Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objectives:To explore the safety and early effectiveness of decompression under full-endoscope and percutaneous pedicle screw fixation in the treatment of single-level thoracolumbar burst fractures.Methods:The clinical data of 9 patients with single-segment thoracolumbar burst fracture treated with spinal canal decompression under full-endoscope and percutaneous pedicle screw fixation from April 2021 to June 2022 in our hospital were analyzed retrospectively,including 7 males and 2 females.The age ranged from 23 to 61(39.3±9.1)years old.According to AO classification,there were 6 cases of type A,2 cases of type B and 1 case of type C.Fracture segments were T12 in 2 cases,L1 in 3 cases,L2 in 3 cases,and L3 in 1 case.According to the classification of American Spinal Injury Association(ASIA)grading,there were 2 cases of type C,2 cases of type D,and 5 cases of type E.The decompression and percutaneous pedicle screw fixation were operated through the same incision in the injured vertebrae for screw placing.The operation-related indexes and complications were recorded.The patients'low back pain was evaluated by visual analogue scale(VAS)score before operation,on 3rd day after operation and at the last follow-up.The sagittal Cobb angle,height ratio of vertebral anterior edge,and the rate of spinal canal occupation were measured on spinal X-ray and CT images,and the recovery of neurological function was evaluated at the last follow-up.Results:All 9 patients successfully completed the operation,and the operative time was 105-145min(1 12.4± 21.2min),bleeding volume was 50-110mL(83.9±19.6mL),and hospitalization time was 7-13d(9.1±1.3d).No serious complications such as wound infection,cerebrospinal fluid leakage,aggravated nerve injury occurred.The follow-up time was 6-13months(8.4±3.9 months),all the fractures healed successfully,and the healing time was 3-6 months(4.7±1.6 months).The VAS score of low back pain on the 3rd day after operation and at final follow-up significantly improved compared with that before operation(P＜0.05),and it was also significantly improved at the last follow-up compared with that on the 3rd day after operation(P＜0.05).The Cobb angle,anterior height ratio of injured vertebrae,and invasion rate of spinal canal were significantly improved compared with those before operation(P＜0.05),respectively,but there was no statistical difference between the last follow-up and postoperative 3d(P＞0.05).One patient recovered from grade C to grade D of ASIA classification,while another three patients with neurological injury recovered completely.Conclusions:Decompression under full-endoscope and percutaneous pedicle screw fixation through the same incision in the injured vertebrae for screw placement in the treatment of single-level thoracolumbar burst fractures can obtain effective nerve root and spinal canal decompression,with good correction and small operative trauma,which is a safe and effective option.

Objective:To investigate the therapeutic efficacy of Ilizarov bone shortening-lengthening technique for tibial defects of bone and soft tissue without vascular injury.Methods:A retrospective analysis was made of the 28 patients who had been treated by Ilizarov bone shortening-lengthening technique at Department of Orthopaedics, Wuxi No.9 People's Hospital from January 2007 to October 2017 for tibial de-fects of bone and soft tissue without vascular injury.They were 20 males and 8 females, aged from 18 to 69 years (average, 36.4 years).By the Gustillo classification, 5 cases belonged to type Ⅱ, 6 to type ⅢA and 17 to type ⅢB.Infection was complicated in 17 cases.After debridement or epluchage, the area of skin defects ranged from 4 cm × 3 cm to 16 cm × 5 cm and the length of bone defects from 4.5 to 11.0 cm (average, 6.9 cm).The wound healing, bone healing, functionary recovery of lower extremity and complications were observed postoperatively.Bone healing and functional recovery of lower extremity were evaluated according to the grading of Association for the Study and Application of the Method of Ilizarov (ASAMI).The complications associated with Ilizarov technique were assessed according to the Paley criteria.Results:The follow-up for all the patients lasted from 12 to 45 months (average, 20.5 months).The healing time for wounds ranged from 13 to 35 days (average, 21.9 days), the healing time for lengthened bone from 6 to 12 months (average, 8.9 months), and the healing time for bone defects at the dock sites from 6 to 11 months (8.3 months).According to the ASAMI grading, the bone healing was excellent in 21 cases and good in 7, giving an excellent to good rate of 100%(28/28) while the functionary recovery of lower extremity was excellent in 10 cases, good in 15, fair in 2 and poor in one, giving an excellent to good rate of 89.3%(25/28).The incidence was 14.3%(4/28) for major complications after Ilizarov surgery, 57.1%(16/28) for minor complications, 60.7%(17/28) for overall complications, and 1.7 times for each case.Conclusion:In the treatment of tibial defects of bone and soft tissue without vascular injury, Ilizarov bone shortening-lengthening technique can deal with the difficulties in repair of soft tissue defects, characterized by simplified wound closure, fast and improved bone healing at the dock sites, reduced complications and satisfactory functionary recovery of lower extremity.

