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.

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: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.

Background and objective Epidermal growth factor receptor (EGFR) mutations occur more frequently in non-small cell lung cancer (NSCLC) of women, never smokers, Asian population and those with adenocarcinoma. Short in-frame deletion in exon 19 and L858R substitution are the most common mutations, which are closely associated with EGFR tyrosine kinase inhibitors (TKIs) treatment response. However, the therapeutic effects of EGFR-TKIs on NSCLC with uncom-monEGFR mutation subtypes remain unclear. hTe aim of this study is to investigate the clinicopathologic feature of uncom-monEGFR mutations and the outcomes of these patients.Methods Twenty-four patients that harbored uncommonEGFR mutations were included in this study. Clinicopathologic features of uncommonEGFR mutations and the outcomes of these patients were analyzed.Results Of the 24 patients, 13 received EGFR-TKIs treatment. hTe response rate of EGFR-TKIs treat-ment was 46.1%, and the median progression-free survival (PFS) was 7.4 months. Mutations on S768I and L861Q composed a major part (8 of 24) of uncommon mutations.Conclusions UncommonEGFR mutations constituted a unique part of the whole group ofEGFR mutations. hTeir composition and sensitivity to EGFR-TKIs were heterogeneous, which requires further assessment in a prospective study.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation.Limited to the standards of tumor tissue samples and detection methods,still some people can't receive target therapy following genetic guidance.This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs.Methods We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation,who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital,analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs.Results The objective response rate (ORR)was 52.8％ and the disease control rate (DCR) was 89.3％.The results showed that,patients with high CEA level before treatment responded better to TKIs (ORR 61.3％ vs 35.9％,DCR 95.2％ vs 74.4％,P＜0.001).Similar phenomena was found in patients with CEA decreased 1 month later (61.5％ vs 25％,P=0.002).Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo,P=0.027).To the opposite,PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo,P=0.029;9.0 mo vs 11.5 mo,P=0.023,respectively).Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1,normal baseline CYFRA21-1 and CEA decline predicted longer PFS.The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo,P=0.003;22.7 mo vs 55.0 mo,P＜0.001,respectively),while independent of CEA.Conclusion High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma.While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

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.