Prevalence and factors associated with insomnia among medical students in China during the COVID-19 pandemic: characterization and associated factors.

BACKGROUND: Insomnia has become an important issue in recent years. Insomnia is affected by many factors. Previous research has shown that during the COVID-19 pandemic, there would be a long-term negative effect on the mental health of medical college students. The state of medical college students' insomnia directly determines the results of medical education and the career development prospects of the medical students themselves. Therefore, it is very important to understand the insomnia situation of medical students in the post-epidemic era. METHODS: This study was conducted 2 years after the global COVID-19 pandemic (April 1-April 23, 2022). The study used an online questionnaire, administered through a web-based survey platform. The Athens Insomnia Scale (AIS), Fear of COVID-19 Scale (FCV-19S), GAD-2, PHQ-2, and socio-demographic information were surveyed by the Questionnaire Star platform. RESULTS: The prevalence of insomnia was 27.80% (636/2289). Grade(P < 0.05), age(P < 0.001), loneliness(P < 0.001), depression(P < 0.001), anxiety(P < 0.001), fear of COVID-19 was highly correlated with insomnia (P < 0.001). Adapting to online class(P < 0.001) was a protective factor of smartphone addiction. CONCLUSIONS: This survey shows that Insomnia was highly prevalent among the Chinese medical college students during the COVID-19 pandemic. Governments and schools should through psychological interventions to address the current situation of insomnia among medical students, and formulate targeted programs and strategies to reduce their psychological problems.

Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration.

Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1ß (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 µM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation (p < 0.01) under IL-1ß stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.

Combined homocysteine and apoE rs429358 and rs7412 polymorphism in association with serum lipid levels and cognition in Chinese community-dwelling older adults.

BACKGROUND: ApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults. METHODS: A cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements. RESULTS: Participants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p <  0.05). Cognition of the subjects was found to be significantly associated with high serum tHcy level and ApoE genetic polymorphism (p <  0.05). Independent of age, BMI, education levels, smoking and alcohol drinking, the worst cognitive ability were detected in the high serum tHcy level subjects with ApoE rs429358C/T and rs7412 C/T as compare with other groups, especially orientation function, memory and delayed recall ability and attention ability. CONCLUSION: High serum tHcy level in combination with ApoE rs429358 and rs7412 variants might be linked with serum lipid levels and cognition, particularly for orientation function and memory and delayed recall ability in old Chinese adults.

A frailty index based on routine laboratory data predicts increased risk of mortality in Chinese community-dwelling adults aged over 55 years: a five-year prospective study.

BACKGROUND: Frailty can be operationalized based on the accumulation of deficits using a frailty index (FI) and is associated with an increased risk of adverse health outcomes. Here, we aim to compare validity of a FI from laboratory data with that of the common clinical FI for prediction of mortality in adults aged 55 + years, also examine whether combined FI could improve identification of adults aged 55 + years at increased risk of death. METHODS: Data for this analysis were obtained from the Beijing Longitudinal Study of Aging that involved 1,257 community-dwelling Chinese people, aged 55 + years at baseline. The main outcome measure was 5-year mortality. An FI-self-report based on 30 self-reported health-related data was constructed. An FI-lab was developed using laboratory data, in addition to pulse, systolic and diastolic blood pressure, pulse pressure, body mass index (BMI) and waist. A combined FI comprised all items from each FI. Kaplan-Meier survival curve and Cox proportional hazards models were performed to evaluate the risk of each FI on death. The area under receiver operating characteristic(ROC) curves were used to compare the discriminative performance of each FI. RESULTS: Of 1257 participants, 155 died and 156 lost at the end of the 5-year follow-up. The mean FI-self-report score was 0.11 ± 0.10, the FI-lab score was 0.33 ± 0.14 and FI-combined score was 0.19 ± 0.09. Higher frailty level defined by each FI was associated with higher risk of death. After adjustment for age and sex, Cox proportional hazards models showed that the higher scores of frailty were associated with a higher risk of mortality for each FI, the hazard ratios for the FI-self-report and FI-lab and FI-combined were 1.04 (1.03 to 1.05) and 1.02 (1.01 to 1.03) and 1.05 (1.04 to 1.07), respectively. The areas under the ROC curve were 0.79 (0.77-0.82) for the FI-self-report, 0.77(0.75-0.80) for the FI-lab and 0.81(0.78-0.82) for FI-combined. CONCLUSIONS: A FI from laboratory data can stratify older adults at increased risk of death alone and in combination with FI based on self-report data. Assessment in clinical settings of creating an FI using routine collected laboratory data needs to be further developed.

