Molecular Subtyping of Mild Cognitive Impairment Based on Genetic Polymorphism and Gene Expression.

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative brain disease in the elderly. Recent studies have revealed the heterogeneous nature of AD. Mild Cognitive Impairment (MCI) is the prodromal stage of AD. OBJECTIVES: In this study, we identified subtypes of MCI based on genetic polymorphism and gene expression. METHODS: We utilized the two types of omics data, namely genetic polymorphism and gene expression profiling, derived from 125 MCI patients' peripheral blood samples from the ADNI-1 dataset. Similarity network fusion (SNF) algorithm was implemented to cluster MCI patient subtypes. And 185 MCI patients in ADNI-2 were utilized to evaluate the effectiveness of this method. Two MCI subtypes were identified by implementing the SNF algorithm. RESULTS: We used Kaplan-Meier analysis and log-rank testing for the conversion from MCI to AD between two subtypes, and p-value is 4.58×10-3. In addition, we compared patients among two MCI subtypes by the following factors: the changes in Alzheimer's Disease cognitive scales and MRI image; significantly enriched pathways based on differentially expressed genes. This study proved that MCI is a heterogeneous disease by concluding that AD development in two MCI subtypes is significantly different. CONCLUSIONS: MCI patients with different molecular characteristics have different risks converting to AD. In addition to evaluating statistics, genetic polymorphism and gene expression profiling from MCI patients' peripheral blood are non-invasiveness and cost-effectiveness markers to identify MCI subtypes for clinical application.

[Risk stratification of type-specific human papillomavirus for cervical precancers: evidence from a cross-sectional study in Shenzhen].

Objective: To analyze the epidemiological genotype features of human papillomavirus (HPV) in cervical infection and their risks for cervical precancers among women in Shenzhen area. Methods: A total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology (LBC), colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia (CIN) 2 and above were estimated. Results: The HPV infection rate in Shenzhen area was 15.9% (432/2 717). The most common HPV genotype was HPV52 (22.9%), followed by HPV16 (12.7%), HPV53 (10.0%), HPV51 (8.6%) and HPV58 (8.1%). Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity (57.1% vs. 42.9%, P<0.05) and an analogous specificity (87.3% vs. 86.9%, P>0.05) in predicting CIN2+ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion (LSIL) positive tested by LBC in predicting CIN2+ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance (ASC-US) positive tested by LBC alone (P<0.05). The specificities of these two methods mentioned above in predicting CIN2+ were 83.5% and 89.2%, respectively, without statistical difference (P>0.05). Conclusions: Women infected by HPV have distinct risks for CIN2+ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL+ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.

[Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China].

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ(2)=54.79, P<0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95%CI) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection (OR (95%CI): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 (OR (95%CI): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion: Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

[Application of liver visualization technologies in hilar tumor resection at the second hepatic portal area].

OBJECTIVE: To discuss the application of liver visualization technology in complex liver tumor resection at the second hepatic portal area. METHODS: Clinical data of 80 cases who received surgery at the second hepatic portal area from August 2014 to September 2015 in the Third Department of Hepatic Surgery of Eastern Hepatobiliary Surgery Hospital were analyzed retrospectively. There were 58 male and 22 female patients aged from 21 to 70 years with median age of 52 years. Median maximum diameter of tumor was 7.6 cm (3.0 to 17.0 cm). Before surgery, liver dimensional graphics produced by liver visualization technology were taken on all patients to observe the relationship between intrahepatic vasculars and the liver tumor, and to calculate the intended resection range and the remaining liver volume in order to make a proper surgery plan. Suitable hepatic vascular occlusion was applied in the tumor resection. Intrahepatic vessel shape and variation, surgical operation, surgical operation time, manner and time of hepatic vascular occlusion, blood loss, liver resection volume, postoperative complications were observed. RESULTS: There were 23 patients who changed surgery plan after liver visualization technology.There were 44 cases with single main hepatic vein compressed by tumors, 32 cases with 2 main hepatic veins, 4 cases with 3 main hepatic veins compressed by tumors.And there were 58 cases with both hepatic vein and inferior vena cava compressed by tumor. Hepatic segments 6 and 7 was removed in 12 cases, 14 cases, hepatic segments 4, 5 and 8 were removed in 8 cases.Right hepatectomy was carried out in 9 patients and left hepatectomy was carried out in 8 patients. Right trisectionectomy was carried out in 3 patients and left trisectionectomy was applied in 5 patients.Local hepatectomy was performed in 12 patients. Nine patients received associating liver partition and portal vein ligation for staged hepatectomy. Four patients underwent total hepatic vascular exclusion, while 16 patients underwent selective hepatic vascular exclusion. The median surgical time was 132 minutes(80 to 240 minutes). Median blood loss volume was 580 ml(100-5 000 ml). Median volume of hepatic resection was 750 ml(30 to 2 000 ml). One patient needed secondary surgery to stop bleeding as a result of postoperative abdominal bleeding.Complication of postoperative bile leakage occurred in 14 cases.Five patients had pleural effusion requiring invasive therapy.Four patients had ascites requiring invasive therapy. Besides, 5 patients had incisive infection while 2 patients were found with pulmonary infection after surgery and two patients occurred biliary obstruction. There was no death case occurred a result of surgery. CONCLUSIONS: Using liver visualization technology to make surgical operation plan can improve surgical safety of the second hepatic portal area and optimize the operation plan. It can also reduce the risk of blood loss and postoperative complications such as liver failure.

