Alzheimer' s disease (AD) is a neurodegenerative disease that gradually impairs cognitive functions. Recently, there has been a conceptual shift toward AD to view the disease as a continuum. Since AD is currently incurable, effective intervention to delay or prevent pathological cognitive decline may best target the early stages of symptomatic disease, such as subjective cognitive decline (SCD), in which cognitive function remains relatively intact. Diagnostic methods for identifying AD, such as cerebrospinal fluid biomarkers and positron emission tomography, are invasive and expensive. Therefore, it is imperative to develop blood biomarkers that are sensitive, less invasive, easier to access, and more cost effective for AD diagnosis. This review aimed to summarize the current data on whether individuals with SCD differ reliably and effectively in subjective and objective performances compared to cognitively normal elderly individuals, and to find one or more convenient and accessible blood biomarkers so that researchers can identify SCD patients with preclinical AD in the population as soon as possible. Owing to the heterogeneity and complicated pathogenesis of AD, it is difficult to make reliable diagnoses using only a single blood marker. This review provides an overview of the progress achieved to date with the use of SCD blood biomarkers in patients with preclinical AD, highlighting the key areas of application and current challenges.

Objective To investigate the efficacy of anti-infective reconstituted bone xenograft (ARBX) combined with external fixation in the treatment of adult infective nonunion of humeral shaft.Methods A retrospective case series study was conducted to analyze the clinical data of 18 patients with infected nonunion of humeral shaft admitted to Xijing Hospital of Air Force Military Medical University from January 2014 to December 2016.There were 10 males and eight females,aged 19-62 years [(36.9 ± 11.8)years].According to Umiarov classification of infective nonunion,there were 11 patients with type Ⅲ and seven with type Ⅳ.All patients were treated with anti-infective reconstituted bone xenograft (ARBX) combined with external fixation.The number of operations,bone healing time,bone healing rate,infection control rate,postoperative weight bearing time,the time of external fixation removal,postoperative complications,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) before and after operation were recorded.Fracture healing and functional recovery were evaluated using the Johner-Wruch lower limb function score.Results The patients were followed up for 12-30 months [(21.3 ±5.6)months].The operation was performed for (1.4 ±0.9) times,with time of bone healing for (16.6 ± 5.8)months,bone healing rate of 83％ (15/18),and infection control rate of 94％ (17/18).The postoperative weight bearing time in 15 patients who obtained bone healing was (3.3 ± 1.5)months after operation,and the external fixation removal time was (18.5 ± 4.2) months after operation.There were three patients with nonunion after operation including one with infection recurrence.Five patients were found with nail tract infection.ESR and CRP at postoperative 3 months [(13.1 ± 8.4)mm/h and (5.6 ± 4.6)mg/L] were significantly lower than those before operation [(47.3 ± 19.2)mm/h and (23.4 ± 7.4) mg/L] (P ＜ 0.05).According to Johner-Wruch lower limb function scores,the results were excellent in nine patients,good in four,fair in one,and poor in four,with excellent and good rate of 72％.Conclusion ARBX combined with External fixation can effectively treat infective nonunion of humeral shaft,improve bone healing rate,and promote function recovery.

Objective To compare the effectiveness of expandable intramedullary nail(EIMN) versus locked compression plate (LCP) in the treatment of humeral shaft fractures of AO types A and B.Methods The clinical data were retrospectively analyzed and compared of the 44 humeral shaft fractures which had been treated between May 2012 and February 2016.There were 26 men and 18 women,from 23 to 66 years of age (average,41.5 years).By AO classification,22 cases were type 12-A and 22 type 12-B.EINM was used in 22 patients with an average age of 41.3 ± 1 1.7 years and LCP in 22 ones with an average age of 41.6 ± 10.3 years.The 2 groups were compared in terms of intraoperative blood loss,operative time,hospital stay,union time,union rate,Constant and Mayo scores at the final follow-ups,and complications as well.Results The 2 groups were compatible without significant differences in the preoperative demographic data (P ＞ 0.05).All the 44 patients were followed up for 10 to 18 months (average,12 months).The intraoperative blood loss (76.4 ± 18.66 mL),operative time (69.1 ± 13.2 min),incision length (5.8 ± 1.5 cm) and union time (13.2 ± 8.4 w) in the EIMN group were significantly better than those in the LCP group (138.6 ± 39.4 mL,96.4 ± 14.2 min,8.5 ± 1.4 cm and 18.4 ± 6.6 w,respectively) (P ＜ 0.05).There was also a significant difference between the 2 groups in the total complication rate[18.2％ (4/22) versus 50.0％ (11/22)] (P ＜0.05).No deep infection or should pain was observed in either group.Conclusions Inthe treatment of humeral shaft fractures of AO types 42-A and 42-B,compared with LCP,EIMN may have advantages of less intraoperative blood loss,operative time,union time and complications.The 2 methods are similar in hospital stay and final functional recovery of the should joint.

