One of the remarkable progresses regarding non-clear cell renal cell carcinoma in the 2024 ASCO-GU symposium was the survival update of KEYNOTE-B61 study, in which tyrosine kinase inhibitor plus immunotherapy (TKI-IO) combination maintained satisfactory efficacy and safety. The distinct response to immunotherapy between papillary versus chromophobe renal cell carcinoma was demonstrated closely correlated with tumor microenvironment. The fusion partner of TFE-rearranged renal cell carcinoma directly determined the tumor biological behavior and therapeutic response.

Objective:To investigate the efficacy of arthroscopic anatomical reconstruction of the ligament with autologous semitendinosus tendon in the treatment of chronic lateral ankle instability (CLAI) complicated with multiple ligament laxity.Methods:A retrospective study was conducted to analyze the 34 patients with CLAI plus multiple ligament laxity who had been treated at Foot and Ankle Surgery Center, The Fourth Hospital of Wuhan from March 2014 to December 2021. They were 8 males and 26 females with an age of (32.2±5.6) years. The patients were divided into 2 groups based on their treatment methods. A reconstruction group of 20 cases were treated by arthroscopic reconstruction of the ligament with autologous semitendinosus tendon while a repair group of 14 cases treated by arthroscopic repair of the ligament with the modified Brostr?m procedure. The 2 groups were compared in terms of surgical time, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS) pain score, talar tilt (TT), anterior translation of the talus (ATT), and complications at the last follow-up.Results:The 2 groups were comparable because there were no statistically significant differences in the general data, AOFAS ankle-hindfoot score, VAS pain score, TT, or ATT before surgery between the 2 groups ( P > 0.05). The surgical time for the reconstruction group [(97.5±11.4) min] was significantly longer than that for the repair group [(53.6±10.7) min] ( P < 0.05). All the 34 patients were followed up for (35.4±3.5) months. The TT, ATT, AOFAS ankle-hindfoot score, and VAS pain score at the last follow-up were all significantly improved compared with the preoperative values in both groups ( P < 0.05). The AOFAS ankle-hindfoot score [(90.6±3.6) points], TT (6.0°±1.5°), and ATT [(3.6±1.4) mm] at the last follow-up in the reconstruction group were all significantly better than those in the repair group [(84.1±11.0) points, 8.6°±4.3°, and (6.6±4.1) mm] ( P < 0.05). There was no statistically significant difference in the VAS pain score between the 2 groups at the last follow-up ( P > 0.05). All incisions healed at one stage without such complications as nerve or vascular injury. CLAI recurrence occurred in 5 cases in the repair group, significant worse than that in the reconstruction group (no recurrence) ( P=0.015). Conclusion:In the treatment of CLAI complicated with multiple ligament laxity, arthroscopic anatomical reconstruction of the ligament with autologous semitendinosus tendon can effectively improve ankle function, enhance ankle stability, and reduce recurrence of the condition.

Objective:To investigate the value of 3D CT reconstruction in diagnosis of chronic lateral ankle instability (CLAI) combined with syndesmotic diastasis (SD).Methods:A retrospective study was conducted to analyze the clinical data of 160 patients with CLAI who had been examined by arthroscopy from January 2018 to September 2022 at Department of Foot and Ankle Surgery, Wuhan Fourth Hospital. There were 64 males and 96 females with an age of (39.8±12.6) years. Eighty-one left and 79 right feet were affected; the time from injury to surgery was (27.3±11.6) months. The patients were divided into a widened interval group and a normal interval group according to the syndesmotic width measured, with 2 mm as a critical value. After preoperative 3D CT reconstruction, the differences in anterior tibiofibular distance, posterior tibiofibular distance, the narrowest tibiofibular distance, fibular translation, fibular rotation, and syndesmotic area (SA) were compared between the 2 groups. Univariate and multivariate analyses were performed successively to identify the risk factors. The receiver operating characteristic (ROC) curve was used to identify the best predictive factor and critical value. According to the findings of previous research, the above analyses were repeated to determine the best predictive factor and critical value respectively in the sex subgroup, fibular morphology subgroup and incisura feature subgroup.Results:The binary logistic regression showed that SA was a risk factor for CLAI combined with SD ( OR=1.196, 95% CI: 1.122 to 1.275, P < 0.001). The ROC curve revealed an area under curve of 0.847 and the difference critical value of 22.06 mm 2 that indicated a sensitivity of 80.4% and a specificity of 78.9%, respectively. Subgroup analyses showed that SA was suitable for male and female patients and patients with different fibular morphologies and incisura features but the difference critical values were different. Conclusion:In 3D CT reconstruction, measurement of SA may help the diagnosis of CLAI combined with SD.

