Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain functional activity and working memory of rats with vascular cognitive impairment (VCI). Methods Eighteen Sprague-Dawley rats were included, in which twelve rats were ligated bilateral common carotid arteries and six rats were not ligated (sham group). The modeled rats were randomly divided into model group (n = 6) and electroacupuncture group (n = 6). The electroacupuncture group received electroacupuncture at Baihui and Shenting for four weeks. They were assessed with Y maze and Morris water maze before and after intervention, and scaned with resting-state functional magnetic resonance imaging after intervention to calculate regional homogeneity (ReHo). Results Compared with the sham group, alternation rate of Y maze decreased (P < 0.001), and escape latency of Morris water maze increased (P < 0.05) in the model group and the electroacupuncture group before intervention. Compared with the model group, alternation rate of Y maze increased (P < 0.05), and escape latency of Morris water maze decreased (P < 0.05) after intervention in the electroacupuncture group. Compared with the sham group, ReHo of bilateral hippocampus, olfactory cortex, sensory cortex and auditory cortex, and left striatum decreased in the model group; compared with the model group, ReHo of bilateral prefrontal lobe, hippocampus and olfactory cortex, and left amygdala increased in the electroacupuncture group. Conclusion Electroacupuncture at Baihui and Shenting can improve the memory function of VCI rats, which may be related to the functional activities of prefrontal lobes, hippocampus and amygdala.

Objective:To summarize the preliminary experience in ward management, medical protection, standardised diagnosis and treatment procedures in trauma microsurgery during the outbreak of COVID-19.Methods:Taking an example from the Department of Trauma and Microsurgery at Zhongnan Hospital of Wuhan University, the orthopedic patients and medical staff with COVID-19 admitted from Decemberm 31, 2019 to March 1, 2020, in-cluding clinical diagnosis and confirmed cases, were analyzed retrospectively. General information, including age, gen- der, basic diseases, contact history, symptoms, lung CT and prognosis, were collected and analysed preliminarily. On January 20, 2020, the COVID-19 outbreak was confirmed as "human to human transmission". COVID-19 infection of patients and medical staff in the wards were analysed, through the update of protection awareness and control measures. Department management, medical protection and standardized control procedures of trauma microsurgery were explored.Results:Five cases with clinical diagnosis or confirmed COVID-19 were included. One was inpatient and the rest 4 were medical staff, aged 25-81 years, 3 with confirmed and 2 with clinical diagnosis of COVID-19. After the treatment by specialists from Department of Infectious Disease and Department of Respiratory Disease, 4 of infected persons were cured and 1 died. Since January 20, 2020, when it was clear that the virus transmitted to people, there was no new case of infection among the medical staff and inpatients after the multidisciplinary collaboration in the ward prevention and control procedures were standardized and took in action.Conclusion:The spread of the COVID-19 can be effectively controlled by standardised diagnosis and treatment procedurs in the word of trauma microsurgery.

Objective To investigate the clinical effect of thin-layer free anterolateral thigh flap with iliotibial tract for reconstruction of heel soft tissue and Achilles tendon defect.Methods From January,2017 to December,2017,11 cases of heel soft tissue and Achilles tendon defect were repaired by thin-layer free anterolateral thigh flap with iliotibial tract.There were 5 cases with tibia/fibula fracture,3 cases with ankle fracture and 1 case with calcaneal fracture.The area of soft tissue defect was 6.5 cm×10.0 cm-8.0 cm×13.0 cm,and the length of Achilles tendon defect was 5.5-11.5 cm.All wounds were treated with debridement and negative pressure sealing drainage technique at first stage.After 6 days,the soft tissue defect around posterior calcaneal region combined with Achilles tendon defect were repaired by the thin-layer free anterolateral thigh flap with iliotibial tract.Reasonable rehabilitation training was established after operation.Results The flaps survived in 11 cases and the donor region healed in one stage.The patients were followed-up for 8 to 20 (mean,15.74) months by outpatient review,calling or WeChat.Slightly bloated in appearance in 2 cases,and were thinned by orthopedic operation 1 year later.The other flaps were well shaped and moderately thick.At the last follow-up,the flaps were soft in texture and elastic.The sensory recovery of the flap was good,and the two-point discriminant perception in the posterior region of the heel was 3.0-5.0(mean,4.11) mm.Thompson's sign was negative,double or one-foot heel lift test was negative,and there was no recurrence of Achilles tendon rupture or skin ulceration in the heel region.The range of motion (ROM) of affected side was (23.1 1±1.17)°of extension and (43.67±1.06)°of flexion,and the ROM of normal side was (23.79±1.03)°of extension and (44.03±0.94)°of flexion.There was no statistical difference between them (P＞0.05).Postoperative follow-up was conducted according to the Thermann's function evaluation system,the evaluated result was excellent in 8 cases,good in 2 cases,and receivability in 1 case.Conclusion It is a reliable and effective method to repair heel soft tissue and Achilles tendon defect by thin-layer free anterolateral thigh flap with iliotibial tract.And this method can better restore foot ankle shape and function.

