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.

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The quality control during the manufacturing process of traditional Chinese medicine TCM)is paramount to ensuring the quality of the final product.However,the sheer diversity of TCM ingredients and the intricacies of the production process pose sig-nificant challenges to achieving precise quality control.The review introduced an intelligent control concept centered on functional sub-stances in TCM quality,which comprehensively explained the scientific essence of TCM quality,and provided a theoretical foundation for determining"what to control"and"how to control"within the complex system of TCM components.Furthermore,through the ad-vanced informatization,digitization,and intelligent technologies,our team has conducted extensive research and construction practices on the intelligent transformation and digital upgrade of traditional Chinese medicine TCM)manufacturing processes.Ultimately,the establishment of a quality control system tailored specifically for TCM manufacturing with functional substances serving as the primary quality target,which presented an opportunity to solve the difficult problem of process quality control in TCM manufacturing.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

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 evaluate the safety and efficacy of foam sclerotherapy for bleeding internal hemorrhoids. Methods: Consecutive adult patients (aged 18-60 years) with bleeding hemorrhoids were prospectively enrolled between March 2017 and March 2018. All patients were randomly assigned to the foam sclerotherapy (FS) group and the liquid sclerotherapy (LS) group. The foam and liquid sclerotherapy of hemorrhoids nucleus was performed by cap-assisted colonic endoscopy. Results: A total of 108 patients were enrolled, including 62 males (57.4%) with mean age of 44.0±7.6 years. There was no significant difference in gender, age, or body mass index between the FS (n = 55) group and the LS (n =53) group. The total amount of lauromacrogol injection in the FS group was 3.7±0.9 mL, which was significantly lower than that in the LS group (8.0±2.2 mL, P<0.001). In the LS group, 8 patients (15.1%) developed bleeding after needle removal, which was significantly higher than that in the FS group [5.5%(3/53), P=0.022]. Significant pain was found in 2 patients (3.8%) in the LS group and 0 in the FS group (P= 0.025). The short-term cure rate and effective rate of the FS group were 87.3% (48/55) and 9.1% (5/55), while those were 69.8% (37/53) and 22.6% (12/53) in the LS group, respectively (P=0.046). Conclusion Foam sclerotherapy is safe and effective in the treatment of bleeding internal hemorrhoids.

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 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.

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer’s disease (AD) induced by Aβ1–42 and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 µg/kg/day), the cognitive impairment of mice induced by Aβ1–42 was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aβ1–42 accumulation in hippocampus. Aβ1–42 induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression, suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.
Alzheimer Disease* ; Animals ; B-Lymphocytes ; Brain ; Brain-Derived Neurotrophic Factor ; Cognition Disorders ; Hippocampus ; Humans ; Hypnosis ; Learning* ; Locomotion ; Malondialdehyde ; Memory Disorders ; Memory* ; Mice* ; Neuroprotection ; Neuroprotective Agents* ; Oxidative Stress ; Water

Objective To evaluate the effect of precision anesthesia strategy on postoperative cognitive function in elderly patients undergoing hip replacement.Methods Seventy elderly patients of both sexes,aged 65-85 yr,weighing 50-75 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective unilateral hip replacement under general anesthesia,with years of education＞6 yr,were divided into 2 groups (n =35 each) using a random number table:precision anesthesia group (group P) and routine anesthesia group (group R).Anesthetic protocol and perioperative management were optimized using precision anesthesia strategy in group P.Routine anesthetic protocol and perioperative management were performed in group R.Peripheral venous blood samples were collected at 1 day before operation (T0) and 1,6,12 and 24 h after operation (T1-4) for determination of serum S100β protein,neuronspecific enolase (NSE),interleukin-1beta (IL-1β),IL-6,tumor necrosis factor-alpha (TNF-α) and Creactive protein (CRP) concentrations by enzyme-linked immunosorbent assay.The patient's cognitive function was assessed using Mini-Mental State Examination (MMSE) at T0 and 3 and 7 days after operation (T5,6).Results Compared with the baseline at T0,the serum S100β protein and NSE concentrations were significantly increased at T1-3,the serum IL-1β,IL-6 and TNF-α concentrations were increased at T1-4,the CRP concentrations were increased at T2,3,MMSE scores were decreased at T5 in group R,and the serum S100β protein,IL-1β and IL-6 concentrations were significantly increased at T1-3,the serum NSE and CRP concentrations were increased at T2,the serum TNF-α concentrations were increased at T1-4,and MMSE cores were decreased at T5 in group P (P＜0.05).Compared with group R,the serum S100β protein and IL-1β concentrations were significantly decreased at T1,2,the serum NSE and TNF-α concentrations were decreased at T1-3,the serum IL-6 concentrations were decreased at T2,3,and MMSE scores were increased at T5 in group P (P＜ 0.05).Conclusion Precision anesthesia strategy can improve postoperative cognitive function in elderly patients undergoing hip replacement,which is related to inhibiting inflammatory responses.