BACKGROUND:High ankle sprain is easily missed and leads to ankle dysfunction.Arthroscopy can detect hidden high ankle sprain.Suture-button elastic fixation can restore the biomechanical stability of the distal tibiofibular syndesmosis. OBJECTIVE:To explore the clinical efficacy of Suture-button elastic fixation for high ankle sprain under ankle arthroscopy. METHODS:A retrospective analysis was performed on 40 cases of high ankle sprain patients treated with Suture-button elastic fixation under ankle arthroscopy from August 2019 to August 2021 in the Department of Foot and Ankle Surgery,Wuhan Fourth Hospital.All patients underwent Suture-button elastic fixation.The American Orthopedic Foot and Ankle Society function score,Visual Analog Scale pain score,ankle range of motion,preoperative imaging data,and arthroscopic tibiofibular syndesmosis separation degree were recorded.Meislin criteria were used to evaluate the curative effect and postoperative complications were recorded. RESULTS AND CONCLUSION:(1)40 patients were followed up for 16-48 months after operation.(2)At the last follow-up,American Orthopedic Foot and Ankle Society score was(88.95±6.64 points).Visual Analog Scale score was(1.78±1.23 points).Ankle dorsiflexion range of motion was(33.50±5.79 degrees).Ankle plantarflexion range of motion was(34.50±5.97 degrees).There were statistically significant differences before and after surgery(P<0.05).(3)There was a low positive correlation between the radiographic separation index and the degree of arthroscopic separation(r=0.612,P<0.01).(4)The curative effect was evaluated by Meislin standard,with an excellent and good rate of 95%(38/40).Postoperative ankle joint pain was relieved,and ankle joint activities were significantly improved.(5)During the follow-up period,all patients had no nerve injury or incision infection.In 1 patient,the internal fixation was removed due to skin irritation and squatting sensation after operation.(6)It is concluded that Suture-button elastic fixation for high ankle sprain is effective under ankle arthroscopy in restoring ankle function and maintaining joint stability without the need for secondary removal,and it is worth clinical application.

