Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Centrifugal blood pumps drive blood flow by regulating blood flow rate,and have been widely used in clinical applications,including extracorporeal membrane oxygenation(ECMO),cardiopulmonary bypass(CPB),and extracorporeal circulation carbon dioxide removal(ECCO2R).However,because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios,blood pumps face different application conditions in clinical use.In this study,the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To compare the outcomes of percutaneous transhepatic one-step biliary fistulation (PTOBF) lithotripsy for type Ⅱa hepatolithiasis performed via the left or right lobe.Methods:A retrospective study was conducted on 79 patients with type Ⅱa hepatolithiasis treated in the First Affiliated Hospital of Guangzhou Medical University from January 2018 to December 2020, including 38 males and 41 females, aged (52.9±14.0) years. All patients had received PTOBF lithotripsy in single channel and divided into left lobe group ( n=40) and right lobe group ( n=39) according to different puncture approaches. Clinical data in immediate and final stone clearance rate, operation time of lithotripsy, intraoperative blood loss, postoperative complications (ascites, biliary tract infection), postoperative hospitalization time, reactive pleural effusion rate, the number of lithotripsy procedures and target bile duct dilatation diameter were compared between the two groups. Results:Compared with left lobe group, right lobe group had higher immediate stone clearance [51.3%(20/39) vs 22.5%(9/40)], less lithotripsy procedures [(2.4±1.0) vs (1.9±1.0)], but had longer postoperative hospitalization time [5(3, 6)d vs 3(2, 6)d] and higher reactive pleural effusion rate [23.1%(9/39) vs 2.5%(1/40)], the differences were all statistically significant (all P<0.05). No significant difference was found in target bile duct dilatation diameter, final stone clearance rate, intraoperative blood loss, postoperative complication rate, and operation time of lithotripsy (all P>0.05). Conclusions:Compared to the left lobe approach, right lobe approach could be prioritized in PTOBF lithotripsy for type Ⅱa hepatolithiasis, considering its higher immediate stone clearance and less lithotripsy procedures, but this surgical approach should pay attention to the occurrence of reactive pleural effusion.

Objective:Examining the risk factors for stone recurrence after percutaneous transhepatic one-step biliary fistulation (PTOBF) and lithotripsy for hepatic bile duct stones.Methods:The clinical data of 70 patients with hepatic bile duct stones combined with bile duct stenosis who underwent PTOBF lithotripsy at the First Hospital of Guangzhou Medical University from September 2016 to February 2023 were analyzed retrospectively, including 28 males and 42 females with the age of (48.9±17.5) years old. The patients were divided into two groups according to stone recurrence: recurrence group ( n=25) and non-recurrence group ( n=45). Clinical data such as age, gender, medical history, number of surgeries, and time with tube were recorded. Follow-up was performed by telephone and outpatient review. Multifactorial logistic regression was used to analyze the influencing factors of stone recurrence. Results:Univariate analysis showed statistically significant differences between the age, stone length diameter, number of stones, stage I undischarged stenosis, and number of surgeries between patients in the recurrent and non-recurrent groups (all P<0.05). Multifactorial logistic regression analysis showed that stone length ≥20 mm ( OR=4.389, 95% CI: 1.111-17.340, P=0.035), stage I undischarged stenosis ( OR=4.638, 95% CI: 1.170-18.385, P=0.029), and multiple number of operations ( OR=1.842, 95% CI: 1.031-3.290, P=0.039) had a high risk of stone recurrence after PTOBF lithotripsy in patients with hepatic bile duct stones. Conclusion:Stone length ≥20 mm, stage I unresolved stenosis, and number of surgeries were independent risk factors for stone recurrence in patients with hepatobiliary stones combined with bile duct stenosis after PTOBF and lithotripsy for hepatic bile duct stones.

Benign anastomotic stenosis remains a common complication after bilojejunal anastomosis. Its pathogenesis includes the histology of bile duct, bile erosion, and inappropriate choice of surgical anastomosis or suture materials. Biliojejunal anastomotic stenosis can be determined preoperatively by MRCP, CT, and three-dimensional image reconstruction. Surgery remains treatment of choice for most cases, including surgical reconstruction and minimally invasive treatment, while the incidence of restenosis, residual stone, and reoperation is still high. Surgeons are still in search of optimal treatment modality to avoid anastomotic stenosis. In this article, we review the literature and summarize the latest clinical progress in the diagnosis and treatment of biliojejunal anastomotic stenosis combined with hepatic ductal stones.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Objective:To investigate the therapeutic effect of percutaneous transhepatic one-step biliary fistulation (PTOBF) combined with rigid choledochoscopy in the treatment of benign hepatic bile duct strictures.Methods:The clinical data of 46 patients with hepatic ductal stenosis and stones undergoing PTOBF combined with rigid choledochoscopy at the First Hospital of Guangzhou Medical University between September 2016 and September 2022 were retrospectively analyzed, including 20 males and 26 females, aged (48.5±17.6) years. The location of stones and strictures, stone retrieval rate, postoperative complications, stricture release rate, stone recurrence rate, and reoperation rate were analyzed to access the safety and effectiveness of this procedure.Results:A total of 58 sites of stenoses were found in 46 patients, and PTOBF lithotripsy combined with rigid choledochoscopy were performed for 77 times. The early postoperative complication rate was 19.6% (9/46), and the stenosis release rate was 93.5% (43/46). The mean follow-up time was (28.1±19.6) months, the complete stone retrieval rate was 91.3% (42/46), the stone recurrence rate was 19.6% (9/46), the reoperation rate was 8.7% (4/46), and the long-term postoperative complication rate was 6.5% (3/46).Conclusion:PTOBF combined with rigid choledochoscopic stenoplasty for benign hepatic duct strictures is a safe and feasible procedure to reduce the stone recurrence and long-term postoperative complications.

