OBJECTIVE: To evaluate the effectiveness of early internal fixation combined with free anterolateral thigh perforator flap (ALTPF) transplantation in the treatment of open ankle fracture-dislocation. METHODS: A retrospective analysis was performed on the clinical data of 13 patients with open ankle fracture-dislocation who were admitted and met the inclusion criteria between January 2021 and May 2024. Among them, there were 9 males and 4 females, with the ages ranging from 23 to 61 years (mean, 45.3 years). Fracture types included 5 cases of simple medial or lateral malleolar fracture-dislocation, 7 cases of bimalleolar (medial and lateral) fracture-dislocation, and 1 case of trimalleolar fracture-dislocation. Additionally, 3 cases were complicated with bone defects (1 medial malleolus defect and 2 lateral malleolus defects). All injuries were classified as type ⅢB according to the Gustilo-Anderson classification for open fractures. The size of wound defects ranged from 7 cm×5 cm to 18 cm×12 cm. The time from injury to surgery was 2-20 hours (mean, 4 hours). All patients underwent emergency thorough debridement upon admission. The fracture-dislocation was temporarily stabilized with an external fixator, and the wound was covered with antibiotic-impregnated bone cement sheets or vacuum sealing drainage. Definitive internal fixation of the fracture and free ALTPF transplantation were performed 5-7 days after the initial emergency procedure. Postoperatively, wound healing, flap survival, and fracture union were monitored. At last follow-up, clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: All 13 patients were followed up 6-24 months (mean, 8.2 months). All flaps survived completely, and all fractures achieved union, with an union time of 3-11 months (mean, 5.5 months). One patient developed a superficial infection at the wound margin, which healed after regular dressing changes and drainage. No internal fixation-related complication (e.g., deep infection, implant loosening, or secondary ankle instability) were observed. At last follow-up, the total AOFAS ankle-hindfoot score was 78.6±13.5, with 3 excellent, 7 good, 2 fair, and 1 poor cases, yielding an excellent and good rate of 76.9%. CONCLUSION Early internal fixation combined with ALTPF transplantation for open ankle fracture-dislocation can shorten the treatment course and maximize the recovery of ankle joint function.
Humans ; Fracture Fixation, Internal/methods* ; Male ; Middle Aged ; Female ; Adult ; Retrospective Studies ; Perforator Flap/transplantation* ; Ankle Fractures/surgery* ; Thigh/surgery* ; Fractures, Open/surgery* ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Fracture Dislocation/surgery*

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg^-1·d^-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg^-1·d^-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg^-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

Objective:To investigate the clinical outcomes of minimally invasive lateral lumbar interbody fusion (LLIF) and the necessity to perform LLIF plus posterior direct decompression in the treatment of severe degenerative lumbar spinal stenosis (DLSS).Methods:In this prospective randomized, controlled trial, we assigned 71 patients, who were 50 to 80 years old, and diagnosed with severe DLSS (Schizas Classification grade C on magnetic resonance imaging), in a 1∶1 ratio to undergo either one-stage LLIF plus posterior internal fixation (treatment group) or CLIF plus posterior internal fixation with laminectomy (control group). Demographic and perioperative data were collected and compared. The clinical outcome measures included Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) score as well as visual analogue scale (VAS). Patients were followed up for at least 1 year.Results:The treatment group included 36 patients with 46 surgical levels, while the control group included 35 patients with 46 surgical levels. The baseline demographic data of the 2 groups were equivalent in preoperative central canal areas, spinal canal anteroposterior diameter, disc height, ODI, ZCQ score for symptom severity and physical function, as well as VAS scores for back and leg pain. The mean operative time, blood loss, drainage volume and hospital stay of the treatment group are