Association Between Blood Pressure Control and Arterial Stiffness in Middle-Aged and Elderly Chinese Patients with Hypertension.

BACKGROUND The severity of arterial stiffness can be evaluated by pulse wave velocity (PWV). This study investigated the association between blood pressure (BP) control and arterial stiffness in middle-aged and elderly Chinese patients with hypertension. MATERIAL AND METHODS Three hundred and twelve hypertensive patients were divided according to whether their hypertension was well-controlled or uncontrolled and stratified according to age. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). The effect of BP control on arterial stiffness and its severity was assessed by multivariate linear and logistic regression analyses. RESULTS Moderate and severe arterial stiffness was detected significantly more often in patients with uncontrolled hypertension than in those with well-controlled hypertension, regardless of age. BaPWV increased by 8.467 cm/s in the study population overall for every 1-mmHg increment in systolic BP and by 8.584, 8.616, and 8.199 cm/s, respectively, in patients aged 45-65, 65-80, and ≥80 years. Regardless of age, the risk of arterial stiffness was 5.93 times higher (95% confidence interval 2.78-12.64) and the risk of a one-grade increase in the severity of arterial stiffness was 4.01 times higher (95% confidence interval 2.51-6.42) in patients with uncontrolled hypertension than in those with well-controlled hypertension. CONCLUSIONS This study found a positive relationship between baPWV and BP and identified uncontrolled BP as a risk factor for arterial stiffness and its severity. Management of BP within a reasonable range may help to ameliorate arterial stiffness.

Discordance between apolipoprotein B or non-HDL-cholesterol and LDL-cholesterol in middle-aged and elderly Chinese patients predicts arterial stiffness.

BACKGROUND: Discordance of lipid parameters is closely associated with residual cardiovascular risk. This study investigated the discordance between non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C), and assessed arterial stiffness risk. METHODS: This study included a total of 402 middle-aged and elderly Northern Chinese individuals whose brachial-ankle pulse wave conduction velocity (baPWV), and clinical and biochemical data were measured. Arterial stiffness was defined by inclusion in the upper quartile of the baPWV. All participants were divided into four mutually exclusive concordance/discordance groups based on the lipid goal for high-risk populations, according to the 2019 European Society of Cardiology / European Atherosclerosis Society guidelines. Discordance was defined as LDL-C ≥ 1.81 mmol/L with non-HDL-C <  2.59 mmol/L, or apoB < 0.80 mmol/L, or vice versa. RESULTS: The mean age of the participants was 65.9 ± 13.0 years; 59.5% of the participants were male. The mean LDL-C was 2.41 ± 0.81 mmol/L, non-HDL-C: 3.06 ± 0.94 mmol/L, and apoB: 0.84 ± 0.21 mmol/L. LDL-C was observed to be discordant with non-HDL-C (20.1%) and apoB (30.8%). When stratified according to LDL-C levels, the baPWV was greater in those patients with higher non-HDL-C or apoB levels. In the adjusted logistic regression model, low LDL-C and high non-HDL-C or apoB discordance were also associated with the risk of arterial stiffness (OR: 13.412 and OR: 13.054, respectively). CONCLUSIONS: There was discordance between LDL-C and non-HDL-C, or apoB in middle-aged and elderly Chinese individuals; this was associated with a higher risk of arterial stiffness. Non-HDL-C or apoB levels could be used to identify individuals who may benefit from more comprehensive lipid modification.