ObjectiveTo observe the effects of Tongmai Kaiqiao pills on the hypoxia-inducible factor-1α （HIF-1α）/adenovirus E1B 19 kD-interacting protein 3 （BNIP3） signaling pathway and mitochondrial autophagy in the hippocampus of the rat model of vascular dementia （VD）. MethodNinety male SD rats underwent adaptive feeding for one week before the study. Ten rats were randomly assigned to the sham group， where the common carotid artery was isolated without ligation. The remaining rats were subjected to sequential ligation of the common carotid artery for the modeling of VD. The successfully modeled rats were randomly assigned into the following groups： model， high-， medium-， and low-dose （27.6， 13.8， 6.9 g·kg^-1， respectively） Tongmai Kaiqiao pills， donepezil hydrochloride （0.45 mg·kg^-1）， and combination （27.6 g·kg^-1 Tongmai Kaiqiao pills + 2.5 mg·kg^-1 HIF-1α inhibitor YC-1） groups. After 4 weeks of treatment， samples were collected. Nissl staining and hematoxylin-eosin staining were performed to observe the loss of neurons and pathological changes， respectively， in the hippocampal region. Western blot was employed to determine the protein levels of HIF-1α， BNIP3， Beclin-1， and microtubule-associated protein 1 light chain 3B （LC3B） in the hippocampal tissue. Transmission electron microscopy was used to observe the mitochondrial ultrastructure and the number of autophagosomes in the hippocampal tissue. Immunofluorescence was employed to observe the fluorescence intensity of HIF-1α， BNIP3， and LC3B in the hippocampal tissue. ResultCompared with the sham group， the model group showed prolonged escape latency （P<0.01）， decreased number of platform crossings （P<0.01）， reduced and disarranged neuronal layers in the hippocampal region， decreased number of Nissl bodies， disrupted mitochondrial cristae， damaged mitochondrial double-membrane structures， increased number of autophagosomes， upregulated expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.05， P<0.01）， and enhanced fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with the model group， Tongmai Kaiqiao pills and donepezil hydrochloride shortened the searching time for the platform （P<0.01） and increased the number of platform crossings （P<0.01）. Moreover， the drugs increased the number of neurons with normal morphology and orderly arrangement and the number of Nissl bodies， alleviated the damage， increased the number of autophagosomes， upregulated the expression of HIF-1α， BNIP3， Beclin1， and LC3B （P<0.05， P<0.01）， and enhanced the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with high-dose Tongmai Kaiqiao pills， the combination group prolonged the escape latency （P<0.01）， reduced the number of crossing platforms （P<0.01）， decreased the number of hippocampal neurons， aggravated the damage， decreased the number of Nissl bodies and autophagosomes， downregulated the expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.01）， and decreased the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.01）. ConclusionTongmai Kaiqiao pills may activate the HIF-1α/BNIP3 signaling pathway to promote the occurrence of mitochondrial autophagy， clear damaged mitochondria， provide energy for healthy cells， reduce neuronal cell death， and restore the brain function， thereby reducing ischemic damage to the hippocampal tissue， improving learning and memory abilities， and exerting therapeutic effects on VD in rats.

Objective:To summarize the clinical characteristics and efficacy of hemorrhage resulted from cortical venous infarction with seizure as the first symptom after craniotomy.Methods:Eleven patients with hemorrhage resulted from cortical venous infarction with seizure as the first symptom after craniotomy admitted to Neurosurgical Center, 988 th Hospital of PLA Joint Logistic Support Force from June 2011 to September 2019 were chosen in our study; primary diseases included meningioma in 7 patients, contusion and laceration of frontal lobe in 2, hypertensive cerebral hemorrhage in 1, and obsessive-compulsive disorder in 1 patient. Epilepsy was the first symptom after craniotomy. Clinical characteristics and efficacy of these patients were analyzed retrospectively; seizure control efficacy was evaluated by Engel grading. Results:First seizure occurred 4 h-7 d after craniotomy in these 11 patients, including 2 with focal sensory retention seizure, 3 with focal bilateral tonic-clonic seizure, and 6 with general tonic-clonic seizure. Follow-up cranial CT revealed hematoma in surgical region, adjacent cortex or subcortex in 9 patients (hematoma volume: 15-50 mL); emergency craniotomy (hematoma clearance) and decompressive craniectomy was performed in 5 patients; only emergency craniotomy (hematoma clearance) was performed in 3 patients; conservative treatment was performed in 1 patient. A small amount of diffuse bleeding with severe cerebral edema in the surgical region appeared in 2 patients, and the transient limb paralysis gradually recovered after 2 months of conservative treatment. Follow-up was performed for (4.5±1.7) years ([2.3-7.0] years). During the last follow-up, 4 patients were normal, 5 patients had mild to moderate hemiplegia, 1 had mild decreased vision in the right eye, and 1 had long-term coma. Epileptic control efficacy analysis indicated that 8 had Engel grading I and 3 grading II.Conclusion:Complete removal of hematoma and inactivated brain tissues can effectively control seizures and rebleeding in patients with hemorrhage resulted from cortical venous infarction.

The ASCO-GU 23 conference was held offline as scheduled after the pandemic. A total of 167 abstracts in the field of renal cell carcinoma has been posted during the conference, covering the first PET/CT diagnostic technology targeting tumors in renal cell carcinoma, risk stratified interpretation of the previous clinical trial results, and exploring the value of tumor and serum biomarkers for precise classification therapy, as well as providing evidence for the therapeutic scheme sequencing.

