OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

In July 2024， the European Association for the Study of the Liver released the latest edition of EASL Clinical Practice Guidelines on liver transplantation. The purpose of the EASL guidelines presented here is not to cover all aspects of liver transplantation， but to focus on important advances since the release of the 2016 edition of EASL guidelines. This article gives an excerpt of the recommendations in the guidelines.

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

Objective:To investigate the molecular mechanism of the 5-methylcytosine(m5C)reader Y-box binding protein 1(YBX1)in participating in the development and progression of colorectal cancer(CRC)by regulating the stability of the ferroptosis inhibitor membrane-spanning 4-domains subfamily A 15(MS4A15).Methods:Bioinformatics databases were used to investigate the mRNA and protein expression levels of YBX1 in CRC.RT-qPCR was used to measure the expression level of YBX1 in CRC cells.LC-MS was used to measure the level of m5C modification in CRC cells and nor-mal colorectal mucosal cells.CCK-8 assay was used to observe the effect of YBX1 on the proliferation of CRC cells,Transwell assay was used to observe its effect on the migration ability of CRC cells,and flow cytometry was sued to observe its effect on the apoptosis of CRC cells.Bioinformatics methods were used to identify the ferrop-tosis inhibitors that can interact with YBX1 and potential m5C modification sites.GEPIA2 was used to analyze the association between the expression of YBX1 and MS4A15.The expression of YBX1 was inhibited,and then the mRNA expression level and m5C modifica-tion level of MS4A15 were analyzed.The catRAPID database was used to find the binding sites between YBX1 protein and MS4A15 mRNA.CRC cells were treated with actinomycin D after inhibition of YBX1 expression,and RT-qPCR was used to measure the stabil-ity of MS4A15 mRNA.The expression of MS4A15 was inhibited,and then the proliferative activity,migration ability,and apoptosis rate of cells were measured,as well as the expression levels of the key indicators for ferroptosis,including MDA,ROS,and Fe2+.Results:High mRNA and protein expression levels of YBX1 were observed in CRC,and YBX1 was highly expressed in CRC cells.The m5C modification level of CRC cells was significantly higher than that of normal colorectal mucosal cells.YBX1 could promote the prolifera-tion and migration of CRC cells and inhibit the apoptosis of CRC cells.The bioinformatics analysis showed that YBX1 was positively correlated with the expression level of the ferroptosis inhibitor MS4A15,and there were multiple m5C modification sites on MS4A15.Inhibition of YBX1 expression could reduce the mRNA expression level and m5C modification level of MS4A15 and the stability of MS4A15 mRNA.There were significant reductions in the proliferative activity and migration ability of CRC cells and a significant in-crease in the apoptosis rate of CRC cells after inhibition of MS4A15 expression,with significant increases in the content of MDA,ROS,and Fe2+.Conclusion:These results show that YBX1 promotes the development and progression of CRC by stabilizing MS4A15 via m5C modification,which provides a promising targeted therapeutic strategy for CRC patients.

To compare the effects of advanced bone flap and no bone flap on the healing of osteotomy gap in open-wedge high tibial osteotomy (OW-HTO) for the treatment of medial compartment osteoarthritis and knee inversion.Methods:A retrospective study was conducted to analyze the 85 patients who had undergone OW-HTO from March 2021 to December 2021 at Trauma Emergency Centre, The Third Hospital of Hebei Medical University for medial compartment osteoarthritis and knee inversion. The patients were divided into 2 groups according to whether bone flap was grafted. In group A of 42 patients who received advanced bone flap intraoperatively, there were 32 females and 10 males with an age of (63.7±6.6) years; in group B of 43 patients who received no advanced bone flap intraoperatively, there were 31 females and 12 males with an age of (63.2±9.4) years. The measures recorded and compared between the 2 groups included: osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 18 months postoperatively; medial proximal tibial angle (MPTA) and femorotibial angle at immediate postoperation and 18 months postoperation; postoperative complications.Results:The differences in preoperative general information between the 2 groups were not statistically significant, showing comparability ( P>0.05). The osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively in group A were significantly higher than those in group B ( P<0.05). The WOMAC (26.1±5.9), VAS (4.1±1.4), and KOOS (47.0±9.7) scores at 6 months postoperatively in group A were significantly lower than those in group B (31.3±8.3, 4.8±1.6, and 56.1±11.9) ( P<0.05), but the differences in the above indicators between the 2 groups at 18 months postoperatively were not statistically significant ( P>0.05). There was no statistically significant difference in MPTA or femorotibial angle at immediate postoperation between the 2 groups ( P>0.05). At 18 months postoperatively, the MPTA in group A (88.7°±1.1°) was significantly better than that in group B (87.7°±1.5°) ( P<0.05). The total complication rate in group B [27.9% (12/43)] was signifcantly higher than that in group A [2.4% (1/42)]( P<0.05). Conclusions:In the OW-HTO treatment of the patients with medial compartment osteoarthritis and knee inversion, application of an advanced bone flap to fill the osteotomy gap can accelerate the gap healing and reduces occurrence of delayed healing or non-healing of the osteotomy gap.