The link of depression, untreated hypertension, and diabetes with mortality in postmenopausal women: A cohort study.

OBJECTIVE: To explore the association of depression, as well as untreated hypertension or diabetes with all-cause death in community-based postmenopausal women in Beijing. METHODS: A cohort of 863 community-based postmenopausal women with no history of cardiovascular heart disease (CHD), stroke, cancer, or dementia was investigated on 20 July-28 September 2009 at baseline. Depression was diagnosed using the 30-item Center for Epidemiologic Studies Depression (CES-D) scale with CES-D ≥ 11. Meanwhile, data on health behavior, physical comorbidity, and social support at baseline were collected. These individuals were followed up from 20 July to 30 August 2014. All-cause mortality and cause of death were surveyed. RESULTS: After a median follow-up of 4.97 years, 120 subjects died of all-cause. Twenty-four died of stroke, 19 died of myocardial infarction, 21 died of cancer. The others died of aging, infection, and accident. Depression and untreated HP were significantly associated with all-cause mortality in Cox models after full adjustment for all of the potential confounders (Depression HR: 2.16, 95%CI: 1.35-3.46; Untreated hypertension HR: 1.84, 95%CI: 1.12-3.02). However, negative correlation of untreated diabetes on all-cause mortality was observed in this population (HR: 1.36, 95%CI: 0.75-2.49). When depression was co-existing with hypertension/diabetes, the HR for mortality elevated significantly (Depression co-existing with hypertension HR = 3.87, 95% CI: 2.07-7.23; Depression co-existing with diabetes HR = 5.02, 95% CI: 1.5-16.79). CONCLUSIONS: It is suggested we should take sufficient care of postmenopausal females with depression and control blood pressure and glucose more effectively. Abbreviations: HP: Hypertension; DM: Diabetes; TC: Cholesterol; TG: Triglyceride; BMI: Body-Mass Index; CES-D: Center for Epidemiologic Studies Depression; CDC: Centers for Disease Control and Prevention; HR: Hazard Ratio; CI: Confidence Interval; ADL: Activities of daily living scale.

Kidney dysfunction is associated with risk of cardiovascular events in middle-aged and elderly population with hypertension: A 5-year community-based cohort study in China
.

AIM: To evaluate the association between kidney dysfunction and cardiovascular disease (CVD) events in a middle-aged and elderly population in China. MATERIALS AND METHODS: In July 2009, a baseline survey of health status was performed in adults aged 55 years and older from Beijing, China. Occurrence of CVD events and mortality in subjects free of CVD at baseline was recorded in a 5-year follow-up period until December 2014. The association of mild (eGFRCKD-EPI 45 - 59 mL/min/1.73m2) and moderate to severe (eGFRCKD-EPI < 45 mL/min/1.73m2) kidney dysfunction with adverse outcomes were analyzed with Cox regression analysis. RESULTS: A total of 1,257 subjects were included in the final analysis. The risk of CVD events in those with mild kidney dysfunction increased by 65% (HR: 1.65, 95% CI: 1.04 - 2.62) as compared to those with normal kidney function. Subjects with both hypertension and CKD experienced more significantly increased risk of CVD events (adjusted HR = 1.87, 95% CI 1.17 - 2.97) and stroke (adjusted HR = 2.24, 95% CI 1.24 - 4.04). Pulse pressure (PP) ≥ 60 mmHg was the strongest risk factor for stroke in patients with CKD, with the adjusted HR value of 1.98 (95% CI 1.08 - 3.64). CONCLUSION: Moderate to severe kidney dysfunction was an independent risk predictor of CVD events. Among subjects with hypertension or poorly controlled blood pressure level, the presence of CKD significantly increased the risks of CVD events and stroke.