Objective To investigate the clinical effects of treating traumatic lesions of the popliteal artery by staged stretching.Methods From July 2011 to March 2016,29 patients with traumatic lesion of the popliteal artery underwent staged stretching after direct end to end anastomosis at Department of Orthopaedics,The 9th People's Hospital of Wuxi.They were 19 males and 10 females,with a mean age of 38.3 years (range,from 16 to 61 years).The average length of popliteal artery lesions was 3.7 cm (range,from 2 to 5 cm).After the keen joint was immobilized at flexion by external fixation,direct end to end anastomosis was performed with a proper segmental vascular freedom.From 4 weeks after operation,the popliteal artery was stretched stage by stage to its original length by gradual adjustment of the external fixation till the knee joint was fully extended.The color,skin temperature,pulp tension and capillary reaction of the toes were closely observed after surgery.CT angiography (CTA) was performed 6 months after surgery.The active range of motion was assessed at 12 months after surgery for the knee and ankle joints on the injured limb.Results All the patients were available for an average follow-up of 2 years (range,from 1 to 3 years).Blood supply was good for all the affected limbs.The staged stretching of the popliteal artery resulted in no rupture of any anastomotic stoma or no thrombus.CTA at 6 months after surgery showed fine patency of the popliteal artery and no formation of false aneurysm or arteriovenous fistula.At 12 months after surgery,the knee function was excellent in 15 cases,good in 10 and fair in 4;the ankle function was excellent in 18 cases,good in 8 and fair in 3.Conclusion Staged stretching is a safe,convenient and effective treatment of traumatic lesions of the popliteal artery.

Objective To compare the effects of bone transport versus induced membrane technique for large segmental tibial defects.Methods The clinical data were analyzed retrospectively of 89 patients with large segmental tibial defect who had been treated at Department of Orthopaedics,Wuxi No.9 People's Hospital from June 2005 to February 2017 using bone transport or induced membrane technique.They were 58males and 31 females,aged from 13 to 74 years (average,38.0 years).The bone transport group had 59cases and the induced membrane technique group 30 cases.The 2 groups were compared in terms of preoperative general data and postoperative bone nonunion,bone healing time,complications and functional recovery of the adjacent joint.Results There were no statistically significant differences between the 2groups in terms of age,gender,cause or type of defects,associated injury,course of disease,functionary scores of the adjacent joint or number of operations,showing compatibility between the 2 groups (P ＞ 0.05).All the patients were followed up for 12 to 48 months (average,20 months).The bone transport group had significandy longer clinical healing time (14.7 ± 5.4 months) and significantly higher incidences of major complications (50.8％),minor complications (57.6％) and overall complications (83.1％) than the induced membrane technique group (11.2 ± 2.8 months,16.7％,26.7％ and 30.0％,respectively) (P ＜ O.05),but significantly lower functionary scores of the adjacent joint (86.4 ± 5.0 points) than the induced membrane technique group (88.8 ± 4.9 points) (P ＜ 0.05).Conclusions Both bone transport and induced membrane technique are effective repairs for large segmental tibial defects.However,induced membrane technique may be superior to bone transport in terms of bone healing,complications and functional recovery.