Objective:To evaluate the reliability and clinical application of a self-established classification system for the lower 1/3 humeral fractures in adults.Methods:A retrospective study was performed to analyze the 88 patients with lower 1/3 humeral fracture who had been admitted to Department of Orthopedics, The Second Hospital of Fuzhou between January 2013 and December 2020. There were 61 males and 27 females with an age of (34.6±12.7) years. The lower 1/3 humeral fractures were classified according to the location of the fracture line, displacement, and bone mass into 3 types: type Ⅰ: transverse and short oblique ones; type Ⅱ: oblique and spiral ones; type Ⅲ: oblique and spiral ones with butterfly-shaped bone mass. After a junior orthopedic surgeon, an intermediate orthopedic surgeon, a senior orthopedic surgeon, and a radiologist had learned this novel classification system, they were asked to classify the lower 1/3 humeral fractures in this cohort independently to assess the reliability of the classification system. Our treatments were based on this novel classification. Open reduction and internal fixation with a unilateral plate through a lateral approach was performed for type Ⅰ fractures, internal fixation with a unilateral plate plus compression screws through a lateral approach for type Ⅱ fractures, and double plate internal fixation through the ulnar and anterolateral approaches for type Ⅲ fractures. The functions of the radial, ulnar, and musculocutaneous nerves and fracture healing time were observed postoperatively. The shoulder and elbow functions were evaluated using Neer shoulder function score and Mayo elbow function score.Results:Of the 88 patients in this cohort, 20 were type Ⅰ, 25 type Ⅱ, and 43 type Ⅲ. The mean Kappa value for inter-observer reliability was 0.878 at the first stage and 0.914 at the second stage, and the mean Kappa value for intra-observer reliability was 0.950. All patients were followed up for (14.1±3.7) months. Iatrogenic injury to the radial nerve was observed in 2 patients, but no injury to the ulnar nerve, the musculocutaneous nerve or important blood vessels or failure of internal fixation was reported. All patients achieved bony union after (12.7±2.0) weeks. The maximum elbow flexion was 137.8°±4.8°, and the maximum elbow extension 2.4°±1.6°. The Mayo elbow function score was (92.0±3.1) points and the Neer shoulder function score (92.2±3.2) points.Conclusions:Our classification system for the lower 1/3 humeral fractures in adults is reliable. As the treatments corresponding to the novel classification system can achieve satisfactory clinical outcomes, the classification system has a clinical value.

Objective:To characterize the biomechanics of distal dynamic locking and distal static locking of proximal femur bionic nails (PFBN) in fixation of intertrochanteric fractures by a finite element analysis.Methods:The CT image data from the hip to the upper tibia from an adult male volunteer were used to establish a three-dimensional model of the femur by Mimics 20.0 and Geomagic 2013 which was processed further into a model of Evans type I intertrochanteric fracture by software NX 12.0. With reference to the internal fixation parameters commonly used, 4 models of PFBN fixation were established: distal single transverse nail dynamic locking (model A), single oblique nail dynamic locking (model B), single nail static locking (model C) and double nail dynamic locking (model D). Abaqus 6.14 software was used to load and analyze the internal fixation stresses and displacements of fracture ends.Results:Under a 2100N loading, the peak stress was located upon the main nail in the 4 models. The smallest peak stress upon the main nail was in Model D (161.9 MPa), decreased by 15.9% compared with model A (192.5 MPa), by 15.6% compared with model B (191.9 MPa), and by 0.9% compared with model C (163.3 MPa). The peak stress upon the fixation screw was the largest in model A (95.3 MPa), the smallest in model B (91.5 MPa), and 91.5 MPa and 92.2 MPa in models C and D, respectively. The overall displacements of the implants, in a descending order, were 10.14 mm in model A, 10.10 mm in model B, 10.09 mm in model C, and 10.05 mm in model D. Similarly, the displacements of fracture ends were 0.125 mm in model A, 0.121 mm in model B, 0.110 mm in model C, and 0.098 mm in model D.Conclusion:Compared with dynamic locking, distal static locking of PFBN provides a better mechanical stability and reduces stress concentration upon internal fixation.