Simultaneous determination of cytokinins by high performance liquid chromatography with resonance Rayleigh scattering and mechanism discussion.

A reliable, highly sensitive and highly selective method of high performance liquid chromatography associated with resonance Rayleigh scattering (HPLC-RRS) was developed to detect three cytokinins, namely, 6-benzylaminopurine (BA), kinetin (KT) and zeatin (ZT). In this work, Pd(ii) is added into the system to form ternary ion association complexes for the first time, which results in a lower limit of detection and extends the application of HPLC-RRS. The experimental conditions were optimized. In order to investigate the reaction mechanism, the ternary ion association complexes were characterized by ultraviolet-visible spectrophotometry, dynamic light scattering, scanning electron microscopy and density functional theory calculations. In a HAc-NaAc buffer solution (pH = 4.1), a ternary complex of cytokinin : Pd(ii) : EryB (1 : 1 : 2) was formed. The detection limits (S/N = 3) of BA, KT, and ZT were 0.9, 1.5 and 2.3 ng mL-1, respectively. In addition, this method was applied for the simultaneous detection of cytokinins in real samples with satisfactory results.

A quadruple-channel fluorescent sensor array based on label-free carbon dots for sensitive detection of tetracyclines.

A quadruple-channel fluorescent sensor array based on label-free carbon dots (CDs) was fabricated to detect and discriminate a series of tetracyclines (TCs), including chlortetracycline (CTC), oxytetracycline (OTC), tetracycline (TC) and doxycycline (DOX). Blue-emitting carbon dots (B-CDs) and green-emitting carbon dots (G-CDs) were prepared to serve as four sensing elements. When the TCs were directly mixed with CDs, the fluorescence quenching phenomenon appeared. Since different TCs exhibited different affinities for sensing elements, the sensor array displays a distinct fluorescence pattern of the fluorescence intensity variation (F0 - F)/F0 for each of these TCs, which is further analyzed by principal component analysis (PCA). The present fluorescent sensor array has the capacity to differentiate TCs at a low concentration of 1 µM. Meanwhile, quantitative detection with a lower limit (0.30 µM) for TCs could be achieved by applying a single element. Moreover, a high accuracy (100%) examination of unknown samples is acquired. Finally, the fluorescent sensor array performs well in distinguishing binary mixtures and could also recognize TCs in milk.

Plasma MicroRNA-34a as a Potential Biomarker for Early Diagnosis of Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) is one of the cancers with high morbidity and mortality in the world. The dysregulation of microRNAs (miRNAs) would affect the development of cancers, which can be used as potential and non-invasive diagnostic marker. miRNA-34a is a tumor suppressor which inhibits EC cell migration and invasion. However, the clinical significance of circulating miRNA-34a remains undiscovered. In this study, we did a preliminary study of plasma miRNA-34a as a potential biomarker for esophageal cancer diagnosis. METHODS: The relationship was analyzed between the expression of microRNA-34a with RT-qPCR in three different cohorts which were collected from patients with 101 esophageal cancers, 31 benign disease and 97 healthy controls. RESULTS: The expression level of plasma miR-34a was upregulated in esophageal cancer. The panel of miR-34a and Cyfra 21-1 had great diagnostic efficiency for the EC patients, the logistic regression model was Y = 0.97*miR-34a + 1.02* Cyfra21-1 - 2.85. The AUC was 0.7981 if the cutoff was 0. 5782. The sensitivity and the specificity were 60.40% and 89.69%, respectively. The sensitivity of miR-34a for the EC patients with stage Tis + I + II was 66.47% and specificity was 60.42%. CONCLUSIONS: Plasma miR-34a may serve as a potential biomarker in detecting early stages of the EC.

Metabolic syndrome and risks of carotid atherosclerosis and cardiovascular events in community-based older adults in China.

