Objective To evaluate the preventive effects of Haishe capsules on the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease(AD).Methods Patients (n=120) with aMCI from our department were recruited and randomly divided into the treatment group and the control group (n=60 in each group).The treatment group was given 0.9 gram of Haishe capsules three times a day while the control group received no drug treatment.Data on the conversion ratio,memory and cognitive function were comparedbetween the groups in a 24-months follow-up.Results By the end of the study,12 patients in the treatment group and 15 in the control group dropped out.Valid data for 93 patients were available for statistical analysis (48 in the treatment group and 45 in the control group).The number of aMCI patients who converted to AD was 6,with a conversion ratio of 12.5％ (6/48);and the number of patients who went through conversion in the control group was 13,with a conversion ratio of 28.8％ (13/45).The difference in conversion between the two groups was statistically significant (x2 =3.83,P＜0.05).After 24 months,MMSE scores for the treatment group (25.52± 1.07) had no significant change compared with baseline levels,while MMSE scores for the control group decreased significantly(24.75--1.49) and were markedly lower than thosefor the treatment group (t=2.85,P＜0.05).MoCA scores for the treatment group (19.39 ±2.01) did not show decline until the end of the study,while those for the control group started to decrease about half way through the study and were lower than scores for the treatment group (t =2.41,P＜0.05).Compared with baseline levels,ADAS-Cogscores for the treatment group (7.62± 1.06) did not increase significantly during the course of the study.ADAS-Cogscores forthe control group were higher at both half way (7.70±0.75) and the end of the study (8.18±0.80)than base line levels,and there was a statistically significant difference in end-of-study ADAS-Cog scores between the two groups(t =-2.6,P＜ 0.05).Conclusions Haishe capsules not only effectively maintain memory and cognitive function,but also delay the conversion from aMCI to AD.

OBJECTIVES: To synthetically analyse the medical malpractice cases of cardiac death in forensic identification, and to explore the generality and characteristic of cause of death, medical malpractice and assessment of participation degree. METHODS: Totally 52 medical malpractice cases of cardiac death examined in the Xiaoshan Branch Office, Hangzhou Minghao Forensic Judical Appraisal Institute, from January 2015 to April 2018 were collected. The general information of cases, medical institutions and situations of hospital stay, cause of death, medical malpractice and assessment of participation degree were retrospectively analysed. RESULTS: In 52 cases, the male to female ratio was 2.25:1, and most subjects aged >50-60. Cardiac death caused by hypertensive heart disease or coronary heart disease was most common （67.3%）, followed by viral myocarditis and cardiomyopathy （13.5%）. There were 24 cases involved surgery, and the survival time after surgery was from 1 h to 118 d with a 7 d medium value. There were 63 medical institutes involved in these medical malpractices. Medical malpractice presented in most hospitals more or less, and the participation degree was >20%-30%. CONCLUSIONS Forensic appraisal contributes to determine causes of death, which not only provides scientific evidence for medical malpractice identification, but also improves diagnosis and treatment levels of medical institutions.
Autopsy ; Cause of Death ; Coronary Disease/mortality* ; Death ; Female ; Forensic Medicine ; Humans ; Hypertension/mortality* ; Male ; Malpractice/statistics & numerical data* ; Middle Aged ; Retrospective Studies

Objective To prepare pH-responsive osmotic nanocarriers (pMPPs),observe their distribution in the genital tract mucosa in mice,and evaluate their radiosensitizing effects in tumor cells.Methods Amphiphilic polymers containing pH-sensitive hydrazone bonds were synthesized and pMPPs were prepared by ultrasonic emulsification.At the same time,the hydrophobic polymer polylactic acid-glycolic acid copolymer (PLGA) and the amphiphilic polymer PLGA-polyethylene glycol without hydrazine bond were selected,and the mucoadhesive nanoparticles(MPs) and mucus-penetrating particles (MPPs) were prepared in the same way.Fluorescence microscopy was used to observe the distribution of three kinds of nanocarriers labeled with fluorescent dye Cy5.5 in the genital tract mucosa.The toxicity of nanocarriers to human cervical cancer cell line HeLa was tested by thiazolyl blue assay.The amphiphilic polymer containing pH-sensitive hydrazone bond was combined with oil-soluble gold nanoparticles to form a multi-encapsulated nanocarrier,and its radiotherapy sensitization effect in HeLa cells was evaluated by thiazole blue assay.Results The pMPPs were successfully prepared with relatively uniform particle size and good dispersion.Fluorescence microscopy showed that pMPPs not only had good mucus permeability,but also could improve the endocytosis efficiency of the nanocarriers in reproductive tract mucosa.The results of thiazolyl blue test showed that when the concentration of the carrier reached to 0.80 mg/ml,the survival rate of HeLa cells in the pMPPs group was higher than 90％ which was higher than that in the MPs and the MPPs groups,indicating that pMPPs had good biosafety.The HeLa cell survival rate of the CMNa group (0.80 mg/ml) was higher than that of the multi-package nanocarrier group under different doses of X-ray irradiation (4 Gy:82.90％ vs.61.79％;8 Gy:64.75 ％ vs.42.36％).This result indicated that compared with the CMNa,a commonly used clinical radiotherapy sensitizer,the multi-encapsulated nanocarriers can more effectively enhance the sensitivity of tumor cells to radiation therapy,thereby improving the lethality of radiation therapy on tumor cells.Conclusion This study solved the conflict between mucus permeation and endocytosis design of nanocarriers in mucosal tissue application,and provided new insight for the treatment of mucosal tissue diseases.