Objective To investigate the augmentation plating for femoral fractures and postoperative femoral nonunion. Methods A retrospective analysis was conducted of 60 patients with femoral fracture or postoperative femoral nonunion who had been treated with augmentation plating from January 2008 to July 2015. They were 36 males and 24 females, aged from 15 to 79 years ( average, 43. 4 years ) . Of them, 20 cases suffered nonunion following intramedullary nailing of femoral shaft fracture, 18 nonunion following lateral plating for femoral distal or lower fracture, and 22 femoral distal or lower fracture complicated with comminuted fracture of medial column. An incision ranging from 6 to 10 cm was made around the fracture ends for augmentative plating for all the patients. Autogenous iliac bone graft was performed in patients with atrophic nonunion or ob-vious gap after reduction of the comminuted fracture. Operation time, intraoperative bleeding, healing time, complications, and functionary recovery of the affected knee were recorded. Results The operation time averaged 121. 5 min and the intraoperative bleeding 356. 3 mL. All the patients were followed up for 12 to 36 months ( average, 16. 9 months ) . All the fractures and nonunions healed after an average time of 4. 2 months ( from 3 to 4 months ) . The time for initial partial weight-bearing averaged 4. 5 weeks ( from 2 to 6 weeks ) and the time for initial full weight bearing 3. 3 months ( from 2 to 4 months ) . Evaluation according to the Karlstrom and Olerud criteria at the last follow-up revealed 29 excellent, 24 good and 7 fair cases, yielding an excellent and good rate of 88. 3％. No infection, loosening, bending or breaking of internal implants, or refracture was noted during follow-ups. Conclusion Augmentation plating through a small incision can lead to fine outcomes for femoral fractures and postoperative femoral nonunion, because it makes up the deficient stability of original in-ternal fixation, reduces the dislocated bone blocks and provides bone grafting to improve defective local bone structure and defective osteogenesis.

BACKGROUND: Lateral locking plate is a classical fixation method to treat lower and distal femoral fractures. However,the incidences of delayed healing, nonunion, plate extubation, and internal fixation rupture exceed 20% after internal fixation.OBJECTIVE: To compare the effectiveness of augmentation plating and single plating for distal and lower femoral fractures with medial comminution.METHODS: Totally 60 patients of lower and distal femoral fractures with medial comminution treated with open reduction and plate fixation were divided into augmentation plating (treatment group, 28 cases) and single lateral plating (control group, 32 cases). We observed the operation time and blood loss, recorded the out-off-bed rehabilitation time, full weight bearing time and complication. The functionary recovery of knee joint was evaluated according to Schatzker-Lambert method for distal femoral fractures in final follow-up.RESULTS AND CONCLUSION: (1) All patients were followed for at least 12 months. All incisions were healed by first intention. (2) The operation time and blood loss in the treatment group were greater than those in the control group (P <0.05). (3) The healing time (3.11±0.31 months), out-off-bed rehabilitation time (4.36±0.91 weeks), full weight bearing time (3.67±0.62 months), complication (0) and excellent and good rate of knee functionary recovery (100%) in the treatment group were better than those in the control group [(5.65±2.33), (7.25±1.02), (6.03±2.61) months, 8, 65.6%] (P < 0.05). (4)Although augmentation plating for treatment of lower and distal femoral fractures with medial comminution prolongs operation time and increases surgical blood loss, the results including the healing rate, complication and satisfaction rate are superior to those treated with single lateral plating.

Objective To investigate the principles and effects of cancellous bone wrapping grafting for treatment of segmental defects of long bone.Methods From January 2008 to December 2015,50 patients with segmental long bone defect were treated by various wrapping grafting with rich autogenous cancellous bone.They were 31 males and 19 females,aged from 13 to 69 years (average,34.6 years).The cancellous bone was wrapped by titanium mesh in 8 cases,by wire mesh in 10,by line binding in 13,and by induced membrane in 19.The bone defect was located at tibia in 22 cases,at radius in 10,at humerus in 8,at ulna in 7 and at femur in 3.The length of bone defect ranged from 3 to 9 cm,averaging 5.9 em.Bone healing,complications and functionary recovery of adjacent joint were recorded.The bone defect healing and functionary recovery of adjacent joint were evaluated according to the Paley criteria.Results The incisions healed by the first intention in 48 cases and by the second in 2.All were followed up for 12 to 48 months (average,19.1 months).All the bone defects healed by the first intention but one treated by induced membrane wrapping which was healed 15 months later by the secondary grafting due to nonunion at ends.The total clinical healing time ranged from 3 to 16 months (average,6.1 months).The last follow-ups showed that all the affected limbs resumed weight-bearing activities.The healing of bone defects was graded as excellent in all but one in the group of induced membrane wrapping.Totally,the functionary recovery of adjacent joint was excellent in 18,good in 22,fair in 7 and poor in 3 cases (an excellent and good rate of 80.0％).Conclusions Cancellous bone wrapping grafting can avoid or significantly reduce loosening and absorption of cancellous bone graft after traditional bone grafting.Although it is effective for treatment of large segmental bone defect,its methods should vary according to the specific conditions of the patient.