significantly less than the control group (157.2±29.1 min vs. 180.6±26.8 min, 75.6±39.1 ml vs. 108.6±43.3 ml, 136.9±73.9 ml vs. 220.5±121.3 ml, 5.3±1.1 d vs. 6.6±2.3 d). There were 2 cases with dura tear and 1 case with wound infection in control group. Thus, the surgical trauma and complications of the control group were more than the treatment group. At 1-year follow-up, the mean ODI score of treatment group improved from 42.24%±10.70% preoperatively to 18.21%±11.49%, the mean ZCQ symptom severity from 2.89±0.38 to 1.61±0.41, the mean ZCQ physical function from 2.31±0.45 to 1.50±0.37, the mean VAS for back from 5.56±1.19 to 1.97±1.13 and the mean VAS for leg from 4.44±1.81 to 0.94±1.26. At 1-year follow-up, the mean ODI score of the control group improved from 43.65%±14.93% preoperatively to 17.36%±12.15%, the mean ZCQ symptom severity from 2.92±0.52 to 1.65±0.39, the mean ZCQ physical function from 2.37±0.52 to 1.55±0.39, the mean VAS for back from 5.63±1.40 to 2.34±1.47, and the mean VAS for leg from 4.37±2.14 to 0.83±1.20. The ZCQ satisfactory score of both groups were not significant different (1.25±0.45 vs. 1.26±0.43, t=0.07, P=0.944). The mean improvement rate of both groups for ODI, ZCQ symptom severity, ZCQ physical function, VAS back and VAS leg at 1-year follow-up were not significant different (55.43%±27.74% vs. 58.36%±25.06%, 43.07%±17.22% vs. 42.66%±12.95%, 32.25%±23.65% vs. 31.71%±23.24%, 62.65%±21.25% vs. 58.37%±22.44%, 78.94%±26.41% vs. 85.45%±20.53%). One adjacent segment disease was found in each group at 1 year follow-up. Conclusion:CLIF+ posterior internal fixation in the treatment of Schizas Grade C DLSS has satisfactory clinical outcome at 1-year follow-up. Laminectomy increases surgical trauma, but does not significantly improve the clinical outcome at 1-year follow-up.

Objective:To investigate the influence of different degrees of facet joint arthropathy on the indirect decompression effect of crenel lumbar interbody fusion (CLIF), and the clinical outcomes of CLIF for the treatment of lumbar spinal stenosis with severe facet joint arthropathy (grade 3).Methods:This study reviewed a total of 269 surgical segments in 156 patients with lumbar spinal stenosis treated with CLIF technique from November 2016 to February 2020. According to preoperative CT images, the facet joint was graded according to Pathria classification. There are 19 segments with grade 0, 156 segments with grade 1, 67 segments with grade 2, and 27 segments with grade 3. Radiographic parameters included disc angle, anterior and posterior disc height, and bilateral intervertebral foramen height on CT, and the midsagittal canal diameter and axial central canal area. In 30 patients with at least one segment of grade 3, the clinical efficacy was assessed using visual analogue scale (VAS) and Oswestry disability index (ODI).Results:The average the anterior and posterior intervertebral space height, intervertebral space angle, height of bilateral intervertebral foramina, spinal canal sagittal diameter and spinal canal area were significantly improved after the operation of grade 3 facet joint degeneration segment compared to preoperation. The preoperative mean spinal canal sagittal diameter and spinal canal area of grade 3 facet joint degeneration segment were significantly less than grade 1 and grade 2. The average change of spinal canal area after grade 3 articular degeneration was significantly less than that of grade 1 and 2, but there was no significant difference with that of grade 0. The posterior decompression rate was 55.56% (15/27) for grade 3, 35.82% (24/67) for grade 2, 16.03% (25/156) for grade 1, and 21.05% (4/19) for grade 0. The posterior decompression rate of grade 3 articular process degeneration was significantly higher than that of other grades ( P<0.001). Severe lateral recess stenosis and 24.24% of severe intervertebral foraminal stenosis were found in 81.48% of grade 3 degenerative segment. The 23 patients were followed up with an average of 21.62±6.52 months, and the average improvement of ODI was 24.10%±11.09%; the average VAS for leg pain and back pain were improved significantly. Conclusion:The degrees of facet joint degeneration do not prevent intervertebral space distraction of CLIF. However, because segments with severe facet joint arthropathy were usually associated with severe spinal canal stenosis, CLIF had a high rate of second-stage posterior decompression in the treatment of lumbar spinal stenosis with severe facet joint arthropathy.