±1.68）cm. There were no statistically significant differences in the above baseline characteristics between the two groups（ P>0.05）.ADM group after electrocautery hemostasis，an ADM patch tailored to the wound size was used to cover the donor site. The edges of the ADM were overlapped with the wound margin and sutured to the submucosal layer using interrupted 4-0 polyglactin sutures. Direct suture group after electrocautery hemostasis，the wound was stretched into a diamond shape and closed in layers by suturing the mucosal layer down to the muscle layer using interrupted 4-0 polyglactin sutures. The primary outcome measures were postoperative tongue complications including hemorrhage，hematoma，and infection（Clavien-Dindo classification）. Secondary outcomes included VAS pain scores，functional recovery（difficulty drinking，difficulty eating，speech impairment，limited mouth opening），and sensory recovery（sensory disturbance，taste disturbance）. Results:The follow-up period ranged from 6 to 24 months，with a mean of 9.2 months. The 6-month follow-up rate was 100%. No Clavien-Dindo grade Ⅲ or higher complications（hemorrhage，hematoma，infection）occurred by the end of follow-up. Regarding secondary outcomes，the VAS pain score on postoperative day 1 was significantly better in the ADM group than in the suture group［0（0，3）vs. 2（0，3），P=0.013］.Functional impact：The incidence of difficulty drinking［24 cases（42.9%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 21 cases（42.0%）］，difficulty eating［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］，and speech impairment［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］on postoperative day 1，day 7，and within the first month，respectively，was significantly lower in the ADM group（all P<0.05）. On postoperative day 1 and day 7，the incidence of limited mouth opening was higher in the ADM group［0 cases vs. 6 cases（12.0%），0 cases vs. 6 cases（12.0%）］（ P<0.05）.Sensory recovery：The incidence of taste disturbance was higher in the ADM group at 7 days［8 cases（14.3%）vs. 0 cases］，1 month［8 cases（14.3%）vs. 0 cases］，and 3 months［8 cases（14.3%）vs. 0 cases］postoperatively（ P<0.05）. The incidence of sensory disturbance was higher in the ADM group at 1 day［20 cases（35.7%）vs. 6 cases（12.0%）］，7 days［16 cases（28.6%）vs. 6 cases（12.0%）］，and 1 month［16 cases（28.6%）vs. 6 cases（12.0%）］postoperatively（ P<0.05）. Pain scores and complication rates were zero in both groups after 6 months. Conclusions:ADM repair improves early recovery but may increase transient sensory complications. Both methods are safe for clinical application.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

Metanephric adenoma is a rare renal epithelial tumor with a low incidence and lack of specific clinical manifestations，resulting in a lack of uniformity in clinical understanding and treatment. Its etiology and pathogenesis are still unclear，and it may be related to the abnormal number and structure of chromosomes 2，7，and 17，as well as mutations in genes such as BRAF V600E，NF1，and NOTCH1，etc. There may be a transformed relationship between this tumor and Wilms’ tumor and papillary renal cell carcinoma. For diagnosis，it has diverse but non-specific clinical manifestations，and it is difficult to accurately differentiate it from other tumors in the imaging examination，and the confirmation of diagnosis relies on pathological and immunohistochemical staining. Treatment is mainly based on surgery to preserve the renal unit，such as partial nephrectomy，etc.，but the difficulty of preoperative diagnosis often leads to over-treatment，and there is a lack of standardized treatment protocols for metastatic posterior renal adenoma. The aim of this article is to provide a reference for the in-depth understanding of posterior renal adenomas and to optimize the clinical diagnosis and treatment strategies.

Objective:To investigate the effect of gracilis flap in repair of radiation-induced vesicovaginal fistula.Methods:The data of 18 patients with radiation-induced vesicovaginal fistula treated in the Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2021 to August 2022 were retrospectively reviewed. Their age was (57.3±10.4) years. All patients underwent radical surgery for cervical cancer, and received (24.6±2.8)(range from 20 to 30)times of radiotherapy after surger. The median time between the end of radiotherapy and the onset of vesicovaginal fistula was 14.0(7.8, 18.2)months. The median duration of fistula urine was 12.0(9.8, 18.0)months. All patients were required to use median 19.5(15.8, 27.5) pads per day before surgery. The life quality score(QOL)of 18 cases was median 5.0(5.0, 6.0) points. Three cases had performed laparoscopic vesicovaginal fistula repair, two cases had underwent transvaginal vesicovaginal fistula repair, one case had underwent transvaginal and laparoscopic vesicovaginal fistula repair successively, and the remaining 12 cases were new vesicovaginal fistulas. Two cases were combined with rectovaginal fistulas. All patients underwent the repair of vesicovaginal fistula with gracilis flap interposition in prone and folded knife position, by transvaginal route, the vesicovaginal fistula was mobilized and the two layers were closed, and the vascular pedicle gracilis flap of left inner leg was romoved under the skin tunnel to repair the vesicovaginal fistula. Meanwhile, two cases combined rectovaginal fistulas were repaired and closed the rectovaginal fistulas. The urinary catheters were removed at 3 weeks after the operation and urination was recorded.Results:All patients underwent smooth surgery in (96.6±13.2) minutes. The median follow-up was 13.0(9.8, 20.2)(range from 6 to 24)months. The median number of urine pads used per day in 18 patients was 2.0(1.0, 11.8), and significantly reduced ( P<0.01).QOL score was median 1.0(0, 4.2) point and significantly reduced ( P<0.01).Successful outcome was achieved in 12 patients with no leakage of urine in the vagina. Two cases developed urinary incontinence and required conservative treatment, but the curative effect was poor. Two cases still had vaginal urine leakage performed vesicovaginal fistula repair again. One case was successfully repaired without significant urine leakage.The other case still had significant urine leakage and the QOL score was 3 points. She refused further treatment for self-satisfied. Two cases still had vesicovaginal fistula and rectovaginal fistula after the surgery, and refused further surgery. Conclusions:Repair with gracilis flap interposition is a surgical method with few complications and reliable surgical effect for patients with radiation-induced vesicovaginal fistula.

OBJECTIVE To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin.METH-ODS The concentrations of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine were determined by UPLC.The effects of temperature,perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods,the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC,and DAS 2.0 software was used to process the data.RESULTS The recovery rate of the probe increased with increasing temperature,and the higher the flow rate,the lower the recovery rate.The pharmacokinetic parameters of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine in microemulsion Cmax were(3.24±0.39)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL-1,respectively,and in AUC0-∞ were(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·mg·mL-1,respectively.CONCLUSION A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microe-mulsion after transdermal administration,which provides a reference for the follow-up investigation and application of crossbow microe-mulsion.