Objective To compare internal fixation with hallow compression screws combined vascularized bone graft(observation group) with only three hallow compression screws(control group) in young patients' Garden III and IV femoral neck fractures. Methods The patients with femoral neck fracture were treated from January, 2004 to December, 2013 were retrospectively reviewed. A total of 417 displaced femoral neck fractures in young and mid-dle-aged patients were long term followed-up. One hundred and thirty-seven patients were underwent open reduction and internal fixation with 3 hallow compression screws combined with a greater trochanter bone graft supported by the profound branch of medial circumflex femoral artery;280 patients were treated by closed reduction with 3 hallow com-pression screws. Results Patients had been followed-up for 5-12 years. At the last follow-up point, the Harris score of flap in observation group(93.68±5.12) were higher than that in control group(92.53±6.12), while it was no sta-tistical difference(P>0.05). It was 0.7％of nonunion incidence rate in the observation group, and incidence of avascular necrosis of femoral head was 6.6％, and incidence of femoral neck shortening was 8.8％. In the control group, inci-dence of avascular necrosis of femoral head was 14.6％, nonunion incidence rate was 4.6％, and incidence of femoral neck shortening was 22.5％. The differences between two groups was statistically significance( P<0.05). Conclusion The open reduction and internal fixation which is hallow compression screws in combination with a greater trochanter bone graft supported by the profound branch of medial circumflex femoral artery is an optimal treatment for young adults with Garden III and IV femoral neck fractures.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Acute Disease ; Animals ; Brain ; diagnostic imaging ; metabolism ; Brain Mapping ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; metabolism ; Male ; Neural Pathways ; diagnostic imaging ; metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Random Allocation ; Rats, Sprague-Dawley

Objective To explore the effect of the use of flap transplantation combined with Masquelet tech-nique in the repair of long bone accompanied with soft tissue defect. Methods The retrospective study includes 16 cases of bone defects over 6.0 cm combined with soft tissue defect from March,2013 to March,2016,13 males and 3 females, of which the ages range from 16 to 65 years. The length of bone defect ranged from 6.0 to 12.0 cm, with an average of 8.5 cm,while the wound defect ranged from 5.2 cm×3.5 cm to 16.0 cm×7.5 cm. There were 8 cases out of 16 involve an infection:3 cases of Staphylococcus aureus(including 1 MRSA),2 cases of Staphylococcus epidermidis, 2 cases of Enterobacter cloacae, and 1 case of Acinetobacter baumannii. The 1 stage surgery in all patients admitted to hospital after complete debridement and external fixation, the clean wounds with bone defect received antibiotic-impregnated bone cement filling operation and a flap transplantation or transposition directly after the debridement, but the infected wounds received vacuum sealing drainage treatment firstly, associated with adequate use of antibi-otics for 1-2 weeks and then the bone cement filling and flap transplantation with infection totally controlled.After 8-12 weeks, we conducted the secondary internal fixation surgery replacing antibiotic-impregnated bone cement with autogenic cancellous bone, vancomycin artificial bone as well as rhBMP-2. All the cases were followed for 6 to 18 months. Results All patients with primary surgery are effectively controlled after 1-4 weeks of anti-infection treat-ment exclusive of the case with MRSA.As the condition of the patient with MRSA relapse,we changed to convention-al treatment: placed a continuous irrigation and suction equipment instead of the bone cement filling, the wound healed completely without fistula formation of osteomyelitis in 6 months after the treatment of Ilizarov technique. All transplantation and transposition flaps survived. As for those who received a secondary bone graft operation, all achieved a bony union in a period of 4-6 months. Conclusion The combination of flap transplantation and Masquelet technique is an effective method to repair limb long bone and soft tissue defect currently.