【Objective】 To investigate the strategies against blood collection and supply in Hainan Province during the COVID-19 epidemic, so as to provide theoretical and technical support for ensuring blood balance and safety under epidemic situation. 【Methods】 Countermeasures of blood collection and supply against the COVID-19 epidemic, taken by blood centers in Hainan, were reviewed, and data from 2016 to 2020 were collected and analyzed to evaluate the effectiveness of countermeasures by comparison. 【Results】 During the COVID-19 epidemic, the total units of blood collected and issued continued to grow and the annual growth rate reached 10.3% in 2020. The proportion of blood donation by groups increased by 0.3%. The number of blood donations by soldiers and medical personnel has increased significantly, reaching 91.2% and 24.7%, respectively. 【Conclusion】 The countermeasures in Hainan during the COVID-19 epidemic achieved remarkable effects and ensured blood safety in the whole province, which provided references and experience for blood collection and supply under public emergencies.

Objective To investgate the application value of low-dose CT scanning in right adrenal vein imaging.Methods A total of 124 patients were enrolled in the study who were suspected as primary aldosteronism and requiring a contrast enhanced CT examination on adrenal glands.Four patients were excluded according to the exclusion criteria,so that the rest 120 patients were divided equally into three groups.Group A was a control group with conventional radiation dose using tube voltage of 120 kV and automatic mA.It was divided into A1,A2 and A3 groups according to arterial phase,portal venous phase and parenchymal phase.Group B was a experimental group with conventional tube voltage of 120 kV and automatic mA,which was divided into B1,B2 and n3 groups according to arterial phase,late arterial phase and portal venous phase.Group C was a low-dose experimental group with a tube voltage of 100 kV and a tube current of 150 mA only in the second phase,the remaining scanning parameters and method were the same as that of group B.The subjective scores of the images of groups A,B and C were statistically analyzed,and the CT values of the right adrenal vein(RAV),the right adrenal gland(RAG),and the fat of anterior abdominal wall at different scan phases were measured.The dose length products (DLP) were recorded and the signal-to-noise ratios (SNR),contrast-to-noise ratios (CNR),effective doses (E) of the three groups were calculated and compared.Results The subjective scores of the two observers were consistent (Kappa value =0.63);the subjective scores of the B2 images were statistically significant (H =7.18,P＜0.05).Difference of subjective scores between B2 and A2was statistically significant (t=-18.03,P＜0.05).The CT values of RAV,SNR,and CNR of the B2 group were higher than those of the A2 group (t=36.99,6.92,9.02,P＜0.05).The radiation dose comparison showed that the effective dose (E) was 45.52％ lower in the low-dose group than the conventional dose group with the statistically significant difference(t =12.19,P＜0.05).Conclusions Using MDCT scanning technique with lower tube voltage and lower tube current of 100 kV-150 mA,the detection rate of right adrenal vein can reach 95％ in the late arterial phase,and the effective dose can be reduced about 45.52％ on the basis of ensuring image quality.

Objective To evaluate the clinical value of CT urography (CTU) in quantitative analysis of single?kidney renal glomerular filtration rate (GFR) in patients with renal tumor and hydronephrosis.Methods A total of 49 patients with renal tumor or hydronephrosis from January 2018 to September 2018 in the Second Hospital of Tianjin Medical University were prospectively collected. In all cases, the CT urography and 99mTc?DTPA renal dynamic imaging data and related clinical data were collected. All patients were divided into two groups: the experimental group (39 patients with a total of 78 kidneys) and the validation group (10 patients with a total of 20 kidneys). According to the presence or absence of renal diseases, the kidneys of the experimental group and the validation group were further divided into four groups, namely, the single kidney group, the tumor group, the stagnant water group and the healthy group. The CT urography protocol consisted of noncontrast, arterial phase, nephrographic, and excretory phase imaging. The total renal GFR was determined by CT measurement of renal clearance of contrast media (CM), and the total CT?GFR was then split into single?kidney CT?GFR by a left and right kidney proportionality factor. Differences between CT?GFR and SPECT?GFR measurements in each group of the experimental group was compared by paired?sample t test. Correlations between CT?GFR and SPECT?GFR in the experimental group and their correlations with RPV was analyzed by Pearson method. The Bland?Altman mapping method was used to evaluate the consistency between CT?GFR and SPECT?GFR in the experimental group. Results Paired difference between single?kidney CT?GFR (48.76 ± 18.50) ml·min-1·1.73 m-2 and single?kidney SPECT?GFR (45.68±17.95) ml·min-1·1.73 m-2 in the experimental group, P<0.05, demonstrating 6.8% systemic overestimation. A good correlation(r=0.80, P<0.01) and consistency (± 22.50 ml·min-1·1.73 m-2, ± 49.2% measurement deviations) was revealed between both measurements. There were positive correlations between CT?GFR and SPECT?GFR in the renal tumor group, hydronephrosis group, and healthy kidney group (r=0.67, 0.92, 0.80; P<0.01) respectively, and with good agreement (95% CI measurement deviation<30 ml·min-1·1.73 m-2). In all validation groups, there was no statistical difference between the estimated and true values of the Gates?GFR (all P>0.05). Pearson Correlation analysis showed that the correlations between CT?GFR and RPV in all experimental groups were better than the correlation between Gates?GFR and RPV (P<0.05). Conclusions This study demonstrated the feasibility of using CT urography to measure single?kidney GFR, verifying its application value in diseases such as kidney tumors and obstructive hydronephrosis, and proved that the proposed single?kidney CT?GFR correlates better than the SPECT?GFR with RPV.

