Objective To evaluate the clinical value of internal carotid artery occlusion in treatment of intractable epistaxis caused by carotid artery siphon traumatic lesions.Methods A total of 37 patients with intractable epistaxis caused by traumatic carotid artery siphon pseudoaneurysm or carotid cavernous fistula were retrospectively analyzed.All the patients underwent embolization from October 1998 to June 2010,including 34 men and 3 women with the age ranged from 25 to 65 years and a average of 40 years.Only lesions were occlued in 12 cases without involving the internal carotid artery,while occlusions of internal carotid artery were performed in the rest 25 cases.Results Thirty-six patients were cured without recurrent hemorrhage after embolization.Only 1 patient with carotid artery occlusion died 48 hours after operation.Conclusion For patients with carotid arterial intractable epistaxis,if the elimanation of the lesions is not applicable and the collateral circulation of Willis ring has a good compensation,the use of detachable balloon or coil occlusion of ipsilateral internal carotid artery is a quick and easy method to save patients' lives.

Objective:To explore the advantages of the modified right renal artery dissection in the laparoscopic resection of right renal carcinoma combined with venous tumor thrombus.Methods:From January 2016 to June 2016, a retrospective analysis of the three-dimensional CT images of renal blood vessels in 70 patients with full abdominal CT plain scan plus enhanced scan from Shandong Provincial Hospital Affiliated to Shandong First Medical University was performed. On the sagittal plane of the right margin of the aorta, the right renal artery was detected to locate above the left renal vein in 14 cases (20.0%), posterior in 33 cases(47.1%), and below in 23 cases(32.9%). In addition, on the sagittal plane of the left margin of the inferior vena cava, the right renal artery was detected to locate above the left renal vein in 1 case (1.4%), posterior in 26 cases(37.1%), and below in 43 cases (61.4%). Based on this finding, 11 patients with right kidney cancer combined with venous tumor thrombus, admitted to Shandong Provincial Hospital Affiliated to Shandong First Medical University from June 2016 to December 2019, were retrospectively analyzed. The average age of the patients was(58.7±6.8)(45-68) years old. The CT three-dimensional reconstruction of the renal blood vessels was shown on the sagittal plane of the right margin of the aorta before the operation, and the right renal artery was detected to locate above the left renal vein in 0 cases, posterior in 7 cases, and lower in 4 cases. On the sagittal plane of the left margin of the inferior vena cava, the right renal artery was detected to locate above the left renal vein in 0 case, behind in 3 cases, and below in 8 cases. Renal tumors are located in the upper middle in 5 cases and in the lower middle in 6 cases. The maximum diameter of the tumor to be resected was 8.5-12.0 cm, with an average of (10.0±1.4) cm. Among them, 4 cases had Mayo grade 0 tumor thrombus, 4 cases were grade Ⅰ tumor thrombus, and 3 cases were grade Ⅱ tumor thrombus. All 11 cases underwent transperitoneal laparoscopic surgery. During the operation, it was found that the relationship between the right renal artery and the left renal vein was consistent with the preoperative three-dimensional reconstruction of renal blood vessels. The modified right renal artery dissection method was used, that is, the right renal artery was detected and ligated between the inferior vena cava and the aorta, using the left renal vein as a mark, and then the right kidneys and vein tumor thrombi were removed.Results:All of the 11 operations in this group were completed successfully. The operation time was (110.5±29.8)(70-150) min, the average time of right renal artery dissection was(28.5±5.8)(16- 33) min, and the amount of intraoperative bleeding was(112.7±83.5)(20-300) ml. No serious complications occurred during the operation in 11 cases. Postoperative pathological examination showed 10 cases of clear cell carcinoma and 1 case of papillary cell carcinoma. The postoperative hospital stay was 4.2 (4.18±0.75) days. There were no complications such as secondary bleeding, infection, lower extremity venous thrombosis or pulmonary embolism. All 11 patients were followed up for 3 to 42 months, with an average of(19.5±12.1) months. One patient died 23 months after the operation, and no tumor recurrence or metastasis occurred in the remaining patients.Conclusions:When the right renal artery runs to the left edge of the inferior vena cava, it is mostly behind the left renal vein. In the laparoscopic resection of right renal cancer with venous tumor thrombus, the modified right renal artery dissection method can quickly find and dissociate the right renal artery. The operation time is short, the intraoperative bleeding is less, and no postoperative complications occur.

OBJECTIVE: To evaluate the operability and effectiveness of a self-developed patellar bone canal locator (hereinafter referred to as "locator") in the reconstruction of the medial patellofemoral ligament (MPFL). METHODS: A total of 38 patients with recurrent patellar dislocation who met the selection criteria admitted between January 2022 and December 2022 were randomly divided into study group (the patellar canal was established with a locator during MPFL reconstruction) and control group (no locator was used in MPFL reconstruction), with 19 cases in each group. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, body mass index, disease duration, patella Wiberg classification, constituent ratio of cartilage injury, Caton index, tibia tubercle-trochlear groove, and preoperative Lysholm score, Kujal score, Tegner score, visual analogue scale (VAS) score, and so on. The Lysholm score, Kujal score, Tegner score, and VAS score were used to evaluate knee joint function before operation and at 3 days,1 month, 3 months, and 6 months after operation. The ideal prepatellar cortical thickness and canal length were measured before operation, and the actual prepatellar cortical thickness and canal length after operation were also measured, and D1 (the distance between the ideal entrance and the actual entrance), D2 (the ideal canal length minus the actual canal length), D3 (the ideal prepatellar cortical thickness minus the actual prepatellar cortical thickness) were calculated. RESULTS: Patients in both groups were followed up 6-8 months (mean, 6.7 months). The incision length and intraoperative blood loss in the study group were smaller than those in the control group, but the operation time was longer than that in the control group, the differences were significant ( P<0.05). There was no complication such as incision infection, effusion, and delayed healing in both groups, and no further dislocation occurred during follow-up. One patient in the study group had persistent pain in the anserine area after operation, and the symptoms were relieved after physiotherapy. The VAS score of the two groups increased significantly at 3 days after operation, and gradually decreased with the extension of time; the change trends of Lysholm score, Kujal score, and Tegner score were opposite to VAS score. Except that the Lysholm score and Kujal score of the study group were higher than those of the control group at 3 days after operation, and the VAS score of the study group was lower than that of the control group at 3 days and 1 month after operation, the differences were significant ( P<0.05), there was no significant difference in the scores between the two groups at other time points ( P>0.05). Patellar bone canal evaluation showed that there was no significant difference in preoperative simulated ideal canal length, prepatellar cortical thickness, and postoperative actual canal length between the two groups ( P>0.05). The postoperative actual prepatellar cortical thickness of the study group was significantly smaller than that of the control group ( P<0.05). D1 and D3 in the study group were significantly higher than those in control group ( P<0.05), but there was no significant difference in D2 between the two groups ( P>0.05). CONCLUSION The locator can improve the accuracy of MPFL reconstruction surgery, reduce the possibility of intraoperative damage to the articular surface of patella and postoperative patellar fractures.
Humans ; Patella/surgery* ; Patellar Dislocation/surgery* ; Patellofemoral Joint/surgery* ; Knee Joint/surgery* ; Joint Dislocations ; Ligaments, Articular/surgery*

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.