BACKGROUND AND OBJECTIVES: Previous studies on the importance of metabolic syndrome (MS) as a cardiovascular risk factor had not focused on older Chinese adults. The present study analyzed the association of MS with carotid atherosclerosis and the risk of cardiovascular events in Chinese adults. METHODS AND STUDY DESIGN: Data of a representative cohort study with 5-year follow-up were used. Community-dwelling people (n=1257) aged ≥55 years without cardiovascular disease (CVD) at baseline were followed up from 2009 to 2014. MS was defined based on the Chinese Diabetes Society criteria under the Chinese Medical Association. Multiple regression analyses were performed to examine the associations of MS with atherosclerosis and CVD events, with adjustment for confounding factors. RESULTS: In a multivariate logistic regression model with adjustment, MS was closely related to common carotid artery intima-media thickness (CCA-IMT) (1.62; 95% CI: 1.19-2.21) and carotid plaque presence (1.38; 95% CI: 1.01-1.89), but not with carotid artery stenosis. At the end of the 5-year follow- up, compared with subjects without MS, hazard ratios and 95% confidence intervals for the different risks in subjects with MS were 1.86 (1.02-3.29) for myocardial infarction (MI), 1.39 (1.01-2.05) for stroke, 1.52 (1.02- 2.37) for CVD death, and 1.13 (0.62-2.58) for total death, after adjusting for age, gender, smoking, drinking, physical activity, uric acid, high-sensitivity C-reactive protein, dietary factors and carotid atherosclerosis status. CONCLUSIONS: MS was significantly associated with IMT and the presence of carotid plaque and with positively increased risks of MI, stroke, and CVD mortality independent of CVD risk factors in older Chinese adults.

Evaluation of a newly developed chemiluminescence immunoassay for detecting cardiac troponin T.

BACKGROUND: To evaluate the performance of a chemiluminescence detection kit for cardiac troponin T (cTnT). METHODS: According to the "Guiding principles on performance analysis of diagnostic reagents in vitro" and the Clinical and Laboratory Standards Institute (CLSI) Guidelines, we assessed the detection limit, linear range, reportable range, accuracy, precision, cross reactivity, interference factors, and matrix effect of the kit, and compared these parameters with that of the commercial electrochemiluminescence detection kit for cTnT (Roche). RESULTS: The minimum detection limit of the kit was 0.01 ng/mL. The linear range was 0.01 ng/mL-25 ng/mL. The reportable range was from 0.01 ng/mL to 100 ng/mL. Precision within the batch was 2.9%-6.4%, and precision between batches was 6.0%; the accuracy was good and the recovery rate reached 96.2%. The cross-reaction test demonstrated that there was no reactivity between cTnT and a variety of troponins. Test results deviated by less than ±10% in the presence of hemoglobin ≤1000 µg/mL, bilirubin ≤250 µg/mL, triglycerides ≤11.25 mg/mL, and rheumatoid factor ≤206 U/mL, suggesting that kit results were not significantly interfered with these factors. Results from the matrix-effect assessment revealed absence of a matrix effect in the tested serum samples. Correlation study revealed that the performance of the kit was very consistent with that of the Roche electrochemiluminescence detection kit (Kappa = 0.900, P < .001) with a high correlation (r = .903, P < .001) and a total matching rate of 95.00%. CONCLUSION: The performance of the evaluated chemiluminescence immunoquantitation kit for cTnT detection was acceptable in all tested parameters, fulfilling requirements for clinical applications.

Evaluation of a newly developed quantitative determination kit for tumor marker CA15-3 with chemiluminescent assay.