Objective:To investigate the safety and effectiveness of robot-assisted total knee arthroplasty (TKA).Methods:From August 2021 to March 2022, the data of 69 patients who received robot-assisted TKA for inflammatory disease of knee in 6 hospitals were collected, including 24 males and 45 females, aged 52±6 years (range, 46-72 years), including 53 cases of knee osteoarthritis,10 cases of rheumatoid arthritis, and 6 cases of traumatic arthritis. Imaging data examination of patients was completed according to the multicenter specification. Preoperatively, the patient's CT data were extracted before surgery and a personalized prosthesis positioning plan was designed by the robotic system to determine the prosthesis size, lower limb force lines, and femoral and tibial osteotomy volumes; intraoperatively, the osteotomy template was robotically controlled to complete the osteotomy according to the prosthesis positioning plan, and the intraoperative osteotomy volumes were measured to verify the accuracy of the robot-assisted TKA osteotomy with the preoperative planning. Postoperatively, the lateral angle of the distal femur, the medial angle of the proximal tibia and the hip-knee-ankle angle were measured in the coronal plane according to radiographs; the postoperative outcome was evaluated 3 months after operation, using the American Knee Society score (KSS), including the KSS knee score and functional score.Results:The operative time was 97.3±2.3 min (range, 80-110 min) and the amount of bleeding was 320.0±6.2 ml (range, 300-350 ml) in 69 patients. Three months after operation, the mean range of motion of knee joint was increased from 82.2°±1.1° before surgery to 119.7°±0.8° after surgery ( t=27.65, P<0.001), and the line of force of lower limb was improved from 160.9°±0.5° before surgery to 178.0°±0.2° after surgery ( t=32.03, P<0.001). KSS-knee score increased from 54.8±0.7 points before operation to 85.0±0.5 points after operation, and KSS-functional score increased from 56.5±0.7 points before operation to 85.9±0.4 points after operation, the difference was statistically significant ( t=35.45, 36.58, P<0.001). The proportion of patients with intraoperative femoral and tibial osteotomies within 2 mm osteotomy error compared with preoperative planning was 97% for the lateral tibial plateau, 100% for the medial tibial plateau, 100% for the lateral distal femur, 99% for the medial distal femur, 93% for the lateral posterior femoral condyle, and 100% for the medial posterior femoral condyle; The proportion of patients with postoperative anteroposterior X-ray measurement angle error within 3° was: 100.0% for the distal lateral femoral angle, 100.0% for the proximal medial tibial angle, and 100% for the hip-knee-ankle angle. No complications occurred in all patients except for one case in which fat liquefaction occurred in the postoperative wound. Conclusion:Robot-assisted TKA is a safe and effective surgical method for the treatment of inflammatory disease of knee with accurate prosthesis installation and good postoperative recovery of lower limb alignment.

Objective:To evaluate the feasibility of indocyanine green fluorescence imaging technology applied in thyroid surgery to identify parathyroid gland.Methods:From Oct 2021 to May 2022, data of 42 patients undergoing thyroidectomy via gasless unilateral axillary approach in Zhejiang Provincial Hospital of Traditional Chinese Medicine were retrospectively analyzed. Cases using intraoperative fluorescence imaging technology(42 cases) were compared with conventional laparocopic approach.Results:The number of parathyroid glands dissected in the study group 1.57±0.61 was higher than that in the control group 0.56± 0.59 ( t=-5.472, P<0.05). The PTH value of the study group was (2.88±1.23)pmol/L on the first day after operation, which was higher than that of the control group (2.16±0.10)pmol/L ( t=-1.844, P<0.05). The blood parathyroid hormone value on the third day(3.22±1.31)pmol/L was higher than that of the control group (2.55±0.81) pmol/L ( t=-2.041, P<0.05). There were 2 cases of hypoparathyroidism in the study group, less than 5 cases in the control group, but there was no significant difference between the two groups( χ2=0.942, P>0.05). There was 1 case of hypocalcemia in the study group and 3 cases in the control group ( χ2=0.731, P>0.05). Conclusion:Using indocyanine green fluorescence imaging technology to identify parathyroid gland is feasible, simple, fast, safe and effective.