Objective:To investigate the clinical features of neonatal testicular torsion and to evaluate the effect and necessity of early intervention.Methods:A retrospective analysis was performed on 11 neonates admitted to the Second Hospital of Shandong University with neonatal testicular torsion from June 2017 to June 2022. Clinical data of these cases including clinical manifestations, ultrasonography findings, surgical management and outcomes were reviewed and analyzed with descriptive statistical methods.Results:The median age of the 11 patients on admission was 2.6 d (1-5 d). The median time from finding abnormal scrotum to admission was 12 h (1-120 h). Various degrees of scrotal swelling or scleroma were found in the patients. Among them, seven patients presented with acute inflammatory signs of cyano sis or skin redness, and testis-like tissue induration could be touched. Ultrasound scan showed abnormal blood flow in the affected testicle in all cases. Emergency scrotal exploration under general anesthesia was performed successfully in all cases and ten of them underwent orchiectomy of the affected testicle plus contralateral orchiopexy. The rest one who was admitted within 1 h after birth only underwent orchiopexy of the affected testicle as the parents refused contralateral testicular exploration. During the operation, 12 twisted testis were observed, including seven with extravaginal torsion, three with intravaginal torsion and two adhering to the surrounding tissue without normal testicular tissue or distinguishable torsion direction or degree. In this study, ten patients had unilateral testicular torsion, which affected the left side in seven cases and the right side in three cases, and one had bilateral testicular torsion, which was diagnosed as left testicle torsion before surgery. During scrotal exploration, the left testicle of this bilateral case was resected due to necrosis, while the right testicle twisted about 180 degrees with good blood flow and was subjected to orchidopexy after reduction. In one case, the unaffected testicle was unfixed and dysplastic during contralateral exploration, which was also subjected to orchidopexy. In the 12 testis with torsion, one testicle of the patient admitted within 1 h after birth and the right testicle of the bilateral case were preserved with a salvage rate of 2/12. Pathological examination showed necrosis in the ten excised testis, and fibrosis and calcification foci in two of them. None of the patients had any perioperative complications and the scrotal incision healed well in all neonates. The patients were followed up for 6-12 months with regular ultrasound. The two preserved testis and the contralateral testis subjected to orchidopexy were located in the scrotum with good blood supply, and no torsion, atrophy or other abnormalities occurred.Conclusions:Neonatal testicular torsion is rarely seen in clinical practice and has no specific manifestations. It has a high excision rate due to testicular necrosis. Early diagnosis and bilateral scrotal exploration are crucial to the prognosis and the keys to save the affected testis and avoid anorchidism.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

【Objective】 To compare the clinical application value of controllable negative pressure suction outer sheath and ordinary flexible endoscope outer sheath in flexible ureteroscopic lithotripsy with holmium laser in the treatment of renal calculi less than or equal to 2 cm in diameter. 【Methods】 A total of 85 patients with renal calculi were selected and randomly divided into negative pressure group (n=45) and ordinary group (n=40). The operation time, complications, infection indexes 2 h after operation, adverse reactions, treatment efficacy and stone-clearance rate were compared between the two groups. 【Results】 The sheath was successfully implanted and holmium laser lithotripsy was performed in both groups. The negative pressure group had significantly shorter operation time than the ordinary group [(43.3±4.9) min vs. (66.2±5.8) min, P<0.05] . There were 1 case of renal pelvis perforation and 1 case of ureteral laceration in the ordinary group (P>0.05). The increase of infection indexes (procalcitonin and leukocyte) 2 h after operation were significantly lower in the negative pressure group than in the ordinary group (P<0.05). The efficacy in the negative pressure group was 91.11% (41/45) and the stone-clearance rate was 95.56% (43/45), which were significantly better than those in the ordinary group (72.50% (29/40) and 80% (32/40), respectively. The total incidence of adverse reactions such as renal colic, gross hematuria and ureteral stone street was higher in the ordinary group than in the negative pressure group (P<0.05). 【Conclusions】 Controllable negative pressure suction sheath in flexible ureteroscopic lithotripsy is more effective, as the circulation perfusion keeps the operation field clear, reduces the operation time and improves the stone-clearance rate, while the negative pressure suction lowers the pelvis pressure to prevent infectious urine from entering the blood.