BACKGROUND: Tumor marker carbohydrate antigen 15-3 (CA15-3) is used as a biomarker to aid to diagnose and monitor the prognosis of breast cancer patients. A new quantitative determination kit for CA15-3 with chemiluminescent assay was developed by Xiamen InnoDx Biotech Co., Ltd, China. Therefore, we conducted the report to evaluate the performance of the kit. METHODS: According to the "Guiding principles on performance analysis of diagnostic reagents in vitro", the calibration curve, limit of detection, reportable range, accuracy, precision, anti-interference capability, cross-reaction and comparison by measuring EDTA plasma and serum were carried out. In addition, the kit was performed in parallel to electrochemiluminescence immunoassay kit (Roche) to analyze the correlation between the two kits. RESULTS: Regression equation of calibration curve of the kit was Y=0.7914X+4.1032 (R2 =.990). Limit of detection was 0.0347 U/mL. The reportable range was 0.5-2400 U/mL. Recovery ratio was 100.0%-104.8%. Coefficient of variations (CVs) of within-run and between-run were 4.8%-7.6% and 5.8%-7.4% respectively. No remarkable interferences (all Bias% were less than ±10%) were detected when samples contained hemoglobin ≤183.8 µmol/L, bilirubin ≤340 µmol/L, triglyceride ≤18.1 mmol/L, or rheumatoid factor ≤400 U/mL. No cross-reaction was present in the kit. Moreover, compared with the results from electrochemiluminescence immunoassay kit (Roche) in 345 serum samples, there was a satisfied correlation coefficient of 0.977 (P<.01), and the kit was simultaneously fit for the detection of EDTA plasma and serum samples. CONCLUSION: The new kit validated satisfactorily, and it can be used for detecting CA15-3 in clinical practice.

Performance evaluation of a chemiluminescence microparticle immunoassay for CK-MB.

BACKGROUND: To verify and evaluate the performance characteristics of a creatine kinase phosphokinase isoenzymes MB (CK-MB) assay kit, which produced by Xiamen Innodx Biotech Co. Ltd. METHODS: Evaluation was carried out according to "Guidelines for principle of analysis performance evaluation of in vitro diagnostic reagent." The performance parameters included detection limit, linearity range, reportable range, recovery test, precision verification, interference test, cross-reactivity, matrix effect, and method comparison. RESULTS: The detection limit was 0.1 ng/mL. The assay had clinical linearity over range of 0.1 ng/mL-500 ng/mL. Reportable range was from 0.1 ng/mL to 1000 ng/mL. The average percent of recovery was 99.66%. The coefficient of variation (CV) for within-run and between-run of low CK-MB sample was 5.55% and 6.16%, respectively. As for high-level sample, it was 7.88% and 7.80%. In medical decision level, the relative deviation (Bias) of all interference tests was lower than 15%. When the sample had mild-hemolysis; hemoglobin ≤15 g/L; triglyceride ≤17 mmol/L; bilirubin ≤427.5 µmol/L; rheumatoid factor ≤206U/mL, there was no significant interference to be found. Moreover, assay kit had no cross-reaction with CK-MM and CK-BB. At last, total diagnostic accuracy of kit was 93.24%, when compared with refer kit. CONCLUSION: Overall the results of the verification study indicated the performance of kit is met the requirements of the clinical test.

Type 2 Fibroblast Growth Factor Receptor Signaling Preserves Stemness and Prevents Differentiation of Prostate Stem Cells from the Basal Compartment.

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, which include basal, luminal, and neuroendocrine cells. Two types of P-SCs have been identified in both human and mouse adult prostates based on prostasphere or organoid cultures, cell lineage tracing, renal capsule implantation, and expression of luminal- and basal-specific proteins. The sphere-forming P-SCs are from the basal cell compartment that express P63, and are therefore designated as basal P-SCs (P-bSCs). Luminal P-SCs (P-lSCs) express luminal cytokeratins and Nkx3.1. Herein, we report that the type 2 FGF receptor (FGFR2) signaling axis is crucial for preserving stemness and preventing differentiation of P-bSCs. FGFR2 signaling mediated by FGFR substrate 2α (FRS2α) is indispensable for formation and maintenance of prostaspheres derived from P63(+) P-bSCs. Ablation of Fgfr2 in P63(+) cells in vitro causes the disintegration of prostaspheres. Ablation of Fgfr2 in vivo reduces the number of P63-expressing basal cells and enriches luminal cells. This suggests a basal stem cell-to-luminal cell differentiation. In addition, ablation of Fgfr2 in P63(+) cells causes defective postnatal development of the prostate. Therefore, the data indicate that FGFR2 signaling is critical for preserving stemness and preventing differentiation of P-bSCs.