Objective To investigate the relationship between learning and memory deficit and demyelination of the corpus callosum in twelve-month old APP/PS1 transgenic mice. Methods Twelve twelve-month old APP/PS1 transgenic mice were as AD group, and age-matched wild type (WT) littermates were as WT group. Learning and memory ability was tested with Morris water maze, and the mor-phology of nerve fiber of corpus callosum was detected with Luxol Fast Blue staining. Immunohistochemistry was used to detect myelin ba-sic protein (MBP) in the corpus callosum. Thioflavine S staining was used to detect amyloid plaque in the corpus callosum. Results Com-pared with WT group, the latency increased (Z>2.873, P<0.01) and the times crossing the location of the platform decreased (t=-7.339, P<0.001) in AD group. The nerve fibers were sparse and disorganized, with a lot of vacuoles in the corpus callosum of AD group. The positive expression of MBP in the corpus callosum was significantly decreased (t=-4.481, P<0.001) in AD group compared with WT group. There were amyloid plaques in the corpus callosum of AD group. Conclusion Twelve-month old APP/PS1 transgenic mice exhibit learning and memory deficit, which may be attributed to the deposition of the amyloid plaque mediated demyelinated injury of the corpus callosum.

Objective To summarize the clinical experience of treating long bone defect with vascularized fibular graft.Methods From January,2008 to January,2015,31 cases of long bone defect were treated with vascularized fibula composite or not composite tissue flap graft.The length of transplanted fibula was 9-20 cm,and the flap area was 5 cm×3 cm to 21 cm×14 cm.All patients were followed up regularly.Limb function was assessed 12 months after surgery.Results Thirty-one cases of vascularized fibular flap survived after surgery.Thirty patients were followed up for 1.5 to 6 years (average,2.5 years).One patient was lost to follow-up.The bone defects of patients followed up were healed.There was one case fracture occurred for trauma,was treated with plaster cast for 6 months and healed.The transplanted fibular thickened for 1.3 to 2.5 years(average,1.6 years).Conclusion Vascularized fibular graft can reconstruct long bone defect for single use and shorten the duration of treatment with a good limb function.For cases combined soft tissue defect,vascularized fibula composite tissue flap can be applied to repair at the meantime.

Objective To explore the effect of electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on motor behaviors, the axonal integrity and nerve bundle of motor cortex and striatum in rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) using diffusion tensor imaging (DTI). Methods Thirty-six adult male Sprague-Dawley rats were randomly assigned to sham opera-tion group (sham group), ischemia control group (model group) and electroacupuncture treatment group (EA group) with twelve rats in each group. The later two groups were occluded their middle cerebral arteries for two hours. Twenty-four hours after modeling, EA group re-ceived electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on the paralyzed limb, once a day, for 14 days. They were assessed with modified Neurological Severity Scores (mNSS) and Rota-rod test, and scanned with small animal magnetic resonance imaging system for T2-weighted image (T2WI) and DTI, the infarct size, related fractional anisotropy (rFA) and related number of tracks of motor cortex and striatum were recorded. Results Compared with the sham group, the score of mNSS increased in the model group and EA group after model-ing, and was lower in EA group than in the model group seven days and 14 days after intervention (P<0.05). Rota-rod test showed that the retention time was significantly longer in EA group than in the model group (P<0.05). T2WI showed that the infarct size was smaller in EA group than in the model group (P<0.05). DTI showed that rFA in motor cortex and striatum was higher in EA group than in the model group (P<0.05), as well as the related number of tracks (P<0.05) in motor cortex. Conclusion Electroacupuncture at Quchi and Zusanli acupoints could improve the motor function in rats with ischemic stroke, which may be related to the recovery of nerve bundle of motor cortex and stri-atum in ischemic side.