Quality of life after surgical resection compared with radiofrequency ablation for small hepatocellular carcinomas.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome measure in studies of cancer therapy. This study aimed to investigate HRQL and survival in patients with small hepatocellular carcinoma (HCC) treated with either surgical resection or percutaneous radiofrequency ablation (RFA). METHODS: Between January 2006 and June 2009, patients with newly diagnosed solitary, small (3 cm or less) HCC were invited to participate in this non-randomized prospective parallel cohort study. The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) instrument was used for assessing HRQL. HRQL and survival were compared between the two treatment groups. RESULTS: A total of 389 patients were enrolled. Questionnaires were completed fully by 99.7 per cent of invited participants (388 of 389) at baseline, 98.7 per cent (383 of 388) at 3 months, 99.0 per cent (379 of 383) at 6 months, 98.4 per cent (365 of 371) at 1 year, 96.6 per cent (336 of 348) at 2 years and 95.1 per cent (289 of 304) at 3 years. There were no significant differences in disease-free and overall survival between the two groups. Patients treated with percutaneous RFA had significantly better HRQL total scores after 3, 6, 12, 24 and 36 months than those who had surgical resection (P < 0.001, P < 0.001, P = 0.001, P = 0.003 and P = 0.025 respectively). On multivariable analysis, the presence of concomitant disease, cirrhosis and surgical resection were significant risk factors associated with a worse HRQL score after treatment. CONCLUSION: Percutaneous RFA produced better post-treatment HRQL than surgical resection for patients with solitary small (no more than 3 cm) HCC.

The membrane potential changes polarity during capacitation of murine epididymal sperm.

The membrane potential in murine epididymal sperm was determined with a voltage-sensitive, fluorescent probe. In freshly collected sperm, the potential was inside-negative, viz., -13 mV, and was associated with an intracellular K+ concentration of about 122 mM. Following incubation of sperm in a medium capable of sustaining capacitation and fertilization efficacy, the potential became gradually positive. An inside-positive potential, +24 mV, was obtained after 40 min of incubation, concomitant with an intracellular K+ concentration of approximately 30 mM. At this time, about 70 percent of sperm had capacitated. An inside-positive membrane potential may play a role in facilitating the acrosome reaction.

Ligand-triggered conformational perturbations elicit changes at the single cysteinyl residue of spinach calmodulin.

Following application of stoichiometric amounts of Ca2+ or specific partner peptides to spinach calmodulin, dynamic changes in the nanosecond range could be monitored at a strategically anchored fluorescence or spin probe. For these studies the single cysteinyl residue 26 of spinach calmodulin was labelled with a thiol-specific proxyl (i.e. 2,2,5,5-tetramethyl-1-pyrrolidinyl-oxyl) spin probe or with a bimane fluorescence probe. With Ca2+ and a specific ligand (mastoparan) present, fluorescence studies (anisotropy, lifetime) indicated that the rotational motion of the protein complex becomes slower relative to the motion of calmodulin in the absence of the specific ligand. The probe's attachment site 26 appears to reside in a fairly polar microenvironment as reported by a series of proxyl spin probes varying in label length. The rotational correlation time of the shortest spin probe markedly changed upon binding of a specific peptide to a calmodulin region distant from that of the monitoring spin probe. We interpret these observations as indicating that ligand-triggered conformational perturbations are eliciting specific responses at the cysteinyl residue 26 of spinach calmodulin.

Frictional resistance to motions of bimane-labelled spinach calmodulin in response to ligand binding.

The single cysteinyl residue 26 of spinach calmodulin was labelled with the thiol-specific bimane fluorescence probe. Following application of stoichiometric quantities of Ca2+ or aluminum ions to the protein, temperature-dependent fluorescence changes (anisotropy, lifetime) could be monitored via the label. From these data the Y function could be constructed which, as a function of temperature, seems to consist of two linear regions which intersect at the critical temperature, Tc. From the Y function the thermal coefficient, b(T), of the frictional resistance to fluorophore rotation could be determined. b(T) was dependent on the type and stoichiometry of the ligand(s) bound to calmodulin. Changes of the thermal coefficient apparently resulted in part from ligand-triggered structural pertubations transmitted over a considerable distance to calmodulin region I, the site of the fluorophore.