Objective: To study the mutation of ENG, ACVRL1, and SMAD4 genes in one of a family of hereditary hemorrhagic telangiectasia (HHT) and explore its molecular pathogenesis. Methods: A family spectrum of a patient with a clinical diagnosis of HHT was surveyed. Peripheral blood samples from proband and their eldest were collected, and ENG, ACVRL1 and SMAD4 gene analysis was performed by chip capture high-throughput sequencing. The mutation detected was verified by Sanger. Results: 9 of the 71 family members were diagnosed with HHT with the main manifestation of recurrent nasal bleeding. Genetic analysis showed that the proband and the eldest son of ENG gene exon 9 frameshift mutation: c.1502-1503insGG (p.Gly501GlyfsX18) , and mutations in ACVRL1 and SMAD4 genes were not detected. Conclusion The frameshift mutation c.1502-1503insGG (p.Gly501GlyfsX18) of the ENG gene is the genetic basis for the pathogenesis of this HHT family.

Objective:To investigate the risk factors for nonunion after surgery for femoral shaft fractures in order to reduce them.Methods:The clinical data were retrospectively analyzed of the 804 patients with femoral shaft fracture who had been treated from January 2014 to December 2020 at Department of Orthopaedics, Xijing Hospital. There were 575 males and 229 females, aged from 18 to 96 years (average, 43.7 years). The patients were divided into 2 groups according to whether nonunion had occurred after surgery: a nonunion group of 112 cases and a fracture healing group of 692 cases. The preoperative general data, such as age, gender and fracture type, as well as intraoperative and postoperative data, such as operation time, internal fixation method, reduction method and internal fixation failure, were compared between the 2 groups. Items with P<0.05 were included in the multivariate logistic regression analysis to identify the risk factors for nonunion. Results:There were statistically significant differences between the nonunion group and the fracture healing group in smoking history, drinking history, injury mechanism, injury type, multiple injuries, fracture AO classification, fixation method, internal fixation failure, postoperative infection and use of non-steroid anti-inflammtory drugs ( P<0.05). Multivariate logistic regression analysis showed that smoking ( OR=3.261, 95% CI: 2.072 to 5.133, P<0.001), high energy injury ( OR=2.010, 95% CI: 1.085 to 3.722, P=0.026), multiple injuries ( OR=3.354, 95% CI: 1.985 to 5.669, P<0.001), AO type 32-C fracture (type 32-C fracture used as a reference, P=0.034), internal fixation failure ( OR=3.517, 95% CI: 1.806 to 6.849, P<0.001), external stent fixation (external stent fixation used as a reference, P=0.009) were the risk factors for nonunion after femoral shaft fractures. Conclusions:After surgery for patients with femoral shaft fracture, special attention should be paid to those with a smoking habit, high-energy injury, multiple injuries, AO type 32-C fracture, external stent fixation or a failed internal fixation, because they are high-risk groups prone to postoperative nonunion.

Objective:To understand the epidemiological characteristics and risk factors of fatal cases of hand, foot, and mouth disease (HFMD) in children under 5 years old in China from 2008 to 2018, and provide evidence for the development of targeted prevention and control measures and reduction of the incidence of fatal HFMD cases.Methods:The incidence data of reported HFMD cases in China during 2008-2018 were collected from the National Notifiable Disease Surveillance Reporting System of China for the analyses on the demographic characteristics, spatial distribution, diagnosis or reporting and pathogen spectrum of the HFMD cases. Then the risk factors causing deaths were analyzed by using logistic regression model.Results:From 2008 to 2018, a total of 3 646 fatal cases of HFMD in children under 5 years old were reported in China. There were more fatal HFMD cases in boys than in girls (1.82∶1), the death mainly occurred in age group 0 to 2 years (87.71%). Adjusted mortality rate of HFMD in children under 5 years old in China declined from 0.87 per 100 000 in 2010 to 0.11 per 100 000 in 2018 (APC=-23.20%). In the 2 523 laboratory-confirmed deaths, 2 323 (92.07%) were EV-A71 infections, but the constituents of CV-A16 and other enterovirus infections increased. The interval from onset to diagnosis M=2( P25-P75:2 -4)d. The interval from onset to death M=3( P25-P75:2 -4)d. Age between 0 and 1 years, EV-A71 infection, longer interval between onset and diagnosis, and living in rural area were the risk factors causing fatal HFMD cases. Conclusions:The number of the fatal cases, the rate of mortality and case fatality HFMD in China had shown downward trends since 2010. EV-A71 is still the main pathogen causing fatal cases, but we should pay more attention to gene pattern of the other enteroviruses except EV-A71 and CV-A16. To reduce the risk of the fatal cases we should strengthen the health education about the immunization of EV-A71 inactivated vaccines and reduce the interval from onset to diagnosis in young children in western provinces and rural areas.