Tumor neovascularization plays an important role in the occurrence, development and metastasis of cancer. Non-invasive quantification and detection of tumor neovascularization is crucial for early diagnosis and prognosis assessment of cancer. Targeted molecular imaging has arisen in vascular targeting imaging and precise treatment based on the molecular characteristics of neovascularization. Aminopeptidase N (APN, or CD13) is a multifunctional membrane-bound exopeptidase that is overexpressed in neovascular endothelial cells and some tumor cells but rarely expressed in normal blood vessels, which makes it a potential target for tumor neovascularization imaging and anti-angiogenic therapy. This review summarizes the application progress and the future development trend of target molecular imaging and precise treatment based on CD13.

Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.
Acids ; chemistry ; Amino Acid Sequence ; Animals ; Capsid Proteins ; chemistry ; genetics ; metabolism ; Enterovirus A, Human ; genetics ; metabolism ; physiology ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; Lysosome-Associated Membrane Glycoproteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping ; Protein Structure, Tertiary ; RNA, Viral ; genetics ; metabolism ; Receptors, Scavenger ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Sf9 Cells ; Static Electricity ; Virion ; genetics ; metabolism ; Virus Attachment

Objective To prepare polyethylene glycol/cyclic asparagines-glycine-arginine functionalized gold nanoparticles (GNPs-PEG@cNGR) and evaluate their effectiveness in CT imaging of breast cancer angiogenesis.Methods The GNPs were synthesized by one-step reduction of chloroauric acid by sodium citrate.The thiolated PEG and cysteine-modified cNGR were coupled to the surface of GNPs through Au-S bonds,respectively.The GNPs-PEG@cNGR was characterized by transmission electron microscopy,Zeta potential/hydration particle size analyzer,and Fourier transform infrared spectrometer.The uptake and CT imaging effect of GNPs-PEG@cNGR were assessed by human umbilical vein endothelial cells (HUVEC) and human hepatoma cells (HepG2) positively expressed for aminopeptidase N (APN/CD 13).The in vivo CT imaging effects on tumor angiogenesis and biocompatibility in mice of GNPs-PEG@cNGR were studied by BALB/c mouse model of 4T1 breast cancer.Results A specific CT molecular probe,i.e.GNPs-PEG@cNGR,was successfully constructed,which can target angiogenesis.The probe was spherical,with a hydration particle size of (35.7± 1.0) nm and a Zeta potential of (-13.54± 1.12) mV,and had good stability and biocompatibility.The GNPs-PEG@cNGR has good CT imaging results and can specifically target CD13-positive HUVEC and HepG2 cells.The CT imaging results in 4T1 breast cancer mice indicated that GNPs-PEG@cNGR could be specifically enriched in the tumor tissue after injection.The CT value of tumors in GNPs-PEG@cNGRz group was higher than that of GNPs-PEG group,and the difference was statistically significant (P＜0.05).Conclusions GNPs-PEG@cNGR can specifically target CD13 positive cells and can be used as a CT contrast agent for imaging tumor angiogenesis.

Chimeric antigen receptor (CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia (ALL). Measurable/minimal residual disease (MRD) monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy. Common MRD detection methods include flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and each method has advantages and limitations. It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse. Thus, how to perform prognostic evaluations, stratify risk based on MRD status, and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice. This review assesses the common and novel MRD assessment methods. In addition, we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as other therapeutic strategies to improve treatment effect. Furthermore, this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.
Humans ; Receptors, Chimeric Antigen/therapeutic use* ; Neoplasm, Residual ; Transplantation, Homologous/methods* ; Transplantation Conditioning/methods* ; Hematopoietic Stem Cell Transplantation/methods* ; Recurrence ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*