Development of a multi-marker model combining HE4, CA125, progesterone, and estradiol for distinguishing benign from malignant pelvic masses in postmenopausal women.

The purpose of this study was to evaluate HE4, CA125, progesterone (Prog), and estradiol (E2) for differentiating pelvic masses in postmenopausal women and aimed to build a multi-marker model which may improve the diagnostic value. HE4, CA125, Prog, and E2 were detected in 57 benign pelvic masses (BPM) and 92 epithelial ovarian cancer (EOC) patients. A total of 66.66 % of the BPM and EOC serum samples were used for building the differentiation model, and the remaining 33.33 % of the BPM and EOC serum samples were used for validation of the differentiation model. After comparing by Z score statistics, HE4 + CA125 + E2 model was chosen as the best multi-marker model. In the training group, the area under curve of the HE4 + CA125 + E2 model was 0.97 (0.93, 1.00), sensitivities of the model for distinguishing BPM from EOC, from early EOC, and from advanced EOC were 90.16, 86.21, and 95.65 %; specificities were 92.11, 92.11, and 92.11 %. In the validation group, sensitivities of HE4 + CA125 + E2 model for distinguishing BPM from EOC, from early EOC, and from advanced EOC were 96.77, 100.00, and 87.50 %, specificities were 84.21, 100.00, and 84.21 %. The multi-marker model showed significant improvement when compared to CA125 or HE4, and it might be an effective pelvic mass differentiation method.

Combined Effect of Hyperhomocysteinemia and Hypertension on the Presence of Early Carotid Artery Atherosclerosis.

BACKGROUND: To examine the individual effect of elevated homocysteine and its combined effect with hypertension on early carotid artery atherosclerosis (ECAS). METHODS: We recruited 1257 subjects from a community-based population in Beijing, China, aged 55 years and older. The definition of hyperhomocysteinemia was referred to as the presence of homocysteine concentrations greater than 15 µmol/L. Carotid intima-media thickness (CIMT), plaque, the sum of plaque thickness (plaque score, PS), and plaque location in common carotid artery were established by ultrasonography. The presence of increased CIMT (≥1.0 mm) and plaque was defined as ECAS. Age, sex, smoking, alcohol drinking, physical activity, total cholesterol, glucose, estimated glomerular filtration rate, hypoglycemic therapy, and lipid-lowering therapy were adjusted by logistic regression analysis. RESULTS: After adjustments for all potential confounders, the risks of presence of plaque, bilateral plaque, and high PS were significantly higher in the group with hyperhomocysteinemia as compared with reference group (the normal homocysteine and normotensive). The odds ratios (ORs) were 1.56 for presence of plaque (95% CI 1.05-2.33), 1.80 for bilateral plaque (95% CI 1.08-2.99), and 1.90 for high PS (95% CI 1.09-3.30), respectively. The group with both hyperhomocysteinemia and hypertension manifested the highest ORs of ECAS. The fully adjusted ORs were 1.67 for increased CIMT (95% CI 1.15-2.42), 2.48 for bilateral plaques (95% CI 1.54-3.99), and 2.69 for high PS (95% CI 1.61-4.47), correspondingly. CONCLUSIONS: Elevated homocysteine had a mild-to-moderate independent effect on ECAS. Combined with hypertension, hyperhomocysteinemia might increase the strength of the above-mentioned effects.