Objective To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections(OIs).The lymphocyte subsets in healthy donors were used as normal control group. Results A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs.The common OIs were cytomegalovirus(CMV)diseases (66/108), Pneumocystis jirovecii pneumonia (PJP, 16/108), other fungal infections (16/108), Epstein-Barr virus (EBV, 15/108) and tuberculosis (14/108). Compared with treated SLE without OIs, total lymphocyte, CD4+T,and CD8+T lymphocyte counts were significantly reduced in SLE with OIs[1 260(780,1 810)cells/μl vs. 565(399,1 043)cells/μl,P<0.001; 485(280,811)cells/μl vs. 173(95,327)cells/μl,P<0.001; 464 (339,764)cells/μl vs.265(158,424)cells/μl,P=0.003,respectively].Conclusions The common OIs in treated SLE patients were CMV diseases,PJP,other fungi,EBV and tuberculosis.OIs are prone to develop in SLE patients with severe lymphocytopenia,especially CD4+T cell depletion.

Alzheimer′s disease (AD) is an incurable disease in the field of major chronic diseases. Subjective cognitive decline (SCD) is a clinical risk factor for AD. The standardized screening and intervention in individuals with SCD are of great importance in early prevention and treatment of AD. According to the clinical criteria proposed by The characterisation of subjective cognitive decline, which was published online in Lancet Neurology, the article summarized the definition of SCD, the latest perspective of clinical standards in SCD, and the results of AD preclinical SCD research. The purpose of this work was to provide concrete guidance and recommendations for making clinical decisions in diagnosis and scientific research on SCD.

Objective To observe the temporary loss(re-falling)of knee range of motion(ROM)during rehabilitation after arthroly-sis for post-traumatic knee stiffness,and analyze the factors related to it. Methods From July,2016 to September,2019,64 patients(68 knees)in Beijing Bo'ai Hospital accepted minimally inva-sive arthrolysis for post-traumatic knee stiffness,and were followed up for twelve months.ROM of flexion and extension of knee was measured before operation,and one,six and twelve weeks,and six and twelve months af-ter operation;while they were asssessed with Hospital for Special Surgery Knee Score(HSS).Multivariate Logis-tic regression was performed on re-falling. Results The ROM and HSS score improved as a whole after operation;however,HSS score improved constantly,but ROM decreased six weeks after operation compared with that one weeks after operation,involving 46 knees of 44 cases.Arthrolysis longer than 12 months from primary injuries,multiple complicated fracture and history of infection were the risk factors for re-falling(OR＞8.058,P＜0.05). Conclusion Minimally invasive arthrolysis is effective on knee function after arthrolysis for post-traumatic knee stiff-ness.However,re-falling of ROM may happen during rehabilitation.Delay of operation,multiple complicated fracture and history of infection may increase the risk of re-falling.

Alzheimer's disease（AD） is an irreversible neurodegenerative disease with clinical manifestations such as memory impairment， aphasia， impaired visuospatial skills， executive function impairment， and personality changes. AD has brought a heavy burden to the family and society due to its unrevealed pathogenesis and the lack of therapeutic approaches. Saponins， a group of oligoglycosides whose aglycones are triterpenes or spirosteroids， are divided into triterpene saponins and steroidal saponins， which have a variety of biological activities. At present， there is no systematic review on the anti-AD effect of saponins. According to the literature published in recent years， the authors summarized the studies of saponins in improving AD based on animal experiments. The results indicated that saponins enhanced learning ability and improved cognitive impairment by inhibiting amyloid β-protein （Aβ） cascade activity， suppressing microtubule-associated protein （tau） hyperphosphorylation， inhibiting neuronal oxidative stress， inhibiting inflammatory factors， regulating apoptosis， inhibiting cholinergic neuronal degeneration， promoting mitochondrial autophagy， regulating intestinal flora， and enhancing energy metabolism， which in turn improved the pathological state of AD animal models. The therapeutic effects of different saponins on AD are different. The present study discussed the effect of different aglycones and sugar chains on the anti-AD activity based on saponins and anti-AD effect to provide new ideas and a theoretical basis for the development and utilization of saponins.