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective:To explore the clinical effect of the application of intraoperative psoas major intramuscular block therapy on the complications related to the approach after multi-segmental crenel lumbar interbody fusion (CLIF).Methods:All of 68 degenerative lumbar scoliosis patients who had received multi-segmental crenel lumbar interbody fusion during January 2020 and June 2020 were retrospectively reviewed. Patients were divided into two groups according to whether the psoas major muscle was treated with block therapy during the operation. The psoas muscle inblock group were filled with gel sponge infiltrated with a mixture of Betamethasone and lidocaine for local block therapy before closing the incision while that in the control group were not filled with gel sponge. There were 33 patients in the control group, 7 males and 26 females with an average of 65.8±7.1 years old (range: 54-81 years old); 35 cases in the block group, 9 males and 26 females with an average of 68.0±6.5 years old (range: 54-85 years old). The complications related to the approach (mainly includes pain, numbness in the front of the thigh, as well as psoas major, quadriceps muscle strength) were recorded respectively 1 day, 1 week, 1 month and 3 months after surgery. The main indicators of outcome including visual analog scale (VAS) of pain, the visual analog scale (VAS) of numbness, muscle strength of psoas major and quadriceps femoris, and the incidence of complications related to the approach were compared between the two groups of patients at different time points after surgery. The clinical outcomes were assessed using the Oswestry disability index (ODI), VAS for low back pain. The radiological outcome was evaluated with Cobb angles and sagittal balance parameters (sagittal vertical axis, SVA).Results:There were no significant differences in age, gender, body mass index (BMI), number of fusion segments, operation time, and intraoperative blood loss between the two groups. The incidence of approach-related complications was 17.1% in the block group and 39.4% in the control group, with statistically significant difference between the two groups ( χ2=4.177, P=0.041). The incidence of postoperative pain, numbness in the front of the thighs, and muscle strength of psoas major in the block group (11.4%, 14.3%) were lower than those in the control group (33.3%, 36.4%) ( χ2=4.740, P=0.029; χ2=4.416, P=0.036). And for numbness in the front of thigh, the block group (14.3) was lower than control group (21.2%), but no significant difference was shown between two groups ( χ2=0.561, P=0.454). However, there was no quadriceps weakness in either group. The VAS scores of painof the block group were lower than those of the control group at 1 day, 1 week, and 1 month after surgery, and the difference was statistically significant ( t=2.220, P=0.031; t=2.235, P=0.031; t=2.086, P=0.044). The difference at 3 months was not statistically significant ( t=0.385, P=0.701). The muscle strength of psoas major of the block group, meanwhile, was higher than those of the control group on the 1day and 1 week after surgery, the difference was statistically significant as well ( t=2.208, P=0.032; t=2.171, P=0.034). The difference at 1 and 3 months was not statistically significant ( t=0.923, P=0.359; t=1.437, P=0.160). No statistically significant differences were found in VAS scores of numbness at 1 day, 1 week, 1 month, and 3 months after surgery. Postoperative low back pain and lumbar spine function were significantly improved in both groups, and there was no statistical significance between the two groups. Coronal Cobb angle and sagittal balance were significantly improved in both groups after surgery, and there was no statistical significance between the two groups. Conclusion:Psoas major intramuscular block therapy can reduce the incidence of early postoperative complications of multi-segmental CLIF. Furthermore, it was found to be effective to alleviate anterior thigh pain within 1 month, and improve psoas major muscle weakness within 1 week.