Objective:To determine the relationship between tibial plateau stresses and malunion by exploring the changes in mechanical conduction in the knee joint after malunion of Hoffa fracture of the tibial plateau.Methods:This study selected 28 knee joint specimens treated with formalin for preservation, half of which were from male and half from female individuals with an age of (51.4±9.5) years. Their structures were intact, and flexion-extension activities normal. X-ray examinations excluded osteoporosis, tuberculosis, and diseases that could have potentially affected bone quality. The knee specimens were divided into a control group (intact tibia) ( n=4) and 6 groups of tibial plateau Hoffa fracture malunion model: 3 vertical malunion groups (groups V1, V2, and V3, with a vertical displacement of 1, 2, and 3 mm, respectively, n=4) and 3 separation malunion groups (groups S3, S5, and S7, with a separation displacement of 3, 5, and 7 mm, respectively), with half males and half females in each group. After a 600N vertical load was applied at passive knee flexions at 0°, 30°, 60°, 90°, and 120°, the stress levels in the medial and lateral compartments of the knee joint were measured using pressure-sensitive films. Results:Under a vertical load of 600 N, when the knee joint was in a neutral position (flexion of 0°), the differences in the medial and lateral tibial plateau stress values were not statistically significant between the malunion models groups and the control group ( P>0.05). When the knee flexion increased to 30°, the medial tibial plateau stress in the V3 and S7 groups was significantly greater than that in the control group ( P<0.05). At a knee flexion of 60°, the medial plateau stress was significantly greater in the V3, S5 and S7 groups than that in the control group, and the differences were significantly greater than the comparisons at a knee flexion of 30° (all P<0.05). When the knee flexion was 90°, the medial plateau stress in the V2, V3, S5 and S7 groups was significantly greater than that in the control group ( P<0.05), but the lateral tibial plateau stress in the V3 group was significantly smaller than that in the control group ( P<0.05). When the knee flexion was further increased to 120°, the differences in the medial and lateral plateau stress values were statistically significant between all the malunion groups and the control group ( P<0.05), and the differences significantly greater than the comparisons at a knee flexion of 90° (all P<0.05). Under a vertical load of 600 N, the differences in the stresses on the medial and lateral plateaus were not statistically significant between the control group and all the malunion groups at a knee flexion of 0° ( P>0.05). When the knee flexion increased to 30°, the difference between the medial and lateral stresses was not statistically significant in the control group ( P>0.05), but was statistically significant in the V3 and S7 groups ( P<0.05). When the knee flexion reached 60°, 90°, and 120°, the differences between the medial and lateral tibial plateau stresses in all the groups were statistically significant ( P<0.05). Conclusions:The peak knee stresses after malunion of Hoffa fracture of the tibial plateau correlate with the severity of malunion and knee flexion angles. The mechanical properties are not significantly different between a mild malunion knee and a normal knee, but a significant displacement (vertical displacement >2 mm and separation displacement ≥5 mm) may increase the peak knee stresses to increase the risk of knee osteoarthritis. When the severity of malunion is certain, an increase in knee flexion angle increases the difference in the peak stress between the medial and lateral tibial plateaus, thus increasing the risk of knee osteoarthritis.

Objective To summarize the management challenges faced by multi-campus hospitals both domestically and internationally,to delineate the experiences in medical administration across multiple campuses,and to propose the"Zhong-zhong"multi-campus medical management pattern based on the practices of Sun Yat-sen University Cancer Center,aiming to pro-vide reference and evidence for domestic peers in the field.Methods This study uses the methods of literature research and case study analysis,and summarizes and condenses the experience of medical management in multi-campus and provides policy sug-gestions through key person interviews and expert consultation.Results SYSUCC carries out multi-campus medical management through six major measures,namely,the organizational system combining vertical and territorial management,the layout of disci-plinary clusters and specialties,multi-channel flow attraction measures,the dynamic adjustment of medical resources,the homog-enization of medical quality,and the high-effective information system.It achieves the high-quality development goals with differ-ential development of various specialties,improved resource utilization efficiency,homogeneous and incremental medical serv-ices,smooth operation of information system,and steady and orderly development of new techniques.Conclusion Domestic public specialized hospitals can achieve homogeneous management and high-quality development across multiple campuses through streamlined organizational structures to enhance management efficiency,optimizing the layout of specialized departments to pro-mote coordinated development,strict control of standards to ensure medical quality,using dynamic adjustments to guide orderly competition among specialized departments,and leveraging information systems to support homogeneous development across multi-ple campuses.

Surgical treatment has been established as the standard method for the treatment of intertrochanteric fractures in the elderly. The design of internal fixation devices has become the key to improve surgical outcomes and reduce postoperative complications. Centered on optimizing biomechanical performance and minimally invasive implantation, coupled with continuous material improvements, the design philosophy of internal fixation devices has also been constantly evolving. There have been several milestone advancements, such as the transition from eccentric fixation to central fixation, the adoption of sliding compression fixation, the replacement of traditional screws with spiral blades, and the shift from single to double (combination) nails. However, the incidence of internal fixation-related complications has remained at a relatively high level of 5% to 10%, without significant breakthroughs. Increasing evidence suggests that in-depth analysis of the anatomy, physiological mechanisms, and mechanical transmission characteristics of the proximal femur can help elucidate the root causes of internal fixation failures. Based on this, the proximal femoral bionic nail (PFBN) has emerged as a new design concept. By fully mimicking the anatomical, mechanical, and biological characteristics of the proximal femur, the PFBN can regulate the local mechanical environment, providing a revolutionary solution and a new approach for the treatment of proximal femoral fractures. This innovative design also has the potential to drive the paradigm shift in the treatment strategies of other fractures.