Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To observe the change patterns of functional connectivity(FC)of basal forebrain subregions in Alzheimer disease(AD)patients.Methods Totally 42 AD patients(AD group)and 41 healthy controls(HC group)were retrospectively enrolled.Seed-based FC analysis was performed on basal forebrain subregions(Ch123 and Ch4)based on their resting-state functional MRI data and compared between groups.Results Compared with HC group,FC between left Ch4 and left hippocampus as well as left posterior cingulate gyrus significantly decreased,but between right Ch4 and right precentral gyrus,as well as right postcentral gyrus increased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Meanwhile,FC between left Ch123 and left superior temporal gyrus,left insula,between right Ch123 and left superior temporal gyrus,left temporal pole significantly increased,while between right Ch123 and right orbital superior frontal gyrus,right orbital inferior frontal gyrus significantly decreased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Conclusion FC changes of different basal forebrain subregions in AD patients were various.

Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To observe the change patterns of functional connectivity(FC)of basal forebrain subregions in Alzheimer disease(AD)patients.Methods Totally 42 AD patients(AD group)and 41 healthy controls(HC group)were retrospectively enrolled.Seed-based FC analysis was performed on basal forebrain subregions(Ch123 and Ch4)based on their resting-state functional MRI data and compared between groups.Results Compared with HC group,FC between left Ch4 and left hippocampus as well as left posterior cingulate gyrus significantly decreased,but between right Ch4 and right precentral gyrus,as well as right postcentral gyrus increased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Meanwhile,FC between left Ch123 and left superior temporal gyrus,left insula,between right Ch123 and left superior temporal gyrus,left temporal pole significantly increased,while between right Ch123 and right orbital superior frontal gyrus,right orbital inferior frontal gyrus significantly decreased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Conclusion FC changes of different basal forebrain subregions in AD patients were various.

Transcranial magnetic stimulation(TMS)is a non-invasive brain stimulation technique which could improve cognitive and memory function in patients with Alzheimer's disease(AD)to some extent.The targeting errors of traditional TMS were often significant.Utilizing various MR techniques could accurately visualize localization information of brain structures and functions,hence being helpful for precise TMS.The progresses of MR-guided TMS for treating AD were reviewed in this article.

Objective To investigate the effect of transcranial alternating current stimulation(tACS)on cerebral blood flow(CBF)in patients with Alzheimer's disease(AD).Methods A ret-rospective study was conducted on 21 mild AD patients admitted in our hospital from September 2019 to April 2022.All of them received tACS treatment for 3 weeks.Mini-mental state examina-tion(MMSE),auditory verbal learning test(AVLT)and MRI were applied to obtain the data at baseline(T0),the end of the treatment(T1)and in three months after treatment(T2).Z-trans-form CBF(zCBF)was performed to reduce individual variability.The changes in MMSE and AVLT scores,as well as brain zCBF and CBF values before and after tACS treatment were ana-lyzed.Spearman correlation analysis was used to examine the relationship of zCBF and CBF with cognitive scores.Results In the AD patients,their MMSE score was significantly increased at T1 than at T0[22.00(20.00,25.00)vs 20.00(18.00,21.50),P＜0.01].Based on voxel analysis,the AD patients exhibited significantly increased zCBF in the bilateral frontal and temporal cortex at T1,and in the right frontal and temporal cortex at T2 when compared with the levels at T0(P＜0.05).The most pronounced increase in zCBF was observed in the right insular.Based on region of inter-est analysis,increased zCBF and CBF in the right frontal and temporal cortex at T1 were observed(P＜0.05).There was a positive correlation between the change of CBF in the right frontal cortex and AVLT-recognition recall at T1(r=0.617,P=0.005)and between the change of CBF in the left frontal cortex and MMSE at T2(r=0.596,P=0.012).Conclusion MRI 3D-ASL can objec-tively evaluate the changes of CBF in AD patients after tACS treatment,and it provides a reliable imaging marker for evaluating the efficacy of tACS.

Objective:To investigate the efficacy of internal fixation maintenance after fracture-related infection (FRI).Methods:Retrospectively analyzed were the data of 81 patients with deep FRI after 6 weeks of internal fixation who had been treated with hardware maintenance at Department of Orthopedics, The Second Hospital Affiliated to School of Medicine, Zhejiang University between 2013 and 2021. They were 61 males and 20 females, aged from 11 to 73 years (average, 11 years). After admission, the patients received bacterial culture, thorough debridement, negative pressure suction, soft tissue repair, and local and intravenous antibiotics. If a joint was affected by FRI, its cavity was cleaned and drained. Infection control and fracture healing were regularly observed in all patients. A treatment was considered successful when the internal fixation was maintained until fracture union, and considered as unsuccessful when the internal fixation was removed before fracture union. Risk factors associated with treatment failure were identified from gender, age, smoking, diabetes, fracture type, methicillin-resistant Staphylococcus aureus (MRSA) infection, methicillin-susceptible staphylococcus (MSSA) infection, Pseudomonas aeruginosa infection, Escherichia coli infection, infection by two kinds of bacteria, negative bacterial culture, early infection (within 2 weeks) and local use of antibiotics.Results:All patients were followed up for an average of 30 months (from 6 to 84 months). Fracture union was achieved in 62 (76.5%) patients with infection control and internal fixation retained. Masquelet technique was used to treat bone defects in 2 patients; a muscle flap or skin flap was used to reconstruct soft tissue coverage in 11 cases; fracture union was achieved by antibiotics and dressing changes in 2 patients with sinus tract. Amputation was performed in one unsuccessful case due to uncontrollable infection, and internal fixation was changed to external fixation in the other 18 unsuccessful cases, of which 3 achieved final bone union after application of Masquelet technique, 7 achieved final bone union after application of bone transfer technique, and 3 achieved soft tissue coverage after reconstruction with flap technique. Pseudomonas aeruginosa infection, open fractures and FRI for more than 2 weeks were high risk factors for failure in internal fixation maintenance ( P<0.05). Conclusions:If internal fixation is still stable and effective, hardware maintenance should be tried first in the patients with FRI within 6 weeks after fracture internal fixation. Muscle flap or skin flap surgery should be performed as soon as possible to effectively control infection and promote fracture union in the patients with soft tissue defects after thorough and effective debridement. History of open fracture, Pseudomonas aeruginosa infection, and FRI for over 2 weeks may be risk factors for failure in internal fixation maintenance.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.