Exosomes represent a class of nanoscale extracellular vesicles that facilitate the exchange of genetic information among various cells.Alzheimer's disease(AD)stands as a progressive neurodegenerative disorder characterized by its subtle and advan-cing onset,representing the foremost form of dementia lacking effective therapeutic interventions.Notably,investigations have illuminated the involvement of exosomes in the pathogenesis of AD,attributing diagnostic and therapeutic significance to their role,particularly concerning exosomal microRNAs(miRNA).The miRNAs carried by exosomes serve as potential biomarkers for AD,while also exhibiting potential benefits in ameliorating cognitive dysfunction in individuals afflicted by AD.This article aims to comprehensively review the origins of exosomes(encom-passing both mesenchymal cell-derived exosomes and brain-de-rived exosomes)and their potential as therapeutic agents targe-ting AD.

BACKGROUND: Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI. METHODS: The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset <12 hours undergoing manual thrombus aspiration and Promus Element stent implantation. Patients were randomly assigned to control group (n=20) or post-dilatation group (n=21) in which a non-compliant balloon was inflated to >16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI. RESULTS: There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P<0.0001), the primary study endpoint, with similar strut coverage (98.5% vs. 98.4%, P=0.63) and 1-year rate of major adverse cardiovascular events (MACE). CONCLUSION In STEMI patients, post-dilatation after stent implantation and thrombus aspiration improved strut apposition up to 7 months without affecting coronary blood flow or 1-year MACE rate. Larger and longer term studies are warranted to further assess safety (ClinicalTrials.gov identifi er: NCT02121223).

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.
Bone Marrow ; Erythrocyte Indices ; Humans ; Karyotyping ; Myelodysplastic Syndromes ; Prognosis

Purpose: The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods: A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. Results: With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. Conclusion No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

According to the procedures for the development of evidence-based medicine guidelines, a multi-disciplinary guideline development working group was established, after three rounds of discussions by the consensus expert group, a new evidencebased guideline for diagnosis and treatment of senile osteoporosis in China(2018) was developed. The grading of recommendations assessment, development and evaluation(GRADE) system was used to rate the quality of evidence and the strength of recommendations. Recommendations were derived from evidence body, and at the same time considered the balance of benefits and harms as well as values and preferences of Chinese patients. The guideline development working group developed 15 recommendations for the diagnosis and treatment of senile osteoporosis. The guideline covered the screening for senile osteoporosis, risk assessment, diagnosis, basic treatment, multiple anti-osteoporosis drugs, therapeutic effect monitoring and evaluation of senile osteoporosis. This guideline aims to serve as a tool for clinicians and patients for best decisions-making in China.

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.
Humans ; Primary Myelofibrosis ; Prognosis ; Retrospective Studies ; Thrombocytopenia

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Genes, p53 ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis ; Tumor Suppressor Protein p53 ; Young Adult

Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.
Adult ; Aged ; Aged, 80 and over ; Anemia, Macrocytic ; Humans ; Lenalidomide ; Middle Aged ; Myelodysplastic Syndromes ; Retrospective Studies ; Thalidomide

Objective To analyze and discuss the content determination of As and Hg from Lilium Lancifolium in Longshan County; To optimize microwave digestion conditions. Methods Automatic microwave digestion appratus was used. Lilium Lancifolium samples from Longshan County were digested in teflon microwave tube with HNO3-H2O2, and As and Hg were measured with atomic fluorescence spectrometry (AFS). Results The content of As was in the range of 0.031–0.507 mg/kg, and the highest content of Hg was 0.024 mg/kg. The regression equation was Y=221.23X+170.72(r=0.995 9),Y=503.52X-682.43,(r=0.999 2).For the production base,the recoveries of As and Hg were 94.32% and 92.48% in the samples, and RSD were 2.14% and 2.70%; for the breeding base, the recoveries of As and Hg were 94.95% and 93.52% in the samples, and RSD were 1.15% and 1.97%. Conclusion The method is simple and reliable, which can be used to the content determination of As and Hg from Lilium Lancifolium, and provide references for the choice of base of production and breeding of Lilium Lancifolium in Longshan County.

BackgroundHand injuries are very common in sports, such as skiing and ball sports. One of the major reasons causing hand and finger deformity is due to ligament and tendon injury. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) can demonstrate the complex anatomy of the fingers and thumb, especially the tendons and ligaments, and provide the accurate diagnosis of clinically important fingers and thumbs deformity due to ligamentous and tendinous injuries during sport activities.

MethodsSixteen fresh un-embalmed cadaveric hands were harvested from eight cadavers. A total of 20 healthy volunteers' hands and 44 patients with fingers or thumb deformity due to sports-related injuries were included in this study. All subjects had MR examination with T1-weighted images and proton density-weighted imaging with fat suppression (PD FS) in axial, coronal, and sagittal plane, respectively. Subsequently, all 16 cadaveric hands were sliced into 2-mm thick slab with a band saw (six in coronal plane, six in sagittal plane, and four in axial plane). The correlation of anatomic sections and the MRI characteristics of tendons of fingers and the ulnar collateral ligament (UCL) at the metacarpal phalangeal joint (MCPJ) of thumb between 20 healthy volunteers and 44 patients (confirmed by surgery) were analyzed.

ResultsThe normal ligaments and tendons in 16 cadaveric hands and 20 volunteers' hands showed uniform low-signal intensity on all the sequences of the MRI. Among 44 patients with tendinous and ligamentous injuries in the fingers or thumb, 12 cases with UCL injury at MCPJ of the thumb (Stener lesion = 8 and non-Stener lesion = 4), 6 cases with the central slip injury, 12 cases with terminal tendon injury, and 14 cases with flexor digitorum profundus injury. The ligaments and tendons disruption manifested as increased signal intensity and poor definition, discontinuity, and heterogeneous signal intensity of the involved ligaments and tendons.

ConclusionsSports injury-related fingers and thumb deformity are relatively common. MRI is an accurate method for evaluation of the anatomy and pathologic conditions of the fingers and thumb. It is a useful tool for accurate diagnosis of the sports-related ligaments and tendons injuries in hand.

Adult ; Athletic Injuries ; diagnosis ; surgery ; Female ; Hand Deformities ; diagnosis ; surgery ; Humans ; Ligaments ; diagnostic imaging ; surgery ; Magnetic Resonance Imaging ; Male ; Metacarpophalangeal Joint ; diagnostic imaging ; surgery ; Middle Aged ; Soft Tissue Injuries ; diagnostic imaging ; surgery ; Tendon Injuries ; diagnostic imaging ; surgery ; Thumb ; abnormalities ; surgery