Automated cell analysis of cerebrospinal fluid with XE-5000.

BACKGROUND: Hematology analyzers have been able to make automated counts of cells present in CSF samples in recent years. Most of them cannot provide reliable counts of the low cell levels usually present in CSF. METHODS: Functional sensitivity, precision, analytical measurement range, and method comparisons were deter- mined according to Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: The functional sensitivity for white blood cells (WBC) and red blood cells (RBC) was 18/µL and 725/µL (minimum reported concentration), respectively. The total precision ranged from 6.1% to 16.3% for WBC counts within the concentration of 33-183/µL and from 4.1% to 19.4% for RBC counts within the concentration of 745-11,350/µL. The within-run precision for WBC was 3.1% at 7,592/µL. The analytical measurement range was 18-10,078/µL for WBC and 725-5,222,550/µL for RBC. There was good correlation between WBC and RBC counts determined by the XE5000 and microscopic examination, according to slopes and R2 method comparisons. The correlation of the two methods for mononuclear cell (MN) counts was 0.907 with the WBC count of 50-5,000/µL. The reliability of WBC counts produced by the XE-5000 was 0.7. CONCLUSIONS: The XE-5000 performed satisfactorily in the CSF assay, but it is still necessary to manually confirm the WBC count when it is less than 18/µL.

Clinical significance of combined testing of YKL-40 with CEA in Chinese colorectal cancer patients.

BACKGROUND: To investigate the practical value of individual and combined testing of plasma levels of YKL-40, CEA, and CA199 for auxiliary diagnosis and detection of recurrence of colorectal cancer. METHODS: ELISA and ECLIA were used to evaluate levels of YKL-40, CEA, and CA199 in 120 colorectal cancer patients (56 initial-diagnosis, 42 post-operative, and 22 recurrent cases). Forty-three patients with benign colorectal disease and 36 healthy patients were enrolled as controls. The relationship between YKL-40 and clinical indicators of tumor pathology was analyzed. The positive rate and diagnostic efficacy of single and combined YKL-40, CEA, and CA199 testing were assessed in patients with colorectal cancer. RESULTS: Plasma YKL-40 in the cancer group was significantly higher than in the benign control and healthy control group, and the mean values were 145.4 ng/mL, 107.7 ng/mL, and 51.3 ng/mL (p < 0.05), respectively. With 72 ng/mL as the diagnostic threshold, the sensitivity and specificity of YKL-40 in colorectal cancer diagnosis were found to be 73.2% and 66.7%, respectively. Early-stage colorectal cancer patients showed a YKL-40 positive rate (73%) significantly higher than those of CEA and CA199 (50% and 32%, respectively; p < 0.05). When YKL-40 testing was combined with CEA or CA199, the positive rate increased to 82.1% and 80.3%, respectively. Through ROC curve analysis of the post-operative recurrent group against the non-recurrent group, the areas under the curve for YKL-40, CEA, and CA199 were found to be 0.907, 0.714, and 0.759, respectively. Based on the Dukes classification, the mean YKL-40 value for stages A/B, C, and D were 120.1 ng/mL, 131.7 ng/mL, and 226.8 ng/mL (p = 0.008), respectively. The plasma YKL-40 level gradually increased as the disease progressed. Lower degrees of tumor differentiation were correlated with higher YKL-40 levels. The mean YKL-40 values of high, medium, and low tumor differentiation groups were 96.8 ng/mL, 127.5 ng/mL, and 225.7 ng/mL (p = 0.004), respectively. CONCLUSIONS: The benefits of using YKL-40 testing are higher than CEA and CA199 for the monitoring of colorectal cancer recurrence. Combined testing of both YKL-40 and CEA was found to be optimal for auxiliary diagnosis of colorectal cancer. Plasma YKL-40 was found to be suitable for auxiliary diagnosis of colorectal cancer.